P20142 (PEPC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gastricsin
EC=3.4.23.3

Alternative name(s):
Pepsinogen C

Gene names

Name:

PGC

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	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	Hydrolyzes a variety of proteins.
Catalytic activity	More restricted specificity than pepsin A, but shows preferential cleavage at Tyr-|-Xaa bonds. High activity on hemoglobin.
Subcellular location	Secreted.
Sequence similarities	Belongs to the peptidase A1 family.
Sequence caution	The sequence AAA60062.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Digestion
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Disulfide bond Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	digestion Traceable author statement Ref.1. Source: ProtInc proteolysis Traceable author statement Ref.1. Source: ProtInc
Cellular_component	extracellular space Traceable author statement Ref.1. Source: ProtInc nucleolus Inferred from direct assay. Source: HPA
Molecular_function	aspartic-type endopeptidase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P20142-1)

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: P20142-2)

The sequence of this isoform differs from the canonical sequence as follows:
     217-388: QQGSSGGAVV...NNRVGFATAA → LVLESSGLGP...PPRSQHHSGA

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 16

16

Ref.9 Ref.10

Propeptide

17 – 59

43

Activation peptide

PRO_0000026056

Chain

60 – 388

329

Gastricsin

PRO_0000026057

Sites

Active site

91

1

Active site

276

1

Amino acid modifications

Disulfide bond

104 ↔ 109

Disulfide bond

267 ↔ 271

Disulfide bond

310 ↔ 343

Natural variations

Alternative sequence

217 – 388

172

QQGSS…FATAA → LVLESSGLGPLLTPSRAAPP SSTLQLPEKPLEQTWNILTP FTKTLPVSNLSRKVTSWAGV GIPVTCLPEAGSGGERRAEC GLGVPTTRGPPRSQHHSGA in isoform 2.

VSP_042312

Experimental info

Sequence conflict

40 – 41

2

GE → ED AA sequence Ref.10

Sequence conflict

52

1

W → S AA sequence Ref.10

Secondary structure

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388

Helix Strand Turn

Details...

