Reviewed, UniProtKB/Swiss-Prot P00791 (PEPA_PIG)

Names and origin

Protein names

Recommended name:
    Pepsin A
    EC=3.4.23.1

Gene names

Name:

PGA

Organism

Sus scrofa (Pig)

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	385 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	Shows particularly broad specificity; although bonds involving phenylalanine and leucine are preferred, many others are also cleaved to some extent.
Catalytic activity	Preferential cleavage: hydrophobic, preferably aromatic, residues in P1 and P1' positions. Cleaves 1-Phe-|-Val-2, 4-Gln-|-His-5, 13-Glu-|-Ala-14, 14-Ala-|-Leu-15, 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17, 23-Gly-|-Phe-24, 24-Phe-|-Phe-25 and 25-Phe-|-Tyr-26 bonds in the B chain of insulin.
Subcellular location	Secreted.
Post-translational modification	Minor amounts of the active enzyme occur with 'Ala-58' at the amino end.
Sequence similarities	Belongs to the peptidase A1 family.

Ontologies

Keywords
Biological process	Digestion
Cellular component	Secreted
Domain	Signal
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Disulfide bond Phosphoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	digestion Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aspartic-type endopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 15

15

Ref.2 Ref.4 Ref.5 Ref.1

Propeptide

16 – 59

44

Activation peptide Ref.3

PRO_0000026026

Chain

60 – 385

326

Pepsin A

PRO_0000026027

Sites

Active site

91

1

Ref.8 Ref.6

Active site

274

1

Ref.8 Ref.6

Amino acid modifications

Modified residue

127

1

Phosphoserine By similarity

Disulfide bond

104 ↔ 109

Ref.3 Ref.6

Disulfide bond

265 ↔ 269

Ref.3 Ref.6

Disulfide bond

308 ↔ 341

Ref.3

Experimental info

Mutagenesis

91

1

D → A: Loss of activity. Ref.2

Sequence conflict

34

1

N → D Ref.4

Sequence conflict

34

1

N → D Ref.5

Sequence conflict

119 – 120

2

DS → SD AA sequence Ref.3

Sequence conflict

128

1

Q → E AA sequence Ref.3

Sequence conflict

288

1

A → AI in AAA31095. Ref.1

Sequence conflict

301

1

D → Y in AAA31096. Ref.2

Sequence conflict

313

1

S → Q AA sequence Ref.6

Sequence conflict

322

1

N → D AA sequence Ref.6

Secondary structure

1

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385

Helix Strand Turn

Details...

Beta strand

62 – 64

3

Beta strand

66 – 68

3

Turn

69 – 71

3

Beta strand

72 – 79

8

Turn

80 – 83

4

Beta strand

84 – 91

8

Beta strand

97 – 101

5

Helix

107 – 111

5

Helix

117 – 119

3

Beta strand

124 – 136

13

Beta strand

138 – 150

13

Beta strand

153 – 165

13

Helix

169 – 173

5

Beta strand

178 – 181

4

Helix

185 – 187

3

Helix

189 – 191

3

Helix

195 – 201

7

Beta strand

205 – 213

9

Beta strand

223 – 226

4

Helix

231 – 233

3

Beta strand

234 – 236

3

Beta strand

239 – 242

4

Turn

246 – 249

4

Beta strand

250 – 253

4

Beta strand

255 – 258

4

Beta strand

261 – 264

4

Beta strand

269 – 273

5

Beta strand

279 – 282

4

Helix

284 – 292

9

Turn

293 – 295

3

Beta strand

302 – 305

4

Helix

310 – 312

3

Beta strand

317 – 321

5

Beta strand

324 – 328

5

Turn

330 – 332

3

Beta strand

333 – 339

7

Beta strand

341 – 347

7

Beta strand

358 – 360

3

Helix

362 – 365

4

Beta strand

368 – 373

6

Turn

374 – 377

4

Beta strand

378 – 384

7

Sequences

	Sequence		Length	Mass (Da)
	P00791-1 [UniParc]. Last modified November 28, 2006. Version 3. Checksum: 27908D6AC0489D2D	FASTA	385	41,262
	10 20 30 40 50 60 MKWLLLLSLV VLSECLVKVP LVRKKSLRQN LIKNGKLKDF LKTHKHNPAS KYFPEAAALI 70 80 90 100 110 120 GDEPLENYLD TEYFGTIGIG TPAQDFTVIF DTGSSNLWVP SVYCSSLACS DHNQFNPDDS 130 140 150 160 170 180 STFEATSQEL SITYGTGSMT GILGYDTVQV GGISDTNQIF GLSETEPGSF LYYAPFDGIL 190 200 210 220 230 240 GLAYPSISAS GATPVFDNLW DQGLVSQDLF SVYLSSNDDS GSVVLLGGID SSYYTGSLNW 250 260 270 280 290 300 VPVSVEGYWQ ITLDSITMDG ETIACSGGCQ AIVDTGTSLL TGPTSAIANI QSDIGASENS 310 320 330 340 350 360 DGEMVISCSS IDSLPDIVFT INGVQYPLSP SAYILQDDDS CTSGFEGMDV PTSSGELWIL 370 380 GDVFIRQYYT VFDRANNKVG LAPVA

