TGFA_HUMAN
ID TGFA_HUMAN Reviewed; 160 AA.
AC P01135; A8K286; Q15577; Q53SK7; Q9BS56; Q9UEI3; Q9UKM1; Q9UKM2; Q9UKM3;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 218.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 expression
RT 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-kb
RT 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, RsaI, and
RT 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 cleft
RT palate only.";
RL Genomics 61:237-242(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5), AND TISSUE 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 alternatively
RT spliced forms of transforming growth factor-alpha mRNA, encoding precursors
RT 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 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., 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 [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., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., 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., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., 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., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 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., 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 (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 project:
RT 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.8.12.5549-5554.1988;
RA Jakobovits E.B., Schlokat U., Vannice J.L., Derynck R., Levinson A.D.;
RT "The human transforming growth factor alpha promoter directs transcription
RT initiation from a single site in the absence of a TATA 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 Alstrom
RT 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-alpha
RT 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., Arribas J.;
RT "A role for a PDZ protein in the early secretory pathway for the targeting
RT 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 proteins
RT 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 AO7-
RT 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., Mueller L.;
RT "Solution structures of human transforming growth factor alpha derived from
RT 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 bind to
CC the EGF receptor/EGFR and to act synergistically with TGF beta to
CC promote anchorage-independent cell proliferation in soft agar.
CC -!- SUBUNIT: Interacts with the PDZ domains of MAGI3, SDCBP and SNTA1. The
CC interaction with SDCBP, is required for the targeting to the cell
CC surface. In the endoplasmic reticulum, in its immature form (i.e. with
CC a prosegment and lacking full N-glycosylation), interacts with CNIH. In
CC the Golgi apparatus, may form a complex with CNIH and GORASP2.
CC Interacts (via cytoplasmic C-terminal domain) with NKD2.
CC {ECO:0000269|PubMed:10230395, ECO:0000269|PubMed:17607000,
CC ECO:0000269|PubMed:18757723}.
CC -!- INTERACTION:
CC P01135; P00533: EGFR; NbExp=4; IntAct=EBI-1034374, EBI-297353;
CC P01135; Q969F2: NKD2; NbExp=3; IntAct=EBI-1034374, EBI-1538629;
CC P01135; O43765: SGTA; NbExp=3; IntAct=EBI-1034374, EBI-347996;
CC P01135; Q9EQJ9: Magi3; Xeno; NbExp=4; IntAct=EBI-1034374, EBI-7455245;
CC P01135-2; O95214: LEPROTL1; NbExp=3; IntAct=EBI-12367411, EBI-750776;
CC P01135-2; O43765: SGTA; NbExp=6; 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 expressed in
CC keratinocytes and tumor-derived cell lines.
CC {ECO:0000269|PubMed:10523832}.
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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 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 PDB; 7SZ5; EM; 3.60 A; C/D=40-89.
DR PDB; 7SZ7; EM; 3.40 A; C/D=40-89.
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 PDBsum; 7SZ5; -.
DR PDBsum; 7SZ7; -.
DR AlphaFoldDB; P01135; -.
DR BMRB; P01135; -.
DR SMR; P01135; -.
DR BioGRID; 112897; 83.
DR DIP; DIP-5765N; -.
DR IntAct; P01135; 10.
DR MINT; P01135; -.
DR STRING; 9606.ENSP00000295400; -.
DR ChEMBL; CHEMBL4662938; -.
DR GlyGen; P01135; 1 site.
DR SwissPalm; P01135; -.
DR BioMuta; TGFA; -.
DR DMDM; 135689; -.
DR MassIVE; P01135; -.
DR PaxDb; P01135; -.
DR PeptideAtlas; P01135; -.
DR PRIDE; P01135; -.
DR ProteomicsDB; 51332; -. [P01135-1]
DR ProteomicsDB; 51333; -. [P01135-2]
DR ProteomicsDB; 51334; -. [P01135-3]
DR ProteomicsDB; 51335; -. [P01135-4]
DR ProteomicsDB; 51336; -. [P01135-5]
DR ABCD; P01135; 10 sequenced antibodies.
DR Antibodypedia; 16331; 1379 antibodies from 39 providers.
DR DNASU; 7039; -.
