Tyrosine-protein kinase receptor TYRO3

Details

Name
Tyrosine-protein kinase receptor TYRO3
Synonyms
  • 2.7.10.1
  • BYK
  • DTK
  • RSE
  • SKY
  • TIF
  • Tyrosine-protein kinase BYK
  • Tyrosine-protein kinase DTK
  • Tyrosine-protein kinase RSE
  • Tyrosine-protein kinase SKY
  • Tyrosine-protein kinase TIF
Gene Name
TYRO3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051686|Tyrosine-protein kinase receptor TYRO3
MALRRSMGRPGLPPLPLPPPPRLGLLLAALASLLLPESAAAGLKLMGAPVKLTVSQGQPV
KLNCSVEGMEEPDIQWVKDGAVVQNLDQLYIPVSEQHWIGFLSLKSVERSDAGRYWCQVE
DGGETEISQPVWLTVEGVPFFTVEPKDLAVPPNAPFQLSCEAVGPPEPVTIVWWRGTTKI
GGPAPSPSVLNVTGVTQSTMFSCEAHNLKGLASSRTATVHLQALPAAPFNITVTKLSSSN
ASVAWMPGADGRALLQSCTVQVTQAPGGWEVLAVVVPVPPFTCLLRDLVPATNYSLRVRC
ANALGPSPYADWVPFQTKGLAPASAPQNLHAIRTDSGLILEWEEVIPEAPLEGPLGPYKL
SWVQDNGTQDELTVEGTRANLTGWDPQKDLIVRVCVSNAVGCGPWSQPLVVSSHDRAGQQ
GPPHSRTSWVPVVLGVLTALVTAAALALILLRKRRKETRFGQAFDSVMARGEPAVHFRAA
RSFNRERPERIEATLDSLGISDELKEKLEDVLIPEQQFTLGRMLGKGEFGSVREAQLKQE
DGSFVKVAVKMLKADIIASSDIEEFLREAACMKEFDHPHVAKLVGVSLRSRAKGRLPIPM
VILPFMKHGDLHAFLLASRIGENPFNLPLQTLIRFMVDIACGMEYLSSRNFIHRDLAARN
CMLAEDMTVCVADFGLSRKIYSGDYYRQGCASKLPVKWLALESLADNLYTVQSDVWAFGV
TMWEIMTRGQTPYAGIENAEIYNYLIGGNRLKQPPECMEDVYDLMYQCWSADPKQRPSFT
CLRMELENILGQLSVLSASQDPLYINIERAEEPTAGGSLELPGRDQPYSGAGDGSGMGAV
GGTPSDCRYILTPGGLAEQPGQAEHQPESPLNETQRLLLLQQGLLPHSSC
Number of residues
890
Molecular Weight
96904.425
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / phosphatidylinositol 3-kinase binding / protein heterodimerization activity / protein tyrosine kinase activity / signal transducer, downstream of receptor, with protein tyrosine kinase activity / transmembrane receptor protein tyrosine kinase activity / virus receptor activity
Processes
apoptotic cell clearance / cell adhesion / forebrain cell migration / natural killer cell differentiation / negative regulation of inflammatory response / negative regulation of innate immune response / negative regulation of lymphocyte activation / negative regulation of neuron apoptotic process / negative regulation of toll-like receptor signaling pathway / neuron cellular homeostasis / neuropeptide signaling pathway / ovulation cycle / phosphatidylinositol 3-kinase signaling / platelet activation / platelet aggregation / protein autophosphorylation / protein kinase B signaling / secretion by cell / signal transduction / spermatogenesis / substrate adhesion-dependent cell spreading / vagina development
Components
endoplasmic reticulum membrane / integral component of plasma membrane / nuclear envelope / nucleus
General Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including TULP1 or GAS6. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with PIK3R1 and thereby enhances PI3-kinase activity. Activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes. TYRO3 signaling plays a role in various processes such as neuron protection from excitotoxic injury, platelet aggregation and cytoskeleton reorganization. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