References

[1]	"Nucleotide sequence and expression in Escherichia coli of cDNA of swine pepsinogen: involvement of the amino-terminal portion of the activation peptide segment in restoration of the functional protein." Tsukagoshi N., Ando Y., Tomita Y., Uchida R., Takemura T., Sasaki T., Yamagata H., Udaka S., Ichihara Y., Takahashi K. Gene 65:285-292(1988) [PubMed: 3044927] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Synthesis, purification, and active-site mutagenesis of recombinant porcine pepsinogen." Lin X.-L., Wong R.N.S., Tang J. J. Biol. Chem. 264:4482-4489(1989) [PubMed: 2494172] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 16-20 AND 60-65, MUTAGENESIS OF ASP-91.
[3]	"Complete amino acid sequence of hog pepsin." Moravek L., Kostka V. FEBS Lett. 43:207-211(1974) [PubMed: 4604255] [Abstract] Cited for: PROTEIN SEQUENCE OF 60-385, DISULFIDE BONDS.
[4]	"N-terminal sequence of swine pepsinogen and pepsin. The site of pepsinogen activation." Stepanov V.M., Baratova L.A., Pugacheva I.B., Belyanova L.P., Revina L.P., Timokhina E.A. Biochem. Biophys. Res. Commun. 54:1164-1170(1973) [PubMed: 4584879] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-134.
[5]	"The amino-terminal sequence of porcine pepsinogen." Ong E.B., Perlmann G.E. J. Biol. Chem. 243:6104-6109(1968) [PubMed: 4881358] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-56.
[6]	"Primary structure of porcine pepsin. III. Amino acid sequence of a cyanogen bromide fragment, CB2A, and the complete structure of porcine pepsin." Sepulveda P., Marciniszyn J.P. Jr., Liu D., Tang J. J. Biol. Chem. 250:5082-5088(1975) [PubMed: 1097438] [Abstract] Cited for: PROTEIN SEQUENCE OF 58-347.
[7]	"Isolation of human, swine, and rat prepepsinogens and calf preprochymosin, and determination of the primary structures of their NH2-terminal signal sequences." Ichihara Y., Sogawa K., Takahashi K. J. Biochem. 98:483-492(1985) [PubMed: 2415509] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 1-26.
[8]	"An aspartic acid residue at the active site of pepsin. The isolation and sequence of the heptapeptide." Bayliss R.S., Knowles J.R., Wybrandt G.B. Biochem. J. 113:377-386(1969) [PubMed: 4897201] [Abstract] Cited for: ACTIVE SITE.
[9]	"X-ray crystallographic studies of pepsin." Andreeva N.S., Gustchina A.E., Fedorov A.A., Shutzkever N.E., Volnova T.V. Adv. Exp. Med. Biol. 95:23-31(1977) [PubMed: 339692] [Abstract] Cited for: CRYSTALLIZATION.
[10]	"X-ray analyses of aspartic proteinases. II. Three-dimensional structure of the hexagonal crystal form of porcine pepsin at 2.3-A resolution." Cooper J.B., Khan G., Taylor G., Tickle I.J., Blundell T.L. J. Mol. Biol. 214:199-222(1990) [PubMed: 2115088] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[11]	"Revised 2.3 A structure of porcine pepsin: evidence for a flexible subdomain." Abad-Zapatero C., Rydel T.J., Erickson J. Proteins 8:62-81(1990) [PubMed: 2217165] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[12]	"Refined structure of porcine pepsinogen at 1.8-A resolution." Sielecki A.R., Fujinaga M., Read R.J., James M.N.G. J. Mol. Biol. 219:671-692(1991) [PubMed: 2056534] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[13]	"The high-resolution crystal structure of porcine pepsinogen." Hartsuck J.E., Koelsch G., Remington S.J. Proteins 13:1-25(1992) [PubMed: 1594574] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Worthington enzyme manual

Cross-references

Sequence databases

EMBLGenBankDDBJ

M20920 mRNA. Translation: AAA31095.1.
J04601 mRNA. Translation: AAA31096.1.

PIR

PEPG. JT0307.

RefSeq

NP_999038.1.

UniGene

Ssc.219

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1F34	X-ray	2.45	A	60-385	[»]
1PSA	X-ray	2.90	A/B	60-385	[»]
1YX9	X-ray	3.00	A	60-385	[»]
2PSG	X-ray	1.80	A	16-385	[»]
3PEP	X-ray	2.30	A	60-385	[»]
3PSG	X-ray	1.65	A	16-385	[»]
4PEP	X-ray	1.80	A	60-385	[»]
5PEP	X-ray	2.34	A	60-385	[»]

ModBase

Search...

Protein family/group databases

MEROPS

A01.001.

Genome annotation databases

GeneID

396892.

KEGG

ssc:396892.

Phylogenomic databases

HOVERGEN

P00791.

Enzyme and pathway databases

BRENDA

3.4.23.1. 249.

Family and domain databases

InterPro

IPR001461. Peptidase_A1.
IPR001969. Peptidase_aspartic_AS.
IPR009007. Peptidase_aspartic_catalytic.
IPR012848. Propep_A1.
[Graphical view]

Gene3D

G3DSA:2.40.70.10. Pept_Aspartc_cat. 1 hit.

PANTHER

PTHR13683. Peptidase_A1. 1 hit.

Pfam

PF07966. A1_Propeptide. 1 hit.
PF00026. Asp. 1 hit.
[Graphical view]

PRINTS

PR00792. PEPSIN.

PROSITE

PS00141. ASP_PROTEASE. 2 hits.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

PEPA_PIG

Accession

Primary (citable) accession number: P00791
Secondary accession number(s): Q29080

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	November 28, 2006
Last modified:	June 16, 2009
This is version 89 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)