CBPA3_HUMAN
ID CBPA3_HUMAN Reviewed; 417 AA.
AC P15088; Q96E94;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Mast cell carboxypeptidase A;
DE Short=MC-CPA;
DE EC=3.4.17.1;
DE AltName: Full=Carboxypeptidase A3;
DE Flags: Precursor;
GN Name=CPA3;
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], AND VARIANT MET-171.
RC TISSUE=Lung;
RX PubMed=2594780; DOI=10.1073/pnas.86.23.9480;
RA Reynolds D.S., Gurley D.S., Stevens R.L., Sugarbaker D.J., Austen K.F.,
RA Serafin W.E.;
RT "Cloning of cDNAs that encode human mast cell carboxypeptidase A, and
RT comparison of the protein with mouse mast cell carboxypeptidase A and rat
RT pancreatic carboxypeptidases.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:9480-9484(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-171.
RC TISSUE=Mast cell;
RX PubMed=1729276; DOI=10.1172/jci115571;
RA Reynolds D.S., Gurley D.S., Austen K.F.;
RT "Cloning and characterization of the novel gene for mast cell
RT carboxypeptidase A.";
RL J. Clin. Invest. 89:273-282(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-171.
RC TISSUE=Bone marrow;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 110-417, AND VARIANT MET-171.
RX PubMed=1629626; DOI=10.1111/1523-1747.ep12616776;
RA Natsuaki M., Stewart C.B., Vanderslice P., Schwartz L.B., Natsuaki M.,
RA Wintroub B.U., Rutter W.J., Goldstein S.M.;
RT "Human skin mast cell carboxypeptidase: functional characterization, cDNA
RT cloning, and genealogy.";
RL J. Invest. Dermatol. 99:138-145(1992).
RN [6]
RP PROTEIN SEQUENCE OF 110-137.
RX PubMed=2708524; DOI=10.1172/jci114061;
RA Goldstein S.M., Kaempfer C.E., Kealey J.T., Wintroub B.U.;
RT "Human mast cell carboxypeptidase. Purification and characterization.";
RL J. Clin. Invest. 83:1630-1636(1989).
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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P00730};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P00730};
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle.
CC Note=Secretory granules.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR EMBL; M27717; AAA35652.1; -; mRNA.
DR EMBL; M73720; AAA59568.1; -; Genomic_DNA.
DR EMBL; M73716; AAA59568.1; JOINED; Genomic_DNA.
DR EMBL; M73717; AAA59568.1; JOINED; Genomic_DNA.
DR EMBL; M73718; AAA59568.1; JOINED; Genomic_DNA.
DR EMBL; M73719; AAA59568.1; JOINED; Genomic_DNA.
DR EMBL; AC092979; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012613; AAH12613.1; -; mRNA.
DR EMBL; S40234; AAB22578.2; -; mRNA.
DR CCDS; CCDS3138.1; -.
DR PIR; A43929; A43929.
DR RefSeq; NP_001861.2; NM_001870.3.
DR AlphaFoldDB; P15088; -.
DR SMR; P15088; -.
DR BioGRID; 107751; 3.
DR IntAct; P15088; 1.
DR STRING; 9606.ENSP00000296046; -.
DR BindingDB; P15088; -.
DR ChEMBL; CHEMBL2645; -.
DR MEROPS; M14.010; -.
DR GlyConnect; 1491; 1 N-Linked glycan (1 site).
DR GlyGen; P15088; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; P15088; -.
DR PhosphoSitePlus; P15088; -.
DR BioMuta; CPA3; -.
DR DMDM; 317373331; -.
DR OGP; P15088; -.
DR jPOST; P15088; -.
DR MassIVE; P15088; -.
DR PaxDb; P15088; -.
DR PeptideAtlas; P15088; -.
DR PRIDE; P15088; -.
DR ProteomicsDB; 53105; -.
DR Antibodypedia; 1510; 201 antibodies from 25 providers.
DR DNASU; 1359; -.
DR Ensembl; ENST00000296046.4; ENSP00000296046.3; ENSG00000163751.4.
DR GeneID; 1359; -.
DR KEGG; hsa:1359; -.
DR MANE-Select; ENST00000296046.4; ENSP00000296046.3; NM_001870.4; NP_001861.2.
DR UCSC; uc003ewm.4; human.
DR CTD; 1359; -.
DR DisGeNET; 1359; -.
DR GeneCards; CPA3; -.
