ID ACE_HUMAN Reviewed; 1306 AA. AC P12821; B0LPF0; B4DXI3; E7EU16; P22966; Q53YX9; Q59GY8; Q7M4L4; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 1. DT 02-SEP-2026, entry version 271. DE RecName: Full=Angiotensin-converting enzyme {ECO:0000303|PubMed:2849100}; DE Short=ACE {ECO:0000303|PubMed:2849100}; DE EC=3.4.15.1 {ECO:0000269|PubMed:10913258, ECO:0000269|PubMed:11076943, ECO:0000269|PubMed:12542396, ECO:0000269|PubMed:1320019, ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:7961923}; DE AltName: Full=Dipeptidyl carboxypeptidase I {ECO:0000303|PubMed:4322742}; DE AltName: Full=Kininase II {ECO:0000303|PubMed:6055465}; DE AltName: CD_antigen=CD143; DE Contains: DE RecName: Full=Angiotensin-converting enzyme, soluble form; DE Flags: Precursor; GN Name=ACE {ECO:0000303|PubMed:2849100, ECO:0000312|HGNC:HGNC:2707}; GN Synonyms=DCP, DCP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC-1). RX PubMed=2849100; DOI=10.1073/pnas.85.24.9386; RA Soubrier F., Alhenc-Gelas F., Hubert C., Allegrini J., John M., Tregear G., RA Corbol P.; RT "Two putative active centers in human angiotensin I-converting enzyme RT revealed by molecular cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 85:9386-9390(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), AND TISSUE RP SPECIFICITY (ISOFORM TESTIS-SPECIFIC). RX PubMed=2547653; DOI=10.1016/0014-5793(89)80897-x; RA Lattion A.L., Soubrier F., Allegrini J., Hubert C., Corvol P., RA Alhenc-Gelas F.; RT "The testicular transcript of the angiotensin I-converting enzyme encodes RT for the ancestral, non-duplicated form of the enzyme."; RL FEBS Lett. 252:99-104(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), AND TISSUE RP SPECIFICITY (ISOFORM TESTIS-SPECIFIC). RX PubMed=2554286; DOI=10.1073/pnas.86.20.7741; RA Ehlers M.R.W., Fox E.A., Strydom D.J., Riordan J.F.; RT "Molecular cloning of human testicular angiotensin-converting enzyme: the RT testis isozyme is identical to the C-terminal half of endothelial RT angiotensin-converting enzyme."; RL Proc. Natl. Acad. Sci. U.S.A. 86:7741-7745(1989). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-261; TRP-561 AND RP SER-1286. RX PubMed=10319862; DOI=10.1038/8760; RA Rieder M.J., Taylor S.L., Clark A.G., Nickerson D.A.; RT "Sequence variation in the human angiotensin converting enzyme."; RL Nat. Genet. 22:59-62(1999). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1239 (ISOFORM SOMATIC-1). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [9] RP PROTEIN SEQUENCE OF 30-46, FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=Lung; RX PubMed=2558109; DOI=10.1093/oxfordjournals.jbchem.a122871; RA Takeuchi K., Shimizu T., Ohishi N., Seyama Y., Takaku F., Yotsumoto H.; RT "Purification of human lung angiotensin-converting enzyme by high- RT performance liquid chromatography: properties and N-terminal amino acid RT sequence."; RL J. Biochem. 106:442-445(1989). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1114-1306 (ISOFORM SOMATIC-2), AND RP ALTERNATIVE SPLICING. RC TISSUE=Umbilical vein endothelial cell; RX PubMed=9642152; DOI=10.1006/bbrc.1998.8813; RA Sugimura K., Tian X.-L., Hoffmann S., Ganten D., Bader M.; RT "Alternative splicing of the mRNA coding for the human endothelial RT angiotensin-converting enzyme: a new mechanism for solubilization."; RL Biochem. Biophys. Res. Commun. 247:466-472(1998). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=6055465; DOI=10.1038/2151402a0; RA Yang H.Y., Erdoes E.G.; RT "Second kininase in human blood plasma."; RL Nature 215:1402-1403(1967). RN [12] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=4322742; DOI=10.1016/0005-2795(70)90017-6; RA Yang H.Y., Erdoes E.G., Levin Y.; RT "A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates RT bradykinin."; RL Biochim. Biophys. Acta 214:374-376(1970). RN [13] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=656131; DOI=10.1016/0006-2952(78)90542-7; RA Erdoes E.G., Johnson A.R., Boyden N.T.; RT "Hydrolysis of enkephalin by cultured human endothelial cells and by RT purified peptidyl dipeptidase."; RL Biochem. Pharmacol. 27:843-848(1978). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=6270633; DOI=10.1016/s0196-9781(81)80027-7; RA Stewart T.A., Weare J.A., Erdoes E.G.; RT "Purification and characterization of human converting enzyme (kininase RT II)."; RL Peptides 2:145-152(1981). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=6208535; DOI=10.1016/0196-9781(84)90020-2; RA Skidgel R.A., Engelbrecht S., Johnson A.R., Erdoes E.G.; RT "Hydrolysis of substance p and neurotensin by converting enzyme and neutral RT endopeptidase."; RL Peptides 5:769-776(1984). RN [16] RP FUNCTION. RX PubMed=2982830; DOI=10.1016/s0021-9258(18)89410-8; RA Norman J.A., Chang J.Y.; RT "Proteolytic conversion of [Met]enkephalin-Arg6-Gly7-Leu8 by brain synaptic RT membranes. Characterization of formed peptides and mechanism of RT proteolysis."; RL J. Biol. Chem. 260:2653-2656(1985). RN [17] RP FUNCTION. RX PubMed=2983326; DOI=10.1073/pnas.82.4.1025; RA Skidgel R.A., Erdoes E.G.; RT "Novel activity of human angiotensin I converting enzyme: release of the RT NH2- and COOH-terminal tripeptides from the luteinizing hormone-releasing RT hormone."; RL Proc. Natl. Acad. Sci. U.S.A. 82:1025-1029(1985). RN [18] RP COFACTOR, AND ZINC-BINDING. RX PubMed=1649623; DOI=10.1021/bi00243a012; RA Ehlers M.R.W., Riordan J.F.; RT "Angiotensin-converting enzyme: zinc- and inhibitor-binding stoichiometries RT of the somatic and testis isozymes."; RL Biochemistry 30:7118-7126(1991). RN [19] RP ALTERNATIVE PROMOTER USAGE, AND FUNCTION (ISOFORM TESTIS-SPECIFIC). RX PubMed=1651327; DOI=10.1016/s0021-9258(18)98626-6; RA Hubert C., Houot A.M., Corvol P., Soubrier F.; RT "Structure of the angiotensin I-converting enzyme gene. Two alternate RT promoters correspond to evolutionary steps of a duplicated gene."; RL J. Biol. Chem. 266:15377-15383(1991). RN [20] RP FUNCTION (ISOFORM TESTIS-SPECIFIC), CATALYTIC ACTIVITY (ISOFORM RP TESTIS-SPECIFIC), ACTIVITY REGULATION (ISOFORM TESTIS-SPECIFIC), AND RP SUBCELLULAR LOCATION (ISOFORM TESTIS-SPECIFIC). RX PubMed=1668266; DOI=10.1016/1046-5928(91)90001-y; RA Ehlers M.R., Chen Y.N., Riordan J.F.; RT "Purification and characterization of recombinant human testis angiotensin- RT converting enzyme expressed in Chinese hamster ovary cells."; RL Protein Expr. Purif. 2:1-9(1991). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992. RX PubMed=1851160; DOI=10.1016/s0021-9258(18)31543-6; RA Wei L., Alhenc-Gelas F., Corvol P., Clauser E.; RT "The two homologous domains of human angiotensin I-converting enzyme are RT both catalytically active."; RL J. Biol. Chem. 266:9002-9008(1991). RN [22] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF RP 390-HIS--HIS-394 AND 988-HIS--HIS-992. RX PubMed=1320019; DOI=10.1016/s0021-9258(18)42224-7; RA Wei L., Clauser E., Alhenc-Gelas F., Corvol P.; RT "The two homologous domains of human angiotensin I-converting enzyme RT interact differently with competitive inhibitors."; RL J. Biol. Chem. 267:13398-13405(1992). RN [23] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=8257427; DOI=10.1042/bj2960373; RA Rieger K.J., Saez-Servent N., Papet M.P., Wdzieczak-Bakala J., Morgat J.L., RA Thierry J., Voelter W., Lenfant M.; RT "Involvement of human plasma angiotensin I-converting enzyme in the RT degradation of the haemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl- RT proline."; RL Biochem. J. 296:373-378(1993). RN [24] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND RP MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992. RX PubMed=7683654; DOI=10.1016/s0021-9258(18)98378-x; RA Jaspard E., Wei L., Alhenc-Gelas F.; RT "Differences in the properties and enzymatic specificities of the two RT active sites of angiotensin I-converting enzyme (kininase II). Studies with RT bradykinin and other natural peptides."; RL J. Biol. Chem. 268:9496-9503(1993). RN [25] RP FUNCTION, SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE RP FORM), AND MUTAGENESIS OF ARG-1166. RX PubMed=8253769; DOI=10.1016/s0021-9258(19)74332-4; RA Beldent V., Michaud A., Wei L., Chauvet M.T., Corvol P.; RT "Proteolytic release of human angiotensin-converting enzyme. Localization RT of the cleavage site."; RL J. Biol. Chem. 268:26428-26434(1993). RN [26] RP FUNCTION. RX PubMed=7523412; DOI=10.1016/s0021-9258(18)47091-3; RA Danilov S., Jaspard E., Churakova T., Towbin H., Savoie F., Wei L., RA Alhenc-Gelas F.; RT "Structure-function analysis of angiotensin I-converting enzyme using RT monoclonal antibodies. Selective inhibition of the amino-terminal active RT site."; RL J. Biol. Chem. 269:26806-26814(1994). RN [27] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF RP 390-HIS--HIS-394; GLU-1016 AND ASP-1020. RX PubMed=7961923; DOI=10.1016/s0021-9258(18)43897-5; RA Williams T.A., Corvol P., Soubrier F.; RT "Identification of two active site residues in human angiotensin I- RT converting enzyme."; RL J. Biol. Chem. 269:29430-29434(1994). RN [28] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY RP REGULATION, AND MUTAGENESIS OF 390-HIS--HIS-394. RX PubMed=7876104; DOI=10.1074/jbc.270.8.3656; RA Rousseau A., Michaud A., Chauvet M.T., Lenfant M., Corvol P.; RT "The hemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro is a natural and RT specific substrate of the N-terminal active site of human angiotensin- RT converting enzyme."; RL J. Biol. Chem. 270:3656-3661(1995). RN [29] RP FUNCTION, SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE RP FORM), PROTEOLYTIC CLEAVAGE, AND CLEAVAGE SITE. RX PubMed=7499427; DOI=10.1074/jbc.270.48.28962; RA Beldent V., Michaud A., Bonnefoy C., Chauvet M.T., Corvol P.; RT "Cell surface localization of proteolysis of human endothelial angiotensin RT I-converting enzyme. Effect of the amino-terminal domain in the RT solubilization process."; RL J. Biol. Chem. 270:28962-28969(1995). RN [30] RP DISULFIDE BONDS. RX PubMed=8755737; DOI=10.1021/bi960243x; RA Sturrock E.D., Yu X.C., Wu Z., Biemann K., Riordan J.F.; RT "Assignment of free and disulfide-bonded cysteine residues in testis RT angiotensin-converting enzyme: functional implications."; RL Biochemistry 35:9560-9566(1996). RN [31] RP SUBCELLULAR LOCATION (ISOFORM TESTIS-SPECIFIC), GLYCOSYLATION AT ASN-103; RP ASN-121; ASN-140; ASN-368 AND ASN-617 (ISOFORM TESTIS-SPECIFIC), AND RP MUTAGENESIS OF ASN-103; ASN-121; ASN-140; ASN-186 AND ASN-617 (ISOFORM RP TESTIS-SPECIFIC). RX PubMed=8626443; DOI=10.1074/jbc.271.11.6429; RA Sadhukhan R., Sen I.; RT "Different glycosylation requirements for the synthesis of enzymatically RT active angiotensin-converting enzyme in mammalian cells and yeast."; RL J. Biol. Chem. 271:6429-6434(1996). RN [32] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=8609242; DOI=10.1172/jci118484; RA Azizi M., Rousseau A., Ezan E., Guyene T.T., Michelet S., Grognet J.M., RA Lenfant M., Corvol P., Menard J.; RT "Acute angiotensin-converting enzyme inhibition increases the plasma level RT of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline."; RL J. Clin. Invest. 