ID ACE_MOUSE Reviewed; 1312 AA. AC P09470; P22967; Q6GTS2; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 30-AUG-2005, sequence version 3. DT 04-NOV-2026, entry version 214. DE RecName: Full=Angiotensin-converting enzyme {ECO:0000303|PubMed:2545691}; DE Short=ACE {ECO:0000303|PubMed:2545691}; DE EC=3.4.15.1 {ECO:0000269|PubMed:16270063}; DE AltName: Full=Dipeptidyl carboxypeptidase I; DE AltName: Full=Kininase II {ECO:0000250|UniProtKB:P12821}; DE AltName: CD_antigen=CD143; DE Contains: DE RecName: Full=Angiotensin-converting enzyme, soluble form {ECO:0000250|UniProtKB:P12821}; DE Flags: Precursor; GN Name=Ace {ECO:0000303|PubMed:2545691, ECO:0000312|MGI:MGI:87874}; GN Synonyms=Dcp1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC). RX PubMed=2545691; DOI=10.1016/s0021-9258(18)80158-2; RA Bernstein K.E., Martin B.M., Edwards A.S., Bernstein E.A.; RT "Mouse angiotensin-converting enzyme is a protein composed of two RT homologous domains."; RL J. Biol. Chem. 264:11945-11951(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), AND PARTIAL RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2164636; DOI=10.1128/mcb.10.8.4294-4302.1990; RA Howard T.E., Shai S.-Y., Langford K.G., Martin B.M., Bernstein K.E.; RT "Transcription of testicular angiotensin-converting enzyme (ACE) is RT initiated within the 12th intron of the somatic ACE gene."; RL Mol. Cell. Biol. 10:4294-4302(1990). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SOMATIC). RC STRAIN=FVB/N; TISSUE=Mammary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-332 (ISOFORM SOMATIC), AND PARTIAL PROTEIN RP SEQUENCE. RX PubMed=2841312; DOI=10.1016/s0021-9258(18)37909-2; RA Bernstein K.E., Martin B.M., Bernstein E.A., Linton J., Striker L., RA Striker G.; RT "The isolation of angiotensin-converting enzyme cDNA."; RL J. Biol. Chem. 263:11021-11024(1988). RN [5] RP PROTEIN SEQUENCE OF 35-54. RC TISSUE=Kidney; RX PubMed=2835538; DOI=10.1038/ki.1988.48; RA Bernstein K.E., Martin B.M., Striker L., Striker G.; RT "Partial protein sequence of mouse and bovine kidney angiotensin converting RT enzyme."; RL Kidney Int. 33:652-655(1988). RN [6] RP ALTERNATIVE PROMOTER USAGE, FUNCTION (ISOFORM TESTIS-SPECIFIC), AND TISSUE RP SPECIFICITY (ISOFORM TESTIS-SPECIFIC). RX PubMed=1651914; DOI=10.1016/s0021-9258(18)98437-1; RA Langford K.G., Shai S.Y., Howard T.E., Kovac M.J., Overbeek P.A., RA Bernstein K.E.; RT "Transgenic mice demonstrate a testis-specific promoter for angiotensin- RT converting enzyme."; RL J. Biol. Chem. 266:15559-15562(1991). RN [7] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=7753170; DOI=10.1038/375146a0; RA Krege J.H., John S.W., Langenbach L.L., Hodgin J.B., Hagaman J.R., RA Bachman E.S., Jennette J.C., O'Brien D.A., Smithies O.; RT "Male-female differences in fertility and blood pressure in ACE-deficient RT mice."; RL Nature 375:146-148(1995). RN [8] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=8642790; RA Esther C.R. Jr., Howard T.E., Marino E.M., Goddard J.M., Capecchi M.R., RA Bernstein K.E.; RT "Mice lacking angiotensin-converting enzyme have low blood pressure, renal RT pathology, and reduced male fertility."; RL Lab. Invest. 74:953-965(1996). RN [9] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=9231832; DOI=10.1161/01.hyp.30.1.128; RA Tian B., Meng Q.C., Chen Y.F., Krege J.H., Smithies O., Oparil S.; RT "Blood pressures and cardiovascular homeostasis in mice having reduced or RT absent angiotensin-converting enzyme gene function."; RL Hypertension 30:128-133(1997). RN [10] RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE. RX PubMed=9664078; DOI=10.1172/jci3545; RA Ramaraj P., Kessler S.P., Colmenares C., Sen G.C.; RT "Selective restoration of male fertility in mice lacking angiotensin- RT converting enzymes by sperm-specific expression of the testicular RT isozyme."; RL J. Clin. Invest. 102:371-378(1998). RN [11] RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE. RX PubMed=9482924; DOI=10.1073/pnas.95.5.2552; RA Hagaman J.R., Moyer J.S., Bachman E.S., Sibony M., Magyar P.L., Welch J.E., RA Smithies O., Krege J.H., O'Brien D.A.; RT "Angiotensin-converting enzyme and male fertility."; RL Proc. Natl. Acad. Sci. U.S.A. 95:2552-2557(1998). RN [12] RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE. RX PubMed=10831599; DOI=10.1074/jbc.m004006200; RA Kessler S.P., Rowe T.M., Gomos J.B., Kessler P.M., Sen G.C.; RT "Physiological non-equivalence of the two isoforms of angiotensin- RT converting enzyme."; RL J. Biol. Chem. 275:26259-26264(2000). