ID   PEPA1_MACFU             Reviewed;         388 AA.
AC   P03954;
DT   23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 2.
DT   03-AUG-2022, entry version 111.
DE   RecName: Full=Pepsin A-1;
DE            EC=3.4.23.1;
DE   AltName: Full=Pepsin III-3;
DE   Flags: Precursor;
GN   Name=PGA;
OS   Macaca fuscata fuscata (Japanese macaque).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Macaca.
OX   NCBI_TaxID=9543;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 16-70.
RC   TISSUE=Gastric mucosa;
RX   PubMed=1935977; DOI=10.1111/j.1432-1033.1991.tb16364.x;
RA   Kageyama T., Tanabe K., Koiwai O.;
RT   "Development-dependent expression of isozymogens of monkey pepsinogens and
RT   structural differences between them.";
RL   Eur. J. Biochem. 202:205-215(1991).
RN   [2]
RP   PROTEIN SEQUENCE OF 16-62.
RX   PubMed=6773933;
RA   Kageyama T., Takahashi K.;
RT   "Monkey pepsinogens and pepsins. IV. The amino acid sequence of the
RT   activation peptide segment of Japanese monkey pepsinogen.";
RL   J. Biochem. 88:9-16(1980).
RN   [3]
RP   PROTEIN SEQUENCE OF 41-388, PHOSPHORYLATION AT SER-130, AND DISULFIDE
RP   BONDS.
RX   PubMed=3514596; DOI=10.1016/s0021-9258(17)38514-9;
RA   Kageyama T., Takahashi K.;
RT   "The complete amino acid sequence of monkey pepsinogen A.";
RL   J. Biol. Chem. 261:4395-4405(1986).
CC   -!- FUNCTION: Shows particularly broad specificity; although bonds
CC       involving phenylalanine and leucine are preferred, many others are also
CC       cleaved to some extent.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Preferential cleavage: hydrophobic, preferably aromatic,
CC         residues in P1 and P1' positions. Cleaves 1-Phe-|-Val-2, 4-Gln-|-His-
CC         5, 13-Glu-|-Ala-14, 14-Ala-|-Leu-15, 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-
CC         17, 23-Gly-|-Phe-24, 24-Phe-|-Phe-25 and 25-Phe-|-Tyr-26 bonds in the
CC         B chain of insulin.; EC=3.4.23.1; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU10094};
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- DEVELOPMENTAL STAGE: Predominant at the juvenile and adult stages.
CC   -!- PTM: Each pepsinogen is converted to corresponding pepsin at pH 2.0 in
CC       part as a result of the release of a 47 AA activation segment and in
CC       part as a result of stepwise proteolytic cleavage via an intermediate
CC       form(s).
CC   -!- MISCELLANEOUS: The expression of pepsinogen genes is regulated by
CC       hormones and related substances.
CC   -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR   EMBL; X59752; CAA42424.1; -; Genomic_DNA.
DR   PIR; S19681; PEMQAJ.
DR   AlphaFoldDB; P03954; -.
DR   SMR; P03954; -.
DR   MEROPS; A01.001; -.
DR   iPTMnet; P03954; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0007586; P:digestion; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd05478; pepsin_A; 1.
DR   Gene3D; 2.40.70.10; -; 2.
DR   InterPro; IPR001461; Aspartic_peptidase_A1.
DR   InterPro; IPR001969; Aspartic_peptidase_AS.
DR   InterPro; IPR012848; Aspartic_peptidase_N.
DR   InterPro; IPR034162; Pepsin_A.
DR   InterPro; IPR033121; PEPTIDASE_A1.
DR   InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR   PANTHER; PTHR47966; PTHR47966; 1.
DR   Pfam; PF07966; A1_Propeptide; 1.
DR   Pfam; PF00026; Asp; 1.
DR   PRINTS; PR00792; PEPSIN.
DR   SUPFAM; SSF50630; SSF50630; 1.
DR   PROSITE; PS00141; ASP_PROTEASE; 2.
DR   PROSITE; PS51767; PEPTIDASE_A1; 1.
PE   1: Evidence at protein level;
KW   Aspartyl protease; Digestion; Direct protein sequencing; Disulfide bond;
KW   Hydrolase; Phosphoprotein; Protease; Secreted; Signal; Zymogen.
FT   SIGNAL          1..15
FT                   /evidence="ECO:0000269|PubMed:1935977,
FT                   ECO:0000269|PubMed:6773933"
FT   PROPEP          16..40
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000269|PubMed:3514596"
FT                   /id="PRO_0000026015"
FT   PROPEP          41..62
FT                   /note="Activation peptide"
FT                   /id="PRO_0000026016"
FT   CHAIN           63..388
FT                   /note="Pepsin A-1"
FT                   /id="PRO_0000026017"
FT   DOMAIN          76..385
FT                   /note="Peptidase A1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        94
FT   ACT_SITE        277
FT   MOD_RES         130
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:3514596"
FT   DISULFID        107..112
FT                   /evidence="ECO:0000269|PubMed:3514596"
FT   DISULFID        268..272
FT                   /evidence="ECO:0000269|PubMed:3514596"
FT   DISULFID        311..344
FT                   /evidence="ECO:0000269|PubMed:3514596"
FT   CONFLICT        262
FT                   /note="N -> D (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   388 AA;  41624 MW;  48C49B0A69FD7516 CRC64;
     MKWLLLLGLV ALSECIIYKV PLVRKKSLRR NLSEHGLLKD FLKKHNLNPA SKYFPQAEAP
     TLIDEQPLEN YLDVEYFGTI GIGTPAQDFT VIFDTGSSNL WVPSVYCSSL ACTNHNLFNP
     QDSSTYQSTS GTLSITYGTG SMTGILGYDT VQVGGISDTN QIFGLSETEP GSFLYYAPFD
     GILGLAYPSI SSSGATPVFD NIWDQGLVSQ DLFSVYLSAD DQSGSVVIFG GIDSSYYTGS
     LNWVPVSVEG YWQISVDSIT MNGEAIACAE GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS
     ENSDGEMVVS CSAISSLPDI VFTINGIQYP VPPSAYILQS QGSCTSGFQG MDVPTESGEL
     WILGDVFIRQ YFTVFDRANN QVGLAPVA