P00730 (CBPA1_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carboxypeptidase A1
EC=3.4.17.1

Gene names

Name:	CPA1
Synonyms:	CPA

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

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)

Function	Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro By similarity.
Catalytic activity	Release of a C-terminal amino acid, but little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.
Cofactor	Binds 1 zinc ion per subunit.
Subunit structure	Monomer. The zymogen is secreted as a ternary complex composed of procarboxypeptidase A, chymotrypsinogen C and proproteinase E.
Subcellular location	Secreted › extracellular space.
Tissue specificity	Pancreas. Ref.8
Sequence similarities	Belongs to the peptidase M14 family.

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
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metallocarboxypeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 16

16

Ref.5

Propeptide

17 – 110

94

Activation peptide

PRO_0000004343

Chain

111 – 419

309

Carboxypeptidase A1

PRO_0000004344

Regions

Region

179 – 182

4

Substrate binding

Region

254 – 255

2

Substrate binding

Region

307 – 308

2

Substrate binding

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

Amino acid modifications

Disulfide bond

248 ↔ 271

Natural variations

Natural variant

289

1

I → V in allelic variant. Ref.14

Natural variant

338

1

E → A in allelic variant. Ref.14

Natural variant

415

1

L → V in allelic variant. Ref.14

Experimental info

Sequence conflict

95

1

S → L AA sequence Ref.5

Sequence conflict

199

1

D → N AA sequence Ref.3

Sequence conflict

203

1

D → N AA sequence Ref.3

Sequence conflict

224

1

D → N AA sequence Ref.3

Sequence conflict

232

1

Q → E AA sequence Ref.3

Sequence conflict

295

1

D → N AA sequence Ref.3

Secondary structure

1

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419

Helix Strand Turn

Details...

Turn

114 – 116

3

Beta strand

119 – 121

3

Helix

125 – 138

14

Turn

140 – 142

3

Beta strand

143 – 150

8

Beta strand

156 – 162

7

Beta strand

164 – 168

5

Beta strand

171 – 176

6

Helix

183 – 199

17

Turn

200 – 202

3

Helix

204 – 212

9

Beta strand

214 – 219

6

Helix

223 – 231

9

Beta strand

244 – 247

4

Helix

253 – 255

3

Beta strand

257 – 260

4

Beta strand

263 – 267

5

Beta strand

273 – 275

3

Helix

284 – 296

13

Beta strand

299 – 306

8

Beta strand

311 – 315

5

Helix

326 – 341

16

Turn

342 – 344

3

Beta strand

349 – 352

4

Helix

353 – 356

4

Helix

364 – 370

7

Beta strand

375 – 380

6

Beta strand

384 – 387

4

Helix

388 – 390

3

Helix

393 – 395

3

Helix

396 – 416

21

Sequences

	Sequence		Length	Mass (Da)
	P00730 [UniParc]. Last modified November 1, 1991. Version 3. Checksum: 21B86407B3BFC452	FASTA	419	47,082
	10 20 30 40 50 60 MQGLLILSVL LGAALGKEDF VGHQVLRITA ADEAEVQTVK ELEDLEHLQL DFWRGPGQPG 70 80 90 100 110 120 SPIDVRVPFP SLQAVKVFLE AHGIRYRIMI EDVQSLLDEE QEQMFASQSR ARSTNTFNYA 130 140 150 160 170 180 TYHTLDEIYD FMDLLVAEHP QLVSKLQIGR SYEGRPIYVL KFSTGGSNRP AIWIDLGIHS 190 200 210 220 230 240 REWITQATGV WFAKKFTEDY GQDPSFTAIL DSMDIFLEIV TNPDGFAFTH SQNRLWRKTR 250 260 270 280 290 300 SVTSSSLCVG VDANRNWDAG FGKAGASSSP CSETYHGKYA NSEVEVKSIV DFVKDHGNFK 310 320 330 340 350 360 AFLSIHSYSQ LLLYPYGYTT QSIPDKTELN QVAKSAVEAL KSLYGTSYKY GSIITTIYQA 370 380 390 400 410 SGGSIDWSYN QGIKYSFTFE LRDTGRYGFL LPASQIIPTA QETWLGVLTI MEHTLNNLY