97:839-844(1996). RN [33] RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=9371719; DOI=10.1042/bj3280587; RA Isaac R.E., Williams T.A., Sajid M., Corvol P., Coates D.; RT "Cleavage of arginyl-arginine and lysyl-arginine from the C-terminus of RT pro-hormone peptides by human germinal angiotensin I-converting enzyme RT (ACE) and the C-domain of human somatic ACE."; RL Biochem. J. 328:587-591(1997). RN [34] RP GLYCOSYLATION AT ASN-38; ASN-54; ASN-111; ASN-146; ASN-509; ASN-695; RP ASN-714; ASN-760; ASN-942 AND ASN-1191, LACK OF GLYCOSYLATION AT ASN-1225, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=9013598; DOI=10.1074/jbc.272.6.3511; RA Yu X.C., Sturrock E.D., Wu Z., Biemann K., Ehlers M.R.W., Riordan J.F.; RT "Identification of N-linked glycosylation sites in human testis RT angiotensin-converting enzyme and expression of an active deglycosylated RT form."; RL J. Biol. Chem. 272:3511-3519(1997). RN [35] RP FUNCTION, AND MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992. RX PubMed=10336644; DOI=10.1046/j.1432-1327.1999.00419.x; RA Isaac R.E., Michaud A., Keen J.N., Williams T.A., Coates D., Wetsel W.C., RA Corvol P.; RT "Hydrolysis by somatic angiotensin-I converting enzyme of basic dipeptides RT from a cholecystokinin/gastrin and a LH-RH peptide extended at the C- RT terminus with gly-Arg/Lys-arg, but not from diarginyl insulin."; RL Eur. J. Biochem. 262:569-574(1999). RN [36] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=10913258; DOI=10.1021/bi9928905; RA Araujo M.C., Melo R.L., Cesari M.H., Juliano M.A., Juliano L., RA Carmona A.K.; RT "Peptidase specificity characterization of C- and N-terminal catalytic RT sites of angiotensin I-converting enzyme."; RL Biochemistry 39:8519-8525(2000). RN [37] RP FUNCTION, SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE RP FORM), PROTEOLYTIC CLEAVAGE, CLEAVAGE SITE, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=10769174; DOI=10.1042/bj3470711; RA Woodman Z.L., Oppong S.Y., Cook S., Hooper N.M., Schwager S.L.U., RA Brandt W.F., Ehlers M.R.W., Sturrock E.D.; RT "Shedding of somatic angiotensin-converting enzyme (ACE) is inefficient RT compared with testis ACE despite cleavage at identical stalk sites."; RL Biochem. J. 347:711-718(2000). RN [38] RP TISSUE SPECIFICITY. RX PubMed=10969042; DOI=10.1161/01.res.87.5.e1; RA Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M., Stagliano N., RA Donovan M., Woolf B., Robison K., Jeyaseelan R., Breitbart R.E., Acton S.; RT "A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) RT converts angiotensin I to angiotensin 1-9."; RL Circ. Res. 87:E1-E9(2000). RN [39] RP TISSUE SPECIFICITY. RX PubMed=10924499; DOI=10.1074/jbc.m002615200; RA Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J.; RT "A human homolog of angiotensin-converting enzyme. Cloning and functional RT expression as a captopril-insensitive carboxypeptidase."; RL J. Biol. Chem. 275:33238-33243(2000). RN [40] RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF RP VARIANT LEU-1228, AND POLYMORPHISM. RX PubMed=11076943; DOI=10.1074/jbc.m007706200; RA Eyries M., Michaud A., Deinum J., Agrapart M., Chomilier J., Kramers C., RA Soubrier F.; RT "Increased shedding of angiotensin-converting enzyme by a mutation RT identified in the stalk region."; RL J. Biol. Chem. 276:5525-5532(2001). RN [41] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, COFACTOR, AND RP MUTAGENESIS OF ARG-529 AND ARG-1127. RX PubMed=11432860; DOI=10.1074/jbc.m101495200; RA Liu X., Fernandez M., Wouters M.A., Heyberger S., Husain A.; RT "Arg(1098) is critical for the chloride dependence of human angiotensin I- RT converting enzyme C-domain catalytic activity."; RL J. Biol. Chem. 276:33518-33525(2001). RN [42] RP FUNCTION, SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE RP FORM), PROTEOLYTIC CLEAVAGE, CLEAVAGE SITE, AND MUTAGENESIS OF ASN-1229. RX PubMed=11274151; DOI=10.1074/jbc.m100339200; RA Alfalah M., Parkin E.T., Jacob R., Sturrock E.D., Mentele R., Turner A.J., RA Hooper N.M., Naim H.Y.; RT "A point mutation in the juxtamembrane stalk of human angiotensin I- RT converting enzyme invokes the action of a distinct secretase."; RL J. Biol. Chem. 276:21105-21109(2001). RN [43] RP FUNCTION. RX PubMed=11604391; DOI=10.1074/jbc.m104068200; RA Hu J., Igarashi A., Kamata M., Nakagawa H.; RT "Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A RT beta); retards A beta aggregation, deposition, fibril formation; and RT inhibits cytotoxicity."; RL J. Biol. Chem. 276:47863-47868(2001). RN [44] RP PHOSPHORYLATION AT SER-1299, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP SER-1299. RX PubMed=12386153; DOI=10.1161/01.res.0000038114.17939.c8; RA Kohlstedt K., Shoghi F., Mueller-Esterl W., Busse R., Fleming I.; RT "CK2 phosphorylates the angiotensin-converting enzyme and regulates its RT retention in the endothelial cell plasma membrane."; RL Circ. Res. 91:749-756(2002). RN [45] RP TISSUE SPECIFICITY. RX PubMed=12459472; DOI=10.1016/s0014-5793(02)03640-2; RA Harmer D., Gilbert M., Borman R., Clark K.L.; RT "Quantitative mRNA expression profiling of ACE 2, a novel homologue of RT angiotensin converting enzyme."; RL FEBS Lett. 532:107-110(2002). RN [46] RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND CLEAVAGE SITE. RX PubMed=12542396; DOI=10.1042/bj20021842; RA Gordon K., Redelinghuys P., Schwager S.L.U., Ehlers M.R.W., RA Papageorgiou A.C., Natesh R., Acharya K.R., Sturrock E.D.; RT "Deglycosylation, processing and crystallization of human testis RT angiotensin-converting enzyme."; RL Biochem. J. 371:437-442(2003). RN [47] RP INDUCTION. RX PubMed=15151696; DOI=10.1186/1741-7015-2-19; RA Goulter A.B., Goddard M.J., Allen J.C., Clark K.L.; RT "ACE2 gene expression is up-regulated in the human failing heart."; RL BMC Med. 2:19-19(2004). RN [48] RP TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=15671045; DOI=10.1093/eurheartj/ehi114; RA Burrell L.M., Risvanis J., Kubota E., Dean R.G., MacDonald P.S., Lu S., RA Tikellis C., Grant S.L., Lew R.A., Smith A.I., Cooper M.E., Johnston C.I.; RT "Myocardial infarction increases ACE2 expression in rat and humans."; RL Eur. Heart J. 26:369-375(2005). RN [49] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-1116 AND TYR-1125. RX PubMed=15615692; DOI=10.1074/jbc.m412638200; RA Naqvi N., Liu K., Graham R.M., Husain A.; RT "Molecular basis of exopeptidase activity in the C-terminal domain of human RT angiotensin I-converting enzyme: insights into the origins of its RT exopeptidase activity."; RL J. Biol. Chem. 280:6669-6675(2005). RN [50] RP FUNCTION, ACTIVE SITES, AND MUTAGENESIS OF GLU-391 AND GLU-989. RX PubMed=16154999; DOI=10.1074/jbc.m508460200; RA Hemming M.L., Selkoe D.J.; RT "Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme RT (ACE) and elevated by an ACE inhibitor."; RL J. Biol. Chem. 280:37644-37650(2005). RN [51] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-509; ASN-695 AND ASN-714. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [52] RP SUBUNIT. RX PubMed=16476786; DOI=10.1124/mol.105.020636; RA Kohlstedt K., Gershome C., Friedrich M., Mueller-Esterl W., RA Alhenc-Gelas F., Busse R., Fleming I.; RT "Angiotensin-converting enzyme (ACE) dimerization is the initial step in RT the ACE inhibitor-induced ACE signaling cascade in endothelial cells."; RL Mol. Pharmacol. 69:1725-1732(2006). RN [53] RP FUNCTION. RX PubMed=18077343; DOI=10.1073/pnas.0706980105; RA Heimann A.S., Gomes I., Dale C.S., Pagano R.L., Gupta A., de Souza L.L., RA Luchessi A.D., Castro L.M., Giorgi R., Rioli V., Ferro E.S., Devi L.A.; RT "Hemopressin is an inverse agonist of CB1 cannabinoid receptors."; RL Proc. Natl. Acad. Sci. U.S.A. 104:20588-20593(2007). RN [54] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITES, AND MUTAGENESIS OF GLU-391 AND RP GLU-989. RX PubMed=19773553; DOI=10.1074/jbc.m109.011437; RA Zou K., Maeda T., Watanabe A., Liu J., Liu S., Oba R., Satoh Y., Komano H., RA Michikawa M.; RT "Abeta42-to-Abeta40- and angiotensin-converting activities in different RT domains of angiotensin-converting enzyme."; RL J. Biol. Chem. 284:31914-31920(2009). RN [55] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-111; ASN-445 AND ASN-714. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [56] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [57] RP PHOSPHORYLATION AT SER-1299, AND MUTAGENESIS OF SER-1299. RX PubMed=21901117; DOI=10.1371/journal.pone.0022803; RA Barauna V.G., Campos L.C., Miyakawa A.A., Krieger J.E.; RT "ACE as a mechanosensor to shear stress influences the control of its own RT regulation via phosphorylation of cytoplasmic Ser(1270)."; RL PLoS ONE 6:e22803-e22803(2011). RN [58] {ECO:0007744|PDB:1O86, ECO:0007744|PDB:1O8A} RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230, X-RAY CRYSTALLOGRAPHY RP (2.0 ANGSTROMS) OF 642-1230 IN COMPLEX WITH CHLORIDE AND LISINOPRIL, ACTIVE RP SITE, AND ACTIVITY REGULATION. RX PubMed=12540854; DOI=10.1038/nature01370; RA Natesh R., Schwager S.L.U., Sturrock E.D., Acharya K.R.; RT "Crystal structure of the human angiotensin-converting enzyme-lisinopril RT complex."; RL Nature 421:551-554(2003). RN [59] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 642-1230 IN COMPLEX WITH RP ENALAPRILAT, AND X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230 IN RP COMPLEX WITH CAPTOPRIL. RX PubMed=15236580; DOI=10.1021/bi049480n; RA Natesh R., Schwager S.L.U., Evans H.R., Sturrock E.D., Acharya K.R.; RT "Structural details on the binding of antihypertensive drugs captopril and RT enalaprilat to human testicular angiotensin I-converting enzyme."; RL Biochemistry 43:8718-8724(2004). RN [60] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 30-641 IN COMPLEX WITH LISINOPRIL; RP ZINC AND CHLORIDE IONS, ACTIVITY REGULATION, AND GLYCOSYLATION AT ASN-54; RP ASN-74; ASN-146; ASN-318 AND ASN-509. RX PubMed=16476442; DOI=10.1016/j.jmb.2006.01.048; RA Corradi H.R., Schwager S.L.U., Nchinda A.T., Sturrock E.D., Acharya K.R.; RT "Crystal structure of the N domain of human somatic angiotensin I- RT converting enzyme provides a structural basis for domain-specific inhibitor RT design."; RL J. Mol. Biol. 357:964-974(2006). RN [61] {ECO:0007744|PDB:2OC2, ECO:0007744|PDB:3NXQ} RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 30-658 IN COMPLEX WITH ZINC, RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, GLYCOSYLATION AT ASN-38; ASN-54; RP ASN-74; ASN-111 ASN-146; ASN-160; ASN-445 AND ASN-509, LACK OF RP GLYCOSYLATION AT ASN-523, AND MUTAGENESIS OF ASN-318; ASN-445 AND ASN-509. RX PubMed=20826823; DOI=10.1074/jbc.m110.167866; RA Anthony C.S., Corradi H.R., Schwager S.L., Redelinghuys P., Georgiadis D., RA Dive V., Acharya K.R., Sturrock E.D.; RT "The N domain of human angiotensin-I-converting enzyme: the role of N- RT glycosylation and the crystal structure in complex with an N domain- RT specific phosphinic