Reviewed, UniProtKB/Swiss-Prot P27677 (PEPA2_MACFU)

Names and origin

Protein names	Recommended name:     Pepsin A-2/A-3     EC=3.4.23.1 Alternative name(s):     Pepsin III-2/III-1
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	Pepsin A-2 is predominant at the 4-month stage. Pepsin A-3 is predominant at fetal stages.
Post-translational modification	Pepsin A-2 is phosphorylated, but not pepsin A-3. Ref.1 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.
Caution	It is not known if this is Pep A-2 or Pep A-3.

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	By similarity
	Propeptide	16 – 40	25	Activation peptide		PRO_0000026018
	Propeptide	41 – 62	22	Activation peptide		PRO_0000026019
	Chain	63 – 388	326	Pepsin A-2/A-3		PRO_0000026020
Sites
	Active site	94	1	By similarity
	Active site	277	1	By similarity
Amino acid modifications
	Modified residue	130	1	Phosphoserine Probable
	Disulfide bond	107 ↔ 112		By similarity
	Disulfide bond	268 ↔ 272		By similarity
	Disulfide bond	311 ↔ 344		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P27677-1 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 706F7ED50FF59C0D	FASTA	388	41,704
	10 20 30 40 50 60 MKWLLLLGLV ALSECIIHKV PLVRKKSLRR NLSEHGLLKD FLKKHNFNPA SKYFPQAEAP 70 80 90 100 110 120 TLIDEQPLEN YLDMEYFGTI GIGTPAQDFT VIFDTGSSNL WVPSVYCSSL ACTNHNRFNP 130 140 150 160 170 180 QDSSTYQSTS GTVSITYGTG SMTGILGYDT VQVGGISDTN QIFGLSETEP GSFLYYAPFD 190 200 210 220 230 240 GILGLAYPSI SSSGATPVFD NIWNQGLVSQ 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 QGSCISGFQG 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 [MRNA], PROTEIN SEQUENCE OF 16-70, PHOSPHORYLATION. Tissue: Gastric mucosa.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X59755 mRNA. Translation: CAA42427.1.
PIR	S19684.
3D structure databases
HSSP	HSSP built from PDB template 1PSN based on UniProtKB P00790.
SMR	P27677. Positions 19-388.
ModBase	Search...
Protein family/group databases
MEROPS	A01.001.
Phylogenomic databases
HOVERGEN	P27677.
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

PEPA2_MACFU

Accession

Primary (citable) accession number: P27677

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	June 16, 2009
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)