PEPA_PIG
ID PEPA_PIG Reviewed; 385 AA.
AC P00791; Q29080;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Pepsin A;
DE EC=3.4.23.1;
DE Flags: Precursor;
GN Name=PGA;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3044927; DOI=10.1016/0378-1119(88)90465-9;
RA Tsukagoshi N., Ando Y., Tomita Y., Uchida R., Takemura T., Sasaki T.,
RA Yamagata H., Udaka S., Ichihara Y., Takahashi K.;
RT "Nucleotide sequence and expression in Escherichia coli of cDNA of swine
RT pepsinogen: involvement of the amino-terminal portion of the activation
RT peptide segment in restoration of the functional protein.";
RL Gene 65:285-292(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 16-20 AND 60-65, AND
RP MUTAGENESIS OF ASP-91.
RX PubMed=2494172; DOI=10.1016/s0021-9258(18)83769-3;
RA Lin X.-L., Wong R.N.S., Tang J.;
RT "Synthesis, purification, and active-site mutagenesis of recombinant
RT porcine pepsinogen.";
RL J. Biol. Chem. 264:4482-4489(1989).
RN [3]
RP PROTEIN SEQUENCE OF 60-385, AND DISULFIDE BONDS.
RX PubMed=4604255; DOI=10.1016/0014-5793(74)81001-x;
RA Moravek L., Kostka V.;
RT "Complete amino acid sequence of hog pepsin.";
RL FEBS Lett. 43:207-211(1974).
RN [4]
RP PROTEIN SEQUENCE OF 16-134.
RX PubMed=4584879; DOI=10.1016/0006-291x(73)90814-0;
RA Stepanov V.M., Baratova L.A., Pugacheva I.B., Belyanova L.P., Revina L.P.,
RA Timokhina E.A.;
RT "N-terminal sequence of swine pepsinogen and pepsin. The site of pepsinogen
RT activation.";
RL Biochem. Biophys. Res. Commun. 54:1164-1170(1973).
RN [5]
RP PROTEIN SEQUENCE OF 16-56.
RX PubMed=4881358; DOI=10.1016/s0021-9258(18)94466-2;
RA Ong E.B., Perlmann G.E.;
RT "The amino-terminal sequence of porcine pepsinogen.";
RL J. Biol. Chem. 243:6104-6109(1968).
RN [6]
RP PROTEIN SEQUENCE OF 58-347.
RX PubMed=1097438; DOI=10.1016/s0021-9258(19)41281-7;
RA Sepulveda P., Marciniszyn J.P. Jr., Liu D., Tang J.;
RT "Primary structure of porcine pepsin. III. Amino acid sequence of a
RT cyanogen bromide fragment, CB2A, and the complete structure of porcine
RT pepsin.";
RL J. Biol. Chem. 250:5082-5088(1975).
RN [7]
RP PARTIAL PROTEIN SEQUENCE OF 1-26.
RX PubMed=2415509; DOI=10.1093/oxfordjournals.jbchem.a135303;
RA Ichihara Y., Sogawa K., Takahashi K.;
RT "Isolation of human, swine, and rat prepepsinogens and calf preprochymosin,
RT and determination of the primary structures of their NH2-terminal signal
RT sequences.";
RL J. Biochem. 98:483-492(1985).
RN [8]
RP ACTIVE SITE.
RX PubMed=4897201; DOI=10.1042/bj1130377;
RA Bayliss R.S., Knowles J.R., Wybrandt G.B.;
RT "An aspartic acid residue at the active site of pepsin. The isolation and
RT sequence of the heptapeptide.";
RL Biochem. J. 113:377-386(1969).
RN [9]
RP CRYSTALLIZATION.
