UniProtKB - Q96IY4 (CBPB2_HUMAN)
Protein
Carboxypeptidase B2
Gene
CPB2
Organism
Homo sapiens (Human)
Status
Functioni
Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin.1 Publication
Catalytic activityi
- Release of C-terminal Arg and Lys from a polypeptide.1 Publication EC:3.4.17.20
Cofactori
Zn2+2 PublicationsNote: Binds 1 zinc ion per subunit.2 Publications
Activity regulationi
TAFI/CPB2 is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. The zymogen is stabilized by interactions with the activation peptide. Release of the activation peptide increases a dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg-324.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 181 | Zinc; catalytic2 Publications | 1 | |
Metal bindingi | 184 | Zinc; catalytic2 Publications | 1 | |
Binding sitei | 239 | SubstrateBy similarity | 1 | |
Metal bindingi | 310 | Zinc; catalytic2 Publications | 1 | |
Binding sitei | 363 | SubstrateBy similarity | 1 | |
Active sitei | 385 | Proton donor/acceptorBy similarity | 1 |
GO - Molecular functioni
- metallocarboxypeptidase activity Source: GO_Central
- zinc ion binding Source: InterPro
GO - Biological processi
- blood coagulation Source: UniProtKB-KW
- cellular response to glucose stimulus Source: Ensembl
- fibrinolysis Source: GO_Central
- liver regeneration Source: Ensembl
- negative regulation of fibrinolysis Source: Ensembl
- negative regulation of hepatocyte proliferation Source: Ensembl
- negative regulation of plasminogen activation Source: Ensembl
- positive regulation of extracellular matrix constituent secretion Source: Ensembl
- proteolysis Source: GO_Central
- regulation of complement activation Source: Reactome
- response to drug Source: Ensembl
- response to heat Source: Ensembl
Keywordsi
Molecular function | Carboxypeptidase, Hydrolase, Metalloprotease, Protease |
Biological process | Blood coagulation, Fibrinolysis, Hemostasis |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.4.17.20, 2681 |
PathwayCommonsi | Q96IY4 |
Reactomei | R-HSA-2022377, Metabolism of Angiotensinogen to Angiotensins R-HSA-977606, Regulation of Complement cascade |
Protein family/group databases
MEROPSi | M14.009 |
Names & Taxonomyi
Protein namesi | Recommended name: Carboxypeptidase B2 (EC:3.4.17.201 Publication)Alternative name(s): Carboxypeptidase U Short name: CPU Plasma carboxypeptidase B Short name: pCPB Thrombin-activable fibrinolysis inhibitor Short name: TAFI |
Gene namesi | Name:CPB2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000080618.13 |
HGNCi | HGNC:2300, CPB2 |
MIMi | 603101, gene |
neXtProti | NX_Q96IY4 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: GO_Central
Keywords - Cellular componenti
SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 1361 |
OpenTargetsi | ENSG00000080618 |
PharmGKBi | PA26822 |
Miscellaneous databases
Pharosi | Q96IY4, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3419 |
DrugBanki | DB05712, AZD-9684 DB11311, Prothrombin |
GuidetoPHARMACOLOGYi | 1594 |
Polymorphism and mutation databases
BioMutai | CPB2 |
