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Q96IY4 (CBPB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Carboxypeptidase B2

EC=3.4.17.20
Alternative name(s):
Carboxypeptidase U
Short name=CPU
Plasma carboxypeptidase B
Short name=pCPB
Thrombin-activable fibrinolysis inhibitor
Short name=TAFI
Gene names
Name:CPB2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length423 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.8

Catalytic activity

Release of C-terminal Arg and Lys from a polypeptide. Ref.8

Cofactor

Binds 1 zinc ion per subunit.

Enzyme regulation

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. Ref.13

Subcellular location

Secreted.

Tissue specificity

Plasma; synthesized in the liver.

Post-translational modification

N-glycosylated. N-glycan at Asn-108: Hex5HexNAc4. Ref.10 Ref.12 Ref.13

Sequence similarities

Belongs to the peptidase M14 family.

Ontologies

Keywords
   Biological processBlood coagulation
Fibrinolysis
Hemostasis
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   LigandMetal-binding
Zinc
   Molecular functionCarboxypeptidase
Hydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

fibrinolysis

Inferred from electronic annotation. Source: UniProtKB-KW

liver regeneration

Inferred from electronic annotation. Source: Ensembl

negative regulation of fibrinolysis

Inferred from electronic annotation. Source: Ensembl

negative regulation of hepatocyte proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of plasminogen activation

Inferred from electronic annotation. Source: Ensembl

positive regulation of extracellular matrix constituent secretion

Inferred from electronic annotation. Source: Ensembl

proteolysis

Traceable author statement PubMed 10651877Ref.1. Source: ProtInc

response to drug

Inferred from electronic annotation. Source: Ensembl

response to heat

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular space

Traceable author statement PubMed 10651877Ref.1. Source: ProtInc

   Molecular_functionmetallocarboxypeptidase activity

Traceable author statement PubMed 10651877Ref.1. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96IY4-1)

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.
Isoform 2 (identifier: Q96IY4-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Propeptide23 – 11492Activation peptide
PRO_0000004377
Chain115 – 423309Carboxypeptidase B2
PRO_0000004378

Sites

Active site3851Nucleophile Ref.13
Metal binding1811Zinc; catalytic
Metal binding1841Zinc; catalytic
Metal binding3101Zinc; catalytic
Site324 – 3252Cleavage; by thrombin

Amino acid modifications

Glycosylation441N-linked (GlcNAc...) Ref.9 Ref.10 Ref.13
Glycosylation731N-linked (GlcNAc...) Ref.9 Ref.10 Ref.13
Glycosylation851N-linked (GlcNAc...) Ref.10 Ref.13
Glycosylation1081N-linked (GlcNAc...) (complex) Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Glycosylation2411N-linked (GlcNAc...); partial Ref.10
Disulfide bond178 ↔ 191 Ref.10 Ref.13 Ref.14
Disulfide bond250 ↔ 274 Ref.10 Ref.13 Ref.14
Disulfide bond265 ↔ 279 Ref.10 Ref.13 Ref.14

Natural variations

Alternative sequence198 – 23437Missing in isoform 2.
VSP_013446
Alternative sequence384 – 42340IELRD…VIRNV → SNPPVEKLLPLSLK in isoform 2.
VSP_013447
Natural variant1691A → T. Ref.1 Ref.4
Corresponds to variant rs3742264 [ dbSNP | Ensembl ].
VAR_032565
Natural variant3471I → T. Ref.1 Ref.3 Ref.4 Ref.5 Ref.7
Corresponds to variant rs1926447 [ dbSNP | Ensembl ].
VAR_022258

Experimental info

Sequence conflict251S → T in BAA90475. Ref.2

Secondary structure

............................................................... 423
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 11, 2011. Version 2.
Checksum: B4D20E03ECDD55EF

FASTA42348,424
        10         20         30         40         50         60 
MKLCSLAVLV PIVLFCEQHV FAFQSGQVLA ALPRTSRQVQ VLQNLTTTYE IVLWQPVTAD 

        70         80         90        100        110        120 
LIVKKKQVHF FVNASDVDNV KAHLNVSGIP CSVLLADVED LIQQQISNDT VSPRASASYY 

       130        140        150        160        170        180 
EQYHSLNEIY SWIEFITERH PDMLTKIHIG SSFEKYPLYV LKVSGKEQAA KNAIWIDCGI 

       190        200        210        220        230        240 
HAREWISPAF CLWFIGHITQ FYGIIGQYTN LLRLVDFYVM PVVNVDGYDY SWKKNRMWRK 

       250        260        270        280        290        300 
NRSFYANNHC IGTDLNRNFA SKHWCEEGAS SSSCSETYCG LYPESEPEVK AVASFLRRNI 

       310        320        330        340        350        360 
NQIKAYISMH SYSQHIVFPY SYTRSKSKDH EELSLVASEA VRAIEKISKN TRYTHGHGSE 

       370        380        390        400        410        420 
TLYLAPGGGD DWIYDLGIKY SFTIELRDTG TYGFLLPERY IKPTCREAFA AVSKIAWHVI 


RNV 

« Hide

Isoform 2 [UniParc].

