CBPB1_HUMAN
ID CBPB1_HUMAN Reviewed; 417 AA.
AC P15086; O60834; Q53XJ0; Q96BQ8;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 4.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Carboxypeptidase B;
DE EC=3.4.17.2 {ECO:0000250|UniProtKB:P00732};
DE AltName: Full=Pancreas-specific protein;
DE Short=PASP;
DE Flags: Precursor;
GN Name=CPB1; Synonyms=CPB, PCPB;
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 PROTEIN SEQUENCE OF 16-40.
RC TISSUE=Pancreas;
RX PubMed=1370825; DOI=10.1016/s0021-9258(18)45919-4;
RA Yamamoto K.K., Pousette A., Chow P., Wilson H., el Shami S., French C.K.;
RT "Isolation of a cDNA encoding a human serum marker for acute pancreatitis.
RT Identification of pancreas-specific protein as pancreatic
RT procarboxypeptidase B.";
RL J. Biol. Chem. 267:2575-2581(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ASN-208.
RC TISSUE=Pancreas;
RX PubMed=9524066; DOI=10.1515/bchm.1998.379.2.149;
RA Aloy P., Catasus L., Villegas V., Reverter D., Vendrell J., Aviles F.X.;
RT "Comparative analysis of the sequences and three-dimensional models of
RT human procarboxypeptidases A1, A2 and B.";
RL Biol. Chem. 379:149-155(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal 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 [6]
RP PROTEIN SEQUENCE OF 16-43, AND TISSUE SPECIFICITY.
RC TISSUE=Pancreas;
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 [7]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 16-417 IN COMPLEX WITH ZINC,
RP DISULFIDE BONDS, AND COFACTOR.
RX PubMed=12162965; DOI=10.1016/s0022-2836(02)00648-4;
RA Barbosa-Pereira P.J., Segura-Martin S., Oliva B., Ferrer-Orta C.,
RA Aviles F.X., Coll M., Gomis-Ruth F.X., Vendrell J.;
RT "Human procarboxypeptidase B: three-dimensional structure and implications
RT for thrombin-activatable fibrinolysis inhibitor (TAFI).";
RL J. Mol. Biol. 321:537-547(2002).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential release of a C-terminal lysine or arginine amino
CC acid.; EC=3.4.17.2; Evidence={ECO:0000250|UniProtKB:P00732};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:12162965};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:12162965};
CC -!- INTERACTION:
CC P15086; P05067: APP; NbExp=3; IntAct=EBI-25936844, EBI-77613;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P00732}. Zymogen
CC granule lumen {ECO:0000250|UniProtKB:P55261}.
CC -!- TISSUE SPECIFICITY: Pancreas. {ECO:0000269|PubMed:2920728}.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR EMBL; M81057; AAA66973.1; -; mRNA.
DR EMBL; AJ224866; CAA12163.1; -; mRNA.
DR EMBL; BT009910; AAP88912.1; -; mRNA.
DR EMBL; CH471052; EAW78903.1; -; Genomic_DNA.
DR EMBL; BC015338; AAH15338.1; -; mRNA.
DR CCDS; CCDS33874.1; -.
DR PIR; A42332; A42332.
DR RefSeq; NP_001862.2; NM_001871.2.
DR PDB; 1KWM; X-ray; 1.60 A; A/B=16-417.
DR PDB; 1ZLI; X-ray; 2.09 A; A=109-417.
DR PDBsum; 1KWM; -.
DR PDBsum; 1ZLI; -.
DR AlphaFoldDB; P15086; -.
DR SMR; P15086; -.
DR BioGRID; 107752; 1.
DR IntAct; P15086; 1.
DR STRING; 9606.ENSP00000417222; -.
DR BindingDB; P15086; -.
DR ChEMBL; CHEMBL2552; -.
DR DrugBank; DB07182; (2S)-2-(3-Carbamimidamidophenyl)-3-[hydroxy(3-phenylpropyl)phosphoryl]propanoic acid.
DR DrugBank; DB07269; (2S)-2-[3-(AMINOMETHYL)PHENYL]-3-[(R)-[(1R)-1-{[(BENZYLOXY)CARBONYL]AMINO}-2-METHYLPROPYL](HYDROXY)PHOSPHORYL]PROPANOIC ACID.
DR DrugBank; DB06921; (2S)-2-[3-(AMINOMETHYL)PHENYL]-3-[(R)-HYDROXY{(1R)-2-METHYL-1-[(PHENYLSULFONYL)AMINO]PROPYL}PHOSPHORYL]PROPANOIC ACID.
DR DrugBank; DB06835; (2S)-2-[3-(AMINOMETHYL)PHENYL]-3-{(S)-HYDROXY[(1R)-2-METHYL-1-{[(2-PHENYLETHYL)SULFONYL]AMINO}PROPYL]PHOSPHORYL}PROPANOIC ACID.
DR DrugBank; DB07157; (5R,6S,8S)-8-[3-(AMINOMETHYL)PHENYL]-6-HYDROXY-5-ISOPROPYL-3-OXO-1-PHENYL-2,7-DIOXA-4-AZA-6-PHOSPHANONAN-9-OIC ACID 6-OXIDE.
DR DrugBank; DB04723; 2-(3-GUANIDINOPHENYL)-3-MERCAPTOPROPANOIC ACID.
DR DrugBank; DB07136; BX-528.
DR DrugBank; DB04272; Citric acid.
DR GuidetoPHARMACOLOGY; 1593; -.
DR MEROPS; M14.003; -.
DR PhosphoSitePlus; P15086; -.
DR BioMuta; CPB1; -.
DR DMDM; 20532382; -.
DR jPOST; P15086; -.
DR MassIVE; P15086; -.
DR MaxQB; P15086; -.
