Hepatocyte growth factor

Details

Name
Hepatocyte growth factor
Synonyms
  • Hepatopoietin-A
  • HPTA
  • Scatter factor
  • SF
Gene Name
HGF
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002230|Hepatocyte growth factor
MWVTKLLPALLLQHVLLHLLLLPIAIPYAEGQRKRRNTIHEFKKSAKTTLIKIDPALKIK
TKKVNTADQCANRCTRNKGLPFTCKAFVFDKARKQCLWFPFNSMSSGVKKEFGHEFDLYE
NKDYIRNCIIGKGRSYKGTVSITKSGIKCQPWSSMIPHEHSFLPSSYRGKDLQENYCRNP
RGEEGGPWCFTSNPEVRYEVCDIPQCSEVECMTCNGESYRGLMDHTESGKICQRWDHQTP
HRHKFLPERYPDKGFDDNYCRNPDGQPRPWCYTLDPHTRWEYCAIKTCADNTMNDTDVPL
ETTECIQGQGEGYRGTVNTIWNGIPCQRWDSQYPHEHDMTPENFKCKDLRENYCRNPDGS
ESPWCFTTDPNIRVGYCSQIPNCDMSHGQDCYRGNGKNYMGNLSQTRSGLTCSMWDKNME
DLHRHIFWEPDASKLNENYCRNPDDDAHGPWCYTGNPLIPWDYCPISRCEGDTTPTIVNL
DHPVISCAKTKQLRVVNGIPTRTNIGWMVSLRYRNKHICGGSLIKESWVLTARQCFPSRD
LKDYEAWLGIHDVHGRGDEKCKQVLNVSQLVYGPEGSDLVLMKLARPAVLDDFVSTIDLP
NYGCTIPEKTSCSVYGWGYTGLINYDGLLRVAHLYIMGNEKCSQHHRGKVTLNESEICAG
AEKIGSGPCEGDYGGPLVCEQHKMRMVLGVIVPGRGCAIPNRPGIFVRVAYYAKWIHKII
LTYKVPQS
Number of residues
728
Molecular Weight
83133.115
Theoretical pI
7.92
GO Classification
Functions
chemoattractant activity / growth factor activity / identical protein binding / serine-type endopeptidase activity
Processes
activation of MAPK activity / blood coagulation / cell chemotaxis / cellular response to hepatocyte growth factor stimulus / epithelial to mesenchymal transition / hepatocyte growth factor receptor signaling pathway / hyaluronan metabolic process / liver development / mitotic nuclear division / myoblast proliferation / negative regulation of autophagy / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / negative regulation of hydrogen peroxide-mediated programmed cell death / negative regulation of release of cytochrome c from mitochondria / organ regeneration / platelet activation / platelet degranulation / positive chemotaxis / positive regulation of angiogenesis / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of DNA biosynthetic process / positive regulation of myelination / positive regulation of neuron projection regeneration / positive regulation of osteoblast differentiation / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of phosphatidylinositol 3-kinase signaling / positive regulation of transcription from RNA polymerase II promoter / proteolysis / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / regulation of p38MAPK cascade
Components
extracellular region / extracellular space / membrane / platelet alpha granule lumen
General Function
Serine-type endopeptidase activity
Specific Function
Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic
Gene sequence
>lcl|BSEQ0010784|Hepatocyte growth factor (HGF)
ATGTGGGTGACCAAACTCCTGCCAGCCCTGCTGCTGCAGCATGTCCTCCTGCATCTCCTC
CTGCTCCCCATCGCCATCCCCTATGCAGAGGGACAAAGGAAAAGAAGAAATACAATTCAT
GAATTCAAAAAATCAGCAAAGACTACCCTAATCAAAATAGATCCAGCACTGAAGATAAAA
ACCAAAAAAGTGAATACTGCAGACCAATGTGCTAATAGATGTACTAGGAATAAAGGACTT
CCATTCACTTGCAAGGCTTTTGTTTTTGATAAAGCAAGAAAACAATGCCTCTGGTTCCCC
TTCAATAGCATGTCAAGTGGAGTGAAAAAAGAATTTGGCCATGAATTTGACCTCTATGAA
AACAAAGACTACATTAGAAACTGCATCATTGGTAAAGGACGCAGCTACAAGGGAACAGTA
TCTATCACTAAGAGTGGCATCAAATGTCAGCCCTGGAGTTCCATGATACCACACGAACAC
AGCTTTTTGCCTTCGAGCTATCGGGGTAAAGACCTACAGGAAAACTACTGTCGAAATCCT
CGAGGGGAAGAAGGGGGACCCTGGTGTTTCACAAGCAATCCAGAGGTACGCTACGAAGTC
TGTGACATTCCTCAGTGTTCAGAAGTTGAATGCATGACCTGCAATGGGGAGAGTTATCGA
GGTCTCATGGATCATACAGAATCAGGCAAGATTTGTCAGCGCTGGGATCATCAGACACCA
CACCGGCACAAATTCTTGCCTGAAAGATATCCCGACAAGGGCTTTGATGATAATTATTGC