inhibitor, RXP407."; RL J. Biol. Chem. 285:35685-35693(2010). RN [62] {ECO:0007744|PDB:2YDM} RP X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 642-1230 IN COMPLEX WITH ZINC RP (ISOFORM TESTIS-SPECIFIC), ACTIVITY REGULATION (ISOFORM TESTIS-SPECIFIC), RP COFACTOR, AND GLYCOSYLATION AT ASN-103 AND ASN-140 (ISOFORM RP TESTIS-SPECIFIC). RX PubMed=21810173; DOI=10.1111/j.1742-4658.2011.08276.x; RA Akif M., Masuyer G., Schwager S.L., Bhuyan B.J., Mugesh G., Isaac R.E., RA Sturrock E.D., Acharya K.R.; RT "Structural characterization of angiotensin I-converting enzyme in complex RT with a selenium analogue of captopril."; RL FEBS J. 278:3644-3650(2011). RN [63] {ECO:0007744|PDB:4APH, ECO:0007744|PDB:4APJ} RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 642-1230 IN COMPLEX WITH ZINC, RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND GLYCOSYLATION AT ASN-677 AND RP ASN-714. RX PubMed=23056909; DOI=10.1038/srep00717; RA Masuyer G., Schwager S.L., Sturrock E.D., Isaac R.E., Acharya K.R.; RT "Molecular recognition and regulation of human angiotensin-I converting RT enzyme (ACE) activity by natural inhibitory peptides."; RL Sci. Rep. 2:717-717(2012). RN [64] {ECO:0007744|PDB:4C2N, ECO:0007744|PDB:4C2O, ECO:0007744|PDB:4C2P, ECO:0007744|PDB:4C2Q, ECO:0007744|PDB:4C2R} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 69-732 IN COMPLEX WITH ZINC RP (ISOFORM TESTIS-SPECIFIC), FUNCTION, COFACTOR, GLYCOSYLATION AT ASN-103 AND RP ASN-140 (ISOFORM TESTIS-SPECIFIC), AND MUTAGENESIS OF ARG-553 (ISOFORM RP TESTIS-SPECIFIC). RX PubMed=24297181; DOI=10.1074/jbc.m113.512335; RA Yates C.J., Masuyer G., Schwager S.L., Akif M., Sturrock E.D., RA Acharya K.R.; RT "Molecular and thermodynamic mechanisms of the chloride-dependent human RT angiotensin-I-converting enzyme (ACE)."; RL J. Biol. Chem. 289:1798-1814(2014). RN [65] {ECO:0007744|PDB:4UFA, ECO:0007744|PDB:4UFB} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 30-657 IN COMPLEX WITH ZINC, RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND GLYCOSYLATION AT ASN-74; RP ASN-445 AND ASN-509. RX PubMed=26403559; DOI=10.1038/srep13742; RA Masuyer G., Douglas R.G., Sturrock E.D., Acharya K.R.; RT "Structural basis of Ac-SDKP hydrolysis by Angiotensin-I converting RT enzyme."; RL Sci. Rep. 5:13742-13742(2015). RN [66] RP INVOLVEMENT IN MVCD3. RX PubMed=10099885; RA Vleming L.J., van der Pijl J.W., Lemkes H.H.P.J., Westendorp R.G.J., RA Maassen J.A., Daha M.R., van Es L.A., van Kooten C.; RT "The DD genotype of the ACE gene polymorphism is associated with RT progression of diabetic nephropathy to end stage renal failure in IDDM."; RL Clin. Nephrol. 51:133-140(1999). RN [67] RP VARIANTS THR-1018; VAL-1051; GLN-1279; SER-1286 AND PRO-1296. RX PubMed=10391210; DOI=10.1038/10297; RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., RA Cooper R., Lipshutz R., Chakravarti A.; RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood- RT pressure homeostasis."; RL Nat. Genet. 22:239-247(1999). RN [68] RP VARIANT LEU-1228, AND ASSOCIATION WITH BENIGN SERUM INCREASE OF RP ANGIOTENSIN-CONVERTING ENZYME. RX PubMed=11551873; DOI=10.1161/hc3601.095932; RA Kramers C., Danilov S.M., Deinum J., Balyasnikova I.V., Scharenborg N., RA Looman M., Boomsma F., de Keijzer M.H., van Duijn C., Martin S., RA Soubrier F., Adema G.J.; RT "Point mutation in the stalk of angiotensin-converting enzyme causes a RT dramatic increase in serum angiotensin-converting enzyme but no RT cardiovascular disease."; RL Circulation 104:1236-1240(2001). RN [69] RP VARIANT LEU-1228, AND ASSOCIATION WITH BENIGN SERUM INCREASE OF RP ANGIOTENSIN-CONVERTING ENZYME. RX PubMed=14694062; DOI=10.1212/01.wnl.0000098990.12845.da; RA Linnebank M., Kesper K., Jeub M., Urbach H., Wuellner U., Klockgether T., RA Schmidt S.; RT "Hereditary elevation of angiotensin converting enzyme suggesting RT neurosarcoidosis."; RL Neurology 61:1819-1820(2003). RN [70] RP INVOLVEMENT IN SUSCEPTIBILITY TO ISCHSTR. RX PubMed=15534175; DOI=10.1001/archneur.61.11.1652; RA Casas J.P., Hingorani A.D., Bautista L.E., Sharma P.; RT "Meta-analysis of genetic studies in ischemic stroke: thirty-two genes RT involving approximately 18,000 cases and 58,000 controls."; RL Arch. Neurol. 61:1652-1661(2004). RN [71] RP INVOLVEMENT IN SUSCEPTIBILITY TO ICH. RX PubMed=15277638; DOI=10.1212/01.wnl.0000130200.12993.0c; RA Slowik A., Turaj W., Dziedzic T., Haefele A., Pera J., Malecki M.T., RA Glodzik-Sobanska L., Szermer P., Figlewicz D.A., Szczudlik A.; RT "DD genotype of ACE gene is a risk factor for intracerebral hemorrhage."; RL Neurology 63:359-361(2004). RN [72] RP INVOLVEMENT IN RTD, AND VARIANT ARG-354. RX PubMed=16116425; DOI=10.1038/ng1623; RA Gribouval O., Gonzales M., Neuhaus T., Aziza J., Bieth E., Laurent N., RA Bouton J.M., Feuillet F., Makni S., Ben Amar H., Laube G., Delezoide A.-L., RA Bouvier R., Dijoud F., Ollagnon-Roman E., Roume J., Joubert M., RA Antignac C., Gubler M.-C.; RT "Mutations in genes in the renin-angiotensin system are associated with RT autosomal recessive renal tubular dysgenesis."; RL Nat. Genet. 37:964-968(2005). RN [73] RP VARIANT ASN-295. RX PubMed=25787250; DOI=10.1073/pnas.1503696112; RA Cromer M.K., Choi M., Nelson-Williams C., Fonseca A.L., Kunstman J.W., RA Korah R.M., Overton J.D., Mane S., Kenney B., Malchoff C.D., Stalberg P., RA Akerstroem G., Westin G., Hellman P., Carling T., Bjoerklund P., RA Lifton R.P.; RT "Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in RT insulin-producing adenomas."; RL Proc. Natl. Acad. Sci. U.S.A. 112:4062-4067(2015). CC -!- FUNCTION: Dipeptidyl carboxypeptidase that removes dipeptides from the CC C-terminus of a variety of circulating hormones, such as angiotensin I, CC bradykinin or enkephalins, thereby playing a key role in the regulation CC of blood pressure, electrolyte homeostasis or synaptic plasticity CC (PubMed:15615692, PubMed:20826823, PubMed:2558109, PubMed:4322742, CC PubMed:7523412, PubMed:7683654). Composed of two similar catalytic CC domains, each possessing a functional active site, with different CC selectivity for substrates (PubMed:10913258, PubMed:1320019, CC PubMed:1851160, PubMed:19773553, PubMed:7683654, PubMed:7876104). Plays CC a major role in the angiotensin-renin system that regulates blood CC pressure and sodium retention by the kidney by converting angiotensin I CC to angiotensin II, resulting in an increase of the vasoconstrictor CC activity of angiotensin (PubMed:11432860, PubMed:1851160, CC PubMed:19773553, PubMed:23056909, PubMed:4322742). Also able to CC inactivate bradykinin, a potent vasodilator, and therefore enhance the CC blood pressure response (PubMed:15615692, PubMed:2558109, CC PubMed:4322742, PubMed:6055465, PubMed:6270633, PubMed:7683654). Acts CC as a regulator of synaptic transmission by mediating cleavage of CC neuropeptide hormones, such as substance P, neurotensin or enkephalins CC (PubMed:15615692, PubMed:6208535, PubMed:6270633, PubMed:656131). CC Catalyzes degradation of different enkephalin neuropeptides (Met- CC enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met- CC enkephalin-Arg-Gly-Leu) (PubMed:2982830, PubMed:6270633, CC PubMed:656131). Acts as a regulator of synaptic plasticity in the CC nucleus accumbens of the brain by mediating cleavage of Met-enkephalin- CC Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met- CC enkephalin (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE CC decreases activation of OPRM1, leading to long-term synaptic CC potentiation of glutamate release (By similarity). Also acts as a CC regulator of hematopoietic stem cell differentiation by mediating CC degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) CC (PubMed:26403559, PubMed:7876104, PubMed:8257427, PubMed:8609242). Acts CC as a regulator of cannabinoid signaling pathway by mediating CC degradation of hemopressin, an antagonist peptide of the cannabinoid CC receptor CNR1 (PubMed:18077343). Involved in amyloid-beta metabolism by CC catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta CC protein 42 peptides, thereby preventing plaque formation CC (PubMed:11604391, PubMed:16154999, PubMed:19773553). Catalyzes cleavage CC of cholecystokinin (maturation of Cholecystokinin-8 and CC Cholecystokinin-5) and Gonadoliberin-1 (both maturation and CC degradation) hormones (PubMed:10336644, PubMed:2983326, PubMed:7683654, CC PubMed:9371719). Degradation of hemoregulatory peptide N-acetyl-SDKP CC (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal CC catalytic domain, while angiotensin I and cholecystokinin cleavage is CC mediated by the C-terminal catalytic region (PubMed:10336644, CC PubMed:19773553, PubMed:7876104). {ECO:0000250|UniProtKB:P09470, CC ECO:0000269|PubMed:10336644, ECO:0000269|PubMed:10913258, CC ECO:0000269|PubMed:11432860, ECO:0000269|PubMed:11604391, CC ECO:0000269|PubMed:1320019, ECO:0000269|PubMed:15615692, CC ECO:0000269|PubMed:16154999, ECO:0000269|PubMed:18077343, CC ECO:0000269|PubMed:1851160, ECO:0000269|PubMed:19773553, CC ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:23056909, CC ECO:0000269|PubMed:2558109, ECO:0000269|PubMed:26403559, CC ECO:0000269|PubMed:2982830, ECO:0000269|PubMed:2983326, CC ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6055465, CC ECO:0000269|PubMed:6208535, ECO:0000269|PubMed:6270633, CC ECO:0000269|PubMed:656131, ECO:0000269|PubMed:7523412, CC ECO:0000269|PubMed:7683654, ECO:0000269|PubMed:7876104, CC ECO:0000269|PubMed:8257427, ECO:0000269|PubMed:8609242, CC ECO:0000269|PubMed:9371719}. CC -!- FUNCTION: [Angiotensin-converting enzyme, soluble form]: Soluble form CC that is released in blood plasma and other body fluids following CC proteolytic cleavage in the juxtamembrane stalk region. CC {ECO:0000269|PubMed:10769174, ECO:0000269|PubMed:11274151, CC ECO:0000269|PubMed:7499427, ECO:0000269|PubMed:8253769}. CC -!- FUNCTION: [Isoform Testis-specific]: Isoform produced by alternative CC promoter usage that is specifically expressed in spermatocytes and CC adult testis, and which is required for male fertility (PubMed:1651327, CC PubMed:1668266). In contrast to somatic isoforms, only contains one CC catalytic domain (PubMed:1651327, PubMed:1668266). Acts as a dipeptidyl CC carboxypeptidase that removes dipeptides from the C-terminus of CC substrates (PubMed:1668266, PubMed:24297181). The identity of CC substrates that are needed for male fertility is unknown (By CC similarity). May also have a glycosidase activity which releases GPI- CC anchored proteins from the membrane by cleaving the mannose linkage in CC the GPI moiety. The GPIase activity was reported to be essential for CC the egg-binding ability of the sperm (By similarity). This activity is CC however unclear and has been challenged by other groups, suggesting CC that it may be indirect (By similarity). {ECO:0000250|UniProtKB:P09470, CC ECO:0000269|PubMed:1651327, ECO:0000269|PubMed:1668266, CC ECO:0000269|PubMed:24297181}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, CC when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion CC of angiotensin I to angiotensin II, with increase in vasoconstrictor CC activity, but no action on angiotensin II.; EC=3.4.15.1; CC Evidence={ECO:0000269|PubMed:10913258, ECO:0000269|PubMed:11076943, CC ECO:0000269|PubMed:12542396, ECO:0000269|PubMed:1320019, CC ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:2558109, CC ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:7961923}; CC -!