430-450
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0051687|Tyrosine-protein kinase receptor TYRO3 (TYRO3)
ATGGCGCTGAGGCGGAGCATGGGGCGGCCGGGGCTCCCGCCGCTGCCGCTGCCGCCGCCA
CCGCGGCTCGGGCTGCTGCTGGCGGCTCTGGCTTCTCTGCTGCTCCCGGAGTCCGCCGCC
GCAGGTCTGAAGCTCATGGGAGCCCCGGTGAAGCTGACAGTGTCTCAGGGGCAGCCGGTG
AAGCTCAACTGCAGTGTGGAGGGGATGGAGGAGCCTGACATCCAGTGGGTGAAGGATGGG
GCTGTGGTCCAGAACTTGGACCAGTTGTACATCCCAGTCAGCGAGCAGCACTGGATCGGC
TTCCTCAGCCTGAAGTCAGTGGAGCGCTCTGACGCCGGCCGGTACTGGTGCCAGGTGGAG
GATGGGGGTGAAACCGAGATCTCCCAGCCAGTGTGGCTCACGGTAGAAGGTGTGCCATTT
TTCACAGTGGAGCCAAAAGATCTGGCAGTGCCACCCAATGCCCCTTTCCAACTGTCTTGT
GAGGCTGTGGGTCCCCCTGAACCTGTTACCATTGTCTGGTGGAGAGGAACTACGAAGATC
GGGGGACCCGCTCCCTCTCCATCTGTTTTAAATGTAACAGGGGTGACCCAGAGCACCATG
TTTTCCTGTGAAGCTCACAACCTAAAAGGCCTGGCCTCTTCTCGCACAGCCACTGTTCAC
CTTCAAGCACTGCCTGCAGCCCCCTTCAACATCACCGTGACAAAGCTTTCCAGCAGCAAC
GCTAGTGTGGCCTGGATGCCAGGTGCTGATGGCCGAGCTCTGCTACAGTCCTGTACAGTT
CAGGTGACACAGGCCCCAGGAGGCTGGGAAGTCCTGGCTGTTGTGGTCCCTGTGCCCCCC
TTTACCTGCCTGCTCCGGGACCTGGTGCCTGCCACCAACTACAGCCTCAGGGTGCGCTGT
GCCAATGCCTTGGGGCCCTCTCCCTATGCTGACTGGGTGCCCTTTCAGACCAAGGGTCTA
GCCCCAGCCAGCGCTCCCCAAAACCTCCATGCCATCCGCACAGATTCAGGCCTCATCTTG
GAGTGGGAAGAAGTGATCCCCGAGGCCCCTTTGGAAGGCCCCCTGGGACCCTACAAACTG
TCCTGGGTTCAAGACAATGGAACCCAGGATGAGCTGACAGTGGAGGGGACCAGGGCCAAT
TTGACAGGCTGGGATCCCCAAAAGGACCTGATCGTACGTGTGTGCGTCTCCAATGCAGTT
GGCTGTGGACCCTGGAGTCAGCCACTGGTGGTCTCTTCTCATGACCGTGCAGGCCAGCAG
GGCCCTCCTCACAGCCGCACATCCTGGGTACCTGTGGTCCTTGGTGTGCTAACGGCCCTG
GTGACGGCTGCTGCCCTGGCCCTCATCCTGCTTCGAAAGAGACGGAAAGAGACGCGGTTT
GGGCAAGCCTTTGACAGTGTCATGGCCCGGGGAGAGCCAGCCGTTCACTTCCGGGCAGCC
CGGTCCTTCAATCGAGAAAGGCCCGAGCGCATCGAGGCCACATTGGACAGCTTGGGCATC
AGCGATGAACTAAAGGAAAAACTGGAGGATGTGCTCATCCCAGAGCAGCAGTTCACCCTG
GGCCGGATGTTGGGCAAAGGAGAGTTTGGTTCAGTGCGGGAGGCCCAGCTGAAGCAAGAG
GATGGCTCCTTTGTGAAAGTGGCTGTGAAGATGCTGAAAGCTGACATCATTGCCTCAAGC
GACATTGAAGAGTTCCTCAGGGAAGCAGCTTGCATGAAGGAGTTTGACCATCCACACGTG
GCCAAACTTGTTGGGGTAAGCCTCCGGAGCAGGGCTAAAGGCCGTCTCCCCATCCCCATG
GTCATCTTGCCCTTCATGAAGCATGGGGACCTGCATGCCTTCCTGCTCGCCTCCCGGATT
GGGGAGAACCCCTTTAACCTACCCCTCCAGACCCTGATCCGGTTCATGGTGGACATTGCC
TGCGGCATGGAGTACCTGAGCTCTCGGAACTTCATCCACCGAGACCTGGCTGCTCGGAAT
TGCATGCTGGCAGAGGACATGACAGTGTGTGTGGCTGACTTCGGACTCTCCCGGAAGATC
TACAGTGGGGACTACTATCGTCAAGGCTGTGCCTCCAAACTGCCTGTCAAGTGGCTGGCC
CTGGAGAGCCTGGCCGACAACCTGTATACTGTGCAGAGTGACGTGTGGGCGTTCGGGGTG
ACCATGTGGGAGATCATGACACGTGGGCAGACGCCATATGCTGGCATCGAAAACGCTGAG
ATTTACAACTACCTCATTGGCGGGAACCGCCTGAAACAGCCTCCGGAGTGTATGGAGGAC
GTGTATGATCTCATGTACCAGTGCTGGAGTGCTGACCCCAAGCAGCGCCCGAGCTTTACT
TGTCTGCGAATGGAACTGGAGAACATCTTGGGCCAGCTGTCTGTGCTATCTGCCAGCCAG
GACCCCTTATACATCAACATCGAGAGAGCTGAGGAGCCCACTGCGGGAGGCAGCCTGGAG
CTACCTGGCAGGGATCAGCCCTACAGTGGGGCTGGGGATGGCAGTGGCATGGGGGCAGTG
