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Protein

Carboxypeptidase B2

Gene

CPB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Blood coagulation, Fibrinolysis, Hemostasis

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS01364-MONOMER.
BRENDAi3.4.17.20. 2681.
ReactomeiR-HSA-2022377. Metabolism of Angiotensinogen to Angiotensins.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:2300. CPB2.

Subcellular locationi

GO - Cellular componenti

  • cell Source: GOC
  • extracellular exosome Source: UniProtKB
  • extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi1361.
OpenTargetsiENSG00000080618.
PharmGKBiPA26822.

Chemistry databases

ChEMBLiCHEMBL3419.
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...)3 Publications1
Glycosylationi73N-linked (GlcNAc...)3 Publications1
Glycosylationi85N-linked (GlcNAc...)2 Publications1
Glycosylationi108N-linked (GlcNAc...) (complex)5 Publications1
Disulfide bondi178 ↔ 1912 Publications
Glycosylationi241N-linked (GlcNAc...); 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.

PTM databases

iPTMnetiQ96IY4.
PhosphoSitePlusiQ96IY4.
UniCarbKBiQ96IY4.

Miscellaneous databases

PMAP-CutDBA8K464.

Expressioni

Tissue specificityi

Plasma; synthesized in the liver.

Gene expression databases

BgeeiENSG00000080618.
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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi26 – 31Combined sources6
Helixi36 – 48Combined sources13
Beta strandi51 – 58Combined sources8
Helixi59 – 61Combined sources3
Beta strandi68 – 73Combined sources6
Helixi74 – 76Combined sources3
Helixi77 – 87Combined sources11
Beta strandi91 – 96Combined sources6
Helixi98 – 107Combined sources10
Turni108 – 110Combined sources3
Helixi117 – 121Combined sources5
Helixi126 – 139Combined sources14
Turni141 – 143Combined sources3
Beta strandi144 – 151Combined sources8
Beta strandi157 – 163Combined sources7
Beta strandi172 – 177Combined sources6
Helixi186 – 201Combined sources16
Turni202 – 204Combined sources3
Helixi206 – 214Combined sources9
Beta strandi215 – 221Combined sources7
Helixi225 – 233Combined sources9
Helixi255 – 257Combined sources3
Turni262 – 265Combined sources4
Beta strandi269 – 271Combined sources3
Helixi287 – 298Combined sources12
Turni299 – 302Combined sources4
Beta strandi303 – 319Combined sources17
Beta strandi321 – 325Combined sources5
Helixi330 – 347Combined sources18
Beta strandi354 – 358Combined sources5
Turni359 – 362Combined sources4
Helixi369 – 374Combined sources6
Turni375 – 377Combined sources3
Beta strandi380 – 387Combined sources8
Beta strandi389 – 392Combined sources4
Helixi393 – 395Combined sources3
Helixi398 – 400Combined sources3
Helixi401 – 422Combined sources22

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...

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.
OMAiLRRNINH.
OrthoDBiEOG091G0HUI.
PhylomeDBiQ96IY4.
TreeFamiTF317197.

Family and domain databases

CDDicd06246. M14_CPB2. 1 hit.
Gene3Di3.30.70.340. 1 hit.
InterProiIPR033849. CPB2.
IPR003146. M14A_act_pep.
IPR000834. Peptidase_M14.
IPR009020. Propept_inh.
[Graphical view]
PfamiPF00246. Peptidase_M14. 1 hit.
PF02244. Propep_M14. 1 hit.
[Graphical view]
PRINTSiPR00765. CRBOXYPTASEA.
SMARTiSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMiSSF54897. SSF54897. 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

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

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 → T.2 PublicationsCorresponds to variant rs3742264dbSNPEnsembl.1
Natural variantiVAR_022258347I → T.5 PublicationsCorresponds to variant rs1926447dbSNPEnsembl.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.
AL157758, AL137141 Genomic DNA. Translation: CAI10904.1.
AL157758, AL137141 Genomic DNA. Translation: CAI10905.1.
AL137141, AL157758 Genomic DNA. Translation: CAI12170.1.
AL137141, AL157758 Genomic DNA. Translation: CAI12171.1.
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]
GeneIDi1361.
KEGGihsa:1361.
UCSCiuc001vaw.4. human. [Q96IY4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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.
AL157758, AL137141 Genomic DNA. Translation: CAI10904.1.
AL157758, AL137141 Genomic DNA. Translation: CAI10905.1.
AL137141, AL157758 Genomic DNA. Translation: CAI12170.1.
AL137141, AL157758 Genomic DNA. Translation: CAI12171.1.
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.
GuidetoPHARMACOLOGYi1594.

Protein family/group databases

MEROPSiM14.009.

PTM databases

iPTMnetiQ96IY4.
PhosphoSitePlusiQ96IY4.
UniCarbKBiQ96IY4.

Polymorphism and mutation databases

DMDMi317373332.

Proteomic databases

PaxDbiQ96IY4.
PeptideAtlasiQ96IY4.
PRIDEiQ96IY4.

Protocols and materials databases

DNASUi1361.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

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

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS01364-MONOMER.
BRENDAi3.4.17.20. 2681.
ReactomeiR-HSA-2022377. Metabolism of Angiotensinogen to Angiotensins.

Miscellaneous databases

EvolutionaryTraceiQ96IY4.
GeneWikiiCarboxypeptidase_B2.
GenomeRNAii1361.
PMAP-CutDBA8K464.
PROiQ96IY4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000080618.
CleanExiHS_CPB2.
ExpressionAtlasiQ96IY4. baseline and differential.
GenevisibleiQ96IY4. HS.

Family and domain databases

CDDicd06246. M14_CPB2. 1 hit.
Gene3Di3.30.70.340. 1 hit.
InterProiIPR033849. CPB2.
IPR003146. M14A_act_pep.
IPR000834. Peptidase_M14.
IPR009020. Propept_inh.
[Graphical view]
PfamiPF00246. Peptidase_M14. 1 hit.
PF02244. Propep_M14. 1 hit.
[Graphical view]
PRINTSiPR00765. CRBOXYPTASEA.
SMARTiSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMiSSF54897. SSF54897. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCBPB2_HUMAN
AccessioniPrimary (citable) accession number: Q96IY4
Secondary accession number(s): A8K464
, Q15114, Q5T9K1, Q5T9K2, Q9P2Y6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 135 of the entry and version 2 of the sequence. [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. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.