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=11303049; DOI=10.1016/s0022-3565(24)29576-8; RA Junot C., Gonzales M.F., Ezan E., Cotton J., Vazeux G., Michaud A., RA Azizi M., Vassiliou S., Yiotakis A., Corvol P., Dive V.; RT "RXP 407, a selective inhibitor of the N-domain of angiotensin I-converting RT enzyme, blocks in vivo the degradation of hemoregulatory peptide acetyl- RT Ser-Asp-Lys-Pro with no effect on angiotensin I hydrolysis."; RL J. Pharmacol. Exp. Ther. 297:606-611(2001). RN [14] RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE. RX PubMed=11723129; DOI=10.1074/jbc.m109474200; RA Kessler S.P., Gomos J.B., Scheidemantel T.S., Rowe T.M., Smith H.L., RA Sen G.C.; RT "The germinal isozyme of angiotensin-converting enzyme can substitute for RT the somatic isozyme in maintaining normal renal structure and functions."; RL J. Biol. Chem. 277:4271-4276(2002). RN [15] RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE. RX PubMed=12777443; DOI=10.1074/jbc.m3023472000; RA Kessler S.P., deS Senanayake P., Scheidemantel T.S., Gomos J.B., Rowe T.M., RA Sen G.C.; RT "Maintenance of normal blood pressure and renal functions are independent RT effects of angiotensin-converting enzyme."; RL J. Biol. Chem. 278:21105-21112(2003). RN [16] RP FUNCTION, AND MUTAGENESIS OF 395-HIS--HIS-399. RX PubMed=14757757; DOI=10.1074/jbc.m400149200; RA Fuchs S., Xiao H.D., Cole J.M., Adams J.W., Frenzel K., Michaud A., RA Zhao H., Keshelava G., Capecchi M.R., Corvol P., Bernstein K.E.; RT "Role of the N-terminal catalytic domain of angiotensin-converting enzyme RT investigated by targeted inactivation in mice."; RL J. Biol. Chem. 279:15946-15953(2004). RN [17] RP TISSUE SPECIFICITY. 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 [18] RP FUNCTION (ISOFORM TESTIS-SPECIFIC), ACTIVITY REGULATION (ISOFORM RP TESTIS-SPECIFIC), ACTIVE SITE, AND MUTAGENESIS OF HIS-993; GLU-994 AND RP HIS-997. RX PubMed=15665832; DOI=10.1038/nm1179; RA Kondoh G., Tojo H., Nakatani Y., Komazawa N., Murata C., Yamagata K., RA Maeda Y., Kinoshita T., Okabe M., Taguchi R., Takeda J.; RT "Angiotensin-converting enzyme is a GPI-anchored protein releasing factor RT crucial for fertilization."; RL Nat. Med. 11:160-166(2005). RN [19] RP FUNCTION (ISOFORM TESTIS-SPECIFIC), DISRUPTION PHENOTYPE, AND MUTAGENESIS RP OF 413-LYS--LYS-417 (ISOFORM TESTIS-SPECIFIC). RX PubMed=16270063; DOI=10.1038/nm1105-1140; RA Fuchs S., Frenzel K., Hubert C., Lyng R., Muller L., Michaud A., Xiao H.D., RA Adams J.W., Capecchi M.R., Corvol P., Shur B.D., Bernstein K.E.; RT "Male fertility is dependent on dipeptidase activity of testis ACE."; RL Nat. Med. 11:1140-1142(2005). RN [20] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-151. RC STRAIN=C57BL/6J; TISSUE=Plasma; RX PubMed=16944957; DOI=10.1021/pr060186m; RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.; RT "Proteome-wide characterization of N-glycosylation events by diagonal RT chromatography."; RL J. Proteome Res. 5:2438-2447(2006). RN [21] RP MUTAGENESIS OF 413-LYS--LYS-417 (ISOFORM TESTIS-SPECIFIC). RX PubMed=17634445; DOI=10.1095/biolreprod.107.060004; RA Deguchi E., Tani T., Watanabe H., Yamada S., Kondoh G.; RT "Dipeptidase-inactivated tACE action in vivo: selective inhibition of RT sperm-zona pellucida binding in the mouse."; RL Biol. Reprod. 77:794-802(2007). RN [22] RP FUNCTION (ISOFORM TESTIS-SPECIFIC). RX PubMed=17135368; DOI=10.1096/fj.06-6678com; RA Kessler S.P., Senanayake P.D., Gaughan C., Sen G.C.; RT "Vascular expression of germinal ACE fails to maintain normal blood RT pressure in ACE-/- mice."; RL FASEB J. 21:156-166(2007). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain cortex; RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200; RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., RA Panse C., Schlapbach R., Mansuy I.M.; RT "Qualitative and quantitative analyses of protein phosphorylation in naive RT and stimulated mouse synaptosomal preparations."; RL Mol. Cell. Proteomics 6:283-293(2007). RN [24] RP DISRUPTION PHENOTYPE. RX PubMed=18443281; DOI=10.1073/pnas.0802690105; RA Jayasooriya A.P., Mathai M.L., Walker L.L., Begg D.P., Denton D.A., RA Cameron-Smith D., Egan G.F., McKinley M.J., Rodger P.D., Sinclair A.J., RA Wark J.D., Weisinger H.S., Jois M., Weisinger R.S.; RT "Mice lacking angiotensin-converting enzyme have increased energy RT expenditure, with reduced fat mass and improved glucose clearance."; RL Proc. Natl. Acad. Sci. U.S.A. 105:6531-6536(2008). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1305, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [26] RP SUBCELLULAR LOCATION. RX PubMed=23535237; DOI=10.1152/ajpcell.00364.2012; RA Xiao L., Haack K.K., Zucker I.H.; RT "Angiotensin II regulates ACE and ACE2 in neurons through p38 mitogen- RT activated protein kinase and extracellular signal-regulated kinase 1/2 RT signaling."; RL Am. J. Physiol. 304:C1073-C1079(2013). RN [27] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND TISSUE SPECIFICITY. RX PubMed=35201898; DOI=10.1126/science.abl5130; RA Trieu B.H., Remmers B.C., Toddes C., Brandner D.D., Lefevre E.M., RA Kocharian A., Retzlaff C.L., Dick R.M., Mashal M.A., Gauthier E.A., Xie W., RA Zhang Y., More S.S., Rothwell P.E.; RT "Angiotensin-converting enzyme gates brain circuit-specific plasticity via RT an endogenous opioid."; RL Science 2022:eabl5130-eabl5130(2022). 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:11723129, PubMed:12777443, PubMed:14757757, PubMed:16270063, CC PubMed:35201898, PubMed:7753170, PubMed:8642790, PubMed:9231832). CC Composed of two similar catalytic domains, each possessing a functional CC active site, with different selectivity for substrates CC (PubMed:11303049). Plays a major role in the angiotensin-renin system CC that regulates blood pressure and sodium retention by the kidney by CC converting angiotensin I to angiotensin II, resulting in an increase of CC the vasoconstrictor activity of angiotensin (PubMed:11303049, CC PubMed:14757757, PubMed:9231832). Also able to inactivate bradykinin, a CC potent vasodilator, and therefore enhance the blood pressure response CC (By similarity). Acts as a regulator of synaptic transmission by CC mediating cleavage of neuropeptide hormones, such as substance P, CC neurotensin or enkephalins (By similarity). Catalyzes degradation of CC different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, CC Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu) CC (PubMed:35201898). 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 (PubMed:35201898). Met-enkephalin-Arg-Phe cleavage by ACE CC decreases activation of OPRM1, leading to long-term synaptic CC potentiation of glutamate release (PubMed:35201898). Also acts as a CC regulator of hematopoietic stem cell differentiation by mediating CC degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) CC (PubMed:11303049). Acts as a regulator of cannabinoid signaling pathway CC by mediating degradation of hemopressin, an antagonist peptide of the CC cannabinoid receptor CNR1 (By similarity). Involved in amyloid-beta CC metabolism by catalyzing degradation of Amyloid-beta protein 40 and CC Amyloid-beta protein 42 peptides, thereby preventing plaque formation CC (By similarity). Catalyzes cleavage of cholecystokinin (maturation of CC Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both CC maturation and degradation) hormones (By similarity). Degradation of CC hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins CC is mediated by the N-terminal catalytic domain, while angiotensin I and CC cholecystokinin cleavage is mediated by the C-terminal catalytic region CC (PubMed:11303049). {ECO:0000250|UniProtKB:P12821, CC ECO:0000269|PubMed:11303049, ECO:0000269|PubMed:11723129, CC ECO:0000269|PubMed:12777443, ECO:0000269|PubMed:14757757, CC ECO:0000269|PubMed:16270063, ECO:0000269|PubMed:35201898, CC ECO:0000269|PubMed:7753170, ECO:0000269|PubMed:8642790, CC ECO:0000269|PubMed:9231832}. 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:0000250|UniProtKB:P12821}. 