CGCAATCCCGATGGCCAGCCGAGGCCATGGTGCTATACTCTTGACCCTCACACCCGCTGG
GAGTACTGTGCAATTAAAACATGCGCTGACAATACTATGAATGACACTGATGTTCCTTTG
GAAACAACTGAATGCATCCAAGGTCAAGGAGAAGGCTACAGGGGCACTGTCAATACCATT
TGGAATGGAATTCCATGTCAGCGTTGGGATTCTCAGTATCCTCACGAGCATGACATGACT
CCTGAAAATTTCAAGTGCAAGGACCTACGAGAAAATTACTGCCGAAATCCAGATGGGTCT
GAATCACCCTGGTGTTTTACCACTGATCCAAACATCCGAGTTGGCTACTGCTCCCAAATT
CCAAACTGTGATATGTCACATGGACAAGATTGTTATCGTGGGAATGGCAAAAATTATATG
GGCAACTTATCCCAAACAAGATCTGGACTAACATGTTCAATGTGGGACAAGAACATGGAA
GACTTACATCGTCATATCTTCTGGGAACCAGATGCAAGTAAGCTGAATGAGAATTACTGC
CGAAATCCAGATGATGATGCTCATGGACCCTGGTGCTACACGGGAAATCCACTCATTCCT
TGGGATTATTGCCCTATTTCTCGTTGTGAAGGTGATACCACACCTACAATAGTCAATTTA
GACCATCCCGTAATATCTTGTGCCAAAACGAAACAATTGCGAGTTGTAAATGGGATTCCA
ACACGAACAAACATAGGATGGATGGTTAGTTTGAGATACAGAAATAAACATATCTGCGGA
GGATCATTGATAAAGGAGAGTTGGGTTCTTACTGCACGACAGTGTTTCCCTTCTCGAGAC
TTGAAAGATTATGAAGCTTGGCTTGGAATTCATGATGTCCACGGAAGAGGAGATGAGAAA
TGCAAACAGGTTCTCAATGTTTCCCAGCTGGTATATGGCCCTGAAGGATCAGATCTGGTT
TTAATGAAGCTTGCCAGGCCTGCTGTCCTGGATGATTTTGTTAGTACGATTGATTTACCT
AATTATGGATGCACAATTCCTGAAAAGACCAGTTGCAGTGTTTATGGCTGGGGCTACACT
GGATTGATCAACTATGATGGCCTATTACGAGTGGCACATCTCTATATAATGGGAAATGAG
AAATGCAGCCAGCATCATCGAGGGAAGGTGACTCTGAATGAGTCTGAAATATGTGCTGGG
GCTGAAAAGATTGGATCAGGACCATGTGAGGGGGATTATGGTGGCCCACTTGTTTGTGAG
CAACATAAAATGAGAATGGTTCTTGGTGTCATTGTTCCTGGTCGTGGATGTGCCATTCCA
AATCGTCCTGGTATTTTTGTCCGAGTAGCATATTATGCAAAATGGATACACAAAATTATT
TTAACATATAAGGTACCACAGTCATAG
Chromosome Location
7
Locus
7q21.1
External Identifiers
ResourceLink
UniProtKB IDP14210
UniProtKB Entry NameHGF_HUMAN
GenBank Protein ID306846
GenBank Gene IDM29145
GenAtlas IDHGF
HGNC IDHGNC:4893
General References
  1. Miyazawa K, Tsubouchi H, Naka D, Takahashi K, Okigaki M, Arakaki N, Nakayama H, Hirono S, Sakiyama O, Takahashi K, et al.: Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor. Biochem Biophys Res Commun. 1989 Sep 15;163(2):967-73. [Article]
  2. Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, Tashiro K, Shimizu S: Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440-3. [Article]
  3. Seki T, Ihara I, Sugimura A, Shimonishi M, Nishizawa T, Asami O, Hagiya M, Nakamura T, Shimizu S: Isolation and expression of cDNA for different forms of hepatocyte growth factor from human leukocyte. Biochem Biophys Res Commun. 1990 Oct 15;172(1):321-7. [Article]
  4. Seki T, Hagiya M, Shimonishi M, Nakamura T, Shimizu S: Organization of the human hepatocyte growth factor-encoding gene. Gene. 1991 Jun 30;102(2):213-9. [Article]
  5. Miyazawa K, Kitamura A, Naka D, Kitamura N: An alternatively processed mRNA generated from human hepatocyte growth factor gene. Eur J Biochem. 1991 Apr 10;197(1):15-22. [Article]
  6. Rubin JS, Chan AM, Bottaro DP, Burgess WH, Taylor WG, Cech AC, Hirschfield DW, Wong J, Miki T, Finch PW, et al.: A broad-spectrum human lung fibroblast-derived mitogen is a variant of hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):415-9. [Article]
  7. Weidner KM, Arakaki N, Hartmann G, Vandekerckhove J, Weingart S, Rieder H, Fonatsch C, Tsubouchi H, Hishida T, Daikuhara Y, et al.: Evidence for the identity of human scatter factor and human hepatocyte growth factor. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7001-5. [Article]
  8. Chan AM, Rubin JS, Bottaro DP, Hirschfield DW, Chedid M, Aaronson SA: Identification of a competitive HGF antagonist encoded by an alternative transcript. Science. 1991 Nov 29;254(5036):1382-5. [Article]