DMDMi | 317373332 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | Sequence analysisAdd BLAST | 22 | |
PropeptideiPRO_0000004377 | 23 – 114 | Activation peptideAdd BLAST | 92 | |
ChainiPRO_0000004378 | 115 – 423 | Carboxypeptidase B2Add BLAST | 309 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 44 | N-linked (GlcNAc...) asparagine3 Publications | 1 | |
Glycosylationi | 73 | N-linked (GlcNAc...) asparagine3 Publications | 1 | |
Glycosylationi | 85 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 108 | N-linked (GlcNAc...) (complex) asparagine5 Publications | 1 | |
Disulfide bondi | 178 ↔ 191 | 2 Publications | ||
Glycosylationi | 241 | N-linked (GlcNAc...) asparagine; partial1 Publication | 1 | |
Disulfide bondi | 250 ↔ 274 | 2 Publications | ||
Disulfide bondi | 265 ↔ 279 | 2 Publications |
Post-translational modificationi
N-glycosylated. N-glycan at Asn-108: Hex5HexNAc4.5 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 324 – 325 | Cleavage; by thrombin | 2 |
Keywords - PTMi
Disulfide bond, Glycoprotein, ZymogenProteomic databases
CPTACi | CPTAC-657 non-CPTAC-2639 |
jPOSTi | Q96IY4 |
MassIVEi | Q96IY4 |
PaxDbi | Q96IY4 |
PeptideAtlasi | Q96IY4 |
PRIDEi | Q96IY4 |
ProteomicsDBi | 76868 [Q96IY4-1] 76869 [Q96IY4-2] |
PTM databases
GlyConnecti | 699, 16 N-Linked glycans (3 sites) |
GlyGeni | Q96IY4, 5 sites, 3 N-linked glycans (3 sites) |
iPTMneti | Q96IY4 |
PhosphoSitePlusi | Q96IY4 |
UniCarbKBi | Q96IY4 |
Expressioni
Tissue specificityi
Plasma; synthesized in the liver.
Gene expression databases
Bgeei | ENSG00000080618, Expressed in liver and 84 other tissues |
ExpressionAtlasi | Q96IY4, baseline and differential |
Genevisiblei | Q96IY4, HS |
Organism-specific databases
HPAi | ENSG00000080618, Tissue enriched (liver) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 107753, 6 interactors |
IntActi | Q96IY4, 1 interactor |
STRINGi | 9606.ENSP00000181383 |
Chemistry databases
BindingDBi | Q96IY4 |
Miscellaneous databases
RNActi | Q96IY4, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q96IY4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96IY4 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 181 – 184 | Substrate bindingBy similarity | 4 | |
Regioni | 256 – 257 | Substrate bindingBy similarity | 2 | |
Regioni | 311 – 312 | Substrate bindingBy similarity | 2 |
Sequence similaritiesi
Belongs to the peptidase M14 family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG2650, Eukaryota |
GeneTreei | ENSGT00940000159160 |
HOGENOMi | CLU_019326_0_0_1 |
InParanoidi | Q96IY4 |
OMAi | NQPAHIR |
OrthoDBi | 524270at2759 |
PhylomeDBi | Q96IY4 |
TreeFami | TF317197 |
Family and domain databases
Gene3Di | 3.30.70.340, 1 hit |
InterProi | View protein in InterPro IPR036990, M14A-like_propep IPR003146, M14A_act_pep IPR000834, Peptidase_M14 |
Pfami | View protein in Pfam PF00246, Peptidase_M14, 1 hit PF02244, Propep_M14, 1 hit |
PRINTSi | PR00765, CRBOXYPTASEA |
SMARTi | View protein in SMART SM00631, Zn_pept, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q96IY4-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKLCSLAVLV PIVLFCEQHV FAFQSGQVLA ALPRTSRQVQ VLQNLTTTYE
