ID   PEPA1_RABIT             Reviewed;         387 AA.
AC   P28712; Q54A54;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-1992, sequence version 1.
DT   03-AUG-2022, entry version 112.
DE   RecName: Full=Pepsin II-1;
DE            EC=3.4.23.1;
DE   AltName: Full=Pepsin A;
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=Stomach;
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; AB089790; BAC07514.1; -; mRNA.
DR   PIR; B38302; B38302.
DR   RefSeq; NP_001164549.1; NM_001171078.1.
DR   AlphaFoldDB; P28712; -.
DR   SMR; P28712; -.
DR   STRING; 9986.ENSOCUP00000015402; -.
DR   MEROPS; A01.001; -.
DR   Ensembl; ENSOCUT00000006740; ENSOCUP00000005828; ENSOCUG00000023022.
DR   GeneID; 100328619; -.
DR   KEGG; ocu:100328619; -.
DR   eggNOG; KOG1339; Eukaryota.
DR   GeneTree; ENSGT00940000155036; -.
DR   HOGENOM; CLU_013253_3_0_1; -.
DR   InParanoid; P28712; -.
DR   OrthoDB; 1619495at2759; -.
DR   Proteomes; UP000001811; Unplaced.
DR   Bgee; ENSOCUG00000023022; Expressed in smooth muscle tissue and 2 other tissues.
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; Phosphoprotein;
KW   Protease; Reference proteome; Secreted; Signal; Zymogen.
FT   SIGNAL          1..15
FT   PROPEP          16..59
FT                   /note="Activation peptide"
FT                   /id="PRO_0000026028"
FT   CHAIN           60..387
FT                   /note="Pepsin II-1"
FT                   /id="PRO_0000026029"
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   MOD_RES         129
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P03954"
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;  42071 MW;  A6EC48F715541A48 CRC64;
     MKWLLLLGLL ALSECIVHKV PLVRKKSLRK NLIEKGLLQD YLKTHTPNLA TKYFPKETFA
     SVSTESLENY LDAEYFGTIS IGTPPQEFTV IFDTGSSNLW VPSTYCSSLA CFLHKRFNPD
     DSSTFQATSE TLSITYGTGS MTGILGYDTV KVGNIEDTNQ IFGLSKTEPG ITFLVAPFDG
     ILGLAYPSIS ASDATPVFDN MWNEGLVSED LFSVYLSSNG EKGSMVMFGG IDSSYYTGSL
     NWVPVSHEGY WQITMDSITI NGETIACADS CQAVVDTGTS LLAGPTSAIS KIQSYIGASK
     NLLGENIISC SAIDSLPDIV FTINNVQYPL PASAYILKED DDCLSGFDGM NLDTSYGELW
     ILGDVFIRQY FTVFDRANNQ VGLAAAA