CBPN_HUMAN
ID CBPN_HUMAN Reviewed; 458 AA.
AC P15169; B1AP59;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Carboxypeptidase N catalytic chain;
DE Short=CPN;
DE EC=3.4.17.3;
DE AltName: Full=Anaphylatoxin inactivator;
DE AltName: Full=Arginine carboxypeptidase;
DE AltName: Full=Carboxypeptidase N polypeptide 1;
DE AltName: Full=Carboxypeptidase N small subunit;
DE AltName: Full=Kininase-1;
DE AltName: Full=Lysine carboxypeptidase;
DE AltName: Full=Plasma carboxypeptidase B;
DE AltName: Full=Serum carboxypeptidase N;
DE Short=SCPN;
DE Flags: Precursor;
GN Name=CPN1; Synonyms=ACBP;
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].
RX PubMed=2912725; DOI=10.1111/j.1432-1033.1989.tb14488.x;
RA Gebhard W., Schube M., Eulitz M.;
RT "cDNA cloning and complete primary structure of the small, active subunit
RT of human carboxypeptidase N (kininase 1).";
RL Eur. J. Biochem. 178:603-607(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP PROTEIN SEQUENCE OF 21-67; 162-190; 329-343 AND 379-416.
RX PubMed=3408501; DOI=10.1016/0006-291x(88)90284-7;
RA Skidgel R.A., Bennett C.D., Schilling J.W., Tan F., Weerasinghe D.K.,
RA Erdoes E.G.;
RT "Amino acid sequence of the N-terminus and selected tryptic peptides of the
RT active subunit of human plasma carboxypeptidase N: comparison with other
RT carboxypeptidases.";
RL Biochem. Biophys. Res. Commun. 154:1323-1329(1988).
RN [6]
RP 3D-STRUCTURE MODELING.
RX PubMed=8267877; DOI=10.1515/bchm3.1993.374.7-12.843;
RA Hendriks D., Vingron M., Vriend G., Wang W., Nalis N., Scharpe S.;
RT "On the specificity of carboxypeptidase N, a comparative study.";
RL Biol. Chem. Hoppe-Seyler 374:843-849(1993).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 21-458, SUBUNIT, DISULFIDE BONDS,
RP AND GLYCOSYLATION AT THR-400; THR-402 AND THR-409.
RX PubMed=17157876; DOI=10.1016/j.jmb.2006.11.025;
RA Keil C., Maskos K., Than M., Hoopes J.T., Huber R., Tan F., Deddish P.A.,
RA Erdos E.G., Skidgel R.A., Bode W.;
RT "Crystal structure of the human carboxypeptidase N (kininase I) catalytic
RT domain.";
RL J. Mol. Biol. 366:504-516(2007).
RN [8]
RP VARIANT CPND ASP-178.
RX PubMed=12560874; DOI=10.1007/s100380300003;
RA Cao H., Hegele R.A.;
RT "DNA polymorphism and mutations in CPN1, including the genomic basis of
RT carboxypeptidase N deficiency.";
RL J. Hum. Genet. 48:20-22(2003).
CC -!- FUNCTION: Protects the body from potent vasoactive and inflammatory
CC peptides containing C-terminal Arg or Lys (such as kinins or
CC anaphylatoxins) which are released into the circulation.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of a C-terminal basic amino acid, preferentially
CC lysine.; EC=3.4.17.3;
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 -!- SUBUNIT: Tetramer of two catalytic chains and two glycosylated inactive
CC chains. {ECO:0000269|PubMed:17157876}.
CC -!- INTERACTION:
CC P15169; Q5SUL5: HLA-A; NbExp=3; IntAct=EBI-2116369, EBI-8561769;
CC P15169; Q92993: KAT5; NbExp=3; IntAct=EBI-2116369, EBI-399080;
CC P15169; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-2116369, EBI-11742507;
CC P15169; Q96CV9: OPTN; NbExp=3; IntAct=EBI-2116369, EBI-748974;
CC P15169; P17252: PRKCA; NbExp=3; IntAct=EBI-2116369, EBI-1383528;
CC P15169; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-2116369, EBI-9090795;
CC P15169; P61981: YWHAG; NbExp=3; IntAct=EBI-2116369, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- TISSUE SPECIFICITY: Synthesized in the liver and secreted in plasma.