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:1651914, CC PubMed:9482924). In contrast to somatic isoforms, only contains one CC catalytic domain (PubMed:16270063). Acts as a dipeptidyl CC carboxypeptidase that removes dipeptides from the C-terminus of CC substrates (PubMed:16270063). The identity of substrates that are CC needed for male fertility is unknown (PubMed:16270063). Isoform Testis- CC specific and isoform Somatic have distinct activities and cannot CC completely compensate for the loss of the other when expressed in CC somatic tissues or testis (PubMed:10831599, PubMed:11723129, CC PubMed:12777443, PubMed:16270063, PubMed:9664078). May also have a CC glycosidase activity which releases GPI-anchored proteins from the CC membrane by cleaving the mannose linkage in the GPI moiety CC (PubMed:15665832). The GPIase activity was reported to be essential for CC the egg-binding ability of the sperm (PubMed:15665832). This activity CC is however unclear and has been challenged by other groups, suggesting CC that it may be indirect (PubMed:16270063). CC {ECO:0000269|PubMed:10831599, ECO:0000269|PubMed:11723129, CC ECO:0000269|PubMed:12777443, ECO:0000269|PubMed:15665832, CC ECO:0000269|PubMed:16270063, ECO:0000269|PubMed:1651914, CC ECO:0000269|PubMed:9482924, ECO:0000269|PubMed:9664078}. 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:11303049}; 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:11303049}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63561; CC Evidence={ECO:0000269|PubMed:11303049}; 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:0000250|UniProtKB:P12821}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71452; CC Evidence={ECO:0000250|UniProtKB:P12821}; 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:0000250|UniProtKB:P12821}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71460; CC Evidence={ECO:0000250|UniProtKB:P12821}; 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:0000250|UniProtKB:P12821}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71464; CC Evidence={ECO:0000250|UniProtKB:P12821}; 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:0000250|UniProtKB:P12821}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71472; CC Evidence={ECO:0000250|UniProtKB:P12821}; 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:0000250|UniProtKB:P12821}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71476; CC Evidence={ECO:0000250|UniProtKB:P12821}; 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:11303049}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71456; CC Evidence={ECO:0000269|PubMed:11303049}; 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:0000250|UniProtKB:P12821}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71484; CC Evidence={ECO:0000250|UniProtKB:P12821}; 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:0000250|UniProtKB:P12821}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71488; CC Evidence={ECO:0000250|UniProtKB:P12821}; 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:0000269|PubMed:35201898}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70676; CC Evidence={ECO:0000269|PubMed:35201898}; 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:16270063}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P12821}; CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P12821}; CC -!- COFACTOR: [Isoform Testis-specific]: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P12821}; CC Note=Isoform Testis-specific only binds 1 Zn(2+) ion per subunit. CC {ECO:0000250|UniProtKB:P12821}; CC -!- COFACTOR: CC Name=chloride; Xref=ChEBI:CHEBI:17996; CC Evidence={ECO:0000250|UniProtKB:P12821}; CC Note=Binds 3 chloride ions per subunit. {ECO:0000250|UniProtKB:P12821}; CC -!- COFACTOR: [Isoform Testis-specific]: CC Name=chloride; Xref=ChEBI:CHEBI:17996; CC Evidence={ECO:0000250|UniProtKB:P12821}; CC -!- ACTIVITY REGULATION: The dipeptidyl carboxypeptidase activity is CC specifically inhibited by lisinopril, captopril and enalaprilat CC (PubMed:15665832, PubMed:35201898). The N-terminal catalytic domain, CC but not the C-terminal catalytic domain, is specifically inhibited by CC the phosphinic peptide RXP 407 (PubMed:11303049). CC {ECO:0000269|PubMed:11303049, ECO:0000269|PubMed:15665832, CC ECO:0000269|PubMed:35201898}. CC -!- ACTIVITY REGULATION: [Isoform Testis-specific]: The putative GPIase CC activity is nearly insensitive to captopril. CC {ECO:0000269|PubMed:15665832}. CC -!- SUBUNIT: Monomer and homodimer; homodimerizes following binding to an CC inhibitor (By similarity). 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:P12821, ECO:0000250|UniProtKB:P12822}. CC -!