ID CBPA1_HUMAN Reviewed; 419 AA. AC P15085; A4D1M1; Q53XU0; Q9BS67; Q9UCF2; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 2. DT 02-SEP-2026, entry version 211. DE RecName: Full=Carboxypeptidase A1 {ECO:0000305}; DE EC=3.4.17.1 {ECO:0000269|PubMed:20385563, ECO:0000269|PubMed:8806703}; DE Flags: Precursor; GN Name=CPA1 {ECO:0000312|HGNC:HGNC:2296}; Synonyms=CPA; 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]. RC TISSUE=Pancreas; RX PubMed=1417781; DOI=10.1042/bj2870299; RA Catasus L., Villegas V., Pascual R., Aviles F.X., Wicker-Planquart C., RA Puigserver A.; RT "cDNA cloning and sequence analysis of human pancreatic procarboxypeptidase RT A1."; RL Biochem. J. 287:299-303(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=8806703; DOI=10.1006/abbi.1996.0310; RA Laethem R.M., Blumenkopf T.A., Cory M., Elwell L., Moxham C.P., Ray P.H., RA Walton L.M., Smith G.K.; RT "Expression and characterization of human pancreatic preprocarboxypeptidase RT A1 and preprocarboxypeptidase A2."; RL Arch. Biochem. Biophys. 332:8-18(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-276. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-276. RC TISSUE=Pancreas; 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 [8] RP PROTEIN SEQUENCE OF 17-43 AND 114-135, AND INTERACTION WITH PROELASTASE 2. RX PubMed=2307232; DOI=10.1016/0014-5793(90)80665-6; RA Moulard M., Michon T., Kerfelec B., Chapus C.; RT "Further studies on the human pancreatic binary complexes involving RT procarboxypeptidase A."; RL FEBS Lett. 261:179-183(1990). RN [9] RP PROTEIN SEQUENCE OF 17-42. RX PubMed=2920728; DOI=10.1111/j.1432-1033.1989.tb14590.x; RA Pascual R., Burgos F.J., Salva M., Soriano F., Mendez E., Aviles F.X.; RT "Purification and properties of five different forms of human RT procarboxypeptidases."; RL Eur. J. Biochem. 179:609-616(1989). RN [10] RP PROTEIN SEQUENCE OF 113-143. RC TISSUE=Pancreas; RX PubMed=8318831; DOI=10.1002/bmc.1130070308; RA Linder D., Linder M., Schade H., Sziegoleit A.; RT "Separation of human pancreatic carboxypeptidase A isoenzymes by high RT performance liquid chromatography."; RL Biomed. Chromatogr. 7:143-145(1993). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 330-396. RX PubMed=1969228; RA Stewart E.A., Craik C.S., Hake L., Bowcock A.M.; RT "Human carboxypeptidase A identifies a BglII RFLP and maps to 7q31-qter."; RL Am. J. Hum. Genet. 46:795-800(1990). RN [12] RP ACTIVITY REGULATION. RX PubMed=23746805; DOI=10.1016/j.str.2013.04.021; RA Alonso del Rivero M., Reytor M.L., Trejo S.A., Chavez M.A., Aviles F.X., RA Reverter D.; RT "A noncanonical mechanism of carboxypeptidase inhibition revealed by the RT crystal structure of the Tri-Kunitz SmCI in complex with human CPA4."; RL Structure 21:1118-1126(2013). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=20385563; DOI=10.1074/jbc.m109.060350; RA Tanco S., Zhang X., Morano C., Aviles F.X., Lorenzo J., Fricker L.D.; RT "Characterization of the substrate specificity of human carboxypeptidase A4 RT and implications for a role in extracellular peptide processing."; RL J. Biol. Chem. 285:18385-18396(2010). RN [14] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 111-419 IN COMPLEX WITH RP POLYACRYLIC ACID AND ZINC IONS, SUBUNIT, AND DISULFIDE BOND. RX PubMed=18566513; DOI=10.1107/s0907444908013474; RA Pallares I., Fernandez D., Comellas-Bigler M., Fernandez-Recio J., RA Ventura S., Aviles F.X., Bode W., Vendrell J.; RT "Direct interaction between a human digestive protease and the mucoadhesive RT poly(acrylic acid)."; RL Acta Crystallogr. D 64:784-791(2008). