CBPB2_RAT
ID CBPB2_RAT Reviewed; 422 AA.
AC Q9EQV9; Q3B7V3; Q5BKB8;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Carboxypeptidase B2;
DE EC=3.4.17.20;
DE AltName: Full=Carboxypeptidase R;
DE Short=CPR;
DE AltName: Full=Carboxypeptidase U;
DE Short=CPU;
DE AltName: Full=Thrombin-activable fibrinolysis inhibitor;
DE Short=TAFI;
DE Flags: Precursor;
GN Name=Cpb2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=11021404; DOI=10.1111/j.1348-0421.2000.tb02555.x;
RA Kato T., Sato T., Matsuo S., Yamamoto T., Campbell W., Hotta N., Okada N.,
RA Okada H.;
RT "Molecular cloning and partial characterization of rat procarboxypeptidase
RT R and carboxypeptidase N.";
RL Microbiol. Immunol. 44:719-728(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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).
CC -!- FUNCTION: Cleaves C-terminal arginine or lysine residues from
CC biologically active peptides such as kinins or anaphylatoxins in the
CC circulation thereby regulating their activities. Down-regulates
CC fibrinolysis by removing C-terminal lysine residues from fibrin that
CC has already been partially degraded by plasmin.
CC {ECO:0000269|PubMed:11021404}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of C-terminal Arg and Lys from a polypeptide.;
CC EC=3.4.17.20;
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 -!- ACTIVITY REGULATION: TAFI/CPB2 is unique among carboxypeptidases in
CC that it spontaneously inactivates with a short half-life, a property
CC that is crucial for its role in controlling blood clot lysis. The
CC zymogen is stabilized by interactions with the activation peptide.
CC Release of the activation peptide increases a dynamic flap mobility and
CC in time this leads to conformational changes that disrupt the catalytic
CC site and expose a cryptic thrombin-cleavage site present at Arg-323 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Plasma; synthesized in the liver.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR EMBL; AB042598; BAB18617.1; -; mRNA.
DR EMBL; BC091133; AAH91133.1; -; mRNA.
DR EMBL; BC107447; AAI07448.1; -; mRNA.
DR RefSeq; NP_446069.1; NM_053617.2.
DR AlphaFoldDB; Q9EQV9; -.
DR SMR; Q9EQV9; -.
DR STRING; 10116.ENSRNOP00000014909; -.
DR MEROPS; M14.009; -.
DR GlyGen; Q9EQV9; 6 sites.
DR PhosphoSitePlus; Q9EQV9; -.
DR PaxDb; Q9EQV9; -.
DR Ensembl; ENSRNOT00000014909; ENSRNOP00000014909; ENSRNOG00000010935.
DR GeneID; 113936; -.
DR KEGG; rno:113936; -.
DR UCSC; RGD:71035; rat.
DR CTD; 1361; -.
DR RGD; 71035; Cpb2.
DR eggNOG; KOG2650; Eukaryota.
DR GeneTree; ENSGT00940000159160; -.
DR HOGENOM; CLU_019326_0_0_1; -.
DR InParanoid; Q9EQV9; -.
DR OMA; WPYGYDC; -.
DR OrthoDB; 524270at2759; -.
DR PhylomeDB; Q9EQV9; -.
DR TreeFam; TF317197; -.
DR BRENDA; 3.4.17.20; 5301.
DR Reactome; R-RNO-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR Reactome; R-RNO-977606; Regulation of Complement cascade.
DR PRO; PR:Q9EQV9; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000010935; Expressed in liver and 12 other tissues.
DR Genevisible; Q9EQV9; RN.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0004180; F:carboxypeptidase activity; IDA:RGD.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0042730; P:fibrinolysis; IMP:RGD.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0051918; P:negative regulation of fibrinolysis; IDA:RGD.
DR GO; GO:2000346; P:negative regulation of hepatocyte proliferation; IMP:RGD.
DR GO; GO:0010757; P:negative regulation of plasminogen activation; IMP:RGD.
DR GO; GO:0003331; P:positive regulation of extracellular matrix constituent secretion; IMP:RGD.
DR GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0009408; P:response to heat; IDA:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR CDD; cd06246; M14_CPB2; 1.
DR Gene3D; 3.30.70.340; -; 1.
DR InterPro; IPR033849; CPB2.
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.
PE 2: Evidence at transcript level;
KW Blood coagulation; Carboxypeptidase; Disulfide bond; Fibrinolysis;
KW Glycoprotein; Hemostasis; Hydrolase; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..113
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000004381"
FT CHAIN 114..422
FT /note="Carboxypeptidase B2"
FT /id="PRO_0000004382"
FT ACT_SITE 384
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00732"
FT BINDING 180..183
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 238
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 255..256
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 310..311
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 362
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT SITE 323..324
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT CARBOHYD 43
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 72
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 177..190
FT /evidence="ECO:0000250|UniProtKB:Q96IY4"
FT DISULFID 249..273
FT /evidence="ECO:0000250|UniProtKB:Q96IY4"
FT DISULFID 264..278
FT /evidence="ECO:0000250|UniProtKB:Q96IY4"
SQ SEQUENCE 422 AA; 48827 MW; FFFD32A51A9366C8 CRC64;
MKLYGLGVLV AIILYEKHGL AFQSGHVLSA LPRTSRQVQL LQNLTTTYEV VLWQPVTAEF
IEKKKEVHFF VNASDVNSVK AYLNASRIPF NVLMNNVEDL IQQQTSNDTV SPRASSSYYE
QYHSLNEIYS WIEVITEQHP DMLQKIYIGS SYEKYPLYVL KVSGKEHRVK NAIWIDCGIH
AREWISPAFC LWFIGYVTQF HGKENTYTRL LRHVDFYIMP VMNVDGYDYT WKKNRMWRKN
RSVHMNNRCV GTDLNRNFAS KHWCEKGASS FSCSETYCGL YPESEPEVKA VADFLRRNIN
HIKAYISMHS YSQQILFPYS YNRSKSKDHE ELSLVASEAV RAIESINKNT RYTHGSGSES
LYLAPGGSDD WIYDLGIKYS FTIELRDTGR YGFLLPERFI KPTCAEALAA VSKIAWHVIR
NS
