P0DJD9 (PEPA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pepsin A-5
EC=3.4.23.1

Alternative name(s):
Pepsinogen-5

Gene names

Name:

PGA5

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	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
Domain	Signal
Molecular function	Aspartyl protease Hydrolase Protease
PTM	Disulfide bond Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	digestion Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
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.6 Ref.7
	Propeptide	16 – 62	47	Activation peptide		PRO_0000415759
	Chain	63 – 388	326	Pepsin A-5		PRO_0000415760
Sites
	Active site	94	1	Ref.10
	Active site	277	1	Ref.10
Amino acid modifications
	Disulfide bond	107 ↔ 112		Ref.10
	Disulfide bond	268 ↔ 272		Ref.10
	Disulfide bond	311 ↔ 344		Ref.10
Experimental info
	Sequence conflict	28	1	L → F in AAA60061. Ref.1
	Sequence conflict	58	1	E → K in AAA60061. Ref.1
	Sequence conflict	92	1	V → L in AAA60061. Ref.1
	Sequence conflict	222	1	K → Q in AAA60061. Ref.1
	Sequence conflict	265	1	T → A in AAA60061. Ref.1
	Sequence conflict	353	1	V → L in AAA60061. Ref.1
	Sequence conflict	371 – 372	2	YF → FY AA sequence Ref.8
	Sequence conflict	376	1	D → E in AAA60061. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P0DJD9 [UniParc]. Last modified February 22, 2012. Version 1. Checksum: 2C456A75DA96CDDA	FASTA	388	41,993
	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 DKSGSVVIFG GIDSSYYTGS 250 260 270 280 290 300 LNWVPVTVEG YWQITVDSIT MNGETIACAE GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS 310 320 330 340 350 360 ENSDGDMVVS CSAISSLPDI VFTINGVQYP VPPSAYILQS EGSCISGFQG MNVPTESGEL 370 380 WILGDVFIRQ YFTVFDRANN QVGLAPVA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[2]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Colon, Kidney and Stomach.
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-100.
[7]	"Activation of human pepsinogens." Foltmann B. FEBS Lett. 241:69-72(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-68.
[8]	"Carboxyl-terminal sequence of human gastricsin and pepsin." Huang W.-Y., Tang J. J. Biol. Chem. 245:2189-2193(1970) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 362-388.
[9]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION.
[10]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 63-388, ACTIVE SITES, DISULFIDE BONDS.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M26032 , M26025, M26026, M26027, M26028, M26029, M26030, M26031 Genomic DNA. Translation: AAA60061.1. AP003037 Genomic DNA. No translation available. CH471076 Genomic DNA. Translation: EAW73928.1. BC029055 mRNA. Translation: AAH29055.1. BC146999 mRNA. Translation: AAI47000.1. BC171889 mRNA. Translation: AAI71889.1.
IPI	IPI00019641.
PIR	PEHU. A00980. A30142. A92058. B30142.
RefSeq	NP_055039.1. NM_014224.2.
UniGene	Hs.432854.
3D structure databases
ProteinModelPortal	P0DJD9.
SMR	P0DJD9. Positions 17-388.
ModBase	Search...
Protein family/group databases
MEROPS	A01.071.
PTM databases
PhosphoSite	P0DJD9.
Proteomic databases
PRIDE	P0DJD9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000312403; ENSP00000309542; ENSG00000256713.
GeneID	5222.
KEGG	hsa:5222.
Organism-specific databases
CTD	5222.
GeneCards	GC11P061008.
HGNC	HGNC:8887. PGA5.
HPA	CAB026358. HPA046875.
MIM	169700. gene. 169730. gene.
neXtProt	NX_P0DJD9.
PharmGKB	PA33224.
GenAtlas	Search...
Phylogenomic databases
KO	K06002.
OMA	SFLYYSP.
PhylomeDB	P0DJD9.
Gene expression databases
ArrayExpress	P0DJD9.
Bgee	P0DJD9.
CleanEx	HS_PGA5.
GermOnline	ENSG00000204973. 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
ChEMBL	CHEMBL3295.
GenomeRNAi	5222.
NextBio	20188.
SOURCE	Search...

Entry information

Entry name

PEPA5_HUMAN

Accession

Primary (citable) accession number: P0DJD9
Secondary accession number(s): A8K749 , B7ZW62, B7ZW75, P00790, Q7M4R0, Q8N1E3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 22, 2012
Last sequence update:	February 22, 2012
Last modified:	April 3, 2013
This is version 14 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.