PEPA3_HUMAN
ID PEPA3_HUMAN Reviewed; 388 AA.
AC P0DJD8; A8K749; B2R7D6; 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 74.
DE RecName: Full=Pepsin A-3;
DE EC=3.4.23.1;
DE AltName: Full=Pepsinogen-3;
DE Flags: Precursor;
GN Name=PGA3;
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 [LARGE SCALE MRNA].
RC TISSUE=Stomach;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
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 MRNA].
RC TISSUE=Brain;
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 [4]
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 [5]
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 [6]
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 [7]
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 [8]
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 [9]
RP IDENTIFICATION.
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 [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; AK312941; BAG35783.1; -; mRNA.
DR EMBL; AK125628; BAG54225.1; -; mRNA.
DR EMBL; AP000437; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC171815; AAI71815.1; -; mRNA.
DR CCDS; CCDS31574.1; -.
DR PIR; A00980; PEHU.
DR PIR; A30142; A30142.
DR PIR; A92058; A92058.
DR PIR; B30142; B30142.
DR RefSeq; NP_001073275.1; NM_001079807.3.
DR AlphaFoldDB; P0DJD8; -.
DR SMR; P0DJD8; -.
DR BioGRID; 569090; 1.
DR STRING; 9606.ENSP00000322192; -.
DR MEROPS; A01.001; -.
DR iPTMnet; P0DJD8; -.
DR PhosphoSitePlus; P0DJD8; -.
DR BioMuta; PGA3; -.
DR DMDM; 378521956; -.
DR jPOST; P0DJD8; -.
DR MassIVE; P0DJD8; -.
DR PaxDb; P0DJD8; -.
DR PeptideAtlas; P0DJD8; -.
DR PRIDE; P0DJD8; -.
DR ProteomicsDB; 52545; -.
DR Antibodypedia; 28068; 204 antibodies from 19 providers.
DR DNASU; 643834; -.
DR Ensembl; ENST00000325558.11; ENSP00000322192.6; ENSG00000229859.10.
DR GeneID; 643834; -.
DR KEGG; hsa:643834; -.
DR MANE-Select; ENST00000325558.11; ENSP00000322192.6; NM_001079807.4; NP_001073275.1.
DR UCSC; uc001nqx.4; human.
DR CTD; 643834; -.
DR DisGeNET; 643834; -.
DR GeneCards; PGA3; -.
DR HGNC; HGNC:8885; PGA3.
DR HPA; ENSG00000229859; Tissue enriched (stomach).
DR MIM; 169700; gene.
DR MIM; 169710; gene.
DR neXtProt; NX_P0DJD8; -.
DR OpenTargets; ENSG00000229859; -.
DR VEuPathDB; HostDB:ENSG00000229859; -.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000155036; -.
DR HOGENOM; CLU_013253_3_0_1; -.
DR InParanoid; P0DJD8; -.
DR OMA; WAGTISV; -.
DR OrthoDB; 1619495at2759; -.
DR PhylomeDB; P0DJD8; -.
DR TreeFam; TF314990; -.
DR PathwayCommons; P0DJD8; -.
DR Reactome; R-HSA-5683826; Surfactant metabolism.
DR BioGRID-ORCS; 643834; 18 hits in 621 CRISPR screens.
DR ChiTaRS; PGA3; human.
DR GenomeRNAi; 643834; -.
DR Pharos; P0DJD8; Tbio.
DR PRO; PR:P0DJD8; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P0DJD8; protein.
DR Bgee; ENSG00000229859; Expressed in body of stomach and 88 other tissues.
DR ExpressionAtlas; P0DJD8; baseline and differential.
DR Genevisible; P0DJD8; 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; Protease; Reference proteome; Secreted; Signal; 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_0000026013"
FT CHAIN 63..388
FT /note="Pepsin A-3"
FT /id="PRO_0000026014"
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 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 92
FT /note="V -> L (in Ref. 1; BAG35783/BAG54225 and 3;
FT AAI71815)"
FT /evidence="ECO:0000305"
FT CONFLICT 371..372
FT /note="YF -> FY (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 388 AA; 41976 MW; 5DA16E41FE198582 CRC64;
MKWLLLLGLV ALSECIMYKV PLIRKKSLRR TLSERGLLKD FLKKHNLNPA RKYFPQWKAP
TLVDEQPLEN YLDMEYFGTI GIGTPAQDFT VVFDTGSSNL WVPSVYCSSL ACTNHNRFNP
EDSSTYQSTS ETVSITYGTG SMTGILGYDT VQVGGISDTN QIFGLSETEP GSFLYYAPFD
GILGLAYPSI SSSGATPVFD NIWNQGLVSQ DLFSVYLSAD DQSGSVVIFG GIDSSYYTGS
LNWVPVTVEG YWQITVDSIT MNGEAIACAE GCQAIVDTGT SLLTGPTSPI ANIQSDIGAS
ENSDGDMVVS CSAISSLPDI VFTINGVQYP VPPSAYILQS EGSCISGFQG MNLPTESGEL
WILGDVFIRQ YFTVFDRANN QVGLAPVA