- CATALYTIC ACTIVITY: CC Reaction=angiotensin I + H2O = L-histidyl-L-leucine + angiotensin II; CC Xref=Rhea:RHEA:63560, ChEBI:CHEBI:15377, ChEBI:CHEBI:58506, CC ChEBI:CHEBI:147350, ChEBI:CHEBI:147392; EC=3.4.15.1; CC Evidence={ECO:0000269|PubMed:11432860, ECO:0000269|PubMed:1851160, CC ECO:0000269|PubMed:19773553, ECO:0000269|PubMed:23056909, CC ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6270633}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63561; CC Evidence={ECO:0000269|PubMed:11432860, ECO:0000269|PubMed:1851160, CC ECO:0000269|PubMed:19773553, ECO:0000269|PubMed:23056909, CC ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6270633}; CC -!- CATALYTIC ACTIVITY: CC Reaction=bradykinin + H2O = L-Phe-L-Arg + bradykinin(1-7); CC Xref=Rhea:RHEA:71451, ChEBI:CHEBI:15377, ChEBI:CHEBI:132988, CC ChEBI:CHEBI:133147, ChEBI:CHEBI:147352; CC Evidence={ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6055465, CC ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:7683654, CC ECO:0000305|PubMed:2558109}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71452; CC Evidence={ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6055465, CC ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:7683654, CC ECO:0000305|PubMed:2558109}; CC -!- CATALYTIC ACTIVITY: CC Reaction=substance P + H2O = substance P(1-9) + L-Leu-L-Met-NH2; CC Xref=Rhea:RHEA:71459, ChEBI:CHEBI:15377, ChEBI:CHEBI:190692, CC ChEBI:CHEBI:190693, ChEBI:CHEBI:190700; CC Evidence={ECO:0000269|PubMed:6208535}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71460; CC Evidence={ECO:0000269|PubMed:6208535}; CC -!- CATALYTIC ACTIVITY: CC Reaction=substance P + H2O = substance P(1-8) + Gly-L-Leu-L-Met-NH2; CC Xref=Rhea:RHEA:71463, ChEBI:CHEBI:15377, ChEBI:CHEBI:190692, CC ChEBI:CHEBI:190694, ChEBI:CHEBI:190699; CC Evidence={ECO:0000269|PubMed:6208535}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71464; CC Evidence={ECO:0000269|PubMed:6208535}; CC -!- CATALYTIC ACTIVITY: CC Reaction=substance P + H2O = L-Phe-L-Phe-Gly-L-Leu-L-Met-NH2 + CC substance P(1-6); Xref=Rhea:RHEA:71471, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:190692, ChEBI:CHEBI:190696, ChEBI:CHEBI:190697; CC Evidence={ECO:0000269|PubMed:6208535}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71472; CC Evidence={ECO:0000269|PubMed:6208535}; CC -!- CATALYTIC ACTIVITY: CC Reaction=neurotensin + H2O = neurotensin(1-11) + L-isoleucyl-L-leucine; CC Xref=Rhea:RHEA:71475, ChEBI:CHEBI:15377, ChEBI:CHEBI:147362, CC ChEBI:CHEBI:190704, ChEBI:CHEBI:190706; CC Evidence={ECO:0000269|PubMed:6208535}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71476; CC Evidence={ECO:0000269|PubMed:6208535}; CC -!- CATALYTIC ACTIVITY: CC Reaction=goralatide + H2O = N-acetyl-L-seryl-L-aspartate + L-lysyl-L- CC proline; Xref=Rhea:RHEA:71455, ChEBI:CHEBI:15377, ChEBI:CHEBI:190701, CC ChEBI:CHEBI:190702, ChEBI:CHEBI:190703; CC Evidence={ECO:0000269|PubMed:26403559, ECO:0000269|PubMed:7876104, CC ECO:0000269|PubMed:8257427}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71456; CC Evidence={ECO:0000269|PubMed:26403559, ECO:0000269|PubMed:7876104, CC ECO:0000269|PubMed:8257427}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Met-enkephalin + H2O = L-phenylalanyl-L-methionine + L- CC tyrosylglycylglycine; Xref=Rhea:RHEA:71483, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:189868, ChEBI:CHEBI:190708, ChEBI:CHEBI:190709; CC Evidence={ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:656131}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71484; CC Evidence={ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:656131}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Leu-enkephalin + H2O = L-tyrosylglycylglycine + L- CC phenylalanyl-L-leucine; Xref=Rhea:RHEA:71487, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:190689, ChEBI:CHEBI:190708, ChEBI:CHEBI:190710; CC Evidence={ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:656131}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71488; CC Evidence={ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:656131}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Met-enkephalin-Arg-Phe + H2O = L-arginyl-L-phenylalanine + CC Met-enkephalin; Xref=Rhea:RHEA:70675, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:189868, ChEBI:CHEBI:189869, ChEBI:CHEBI:189870; CC Evidence={ECO:0000250|UniProtKB:P09470}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70676; CC Evidence={ECO:0000250|UniProtKB:P09470}; CC -!- CATALYTIC ACTIVITY: [Isoform Testis-specific]: CC Reaction=Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, CC when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion CC of angiotensin I to angiotensin II, with increase in vasoconstrictor CC activity, but no action on angiotensin II.; EC=3.4.15.1; CC Evidence={ECO:0000269|PubMed:1668266}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:12540854, ECO:0000269|PubMed:16476442, CC ECO:0000269|PubMed:1649623, ECO:0000269|PubMed:20826823, CC ECO:0000269|PubMed:23056909, ECO:0000269|PubMed:26403559, CC ECO:0000269|PubMed:7961923}; CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:12540854, CC ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:1649623}; CC -!- COFACTOR: [Isoform Testis-specific]: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:1649623, ECO:0000269|PubMed:21810173, CC ECO:0000269|PubMed:24297181}; CC Note=Isoform Testis-specific only binds 1 Zn(2+) ion per subunit. CC {ECO:0000269|PubMed:1649623, ECO:0000269|PubMed:21810173, CC ECO:0000269|PubMed:24297181}; CC -!- COFACTOR: CC Name=chloride; Xref=ChEBI:CHEBI:17996; CC Evidence={ECO:0000269|PubMed:11432860, ECO:0000269|PubMed:12540854, CC ECO:0000269|PubMed:16476442}; CC Note=Binds 3 chloride ions per subunit. {ECO:0000269|PubMed:12540854, CC ECO:0000269|PubMed:16476442}; CC -!- COFACTOR: [Isoform Testis-specific]: CC Name=chloride; Xref=ChEBI:CHEBI:17996; CC Evidence={ECO:0000269|PubMed:24297181}; CC -!- ACTIVITY REGULATION: The dipeptidyl carboxypeptidase activity is CC strongly activated by chloride (PubMed:11432860, PubMed:12540854, CC PubMed:15615692, PubMed:16476442, PubMed:7683654). The dipeptidyl CC carboxypeptidase activity is specifically inhibited by lisinopril, CC captopril and enalaprilat (PubMed:12540854, PubMed:1320019, CC PubMed:16476442, PubMed:6208535, PubMed:6270633, PubMed:7876104, CC PubMed:8609242). {ECO:0000269|PubMed:11432860, CC ECO:0000269|PubMed:12540854, ECO:0000269|PubMed:1320019, CC ECO:0000269|PubMed:15615692, ECO:0000269|PubMed:16476442, CC ECO:0000269|PubMed:6208535, ECO:0000269|PubMed:6270633, CC ECO:0000269|PubMed:7683654, ECO:0000269|PubMed:7876104, CC ECO:0000269|PubMed:8609242}. CC -!- ACTIVITY REGULATION: [Isoform Testis-specific]: Strongly inhibited by CC lisinopril and captopril. {ECO:0000269|PubMed:1668266, CC ECO:0000269|PubMed:21810173}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=2.51 mM for Hip-His-Leu {ECO:0000269|PubMed:11076943, CC ECO:0000269|PubMed:12542396}; CC KM=30 uM for angiotensin I {ECO:0000305|PubMed:6270633}; CC KM=16 uM for angiotensin I {ECO:0000269|PubMed:1851160}; CC KM=1 uM for bradykinin {ECO:0000305|PubMed:6270633}; CC KM=0.18 uM for bradykinin {ECO:0000269|PubMed:7683654}; CC KM=1000 uM for Met-enkephalin {ECO:0000269|PubMed:6270633}; CC KM=1000 uM for Leu-enkephalin {ECO:0000269|PubMed:6270633}; CC KM=41 uM for hemoregulatory peptide N-acetyl-SDKP (AcSDKP) CC {ECO:0000269|PubMed:7876104}; CC KM=31 uM for hemoregulatory peptide N-acetyl-SDKP (AcSDKP) for the CC active site at the N-terminus {ECO:0000269|PubMed:7876104}; CC KM=39 uM for hemoregulatory peptide N-acetyl-SDKP (AcSDKP) for the CC active site at the C-terminus {ECO:0000269|PubMed:7876104}; CC KM=9 uM for GWMDFGRR peptide (Cholecystokinin-5-GRR) CC {ECO:0000269|PubMed:9371719}; CC Note=kcat is 500 min(-1) for angiotensin I (PubMed:6270633). kcat is CC 500 min(-1) for bradykinin (PubMed:6270633). kcat is 3500 min(-1) for CC Met-enkephalin (PubMed:6270633). kcat is 700 min(-1) for CC Leu-enkephalin (PubMed:6270633). kcat is 12 sec(-1) for the CC hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:7876104). CC {ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:7876104}; CC -!- SUBUNIT: Monomer and homodimer; homodimerizes following binding to an CC inhibitor (PubMed:16476786). Interacts with calmodulin (CALM1, CALM2 or CC CALM3); interaction takes place in the cytoplasmic region and regulates CC phosphorylation and proteolytic cleavage (By similarity). CC {ECO:0000250|UniProtKB:P12822, ECO:0000269|PubMed:16476786}. CC -!- INTERACTION: CC P12821-3; P05556: ITGB1; NbExp=2; IntAct=EBI-25497695, EBI-703066; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12386153}; CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasm CC {ECO:0000250|UniProtKB:P09470}. Note=Detected in both cell membrane and CC cytoplasm in neurons. {ECO:0000250|UniProtKB:P09470}. CC -!- SUBCELLULAR LOCATION: [Angiotensin-converting enzyme, soluble form]: CC Secreted {ECO:0000269|PubMed:10769174, ECO:0000269|PubMed:11274151, CC ECO:0000269|PubMed:7499427, ECO:0000269|PubMed:8253769}. CC -!- SUBCELLULAR LOCATION: [Isoform Testis-specific]: Cell membrane CC {ECO:0000269|PubMed:1668266, ECO:0000269|PubMed:8626443}; Single-pass CC type I membrane protein {ECO:0000255}. Secreted CC {ECO:0000269|PubMed:1668266}. Note=The testis-specific isoform can be CC cleaved before the transmembrane region, releasing a soluble form. CC {ECO:0000269|PubMed:1668266}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=4; CC Name=Somatic-1; CC IsoId=P12821-1; Sequence=Displayed; CC Name=Somatic-2; Synonyms=Soluble; CC IsoId=P12821-2; Sequence=VSP_029932, VSP_029933; CC Name=Testis-specific; Synonyms=ACE-T, ACEt CC {ECO:0000303|PubMed:8626443}, tACE {ECO:0000303|PubMed:1668266, CC ECO:0000303|PubMed:21810173}, hTACE {ECO:0000303|PubMed:1668266}; CC IsoId=P12821-3, P22966-1; Sequence=VSP_035120, VSP_035121; CC Name=4; CC IsoId=P12821-4; Sequence=VSP_054836, VSP_054837; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in CC lung, kidney, heart, gastrointestinal system and prostate. CC {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042, CC ECO:0000269|PubMed:12459472, ECO:0000269|PubMed:15671045}. CC -!- TISSUE SPECIFICITY: [Isoform Testis-specific]: Specifically expressed CC in spermatocytes and adult testis. {ECO:0000269|PubMed:2547653, CC ECO:0000269|PubMed:2554286}. CC -!- INDUCTION: Up-regulated in failing heart. {ECO:0000269|PubMed:15151696, CC ECO:0000269|PubMed:15671045}. CC -!