DR PaxDb; P15086; -.
DR PeptideAtlas; P15086; -.
DR PRIDE; P15086; -.
DR ProteomicsDB; 53104; -.
DR Antibodypedia; 18185; 410 antibodies from 35 providers.
DR DNASU; 1360; -.
DR Ensembl; ENST00000282957.9; ENSP00000282957.4; ENSG00000153002.12.
DR Ensembl; ENST00000491148.5; ENSP00000417222.1; ENSG00000153002.12.
DR GeneID; 1360; -.
DR KEGG; hsa:1360; -.
DR MANE-Select; ENST00000282957.9; ENSP00000282957.4; NM_001871.3; NP_001862.2.
DR UCSC; uc003ewl.4; human.
DR CTD; 1360; -.
DR DisGeNET; 1360; -.
DR GeneCards; CPB1; -.
DR HGNC; HGNC:2299; CPB1.
DR HPA; ENSG00000153002; Tissue enriched (pancreas).
DR MIM; 114852; gene.
DR neXtProt; NX_P15086; -.
DR OpenTargets; ENSG00000153002; -.
DR PharmGKB; PA26821; -.
DR VEuPathDB; HostDB:ENSG00000153002; -.
DR eggNOG; KOG2650; Eukaryota.
DR GeneTree; ENSGT00940000157819; -.
DR HOGENOM; CLU_019326_0_0_1; -.
DR InParanoid; P15086; -.
DR OMA; LYKAYGC; -.
DR OrthoDB; 524270at2759; -.
DR PhylomeDB; P15086; -.
DR TreeFam; TF317197; -.
DR BRENDA; 3.4.17.2; 2681.
DR PathwayCommons; P15086; -.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR SignaLink; P15086; -.
DR BioGRID-ORCS; 1360; 13 hits in 1067 CRISPR screens.
DR ChiTaRS; CPB1; human.
DR EvolutionaryTrace; P15086; -.
DR GenomeRNAi; 1360; -.
DR Pharos; P15086; Tchem.
DR PRO; PR:P15086; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P15086; protein.
DR Bgee; ENSG00000153002; Expressed in body of pancreas and 93 other tissues.
DR ExpressionAtlas; P15086; baseline and differential.
DR Genevisible; P15086; HS.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004180; F:carboxypeptidase activity; IDA:MGI.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IDA:MGI.
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; PS00132; CARBOXYPEPT_ZN_1; 1.
DR PROSITE; PS00133; CARBOXYPEPT_ZN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Secreted; Signal; Zinc;
KW Zymogen.
FT SIGNAL 1..15
FT /evidence="ECO:0000269|PubMed:1370825,
FT ECO:0000269|PubMed:2920728"
FT PROPEP 16..110
FT /note="Activation peptide"
FT /id="PRO_0000004371"
FT CHAIN 111..417
FT /note="Carboxypeptidase B"
FT /id="PRO_0000004372"
FT ACT_SITE 378
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00732"
FT BINDING 176..179
FT /ligand="substrate"
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:0000269|PubMed:12162965"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12162965"
FT BINDING 234
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 251..252
FT /ligand="substrate"
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:0000269|PubMed:12162965"
FT BINDING 305..306
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 356
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT DISULFID 173..186
FT /evidence="ECO:0000269|PubMed:12162965"
FT DISULFID 245..268
FT /evidence="ECO:0000269|PubMed:12162965"
FT DISULFID 259..273
FT /evidence="ECO:0000269|PubMed:12162965"
FT VARIANT 208
FT /note="D -> N (in dbSNP:rs1059502)"
FT /evidence="ECO:0000269|PubMed:9524066"
FT /id="VAR_048598"
FT CONFLICT 16
FT /note="H -> A (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 17
FT /note="H -> Q (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="H -> Q (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="Missing (in Ref. 1; AAA66973)"
FT /evidence="ECO:0000305"
FT HELIX 19..22
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 26..32
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 35..47
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 63..71
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 76..85
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 97..103
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 122..135
FT /evidence="ECO:0007829|PDB:1KWM"
FT TURN 137..139
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 140..147
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 153..160
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 168..172
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 181..196
FT /evidence="ECO:0007829|PDB:1KWM"
FT TURN 197..199
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 201..209
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 220..228
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 281..292
FT /evidence="ECO:0007829|PDB:1KWM"
FT TURN 293..296
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 297..304
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 309..313
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 315..318
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 324..342
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 347..350
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 351..354
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 362..368
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 372..378
FT /evidence="ECO:0007829|PDB:1KWM"
FT STRAND 382..385
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 386..388
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:1KWM"
FT HELIX 394..413
FT /evidence="ECO:0007829|PDB:1KWM"
SQ SEQUENCE 417 AA; 47368 MW; EBBB98B27F5D5AF9 CRC64;
MLALLVLVTV ALASAHHGGE HFEGEKVFRV NVEDENHINI IRELASTTQI DFWKPDSVTQ
IKPHSTVDFR VKAEDTVTVE NVLKQNELQY KVLISNLRNV VEAQFDSRVR ATGHSYEKYN
KWETIEAWTQ QVATENPALI SRSVIGTTFE GRAIYLLKVG KAGQNKPAIF MDCGFHAREW
ISPAFCQWFV REAVRTYGRE IQVTELLDKL DFYVLPVLNI DGYIYTWTKS RFWRKTRSTH
TGSSCIGTDP NRNFDAGWCE IGASRNPCDE TYCGPAAESE KETKALADFI RNKLSSIKAY
LTIHSYSQMM IYPYSYAYKL GENNAELNAL AKATVKELAS LHGTKYTYGP GATTIYPAAG
GSDDWAYDQG IRYSFTFELR DTGRYGFLLP ESQIRATCEE TFLAIKYVAS YVLEHLY
