P48052 (CBPA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carboxypeptidase A2
EC=3.4.17.15

Gene names

Name:

CPA2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	419 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)

Catalytic activity	Similar to that of carboxypeptidase A (EC 3.4.17.1), but with a preference for bulkier C-terminal residues.
Cofactor	Binds 1 zinc ion per subunit.
Subcellular location	Secreted.
Sequence similarities	Belongs to the peptidase M14 family.
Sequence caution	The sequence AAA74425.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH07009.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH14571.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH15140.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence EAL24092.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW vacuolar protein catabolic process Traceable author statement Ref.7. Source: ProtInc
Cellular_component	extracellular region Inferred from direct assay Ref.7. Source: UniProtKB
Molecular_function	metallocarboxypeptidase activity Inferred from direct assay Ref.7. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Propeptide

19 – 114

96

Activation peptide

PRO_0000004353

Chain

115 – 419

305

Carboxypeptidase A2

PRO_0000004354

Regions

Region

179 – 182

4

Substrate binding By similarity

Region

254 – 255

2

Substrate binding By similarity

Region

307 – 308

2

Substrate binding By similarity

Sites

Active site

380

1

Nucleophile

Metal binding

179

1

Zinc; catalytic

Metal binding

182

1

Zinc; catalytic

Metal binding

306

1

Zinc; catalytic

Binding site

237

1

Substrate By similarity

Amino acid modifications

Disulfide bond

248 ↔ 271

Disulfide bond

320 ↔ 354

Natural variations

Natural variant

82

1

E → G. Ref.3 Ref.6
Corresponds to variant rs17850135 [ dbSNP | Ensembl ].

VAR_031204

Experimental info

Sequence conflict

19

1

L → S AA sequence Ref.7

Sequence conflict

39

1

K → N AA sequence Ref.7

Sequence conflict

304

1

T → I in AAA74425. Ref.4

Secondary structure

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419

Helix Strand Turn

Details...