- PTM: [Angiotensin-converting enzyme, soluble form]: Produced following CC proteolytic cleavage by secretase enzymes that cleave the transmembrane CC form in the juxtamembrane stalk region upstream of the transmembrane CC region (PubMed:10769174, PubMed:11274151, PubMed:7499427, CC PubMed:8253769). Cleavage can take place at different sites of the CC juxtamembrane stalk region (PubMed:10769174, PubMed:11274151, CC PubMed:7499427, PubMed:8253769). {ECO:0000269|PubMed:10769174, CC ECO:0000269|PubMed:11274151, ECO:0000269|PubMed:7499427, CC ECO:0000269|PubMed:8253769}. CC -!- PTM: Phosphorylated by CK2 on Ser-1299; which allows membrane retention CC (PubMed:12386153). Phosphorylated on tyrosine residues on its CC extracellular part, promoting cleavage by secretase enzymes and CC formation of the soluble form (Angiotensin-converting enzyme, soluble CC form) (By similarity). {ECO:0000250|UniProtKB:P12822, CC ECO:0000269|PubMed:12386153}. CC -!- POLYMORPHISM: Genetic variants in ACE are associated with CC interindividual variability of angiotensin I-converting enzyme plasma CC levels [MIM:621420]. {ECO:0000269|PubMed:11076943, CC ECO:0000269|PubMed:11551873, ECO:0000269|PubMed:14694062}. CC -!- DISEASE: Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute CC neurologic event leading to death of neural tissue of the brain and CC resulting in loss of motor, sensory and/or cognitive function. Ischemic CC strokes, resulting from vascular occlusion, is considered to be a CC highly complex disease consisting of a group of heterogeneous disorders CC with multiple genetic and environmental risk factors. CC {ECO:0000269|PubMed:15534175}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal CC recessive severe disorder of renal tubular development characterized by CC persistent fetal anuria and perinatal death, probably due to pulmonary CC hypoplasia from early-onset oligohydramnios (the Potter phenotype). CC {ECO:0000269|PubMed:16116425}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Microvascular complications of diabetes 3 (MVCD3) CC [MIM:612624]: Pathological conditions that develop in numerous tissues CC and organs as a consequence of diabetes mellitus. They include diabetic CC retinopathy, diabetic nephropathy leading to end-stage renal disease, CC and diabetic neuropathy. Diabetic retinopathy remains the major cause CC of new-onset blindness among diabetic adults. It is characterized by CC vascular permeability and increased tissue ischemia and angiogenesis. CC {ECO:0000269|PubMed:10099885}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Intracerebral hemorrhage (ICH) [MIM:614519]: A pathological CC condition characterized by bleeding into one or both cerebral CC hemispheres including the basal ganglia and the cerebral cortex. It is CC often associated with hypertension and craniocerebral trauma. CC Intracerebral bleeding is a common cause of stroke. CC {ECO:0000269|PubMed:15277638}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Inhibitors of ACE are commonly used to treat CC hypertension and some types of renal and cardiac dysfunction. CC -!- MISCELLANEOUS: [Isoform Somatic-2]: Incomplete sequence. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92208.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J04144; AAA51684.1; -; mRNA. DR EMBL; M26657; AAA60611.1; -; mRNA. DR EMBL; X16295; CAA34362.1; -; mRNA. DR EMBL; AF118569; AAD28560.1; -; Genomic_DNA. DR EMBL; AY436326; AAR03504.1; -; Genomic_DNA. DR EMBL; AK301988; BAG63395.1; -; mRNA. DR EMBL; EU332840; ABY87529.1; -; Genomic_DNA. DR EMBL; AB208971; BAD92208.1; ALT_INIT; mRNA. DR EMBL; AC113554; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS11637.1; -. [P12821-1] DR CCDS; CCDS45755.1; -. [P12821-3] DR CCDS; CCDS54155.1; -. [P12821-4] DR PIR; A31759; A31759. DR PIR; PW0053; PW0053. DR PIR; S05238; S05238. DR RefSeq; NP_000780.1; NM_000789.4. [P12821-1] DR RefSeq; NP_001171528.1; NM_001178057.2. [P12821-4] DR RefSeq; NP_690043.1; NM_152830.3. [P12821-3] DR PDB; 1O86; X-ray; 2.00 A; A=642-1230. DR PDB; 1O8A; X-ray; 2.00 A; A=642-1230. DR PDB; 1UZE; X-ray; 1.82 A; A=642-1230. DR PDB; 1UZF; X-ray; 2.00 A; A=642-1230. DR PDB; 2C6F; X-ray; 3.01 A; A/B=30-641. DR PDB; 2C6N; X-ray; 3.00 A; A/B=30-641. DR PDB; 2IUL; X-ray; 2.01 A; A=642-1232. DR PDB; 2IUX; X-ray; 2.80 A; A=642-1232. DR PDB; 2OC2; X-ray; 2.25 A; A=642-1232. DR PDB; 2XY9; X-ray; 1.97 A; A=645-1228. DR PDB; 2XYD; X-ray; 2.15 A; A/B=30-639. DR PDB; 2YDM; X-ray; 2.44 A; A=642-1230. DR PDB; 3BKK; X-ray; 2.17 A; A=642-1232. DR PDB; 3BKL; X-ray; 2.18 A; A=642-1232. DR PDB; 3L3N; X-ray; 2.30 A; A=642-1232. DR PDB; 3NXQ; X-ray; 1.99 A; A/B=30-658. DR PDB; 4APH; X-ray; 1.99 A; A=642-1230. DR PDB; 4APJ; X-ray; 2.60 A; A=642-1230. DR PDB; 4BXK; X-ray; 2.20 A; A/B=30-657. DR PDB; 4BZR; X-ray; 1.84 A; A=642-1230. DR PDB; 4BZS; X-ray; 2.10 A; A/B=30-657. DR PDB; 4C2N; X-ray; 2.59 A; A=642-1230. DR PDB; 4C2O; X-ray; 1.80 A; A=642-1230. DR PDB; 4C2P; X-ray; 1.99 A; A=642-1230. DR PDB; 4C2Q; X-ray; 2.40 A; A=642-1230. DR PDB; 4C2R; X-ray; 2.30 A; A=642-1230. DR PDB; 4CA5; X-ray; 1.85 A; A=642-1230. DR PDB; 4CA6; X-ray; 1.91 A; A/B=30-639. DR PDB; 4UFA; X-ray; 1.80 A; A/B=30-657. DR PDB; 4UFB; X-ray; 1.80 A; A/B/C/D=30-657. DR PDB; 5AM8; X-ray; 1.90 A; A/B/C/D=30-658. DR PDB; 5AM9; X-ray; 1.80 A; A/B/C/D=30-658. DR PDB; 5AMA; X-ray; 1.80 A; A/B/C/D=30-658. DR PDB; 5AMB; X-ray; 1.55 A; A/B=30-658. DR PDB; 5AMC; X-ray; 1.65 A; A/B=30-658. DR PDB; 6EN5; X-ray; 1.75 A; A/B/C/D=30-657. DR PDB; 6EN6; X-ray; 1.80 A; A/B/C/D=30-657. DR PDB; 6F9R; X-ray; 1.85 A; A/B=30-657. DR PDB; 6F9T; X-ray; 1.60 A; A=642-1232. DR PDB; 6F9U; X-ray; 1.90 A; A=642-1232. DR PDB; 6F9V; X-ray; 1.69 A; A/B=30-657. DR PDB; 6H5W; X-ray; 1.37 A; A=642-1232. DR PDB; 6H5X; X-ray; 1.80 A; A/B=30-657. DR PDB; 6QS1; X-ray; 1.80 A; A/B=30-657. DR PDB; 6TT1; X-ray; 1.80 A; A/B=30-657. DR PDB; 6TT3; X-ray; 1.70 A; A/B=30-657. DR PDB; 6TT4; X-ray; 1.80 A; A/B=30-657. DR PDB; 6ZPQ; X-ray; 1.85 A; A/B/C/D=30-657. DR PDB; 6ZPT; X-ray; 2.80 A; A/B/C/D=30-657. DR PDB; 6ZPU; X-ray; 2.00 A; A=642-1238. DR PDB; 7Q24; X-ray; 2.00 A; A/B=30-657. DR PDB; 7Q25; X-ray; 1.60 A; A/B=30-657. DR PDB; 7Q26; X-ray; 1.70 A; A/B=30-657. DR PDB; 7Q27; X-ray; 1.50 A; A=642-1238. DR PDB; 7Q28; X-ray; 1.65 A; A=642-1238. DR PDB; 7Q29; X-ray; 1.60 A; A=642-1238. DR PDB; 7Q3Y; EM; 4.34 A; A=30-1240. DR PDB; 7Q49; EM; 3.72 A; A=30-1240. DR PDB; 7Q4C; EM; 4.08 A; A=30-1240. DR PDB; 7Q4D; EM; 3.78 A; A/B=30-1240. DR PDB; 7Q4E; EM; 3.63 A; A=30-1240. DR PDB; 7Z6Z; X-ray; 1.75 A; A/B=30-657. DR PDB; 7Z70; X-ray; 1.85 A; A=642-1238. DR PDB; 8QFX; X-ray; 1.60 A; A/B/C/D=30-657. DR PDB; 8QHL; X-ray; 1.90 A; A/B=30-657. DR PDB; 9CLX; EM; 3.65 A; A/B=1-1235. DR PDB; 9D55; EM; 3.15 A; A/B=1-1235. DR PDB; 9D5M; EM; 3.05 A; A/B=1-1235. DR PDB; 9D5S; EM; 2.99 A; 1/A=1-1235. DR PDB; 9GBL; X-ray; 2.40 A; A=642-1238. DR PDB; 9GBM; X-ray; 1.90 A; A=642-1238. DR PDB; 9GBN; X-ray; 2.00 A; A=642-1238. DR PDB; 9GBO; X-ray; 2.00 A; A=642-1238. DR PDB; 9GBP; X-ray; 2.00 A; A/B=30-657. DR PDB; 9GBQ; X-ray; 1.90 A; A/B=30-657. DR PDB; 9GBR; X-ray; 1.90 A; A/B=30-657. DR PDB; 9GBS; X-ray; 1.90 A; A/B=30-657. DR PDB; 9H1A; X-ray; 1.85 A; A/B=30-657. DR PDB; 9H1B; X-ray; 1.70 A; A/B=30-657. DR PDB; 9H1C; X-ray; 1.80 A; A=642-1238. DR PDB; 9H1D; X-ray; 1.80 A; A=642-1238. DR PDB; 9H1E; X-ray; 1.45 A; A=642-1238. DR PDB; 9QAM; X-ray; 1.85 A; A=645-1222. DR PDB; 9QAN; X-ray; 1.50 A; A=642-1238. DR PDB; 9QAO; X-ray; 2.30 A; A=645-1222. DR PDB; 9QAP; X-ray; 1.50 A; A=645-1222. DR PDB; 9QAQ; X-ray; 1.90 A; A=645-1222. DR PDB; 9QAR; X-ray; 2.00 A; A/B=30-638. DR PDB; 9QAS; X-ray; 2.20 A; A/B=30-638. DR PDB; 9QAT; X-ray; 2.20 A; A/B=30-638. DR PDB; 9QAU; X-ray; 2.00 A; A/B=30-637. DR PDB; 9QAV; X-ray; 2.30 A; A/B=30-638. DR PDB; 9SS7; X-ray; 1.95 A; A=646-1229. DR PDB; 9SS8; X-ray; 2.00 A; A/B=30-657. DR PDB; 9SS9; X-ray; 2.50 A; A/B=30-657. DR PDB; 9SSA; X-ray; 1.90 A; A=642-1238. DR PDB; 9SSB; X-ray; 2.00 A; A/B/C/D=30-657. DR AlphaFoldDB; P12821; -. DR EMDB; EMD-13797; -. DR EMDB; EMD-13799; -. DR EMDB; EMD-13801; -. DR EMDB; EMD-13802; -. DR EMDB; EMD-13803; -. DR EMDB; EMD-13804; -. DR EMDB; EMD-31073; -. DR EMDB; EMD-45733; -. DR EMDB; EMD-46574; -. DR EMDB; EMD-46579; -. DR EMDB; EMD-46581; -. DR MDposit; P12821; -. DR MDRepo; P12821; -. DR SMR; P12821; -. DR BioGRID; 108004; 22. DR CORUM; P12821; -. DR FunCoup; P12821; 323. DR IntAct; P12821; 8. DR MINT; P12821; -. DR NDEx; IQUERY-CP-ACE; 15 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000290866; -. DR BindingDB; P12821; -. DR ChEMBL; CHEMBL1808; -. DR DrugBank; DB14511; Acetate. DR DrugBank; DB21364; Alacepril. DR DrugBank; DB00542; Benazepril. DR DrugBank; DB04286; beta-D-Ribopyranose. DR DrugBank; DB00616; Candoxatril. DR DrugBank; DB01197; Captopril. DR DrugBank; DB01340; Cilazapril. DR DrugBank; DB15565; Cilazaprilat. DR DrugBank; DB13312; Delapril. DR DrugBank; DB01089; Deserpidine. DR DrugBank; DB00584; Enalapril. DR DrugBank; DB09477; Enalaprilat. DR DrugBank; DB02032; Epicaptopril. DR DrugBank; DB00492; Fosinopril. DR DrugBank; DB12923; Gallopamil. DR DrugBank; DB00999; Hydrochlorothiazide. DR DrugBank; DB19598; Idrapril. DR DrugBank; DB06604; Ilepatril. DR DrugBank; DB11783; Imidapril. DR DrugBank; DB12665; Isoquercetin. DR DrugBank; DB00722; Lisinopril. DR DrugBank; DB00691; Moexipril. DR DrugBank; DB14210; Moexiprilat. DR DrugBank; DB03740; N-acetyl-alpha-D-glucosamine. DR DrugBank; DB00886; Omapatrilat. DR DrugBank; DB00790; Perindopril. DR DrugBank; DB00881; Quinapril. DR DrugBank; DB00178; Ramipril. DR DrugBank; DB01180; Rescinnamine. DR DrugBank; DB01348; Spirapril. DR DrugBank; DB08836; Temocapril. DR DrugBank; DB00519; Trandolapril. DR DrugBank; DB20306; Utibapril. DR DrugBank; DB13166; Zofenopril. DR DrugCentral; P12821; -. DR GuidetoPHARMACOLOGY; 1613; -. DR MEROPS; M02.001; -. DR MEROPS; M02.004; -. DR GlyConnect; P12821; 23 N-Linked glycans (7 sites). DR GlyCosmos; P12821; 22 sites, 25 glycans. DR GlyGen; P12821; 20 sites, 124 N-linked glycans (13 sites). DR iPTMnet; P12821; -. DR PhosphoSitePlus; P12821; -. DR BioMuta; ACE; -. DR DMDM; 113045; -. DR CPTAC; CPTAC-2597; -. DR jPOST; P12821; -. DR MassIVE; P12821; -. DR PaxDb; 9606-ENSP00000290866; -. DR PeptideAtlas; P12821; -. DR ProteomicsDB; 52874; -. [P12821-1] DR ProteomicsDB; 52875; -. [P12821-2] DR ProteomicsDB; 52876; -. [P12821-3] DR ProteomicsDB; 52877; -. [P12821-4] DR ABCD; P12821; 1 sequenced antibody. DR Antibodypedia; 31288; 930 antibodies from 46 providers. DR DNASU; 1636; -. DR Ensembl; ENST00000290863.10; ENSP00000290863.6; ENSG00000159640.18. [P12821-3] DR Ensembl; ENST00000290866.10; ENSP00000290866.4; ENSG00000159640.18. [P12821-1] DR Ensembl; ENST00000413513.7; ENSP00000392247.3; ENSG00000159640.18. [P12821-4] DR GeneID; 1636; -. DR KEGG; hsa:1636; -. DR MANE-Select; ENST00000290866.10; ENSP00000290866.4; NM_000789.4; NP_000780.1. DR UCSC; uc002jau.3; human. [P12821-1] DR AGR; HGNC:2707; -. DR ClinPGx; PA139; -. DR CTD; 1636; -. DR DisGeNET; 