60 70 80 90 100
IVLWQPVTAD LIVKKKQVHF FVNASDVDNV KAHLNVSGIP CSVLLADVED
110 120 130 140 150
LIQQQISNDT VSPRASASYY EQYHSLNEIY SWIEFITERH PDMLTKIHIG
160 170 180 190 200
SSFEKYPLYV LKVSGKEQAA KNAIWIDCGI HAREWISPAF CLWFIGHITQ
210 220 230 240 250
FYGIIGQYTN LLRLVDFYVM PVVNVDGYDY SWKKNRMWRK NRSFYANNHC
260 270 280 290 300
IGTDLNRNFA SKHWCEEGAS SSSCSETYCG LYPESEPEVK AVASFLRRNI
310 320 330 340 350
NQIKAYISMH SYSQHIVFPY SYTRSKSKDH EELSLVASEA VRAIEKISKN
360 370 380 390 400
TRYTHGHGSE TLYLAPGGGD DWIYDLGIKY SFTIELRDTG TYGFLLPERY
410 420
IKPTCREAFA AVSKIAWHVI RNV
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087WSY5 | A0A087WSY5_HUMAN | Carboxypeptidase B2 | CPB2 | 386 | Annotation score: | ||
A0A6Q8PG06 | A0A6Q8PG06_HUMAN | Carboxypeptidase B2 | CPB2 | 220 | Annotation score: | ||
A0A6Q8PHS9 | A0A6Q8PHS9_HUMAN | Carboxypeptidase B2 | CPB2 | 207 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 25 | S → T in BAA90475 (Ref. 2) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032565 | 169 | A → T2 PublicationsCorresponds to variant dbSNP:rs3742264Ensembl. | 1 | |
Natural variantiVAR_022258 | 347 | I → T5 PublicationsCorresponds to variant dbSNP:rs1926447Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_013446 | 198 – 234 | Missing in isoform 2. 1 PublicationAdd BLAST | 37 | |
Alternative sequenceiVSP_013447 | 384 – 423 | IELRD…VIRNV → SNPPVEKLLPLSLK in isoform 2. 1 PublicationAdd BLAST | 40 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M75106 mRNA Translation: AAA60042.1 AB011969 mRNA Translation: BAA90475.1 BT006936 mRNA Translation: AAP35582.1 AK290829 mRNA Translation: BAF83518.1 AY714780 Genomic DNA Translation: AAT97987.1 AL137141 Genomic DNA No translation available. AL157758 Genomic DNA No translation available. BC007057 mRNA Translation: AAH07057.1 |
CCDSi | CCDS9401.1 [Q96IY4-1] |
PIRi | A41204 |
RefSeqi | NP_001265470.1, NM_001278541.1 NP_001863.3, NM_001872.4 [Q96IY4-1] |
Genome annotation databases
Ensembli | ENST00000181383; ENSP00000181383; ENSG00000080618 [Q96IY4-1] |
GeneIDi | 1361 |
KEGGi | hsa:1361 |
UCSCi | uc001vaw.4, human [Q96IY4-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
SeattleSNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M75106 mRNA Translation: AAA60042.1 AB011969 mRNA Translation: BAA90475.1 BT006936 mRNA Translation: AAP35582.1 AK290829 mRNA Translation: BAF83518.1 AY714780 Genomic DNA Translation: AAT97987.1 AL137141 Genomic DNA No translation available. AL157758 Genomic DNA No translation available. BC007057 mRNA Translation: AAH07057.1 |
CCDSi | CCDS9401.1 [Q96IY4-1] |
PIRi | A41204 |
RefSeqi | NP_001265470.1, NM_001278541.1 NP_001863.3, NM_001872.4 [Q96IY4-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3D66 | X-ray | 3.10 | A/B/C | 24-423 | [»] | |
3D67 | X-ray | 3.40 | A/B/C | 24-423 | [»] | |
3D68 | X-ray | 2.80 | A/B/C | 24-423 | [»] | |
3LMS | X-ray | 2.50 | A | 115-423 | [»] | |
4P10 | X-ray | 2.00 | A | 23-423 | [»] | |
5HVF | X-ray | 2.85 | A | 23-423 | [»] | |
5HVG | X-ray | 3.05 | A/C | 23-423 | [»] | |
5HVH | X-ray | 3.00 | A | 23-423 | [»] | |
