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UniProtKB - Q96IY4 (CBPB2_HUMAN)

Protein

Carboxypeptidase B2

Gene

CPB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

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 keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi181Zinc; catalytic2 Publications1
Metal bindingi184Zinc; catalytic2 Publications1
Binding sitei239SubstrateBy similarity1
Metal bindingi310Zinc; catalytic2 Publications1
Binding sitei363SubstrateBy similarity1
Active sitei385Proton donor/acceptorBy similarity1

GO - Molecular functioni

  • metallocarboxypeptidase activity Source: GO_Central
  • zinc ion binding Source: InterPro
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionCarboxypeptidase, Hydrolase, Metalloprotease, Protease
Biological processBlood coagulation, Fibrinolysis, Hemostasis
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.17.20 2681
ReactomeiR-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
R-HSA-977606 Regulation of Complement cascade

Protein family/group databases

MEROPSiM14.009

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000080618.13
HGNCiHGNC:2300 CPB2
MIMi603101 gene
neXtProtiNX_Q96IY4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi1361
OpenTargetsiENSG00000080618
PharmGKBiPA26822

Chemistry databases

ChEMBLiCHEMBL3419
DrugBankiDB05712 AZD-9684
GuidetoPHARMACOLOGYi1594

Polymorphism and mutation databases

DMDMi317373332

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
PropeptideiPRO_000000437723 – 114Activation peptideAdd BLAST92
ChainiPRO_0000004378115 – 423Carboxypeptidase B2Add BLAST309

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi44N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi73N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi85N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi108N-linked (GlcNAc...) (complex) asparagine5 Publications1
Disulfide bondi178 ↔ 1912 Publications
Glycosylationi241N-linked (GlcNAc...) asparagine; partial1 Publication1
Disulfide bondi250 ↔ 2742 Publications
Disulfide bondi265 ↔ 2792 Publications

Post-translational modificationi

N-glycosylated. N-glycan at Asn-108: Hex5HexNAc4.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei324 – 325Cleavage; by thrombin2

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ96IY4
PeptideAtlasiQ96IY4
PRIDEiQ96IY4
ProteomicsDBi76868
76869 [Q96IY4-2]

PTM databases

GlyConnecti699
iPTMnetiQ96IY4
PhosphoSitePlusiQ96IY4
UniCarbKBiQ96IY4

Expressioni

Tissue specificityi

Plasma; synthesized in the liver.

Gene expression databases

BgeeiENSG00000080618 Expressed in 67 organ(s), highest expression level in liver
CleanExiHS_CPB2
ExpressionAtlasiQ96IY4 baseline and differential
GenevisibleiQ96IY4 HS

Organism-specific databases

HPAiHPA004146

Interactioni

Protein-protein interaction databases

BioGridi107753, 6 interactors
IntActiQ96IY4, 1 interactor
STRINGi9606.ENSP00000181383

Chemistry databases

BindingDBiQ96IY4

Structurei

Secondary structure

1423
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ96IY4
SMRiQ96IY4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96IY4

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni181 – 184Substrate bindingBy similarity4
Regioni256 – 257Substrate bindingBy similarity2
Regioni311 – 312Substrate bindingBy similarity2

Sequence similaritiesi

Belongs to the peptidase M14 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2650 Eukaryota
COG2866 LUCA
GeneTreeiENSGT00760000119103
HOGENOMiHOG000252968
HOVERGENiHBG050815
InParanoidiQ96IY4
KOiK01300
OMAiNQPAHIR
OrthoDBiEOG091G0HUI
PhylomeDBiQ96IY4
TreeFamiTF317197

Family and domain databases

CDDicd06246 M14_CPB2, 1 hit
Gene3Di3.30.70.340, 1 hit
InterProiView protein in InterPro
IPR033849 CPB2
IPR036990 M14A-like_propep
IPR003146 M14A_act_pep
IPR000834 Peptidase_M14
PfamiView protein in Pfam
PF00246 Peptidase_M14, 1 hit
PF02244 Propep_M14, 1 hit
PRINTSiPR00765 CRBOXYPTASEA
SMARTiView protein in SMART
SM00631 Zn_pept, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q96IY4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:423
Mass (Da):48,424
Last modified:January 11, 2011 - v2
Checksum:iB4D20E03ECDD55EF
GO
Isoform 2 (identifier: Q96IY4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     198-234: Missing.
     384-423: IELRDTGTYGFLLPERYIKPTCREAFAAVSKIAWHVIRNV → SNPPVEKLLPLSLK