RX PubMed=339692; DOI=10.1007/978-1-4757-0719-9_2;
RA Andreeva N.S., Gustchina A.E., Fedorov A.A., Shutzkever N.E., Volnova T.V.;
RT "X-ray crystallographic studies of pepsin.";
RL Adv. Exp. Med. Biol. 95:23-31(1977).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=2115088; DOI=10.1016/0022-2836(90)90156-g;
RA Cooper J.B., Khan G., Taylor G., Tickle I.J., Blundell T.L.;
RT "X-ray analyses of aspartic proteinases. II. Three-dimensional structure of
RT the hexagonal crystal form of porcine pepsin at 2.3-A resolution.";
RL J. Mol. Biol. 214:199-222(1990).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=2217165; DOI=10.1002/prot.340080109;
RA Abad-Zapatero C., Rydel T.J., Erickson J.;
RT "Revised 2.3 A structure of porcine pepsin: evidence for a flexible
RT subdomain.";
RL Proteins 8:62-81(1990).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RX PubMed=2056534; DOI=10.1016/0022-2836(91)90664-r;
RA Sielecki A.R., Fujinaga M., Read R.J., James M.N.G.;
RT "Refined structure of porcine pepsinogen at 1.8-A resolution.";
RL J. Mol. Biol. 219:671-692(1991).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
RX PubMed=1594574; DOI=10.1002/prot.340130102;
RA Hartsuck J.E., Koelsch G., Remington S.J.;
RT "The high-resolution crystal structure of porcine pepsinogen.";
RL Proteins 13:1-25(1992).
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: Minor amounts of the active enzyme occur with 'Ala-58' at the
CC amino end.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Worthington enzyme manual;
CC URL="https://www.worthington-biochem.com/PM/";
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DR EMBL; M20920; AAA31095.1; -; mRNA.
DR EMBL; J04601; AAA31096.1; -; mRNA.
DR PIR; JT0307; PEPG.
DR PDB; 1F34; X-ray; 2.45 A; A=60-385.
DR PDB; 1PSA; X-ray; 2.90 A; A/B=60-385.
DR PDB; 1YX9; X-ray; 3.00 A; A=60-385.
DR PDB; 2PSG; X-ray; 1.80 A; A=16-385.
DR PDB; 3PEP; X-ray; 2.30 A; A=60-385.
DR PDB; 3PSG; X-ray; 1.65 A; A=16-385.
DR PDB; 4PEP; X-ray; 1.80 A; A=60-385.
DR PDB; 5PEP; X-ray; 2.34 A; A=60-385.
DR PDB; 6XCT; X-ray; 1.99 A; A=60-385.
DR PDB; 6XCY; X-ray; 2.05 A; A=60-385.
DR PDB; 6XCZ; X-ray; 1.89 A; A=60-385.
DR PDB; 6XD2; X-ray; 1.90 A; A=60-385.
DR PDBsum; 1F34; -.
DR PDBsum; 1PSA; -.
DR PDBsum; 1YX9; -.
DR PDBsum; 2PSG; -.
DR PDBsum; 3PEP; -.
DR PDBsum; 3PSG; -.
DR PDBsum; 4PEP; -.
DR PDBsum; 5PEP; -.
DR PDBsum; 6XCT; -.
DR PDBsum; 6XCY; -.
DR PDBsum; 6XCZ; -.
DR PDBsum; 6XD2; -.
DR AlphaFoldDB; P00791; -.
DR BMRB; P00791; -.
DR PCDDB; P00791; -.
DR SMR; P00791; -.
DR MINT; P00791; -.
DR STRING; 9823.ENSSSCP00000013926; -.
DR BindingDB; P00791; -.
DR ChEMBL; CHEMBL2714; -.
DR Allergome; 2924; Sus s Pepsin.
DR MEROPS; A01.001; -.
DR PaxDb; P00791; -.
DR PeptideAtlas; P00791; -.
DR PRIDE; P00791; -.
DR Ensembl; ENSSSCT00000014312; ENSSSCP00000013926; ENSSSCG00000013092.
DR Ensembl; ENSSSCT00005071024; ENSSSCP00005044265; ENSSSCG00005044113.
DR Ensembl; ENSSSCT00015022688; ENSSSCP00015008841; ENSSSCG00015017091.
DR Ensembl; ENSSSCT00025107631; ENSSSCP00025048575; ENSSSCG00025077434.
DR Ensembl; ENSSSCT00030085988; ENSSSCP00030039649; ENSSSCG00030061514.
DR Ensembl; ENSSSCT00035075724; ENSSSCP00035030866; ENSSSCG00035056668.
DR Ensembl; ENSSSCT00040080009; ENSSSCP00040034607; ENSSSCG00040058917.
DR Ensembl; ENSSSCT00050064505; ENSSSCP00050027794; ENSSSCG00050047341.
DR Ensembl; ENSSSCT00060103137; ENSSSCP00060044987; ENSSSCG00060075334.
DR Ensembl; ENSSSCT00065107886; ENSSSCP00065048135; ENSSSCG00065077961.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000155036; -.