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 112-418 IN COMPLEX WITH ASCARIS RP CARBOXYPEPTIDASE INHIBITOR AND ZINC IONS, SUBUNIT, AND DISULFIDE BOND. RX PubMed=19179285; DOI=10.1073/pnas.0812623106; RA Sanglas L., Aviles F.X., Huber R., Gomis-Rueth F.X., Arolas J.L.; RT "Mammalian metallopeptidase inhibition at the defense barrier of Ascaris RT parasite."; RL Proc. Natl. Acad. Sci. U.S.A. 106:1743-1747(2009). CC -!- FUNCTION: Carboxypeptidase that catalyzes the release of a C-terminal CC amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or CC -Pro (PubMed:20385563, PubMed:8806703). Catalyzes the conversion of CC leukotriene C4 to leukotriene F4 via the hydrolysis of an amide bond CC (By similarity). {ECO:0000250|UniProtKB:P00730, CC ECO:0000269|PubMed:20385563, ECO:0000269|PubMed:8806703}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Release of a C-terminal amino acid, but little or no action CC with -Asp, -Glu, -Arg, -Lys or -Pro.; EC=3.4.17.1; CC Evidence={ECO:0000269|PubMed:20385563, ECO:0000269|PubMed:8806703}; CC -!- CATALYTIC ACTIVITY: CC Reaction=leukotriene C4 + H2O = leukotriene F4 + glycine; CC Xref=Rhea:RHEA:50740, ChEBI:CHEBI:15377, ChEBI:CHEBI:57305, CC ChEBI:CHEBI:57973, ChEBI:CHEBI:133618; CC Evidence={ECO:0000250|UniProtKB:P00730}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50741; CC Evidence={ECO:0000250|UniProtKB:P00730}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:18566513}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:18566513}; CC -!- ACTIVITY REGULATION: Inhibited by interaction with the S.magnifica CC carboxypeptidase inhibitor SmCI. {ECO:0000269|PubMed:23746805}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=20.4 uM for 3-(2-furyl)acryloyl-Phe-Phe (at 25 degrees Celsius) CC {ECO:0000269|PubMed:20385563}; CC KM=166 uM for 3-(2-furyl)acryloyl-Phe-Trp (at 25 degrees Celsius) CC {ECO:0000269|PubMed:20385563}; CC KM=15.7 uM for 3-(2-furyl)acryloyl-Phe-Leu (at 25 degrees Celsius) CC {ECO:0000269|PubMed:20385563}; CC KM=9.33 uM for 3-(2-furyl)acryloyl-Phe-Ile (at 25 degrees Celsius) CC {ECO:0000269|PubMed:20385563}; CC KM=128 uM for 3-(2-furyl)acryloyl-Phe-Met (at 25 degrees Celsius) CC {ECO:0000269|PubMed:20385563}; CC KM=300 uM for 3-(2-furyl)acryloyl-Phe-Ala (at 25 degrees Celsius) CC {ECO:0000269|PubMed:20385563}; CC KM=8.95 uM for 3-(2-furyl)acryloyl-Phe-Val (at 25 degrees Celsius) CC {ECO:0000269|PubMed:20385563}; CC Note=kcat is 76.6 sec(-1) with 3-(2-furyl)acryloyl-Phe-Phe as CC substrate (at 25 degrees Celsius) (PubMed:20385563). kcat is 81.3 CC sec(-1) with 3-(2-furyl)acryloyl-Phe-Trp as substrate (at 25 degrees CC Celsius) (PubMed:20385563). kcat is 34 sec(-1) with CC 3-(2-furyl)acryloyl-Phe-Leu as substrate (at 25 degrees Celsius) CC (PubMed:20385563). kcat is 9.77 sec(-1) with CC 3-(2-furyl)acryloyl-Phe-Ile as substrate (at 25 degrees Celsius) CC (PubMed:20385563). kcat is 51.8 sec(-1) with CC 3-(2-furyl)acryloyl-Phe-Met as substrate (at 25 degrees Celsius) CC (PubMed:20385563). kcat is 78 sec(-1) with CC 3-(2-furyl)acryloyl-Phe-Ala as substrate (at 25 degrees Celsius) CC (PubMed:20385563). kcat is 12.3 sec(-1) with CC 3-(2-furyl)acryloyl-Phe-Val as substrate (at 25 degrees Celsius) CC (PubMed:20385563). {ECO:0000269|PubMed:20385563}; CC -!