EPGN_HUMAN
ID EPGN_HUMAN Reviewed; 154 AA.
AC Q6UW88; A1BMM3; A1BMM4; A1BMM5; A1BMM6; A1BMM7; A1BMM8; A8K090;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Epigen;
DE AltName: Full=Epithelial mitogen;
DE Short=EPG;
DE Flags: Precursor;
GN Name=EPGN; ORFNames=UNQ3072/PRO9904;
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 [MRNA] (ISOFORMS 1; 3; 4; 5; 6 AND 7).
RA Johnstone L.S., Abumaree M., Martin J., Webster G., Murison G.;
RT "Human keratinocytes express several alternatively spliced forms of EPIGEN,
RT encoding directly secreted and intracellular proteins.";
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP PROTEIN SEQUENCE OF 23-37.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [5]
RP FUNCTION.
RX PubMed=15611079; DOI=10.1074/jbc.m413919200;
RA Kochupurakkal B.S., Harari D., Di-Segni A., Maik-Rachline G., Lyass L.,
RA Gur G., Kerber G., Citri A., Lavi S., Eilam R., Chalifa-Caspi V.,
RA Eshhar Z., Pikarsky E., Pinkas-Kramarski R., Bacus S.S., Yarden Y.;
RT "Epigen, the last ligand of ErbB receptors, reveals intricate relationships
RT between affinity and mitogenicity.";
RL J. Biol. Chem. 280:8503-8512(2005).
CC -!- FUNCTION: Promotes the growth of epithelial cells. May stimulate the
CC phosphorylation of EGFR and mitogen-activated protein kinases.
CC {ECO:0000269|PubMed:15611079}.
CC -!- INTERACTION:
CC Q6UW88; P00533: EGFR; NbExp=3; IntAct=EBI-15482510, EBI-297353;
CC Q6UW88-2; Q08AM2: ADAM33; NbExp=3; IntAct=EBI-17468158, EBI-10225815;
CC Q6UW88-2; Q07325: CXCL9; NbExp=3; IntAct=EBI-17468158, EBI-3911467;
CC Q6UW88-2; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-17468158, EBI-3923617;
CC Q6UW88-2; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-17468158, EBI-6268651;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane {ECO:0000305}; Single-pass
CC type I membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Membrane {ECO:0000305}; Single-pass
CC type I membrane protein {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 6]: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=1;
CC IsoId=Q6UW88-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6UW88-2; Sequence=VSP_036655, VSP_036658;
CC Name=3; Synonyms=B;
CC IsoId=Q6UW88-3; Sequence=VSP_036657;
CC Name=4; Synonyms=E;
CC IsoId=Q6UW88-4; Sequence=VSP_036656;
CC Name=5; Synonyms=F;
CC IsoId=Q6UW88-5; Sequence=VSP_036655, VSP_036657;
CC Name=6; Synonyms=G;
CC IsoId=Q6UW88-6; Sequence=VSP_036655, VSP_036656;
CC Name=7; Synonyms=D;
CC IsoId=Q6UW88-7; Sequence=VSP_036654, VSP_036656;
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DR EMBL; DQ235264; ABB60043.1; -; mRNA.
DR EMBL; DQ235265; ABB60044.1; -; mRNA.
DR EMBL; DQ235266; ABB60045.1; -; mRNA.
DR EMBL; DQ235267; ABB60046.1; -; mRNA.
DR EMBL; DQ235268; ABB60047.1; -; mRNA.
DR EMBL; DQ235269; ABB60048.1; -; mRNA.
DR EMBL; AY358920; AAQ89279.1; -; mRNA.
DR EMBL; AK289455; BAF82144.1; -; mRNA.
DR CCDS; CCDS59475.1; -. [Q6UW88-5]
DR CCDS; CCDS59476.1; -. [Q6UW88-6]
DR CCDS; CCDS59477.1; -. [Q6UW88-3]
DR CCDS; CCDS59478.1; -. [Q6UW88-1]
DR CCDS; CCDS59479.1; -. [Q6UW88-4]
DR RefSeq; NP_001257918.1; NM_001270989.1. [Q6UW88-1]
DR RefSeq; NP_001257919.1; NM_001270990.1. [Q6UW88-3]
DR RefSeq; NP_001257920.1; NM_001270991.1. [Q6UW88-5]
DR RefSeq; NP_001257921.1; NM_001270992.1. [Q6UW88-4]
DR RefSeq; NP_001257922.1; NM_001270993.1. [Q6UW88-6]
DR RefSeq; XP_005265723.1; XM_005265666.4.
DR PDB; 5WB8; X-ray; 3.00 A; B/C=49-108.
DR PDBsum; 5WB8; -.
DR AlphaFoldDB; Q6UW88; -.
DR SMR; Q6UW88; -.
DR BioGRID; 129094; 18.
DR IntAct; Q6UW88; 7.
DR STRING; 9606.ENSP00000411898; -.
DR GlyGen; Q6UW88; 2 sites.
DR iPTMnet; Q6UW88; -.
DR PhosphoSitePlus; Q6UW88; -.
DR BioMuta; EPGN; -.
DR DMDM; 229464464; -.
DR EPD; Q6UW88; -.
DR MassIVE; Q6UW88; -.
DR PeptideAtlas; Q6UW88; -.
DR PRIDE; Q6UW88; -.
