ID TGFA_HUMAN Reviewed; 160 AA. AC P01135; A8K286; Q15577; Q53SK7; Q9BS56; Q9UEI3; Q9UKM1; Q9UKM2; AC Q9UKM3; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 13-FEB-2019, entry version 198. DE RecName: Full=Protransforming growth factor alpha; DE Contains: DE RecName: Full=Transforming growth factor alpha; DE Short=TGF-alpha; DE AltName: Full=EGF-like TGF; DE Short=ETGF; DE AltName: Full=TGF type 1; DE Flags: Precursor; GN Name=TGFA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=6088071; DOI=10.1016/0092-8674(84)90550-6; RA Derynck R., Roberts A.B., Winkler M.E., Chen E.Y., Goeddel D.V.; RT "Human transforming growth factor-alpha: precursor structure and RT expression in E. coli."; RL Cell 38:287-297(1984). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2464748; DOI=10.1210/mend-2-11-1056; RA Jakowlew S.B., Kondaiah P., Dillard P.J., Sporn M.B., Roberts A.B.; RT "A novel low molecular weight ribonucleic acid (RNA) related to RT transforming growth factor alpha messenger RNA."; RL Mol. Endocrinol. 2:1056-1063(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=8224876; DOI=10.1016/0378-1119(93)90210-T; RA Qian J.F., Lazar-Wesley E., Breugnot C., May E.; RT "Human transforming growth factor alpha: sequence analysis of the 4.5- RT kb and 1.6-kb mRNA species."; RL Gene 132:291-296(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8100397; RA Qian J.F., Feingold J., Stoll C., May E.; RT "Transforming growth factor-alpha: characterization of the BamHI, RT RsaI, and TaqI polymorphic regions."; RL Am. J. Hum. Genet. 53:168-175(1993). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10552925; DOI=10.1006/geno.1999.5962; RA Machida J., Yoshiura K., Funkhauser C.D., Natsume N., Kawai T., RA Murray J.C.; RT "Transforming growth factor-alpha (TGFA): genomic structure, boundary RT sequences, and mutation analysis in nonsyndromic cleft lip/palate and RT cleft palate only."; RL Genomics 61:237-242(1999). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5), AND TISSUE RP SPECIFICITY. RX PubMed=10523832; DOI=10.1038/sj.onc.1203091; RA Xu X., Liao J., Creek K.E., Pirisi L.; RT "Human keratinocytes and tumor-derived cell lines express RT alternatively spliced forms of transforming growth factor-alpha mRNA, RT encoding precursors lacking carboxyl-terminal valine residues."; RL Oncogene 18:5554-5562(1999). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) System Donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Thalamus; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Kidney; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58. RX PubMed=2907605; DOI=10.1128/MCB.8.12.5549; RA Jakobovits E.B., Schlokat U., Vannice J.L., Derynck R., Levinson A.D.; RT "The human transforming growth factor alpha promoter directs RT transcription initiation from a single site in the absence of a TATA RT sequence."; RL Mol. Cell. Biol. 8:5549-5554(1988). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-31. RX PubMed=10066034; DOI=10.1034/j.1399-0004.1999.550111.x; RA Collin G.B., Marshall J.D., Naggert J.K., Nishina P.M.; RT "TGFA: exon-intron structure and evaluation as a candidate gene for RT Alstrom syndrome."; RL Clin. Genet. 