1636; -. DR GeneCards; ACE; -. DR HGNC; HGNC:2707; ACE. DR HPA; ENSG00000159640; Tissue enhanced (intestine, testis). DR MalaCards; ACE; -. DR MIM; 106180; gene. DR MIM; 267430; phenotype. DR MIM; 601367; phenotype. DR MIM; 612624; phenotype. DR MIM; 614519; phenotype. DR MIM; 621420; phenotype. DR NIAGADS; ENSG00000159640; -. DR OpenTargets; ENSG00000159640; -. DR Orphanet; 97369; Renal tubular dysgenesis of genetic origin. DR VEuPathDB; HostDB:ENSG00000159640; -. DR eggNOG; KOG3690; Eukaryota. DR GeneTree; ENSGT00940000162051; -. DR HOGENOM; CLU_014364_3_0_1; -. DR InParanoid; P12821; -. DR OMA; GMPPEFW; -. DR OrthoDB; 10029630at2759; -. DR PAN-GO; P12821; 6 GO annotations based on evolutionary models. DR PhylomeDB; P12821; -. DR BioCyc; MetaCyc:HS08412-MONOMER; -. DR BRENDA; 3.4.15.1; 2681. DR PathwayCommons; P12821; -. DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins. DR SABIO-RK; P12821; -. DR SignaLink; P12821; -. DR SIGNOR; P12821; -. DR Agora; ENSG00000159640; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 1636; 16 hits in 1169 CRISPR screens. DR ChiTaRS; ACE; human. DR EvolutionaryTrace; P12821; -. DR GeneWiki; Angiotensin-converting_enzyme; -. DR GenomeRNAi; 1636; -. DR Pharos; P12821; Tclin. DR PRO; PR:P12821; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P12821; protein. DR Bgee; ENSG00000159640; Expressed in ileal mucosa and 109 other cell types or tissues. DR ExpressionAtlas; P12821; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005768; C:endosome; IDA:BHF-UCL. DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0003779; F:actin binding; IDA:UniProtKB. DR GO; GO:0031711; F:bradykinin receptor binding; IPI:BHF-UCL. DR GO; GO:0031404; F:chloride ion binding; IDA:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB. DR GO; GO:0008238; F:exopeptidase activity; IDA:BHF-UCL. DR GO; GO:0004181; F:metallocarboxypeptidase activity; IEA:Ensembl. DR GO; GO:0070573; F:metallodipeptidase activity; IDA:UniProtKB. DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB. DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB. DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:BHF-UCL. DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IPI:BHF-UCL. DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB. DR GO; GO:0008241; F:peptidyl-dipeptidase activity; IDA:UniProtKB. DR GO; GO:0008240; F:tripeptidyl-peptidase activity; IDA:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; IDA:BHF-UCL. DR GO; GO:0050435; P:amyloid-beta metabolic process; IDA:BHF-UCL. DR GO; GO:0002003; P:angiotensin maturation; IDA:UniProtKB. DR GO; GO:0038166; P:angiotensin-activated signaling pathway; ISS:BHF-UCL. DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:BHF-UCL. DR GO; GO:0050482; P:arachidonate secretion; IDA:BHF-UCL. DR GO; GO:0097746; P:blood vessel diameter maintenance; IC:BHF-UCL. DR GO; GO:0001974; P:blood vessel remodeling; IC:BHF-UCL. DR GO; GO:0010815; P:bradykinin catabolic process; IDA:UniProtKB. DR GO; GO:0071838; P:cell proliferation in bone marrow; ISS:BHF-UCL. DR GO; GO:0060047; P:heart contraction; ISS:BHF-UCL. DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IC:BHF-UCL. DR GO; GO:0042447; P:hormone catabolic process; IDA:UniProtKB. DR GO; GO:0042445; P:hormone metabolic process; IDA:UniProtKB. DR GO; GO:0001822; P:kidney development; IMP:BHF-UCL. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0032943; P:mononuclear cell proliferation; IC:BHF-UCL. DR GO; GO:1903597; P:negative regulation of gap junction assembly; ISS:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0002446; P:neutrophil mediated immunity; ISS:BHF-UCL. DR GO; GO:0043171; P:peptide catabolic process; IDA:BHF-UCL. DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IBA:GO_Central. DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IEA:Ensembl. DR GO; GO:0006508; P:proteolysis; TAS:UniProtKB. DR GO; GO:0060177; P:regulation of angiotensin metabolic process; IDA:BHF-UCL. DR GO; GO:0008217; P:regulation of blood pressure; ISS:BHF-UCL. DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISS:BHF-UCL. DR GO; GO:1902033; P:regulation of hematopoietic stem cell proliferation; ISS:BHF-UCL. DR GO; GO:0002019; P:regulation of renal output by angiotensin; IC:BHF-UCL. DR GO; GO:0014910; P:regulation of smooth muscle cell migration; ISS:BHF-UCL. DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB. DR GO; GO:0003081; P:regulation of systemic arterial blood pressure by renin-angiotensin; IMP:BHF-UCL. DR GO; GO:0019229; P:regulation of vasoconstriction; IC:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; ISS:BHF-UCL. DR GO; GO:0010814; P:substance P catabolic process; IDA:UniProtKB. DR CDD; cd06461; M2_ACE; 2. DR InterPro; IPR001548; Peptidase_M2. DR PANTHER; PTHR10514; ANGIOTENSIN-CONVERTING ENZYME; 1. DR PANTHER; PTHR10514:SF25; ANGIOTENSIN-CONVERTING ENZYME; 1. DR Pfam; PF01401; Peptidase_M2; 2. DR PRINTS; PR00791; PEPDIPTASEA. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 2. DR PROSITE; PS52011; PEPTIDASE_M2; 2. DR PROSITE; PS00142; ZINC_PROTEASE; 2. DR PDBsum; 1O86; -. DR PDBsum; 1O8A; -. DR PDBsum; 1UZE; -. DR PDBsum; 1UZF; -. DR PDBsum; 2C6F; -. DR PDBsum; 2C6N; -. DR PDBsum; 2IUL; -. DR PDBsum; 2IUX; -. DR PDBsum; 2OC2; -. DR PDBsum; 2XY9; -. DR PDBsum; 2XYD; -. DR PDBsum; 2YDM; -. DR PDBsum; 3BKK; -. DR PDBsum; 3BKL; -. DR PDBsum; 3L3N; -. DR PDBsum; 3NXQ; -. DR PDBsum; 4APH; -. DR PDBsum; 4APJ; -. DR PDBsum; 4BXK; -. DR PDBsum; 4BZR; -. DR PDBsum; 4BZS; -. DR PDBsum; 4C2N; -. DR PDBsum; 4C2O; -. DR PDBsum; 4C2P; -. DR PDBsum; 4C2Q; -. DR PDBsum; 4C2R; -. DR PDBsum; 4CA5; -. DR PDBsum; 4CA6; -. DR PDBsum; 4UFA; -. DR PDBsum; 4UFB; -. DR PDBsum; 5AM8; -. DR PDBsum; 5AM9; -. DR PDBsum; 5AMA; -. DR PDBsum; 5AMB; -. DR PDBsum; 5AMC; -. DR PDBsum; 6EN5; -. DR PDBsum; 6EN6; -. DR PDBsum; 6F9R; -. DR PDBsum; 6F9T; -. DR PDBsum; 6F9U; -. DR PDBsum; 6F9V; -. DR PDBsum; 6H5W; -. DR PDBsum; 6H5X; -. DR PDBsum; 6QS1; -. DR PDBsum; 6TT1; -. DR PDBsum; 6TT3; -. DR PDBsum; 6TT4; -. DR PDBsum; 6ZPQ; -. DR PDBsum; 6ZPT; -. DR PDBsum; 6ZPU; -. DR PDBsum; 7Q24; -. DR PDBsum; 7Q25; -. DR PDBsum; 7Q26; -. DR PDBsum; 7Q27; -. DR PDBsum; 7Q28; -. DR PDBsum; 7Q29; -. DR PDBsum; 7Q3Y; -. DR PDBsum; 7Q49; -. DR PDBsum; 7Q4C; -. DR PDBsum; 7Q4D; -. DR PDBsum; 7Q4E; -. DR PDBsum; 7Z6Z; -. DR PDBsum; 7Z70; -. DR PDBsum; 8QFX; -. DR PDBsum; 8QHL; -. DR PDBsum; 9CLX; -. DR PDBsum; 9D55; -. DR PDBsum; 9D5M; -. DR PDBsum; 9D5S; -. DR PDBsum; 9GBL; -. DR PDBsum; 9GBM; -. DR PDBsum; 9GBN; -. DR PDBsum; 9GBO; -. DR PDBsum; 9GBP; -. DR PDBsum; 9GBQ; -. DR PDBsum; 9GBR; -. DR PDBsum; 9GBS; -. DR PDBsum; 9H1A; -. DR PDBsum; 9H1B; -. DR PDBsum; 9H1C; -. DR PDBsum; 9H1D; -. DR PDBsum; 9H1E; -. DR PDBsum; 9QAM; -. DR PDBsum; 9QAN; -. DR PDBsum; 9QAO; -. DR PDBsum; 9QAP; -. DR PDBsum; 9QAQ; -. DR PDBsum; 9QAR; -. DR PDBsum; 9QAS; -. DR PDBsum; 9QAT; -. DR PDBsum; 9QAU; -. DR PDBsum; 9QAV; -. DR PDBsum; 9SS7; -. DR PDBsum; 9SS8; -. DR PDBsum; 9SS9; -. DR PDBsum; 9SSA; -. DR PDBsum; 9SSB; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative promoter usage; Alternative splicing; KW Calmodulin-binding; Carboxypeptidase; Cell membrane; Cytoplasm; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase; KW Membrane; Metal-binding; Metalloprotease; Phosphoprotein; Protease; KW Proteomics identification; Reference proteome; Repeat; Secreted; Signal; KW Transmembrane; Transmembrane helix; Zinc. FT SIGNAL 1..29 FT /evidence="ECO:0000269|PubMed:2558109" FT CHAIN 30..1306 FT /note="Angiotensin-converting enzyme" FT /id="PRO_0000028530" FT CHAIN 30..1232 FT /note="Angiotensin-converting enzyme, soluble form" FT /evidence="ECO:0000305|PubMed:10769174" FT /id="PRO_0000028531" FT TOPO_DOM 30..1256 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1257..1277 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1278..1306 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 40..624 FT /note="Peptidase M2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT DOMAIN 643..1222 FT /note="Peptidase M2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT REGION 1215..1256 FT /note="Juxtamembrane stalk" FT /evidence="ECO:0000269|PubMed:11274151" FT ACT_SITE 391 FT /note="Proton acceptor 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854, ECO:0000305|PubMed:16154999, FT ECO:0000305|PubMed:19773553" FT ACT_SITE 520 FT /note="Proton donor 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT ACT_SITE 989 FT /note="Proton acceptor 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854, ECO:0000305|PubMed:16154999, FT ECO:0000305|PubMed:19773553" FT ACT_SITE 1118 FT /note="Proton donor 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT BINDING 231 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:16476442" FT BINDING 390 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:20826823, FT ECO:0000269|PubMed:26403559, ECO:0007744|PDB:2OC2, FT ECO:0007744|PDB:3NXQ" FT BINDING 394 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:20826823, FT ECO:0000269|PubMed:26403559, ECO:0007744|PDB:2OC2, FT ECO:0007744|PDB:3NXQ" FT BINDING 418 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:20826823, FT ECO:0000269|PubMed:26403559, ECO:0007744|PDB:2OC2, FT ECO:0007744|PDB:3NXQ" FT BINDING 529 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:16476442" FT BINDING 791 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854" FT BINDING 829 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854" FT BINDING 988 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854, ECO:0000269|PubMed:16476442, FT ECO:0000269|PubMed:23056909, ECO:0007744|PDB:4APH" FT BINDING 992 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854, ECO:0000269|PubMed:16476442, FT ECO:0000269|PubMed:23056909, ECO:0007744|PDB:4APH" FT BINDING 1016 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854, ECO:0000269|PubMed:16476442, FT ECO:0000269|PubMed:23056909, ECO:0000269|PubMed:7961923, FT ECO:0007744|PDB:4APH" FT BINDING 1090 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854" FT BINDING 1094 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854" FT BINDING 1127 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:12540854, ECO:0000305|PubMed:11432860" FT SITE 523 FT /note="Not glycosylated" FT /evidence="ECO:0000269|PubMed:20826823" FT SITE 1166..1167 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:7499427, FT ECO:0000269|PubMed:8253769" FT SITE 1225 FT /note="Not glycosylated" FT /evidence="ECO:0000269|PubMed:9013598" FT SITE 1232..1233 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:10769174" FT MOD_RES 1299 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12386153, FT ECO:0000269|PubMed:21901117" FT CARBOHYD 38 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20826823, FT ECO:0000305|PubMed:9013598" FT CARBOHYD 54 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16476442, FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:9013598" FT CARBOHYD 74 