CBPB2_BOVIN
ID CBPB2_BOVIN Reviewed; 423 AA.
AC Q2KIG3;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Carboxypeptidase B2;
DE EC=3.4.17.20;
DE AltName: Full=Carboxypeptidase U;
DE Short=CPU;
DE AltName: Full=Plasma carboxypeptidase B;
DE Short=pCPB;
DE AltName: Full=Thrombin-activable fibrinolysis inhibitor;
DE Short=TAFI;
DE Flags: Precursor;
GN Name=CPB2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Testis;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 23-423 IN COMPLEX WITH ZINC IONS,
RP GLYCOSYLATION AT ASN-44; ASN-73; ASN-85 AND ASN-108, ACTIVE SITE,
RP ZINC-BINDING SITES, DISULFIDE BONDS, AND COFACTOR.
RX PubMed=18669641; DOI=10.1074/jbc.m804003200;
RA Anand K., Pallares I., Valnickova Z., Christensen T., Vendrell J.,
RA Wendt K.U., Schreuder H.A., Enghild J.J., Aviles F.X.;
RT "The crystal structure of thrombin-activable fibrinolysis inhibitor (TAFI)
RT provides the structural basis for its intrinsic activity and the short
RT half-life of TAFIa.";
RL J. Biol. Chem. 283:29416-29423(2008).
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 -!- 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:0000269|PubMed:18669641};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:18669641};
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-324 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9JHH6}.
CC -!- SIMILARITY: Belongs to the peptidase M14 family. {ECO:0000305}.
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DR EMBL; BC112649; AAI12650.1; -; mRNA.
DR RefSeq; NP_001039462.1; NM_001045997.2.
DR PDB; 3D4U; X-ray; 1.70 A; A=115-423.
DR PDB; 3DGV; X-ray; 2.50 A; A/B/C=23-423.
DR PDB; 3OSL; X-ray; 6.00 A; A/C=23-423.
DR PDBsum; 3D4U; -.
DR PDBsum; 3DGV; -.
DR PDBsum; 3OSL; -.
DR AlphaFoldDB; Q2KIG3; -.
DR SMR; Q2KIG3; -.
DR STRING; 9913.ENSBTAP00000009300; -.
DR MEROPS; M14.009; -.
DR iPTMnet; Q2KIG3; -.
DR PaxDb; Q2KIG3; -.
DR PRIDE; Q2KIG3; -.
DR Ensembl; ENSBTAT00000009300; ENSBTAP00000009300; ENSBTAG00000007073.
DR GeneID; 508222; -.
DR KEGG; bta:508222; -.
DR CTD; 1361; -.
DR VEuPathDB; HostDB:ENSBTAG00000007073; -.
DR VGNC; VGNC:27646; CPB2.
DR eggNOG; KOG2650; Eukaryota.
DR GeneTree; ENSGT00940000159160; -.
DR HOGENOM; CLU_019326_0_0_1; -.
DR InParanoid; Q2KIG3; -.
DR OMA; WPYGYDC; -.
DR OrthoDB; 524270at2759; -.
DR TreeFam; TF317197; -.
DR BRENDA; 3.4.17.20; 908.
DR EvolutionaryTrace; Q2KIG3; -.
DR Proteomes; UP000009136; Chromosome 12.
DR Bgee; ENSBTAG00000007073; Expressed in liver and 30 other tissues.
DR ExpressionAtlas; Q2KIG3; baseline.
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:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR GO; GO:0042730; P:fibrinolysis; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR CDD; cd06246; M14_CPB2; 1.
DR DisProt; DP01424; -.
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 1: Evidence at protein level;
KW 3D-structure; Blood coagulation; Carboxypeptidase; Disulfide bond;
KW Fibrinolysis; Glycoprotein; Hemostasis; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Secreted; Signal; Zinc;
KW Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..114
FT /note="Activation peptide"
FT /id="PRO_0000282869"
FT CHAIN 115..423
FT /note="Carboxypeptidase B2"
FT /id="PRO_0000282870"
FT ACT_SITE 385
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00732"
FT BINDING 181..184
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18669641"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18669641"
FT BINDING 239
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 256..257
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 310
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18669641"
FT BINDING 311..312
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT BINDING 363
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00730"
FT SITE 324..325
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18669641"
FT CARBOHYD 73
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18669641"
FT CARBOHYD 85
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18669641"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18669641"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 178..191
FT /evidence="ECO:0000269|PubMed:18669641"
FT DISULFID 250..274
FT /evidence="ECO:0000269|PubMed:18669641"
FT DISULFID 265..279
FT /evidence="ECO:0000269|PubMed:18669641"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:3DGV"
FT HELIX 36..48
FT /evidence="ECO:0007829|PDB:3DGV"
FT STRAND 49..58
FT /evidence="ECO:0007829|PDB:3DGV"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:3DGV"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:3DGV"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:3DGV"
FT HELIX 77..86
FT /evidence="ECO:0007829|PDB:3DGV"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:3DGV"
FT HELIX 98..105
FT /evidence="ECO:0007829|PDB:3DGV"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:3DGV"
FT STRAND 109..112
FT /evidence="ECO:0007829|PDB:3DGV"
FT HELIX 119..121
FT /evidence="ECO:0007829|PDB:3D4U"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:3D4U"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 144..151
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 173..177
FT /evidence="ECO:0007829|PDB:3D4U"
FT HELIX 186..200
FT /evidence="ECO:0007829|PDB:3D4U"
FT TURN 202..204
FT /evidence="ECO:0007829|PDB:3DGV"
FT HELIX 206..214
FT /evidence="ECO:0007829|PDB:3DGV"
FT STRAND 216..221
FT /evidence="ECO:0007829|PDB:3D4U"
FT HELIX 225..233
FT /evidence="ECO:0007829|PDB:3D4U"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:3D4U"
FT TURN 262..265
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:3D4U"
FT HELIX 287..298
FT /evidence="ECO:0007829|PDB:3D4U"
FT TURN 299..302
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 303..310
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 312..319
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 321..325
FT /evidence="ECO:0007829|PDB:3DGV"
FT HELIX 330..347
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 354..357
FT /evidence="ECO:0007829|PDB:3D4U"
FT HELIX 358..361
FT /evidence="ECO:0007829|PDB:3D4U"
FT HELIX 369..376
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 379..385
FT /evidence="ECO:0007829|PDB:3D4U"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:3D4U"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:3D4U"
FT HELIX 401..422
FT /evidence="ECO:0007829|PDB:3D4U"
SQ SEQUENCE 423 AA; 48822 MW; 361E7FE3F885080E CRC64;
MKLYSLGVLV ATVLFCGEHA FAFQRGQVLS ALPRTSRQVQ ILQNVTTTYK IVLWQPVAAE
YIVKGYEVHF FVNASDVSNV KAHLNASRIP FRVLVENVED LIRQQTSNDT ISPRASSSYY
EQYHSLNEIY SWIEVMTERY PDMVEKIHIG SSYEKYPLYV LKVSKKEQRA KNAMWIDCGI
HAREWISPAF CLWFVGSVTY YYGKEKMHTN LLKHMDFYIM PVVNVDGYDY TWKKDRMWRK
NRSLHEKNAC VGTDLNRNFA SKHWCGEGAS SSSCSEIYCG TYPESEPEVK AVADFLRRNI
KHIKAYISMH SYSQKIVFPY SYSRSRSKDH EELSLVAREA VFAMENIHRN IRYTHGSGSE
SLYLAPGGSD DWIYDLGIKY SFTFELRDKG KYGFLLPESY IRPTCSEALV AVAKIASHVV
KNV