DR TopDownProteomics; Q6UW88-2; -. [Q6UW88-2]
DR Antibodypedia; 24613; 176 antibodies from 27 providers.
DR DNASU; 255324; -.
DR Ensembl; ENST00000332112.8; ENSP00000330375.4; ENSG00000182585.10. [Q6UW88-2]
DR Ensembl; ENST00000413830.6; ENSP00000411898.1; ENSG00000182585.10. [Q6UW88-1]
DR Ensembl; ENST00000502358.5; ENSP00000426678.1; ENSG00000182585.10. [Q6UW88-4]
DR Ensembl; ENST00000503098.5; ENSP00000425890.1; ENSG00000182585.10. [Q6UW88-3]
DR Ensembl; ENST00000505212.5; ENSP00000424392.1; ENSG00000182585.10. [Q6UW88-6]
DR Ensembl; ENST00000509145.5; ENSP00000426630.1; ENSG00000182585.10. [Q6UW88-7]
DR Ensembl; ENST00000514968.5; ENSP00000426550.1; ENSG00000182585.10. [Q6UW88-5]
DR GeneID; 255324; -.
DR KEGG; hsa:255324; -.
DR MANE-Select; ENST00000413830.6; ENSP00000411898.1; NM_001270989.2; NP_001257918.1.
DR UCSC; uc003hhw.5; human. [Q6UW88-1]
DR CTD; 255324; -.
DR DisGeNET; 255324; -.
DR GeneCards; EPGN; -.
DR HGNC; HGNC:17470; EPGN.
DR HPA; ENSG00000182585; Tissue enriched (esophagus).
DR MIM; 618717; gene.
DR neXtProt; NX_Q6UW88; -.
DR OpenTargets; ENSG00000182585; -.
DR PharmGKB; PA162385143; -.
DR VEuPathDB; HostDB:ENSG00000182585; -.
DR eggNOG; ENOG502S4QW; Eukaryota.
DR GeneTree; ENSGT00510000048556; -.
DR HOGENOM; CLU_144237_1_0_1; -.
DR InParanoid; Q6UW88; -.
DR OMA; DKPSCIC; -.
DR OrthoDB; 1425022at2759; -.
DR PhylomeDB; Q6UW88; -.
DR TreeFam; TF335931; -.
DR PathwayCommons; Q6UW88; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-177929; Signaling by EGFR.
DR Reactome; R-HSA-179812; GRB2 events in EGFR signaling.
DR Reactome; R-HSA-180292; GAB1 signalosome.
DR Reactome; R-HSA-180336; SHC1 events in EGFR signaling.
DR Reactome; R-HSA-182971; EGFR downregulation.
DR Reactome; R-HSA-212718; EGFR interacts with phospholipase C-gamma.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-5638303; Inhibition of Signaling by Overexpressed EGFR.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR SignaLink; Q6UW88; -.
DR SIGNOR; Q6UW88; -.
DR BioGRID-ORCS; 255324; 9 hits in 1023 CRISPR screens.
DR GenomeRNAi; 255324; -.
DR Pharos; Q6UW88; Tbio.
DR PRO; PR:Q6UW88; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q6UW88; protein.
DR Bgee; ENSG00000182585; Expressed in esophagus mucosa and 79 other tissues.
DR ExpressionAtlas; Q6UW88; baseline and differential.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:HGNC-UCL.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:HGNC-UCL.
DR GO; GO:0008083; F:growth factor activity; IDA:HGNC-UCL.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IDA:HGNC-UCL.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:HGNC-UCL.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IDA:HGNC-UCL.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:HGNC-UCL.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:HGNC-UCL.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:HGNC-UCL.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR015497; EGF_rcpt_ligand.
DR PANTHER; PTHR10740; PTHR10740; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disulfide bond; EGF-like domain; Glycoprotein; Growth factor; Membrane;
KW Reference proteome; Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 23..154
FT /note="Epigen"
FT /id="PRO_0000045462"
FT TOPO_DOM 23..110
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 132..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 56..96
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 60..73
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 68..84
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 86..95
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 15..44
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_036654"
FT VAR_SEQ 36..44
FT /note="Missing (in isoform 2, isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:12975309, ECO:0000303|Ref.1"
FT /id="VSP_036655"
FT VAR_SEQ 87..137
FT /note="Missing (in isoform 4, isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_036656"
FT VAR_SEQ 96..137
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_036657"
FT VAR_SEQ 137..154
FT /note="CLKLKSPYNVCSGERRPL -> YEKDKI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_036658"
FT CONFLICT 9
FT /note="V -> A (in Ref. 1; ABB60048)"
FT /evidence="ECO:0000305"
FT CONFLICT 62
FT /note="E -> G (in Ref. 1; ABB60047)"
FT /evidence="ECO:0000305"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:5WB8"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:5WB8"
FT TURN 77..80
FT /evidence="ECO:0007829|PDB:5WB8"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:5WB8"
FT TURN 92..95
FT /evidence="ECO:0007829|PDB:5WB8"
SQ SEQUENCE 154 AA; 17091 MW; BC78016BE3026474 CRC64;
MALGVPISVY LLFNAMTALT EEAAVTVTPP ITAQQGNWTV NKTEADNIEG PIALKFSHLC
LEDHNSYCIN GACAFHHELE KAICRCFTGY TGERCEHLTL TSYAVDSYEK YIAIGIGVGL
LLSGFLVIFY CYIRKRCLKL KSPYNVCSGE RRPL