55:61-62(1999). RN [14] RP DISULFIDE BONDS. RX PubMed=1632509; DOI=10.1016/0003-2697(92)90331-Z; RA Bean M.F., Carr S.A.; RT "Characterization of disulfide bond position in proteins and sequence RT analysis of cystine-bridged peptides by tandem mass spectrometry."; RL Anal. Biochem. 201:216-226(1992). RN [15] RP PALMITOYLATION AT CYS-153 AND CYS-154. RX PubMed=8910478; DOI=10.1074/jbc.271.45.28502; RA Shum L., Turck C.W., Derynck R.; RT "Cysteines 153 and 154 of transmembrane transforming growth factor- RT alpha are palmitoylated and mediate cytoplasmic protein association."; RL J. Biol. Chem. 271:28502-28508(1996). RN [16] RP INTERACTION WITH SNTA1 AND SDCBP. RX PubMed=10230395; DOI=10.1016/S1097-2765(00)80470-0; RA Fernandez-Larrea J., Merlos-Suarez A., Urena J.M., Baselga J., RA Arribas J.; RT "A role for a PDZ protein in the early secretory pathway for the RT targeting of proTGF-alpha to the cell surface."; RL Mol. Cell 3:423-433(1999). RN [17] RP INTERACTION WITH CNIH AND GORASP2. RX PubMed=17607000; DOI=10.1242/jcs.004200; RA Perez Castro C., Piscopo D., Nakagawa T., Derynck R.; RT "Cornichon regulates transport and secretion of TGFalpha-related RT proteins in metazoan cells."; RL J. Cell Sci. 120:2454-2466(2007). RN [18] RP INTERACTION WITH NKD2. RX PubMed=18757723; DOI=10.1073/pnas.0806298105; RA Ding W., Li C., Hu T., Graves-Deal R., Fotia A.B., Weissman A.M., RA Coffey R.J.; RT "EGF receptor-independent action of TGF-alpha protects Naked2 from RT AO7-mediated ubiquitylation and proteasomal degradation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:13433-13438(2008). RN [19] RP STRUCTURE BY NMR OF TGF-ALPHA. RX PubMed=2261437; DOI=10.1021/bi00486a005; RA Kline T.P., Brown F.K., Brown S.C., Jeffs P.W., Kopple K.D., RA Mueller L.; RT "Solution structures of human transforming growth factor alpha derived RT from 1H NMR data."; RL Biochemistry 29:7805-7813(1990). RN [20] RP STRUCTURE BY NMR OF TGF-ALPHA. RX PubMed=2050136; DOI=10.1111/j.1432-1033.1991.tb16050.x; RA Harvey T.S., Wilkinson A.J., Tappin M.J., Cooke R.M., Campbell I.D.; RT "The solution structure of human transforming growth factor alpha."; RL Eur. J. Biochem. 198:555-562(1991). RN [21] RP STRUCTURE BY NMR OF TGF-ALPHA. RX PubMed=8338831; DOI=10.1021/bi00080a003; RA Moy F.J., Li Y.C., Rauenbuehler P., Winkler M.E., Scheraga H.A., RA Montelione G.T.; RT "Solution structure of human type-alpha transforming growth factor RT determined by heteronuclear NMR spectroscopy and refined by energy RT minimization with restraints."; RL Biochemistry 32:7334-7353(1993). CC -!- FUNCTION: TGF alpha is a mitogenic polypeptide that is able to CC bind to the EGF receptor/EGFR and to act synergistically with TGF CC beta to promote anchorage-independent cell proliferation in soft CC agar. CC -!