DR Ensembl; ENST00000295400.11; ENSP00000295400.6; ENSG00000163235.16. [P01135-1]
DR Ensembl; ENST00000418333.6; ENSP00000404099.2; ENSG00000163235.16. [P01135-2]
DR Ensembl; ENST00000445399.5; ENSP00000387493.1; ENSG00000163235.16. [P01135-3]
DR GeneID; 7039; -.
DR KEGG; hsa:7039; -.
DR MANE-Select; ENST00000295400.11; ENSP00000295400.6; NM_003236.4; NP_003227.1.
DR UCSC; uc002sgs.4; human. [P01135-1]
DR CTD; 7039; -.
DR DisGeNET; 7039; -.
DR GeneCards; TGFA; -.
DR HGNC; HGNC:11765; TGFA.
DR HPA; ENSG00000163235; Tissue enhanced (brain).
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 VEuPathDB; HostDB:ENSG00000163235; -.
DR eggNOG; ENOG502S1CF; Eukaryota.
DR GeneTree; ENSGT00940000160058; -.
DR HOGENOM; CLU_109645_1_0_1; -.
DR InParanoid; P01135; -.
DR OMA; SACCHSE; -.
DR OrthoDB; 1401257at2759; -.
DR PhylomeDB; P01135; -.
DR TreeFam; TF332938; -.
DR PathwayCommons; P01135; -.
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-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR SignaLink; P01135; -.
DR SIGNOR; P01135; -.
DR BioGRID-ORCS; 7039; 4 hits in 1079 CRISPR screens.
DR ChiTaRS; TGFA; human.
DR EvolutionaryTrace; P01135; -.
DR GeneWiki; TGF_alpha; -.
DR GenomeRNAi; 7039; -.
DR Pharos; P01135; Tbio.
DR PRO; PR:P01135; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P01135; protein.
DR Bgee; ENSG00000163235; Expressed in esophagus squamous epithelium and 174 other tissues.
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:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
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:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
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-UCL.
DR GO; GO:0048018; F:receptor ligand activity; IDA:MGI.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0038134; P:ERBB2-EGFR signaling pathway; IDA:MGI.
DR GO; GO:0072574; P:hepatocyte proliferation; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:GO_Central.
DR GO; GO:0060749; P:mammary gland alveolus development; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
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-UCL.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA: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 GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR IDEAL; IID00290; -.
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; Disulfide bond;
KW EGF-like domain; Glycoprotein; Growth factor; Lipoprotein; Membrane;
KW Mitogen; Palmitate; Reference proteome; Secreted; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..160
FT /note="Protransforming growth factor alpha"
FT /id="PRO_0000302744"
FT PROPEP 24..39
FT /note="Removed in mature form"
FT /id="PRO_0000007752"
FT CHAIN 40..89
FT /note="Transforming growth factor alpha"
FT /id="PRO_0000007753"
FT PROPEP 90..160
FT /note="Removed in mature form"
FT /id="PRO_0000007754"
FT TOPO_DOM 24..98
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 125..160
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 43..83
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT LIPID 153
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:8910478"
FT LIPID 154
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:8910478"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 47..60
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:1632509"
FT DISULFID 55..71
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:1632509"
FT DISULFID 73..82
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000269|PubMed:1632509"
FT VAR_SEQ 32
FT /note="Missing (in isoform 2, isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:10523832,
FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.7"
FT /id="VSP_038369"
FT VAR_SEQ 159..160
FT /note="VV -> ATLG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10523832"
FT /id="VSP_038370"
FT VAR_SEQ 159..160
FT /note="VV -> GCRLY (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:10523832"
FT /id="VSP_038371"
FT VARIANT 109
FT /note="V -> M (in dbSNP:rs11466259)"
FT /id="VAR_024271"
FT CONFLICT 58
FT /note="G -> A (in Ref. 2; AAA61157)"
FT /evidence="ECO:0000305"
FT CONFLICT 65
FT /note="Q -> H (in Ref. 2; AAA61157)"
FT /evidence="ECO:0000305"
FT CONFLICT 159
FT /note="V -> L (in Ref. 2; AAA61157)"
FT /evidence="ECO:0000305"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:1MOX"
FT HELIX 51..54
FT /evidence="ECO:0007829|PDB:1YUF"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:1MOX"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:1MOX"
FT STRAND 68..73
FT /evidence="ECO:0007829|PDB:1MOX"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:1MOX"
FT STRAND 84..86
FT /evidence="ECO:0007829|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
