ID   PEPA3_RABIT             Reviewed;         387 AA.
AC   P27822;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   03-AUG-2022, entry version 117.
DE   RecName: Full=Pepsin-3;
DE            EC=3.4.23.1;
DE   AltName: Full=Pepsin A;
DE   AltName: Full=Pepsin III;
DE   Flags: Precursor;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Japanese white; TISSUE=Gastric mucosa;
RX   PubMed=2129536; DOI=10.1016/s0021-9258(17)44864-2;
RA   Kageyama T., Tanabe K., Koiwai O.;
RT   "Structure and development of rabbit pepsinogens. Stage-specific zymogens,
RT   nucleotide sequences of cDNAs, molecular evolution, and gene expression
RT   during development.";
RL   J. Biol. Chem. 265:17031-17038(1990).
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: Pepsinogens in group I, II, and III where the
CC       predominant zymogens at late postnatal stage.
CC   -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR   EMBL; M59237; AAA85370.1; -; mRNA.
DR   PIR; E38302; E38302.
DR   RefSeq; NP_001164550.1; NM_001171079.1.
DR   AlphaFoldDB; P27822; -.
DR   SMR; P27822; -.
DR   STRING; 9986.ENSOCUP00000001544; -.
DR   MEROPS; A01.001; -.
DR   GeneID; 100328620; -.
DR   KEGG; ocu:100328620; -.
DR   eggNOG; KOG1339; Eukaryota.
DR   OrthoDB; 1619495at2759; -.
DR   Proteomes; UP000001811; Unplaced.
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   2: Evidence at transcript level;
KW   Aspartyl protease; Digestion; Disulfide bond; Hydrolase; Protease;
KW   Reference proteome; Secreted; Signal; Zymogen.
FT   SIGNAL          1..15
FT   PROPEP          16..59
FT                   /note="Activation peptide"
FT                   /id="PRO_0000026034"
FT   CHAIN           60..387
FT                   /note="Pepsin-3"
FT                   /id="PRO_0000026035"
FT   DOMAIN          75..384
FT                   /note="Peptidase A1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        93
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   ACT_SITE        276
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT   DISULFID        106..111
FT                   /evidence="ECO:0000250"
FT   DISULFID        267..271
FT                   /evidence="ECO:0000250"
FT   DISULFID        310..343
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   387 AA;  41969 MW;  15A59AC81F36F9EF CRC64;
     MKWLLLLGLL ALSECIIHKV PLVRKKSLRK NLIEKGLLKD YLKTHTPNLA TKYLPKAAFD
     SVPTETLENY LDTEYFGTIG IGTPAQDFTV IFDTGSSNLW VPSVYCSSAA CSVHNQFNPE
     DSSTFQATSE SLSITYGTGS MTGFLGYDTV KVGNIEDTNQ IFGLSESEPG SFLYYAPFDG
     ILGLAYPSIS SSDATPVFDN MWNEGLVSED LFSVYLSSDD ESGSVVMFGG IDSSYYTGSL
     NWVPVSYEGY WQITLDSITM DGETIACADS CQAIVDTGTS LLAGPTSAIS NIQSYIGASE
     NSDGEMIVSC SSMYSLPNIV FTINGVQYPV PASAYILEED DACISGFEGM NLDTYTGELW
     ILGDVFIRQY FTVFDRANNQ LGLAAAA