- SUBUNIT: Monomer. May form a complex with proelastase 2. CC {ECO:0000269|PubMed:18566513, ECO:0000269|PubMed:19179285}. CC -!- INTERACTION: CC P15085; P19399; Xeno; NbExp=2; IntAct=EBI-1642148, EBI-15754788; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9UI42}. CC -!- SIMILARITY: Belongs to the peptidase M14 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; X67318; CAA47732.1; -; mRNA. DR EMBL; AK291493; BAF84182.1; -; mRNA. DR EMBL; BT007313; AAP35977.1; -; mRNA. DR EMBL; CH236950; EAL24089.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83763.1; -; Genomic_DNA. DR EMBL; BC005279; AAH05279.1; -; mRNA. DR CCDS; CCDS5820.1; -. DR PIR; S29127; S29127. DR RefSeq; NP_001859.1; NM_001868.4. DR PDB; 2V77; X-ray; 1.60 A; A/B=111-419. DR PDB; 3FJU; X-ray; 1.60 A; A=112-418. DR PDB; 4UEE; X-ray; 2.27 A; A/B=111-419. DR PDB; 4UEZ; X-ray; 2.29 A; A/B=111-419. DR PDB; 5OM9; X-ray; 1.80 A; A/B=1-419. DR PDB; 6I6Z; X-ray; 1.72 A; A/B=111-418. DR AlphaFoldDB; P15085; -. DR MDRepo; P15085; -. DR SMR; P15085; -. DR BioGRID; 107749; 2. DR DIP; DIP-48699N; -. DR FunCoup; P15085; 160. DR IntAct; P15085; 3. DR STRING; 9606.ENSP00000011292; -. DR BindingDB; P15085; -. DR ChEMBL; CHEMBL2088; -. DR DrugBank; DB06924; (2R)-2-benzyl-3-nitropropanoic acid. DR DrugBank; DB07484; (2R)-4,4-dihydroxy-5-nitro-2-(phenylmethyl)pentanoic acid. DR DrugBank; DB02494; (S)-3-phenyllactic acid. DR DrugBank; DB03441; 2-Benzyl-3-Iodopropanoic Acid. DR DrugBank; DB04316; D-[(N-Hydroxyamino)Carbonyl]Phenylalanine. DR DrugBank; DB03201; D-Cysteine. DR DrugBank; DB11095; Desirudin. DR DrugBank; DB02652; L-[(N-Hydroxyamino)Carbonyl]Phenylalanine. DR DrugBank; DB07506; L-BENZYLSUCCINIC ACID. DR DrugBank; DB04058; N-Carbamoylphenylalanine. DR DrugBank; DB07351; O-(((1R)-((N-(PHENYL-METHOXY-CARBONYL)-ALANYL)-AMINO)METHYL)HYDROXYPHOSPHINYL)3-L-PHENYLLACTATE. DR DrugBank; DB08762; O-(((1R)-((N-PHENYLMETHOXYCARBONYL-L-ALANYL)AMINO)ETHYL)HYDROXYPHOSPHONO)-L-BENZYLACETIC ACID. DR DrugBank; DB08368; OCTANE-1,3,5,7-TETRACARBOXYLIC ACID. DR DrugBank; DB03012; Phenylalanine-N-Sulfonamide. DR GuidetoPHARMACOLOGY; 1587; -. DR MEROPS; M14.001; -. DR iPTMnet; P15085; -. DR PhosphoSitePlus; P15085; -. DR BioMuta; CPA1; -. DR DMDM; 399196; -. DR MassIVE; P15085; -. DR PaxDb; 9606-ENSP00000011292; -. DR PeptideAtlas; P15085; -. DR ProteomicsDB; 53103; -. DR Pumba; P15085; -. DR Antibodypedia; 17964; 631 antibodies from 41 providers. DR DNASU; 1357; -. DR Ensembl; ENST00000011292.8; ENSP00000011292.3; ENSG00000091704.10. DR GeneID; 1357; -. DR KEGG; hsa:1357; -. DR MANE-Select; ENST00000011292.8; ENSP00000011292.3; NM_001868.4; NP_001859.1. DR UCSC; uc003vpx.4; human. DR AGR; HGNC:2296; -. DR ClinPGx; PA26816; -. DR CTD; 1357; -. DR DisGeNET; 1357; -. DR GeneCards; CPA1; -. DR HGNC; HGNC:2296; CPA1. DR HPA; ENSG00000091704; Tissue enriched (pancreas). DR MalaCards; CPA1; -. DR MIM; 114850; gene. DR OpenTargets; ENSG00000091704; -. DR Orphanet; 676; Autosomal dominant hereditary chronic pancreatitis. DR VEuPathDB; HostDB:ENSG00000091704; -. DR eggNOG; KOG2650; Eukaryota. DR GeneTree; ENSGT00940000158082; -. DR InParanoid; P15085; -. DR OMA; MFAFHSQ; -. DR OrthoDB; 3626597at2759; -. DR PAN-GO; P15085; 3 GO annotations