Beta strand

26 – 30

5

Helix

35 – 46

12

Helix

48 – 50

3

Beta strand

53 – 56

4

Beta strand

65 – 69

5

Helix

71 – 73

3

Helix

74 – 83

10

Beta strand

88 – 93

6

Helix

95 – 112

18

Turn

113 – 115

3

Beta strand

120 – 122

3

Helix

126 – 139

14

Turn

141 – 143

3

Beta strand

144 – 151

8

Beta strand

157 – 163

7

Beta strand

166 – 168

3

Beta strand

171 – 175

5

Helix

183 – 199

17

Turn

200 – 202

3

Helix

204 – 212

9

Beta strand

214 – 219

6

Helix

223 – 231

9

Helix

253 – 255

3

Beta strand

257 – 260

4

Beta strand

263 – 267

5

Helix

284 – 296

13

Beta strand

299 – 306

8

Beta strand

311 – 315

5

Beta strand

317 – 319

3

Helix

326 – 341

16

Turn

342 – 344

3

Beta strand

349 – 352

4

Helix

353 – 356

4

Helix

364 – 371

8

Beta strand

375 – 380

6

Beta strand

384 – 387

4

Helix

393 – 395

3

Helix

396 – 416

21

Sequences

	Sequence		Length	Mass (Da)
	P48052 [UniParc]. Last modified April 20, 2010. Version 3. Checksum: 00269F2AE50CA38D	FASTA	419	47,030
	10 20 30 40 50 60 MAMRLILFFG ALFGHIYCLE TFVGDQVLEI VPSNEEQIKN LLQLEAQEHL QLDFWKSPTT 70 80 90 100 110 120 PGETAHVRVP FVNVQAVKVF LESQGIAYSI MIEDVQVLLD KENEEMLFNR RRERSGNFNF 130 140 150 160 170 180 GAYHTLEEIS QEMDNLVAEH PGLVSKVNIG SSFENRPMNV LKFSTGGDKP AIWLDAGIHA 190 200 210 220 230 240 REWVTQATAL WTANKIVSDY GKDPSITSIL DALDIFLLPV TNPDGYVFSQ TKNRMWRKTR 250 260 270 280 290 300 SKVSGSLCVG VDPNRNWDAG FGGPGASSNP CSDSYHGPSA NSEVEVKSIV DFIKSHGKVK 310 320 330 340 350 360 AFITLHSYSQ LLMFPYGYKC TKLDDFDELS EVAQKAAQSL RSLHGTKYKV GPICSVIYQA 370 380 390 400 410 SGGSIDWSYD YGIKYSFAFE LRDTGRYGFL LPARQILPTA EETWLGLKAI MEHVRDHPY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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], VARIANT GLY-82. Tissue: Brain and Pancreas.
[4]	"The sequence and conformation of human pancreatic procarboxypeptidase A2. cDNA cloning, sequence analysis, and three-dimensional model." Catasus L., Vendrell J., Aviles F.X., Carreira S., Puigserver A., Billeter M. J. Biol. Chem. 270:6651-6657(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-419, 3D-STRUCTURE MODELING. Tissue: Pancreas.
[5]	"Expression and characterization of human pancreatic preprocarboxypeptidase A1 and preprocarboxypeptidase A2." Laethem R.M., Blumenkopf T.A., Cory M., Elwell L., Moxham C.P., Ray P.H., Walton L.M., Smith G.K. Arch. Biochem. Biophys. 332:8-18(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-419, CHARACTERIZATION.
[6]	"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] OF 3-419, VARIANT GLY-82.
[7]	"Purification and properties of five different forms of human procarboxypeptidases." Pascual R., Burgos F.J., Salva M., Soriano F., Mendez E., Aviles F.X. Eur. J. Biochem. 179:609-616(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-45, CHARACTERIZATION.
[8]	"Separation of human pancreatic carboxypeptidase A isoenzymes by high performance liquid chromatography." Linder D., Linder M., Schade H., Sziegoleit A. Biomed. Chromatogr. 7:143-145(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 115-144. Tissue: Pancreas.
[9]	"The three-dimensional structure of human procarboxypeptidase A2. Deciphering the basis of the inhibition, activation and intrinsic activity of the zymogen." Garcia-Saez I., Reverter D., Vendrell J., Aviles F.X., Coll M. EMBO J. 16:6906-6913(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[10]	"Characterisation and preliminary X-ray diffraction analysis of human pancreatic procarboxypeptidase A2." Reverter D., Garcia-Saez I., Catasus L., Vendrell J., Coll M., Aviles F.X. FEBS Lett. 420:7-10(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 19-419.
[11]	"Structure of a novel leech carboxypeptidase inhibitor determined free in solution and in complex with human carboxypeptidase A2." Reverter D., Fernandez-Catalan C., Baumgartner R., Pfander R., Huber R., Bode W., Vendrell J., Holak T.A., Aviles F.X. Nat. Struct. Biol. 7:322-328(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 118-419.
[12]	"A large scale test of computational protein design: folding and stability of nine completely redesigned globular proteins." Dantas G., Kuhlman B., Callender D., Wong M., Baker D. J. Mol. Biol. 332:449-460(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[13]	"NMR solution structure of the activation domain of human procarboxypeptidase A2." Jimenez M.A., Villegas V., Santoro J., Serrano L., Vendrell J., Aviles F.X., Rico M. Protein Sci. 12:296-305(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 19-96.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AC024085 Genomic DNA. No translation available.
CH236950 Genomic DNA. Translation: EAL24092.1. Sequence problems.
BC007009 mRNA. Translation: AAH07009.1. Different initiation.
BC014571 mRNA. Translation: AAH14571.1. Different initiation.
BC015140 mRNA. Translation: AAH15140.1. Different initiation.
U19977 mRNA. Translation: AAA74425.1. Different initiation.
BT007403 mRNA. Translation: AAP36067.1.

IPI

IPI00941312.

PIR

A56171.

RefSeq

NP_001860.2. NM_001869.2.

UniGene

Hs.490038.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AYE	X-ray	1.80	A	19-419	[»]
1DTD	X-ray	1.65	A	118-419	[»]
1O6X	NMR	-	A	19-96	[»]

ProteinModelPortal

P48052.

SMR

P48052. Positions 19-419.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-125621.

STRING

9606.ENSP00000222481.

Protein family/group databases

MEROPS

M14.002.

PTM databases

PhosphoSite

P48052.

Polymorphism databases

DMDM

294862522.

Proteomic databases

PaxDb

P48052.

PRIDE

P48052.

Protocols and materials databases

DNASU

1358.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222481; ENSP00000222481; ENSG00000158516.

GeneID

1358.

KEGG

hsa:1358.

UCSC

uc003vpq.3. human.

Organism-specific databases

CTD

1358.

GeneCards

GC07P129906.

HGNC

HGNC:2297. CPA2.

HPA

HPA020342.
HPA021317.

MIM

600688. gene.

neXtProt

NX_P48052.

PharmGKB

PA26817.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2866.

HOVERGEN

HBG050815.

InParanoid

P48052.

KO

K01298.

OMA

ITYSIMI.

OrthoDB

EOG4320Z5.

Enzyme and pathway databases

SABIO-RK

P48052.

Gene expression databases

Bgee

P48052.

CleanEx

HS_CPA2.

Genevestigator

P48052.

GermOnline

ENSG00000158516. Homo sapiens.

Family and domain databases

Gene3D

3.30.70.340. 1 hit.

InterPro

IPR000834. Peptidase_M14.
IPR003146. Prot_inh_M14A.
IPR009020. Prot_inh_propept.
[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]

SUPFAM

SSF54897. Prot_inh_propept. 1 hit.

PROSITE

PS00132. CARBOXYPEPT_ZN_1. 1 hit.
PS00133. CARBOXYPEPT_ZN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P48052.

ChEMBL

CHEMBL4939.

EvolutionaryTrace

P48052.

GenomeRNAi

1358.

NextBio

5501.

SOURCE

Search...

Entry information

Entry name

CBPA2_HUMAN

Accession

Primary (citable) accession number: P48052
Secondary accession number(s): A4D1M4 , C9JIK1, Q53XS1, Q96A12, Q96QN3, Q9UCF1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	April 20, 2010
Last modified:	April 3, 2013
This is version 139 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.