- SUBCELLULAR LOCATION: [Isoform Somatic]: Cell membrane CC {ECO:0000269|PubMed:23535237}; Single-pass type I membrane protein CC {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:23535237}. Note=Detected CC in both cell membrane and cytoplasm in neurons. CC {ECO:0000269|PubMed:23535237}. CC -!- SUBCELLULAR LOCATION: [Angiotensin-converting enzyme, soluble form]: CC Secreted {ECO:0000250|UniProtKB:P12821}. CC -!- SUBCELLULAR LOCATION: [Isoform Testis-specific]: Cell membrane CC {ECO:0000250|UniProtKB:P12821}; Single-pass type I membrane protein CC {ECO:0000255}. Secreted {ECO:0000250|UniProtKB:P12821}. Note=The CC testis-specific isoform can be cleaved before the transmembrane region, CC releasing a soluble form. {ECO:0000250|UniProtKB:P12821}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=2; CC Name=Somatic; Synonyms=sACE {ECO:0000303|PubMed:16270063}; CC IsoId=P09470-1; Sequence=Displayed; CC Name=Testis-specific; Synonyms=ACE-T, tACE CC {ECO:0000303|PubMed:16270063}, germinal ACE CC {ECO:0000303|PubMed:11723129}, gACE {ECO:0000303|PubMed:11723129}; CC IsoId=P09470-2, P22967-1; Sequence=VSP_037638, VSP_037639; CC -!- TISSUE SPECIFICITY: [Isoform Somatic]: Highly expressed in kidney and CC lung; not expressed in the liver (PubMed:16154999). In the brain, CC expressed in the cerebral cortex, hippocampus, cerebellum and basal CC ganglia/brainstem (PubMed:16154999). Highly expressed in dopamine CC receptor DRD1-expressing neurons in the dorsal striatum and the nucleus CC accumbens of the brain (PubMed:35201898). {ECO:0000269|PubMed:16154999, CC ECO:0000269|PubMed:35201898}. CC -!- TISSUE SPECIFICITY: [Isoform Testis-specific]: Specifically expressed CC in spermatocytes, adult testis. {ECO:0000269|PubMed:1651914}. 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. Cleavage can take place at different sites of the juxtamembrane CC stalk region. {ECO:0000250|UniProtKB:P12821}. CC -!- PTM: Phosphorylated by CK2 on Ser-1305; which allows membrane retention CC (By similarity). 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:P12821, CC ECO:0000250|UniProtKB:P12822}. CC -!- DISRUPTION PHENOTYPE: Mice display low blood pressure (hypotension), CC elevated serum potassium, anemia, urine concentration defects and gross CC renal structural defects (PubMed:11723129, PubMed:12777443, CC PubMed:8642790, PubMed:9231832). Male mice also have reduced fertility: CC sperm show defects in transport within the oviducts and in binding to CC zonae pellucidae (PubMed:7753170, PubMed:9482924). Mice also show CC impaired metabolism, characterized by increased energy expenditure, CC reduced fat mass and improved glucose clearance (PubMed:18443281). CC Expression of isoform Somatic in testis in knockout mice does not CC restore male fertility (PubMed:10831599). In contrast, expression of CC isoform Testis-specific in the sperm of knockout mice only restores CC fertility without curing other defects (PubMed:9664078). Isoform CC Testis-specific can substitute for isoform Somatic for normal kidney CC structure but not for normal blood pressure when expressed in vascular CC cells of knockout mice (PubMed:11723129, PubMed:12777443, CC PubMed:16270063). {ECO:0000269|PubMed:10831599, CC ECO:0000269|PubMed:11723129, ECO:0000269|PubMed:12777443, CC ECO:0000269|PubMed:16270063, ECO:0000269|PubMed:18443281, CC ECO:0000269|PubMed:7753170, ECO:0000269|PubMed:8642790, CC ECO:0000269|PubMed:9231832, ECO:0000269|PubMed:9482924, CC ECO:0000269|PubMed:9664078}. CC -!- DISRUPTION PHENOTYPE: [Isoform Somatic]: Mice lacking somatic isoform CC display normal male fertility. {ECO:0000269|PubMed:9482924}. CC -!- SIMILARITY: Belongs to the peptidase M2 family. {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; J04946; AAA37147.1; -; mRNA. DR EMBL; J04947; AAA37148.1; -; mRNA. DR EMBL; M55333; AAA37149.1; -; mRNA. DR EMBL; M61094; AAA37150.1; -; Genomic_DNA. DR EMBL; BC040404; AAH40404.1; -; mRNA. DR EMBL; J03940; AAA37146.1; -; mRNA. DR CCDS; CCDS25543.1; -. [P09470-1] DR CCDS; CCDS25544.1; -. [P09470-2] DR PIR; A34171; A34171. DR PIR; A35655; A35655. DR RefSeq; NP_033728.1; NM_009598.3. [P09470-2] DR RefSeq; NP_997507.1; NM_207624.6. [P09470-1] DR SMR; P09470; -. DR BioGRID; 197920; 3. DR STRING; 10090.ENSMUSP00000001963; -. DR BindingDB; P09470; -. DR ChEMBL; CHEMBL2994; -. DR MEROPS; M02.001; -. DR MEROPS; M02.004; -. DR GlyConnect; P09470; 9 N-Linked glycans (5 sites). DR GlyCosmos; P09470; 