based on evolutionary models. DR PhylomeDB; P15085; -. DR BRENDA; 3.4.17.1; 2681. DR PathwayCommons; P15085; -. DR Reactome; R-HSA-9925561; Developmental Lineage of Pancreatic Acinar Cells. DR SignaLink; P15085; -. DR Agora; ENSG00000091704; -. DR BioGRID-ORCS; 1357; 8 hits in 1143 CRISPR screens. DR ChiTaRS; CPA1; human. DR EvolutionaryTrace; P15085; -. DR GeneWiki; Carboxypeptidase_A1; -. DR GenomeRNAi; 1357; -. DR Pharos; P15085; Tchem. DR PRO; PR:P15085; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P15085; protein. DR Bgee; ENSG00000091704; Expressed in body of pancreas and 95 other cell types or tissues. DR ExpressionAtlas; P15085; baseline and differential. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0004181; F:metallocarboxypeptidase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006691; P:leukotriene metabolic process; ISS:UniProtKB. DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl. DR GO; GO:0006508; P:proteolysis; IBA:GO_Central. DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl. DR CDD; cd03870; M14_CPA; 1. DR FunFam; 3.40.630.10:FF:000132; Carboxypeptidase A1; 1. DR FunFam; 3.30.70.340:FF:000001; Carboxypeptidase A5; 1. DR Gene3D; 3.30.70.340; Metallocarboxypeptidase-like; 1. DR Gene3D; 3.40.630.10; Zn peptidases; 1. DR InterPro; IPR057246; CARBOXYPEPT_ZN_1. DR InterPro; IPR057247; CARBOXYPEPT_ZN_2. DR InterPro; IPR034248; CPA_M14_CPD. DR InterPro; IPR036990; M14A-like_propep. DR InterPro; IPR003146; M14A_act_pep. DR InterPro; IPR000834; Peptidase_M14. DR PANTHER; PTHR11705:SF94; CARBOXYPEPTIDASE A1; 1. DR PANTHER; PTHR11705; PROTEASE FAMILY M14 CARBOXYPEPTIDASE A,B; 1. DR Pfam; PF00246; Peptidase_M14; 1. DR Pfam; PF02244; Propep_M14; 1. DR PRINTS; PR00765; CRBOXYPTASEA. DR SMART; SM00631; Zn_pept; 1. DR SUPFAM; SSF54897; Protease propeptides/inhibitors; 1. DR SUPFAM; SSF53187; Zn-dependent exopeptidases; 1. DR PROSITE; PS00132; CARBOXYPEPT_ZN_1; 1. DR PROSITE; PS00133; CARBOXYPEPT_ZN_2; 1. DR PROSITE; PS52035; PEPTIDASE_M14; 1. DR PDBsum; 2V77; -. DR PDBsum; 3FJU; -. DR PDBsum; 4UEE; -. DR PDBsum; 4UEZ; -. DR PDBsum; 5OM9; -. DR PDBsum; 6I6Z; -. PE 1: Evidence at protein level; KW 3D-structure; Carboxypeptidase; Direct protein sequencing; Disulfide bond; KW Hydrolase; Metal-binding; Metalloprotease; Protease; KW Proteomics identification; Reference proteome; Secreted; Signal; Zinc; KW Zymogen. FT SIGNAL 1..16 FT /evidence="ECO:0000269|PubMed:2307232, FT ECO:0000269|PubMed:2920728" FT PROPEP 17..110 FT /note="Activation peptide" FT /id="PRO_0000004345" FT CHAIN 111..419 FT /note="Carboxypeptidase A1" FT /id="PRO_0000004346" FT DOMAIN 121..414 FT /note="Peptidase M14" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379" FT ACT_SITE 380 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379" FT BINDING 179..182 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:18566513, FT ECO:0007744|PDB:2V77" FT BINDING 179 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379, FT ECO:0000269|PubMed:18566513, ECO:0007744|PDB:2V77" FT BINDING 182 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379, FT ECO:0000269|PubMed:18566513, ECO:0007744|PDB:2V77" FT BINDING 237 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:18566513, FT ECO:0007744|PDB:2V77" FT BINDING 254..255 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:18566513, FT ECO:0007744|PDB:2V77" FT