PEPA5_HUMAN
ID PEPA5_HUMAN Reviewed; 388 AA.
AC P0DJD9; A8K749; B7ZW62; B7ZW75; P00790; Q7M4R0; Q8N1E3;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Pepsin A-5;
DE EC=3.4.23.1;
DE AltName: Full=Pepsinogen-5;
DE Flags: Precursor;
GN Name=PGA5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=2714789; DOI=10.1016/0888-7543(89)90325-x;
RA Evers M.P.J., Zelle B., Bebelman J.-P., van Beusechem V., Kraakman L.,
RA Hoffer M.J.V., Pronk J.C., Mager W.H., Planta R.J., Eriksson A.W.,
RA Frants R.R.;
RT "Nucleotide sequence comparison of five human pepsinogen A (PGA) genes:
RT evolution of the PGA multigene family.";
RL Genomics 4:232-239(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Colon, Kidney, and Stomach;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PARTIAL PROTEIN SEQUENCE OF 1-28.
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 [6]
RP PROTEIN SEQUENCE OF 16-100.
RX PubMed=2515193; DOI=10.1093/oxfordjournals.jbchem.a122952;
RA Athauda S.B.P., Tanji M., Kageyama T., Takahashi K.;
RT "A comparative study on the NH2-terminal amino acid sequences and some
RT other properties of six isozymic forms of human pepsinogens and pepsins.";
RL J. Biochem. 106:920-927(1989).
RN [7]
RP PROTEIN SEQUENCE OF 16-68.
RX PubMed=3197840; DOI=10.1016/0014-5793(88)81033-0;
RA Foltmann B.;
RT "Activation of human pepsinogens.";
RL FEBS Lett. 241:69-72(1988).
RN [8]
RP PROTEIN SEQUENCE OF 362-388.
RX PubMed=4909888; DOI=10.1016/s0021-9258(18)63137-0;
RA Huang W.-Y., Tang J.;
RT "Carboxyl-terminal sequence of human gastricsin and pepsin.";
RL J. Biol. Chem. 245:2189-2193(1970).
RN [9]
RP IDENTIFICATION.
RX PubMed=6300126; DOI=10.1016/s0021-9258(18)32572-9;
RA Sogawa K., Fujii-Kuriyama Y., Mizukami Y., Ichihara Y., Takahashi K.;
RT "Primary structure of human pepsinogen gene.";
RL J. Biol. Chem. 258:5306-5311(1983).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 63-388, ACTIVE SITES, AND
RP DISULFIDE BONDS.
RX PubMed=7663352; DOI=10.1002/pro.5560040516;
RA Fujinaga M., Chernaia M.M., Tarasova N.I., Mosimann S.C., James M.N.G.;
RT "Crystal structure of human pepsin and its complex with pepstatin.";
RL Protein Sci. 4:960-972(1995).
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 -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR EMBL; M26032; AAA60061.1; -; Genomic_DNA.
DR EMBL; M26025; AAA60061.1; JOINED; Genomic_DNA.
DR EMBL; M26026; AAA60061.1; JOINED; Genomic_DNA.
DR EMBL; M26027; AAA60061.1; JOINED; Genomic_DNA.
DR EMBL; M26028; AAA60061.1; JOINED; Genomic_DNA.
DR EMBL; M26029; AAA60061.1; JOINED; Genomic_DNA.
DR EMBL; M26030; AAA60061.1; JOINED; Genomic_DNA.
DR EMBL; M26031; AAA60061.1; JOINED; Genomic_DNA.
DR EMBL; AP003037; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW73928.1; -; Genomic_DNA.
DR EMBL; BC029055; AAH29055.1; -; mRNA.
DR EMBL; BC146999; AAI47000.1; -; mRNA.
DR EMBL; BC171889; AAI71889.1; -; mRNA.
DR CCDS; CCDS8001.1; -.
DR PIR; A00980; PEHU.
DR PIR; A30142; A30142.
DR PIR; A92058; A92058.
DR PIR; B30142; B30142.
DR RefSeq; NP_055039.1; NM_014224.4.
DR AlphaFoldDB; P0DJD9; -.
DR SMR; P0DJD9; -.
DR BioGRID; 111243; 1.
DR STRING; 9606.ENSP00000309542; -.
DR BindingDB; P0DJD9; -.
DR ChEMBL; CHEMBL3295; -.
DR DrugBank; DB00364; Sucralfate.
DR DrugCentral; P0DJD9; -.
DR GuidetoPHARMACOLOGY; 2390; -.
DR MEROPS; A01.070; -.
DR MEROPS; A01.071; -.
DR iPTMnet; P0DJD9; -.
DR PhosphoSitePlus; P0DJD9; -.
DR BioMuta; PGA5; -.
DR DMDM; 378522017; -.
DR jPOST; P0DJD9; -.