Show »
Length:360
Mass (Da):40,922
Checksum:i2C011F6D4265F4B8
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WSY5A0A087WSY5_HUMAN
Carboxypeptidase B2
CPB2
386Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25S → T in BAA90475 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032565169A → T2 PublicationsCorresponds to variant dbSNP:rs3742264Ensembl.1
Natural variantiVAR_022258347I → T5 PublicationsCorresponds to variant dbSNP:rs1926447Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013446198 – 234Missing in isoform 2. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_013447384 – 423IELRD…VIRNV → SNPPVEKLLPLSLK in isoform 2. 1 PublicationAdd BLAST40

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
CCDSiCCDS9401.1 [Q96IY4-1]
PIRiA41204
RefSeqiNP_001265470.1, NM_001278541.1
NP_001863.3, NM_001872.4 [Q96IY4-1]
UniGeneiHs.512937

Genome annotation databases

EnsembliENST00000181383; ENSP00000181383; ENSG00000080618 [Q96IY4-1]
ENST00000645658; ENSP00000496703; ENSG00000080618 [Q96IY4-1]
GeneIDi1361
KEGGihsa:1361
UCSCiuc001vaw.4 human [Q96IY4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
CCDSiCCDS9401.1 [Q96IY4-1]
PIRiA41204
RefSeqiNP_001265470.1, NM_001278541.1
NP_001863.3, NM_001872.4 [Q96IY4-1]
UniGeneiHs.512937

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3D66X-ray3.10A/B/C24-423[»]
3D67X-ray3.40A/B/C24-423[»]
3D68X-ray2.80A/B/C24-423[»]
3LMSX-ray2.50A115-423[»]
4P10X-ray2.00A23-423[»]
5HVFX-ray2.85A23-423[»]
5HVGX-ray3.05A/C23-423[»]
5HVHX-ray3.00A23-423[»]
ProteinModelPortaliQ96IY4
SMRiQ96IY4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107753, 6 interactors
IntActiQ96IY4, 1 interactor
STRINGi9606.ENSP00000181383

Chemistry databases

BindingDBiQ96IY4
ChEMBLiCHEMBL3419
DrugBankiDB05712 AZD-9684
GuidetoPHARMACOLOGYi1594

Protein family/group databases

MEROPSiM14.009

PTM databases

GlyConnecti699
iPTMnetiQ96IY4
PhosphoSitePlusiQ96IY4
UniCarbKBiQ96IY4

Polymorphism and mutation databases

DMDMi317373332

Proteomic databases

PaxDbiQ96IY4
PeptideAtlasiQ96IY4
PRIDEiQ96IY4
ProteomicsDBi76868
76869 [Q96IY4-2]

Protocols and materials databases

DNASUi1361
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000181383; ENSP00000181383; ENSG00000080618 [Q96IY4-1]
ENST00000645658; ENSP00000496703; ENSG00000080618 [Q96IY4-1]
GeneIDi1361
KEGGihsa:1361
UCSCiuc001vaw.4 human [Q96IY4-1]

Organism-specific databases

CTDi1361
DisGeNETi1361
EuPathDBiHostDB:ENSG00000080618.13
GeneCardsiCPB2
HGNCiHGNC:2300 CPB2
HPAiHPA004146
MIMi603101 gene
neXtProtiNX_Q96IY4
OpenTargetsiENSG00000080618
PharmGKBiPA26822
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2650 Eukaryota
COG2866 LUCA
GeneTreeiENSGT00760000119103
HOGENOMiHOG000252968
HOVERGENiHBG050815
InParanoidiQ96IY4
KOiK01300
OMAiNQPAHIR
OrthoDBiEOG091G0HUI
PhylomeDBiQ96IY4
TreeFamiTF317197

Enzyme and pathway databases

BRENDAi3.4.17.20 2681
ReactomeiR-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
R-HSA-977606 Regulation of Complement cascade

Miscellaneous databases

ChiTaRSiCPB2 human
EvolutionaryTraceiQ96IY4
GeneWikiiCarboxypeptidase_B2
GenomeRNAii1361
PROiPR:Q96IY4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000080618 Expressed in 67 organ(s), highest expression level in liver
CleanExiHS_CPB2
ExpressionAtlasiQ96IY4 baseline and differential
GenevisibleiQ96IY4 HS

Family and domain databases

CDDicd06246 M14_CPB2, 1 hit
Gene3Di3.30.70.340, 1 hit
InterProiView protein in InterPro
IPR033849 CPB2
IPR036990 M14A-like_propep
IPR003146 M14A_act_pep
IPR000834 Peptidase_M14
PfamiView protein in Pfam
PF00246 Peptidase_M14, 1 hit
PF02244 Propep_M14, 1 hit
PRINTSiPR00765 CRBOXYPTASEA
SMARTiView protein in SMART
SM00631 Zn_pept, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCBPB2_HUMAN
AccessioniPrimary (citable) accession number: Q96IY4
Secondary accession number(s): A8K464
, Q15114, Q5T9K1, Q5T9K2, Q9P2Y6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: January 11, 2011
Last modified: November 7, 2018
This is version 150 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
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