Reviewed, UniProtKB/Swiss-Prot P03954 (PEPA1_MACFU)

Names and origin

Protein names

Recommended name:
    Pepsin A-1
    EC=3.4.23.1
Alternative name(s):
    Pepsin III-3

Gene names

Name:

PGA

Organism

Macaca fuscata fuscata (Japanese macaque)

Taxonomic identifier

9543 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca

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.
Developmental stage	Predominant at the juvenile and adult stages.
Post-translational modification	Each pepsinogen is converted to corresponding pepsin at pH 2.0 in part as a result of the release of a 47 AA activation segment and in part as a result of stepwise proteolytic cleavage via an intermediate form(s).
Miscellaneous	The expression of pepsinogen genes is regulated by hormones and related substances.
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	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.1 Ref.2
	Propeptide	16 – 40	25	Activation peptide Ref.3		PRO_0000026015
	Propeptide	41 – 62	22	Activation peptide		PRO_0000026016
	Chain	63 – 388	326	Pepsin A-1		PRO_0000026017
Sites
	Active site	94	1
	Active site	277	1
Amino acid modifications
	Modified residue	130	1	Phosphoserine Ref.3
	Disulfide bond	107 ↔ 112		Ref.3
	Disulfide bond	268 ↔ 272		Ref.3
	Disulfide bond	311 ↔ 344		Ref.3
Experimental info
	Sequence conflict	262	1	N → D AA sequence Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P03954-1 [UniParc]. Last modified August 1, 1992. Version 2. Checksum: 48C49B0A69FD7516	FASTA	388	41,624
	10 20 30 40 50 60 MKWLLLLGLV ALSECIIYKV PLVRKKSLRR NLSEHGLLKD FLKKHNLNPA SKYFPQAEAP 70 80 90 100 110 120 TLIDEQPLEN YLDVEYFGTI GIGTPAQDFT VIFDTGSSNL WVPSVYCSSL ACTNHNLFNP 130 140 150 160 170 180 QDSSTYQSTS GTLSITYGTG SMTGILGYDT VQVGGISDTN QIFGLSETEP GSFLYYAPFD 190 200 210 220 230 240 GILGLAYPSI SSSGATPVFD NIWDQGLVSQ DLFSVYLSAD DQSGSVVIFG GIDSSYYTGS 250 260 270 280 290 300 LNWVPVSVEG YWQISVDSIT MNGEAIACAE GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS 310 320 330 340 350 360 ENSDGEMVVS CSAISSLPDI VFTINGIQYP VPPSAYILQS QGSCTSGFQG MDVPTESGEL 370 380 WILGDVFIRQ YFTVFDRANN QVGLAPVA

References

[1]	"Development-dependent expression of isozymogens of monkey pepsinogens and structural differences between them." Kageyama T., Tanabe K., Koiwai O. Eur. J. Biochem. 202:205-215(1991) [PubMed: 1935977] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 16-70. Tissue: Gastric mucosa.
[2]	"Monkey pepsinogens and pepsins. IV. The amino acid sequence of the activation peptide segment of Japanese monkey pepsinogen." Kageyama T., Takahashi K. J. Biochem. 88:9-16(1980) [PubMed: 6773933] [Abstract] Cited for: PROTEIN SEQUENCE OF 16-62.
[3]	"The complete amino acid sequence of monkey pepsinogen A." Kageyama T., Takahashi K. J. Biol. Chem. 261:4395-4405(1986) [PubMed: 3514596] [Abstract] Cited for: PROTEIN SEQUENCE OF 41-388, PHOSPHORYLATION AT SER-130, DISULFIDE BONDS.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X59752 Genomic DNA. Translation: CAA42424.1.
PIR	PEMQAJ. S19681.
3D structure databases
HSSP	HSSP built from PDB template 1PSN based on UniProtKB P00790.
SMR	P03954. Positions 17-388.
ModBase	Search...
Protein family/group databases
MEROPS	A01.001.
Phylogenomic databases
HOVERGEN	P03954.
Enzyme and pathway databases
BRENDA	3.4.23.1. 276174.
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. 2 hits.
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

PEPA1_MACFU

Accession

Primary (citable) accession number: P03954

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 23, 1986
Last sequence update:	August 1, 1992
Last modified:	June 16, 2009
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)