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16476442, FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:26403559, FT ECO:0007744|PDB:3NXQ" FT CARBOHYD 111 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:9013598" FT CARBOHYD 146 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16476442, FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:9013598" FT CARBOHYD 160 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20826823" FT CARBOHYD 318 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16476442" FT CARBOHYD 445 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:26403559, FT ECO:0007744|PDB:3NXQ" FT CARBOHYD 509 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:20826823, FT ECO:0000269|PubMed:26403559, ECO:0000269|PubMed:9013598, FT ECO:0007744|PDB:3NXQ" FT CARBOHYD 677 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:23056909, FT ECO:0007744|PDB:4APH" FT CARBOHYD 695 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:9013598" FT CARBOHYD 714 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:23056909, FT ECO:0000269|PubMed:9013598, ECO:0007744|PDB:4APH" FT CARBOHYD 760 FT /note="N-linked (GlcNAc...) asparagine; partial" FT /evidence="ECO:0000269|PubMed:9013598" FT CARBOHYD 942 FT /note="N-linked (GlcNAc...) asparagine; partial" FT /evidence="ECO:0000269|PubMed:9013598" FT CARBOHYD 1191 FT /note="N-linked (GlcNAc...) asparagine; partial" FT /evidence="ECO:0000269|PubMed:9013598" FT DISULFID 157..165 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:8755737" FT DISULFID 359..377 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT DISULFID 545..557 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT DISULFID 757..763 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:8755737" FT DISULFID 957..975 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:8755737" FT DISULFID 1143..1155 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000269|PubMed:8755737" FT VAR_SEQ 1..641 FT /note="MGAASGRRGPGLLLPLPLLLLLPPQPALALDPGLQPGNFSADEAGAQLFAQS FT YNSSAEQVLFQSVAASWAHDTNITAENARRQEEAALLSQEFAEAWGQKAKELYEPIWQN FT FTDPQLRRIIGAVRTLGSANLPLAKRQQYNALLSNMSRIYSTAKVCLPNKTATCWSLDP FT DLTNILASSRSYAMLLFAWEGWHNAAGIPLKPLYEDFTALSNEAYKQDGFTDTGAYWRS FT WYNSPTFEDDLEHLYQQLEPLYLNLHAFVRRALHRRYGDRYINLRGPIPAHLLGDMWAQ FT SWENIYDMVVPFPDKPNLDVTSTMLQQGWNATHMFRVAEEFFTSLELSPMPPEFWEGSM FT LEKPADGREVVCHASAWDFYNRKDFRIKQCTRVTMDQLSTVHHEMGHIQYYLQYKDLPV FT SLRRGANPGFHEAIGDVLALSVSTPEHLHKIGLLDRVTNDTESDINYLLKMALEKIAFL FT PFGYLVDQWRWGVFSGRTPPSRYNFDWWYLRTKYQGICPPVTRNETHFDAGAKFHVPNV FT TPYIRYFVSFVLQFQFHEALCKEAGYEGPLHQCDIYRSTKAGAKLRKVLQAGSSRPWQE FT VLKDMVGLDALDAQPLLKYFQPVTQWLQEQNQQNGEVLGWPEYQWHPPLPDNYPEGID FT -> MGQGWATAGLPSLLFLLLCYGHPLLVPSQEASQQVTVTHGTSSQATTSSQTTTHQA FT TAHQTSAQSPN (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054836" FT VAR_SEQ 1..574 FT /note="Missing (in isoform Testis-specific)" FT /evidence="ECO:0000303|PubMed:2547653, FT ECO:0000303|PubMed:2554286" FT /id="VSP_035120" FT VAR_SEQ 575..641 FT /note="AGSSRPWQEVLKDMVGLDALDAQPLLKYFQPVTQWLQEQNQQNGEVLGWPEY FT QWHPPLPDNYPEGID -> MGQGWATAGLPSLLFLLLCYGHPLLVPSQEASQQVTVTHG FT TSSQATTSSQTTTHQATAHQTSAQSPN (in isoform Testis-specific)" FT /evidence="ECO:0000303|PubMed:2547653, FT ECO:0000303|PubMed:2554286" FT /id="VSP_035121" FT VAR_SEQ 1128..1168 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054837" FT VAR_SEQ 1137..1145 FT /note="QFHEALCQA -> HPFSQHTAA (in isoform Somatic-2)" FT /evidence="ECO:0000303|PubMed:9642152" FT /id="VSP_029932" FT VAR_SEQ 1146..1306 FT /note="Missing (in isoform Somatic-2)" FT /evidence="ECO:0000303|PubMed:9642152" FT /id="VSP_029933" FT VARIANT 154 FT /note="A -> T (in dbSNP:rs13306087)" FT /id="VAR_029139" FT VARIANT 183 FT /note="A -> T (in dbSNP:rs12720754)" FT /id="VAR_029140" FT VARIANT 244 FT /note="Y -> C (in dbSNP:rs3730025)" FT /id="VAR_023430" FT VARIANT 260 FT /note="R -> C (in dbSNP:rs147670020)" FT /id="VAR_054000" FT VARIANT 260 FT /note="R -> L (in dbSNP:rs4303)" FT /id="VAR_054001" FT VARIANT 261 FT /note="A -> S (in dbSNP:rs4303)" FT /evidence="ECO:0000269|PubMed:10319862" FT /id="VAR_011707" FT VARIANT 295 FT /note="D -> N (in dbSNP:rs989500910)" FT /evidence="ECO:0000269|PubMed:25787250" FT /id="VAR_074173" FT VARIANT 351 FT /note="P -> L (in dbSNP:rs2229839)" FT /id="VAR_023431" FT VARIANT 354 FT /note="G -> R (in dbSNP:rs56394458)" FT /evidence="ECO:0000269|PubMed:16116425" FT /id="VAR_035434" FT VARIANT 379 FT /note="R -> Q (in dbSNP:rs13306085)" FT /id="VAR_029141" FT VARIANT 524 FT /note="V -> A (in dbSNP:rs12720746)" FT /id="VAR_029142" FT VARIANT 561 FT /note="R -> W (in dbSNP:rs4314)" FT /evidence="ECO:0000269|PubMed:10319862" FT /id="VAR_011708" FT VARIANT 592 FT /note="D -> G (in dbSNP:rs12709426)" FT /id="VAR_020053" FT VARIANT 828 FT /note="M -> T (in dbSNP:rs13306091)" FT /id="VAR_034602" FT VARIANT 916 FT /note="T -> M (in dbSNP:rs3730043)" FT /id="VAR_023432" FT VARIANT 1018 FT /note="I -> T (in dbSNP:rs4976)" FT /evidence="ECO:0000269|PubMed:10391210" FT /id="VAR_014189" FT VARIANT 1051 FT /note="F -> V (in dbSNP:rs4977)" FT /evidence="ECO:0000269|PubMed:10391210" FT /id="VAR_014190" FT VARIANT 1187 FT /note="T -> M (in dbSNP:rs12709442)" FT /id="VAR_023433" FT VARIANT 1228 FT /note="P -> L (associated with high ACE plasma levels; no FT effect on activity; increases secretion; rate of FT solubilization is 2.5-fold higher than wild-type; FT dbSNP:rs121912703)" FT /evidence="ECO:0000269|PubMed:11076943, FT ECO:0000269|PubMed:11551873, ECO:0000269|PubMed:14694062" FT /id="VAR_023434" FT VARIANT 1279 FT /note="R -> Q (in dbSNP:rs4980)" FT /evidence="ECO:0000269|PubMed:10391210" FT /id="VAR_014191" FT VARIANT 1286 FT /note="R -> S (in dbSNP:rs4364)" FT /evidence="ECO:0000269|PubMed:10319862, FT ECO:0000269|PubMed:10391210" FT /id="VAR_011709" FT VARIANT 1296 FT /note="Q -> P (in dbSNP:rs4981)" FT /evidence="ECO:0000269|PubMed:10391210" FT /id="VAR_014192" FT MUTAGEN 318 FT /note="N->D: In Ndom123456 mutant; abolished dipeptidyl FT carboxypeptidase activity; when associated with D-445 and FT D-509. In Ndom1234569 mutant; does not affect dipeptidyl FT carboxypeptidase activity; when associated with D-445." FT /evidence="ECO:0000269|PubMed:20826823" FT MUTAGEN 390..394 FT /note="HEMGH->KEMGK: Abolished dipeptidyl carboxypeptidase FT activity; when associated with 988-K--K-992. Abolished FT N-terminal active sites, leading to impaired ability to FT degrade the hemoregulatory peptide N-acetyl-SDKP (AcSDKP). FT In contrast, does not affect cleavage of other substrates, FT such as Cholecystokinin-5." FT /evidence="ECO:0000269|PubMed:10336644, FT ECO:0000269|PubMed:1320019, ECO:0000269|PubMed:1851160, FT ECO:0000269|PubMed:7683654, ECO:0000269|PubMed:7876104, FT ECO:0000269|PubMed:7961923" FT MUTAGEN 391 FT /note="E->D: Abolished peptidase activity, leading to FT increased levels of amyloid-beta; when associated with FT D-989." FT /evidence="ECO:0000269|PubMed:16154999, FT ECO:0000269|PubMed:19773553" FT MUTAGEN 445 FT /note="N->D: In Ndom123456 mutant; abolished dipeptidyl FT carboxypeptidase activity; when associated with D-318 and FT D-445. In Ndom1234569 mutant; does not affect dipeptidyl FT carboxypeptidase activity; when associated with D-318." FT /evidence="ECO:0000269|PubMed:20826823" FT MUTAGEN 509 FT /note="N->D: In Ndom123456 mutant; abolished dipeptidyl FT carboxypeptidase activity; when associated with D-318 and FT D-445." FT /evidence="ECO:0000269|PubMed:20826823" FT MUTAGEN 529 FT /note="R->Q: Abolished dependence to chloride, leading to FT reduced peptidyl dipeptidase activity." FT /evidence="ECO:0000269|PubMed:11432860" FT MUTAGEN 988..992 FT /note="HEMGH->KEMGK: Abolished dipeptidyl carboxypeptidase FT activity; when associated with 390-K--K-394. Abolishes the FT second active site, preventing maturation of FT Cholecystokinin-5." FT /evidence="ECO:0000269|PubMed:10336644, FT ECO:0000269|PubMed:1320019, ECO:0000269|PubMed:1851160, FT ECO:0000269|PubMed:7683654" FT MUTAGEN 989 FT /note="E->D: Abolished peptidase activity, leading to FT increased levels of amyloid-beta; when associated with FT D-391." FT /evidence="ECO:0000269|PubMed:16154999, FT ECO:0000269|PubMed:19773553" FT MUTAGEN 1016 FT /note="E->D: Strongly decreased dipeptidyl carboxypeptidase FT activity; when associated with 390-K--K-394." FT /evidence="ECO:0000269|PubMed:7961923" FT MUTAGEN 1016 FT /note="E->V: Abolished dipeptidyl carboxypeptidase FT activity; when associated with 390-K--K-394." FT /evidence="ECO:0000269|PubMed:7961923" FT MUTAGEN 1020 FT /note="D->E,A: Decreased dipeptidyl carboxypeptidase FT activity; when associated with 390-K--K-394." FT /evidence="ECO:0000269|PubMed:7961923" FT MUTAGEN 1116 FT /note="K->A: Decreased ability to cleave substance P and FT bradykinin. Reduced binding to captopril inhibitor." FT /evidence="ECO:0000269|PubMed:15615692" FT MUTAGEN 1125 FT /note="Y->F: Decreased ability to cleave substance P and FT captopril inhibitor." FT /evidence="ECO:0000269|PubMed:15615692" FT MUTAGEN 1127 FT /note="R->Q: Abolished dependence to chloride, leading to FT reduced peptidyl dipeptidase activity." FT /evidence="ECO:0000269|PubMed:11432860" FT MUTAGEN 1166 FT /note="R->Q: Does not prevent cleavage and secretion of the FT soluble form, suggesting that processing can take place at FT different sites." FT /evidence="ECO:0000269|PubMed:8253769" FT MUTAGEN 1229 FT /note="N->Q: Increased cleavage and secretion of the FT soluble form by generating a new cleavage site." FT /evidence="ECO:0000269|PubMed:11274151" FT MUTAGEN 1299 FT /note="S->A: Abolishes phosphorylation and decreases FT membrane retention." FT /evidence="ECO:0000269|PubMed:12386153, FT ECO:0000269|PubMed:21901117" FT CONFLICT 35 FT /note="Q -> E (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 42 FT /note="D -> R (in Ref. 9; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 32..34 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 43..72 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 77..105 FT /evidence="ECO:0007829|PDB:5AMB" FT TURN 106..108 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 115..124 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 128..131 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 134..153 FT /evidence="ECO:0007829|PDB:5AMB" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:5AMB" FT STRAND 159..161 FT /evidence="ECO:0007829|PDB:4BZS" FT STRAND 165..167 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 168..172 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 173..178 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 182..216 FT /evidence="ECO:0007829|PDB:5AMB" FT TURN 217..219 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 223..229 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 236..266 FT /evidence="ECO:0007829|PDB:5AMB" FT TURN 268..270 FT /evidence="ECO:0007829|PDB:5AMB" FT STRAND 281..284 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 291..293 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 294..297 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 