References

[1]	"Cloning and nucleotide sequence of a bovine pancreatic preprocarboxypeptidase A cDNA." le Hueerou I., Guilloteau P., Toullec R., Puigserver A., Wicker C. Biochem. Biophys. Res. Commun. 175:110-116(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pancreas.
[2]	"Cloning, sequencing and expression of the gene encoding a major allotypic preprocarboxypeptidase A from bovine pancreas." Goo J.H., Kim K.H., Choi K.Y. Gene 165:333-334(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pancreas.
[3]	"Amino acid sequence of bovine carboxypeptidase A. Tryptic and chymotryptic peptides of the cyanogen bromide fragment F-I." Bradshaw R.A., Walsh K.A., Neurath H. Biochemistry 10:938-950(1971) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 111-417.
[4]	"Characterization of bovine carboxypeptidase A (Allan)." Petra P.H., Hermodson M.A., Walsh K.A., Neurath H. Biochemistry 10:4023-4025(1971) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION TO 138 AND 141.
[5]	"The amino acid sequence of the activation peptide of bovine pro-carboxypeptidase A." Wade R.D., Hass G.M., Kumar S., Walsh K.A., Neurath H. Biochimie 70:1137-1142(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-120.
[6]	"Refined crystal structure of carboxypeptidase A at 1.54-A resolution." Rees D.C., Lewis M., Lipscomb W.N. J. Mol. Biol. 168:367-387(1983) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS).
[7]	"High-resolution structure of the complex between carboxypeptidase A and L-phenyl lactate." Teplyakov A., Wilson K.S., Orioli P., Mangani S. Acta Crystallogr. D 49:534-540(1993) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC IONS AND SUBSTRATE ANALOG.
[8]	"The three-dimensional structure of the native ternary complex of bovine pancreatic procarboxypeptidase A with proproteinase E and chymotrypsinogen C." Gomis-Rueth F.-X., Gomez M., Bode W., Huber R., Aviles F.X. EMBO J. 14:4387-4394(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF COMPLEX WITH CPA1 AND CTRC, TISSUE SPECIFICITY.
[9]	"Carboxypeptidase A: native, zinc-removed and mercury-replaced forms." Greenblatt H.M., Feinberg H., Tucker P.A., Shoham G. Acta Crystallogr. D 54:289-305(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 111-419 OF APOENZYME AND IN COMPLEX WITH ZINC IONS.
[10]	"Crystal structure of carboxypeptidase A complexed with D-cysteine at 1.75 A -- inhibitor-induced conformational changes." van Aalten D.M.F., Chong C.R., Joshua-Tor L. Biochemistry 39:10082-10089(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC IONS AND INHIBITOR.
[11]	"Insight into the stereochemistry in the inhibition of carboxypeptidase A with N-(hydroxyaminocarbonyl)phenylalanine: binding modes of an enantiomeric pair of the inhibitor to carboxypeptidase A." Cho J.H., Kim D.H., Chung S.J., Ha N.-C., Oh B.-H., Yong Choi K. Bioorg. Med. Chem. 10:2015-2022(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC IONS AND SUBSTRATE ANALOG.
[12]	"Sulfamide-based inhibitors for carboxypeptidase A. Novel type transition state analogue inhibitors for zinc proteases." Park J.D., Kim D.H., Kim S.-J., Woo J.-R., Ryu S.E. J. Med. Chem. 45:5295-5302(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC IONS AND SUBSTRATE ANALOG.
[13]	"Refined structure of bovine carboxypeptidase A at 1.25 A resolution." Kilshtain-Vardi A., Glick M., Greenblatt H.M., Goldblum A., Shoham G. Acta Crystallogr. D 59:323-333(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 111-417 IN COMPLEX WITH ZINC IONS.
[14]	"Identification of the amino acid replacements characterizing the allotypic forms of bovine carboxypeptidase A." Petra P.H., Bradshaw R.A., Walsh K.A., Neurath H. Biochemistry 8:2762-2768(1969) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALLELIC VAL-289; ALA-338 AND VAL-415.
+	Additional computationally mapped references.

Web resources

Worthington enzyme manual

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M61851 mRNA. Translation: AAA30426.1.
Z33906 mRNA. Translation: CAA83955.1.

IPI

IPI00703168.

PIR

CPBOA. JN0126.

RefSeq

NP_777175.1. NM_174750.2.

UniGene

Bt.4052.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ARL	X-ray	1.88	A	111-417	[»]
1ARM	X-ray	1.76	A	111-419	[»]
1BAV	X-ray	1.60	A/B/C/D	111-419	[»]
1CBX	X-ray	2.00	A	111-417	[»]
1CPS	X-ray	2.25	A	111-417	[»]
1CPX	X-ray	2.00	A	111-417	[»]
1EE3	X-ray	1.70	P	111-419	[»]
1ELL	X-ray	1.76	P	111-419	[»]
1ELM	X-ray	2.00	P	111-419	[»]
1F57	X-ray	1.75	A	111-417	[»]
1HDQ	X-ray	2.30	A	111-417	[»]
1HDU	X-ray	1.75	A/B/D/E	111-417	[»]
1HEE	X-ray	1.75	A/B/D/E	111-417	[»]
1IY7	X-ray	2.00	A	111-417	[»]
1M4L	X-ray	1.25	A	111-417	[»]
1PYT	X-ray	2.35	A	17-110	[»]
			B	111-419	[»]
1YME	X-ray	1.53	A	111-419	[»]
1ZLH	X-ray	1.70	A	111-419	[»]
2ABZ	X-ray	2.16	A/B	111-419	[»]
2CTB	X-ray	1.50	A	111-417	[»]
2CTC	X-ray	1.40	A	111-417	[»]
2RFH	X-ray	1.70	A	111-417	[»]
3CPA	X-ray	2.00	A	111-417	[»]
3FVL	X-ray	1.85	A/C/E	111-417	[»]
3FX6	X-ray	1.85	A/C/E	111-417	[»]
3I1U	X-ray	1.39	A	111-419	[»]
3KGQ	X-ray	1.70	A	111-419	[»]
4CPA	X-ray	2.50	A/B	111-417	[»]
5CPA	X-ray	1.54	A	111-417	[»]
6CPA	X-ray	2.00	A	111-417	[»]
7CPA	X-ray	2.00	A	111-417	[»]
8CPA	X-ray	2.00	A	111-417	[»]

ProteinModelPortal

P00730.

SMR

P00730. Positions 17-419.

ModBase

Search...

Protein-protein interaction databases

STRING

9913.ENSBTAP00000017727.

Protein family/group databases

MEROPS

M14.001.

Proteomic databases

PRIDE

P00730.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

286762.

KEGG

bta:286762.

Organism-specific databases

CTD

1357.

Phylogenomic databases

eggNOG

COG2866.

HOGENOM

HOG000252967.

HOVERGEN

HBG050815.

KO

K08779.

Enzyme and pathway databases

SABIO-RK

P00730.

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

P00730.

ChEMBL

CHEMBL3481.

EvolutionaryTrace

P00730.

NextBio

20806424.

Entry information

Entry name

CBPA1_BOVIN

Accession

Primary (citable) accession number: P00730

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	November 1, 1991
Last modified:	April 3, 2013
This is version 133 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program