SMRi | Q96IY4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107753, 6 interactors |
IntActi | Q96IY4, 1 interactor |
STRINGi | 9606.ENSP00000181383 |
Chemistry databases
BindingDBi | Q96IY4 |
ChEMBLi | CHEMBL3419 |
DrugBanki | DB05712, AZD-9684 DB11311, Prothrombin |
GuidetoPHARMACOLOGYi | 1594 |
Protein family/group databases
MEROPSi | M14.009 |
PTM databases
GlyConnecti | 699, 16 N-Linked glycans (3 sites) |
GlyGeni | Q96IY4, 5 sites, 3 N-linked glycans (3 sites) |
iPTMneti | Q96IY4 |
PhosphoSitePlusi | Q96IY4 |
UniCarbKBi | Q96IY4 |
Polymorphism and mutation databases
BioMutai | CPB2 |
DMDMi | 317373332 |
Proteomic databases
CPTACi | CPTAC-657 non-CPTAC-2639 |
jPOSTi | Q96IY4 |
MassIVEi | Q96IY4 |
PaxDbi | Q96IY4 |
PeptideAtlasi | Q96IY4 |
PRIDEi | Q96IY4 |
ProteomicsDBi | 76868 [Q96IY4-1] 76869 [Q96IY4-2] |
Protocols and materials databases
ABCDi | Q96IY4, 2 sequenced antibodies |
Antibodypediai | 1324, 586 antibodies |
DNASUi | 1361 |
Genome annotation databases
Ensembli | ENST00000181383; ENSP00000181383; ENSG00000080618 [Q96IY4-1] |
GeneIDi | 1361 |
KEGGi | hsa:1361 |
UCSCi | uc001vaw.4, human [Q96IY4-1] |
Organism-specific databases
CTDi | 1361 |
DisGeNETi | 1361 |
EuPathDBi | HostDB:ENSG00000080618.13 |
GeneCardsi | CPB2 |
HGNCi | HGNC:2300, CPB2 |
HPAi | ENSG00000080618, Tissue enriched (liver) |
MIMi | 603101, gene |
neXtProti | NX_Q96IY4 |
OpenTargetsi | ENSG00000080618 |
PharmGKBi | PA26822 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2650, Eukaryota |
GeneTreei | ENSGT00940000159160 |
HOGENOMi | CLU_019326_0_0_1 |
InParanoidi | Q96IY4 |
OMAi | NQPAHIR |
OrthoDBi | 524270at2759 |
PhylomeDBi | Q96IY4 |
TreeFami | TF317197 |
Enzyme and pathway databases
BRENDAi | 3.4.17.20, 2681 |
PathwayCommonsi | Q96IY4 |
Reactomei | R-HSA-2022377, Metabolism of Angiotensinogen to Angiotensins R-HSA-977606, Regulation of Complement cascade |
Miscellaneous databases
BioGRID-ORCSi | 1361, 1 hit in 840 CRISPR screens |
ChiTaRSi | CPB2, human |
EvolutionaryTracei | Q96IY4 |
GeneWikii | Carboxypeptidase_B2 |
GenomeRNAii | 1361 |
Pharosi | Q96IY4, Tchem |
PROi | PR:Q96IY4 |
RNActi | Q96IY4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000080618, Expressed in liver and 84 other tissues |
ExpressionAtlasi | Q96IY4, baseline and differential |
Genevisiblei | Q96IY4, HS |
Family and domain databases
Gene3Di | 3.30.70.340, 1 hit |
InterProi | View protein in InterPro IPR036990, M14A-like_propep IPR003146, M14A_act_pep IPR000834, Peptidase_M14 |
Pfami | View protein in Pfam PF00246, Peptidase_M14, 1 hit PF02244, Propep_M14, 1 hit |
PRINTSi | PR00765, CRBOXYPTASEA |
SMARTi | View protein in SMART SM00631, Zn_pept, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CBPB2_HUMAN | |
Accessioni | Q96IY4Primary (citable) accession number: Q96IY4 Secondary accession number(s): A8K464 Q9P2Y6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 26, 2005 |
Last sequence update: | January 11, 2011 | |
Last modified: | December 2, 2020 | |
This is version 164 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Peptidase families
Classification of peptidase families and list of entries