BINDING 306 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01379, FT ECO:0000269|PubMed:18566513, ECO:0007744|PDB:2V77" FT BINDING 307..308 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:18566513, FT ECO:0007744|PDB:2V77" FT BINDING 358 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:18566513, FT ECO:0007744|PDB:2V77" FT DISULFID 248..271 FT /evidence="ECO:0000269|PubMed:18566513, FT ECO:0000269|PubMed:19179285" FT VARIANT 208 FT /note="A -> T (in dbSNP:rs34474469)" FT /id="VAR_048593" FT VARIANT 276 FT /note="H -> R (in dbSNP:rs17849959)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4" FT /id="VAR_054311" FT CONFLICT 139..141 FT /note="NPH -> HPG (in Ref. 10; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 24..28 FT /evidence="ECO:0007829|PDB:5OM9" FT HELIX 33..43 FT /evidence="ECO:0007829|PDB:5OM9" FT HELIX 46..48 FT /evidence="ECO:0007829|PDB:5OM9" FT STRAND 51..54 FT /evidence="ECO:0007829|PDB:5OM9" FT STRAND 63..67 FT /evidence="ECO:0007829|PDB:5OM9" FT HELIX 69..71 FT /evidence="ECO:0007829|PDB:5OM9" FT HELIX 72..81 FT /evidence="ECO:0007829|PDB:5OM9" FT STRAND 86..91 FT /evidence="ECO:0007829|PDB:5OM9" FT HELIX 93..104 FT /evidence="ECO:0007829|PDB:5OM9" FT TURN 114..116 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 125..138 FT /evidence="ECO:0007829|PDB:3FJU" FT TURN 140..142 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 143..150 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 156..162 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 164..168 FT /evidence="ECO:0007829|PDB:4UEE" FT STRAND 171..176 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 183..199 FT /evidence="ECO:0007829|PDB:3FJU" FT TURN 200..202 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 204..212 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 214..219 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 223..231 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 253..255 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 257..260 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 263..268 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 284..296 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 299..309 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 311..315 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 326..344 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 346..348 FT /evidence="ECO:0007829|PDB:4UEE" FT STRAND 349..352 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 353..356 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 364..370 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 374..382 FT /evidence="ECO:0007829|PDB:3FJU" FT STRAND 384..387 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 393..395 FT /evidence="ECO:0007829|PDB:3FJU" FT HELIX 396..416 FT /evidence="ECO:0007829|PDB:3FJU" SQ SEQUENCE 419 AA; 47140 MW; 439FAFFFAEE958B1 CRC64; MRGLLVLSVL LGAVFGKEDF VGHQVLRISV ADEAQVQKVK ELEDLEHLQL DFWRGPAHPG SPIDVRVPFP SIQAVKIFLE SHGISYETMI EDVQSLLDEE QEQMFAFRSR ARSTDTFNYA TYHTLEEIYD FLDLLVAENP HLVSKIQIGN TYEGRPIYVL KFSTGGSKRP AIWIDTGIHS REWVTQASGV WFAKKITQDY GQDAAFTAIL DTLDIFLEIV TNPDGFAFTH STNRMWRKTR SHTAGSLCIG VDPNRNWDAG FGLSGASSNP CSETYHGKFA NSEVEVKSIV DFVKDHGNIK AFISIHSYSQ LLMYPYGYKT EPVPDQDELD QLSKAAVTAL ASLYGTKFNY GSIIKAIYQA SGSTIDWTYS QGIKYSFTFE LRDTGRYGFL LPASQIIPTA KETWLALLTI MEHTLNHPY //