DR MassIVE; P0DJD9; -.
DR PaxDb; P0DJD9; -.
DR PeptideAtlas; P0DJD9; -.
DR PRIDE; P0DJD9; -.
DR Antibodypedia; 65697; 191 antibodies from 23 providers.
DR DNASU; 5222; -.
DR Ensembl; ENST00000312403.10; ENSP00000309542.6; ENSG00000256713.8.
DR GeneID; 5222; -.
DR KEGG; hsa:5222; -.
DR MANE-Select; ENST00000312403.10; ENSP00000309542.6; NM_014224.5; NP_055039.1.
DR UCSC; uc001nqz.4; human.
DR CTD; 5222; -.
DR DisGeNET; 5222; -.
DR GeneCards; PGA5; -.
DR HGNC; HGNC:8887; PGA5.
DR HPA; ENSG00000256713; Tissue enriched (stomach).
DR MIM; 169700; gene.
DR MIM; 169730; gene.
DR neXtProt; NX_P0DJD9; -.
DR OpenTargets; ENSG00000256713; -.
DR PharmGKB; PA33224; -.
DR VEuPathDB; HostDB:ENSG00000256713; -.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000155036; -.
DR HOGENOM; CLU_013253_3_0_1; -.
DR InParanoid; P0DJD9; -.
DR OMA; SECCIRI; -.
DR OrthoDB; 1619495at2759; -.
DR PhylomeDB; P0DJD9; -.
DR TreeFam; TF314990; -.
DR PathwayCommons; P0DJD9; -.
DR Reactome; R-HSA-5683826; Surfactant metabolism.
DR BioGRID-ORCS; 5222; 6 hits in 232 CRISPR screens.
DR ChiTaRS; PGA5; human.
DR GeneWiki; PGA5; -.
DR GenomeRNAi; 5222; -.
DR Pharos; P0DJD9; Tclin.
DR PRO; PR:P0DJD9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P0DJD9; protein.
DR Bgee; ENSG00000256713; Expressed in body of stomach and 90 other tissues.
DR ExpressionAtlas; P0DJD9; baseline and differential.
DR Genevisible; P0DJD9; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0097486; C:multivesicular body lumen; TAS:Reactome.
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 Aspartyl protease; Digestion; Direct protein sequencing; Disulfide bond;
KW Hydrolase; Phosphoprotein; Protease; Reference proteome; Secreted; Signal;
KW Zymogen.
FT SIGNAL 1..15
FT /evidence="ECO:0000269|PubMed:2515193,
FT ECO:0000269|PubMed:3197840"
FT PROPEP 16..62
FT /note="Activation peptide"
FT /id="PRO_0000415759"
FT CHAIN 63..388
FT /note="Pepsin A-5"
FT /id="PRO_0000415760"
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 ECO:0000269|PubMed:7663352"
FT ACT_SITE 277
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094,
FT ECO:0000269|PubMed:7663352"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P03954"
FT DISULFID 107..112
FT /evidence="ECO:0000269|PubMed:7663352"
FT DISULFID 268..272
FT /evidence="ECO:0000269|PubMed:7663352"
FT DISULFID 311..344
FT /evidence="ECO:0000269|PubMed:7663352"
FT CONFLICT 28
FT /note="L -> F (in Ref. 1; AAA60061)"
FT /evidence="ECO:0000305"
FT CONFLICT 58
FT /note="E -> K (in Ref. 1; AAA60061)"
FT /evidence="ECO:0000305"
FT CONFLICT 92
FT /note="V -> L (in Ref. 1; AAA60061)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="K -> Q (in Ref. 1; AAA60061)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="T -> A (in Ref. 1; AAA60061)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="V -> L (in Ref. 1; AAA60061)"
FT /evidence="ECO:0000305"
FT CONFLICT 371..372
FT /note="YF -> FY (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="D -> E (in Ref. 1; AAA60061)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 388 AA; 41993 MW; 2C456A75DA96CDDA CRC64;
MKWLLLLGLV ALSECIMYKV PLIRKKSLRR TLSERGLLKD FLKKHNLNPA RKYFPQWEAP
TLVDEQPLEN YLDMEYFGTI GIGTPAQDFT VVFDTGSSNL WVPSVYCSSL ACTNHNRFNP
EDSSTYQSTS ETVSITYGTG SMTGILGYDT VQVGGISDTN QIFGLSETEP GSFLYYAPFD
GILGLAYPSI SSSGATPVFD NIWNQGLVSQ DLFSVYLSAD DKSGSVVIFG GIDSSYYTGS
LNWVPVTVEG YWQITVDSIT MNGETIACAE GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS
ENSDGDMVVS CSAISSLPDI VFTINGVQYP VPPSAYILQS EGSCISGFQG MNVPTESGEL
WILGDVFIRQ YFTVFDRANN QVGLAPVA
