Reviewed, UniProtKB/Swiss-Prot Q96IY4 (CBPB2_HUMAN)

Names and origin

Protein names

Recommended name:
    Carboxypeptidase B2
    EC=3.4.17.20
Alternative name(s):
    Carboxypeptidase U
      Short name=CPU
    Thrombin-activable fibrinolysis inhibitor
      Short name=TAFI
    Plasma carboxypeptidase B
      Short name=pCPB

Gene names

Name:

CPB2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	423 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Catalytic activity	Release of C-terminal Arg and Lys from a polypeptide.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Secreted.
Tissue specificity	Plasma; synthesized in the liver.
Sequence similarities	Belongs to the peptidase M14 family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Ref.1 Traceable author statement. Source: ProtInc
Molecular function	metallocarboxypeptidase activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Propeptide	23 – 114	92	Activation peptide		PRO_0000004377
	Chain	115 – 423	309	Carboxypeptidase B2		PRO_0000004378
Sites
	Active site	385	1	Nucleophile By similarity
	Metal binding	181	1	Zinc By similarity
	Metal binding	184	1	Zinc By similarity
	Metal binding	310	1	Zinc By similarity
Amino acid modifications
	Glycosylation	44	1	N-linked (GlcNAc...) Ref.8 Ref.9
	Glycosylation	73	1	N-linked (GlcNAc...) Ref.8 Ref.9
	Glycosylation	85	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	108	1	N-linked (GlcNAc...) Ref.8 Ref.9
	Glycosylation	241	1	N-linked (GlcNAc...); partial Ref.9
	Disulfide bond	178 ↔ 191		Ref.9
	Disulfide bond	250 ↔ 274		Ref.9
	Disulfide bond	265 ↔ 279		Ref.9
Natural variations
	Alternative sequence	198 – 234	37	Missing in isoform 2.		VSP_013446
	Alternative sequence	384 – 423	40	IELRD…VIRNV → SNPPVEKLLPLSLK in isoform 2.		VSP_013447
	Natural variant	169	1	A → T: dbSNP rs3742264. Ref.1 Ref.4		VAR_032565
	Natural variant	347	1	T → I: dbSNP rs1926447. Ref.2 Ref.5 Ref.6		VAR_022258
Experimental info
	Sequence conflict	25	1	S → T in BAA90475. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 9B383E03F6EE7CF5	FASTA	423	48,412
	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 VRAIEKTSKN TRYTHGHGSE 370 380 390 400 410 420 TLYLAPGGGD DWIYDLGIKY SFTIELRDTG TYGFLLPERY IKPTCREAFA AVSKIAWHVI RNV
	Isoform 2. Checksum: 2C010BEB991CC4B8	FASTA	360	40,910
	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 CLWFIGHNRM WRKNRSFYAN NHCIGTDLNR NFASKHWCEE GASSSSCSET 250 260 270 280 290 300 YCGLYPESEP EVKAVASFLR RNINQIKAYI SMHSYSQHIV FPYSYTRSKS KDHEELSLVA 310 320 330 340 350 360 SEAVRAIEKT SKNTRYTHGH GSETLYLAPG GGDDWIYDLG IKYSFTSNPP VEKLLPLSLK

References

	« Hide 'large scale' referencesShow '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: 1939207] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, INTERACTION WITH PLASMINOGEN, VARIANT THR-169. 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), VARIANT ILE-347.
[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).
[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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-169. Tissue: Liver.
[5]	SeattleSNPs variation discovery resource Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-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. , 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: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-347.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Skeletal muscle.
[8]	"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: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-44; ASN-73 AND ASN-108, MASS SPECTROMETRY. Tissue: Plasma.
[9]	"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: 16445295] [Abstract] Cited for: GLYCOSYLATION AT ASN-44; ASN-73; ASN-85; ASN-108 AND ASN-241, DISULFIDE BONDS.
[10]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-108, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00293057.
IPI00329775.

PIR

A41204.

RefSeq

NP_001863.2.
NP_057497.3.

UniGene

Hs.512937

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein family/group databases

MEROPS

M14.009.

PTM databases

PhosphoSite

Q96IY4.

Proteomic databases

PRIDE

Q96IY4.

Genome annotation databases

Ensembl

ENSG00000080618. Homo sapiens. [Contig view]

GeneID

1361.

KEGG

hsa:1361.

Organism-specific databases

GeneCards

GC13M045525.

HGNC

HGNC:2300. CPB2.

HPA

HPA004146.

MIM

603101. gene.

PharmGKB

PA26822.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q96IY4.

HOVERGEN

Q96IY4.

Enzyme and pathway databases

BRENDA

3.4.17.20. 247.

Gene expression databases

ArrayExpress

Q96IY4.

Bgee

Q96IY4.

CleanEx

HS_CPB2.

GermOnline

ENSG00000080618. Homo sapiens.

Family and domain databases

InterPro

IPR000834. Peptidase_M14.
IPR003146. Prot_inh_M14A.
[Graphical view]

Pfam

PF00246. Peptidase_M14. 1 hit.
PF02244. Propep_M14. 1 hit.
[Graphical view]

PRINTS

PR00765. CRBOXYPTASEA.

SMART

SM00631. Zn_pept. 1 hit.
[Graphical view]

PROSITE

PS00132. CARBOXYPEPT_ZN_1. False negative.
PS00133. CARBOXYPEPT_ZN_2. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

5513.

SOURCE

Search...

Entry information

Entry name

CBPB2_HUMAN

Accession

Primary (citable) accession number: Q96IY4
Secondary accession number(s): A8K464 , Q15114, Q5T9K1, Q5T9K2, Q9P2Y6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2005
Last sequence update:	December 1, 2001
Last modified:	June 16, 2009
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)