Beta strand

19 – 25

7

Helix

29 – 36

8

Helix

50 – 54

5

Beta strand

73 – 79

7

Turn

80 – 83

4

Beta strand

84 – 91

8

Beta strand

97 – 101

5

Helix

107 – 110

4

Helix

117 – 119

3

Beta strand

124 – 132

9

Beta strand

139 – 150

12

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 – 214

10

Beta strand

223 – 227

5

Beta strand

234 – 246

13

Turn

247 – 250

4

Beta strand

251 – 259

9

Turn

266 – 269

4

Beta strand

271 – 275

5

Beta strand

281 – 285

5

Helix

286 – 288

3

Helix

289 – 295

7

Beta strand

306 – 308

3

Turn

310 – 312

3

Helix

313 – 315

3

Beta strand

319 – 323

5

Beta strand

326 – 330

5

Helix

332 – 335

4

Beta strand

336 – 338

3

Beta strand

340 – 345

6

Beta strand

347 – 350

4

Beta strand

360 – 363

4

Helix

365 – 368

4

Beta strand

371 – 376

6

Turn

377 – 380

4

Beta strand

381 – 387

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: F862DFDC1438BB92	FASTA	388	42,426
	10 20 30 40 50 60 MKWMVVVLVC LQLLEAAVVK VPLKKFKSIR ETMKEKGLLG EFLRTHKYDP AWKYRFGDLS 70 80 90 100 110 120 VTYEPMAYMD AAYFGEISIG TPPQNFLVLF DTGSSNLWVP SVYCQSQACT SHSRFNPSES 130 140 150 160 170 180 STYSTNGQTF SLQYGSGSLT GFFGYDTLTV QSIQVPNQEF GLSENEPGTN FVYAQFDGIM 190 200 210 220 230 240 GLAYPALSVD EATTAMQGMV QEGALTSPVF SVYLSNQQGS SGGAVVFGGV DSSLYTGQIY 250 260 270 280 290 300 WAPVTQELYW QIGIEEFLIG GQASGWCSEG CQAIVDTGTS LLTVPQQYMS ALLQATGAQE 310 320 330 340 350 360 DEYGQFLVNC NSIQNLPSLT FIINGVEFPL PPSSYILSNN GYCTVGVEPT YLSSQNGQPL 370 380 WILGDVFLRS YYSVYDLGNN RVGFATAA
	Isoform 2 [UniParc]. Checksum: 79BD7C79ABDF8879	FASTA	315	34,208
	10 20 30 40 50 60 MKWMVVVLVC LQLLEAAVVK VPLKKFKSIR ETMKEKGLLG EFLRTHKYDP AWKYRFGDLS 70 80 90 100 110 120 VTYEPMAYMD AAYFGEISIG TPPQNFLVLF DTGSSNLWVP SVYCQSQACT SHSRFNPSES 130 140 150 160 170 180 STYSTNGQTF SLQYGSGSLT GFFGYDTLTV QSIQVPNQEF GLSENEPGTN FVYAQFDGIM 190 200 210 220 230 240 GLAYPALSVD EATTAMQGMV QEGALTSPVF SVYLSNLVLE SSGLGPLLTP SRAAPPSSTL 250 260 270 280 290 300 QLPEKPLEQT WNILTPFTKT LPVSNLSRKV TSWAGVGIPV TCLPEAGSGG ERRAECGLGV 310 PTTRGPPRSQ HHSGA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of human pepsinogen C gene." Hayano T., Sogawa K., Ichihara Y., Fujii-Kuriyama Y., Takahashi K. J. Biol. Chem. 263:1382-1385(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	Erratum Hayano T., Sogawa K., Ichihara Y., Fujii-Kuriyama Y., Takahashi K. J. Biol. Chem. 263:14592-14592(1988)
[3]	"Human pepsinogen C (progastricsin). Isolation of cDNA clones, localization to chromosome 6, and sequence homology with pepsinogen A." Taggart R.T., Cass L.G., Mohandas T.K., Derby P., Barr P.J., Pals G., Bell G.I. J. Biol. Chem. 264:375-379(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Human pepsinogen C (progastricsin) polymorphism: evidence for a single locus located at 6p21.1-pter." Pals G., Azuma T., Mohandas T.K., Bell G.I., Bacon J., Samloff I.M., Walz D.A., Barr P.J., Taggart R.T. Genomics 4:137-148(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[5]	"cDNA sequence of human gastricsin." Wong R.N.S., Tang J. Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Stomach.
[7]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] (ISOFORM 1). Tissue: Liver.
[9]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-101.
[10]	"Human progastricsin. Analysis of intermediates during activation into gastricsin and determination of the amino acid sequence of the propart." Foltmann B., Jensen A.L. Eur. J. Biochem. 128:63-70(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 17-64.
[11]	"Crystal and molecular structures of human progastricsin at 1.62-A resolution." Moore S.A., Sielecki A.R., Chernaia M.M., Tarasova N.I., James M.N.G. J. Mol. Biol. 247:466-485(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS).
[12]	"Structural characterization of activation 'intermediate 2' on the pathway to human gastricsin." Khan A.R., Cherney M.M., Tarasova N.I., James M.N. Nat. Struct. Biol. 4:1010-1015(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.36 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M18667 , M18659, M18660, M18661, M18662, M18663, M18664, M18665, M18666 Genomic DNA. Translation: AAA60062.1. Different initiation.
J04443 mRNA. Translation: AAA60074.1.
M23077 , M23069, M23070, M23071, M23072, M23073, M23074, M23075 Genomic DNA. Translation: AAA60063.1.
U75272 mRNA. Translation: AAB18273.1.
AK301298 mRNA. Translation: BAG62855.1.
AL365205 Genomic DNA. Translation: CAI13181.1.
BC073740 mRNA. Translation: AAH73740.1.

IPI

IPI00022213.

PIR

A29937.

RefSeq

NP_001159896.1. NM_001166424.1.
NP_002621.1. NM_002630.3.

UniGene

Hs.1867.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AVF	X-ray	2.36	A/J	60-388	[»]
			P/Q	17-42	[»]
1HTR	X-ray	1.62	B	60-388	[»]
			P	17-59	[»]

ProteinModelPortal

P20142.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000362116.

Protein family/group databases

MEROPS

A01.003.

PTM databases

PhosphoSite

P20142.

Polymorphism databases

DMDM

129796.

Proteomic databases

PaxDb

P20142.

PRIDE

P20142.

Protocols and materials databases

DNASU

5225.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373025; ENSP00000362116; ENSG00000096088.
ENST00000425343; ENSP00000405094; ENSG00000096088.

GeneID

5225.

KEGG

hsa:5225.

UCSC

uc003ora.2. human.

Organism-specific databases

CTD

5225.

GeneCards

GC06M041704.

HGNC

HGNC:8890. PGC.

HPA

HPA031717.
HPA031718.

MIM

169740. gene.

neXtProt

NX_P20142.

PharmGKB

PA33228.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG248684.

HOGENOM

HOG000197681.

HOVERGEN

HBG000482.

InParanoid

P20142.

KO

K01377.

OMA

ASGWCSE.

OrthoDB

EOG4WH8MB.

PhylomeDB

P20142.

Gene expression databases

ArrayExpress

P20142.

Bgee

P20142.

CleanEx

HS_PGC.

Genevestigator

P20142.

GermOnline

ENSG00000096088. Homo sapiens.

Family and domain databases

Gene3D

2.40.70.10. 2 hits.

InterPro

IPR001461. Peptidase_A1.
IPR021109. Peptidase_aspartic.
IPR001969. Peptidase_aspartic_AS.
IPR012848. Propep_A1.
[Graphical view]

PANTHER

PTHR13683. PTHR13683. 1 hit.

Pfam

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

PRINTS

PR00792. PEPSIN.

SUPFAM

SSF50630. Pept_Aspartic. 1 hit.

PROSITE

PS00141. ASP_PROTEASE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P20142.

ChEMBL

CHEMBL2136.

ChiTaRS

PGC. human.

EvolutionaryTrace

P20142.

GenomeRNAi

5225.

NextBio

20200.

PMAP-CutDB

P20142.

SOURCE

Search...

Entry information

Entry name

PEPC_HUMAN

Accession

Primary (citable) accession number: P20142
Secondary accession number(s): B4DVZ3, Q5T3D7, Q5T3D8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	May 1, 2013
This is version 133 of the entry and version 1 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.