14 sites, 16 glycans. DR GlyGen; P09470; 15 sites, 16 N-linked glycans (8 sites), 1 O-linked glycan (1 site). DR iPTMnet; P09470; -. DR PhosphoSitePlus; P09470; -. DR PaxDb; 10090-ENSMUSP00000001963; -. DR PeptideAtlas; P09470; -. DR ProteomicsDB; 285580; -. [P09470-1] DR ProteomicsDB; 285581; -. [P09470-2] DR jPOST; P09470; -. DR DNASU; 11421; -. DR Ensembl; ENSMPUT00000015095; ENSMPUP00000014859; ENSMPUG00000014969. DR Ensembl; ENSMUST00000001963.14; ENSMUSP00000001963.8; ENSMUSG00000020681.15. [P09470-1] DR Ensembl; ENSMUST00000001964.8; ENSMUSP00000001964.8; ENSMUSG00000020681.15. [P09470-2] DR GeneID; 11421; -. DR KEGG; mmu:11421; -. DR UCSC; uc007lxu.2; mouse. [P09470-1] DR UCSC; uc007lxw.2; mouse. [P09470-2] DR CTD; 1636; -. DR VEuPathDB; HostDB:ENSMUSG00000020681; -. DR AGR; MGI:87874; -. DR MGI; MGI:87874; Ace. DR eggNOG; KOG3690; Eukaryota. DR GeneTree; ENSGT00940000162051; -. DR HOGENOM; CLU_014364_3_0_1; -. DR InParanoid; P09470; -. DR OMA; AADYMMN; -. DR OrthoDB; 10029630at2759; -. DR PhylomeDB; P09470; -. DR BRENDA; 3.4.15.1; 3474. DR Reactome; R-MMU-2022377; Metabolism of Angiotensinogen to Angiotensins. DR PRO; PR:P09470; -. DR Bgee; ENSMUSG00000020681; Expressed in small intestine Peyer's patch and 193 other cell types or tissues. DR ExpressionAtlas; P09470; baseline and differential. DR CDD; cd06461; M2_ACE; 2. DR FunFam; 1.10.1370.30:FF:000004; Angiotensin-converting enzyme; 2. DR Gene3D; 1.10.1370.30; -; 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 GO; GO:0009925; C:basal plasma membrane; ISO:GO_Central. DR GO; GO:0031526; C:brush border membrane; ISO:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005768; C:endosome; ISO:GO_Central. DR GO; GO:0009897; C:external side of plasma membrane; ISO:GO_Central. DR GO; GO:0070062; C:extracellular exosome; ISO:GO_Central. DR GO; GO:0005576; C:extracellular region; IDA:MGI. DR GO; GO:0005764; C:lysosome; ISO:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0097225; C:sperm midpiece; ISO:GO_Central. DR GO; GO:0031982; C:vesicle; ISO:GO_Central. DR GO; GO:0003779; F:actin binding; ISO:GO_Central. DR GO; GO:0031711; F:bradykinin receptor binding; ISO:GO_Central. DR GO; GO:0031404; F:chloride ion binding; ISS:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; ISO:GO_Central. DR GO; GO:0008238; F:exopeptidase activity; ISO:GO_Central. DR GO; GO:1901363; F:heterocyclic compound binding; ISO:GO_Central. DR GO; GO:0004181; F:metallocarboxypeptidase activity; IDA:MGI. DR GO; GO:0070573; F:metallodipeptidase activity; ISS:UniProtKB. DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB. DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB. DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:GO_Central. DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; ISO:GO_Central. DR GO; GO:0008233; F:peptidase activity; IMP:MGI. DR GO; GO:0008241; F:peptidyl-dipeptidase activity; IDA:UniProtKB. DR GO; GO:0008240; F:tripeptidyl-peptidase activity; ISO:GO_Central. DR GO; GO:0008270; F:zinc ion binding; ISO:GO_Central. DR GO; GO:0050435; P:amyloid-beta metabolic process; ISO:GO_Central. DR GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; ISO:GO_Central. DR GO; GO:0002003; P:angiotensin maturation; IDA:UniProtKB. DR GO; GO:0038166; P:angiotensin-activated signaling pathway; IMP:BHF-UCL. DR GO; GO:0031100; P:animal organ regeneration; ISO:GO_Central. DR GO; GO:0050482; P:arachidonate secretion; ISO:GO_Central. DR GO; GO:0010815; P:bradykinin catabolic process; ISS:UniProtKB. DR GO; GO:0071838; P:cell proliferation in bone marrow; IMP:BHF-UCL. DR GO; GO:0042755; P:eating behavior; ISO:GO_Central. DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; ISO:GO_Central. DR GO; GO:0060047; P:heart contraction; IMP:MGI. DR GO; GO:0042447; P:hormone catabolic process; IDA:UniProtKB. DR GO; GO:0042445; P:hormone metabolic process; ISO:GO_Central. DR GO; GO:0001822; P:kidney development; IMP:UniProtKB. DR GO; GO:0048286; P:lung alveolus development; ISO:GO_Central. DR GO; GO:0002034; P:maintenance of blood vessel diameter homeostasis by renin-angiotensin; ISO:GO_Central. DR GO; GO:0008584; P:male gonad development; IMP:UniProtKB. DR GO; GO:0090281; P:negative regulation of calcium ion import; ISO:GO_Central. DR GO; GO:0046325; P:negative regulation of D-glucose import across plasma membrane; ISO:GO_Central. DR GO; GO:1903597; P:negative regulation of gap junction assembly; IMP:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0002446; P:neutrophil mediated immunity; IMP:MGI. DR GO; GO:0043171; P:peptide catabolic process; ISO:GO_Central. DR GO; GO:0006518; P:peptide metabolic process; ISO:GO_Central. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:GO_Central. DR GO; GO:0045777; P:positive regulation of blood pressure; ISO:GO_Central. DR GO; GO:0050769; P:positive regulation of neurogenesis; ISO:GO_Central. DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IMP:MGI. DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:GO_Central. DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0060177; P:regulation of angiotensin metabolic process; ISO:GO_Central. DR GO; GO:0008217; P:regulation of blood pressure; IDA:BHF-UCL. DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL. DR GO; GO:1902033; P:regulation of hematopoietic stem cell proliferation; IMP:BHF-UCL. DR GO; GO:0014910; P:regulation of smooth muscle cell migration; ISO:GO_Central. DR GO; GO:0048167; P:regulation of synaptic plasticity; IDA:UniProtKB. DR GO; GO:0003081; P:regulation of systemic arterial blood pressure by renin-angiotensin; ISO:GO_Central. DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:GO_Central. DR GO; GO:0007283; P:spermatogenesis; IMP:MGI. DR GO; GO:0010814; P:substance P catabolic process; ISS:UniProtKB. DR GO; GO:0042310; P:vasoconstriction; ISO:GO_Central. DR GO; GO:0042311; P:vasodilation; ISO:GO_Central. DR Proteomes; UP000000589; Chromosome 11. DR DrugCentral; P09470; -. DR Antibodypedia; 31288; 1054 antibodies from 47 providers. DR RNAct; P09470; protein. DR BioGRID-ORCS; 11421; 2 hits in 78 CRISPR screens. DR AlphaFoldDB; P09470; -. DR FunCoup; P09470; 119. PE 1: Evidence at protein level; KW Alternative promoter usage; Calmodulin-binding; Carboxypeptidase; KW Cell membrane; Cytoplasm; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; KW Phosphoprotein; Protease; Reference proteome; Repeat; Secreted; Signal; KW Transmembrane; Transmembrane helix; Zinc. FT SIGNAL 1..34 FT /evidence="ECO:0000269|PubMed:2835538" FT CHAIN 35..1312 FT /note="Angiotensin-converting enzyme" FT /id="PRO_0000028539" FT CHAIN 35..1237 FT /note="Angiotensin-converting enzyme, soluble form" FT /evidence="ECO:0000250|UniProtKB:P12821" FT /id="PRO_0000028540" FT TOPO_DOM 35..1264 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1265..1281 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 1282..1312 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 45..629 FT /note="Peptidase M2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT DOMAIN 648..1227 FT /note="Peptidase M2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT REGION 1220..1261 FT /note="Juxtamembrane stalk" FT /evidence="ECO:0000250|UniProtKB:P12821" FT ACT_SITE 396 FT /note="Proton acceptor 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT ACT_SITE 525 FT /note="Proton donor 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT ACT_SITE 994 FT /note="Proton acceptor 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355, FT ECO:0000305|PubMed:15665832" FT ACT_SITE 1123 FT /note="Proton donor 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT BINDING 236 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT BINDING 395 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 BINDING 399 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 BINDING 423 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 BINDING 534 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT BINDING 796 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT BINDING 834 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT BINDING 993 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:0000305|PubMed:15665832" FT BINDING 997 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:0000305|PubMed:15665832" FT BINDING 1021 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 BINDING 1095 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT BINDING 1099 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT BINDING 1132 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT MOD_RES 1305 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT CARBOHYD 59 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 79 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 116 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 151 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16944957" FT CARBOHYD 165 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 323 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 514 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 682 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 700 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000250|UniProtKB:P12821" FT CARBOHYD 719 FT /note="N-linked (GlcNAc...) (complex) asparagine" FT /evidence="ECO:0000250|UniProtKB:P12821" FT CARBOHYD 765 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 947 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1196 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 162..170 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT DISULFID 364..382 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT DISULFID 550..562 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT DISULFID 762..768 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT DISULFID 962..980 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT DISULFID 1148..1160 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01355" FT VAR_SEQ 1..580 FT /note="Missing (in isoform Testis-specific)" FT /evidence="ECO:0000303|PubMed:2164636" FT /id="VSP_037638" FT VAR_SEQ 581..646 FT /note="GCSRPWQEVLKDLVGSDALDAKALLEYFQPVSQWLEEQNQRNGEVLGWPENQ FT WRPPLPDNYPEGID -> MGQGWATPGLPSFLFLLLCCGHHLLVLSQVATDHVTANQGI FT TNQATTRSQTTTHQATIDQTTQIPN (in isoform Testis-specific)" FT /evidence="ECO:0000303|PubMed:2164636" FT /id="VSP_037639" FT MUTAGEN 395..399 FT /note="HEMGH->KEMGK: In ACE(7/7) mutant; knockin mice have FT normal blood pressure, renal function, and hematocrit. FT Knockin mice show normal plasma levels of angiotensin II FT but an elevation of plasma and urine peptide N-acetyl-SDKP FT (AcSDKP)." FT /evidence="ECO:0000269|PubMed:14757757" FT MUTAGEN 993 FT /note="H->K: Abolishes peptidase activity but no effect on FT GPIase activity; when associated with K-997." FT /evidence="ECO:0000269|PubMed:15665832" FT MUTAGEN 994 FT /note="E->D: Abolishes peptidase activity but no effect on FT GPIase activity." FT /evidence="ECO:0000269|PubMed:15665832" FT MUTAGEN 997 FT /note="H->K: Abolishes peptidase activity but no effect on FT GPIase activity; when associated with K-993." FT /evidence="ECO:0000269|PubMed:15665832" FT CONFLICT 568 FT /note="A -> T (in Ref. 1; AAA37147)" FT /evidence="ECO:0000305" FT MUTAGEN P09470-2:413..417 FT /note="HEMGH->KEMGK: Abolished dipeptidyl carboxypeptidase FT activity. Knockin mice expressed in a knockout background FT display defects in male fertility. They however show normal FT blood pressure and kidney morphology." FT /evidence="ECO:0000269|PubMed:16270063, FT ECO:0000269|PubMed:17135368" SQ SEQUENCE 1312 AA; 150918 MW; 7DF9F5BE91762DFF CRC64; MGAASGQRGR WPLSPPLLML SLLVLLLQPS PAPALDPGLQ PGNFSPDEAG AQLFAESYNS SAEVVMFQST VASWAHDTNI TEENARRQEE AALVSQEFAE VWGKKAKELY ESIWQNFTDS KLRRIIGSIR TLGPANLPLA QRQQYNSLLS NMSRIYSTGK VCFPNKTATC WSLDPELTNI LASSRSYAKL LFAWEGWHDA VGIPLKPLYQ DFTAISNEAY RQDDFSDTGA FWRSWYESPS FEESLEHIYH QLEPLYLNLH AYVRRALHRR YGDKYVNLRG PIPAHLLGDM WAQSWENIYD MVVPFPDKPN LDVTSTMVQK GWNATHMFRV SEEFFTSLGL SPMPPEFWAE SMLEKPTDGR EVVCHASAWD FYNRKDFRIK QCTRVTMEQL ATVHHEMGHV QYYLQYKDLH VSLRRGANPG FHEAIGDVLA LSVSTPAHLH KIGLLDHVTN DIESDINYLL KMALEKIAFL PFGYLVDQWR WGVFSGRTPP SRYNFDWWYL RTKYQGICPP VARNETHFDA GAKFHIPNVT PYIRYFVSFV LQFQFHQALC KEAGHQGPLH QCDIYQSAQA GAKLKQVLQA GCSRPWQEVL KDLVGSDALD AKALLEYFQP VSQWLEEQNQ RNGEVLGWPE NQWRPPLPDN YPEGIDLETD EAKADRFVEE YDRTAQVLLN EYAEANWQYN TNITIEGSKI LLEKSTEVSN HTLKYGTRAK TFDVSNFQNS SIKRIIKKLQ NLDRAVLPPK ELEEYNQILL DMETTYSLSN ICYTNGTCMP LEPDLTNMMA TSRKYEELLW AWKSWRDKVG RAILPFFPKY VEFSNKIAKL NGYTDAGDSW RSLYESDNLE QDLEKLYQEL QPLYLNLHAY VRRSLHRHYG SEYINLDGPI PAHLLGNMWA QTWSNIYDLV APFPSAPNID ATEAMIKQGW TPRRIFKEAD NFFTSLGLLP VPPEFWNKSM LEKPTDGREV VCHPSAWDFY NGKDFRIKQC TSVNMEDLVI AHHEMGHIQY FMQYKDLPVT FREGANPGFH EAIGDIMALS VSTPKHLYSL NLLSTEGSGY EYDINFLMKM ALDKIAFIPF SYLIDQWRWR VFDGSITKEN YNQEWWSLRL KYQGLCPPVP RSQGDFDPGS KFHVPANVPY VRYFVSFIIQ FQFHEALCRA AGHTGPLHKC DIYQSKEAGK LLADAMKLGY SKPWPEAMKL ITGQPNMSAS AMMNYFKPLT EWLVTENRRH GETLGWPEYN WAPNTARAEG STAESNRVNF LGLYLEPQQA RVGQWVLLFL GVALLVATVG LAHRLYNIRN HHSLRRPHRG PQFGSEVELR HS //