CC -!- DISEASE: Carboxypeptidase N deficiency (CPND) [MIM:212070]: Patients
CC affected present some combination of angioedema or chronic urticaria,
CC as well as hay fever or asthma, and have also slightly depressed serum
CC carboxy peptidase N, suggestive of autosomal recessive inheritance of
CC this disorder. {ECO:0000269|PubMed:12560874}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
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; X14329; CAA32507.1; -; mRNA.
DR EMBL; AK313972; BAG36687.1; -; mRNA.
DR EMBL; CH471066; EAW49848.1; -; Genomic_DNA.
DR EMBL; BC027897; AAH27897.1; -; mRNA.
DR CCDS; CCDS7486.1; -.
DR PIR; A30798; A30798.
DR PIR; S02074; S02074.
DR RefSeq; NP_001299.1; NM_001308.2.
DR PDB; 2NSM; X-ray; 2.10 A; A=23-458.
DR PDBsum; 2NSM; -.
DR AlphaFoldDB; P15169; -.
DR SMR; P15169; -.
DR BioGRID; 107761; 21.
DR CORUM; P15169; -.
DR IntAct; P15169; 14.
DR STRING; 9606.ENSP00000359446; -.
DR BindingDB; P15169; -.
DR ChEMBL; CHEMBL4713; -.
DR DrugBank; DB12271; ORE-1001.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR GuidetoPHARMACOLOGY; 1597; -.
DR MEROPS; M14.004; -.
DR GlyGen; P15169; 3 sites.
DR iPTMnet; P15169; -.
DR PhosphoSitePlus; P15169; -.
DR BioMuta; CPN1; -.
DR DMDM; 115896; -.
DR jPOST; P15169; -.
DR MassIVE; P15169; -.
DR PaxDb; P15169; -.
DR PeptideAtlas; P15169; -.
DR PRIDE; P15169; -.
DR ProteomicsDB; 53115; -.
DR Antibodypedia; 31135; 250 antibodies from 29 providers.
DR DNASU; 1369; -.
DR Ensembl; ENST00000370418.8; ENSP00000359446.3; ENSG00000120054.12.
DR GeneID; 1369; -.
DR KEGG; hsa:1369; -.
DR MANE-Select; ENST00000370418.8; ENSP00000359446.3; NM_001308.3; NP_001299.1.
DR UCSC; uc001kql.3; human.
DR CTD; 1369; -.
DR DisGeNET; 1369; -.
DR GeneCards; CPN1; -.
DR HGNC; HGNC:2312; CPN1.
DR HPA; ENSG00000120054; Tissue enriched (liver).
DR MalaCards; CPN1; -.
DR MIM; 212070; phenotype.
DR MIM; 603103; gene.
DR neXtProt; NX_P15169; -.
DR OpenTargets; ENSG00000120054; -.
DR PharmGKB; PA26829; -.
DR VEuPathDB; HostDB:ENSG00000120054; -.
DR eggNOG; KOG2649; Eukaryota.
DR GeneTree; ENSGT00940000158235; -.
DR HOGENOM; CLU_006722_1_3_1; -.
DR InParanoid; P15169; -.
DR OMA; MGDYFRL; -.
DR OrthoDB; 101221at2759; -.
DR PhylomeDB; P15169; -.
DR TreeFam; TF315592; -.
DR BRENDA; 3.4.17.3; 2681.
DR PathwayCommons; P15169; -.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SignaLink; P15169; -.
DR SIGNOR; P15169; -.
DR BioGRID-ORCS; 1369; 7 hits in 1066 CRISPR screens.
DR ChiTaRS; CPN1; human.
DR EvolutionaryTrace; P15169; -.
DR GeneWiki; CPN1; -.