- SUBUNIT: Interacts with the PDZ domains of MAGI3, SDCBP and SNTA1. CC The interaction with SDCBP, is required for the targeting to the CC cell surface. In the endoplasmic reticulum, in its immature form CC (i.e. with a prosegment and lacking full N-glycosylation), CC interacts with CNIH. In the Golgi apparatus, may form a complex CC with CNIH and GORASP2. Interacts (via cytoplasmic C-terminal CC domain) with NKD2. {ECO:0000269|PubMed:10230395, CC ECO:0000269|PubMed:17607000, ECO:0000269|PubMed:18757723}. CC -!- INTERACTION: CC P00533:EGFR; NbExp=2; IntAct=EBI-1034374, EBI-297353; CC Q9EQJ9:Magi3 (xeno); NbExp=4; IntAct=EBI-1034374, EBI-7455245; CC Q969F2:NKD2; NbExp=3; IntAct=EBI-1034374, EBI-1538629; CC O43765:SGTA; NbExp=4; IntAct=EBI-12367411, EBI-347996; CC -!- SUBCELLULAR LOCATION: Transforming growth factor alpha: Secreted, CC extracellular space. CC -!- SUBCELLULAR LOCATION: Protransforming growth factor alpha: Cell CC membrane; Single-pass type I membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P01135-1; Sequence=Displayed; CC Name=2; CC IsoId=P01135-2; Sequence=VSP_038369; CC Name=3; Synonyms=VaII; CC IsoId=P01135-3; Sequence=VSP_038369, VSP_038370; CC Name=4; Synonyms=VaI; CC IsoId=P01135-4; Sequence=VSP_038371; CC Name=5; Synonyms=VaIM; CC IsoId=P01135-5; Sequence=VSP_038369, VSP_038371; CC -!- TISSUE SPECIFICITY: Isoform 1, isoform 3 and isoform 4 are CC expressed in keratinocytes and tumor-derived cell lines. CC {ECO:0000269|PubMed:10523832}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; K03222; AAA61159.1; -; mRNA. DR EMBL; M31172; AAA61157.1; -; mRNA. DR EMBL; X70340; CAA49806.1; -; mRNA. DR EMBL; AF123243; AAF13491.1; -; Genomic_DNA. DR EMBL; AF123238; AAF13491.1; JOINED; Genomic_DNA. DR EMBL; AF123239; AAF13491.1; JOINED; Genomic_DNA. DR EMBL; AF123240; AAF13491.1; JOINED; Genomic_DNA. DR EMBL; AF123241; AAF13491.1; JOINED; Genomic_DNA. DR EMBL; AF123242; AAF13491.1; JOINED; Genomic_DNA. DR EMBL; AY325886; AAP97822.2; -; Genomic_DNA. DR EMBL; AY325885; AAP97822.2; JOINED; Genomic_DNA. DR EMBL; AY326405; AAP97822.2; JOINED; Genomic_DNA. DR EMBL; AY327131; AAP97822.2; JOINED; Genomic_DNA. DR EMBL; AY327132; AAP97822.2; JOINED; Genomic_DNA. DR EMBL; AY329368; AAP97822.2; JOINED; Genomic_DNA. DR EMBL; AF149096; AAF05089.1; -; mRNA. DR EMBL; AF149097; AAF05090.1; -; mRNA. DR EMBL; AF149098; AAF05091.1; -; mRNA. DR EMBL; BT006833; AAP35479.1; -; mRNA. DR EMBL; AK290151; BAF82840.1; -; mRNA. DR EMBL; AC005234; AAY14793.1; -; Genomic_DNA. DR EMBL; AC017084; AAY14705.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99810.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99812.1; -; Genomic_DNA. DR EMBL; BC005308; AAH05308.1; -; mRNA. DR EMBL; M22440; AAA52530.1; -; Genomic_DNA. DR EMBL; AF075584; AAD12238.1; -; Genomic_DNA. DR EMBL; AF075583; AAD12238.1; JOINED; Genomic_DNA. DR CCDS; CCDS1905.1; -. [P01135-1] DR CCDS; CCDS46316.1; -. [P01135-2] DR PIR; JN0876; WFHU1. DR RefSeq; NP_001093161.1; NM_001099691.2. [P01135-2] DR RefSeq; NP_001295087.1; NM_001308158.1. DR RefSeq; NP_001295088.1; NM_001308159.1. DR RefSeq; NP_003227.1; NM_003236.3. [P01135-1] DR UniGene; Hs.170009; -. DR UniGene; Hs.628298; -. DR PDB; 1GK5; NMR; -; A=83-89. DR PDB; 1MOX; X-ray; 