Checksum: 2C011F6D4265F4B8
Show »

FASTA36040,922

References

« Hide 'large scale' references
[1]"Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma."
Eaton D.L., Malloy B.E., Tsai S.P., Henzel W., Drayna D.
J. Biol. Chem. 266:21833-21838(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, INTERACTION WITH PLASMINOGEN, VARIANTS THR-169 AND THR-347.
Tissue: Liver.
[2]"Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma."
Matsumoto A.
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-347.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS THR-169 AND THR-347.
Tissue: Liver.
[5]SeattleSNPs variation discovery resource
Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-347.
[6]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-347.
Tissue: Skeletal muscle.
[8]"Characterization of plasmin-mediated activation of plasma procarboxypeptidase B. Modulation by glycosaminoglycans."
Mao S.S., Cooper C.M., Wood T., Shafer J.A., Gardell S.J.
J. Biol. Chem. 274:35046-35052(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY.
[9]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44; ASN-73 AND ASN-108.
Tissue: Plasma.
[10]"Post-translational modifications of human thrombin-activatable fibrinolysis inhibitor (TAFI): evidence for a large shift in the isoelectric point and reduced solubility upon activation."
Valnickova Z., Christensen T., Skottrup P., Thogersen I.B., Hojrup P., Enghild J.J.
Biochemistry 45:1525-1535(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-44; ASN-73; ASN-85; ASN-108 AND ASN-241, DISULFIDE BONDS.
[11]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-108.
Tissue: Liver.
[12]"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD."
Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.
Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-108, STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY.
[13]"Crystal structures of TAFI elucidate the inactivation mechanism of activated TAFI: a novel mechanism for enzyme autoregulation."
Marx P.F., Brondijk T.H., Plug T., Romijn R.A., Hemrika W., Meijers J.C., Huizinga E.G.
Blood 112:2803-2809(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 24-423 ALONE AND IN COMPLEX WITH INHIBITOR, GLYCOSYLATION AT ASN-44; ASN-73; ASN-85 AND ASN-108, ACTIVE SITE, ZINC-BINDING SITES, ENZYME REGULATION, DISULFIDE BONDS.
[14]"Insights into the molecular inactivation mechanism of human activated thrombin-activatable fibrinolysis inhibitor."
Sanglas L., Arolas J.L., Valnickova Z., Aviles F.X., Enghild J.J., Gomis-Ruth F.X.
J. Thromb. Haemost. 8:1056-1065(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 115-423 IN COMPLEX WITH INHIBITOR, DISULFIDE BONDS.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA41204.
RefSeqNP_001265470.1. NM_001278541.1.
NP_001863.3. NM_001872.4.
UniGeneHs.512937.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalQ96IY4.
SMRQ96IY4. Positions 24-423.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107753. 7 interactions.
IntActQ96IY4. 1 interaction.
STRING9606.ENSP00000181383.

Chemistry

BindingDBQ96IY4.
ChEMBLCHEMBL3419.

Protein family/group databases

MEROPSM14.009.

PTM databases

PhosphoSiteQ96IY4.

Polymorphism databases

DMDM317373332.

Proteomic databases

PaxDbQ96IY4.
PRIDEQ96IY4.

Protocols and materials databases

DNASU1361.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000181383; ENSP00000181383; ENSG00000080618. [Q96IY4-1]
GeneID1361.
KEGGhsa:1361.
UCSCuc001vaw.3. human. [Q96IY4-1]

Organism-specific databases

CTD1361.
GeneCardsGC13M046627.
HGNCHGNC:2300. CPB2.
HPAHPA004146.
MIM603101. gene.
neXtProtNX_Q96IY4.
PharmGKBPA26822.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2866.
HOGENOMHOG000252968.
HOVERGENHBG050815.
InParanoidQ96IY4.
KOK01300.
OMAEIYSWIE.
OrthoDBEOG7RZ5Q9.
PhylomeDBQ96IY4.
TreeFamTF317197.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

BgeeQ96IY4.
CleanExHS_CPB2.
GenevestigatorQ96IY4.

Family and domain databases

Gene3D3.30.70.340. 1 hit.
InterProIPR000834. Peptidase_M14.
IPR003146. Prot_inh_M14A.
IPR009020. Prot_inh_propept.
[Graphical view]
PfamPF00246. Peptidase_M14. 1 hit.
PF02244. Propep_M14. 1 hit.
[Graphical view]
PRINTSPR00765. CRBOXYPTASEA.
SMARTSM00631. Zn_pept. 1 hit.
[Graphical view]
SUPFAMSSF54897. SSF54897. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ96IY4.
GeneWikiCarboxypeptidase_B2.
GenomeRNAi1361.
NextBio5513.
PMAP-CutDBA8K464.
PROQ96IY4.
SOURCESearch...

Entry information

Entry nameCBPB2_HUMAN
AccessionPrimary (citable) accession number: Q96IY4
Secondary accession number(s): A8K464 expand/collapse secondary AC list , Q15114, Q5T9K1, Q5T9K2, Q9P2Y6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: January 11, 2011
Last modified: April 16, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM