ID   PEPA4_MACFU             Reviewed;         388 AA.
AC   P27678;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   03-AUG-2022, entry version 98.
DE   RecName: Full=Pepsin A-4;
DE            EC=3.4.23.1;
DE   AltName: Full=Pepsin I/II;
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 [MRNA], 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).
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   -!- 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; X59753; CAA42425.1; -; mRNA.
DR   PIR; S19682; S19682.
DR   AlphaFoldDB; P27678; -.
DR   SMR; P27678; -.
DR   MEROPS; A01.001; -.
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   Glycoprotein; Hydrolase; Phosphoprotein; Protease; Secreted; Signal;
KW   Zymogen.
FT   SIGNAL          1..15
FT                   /evidence="ECO:0000250"
FT   PROPEP          16..38
FT                   /note="Activation peptide"
FT                   /id="PRO_0000026021"
FT   PROPEP          39..62
FT                   /note="Activation peptide"
FT                   /id="PRO_0000026022"
FT   CHAIN           63..388
FT                   /note="Pepsin A-4"
FT                   /id="PRO_0000026023"
FT   DOMAIN          76..385
FT                   /note="Peptidase A1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        94
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   ACT_SITE        277
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   MOD_RES         130
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P03954"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine"
FT   DISULFID        107..112
FT                   /evidence="ECO:0000250"
FT   DISULFID        268..272
FT                   /evidence="ECO:0000250"
FT   DISULFID        311..344
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   388 AA;  41955 MW;  A2923AB1F7FCDEB9 CRC64;
     MKWLLLLGLV ALSECIIYKV PLVRKKSLRR NLSEHGLLKD FLKKHNLNPA SKYFPQAEAP
     TLIDEQPLEN YLDVEYFGTI GIGTPAQNFT VVFDTGSSNL WVPSVYCYSL ACMDHNLFNP
     QDSSTYRATS KTVSITYGTG SMTGILGYDT VKVGGISDTN QIFGLSETEP GFFLYFAPFD
     GILGLAYPSI SSSGATPVFD NIWNQRLVSQ DLFSVYLSAD DQSGSVVIFG GIDSSYYTGS
     LNWVPVSVEG YWQISVDSIT MNGKTIACAK GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS
     ENSDGEMVVS CSAISSLPDI VFTINGVQYP LPPSAYILQS QGSCTSGFQG MDVPTESGEL
     WILGDVFIRQ YFTVFDRANN QVGLAPVA