2.50 A; C/D=40-89. DR PDB; 1YUF; NMR; -; A=40-89. DR PDB; 1YUG; NMR; -; A=40-89. DR PDB; 2TGF; NMR; -; A=40-89. DR PDB; 3E50; X-ray; 2.30 A; C/D=40-89. DR PDB; 3TGF; NMR; -; A=40-89. DR PDB; 4TGF; NMR; -; A=40-89. DR PDB; 5KN5; X-ray; 2.80 A; C/F=49-88. DR PDBsum; 1GK5; -. DR PDBsum; 1MOX; -. DR PDBsum; 1YUF; -. DR PDBsum; 1YUG; -. DR PDBsum; 2TGF; -. DR PDBsum; 3E50; -. DR PDBsum; 3TGF; -. DR PDBsum; 4TGF; -. DR PDBsum; 5KN5; -. DR ProteinModelPortal; P01135; -. DR SMR; P01135; -. DR BioGrid; 112897; 68. DR DIP; DIP-5765N; -. DR IntAct; P01135; 10. DR MINT; P01135; -. DR STRING; 9606.ENSP00000295400; -. DR SwissPalm; P01135; -. DR BioMuta; TGFA; -. DR DMDM; 135689; -. DR jPOST; P01135; -. DR PaxDb; P01135; -. DR PeptideAtlas; P01135; -. DR PRIDE; P01135; -. DR ProteomicsDB; 51332; -. DR ProteomicsDB; 51333; -. [P01135-2] DR ProteomicsDB; 51334; -. [P01135-3] DR ProteomicsDB; 51335; -. [P01135-4] DR ProteomicsDB; 51336; -. [P01135-5] DR DNASU; 7039; -. DR Ensembl; ENST00000295400; ENSP00000295400; ENSG00000163235. [P01135-1] DR Ensembl; ENST00000418333; ENSP00000404099; ENSG00000163235. [P01135-2] DR Ensembl; ENST00000445399; ENSP00000387493; ENSG00000163235. [P01135-3] DR GeneID; 7039; -. DR KEGG; hsa:7039; -. DR UCSC; uc002sgs.4; human. [P01135-1] DR CTD; 7039; -. DR DisGeNET; 7039; -. DR EuPathDB; HostDB:ENSG00000163235.15; -. DR GeneCards; TGFA; -. DR HGNC; HGNC:11765; TGFA. DR HPA; HPA042297; -. DR MalaCards; TGFA; -. DR MIM; 190170; gene. DR neXtProt; NX_P01135; -. DR OpenTargets; ENSG00000163235; -. DR Orphanet; 2227; NON RARE IN EUROPE: Hypodontia. DR Orphanet; 99798; Oligodontia. DR PharmGKB; PA36480; -. DR eggNOG; ENOG410IVW5; Eukaryota. DR eggNOG; ENOG4111Z4I; LUCA. DR GeneTree; ENSGT00940000160058; -. DR HOGENOM; HOG000013036; -. DR HOVERGEN; HBG000330; -. DR InParanoid; P01135; -. DR KO; K08774; -. DR OMA; CQALICR; -. DR OrthoDB; 1314811at2759; -. DR PhylomeDB; P01135; -. DR TreeFam; TF332938; -. 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-204005; COPII-mediated vesicle transport. 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-5694530; Cargo concentration in the ER. 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-8866910; TFAP2 (AP-2) family regulates transcription of growth factors and their receptors. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR SignaLink; P01135; -. DR SIGNOR; P01135; -. DR ChiTaRS; TGFA; human. DR EvolutionaryTrace; P01135; -. DR GeneWiki; TGF_alpha; -. DR GenomeRNAi; 7039; -. DR PMAP-CutDB; P01135; -. DR PRO; PR:P01135; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; ENSG00000163235; Expressed in 192 organ(s), highest expression level in pigmented layer of retina. DR ExpressionAtlas; P01135; baseline and differential. DR Genevisible; P01135; HS. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:BHF-UCL. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; TAS:Reactome. DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0000139; C:Golgi membrane; IEA:GOC. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; NAS:ProtInc. DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:UniProtKB. DR GO; GO:0008083; F:growth factor activity; IDA:HGNC. DR GO; GO:0000187; P:activation of MAPK activity; IDA:HGNC. DR GO; GO:0008283; P:cell population proliferation; TAS:ProtInc. DR GO; GO:0048208; P:COPII vesicle coating; TAS:Reactome. DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; TAS:Reactome. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IDA:HGNC. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:HGNC. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:HGNC. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; TAS:Reactome. DR InterPro; IPR013032; EGF-like_CS. 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; Cell membrane; Complete proteome; KW Disulfide bond; EGF-like domain; Glycoprotein; Growth factor; KW Lipoprotein; Membrane; Mitogen; Palmitate; Polymorphism; KW Reference proteome; Secreted; Signal; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 23 {ECO:0000255}. FT CHAIN 24 160 Protransforming growth factor alpha. FT /FTId=PRO_0000302744. FT PROPEP 24 39 Removed in mature form. FT /FTId=PRO_0000007752. FT CHAIN 40 89 Transforming growth factor alpha. FT /FTId=PRO_0000007753. FT PROPEP 90 160 Removed in mature form. FT /FTId=PRO_0000007754. FT TOPO_DOM 24 98 Extracellular. {ECO:0000255}. FT TRANSMEM 99 124 Helical. {ECO:0000255}. FT TOPO_DOM 125 160 Cytoplasmic. {ECO:0000255}. FT DOMAIN 43 83 EGF-like. {ECO:0000255|PROSITE- FT ProRule:PRU00076}. FT LIPID 153 153 S-palmitoyl cysteine. FT {ECO:0000269|PubMed:8910478}. FT LIPID 154 154 S-palmitoyl cysteine. FT {ECO:0000269|PubMed:8910478}. FT CARBOHYD 25 25 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 47 60 {ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:1632509}. FT DISULFID 55 71 {ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:1632509}. FT DISULFID 73 82 {ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:1632509}. FT VAR_SEQ 32 32 Missing (in isoform 2, isoform 3 and FT isoform 5). {ECO:0000303|PubMed:10523832, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.7}. FT /FTId=VSP_038369. FT VAR_SEQ 159 160 VV -> ATLG (in isoform 3). FT {ECO:0000303|PubMed:10523832}. FT /FTId=VSP_038370. FT VAR_SEQ 159 160 VV -> GCRLY (in isoform 4 and isoform 5). FT {ECO:0000303|PubMed:10523832}. FT /FTId=VSP_038371. FT VARIANT 109 109 V -> M (in dbSNP:rs11466259). FT /FTId=VAR_024271. FT CONFLICT 58 58 G -> A (in Ref. 2; AAA61157). FT {ECO:0000305}. FT CONFLICT 65 65 Q -> H (in Ref. 2; AAA61157). FT {ECO:0000305}. FT CONFLICT 159 159 V -> L (in Ref. 2; AAA61157). FT {ECO:0000305}. FT STRAND 43 45 {ECO:0000244|PDB:1MOX}. FT HELIX 51 54 {ECO:0000244|PDB:1YUF}. FT STRAND 58 63 {ECO:0000244|PDB:1MOX}. FT TURN 64 67 {ECO:0000244|PDB:1MOX}. FT STRAND 68 73 {ECO:0000244|PDB:1MOX}. FT STRAND 77 79 {ECO:0000244|PDB:1MOX}. FT STRAND 84 86 {ECO:0000244|PDB:5KN5}. SQ SEQUENCE 160 AA; 17006 MW; D692184F9353DE47 CRC64; MVPSAGQLAL FALGIVLAAC QALENSTSPL SADPPVAAAV VSHFNDCPDS HTQFCFHGTC RFLVQEDKPA CVCHSGYVGA RCEHADLLAV VAASQKKQAI TALVVVSIVA LAVLIITCVL IHCCQVRKHC EWCRALICRH EKPSALLKGR TACCHSETVV //