309..314 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 319..332 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 336..339 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 340..345 FT /evidence="ECO:0007829|PDB:5AMB" FT STRAND 352..354 FT /evidence="ECO:0007829|PDB:8QFX" FT STRAND 362..365 FT /evidence="ECO:0007829|PDB:5AMB" FT STRAND 367..370 FT /evidence="ECO:0007829|PDB:5AMB" FT STRAND 372..375 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 382..401 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 406..408 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 414..428 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 431..436 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 441..444 FT /evidence="ECO:0007829|PDB:5AMC" FT HELIX 447..461 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 464..480 FT /evidence="ECO:0007829|PDB:5AMB" FT STRAND 481..483 FT /evidence="ECO:0007829|PDB:6ZPT" FT HELIX 485..487 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 488..495 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 496..500 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 514..517 FT /evidence="ECO:0007829|PDB:5AMB" FT TURN 519..524 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 528..547 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 554..556 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 563..575 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 581..589 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 597..617 FT /evidence="ECO:0007829|PDB:5AMB" FT HELIX 619..621 FT /evidence="ECO:0007829|PDB:8QHL" FT HELIX 630..633 FT /evidence="ECO:0007829|PDB:5AMB" FT TURN 634..637 FT /evidence="ECO:0007829|PDB:7Q25" FT HELIX 638..640 FT /evidence="ECO:0007829|PDB:7Q25" FT HELIX 641..643 FT /evidence="ECO:0007829|PDB:5AM9" FT HELIX 646..675 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 677..679 FT /evidence="ECO:0007829|PDB:9GBN" FT HELIX 680..704 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 709..711 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 715..724 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 728..731 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 734..753 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 755..757 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 759..761 FT /evidence="ECO:0007829|PDB:1UZE" FT STRAND 763..765 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 766..770 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 771..776 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 780..790 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 791..795 FT /evidence="ECO:0007829|PDB:6H5W" FT TURN 799..801 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 802..815 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 821..826 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 827..829 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 834..844 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 846..864 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 866..868 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 879..882 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 889..891 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 892..895 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 902..904 FT /evidence="ECO:0007829|PDB:7Z70" FT HELIX 906..912 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 917..930 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 934..937 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 938..943 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 945..947 FT /evidence="ECO:0007829|PDB:4APJ" FT STRAND 950..952 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 960..963 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 965..968 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 970..973 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 980..998 FT /evidence="ECO:0007829|PDB:6H5W" FT TURN 999..1001 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1004..1006 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1012..1026 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1029..1034 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 1037..1040 FT /evidence="ECO:0007829|PDB:7Q28" FT HELIX 1045..1059 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1062..1077 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1083..1085 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1086..1093 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1094..1098 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1112..1115 FT /evidence="ECO:0007829|PDB:6H5W" FT TURN 1117..1122 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1126..1145 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1152..1154 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1161..1171 FT /evidence="ECO:0007829|PDB:6H5W" FT TURN 1172..1175 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1179..1187 FT /evidence="ECO:0007829|PDB:6H5W" FT STRAND 1188..1191 FT /evidence="ECO:0007829|PDB:3BKL" FT HELIX 1195..1215 FT /evidence="ECO:0007829|PDB:6H5W" FT HELIX 1217..1219 FT /evidence="ECO:0007829|PDB:9GBO" FT TURN 1222..1225 FT /evidence="ECO:0007829|PDB:6F9T" FT BINDING P12821-3:414 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:24297181, FT ECO:0007744|PDB:4C2N, ECO:0007744|PDB:4C2P, FT ECO:0007744|PDB:4C2Q, ECO:0007744|PDB:4C2R" FT BINDING P12821-3:418 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:24297181, FT ECO:0007744|PDB:4C2N, ECO:0007744|PDB:4C2P, FT ECO:0007744|PDB:4C2Q, ECO:0007744|PDB:4C2R" FT BINDING P12821-3:442 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:24297181, FT ECO:0007744|PDB:4C2N, ECO:0007744|PDB:4C2P, FT ECO:0007744|PDB:4C2Q, ECO:0007744|PDB:4C2R" FT CARBOHYD P12821-3:103 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21810173, FT ECO:0000269|PubMed:24297181, ECO:0000269|PubMed:8626443, FT ECO:0007744|PDB:4C2O" FT CARBOHYD P12821-3:121 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:8626443" FT CARBOHYD P12821-3:140 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:21810173, FT ECO:0000269|PubMed:24297181, ECO:0000269|PubMed:8626443, FT ECO:0007744|PDB:4C2O" FT CARBOHYD P12821-3:368 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:8626443" FT CARBOHYD P12821-3:617 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:8626443" FT VARIANT P12821-3:32 FT /note="S -> P (in dbSNP:rs4317)" FT /evidence="ECO:0000305" FT /id="VAR_082898" FT VARIANT P12821-3:49 FT /note="S -> G (in dbSNP:rs4318)" FT /evidence="ECO:0000305" FT /id="VAR_082899" FT MUTAGEN P12821-3:103 FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation FT leading to impaired stability and degradation; when FT associated with D-121, D-140, D-368 and D-617. In ACE(t)g2 FT mutant; decreased N-glycosylation without affecting FT stability; when associated with D-140, D-368 and D-617. In FT ACE(t)g3 mutant; decreased N-glycosylation leading to FT impaired stability and degradation; when associated with FT D-121, D-368 and D-617." FT /evidence="ECO:0000269|PubMed:8626443" FT MUTAGEN P12821-3:121 FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation FT leading to impaired stability and degradation; when FT associated with D-103, D-140, D-368 and D-617. In ACE(t)g1 FT mutant; decreased N-glycosylation without affecting FT stability; when associated with D-140, D-368 and D-617. In FT ACE(t)g3 mutant; decreased N-glycosylation leading to FT impaired stability and degradation; when associated with FT D-103, D-368 and D-617." FT /evidence="ECO:0000269|PubMed:8626443" FT MUTAGEN P12821-3:140 FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation FT leading to impaired stability and degradation; when FT associated with D-103, D-121, D-368 and D-617. In ACE(t)g1 FT mutant; decreased N-glycosylation without affecting FT stability; when associated with D-121, D-368 and D-617. In FT ACE(t)g2 mutant; decreased N-glycosylation without FT affecting stability; when associated with D-103, D-368 and FT D-617." FT /evidence="ECO:0000269|PubMed:8626443" FT MUTAGEN P12821-3:368 FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation FT leading to impaired stability and degradation; when FT associated with D-103, D-121, D-140 and D-617. In ACE(t)g1 FT mutant; decreased N-glycosylation without affecting FT stability; when associated with D-121, D-140 and D-617. In FT ACE(t)g2 mutant; decreased N-glycosylation without FT affecting stability; when associated with D-103, D-140 and FT D-617. In ACE(t)g3 mutant; decreased N-glycosylation FT leading to impaired stability and degradation; when FT associated with D-103, D-121 and D-617." FT /evidence="ECO:0000269|PubMed:8626443" FT MUTAGEN P12821-3:553 FT /note="R->K,Q: Abolished binding to chloride ion." FT /evidence="ECO:0000269|PubMed:24297181" FT MUTAGEN P12821-3:617 FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation FT leading to impaired stability and degradation; when FT associated with D-103, D-121, D-140 and D-368. In ACE(t)g1 FT mutant; decreased N-glycosylation without affecting FT stability; when associated with D-121, D-140 and D-368. In FT ACE(t)g2 mutant; decreased N-glycosylation without FT affecting stability; when associated with D-103, D-140 and FT D-368. In ACE(t)g3 mutant; decreased N-glycosylation FT leading to impaired stability and degradation; when FT associated with D-103, D-121 and D-368." FT /evidence="ECO:0000269|PubMed:8626443" SQ SEQUENCE 1306 AA; 149715 MW; 1B33BCA7301A26AA CRC64; MGAASGRRGP GLLLPLPLLL LLPPQPALAL DPGLQPGNFS ADEAGAQLFA QSYNSSAEQV LFQSVAASWA HDTNITAENA RRQEEAALLS QEFAEAWGQK AKELYEPIWQ NFTDPQLRRI IGAVRTLGSA NLPLAKRQQY NALLSNMSRI YSTAKVCLPN KTATCWSLDP DLTNILASSR SYAMLLFAWE GWHNAAGIPL KPLYEDFTAL SNEAYKQDGF TDTGAYWRSW YNSPTFEDDL EHLYQQLEPL YLNLHAFVRR ALHRRYGDRY INLRGPIPAH LLGDMWAQSW ENIYDMVVPF PDKPNLDVTS TMLQQGWNAT HMFRVAEEFF TSLELSPMPP EFWEGSMLEK PADGREVVCH ASAWDFYNRK DFRIKQCTRV TMDQLSTVHH EMGHIQYYLQ YKDLPVSLRR GANPGFHEAI GDVLALSVST PEHLHKIGLL DRVTNDTESD INYLLKMALE KIAFLPFGYL VDQWRWGVFS GRTPPSRYNF DWWYLRTKYQ GICPPVTRNE THFDAGAKFH VPNVTPYIRY FVSFVLQFQF HEALCKEAGY EGPLHQCDIY RSTKAGAKLR KVLQAGSSRP WQEVLKDMVG LDALDAQPLL KYFQPVTQWL QEQNQQNGEV LGWPEYQWHP PLPDNYPEGI DLVTDEAEAS KFVEEYDRTS QVVWNEYAEA NWNYNTNITT ETSKILLQKN MQIANHTLKY GTQARKFDVN QLQNTTIKRI IKKVQDLERA ALPAQELEEY NKILLDMETT YSVATVCHPN GSCLQLEPDL TNVMATSRKY EDLLWAWEGW RDKAGRAILQ FYPKYVELIN QAARLNGYVD AGDSWRSMYE TPSLEQDLER LFQELQPLYL NLHAYVRRAL HRHYGAQHIN LEGPIPAHLL GNMWAQTWSN IYDLVVPFPS APSMDTTEAM LKQGWTPRRM FKEADDFFTS LGLLPVPPEF WNKSMLEKPT DGREVVCHAS AWDFYNGKDF RIKQCTTVNL EDLVVAHHEM GHIQYFMQYK DLPVALREGA NPGFHEAIGD VLALSVSTPK HLHSLNLLSS EGGSDEHDIN FLMKMALDKI AFIPFSYLVD QWRWRVFDGS ITKENYNQEW WSLRLKYQGL CPPVPRTQGD FDPGAKFHIP SSVPYIRYFV SFIIQFQFHE ALCQAAGHTG PLHKCDIYQS KEAGQRLATA MKLGFSRPWP EAMQLITGQP NMSASAMLSY FKPLLDWLRT ENELHGEKLG WPQYNWTPNS ARSEGPLPDS GRVSFLGLDL DAQQARVGQW LLLFLGIALL VATLGLSQRL FSIRHRSLHR HSHGPQFGSE VELRHS //