  9. Hartmann G, Naldini L, Weidner KM, Sachs M, Vigna E, Comoglio PM, Birchmeier W: A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11574-8. [Article]
  10. Cioce V, Csaky KG, Chan AM, Bottaro DP, Taylor WG, Jensen R, Aaronson SA, Rubin JS: Hepatocyte growth factor (HGF)/NK1 is a naturally occurring HGF/scatter factor variant with partial agonist/antagonist activity. J Biol Chem. 1996 May 31;271(22):13110-5. [Article]
  11. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [Article]
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  13. 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. [Article]
  14. Miyazawa K, Kitamura A, Kitamura N: Structural organization and the transcription initiation site of the human hepatocyte growth factor gene. Biochemistry. 1991 Sep 24;30(38):9170-6. [Article]
  15. Yoshiyama Y, Arakaki N, Naka D, Takahashi K, Hirono S, Kondo J, Nakayama H, Gohda E, Kitamura N, Tsubouchi H, et al.: Identification of the N-terminal residue of the heavy chain of both native and recombinant human hepatocyte growth factor. Biochem Biophys Res Commun. 1991 Mar 15;175(2):660-7. [Article]
  16. Shimizu N, Hara H, Sogabe T, Sakai H, Ihara I, Inoue H, Nakamura T, Shimizu S: Hepatocyte growth factor is linked by O-glycosylated oligosaccharide on the alpha chain. Biochem Biophys Res Commun. 1992 Dec 30;189(3):1329-35. [Article]
  17. Lokker NA, Mark MR, Luis EA, Bennett GL, Robbins KA, Baker JB, Godowski PJ: Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding. EMBO J. 1992 Jul;11(7):2503-10. [Article]
  18. Schultz JM, Khan SN, Ahmed ZM, Riazuddin S, Waryah AM, Chhatre D, Starost MF, Ploplis B, Buckley S, Velasquez D, Kabra M, Lee K, Hassan MJ, Ali G, Ansar M, Ghosh M, Wilcox ER, Ahmad W, Merlino G, Leal SM, Riazuddin S, Friedman TB, Morell RJ: Noncoding mutations of HGF are associated with nonsyndromic hearing loss, DFNB39. Am J Hum Genet. 2009 Jul;85(1):25-39. doi: 10.1016/j.ajhg.2009.06.003. Epub 2009 Jul 2. [Article]
  19. Tanaka K, Arao T, Tamura D, Aomatsu K, Furuta K, Matsumoto K, Kaneda H, Kudo K, Fujita Y, Kimura H, Yanagihara K, Yamada Y, Okamoto I, Nakagawa K, Nishio K: SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer. PLoS One. 2012;7(1):e27922. doi: 10.1371/journal.pone.0027922. Epub 2012 Jan 5. [Article]
  20. Zhou H, Mazzulla MJ, Kaufman JD, Stahl SJ, Wingfield PT, Rubin JS, Bottaro DP, Byrd RA: The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site. Structure. 1998 Jan 15;6(1):109-16. [Article]
  21. Ultsch M, Lokker NA, Godowski PJ, de Vos AM: Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 A resolution. Structure. 1998 Nov 15;6(11):1383-93. [Article]
  22. Stamos J, Lazarus RA, Yao X, Kirchhofer D, Wiesmann C: Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor. EMBO J. 2004 Jun 16;23(12):2325-35. Epub 2004 May 27. [Article]
  23. Tolbert WD, Daugherty-Holtrop J, Gherardi E, Vande Woude G, Xu HE: Structural basis for agonism and antagonism of hepatocyte growth factor. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13264-9. doi: 10.1073/pnas.1005183107. Epub 2010 Jul 12. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02264O2-Sulfo-Glucuronic AcidexperimentalunknownDetails
DB03959N,O6-Disulfo-GlucosamineexperimentalunknownDetails
DB12307ForetinibinvestigationalunknownDetails
DB05434ABT-510investigationalunknownDetails
DB01109Heparinapproved, investigationalunknownDetails