GGTGGCACTCCCAGTGACTGTCGGTACATACTCACCCCCGGAGGGCTGGCTGAGCAGCCA
GGGCAGGCAGAGCACCAGCCAGAGAGTCCCCTCAATGAGACACAGAGGCTTTTGCTGCTG
CAGCAAGGGCTACTGCCACACAGTAGCTGTTAG
Chromosome Location
15
Locus
15q15.1
External Identifiers
ResourceLink
UniProtKB IDQ06418
UniProtKB Entry NameTYRO3_HUMAN
HGNC IDHGNC:12446
General References
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  2. Ohashi K, Mizuno K, Kuma K, Miyata T, Nakamura T: Cloning of the cDNA for a novel receptor tyrosine kinase, Sky, predominantly expressed in brain. Oncogene. 1994 Mar;9(3):699-705. [Article]
  3. Crosier KE, Hall LR, Lewis PM, Morris CM, Wood CR, Morris JC, Crosier PS: Isolation and characterization of the human DTK receptor tyrosine kinase. Growth Factors. 1994;11(2):137-44. [Article]
  4. Kajii Y, Ninomiya D, Kato M, Mizuguchi M, Saji M, Katsumoto T, Ohno K, Takashima S, Onodera K: A tyrosine kinase-like molecule is localized in the nuclear membrane of neurons: hippocampal behavior under stress. Biol Cell. 1996;88(1-2):45-54. [Article]
  5. 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]
  6. Polvi A, Armstrong E, Lai C, Lemke G, Huebner K, Spritz RA, Guida LC, Nicholls RD, Alitalo K: The human TYRO3 gene and pseudogene are located in chromosome 15q14-q25. Gene. 1993 Dec 8;134(2):289-93. [Article]
  7. Toshima J, Ohashi K, Iwashita S, Mizuno K: Autophosphorylation activity and association with Src family kinase of Sky receptor tyrosine kinase. Biochem Biophys Res Commun. 1995 Apr 17;209(2):656-63. [Article]
  8. Godowski PJ, Mark MR, Chen J, Sadick MD, Raab H, Hammonds RG: Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3. Cell. 1995 Aug 11;82(3):355-8. [Article]
  9. Hafizi S, Dahlback B: Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev. 2006 Aug;17(4):295-304. Epub 2006 Jun 5. [Article]
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  11. Lemke G, Rothlin CV: Immunobiology of the TAM receptors. Nat Rev Immunol. 2008 May;8(5):327-36. doi: 10.1038/nri2303. [Article]
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  13. Shimojima M, Stroher U, Ebihara H, Feldmann H, Kawaoka Y: Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry. J Virol. 2012 Feb;86(4):2067-78. doi: 10.1128/JVI.06451-11. Epub 2011 Dec 7. [Article]
  14. Shimojima M, Kawaoka Y: Cell surface molecules involved in infection mediated by lymphocytic choriomeningitis virus glycoprotein. J Vet Med Sci. 2012 Oct;74(10):1363-6. Epub 2012 Jun 1. [Article]
  15. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]
  16. Moller-Tank S, Maury W: Phosphatidylserine receptors: enhancers of enveloped virus entry and infection. Virology. 2014 Nov;468-470:565-80. doi: 10.1016/j.virol.2014.09.009. Epub 2014 Sep 29. [Article]
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  18. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails