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Identification
HMDB Protein ID HMDBP12416
Secondary Accession Numbers None
Name Protransforming growth factor alpha
Synonyms Not Available
Gene Name TGFA
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function TGF alpha is a mitogenic polypeptide that is able to bind to the EGF receptor/EGFR and to act synergistically with TGF beta to promote anchorage-independent cell proliferation in soft agar.
Pathways
  • Colorectal cancer
  • EGFR tyrosine kinase inhibitor resistance
  • ErbB signaling pathway
  • Estrogen signaling pathway
  • Glioma
  • Hepatocellular carcinoma
  • MAPK signaling pathway
  • Non-small cell lung cancer
  • Pancreatic cancer
  • PI3K-Akt signaling pathway
  • Prostate cancer
  • Ras signaling pathway
  • Renal cell carcinoma
Reactions Not Available
GO Classification
Biological Process
signal transduction
positive regulation of cell proliferation
COPII vesicle coating
membrane organization
positive regulation of epidermal growth factor-activated receptor activity
ER to Golgi vesicle-mediated transport
positive regulation of mitotic nuclear division
regulation of transcription from RNA polymerase II promoter
negative regulation of epidermal growth factor receptor signaling pathway
positive regulation of protein kinase B signaling cascade
MAPK cascade
positive regulation of epithelial cell proliferation
positive regulation of cell division
epidermal growth factor receptor signaling pathway
intracellular signal transduction
activation of MAPK activity
Cellular Component
endoplasmic reticulum membrane
cell surface
clathrin-coated endocytic vesicle membrane
endoplasmic reticulum-Golgi intermediate compartment membrane
ER to Golgi transport vesicle membrane
plasma membrane
perinuclear region of cytoplasm
basolateral plasma membrane
extracellular region
extracellular space
cytoplasmic vesicle
integral to membrane
Molecular Function
epidermal growth factor receptor binding
growth factor activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 160
Molecular Weight 17005.785
Theoretical pI 7.539
Pfam Domain Function Not Available
Signals
  • 1-23;
Transmembrane Regions
  • 99-124;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P01135
UniProtKB/Swiss-Prot Entry Name TGFA_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621 ]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  4. Derynck R, Roberts AB, Winkler ME, Chen EY, Goeddel DV: Human transforming growth factor-alpha: precursor structure and expression in E. coli. Cell. 1984 Aug;38(1):287-97. [PubMed:6088071 ]
  5. Jakowlew SB, Kondaiah P, Dillard PJ, Sporn MB, Roberts AB: A novel low molecular weight ribonucleic acid (RNA) related to transforming growth factor alpha messenger RNA. Mol Endocrinol. 1988 Nov;2(11):1056-63. [PubMed:2464748 ]
  6. Qian JF, Lazar-Wesley E, Breugnot C, May E: Human transforming growth factor alpha: sequence analysis of the 4.5-kb and 1.6-kb mRNA species. Gene. 1993 Oct 15;132(2):291-6. [PubMed:8224876 ]
  7. Qian JF, Feingold J, Stoll C, May E: Transforming growth factor-alpha: characterization of the BamHI, RsaI, and TaqI polymorphic regions. Am J Hum Genet. 1993 Jul;53(1):168-75. [PubMed:8100397 ]
  8. Machida J, Yoshiura Ki, Funkhauser CD, Natsume N, Kawai T, Murray JC: Transforming growth factor-alpha (TGFA): genomic structure, boundary sequences, and mutation analysis in nonsyndromic cleft lip/palate and cleft palate only. Genomics. 1999 Nov 1;61(3):237-42. [PubMed:10552925 ]
  9. Jakobovits EB, Schlokat U, Vannice JL, Derynck R, Levinson AD: The human transforming growth factor alpha promoter directs transcription initiation from a single site in the absence of a TATA sequence. Mol Cell Biol. 1988 Dec;8(12):5549-54. [PubMed:2907605 ]
  10. Bean MF, Carr SA: Characterization of disulfide bond position in proteins and sequence analysis of cystine-bridged peptides by tandem mass spectrometry. Anal Biochem. 1992 Mar;201(2):216-26. [PubMed:1632509 ]
  11. Shum L, Turck CW, Derynck R: Cysteines 153 and 154 of transmembrane transforming growth factor-alpha are palmitoylated and mediate cytoplasmic protein association. J Biol Chem. 1996 Nov 8;271(45):28502-8. [PubMed:8910478 ]
  12. Fernandez-Larrea J, Merlos-Suarez A, Urena JM, Baselga J, Arribas J: A role for a PDZ protein in the early secretory pathway for the targeting of proTGF-alpha to the cell surface. Mol Cell. 1999 Apr;3(4):423-33. [PubMed:10230395 ]
  13. Kline TP, Brown FK, Brown SC, Jeffs PW, Kopple KD, Mueller L: Solution structures of human transforming growth factor alpha derived from 1H NMR data. Biochemistry. 1990 Aug 28;29(34):7805-13. [PubMed:2261437 ]
  14. Harvey TS, Wilkinson AJ, Tappin MJ, Cooke RM, Campbell ID: The solution structure of human transforming growth factor alpha. Eur J Biochem. 1991 Jun 15;198(3):555-62. [PubMed:2050136 ]
  15. Moy FJ, Li YC, Rauenbuehler P, Winkler ME, Scheraga HA, Montelione GT: Solution structure of human type-alpha transforming growth factor determined by heteronuclear NMR spectroscopy and refined by energy minimization with restraints. Biochemistry. 1993 Jul 27;32(29):7334-53. [PubMed:8338831 ]
  16. Xu X, Liao J, Creek KE, Pirisi L: Human keratinocytes and tumor-derived cell lines express alternatively spliced forms of transforming growth factor-alpha mRNA, encoding precursors lacking carboxyl-terminal valine residues. Oncogene. 1999 Sep 30;18(40):5554-62. doi: 10.1038/sj.onc.1203091. [PubMed:10523832 ]
  17. Collin GB, Marshall JD, Naggert JK, Nishina PM: TGFA: exon-intron structure and evaluation as a candidate gene for Alstrom syndrome. Clin Genet. 1999 Jan;55(1):61-2. doi: 10.1034/j.1399-0004.1999.550111.x. [PubMed:10066034 ]
  18. Castro CP, Piscopo D, Nakagawa T, Derynck R: Cornichon regulates transport and secretion of TGFalpha-related proteins in metazoan cells. J Cell Sci. 2007 Jul 15;120(Pt 14):2454-66. doi: 10.1242/jcs.004200. [PubMed:17607000 ]
  19. Ding W, Li C, Hu T, Graves-Deal R, Fotia AB, Weissman AM, Coffey RJ: EGF receptor-independent action of TGF-alpha protects Naked2 from AO7-mediated ubiquitylation and proteasomal degradation. Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13433-8. doi: 10.1073/pnas.0806298105. Epub 2008 Aug 29. [PubMed:18757723 ]