DR HGNC; HGNC:2298; CPA3.
DR HPA; ENSG00000163751; Tissue enhanced (gallbladder, lung).
DR MIM; 114851; gene.
DR neXtProt; NX_P15088; -.
DR OpenTargets; ENSG00000163751; -.
DR PharmGKB; PA26818; -.
DR VEuPathDB; HostDB:ENSG00000163751; -.
DR eggNOG; KOG2650; Eukaryota.
DR GeneTree; ENSGT00940000161551; -.
DR HOGENOM; CLU_019326_0_0_1; -.
DR InParanoid; P15088; -.
DR OMA; WYPGATH; -.
DR OrthoDB; 524270at2759; -.
DR PhylomeDB; P15088; -.
DR TreeFam; TF317197; -.
DR BRENDA; 3.4.17.1; 2681.
DR PathwayCommons; P15088; -.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR SignaLink; P15088; -.
DR BioGRID-ORCS; 1359; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; CPA3; human.
DR GeneWiki; CPA3; -.
DR GenomeRNAi; 1359; -.
DR Pharos; P15088; Tchem.
DR PRO; PR:P15088; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P15088; protein.
DR Bgee; ENSG00000163751; Expressed in gall bladder and 139 other tissues.
DR Genevisible; P15088; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0030141; C:secretory granule; NAS:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; EXP:Reactome.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002003; P:angiotensin maturation; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR CDD; cd03871; M14_CPB; 1.
DR Gene3D; 3.30.70.340; -; 1.
DR InterPro; IPR034253; CPB_M14_CPD.
DR InterPro; IPR036990; M14A-like_propep.
DR InterPro; IPR003146; M14A_act_pep.
DR InterPro; IPR000834; Peptidase_M14.
DR Pfam; PF00246; Peptidase_M14; 1.
DR Pfam; PF02244; Propep_M14; 1.
DR PRINTS; PR00765; CRBOXYPTASEA.
DR SMART; SM00631; Zn_pept; 1.
DR PROSITE; PS00133; CARBOXYPEPT_ZN_2; 1.
PE 1: Evidence at protein level;
KW Carboxypeptidase; Cytoplasmic vesicle; Direct protein sequencing;
KW Disulfide bond; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Reference proteome; Signal; Zinc; Zymogen.
FT SIGNAL 1..15
FT PROPEP 16..109
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:2708524"
FT /id="PRO_0000004395"
FT CHAIN 110..417
FT /note="Mast cell carboxypeptidase A"
FT /id="PRO_0000004396"
FT ACT_SITE 378
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 304
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT DISULFID 173..186
FT /evidence="ECO:0000250"
FT DISULFID 245..268
FT /evidence="ECO:0000250"
FT VARIANT 81
FT /note="A -> S (in dbSNP:rs2270523)"
FT /id="VAR_048602"
FT VARIANT 171
FT /note="T -> M (in dbSNP:rs12489516)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1629626, ECO:0000269|PubMed:1729276,
FT ECO:0000269|PubMed:2594780"
FT /id="VAR_033725"
FT CONFLICT 63
FT /note="N -> K (in Ref. 4; AAH12613)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="G -> R (in Ref. 5; AAB22578)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="I -> T (in Ref. 5; AAB22578)"
FT /evidence="ECO:0000305"
FT CONFLICT 355
FT /note="I -> N (in Ref. 5; AAB22578)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 417 AA; 48670 MW; ACB9038758117F9A CRC64;
MRLILPVGLI ATTLAIAPVR FDREKVFRVK PQDEKQADII KDLAKTNELD FWYPGATHHV
AANMMVDFRV SEKESQAIQS ALDQNKMHYE ILIHDLQEEI EKQFDVKEDI PGRHSYAKYN
NWEKIVAWTE KMMDKYPEMV SRIKIGSTVE DNPLYVLKIG EKNERRKAIF TDCGIHAREW
VSPAFCQWFV YQATKTYGRN KIMTKLLDRM NFYILPVFNV DGYIWSWTKN RMWRKNRSKN
QNSKCIGTDL NRNFNASWNS IPNTNDPCAD NYRGSAPESE KETKAVTNFI RSHLNEIKVY
ITFHSYSQML LFPYGYTSKL PPNHEDLAKV AKIGTDVLST RYETRYIYGP IESTIYPISG
SSLDWAYDLG IKHTFAFELR DKGKFGFLLP ESRIKPTCRE TMLAVKFIAK YILKHTS