DR HOGENOM; CLU_013253_3_0_1; -.
DR InParanoid; P00791; -.
DR OMA; ENYMDME; -.
DR TreeFam; TF314990; -.
DR BRENDA; 3.4.23.1; 6170.
DR SABIO-RK; P00791; -.
DR EvolutionaryTrace; P00791; -.
DR Proteomes; UP000008227; Chromosome 2.
DR Proteomes; UP000314985; Unplaced.
DR Bgee; ENSSSCG00000013092; Expressed in duodenum and 8 other tissues.
DR Genevisible; P00791; SS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0007586; P:digestion; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
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 3D-structure; Aspartyl protease; Digestion; Direct protein sequencing;
KW Disulfide bond; Hydrolase; Phosphoprotein; Protease; Reference proteome;
KW Secreted; Signal; Zymogen.
FT SIGNAL 1..15
FT /evidence="ECO:0000269|PubMed:2494172,
FT ECO:0000269|PubMed:3044927, ECO:0000269|PubMed:4584879,
FT ECO:0000269|PubMed:4881358"
FT PROPEP 16..59
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:2494172,
FT ECO:0000269|PubMed:4604255"
FT /id="PRO_0000026026"
FT CHAIN 60..385
FT /note="Pepsin A"
FT /id="PRO_0000026027"
FT DOMAIN 73..382
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 91
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094,
FT ECO:0000269|PubMed:1097438, ECO:0000269|PubMed:4897201"
FT ACT_SITE 274
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094,
FT ECO:0000269|PubMed:1097438, ECO:0000269|PubMed:4897201"
FT MOD_RES 127
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03954"
FT DISULFID 104..109
FT /evidence="ECO:0000269|PubMed:1097438,
FT ECO:0000269|PubMed:4604255"
FT DISULFID 265..269
FT /evidence="ECO:0000269|PubMed:1097438,
FT ECO:0000269|PubMed:4604255"
FT DISULFID 308..341
FT /evidence="ECO:0000269|PubMed:4604255"
FT MUTAGEN 91
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:2494172"
FT CONFLICT 34
FT /note="N -> D (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 119..120
FT /note="DS -> SD (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="Q -> E (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="A -> AI (in Ref. 1; AAA31095)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="D -> Y (in Ref. 2; AAA31096)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="S -> Q (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 322
FT /note="N -> D (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 17..23
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 27..33
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 37..43
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:2PSG"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:6XCZ"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:3PSG"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:4PEP"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:3PSG"
FT TURN 80..83
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 97..101
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 124..136
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 138..150
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 153..163
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 169..173
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 195..201
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 205..214
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:2PSG"
FT STRAND 222..226
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 239..242
FT /evidence="ECO:0007829|PDB:3PSG"
FT TURN 246..249
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 250..253
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 255..264
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 279..283
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 284..293
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:2PSG"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:2PSG"
FT HELIX 308..313
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 317..321
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 324..328
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 330..333
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 341..348
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:2PSG"
FT STRAND 357..360
FT /evidence="ECO:0007829|PDB:3PSG"
FT HELIX 362..365
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 368..373
FT /evidence="ECO:0007829|PDB:3PSG"
FT TURN 374..377
FT /evidence="ECO:0007829|PDB:3PSG"
FT STRAND 378..384
FT /evidence="ECO:0007829|PDB:3PSG"
SQ SEQUENCE 385 AA; 41262 MW; 27908D6AC0489D2D CRC64;
MKWLLLLSLV VLSECLVKVP LVRKKSLRQN LIKNGKLKDF LKTHKHNPAS KYFPEAAALI
GDEPLENYLD TEYFGTIGIG TPAQDFTVIF DTGSSNLWVP SVYCSSLACS DHNQFNPDDS
STFEATSQEL SITYGTGSMT GILGYDTVQV GGISDTNQIF GLSETEPGSF LYYAPFDGIL
GLAYPSISAS GATPVFDNLW DQGLVSQDLF SVYLSSNDDS GSVVLLGGID SSYYTGSLNW
VPVSVEGYWQ ITLDSITMDG ETIACSGGCQ AIVDTGTSLL TGPTSAIANI QSDIGASENS
DGEMVISCSS IDSLPDIVFT INGVQYPLSP SAYILQDDDS CTSGFEGMDV PTSSGELWIL
GDVFIRQYYT VFDRANNKVG LAPVA