DR GenomeRNAi; 1369; -.
DR Pharos; P15169; Tchem.
DR PRO; PR:P15169; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P15169; protein.
DR Bgee; ENSG00000120054; Expressed in right lobe of liver and 32 other tissues.
DR ExpressionAtlas; P15169; baseline and differential.
DR Genevisible; P15169; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0010815; P:bradykinin catabolic process; IEA:Ensembl.
DR GO; GO:0006518; P:peptide metabolic process; IBA:GO_Central.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR CDD; cd03864; M14_CPN; 1.
DR InterPro; IPR008969; CarboxyPept-like_regulatory.
DR InterPro; IPR027063; CPN1.
DR InterPro; IPR033814; M14_CPN.
DR InterPro; IPR000834; Peptidase_M14.
DR PANTHER; PTHR11532:SF80; PTHR11532:SF80; 1.
DR Pfam; PF00246; Peptidase_M14; 1.
DR PRINTS; PR00765; CRBOXYPTASEA.
DR SMART; SM00631; Zn_pept; 1.
DR SUPFAM; SSF49464; SSF49464; 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; Direct protein sequencing; Disease variant;
KW Disulfide bond; Glycoprotein; Hydrolase; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:3408501"
FT CHAIN 21..458
FT /note="Carboxypeptidase N catalytic chain"
FT /id="PRO_0000004394"
FT REGION 21..340
FT /note="Catalytic"
FT REGION 423..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 308
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P14384"
FT BINDING 86
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 89
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 216
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT CARBOHYD 400
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000305|PubMed:17157876"
FT CARBOHYD 402
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000305|PubMed:17157876"
FT CARBOHYD 409
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000305|PubMed:17157876"
FT DISULFID 42..104
FT /evidence="ECO:0000269|PubMed:17157876"
FT DISULFID 271..311
FT /evidence="ECO:0000269|PubMed:17157876"
FT VARIANT 178
FT /note="G -> D (in CPND; dbSNP:rs61751507)"
FT /evidence="ECO:0000269|PubMed:12560874"
FT /id="VAR_042415"
FT CONFLICT 42
FT /note="C -> R (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="T -> E (in Ref. 5; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 28..41
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 46..53
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 91..109
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 112..120
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 122..127
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 131..139
FT /evidence="ECO:0007829|PDB:2NSM"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:2NSM"
FT TURN 146..150
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 167..176
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 189..192
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 195..206
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 209..216
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 218..225
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 248..261
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 282..285
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 292..299
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 303..314
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:2NSM"
FT HELIX 320..336
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 341..347
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 358..361
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 364..369
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 374..378
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 382..390
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 397..403
FT /evidence="ECO:0007829|PDB:2NSM"
FT STRAND 405..407
FT /evidence="ECO:0007829|PDB:2NSM"
SQ SEQUENCE 458 AA; 52286 MW; 9BEF3E459E291E39 CRC64;
MSDLLSVFLH LLLLFKLVAP VTFRHHRYDD LVRTLYKVQN ECPGITRVYS IGRSVEGRHL
YVLEFSDHPG IHEPLEPEVK YVGNMHGNEA LGRELMLQLS EFLCEEFRNR NQRIVQLIQD
TRIHILPSMN PDGYEVAAAQ GPNKPGYLVG RNNANGVDLN RNFPDLNTYI YYNEKYGGPN
HHLPLPDNWK SQVEPETRAV IRWMHSFNFV LSANLHGGAV VANYPYDKSF EHRVRGVRRT
ASTPTPDDKL FQKLAKVYSY AHGWMFQGWN CGDYFPDGIT NGASWYSLSK GMQDFNYLHT
NCFEITLELS CDKFPPEEEL QREWLGNREA LIQFLEQVHQ GIKGMVLDEN YNNLANAVIS
VSGINHDVTS GDHGDYFRLL LPGIYTVSAT APGYDPETVT VTVGPAEPTL VNFHLKRSIP
QVSPVRRAPS RRHGVRAKVQ PQARKKEMEM RQLQRGPA
