Reviewed, UniProtKB/Swiss-Prot P00790 (PEPA_HUMAN)

Names and origin

Protein names

Recommended name:
    Pepsin A
    EC=3.4.23.1

Gene names

Name:	PGA3
AND
Name:	PGA4
AND
Name:	PGA5

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	388 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.
Sequence similarities	Belongs to the peptidase A1 family.

Ontologies

Keywords
Biological process	Digestion
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Phosphoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	digestion Non-traceable author statement. Source: UniProtKB proteolysis Non-traceable author statement. Source: UniProtKB
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	aspartic-type endopeptidase activity Ref.1 Traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 15

15

Propeptide

16 – 62

47

Activation peptide

PRO_0000026013

Chain

63 – 388

326

Pepsin A

PRO_0000026014

Sites

Active site

94

1

Active site

277

1

Amino acid modifications

Modified residue

130

1

Phosphoserine Potential

Disulfide bond

107 ↔ 112

Disulfide bond

268 ↔ 272

Disulfide bond

311 ↔ 344

Natural variations

Natural variant

28

1

L → F in isozyme 5.

VAR_006481

Natural variant

58

1

E → K in isozyme 3A, isozyme 4 and isozyme 5.

VAR_006482

Natural variant

92

1

V → L in isozyme 4 and isozyme 5.

VAR_006483

Natural variant

222

1

Q → K

VAR_006484

Natural variant

265

1

A → T

VAR_006485

Natural variant

353

1

L → V: dbSNP rs17595.

VAR_006486

Natural variant

376

1

D → E

VAR_006487

Experimental info

Sequence conflict

291

1

A → T in BAF84553. Ref.3

Sequence conflict

371 – 372

2

YF → FY AA sequence Ref.8

Secondary structure

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388

Helix Strand Turn

Details...

Beta strand

64 – 67

4

Beta strand

69 – 71

3

Turn

72 – 74

3

Beta strand

75 – 82

8

Turn

83 – 86

4

Beta strand

87 – 94

8

Beta strand

100 – 104

5

Helix

110 – 113

4

Helix

120 – 122

3

Beta strand

132 – 136

5

Beta strand

141 – 153

13

Beta strand

156 – 168

13

Helix

173 – 176

4

Beta strand

177 – 184

8

Helix

188 – 190

3

Helix

192 – 194

3

Helix

198 – 204

7

Beta strand

208 – 216

9

Beta strand

226 – 229

4

Helix

234 – 236

3

Beta strand

242 – 245

4

Turn

249 – 252

4

Beta strand

253 – 256

4

Beta strand

259 – 261

3

Beta strand

264 – 267

4

Beta strand

272 – 276

5

Beta strand

282 – 285

4

Helix

287 – 296

10

Beta strand

307 – 309

3

Helix

311 – 316

6

Beta strand

320 – 324

5

Beta strand

327 – 331

5

Helix

333 – 336

4

Beta strand

337 – 339

3

Beta strand

344 – 350

7

Beta strand

358 – 363

6

Helix

365 – 368

4

Beta strand

371 – 376

6

Turn

377 – 380

4

Beta strand

381 – 387

7

Sequences

	Sequence		Length	Mass (Da)
	P00790-1 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: C9CB89BA08F4D78B	FASTA	388	41,977
	10 20 30 40 50 60 MKWLLLLGLV ALSECIMYKV PLIRKKSLRR TLSERGLLKD FLKKHNLNPA RKYFPQWEAP 70 80 90 100 110 120 TLVDEQPLEN YLDMEYFGTI GIGTPAQDFT VVFDTGSSNL WVPSVYCSSL ACTNHNRFNP 130 140 150 160 170 180 EDSSTYQSTS ETVSITYGTG SMTGILGYDT VQVGGISDTN QIFGLSETEP GSFLYYAPFD 190 200 210 220 230 240 GILGLAYPSI SSSGATPVFD NIWNQGLVSQ DLFSVYLSAD DQSGSVVIFG GIDSSYYTGS 250 260 270 280 290 300 LNWVPVTVEG YWQITVDSIT MNGEAIACAE GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS 310 320 330 340 350 360 ENSDGDMVVS CSAISSLPDI VFTINGVQYP VPPSAYILQS EGSCISGFQG MNLPTESGEL 370 380 WILGDVFIRQ YFTVFDRANN QVGLAPVA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of human pepsinogen gene." Sogawa K., Fujii-Kuriyama Y., Mizukami Y., Ichihara Y., Takahashi K. J. Biol. Chem. 258:5306-5311(1983) [PubMed: 6300126] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Nucleotide sequence comparison of five human pepsinogen A (PGA) genes: evolution of the PGA multigene family." Evers M.P.J., Zelle B., Bebelman J.-P., van Beusechem V., Kraakman L., Hoffer M.J.V., Pronk J.C., Mager W.H., Planta R.J., Eriksson A.W., Frants R.R. Genomics 4:232-239(1989) [PubMed: 2714789] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOZYME 5). Tissue: Placenta.
[3]	"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]. Tissue: Skeletal muscle.
[4]	"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], VARIANTS LYS-222; THR-265 AND VAL-353. Tissue: Colon and Kidney.
[5]	"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 1-28.
[6]	"A comparative study on the NH2-terminal amino acid sequences and some other properties of six isozymic forms of human pepsinogens and pepsins." Athauda S.B.P., Tanji M., Kageyama T., Takahashi K. J. Biochem. 106:920-927(1989) [PubMed: 2515193] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-100 (ISOZYMES 2; 3; 3A; 4 AND 5).
[7]	"Activation of human pepsinogens." Foltmann B. FEBS Lett. 241:69-72(1988) [PubMed: 3197840] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-68 (ISOZYMES 3 AND 5).
[8]	"Carboxyl-terminal sequence of human gastricsin and pepsin." Huang W.-Y., Tang J. J. Biol. Chem. 245:2189-2193(1970) [PubMed: 4909888] [Abstract] Cited for: PROTEIN SEQUENCE OF 362-388.
[9]	"Crystal structure of human pepsin and its complex with pepstatin." Fujinaga M., Chernaia M.M., Tarasova N.I., Mosimann S.C., James M.N.G. Protein Sci. 4:960-972(1995) [PubMed: 7663352] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 63-388.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	J00287 , J00279, J00280, J00281, J00282, J00283, J00284, J00285, J00286 Genomic DNA. Translation: AAA98529.1. M26032 , M26025, M26026, M26027, M26028, M26029, M26030, M26031 Genomic