Tyrosine-protein kinase Tec

Details

Name
Tyrosine-protein kinase Tec
Synonyms
  • 2.7.10.2
  • PSCTK4
Gene Name
TEC
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051648|Tyrosine-protein kinase Tec
MNFNTILEEILIKRSQQKKKTSPLNYKERLFVLTKSMLTYYEGRAEKKYRKGFIDVSKIK
CVEIVKNDDGVIPCQNKYPFQVVHDANTLYIFAPSPQSRDLWVKKLKEEIKNNNNIMIKY
HPKFWTDGSYQCCRQTEKLAPGCEKYNLFESSIRKALPPAPETKKRRPPPPIPLEEEDNS
EEIVVAMYDFQAAEGHDLRLERGQEYLILEKNDVHWWRARDKYGNEGYIPSNYVTGKKSN
NLDQYEWYCRNMNRSKAEQLLRSEDKEGGFMVRDSSQPGLYTVSLYTKFGGEGSSGFRHY
HIKETTTSPKKYYLAEKHAFGSIPEIIEYHKHNAAGLVTRLRYPVSVKGKNAPTTAGFSY
EKWEINPSELTFMRELGSGLFGVVRLGKWRAQYKVAIKAIREGAMCEEDFIEEAKVMMKL
THPKLVQLYGVCTQQKPIYIVTEFMERGCLLNFLRQRQGHFSRDVLLSMCQDVCEGMEYL
ERNSFIHRDLAARNCLVSEAGVVKVSDFGMARYVLDDQYTSSSGAKFPVKWCPPEVFNYS
RFSSKSDVWSFGVLMWEVFTEGRMPFEKYTNYEVVTMVTRGHRLYQPKLASNYVYEVMLR
CWQEKPEGRPSFEDLLRTIDELVECEETFGR
Number of residues
631
Molecular Weight
73580.73
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / metal ion binding / non-membrane spanning protein tyrosine kinase activity / phospholipid binding
Processes
adaptive immune response / B cell receptor signaling pathway / cell differentiation / cytokine-mediated signaling pathway / Fc-epsilon receptor signaling pathway / innate immune response / integrin-mediated signaling pathway / intracellular signal transduction / peptidyl-tyrosine autophosphorylation / peptidyl-tyrosine phosphorylation / positive regulation of peptidyl-tyrosine phosphorylation / protein phosphorylation / regulation of cell proliferation / regulation of platelet activation / tissue regeneration / transmembrane receptor protein tyrosine kinase signaling pathway
Components
cytoskeleton / cytosol / extrinsic component of cytoplasmic side of plasma membrane / plasma membrane
General Function
Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskeleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC regulates also FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051649|Tyrosine-protein kinase Tec (TEC)
ATGAATTTTAACACTATTTTGGAGGAGATTCTTATTAAAAGGTCACAGCAGAAAAAGAAG
ACATCGCCCTTAAACTACAAAGAGAGACTTTTTGTACTTACAAAGTCCATGCTAACCTAC
TATGAGGGTCGAGCAGAGAAGAAATACAGAAAGGGGTTTATTGATGTTTCAAAAATCAAG
TGTGTGGAAATAGTGAAGAATGATGATGGTGTCATTCCCTGTCAAAATAAGTATCCATTT
CAGGTTGTTCATGATGCTAACACACTTTACATTTTTGCACCTAGTCCACAAAGCAGGGAC
CTGTGGGTGAAGAAGTTAAAAGAAGAAATAAAGAACAACAATAATATTATGATTAAATAT
CATCCTAAATTCTGGACAGATGGAAGTTATCAGTGTTGTAGACAAACTGAAAAATTAGCA
CCCGGATGTGAAAAATACAATCTTTTTGAGAGCAGTATAAGAAAAGCACTACCTCCAGCA
CCAGAAACAAAGAAGCGAAGGCCTCCCCCACCAATTCCACTAGAAGAAGAAGATAATAGT
GAAGAAATCGTTGTAGCCATGTATGATTTCCAAGCAGCAGAAGGACATGATCTCAGATTA
GAGAGAGGCCAAGAGTATCTCATTTTAGAAAAGAATGATGTTCATTGGTGGAGAGCAAGA
GATAAATATGGGAATGAAGGATATATCCCAAGTAATTACGTAACGGGAAAGAAATCAAAC
AACTTAGATCAATATGAATGGTATTGCAGAAATATGAATAGAAGCAAGGCAGAGCAACTC
CTCCGCAGTGAAGATAAAGAAGGTGGTTTTATGGTAAGGGATTCCAGTCAACCAGGCTTG
TACACAGTCTCCCTTTATACCAAGTTTGGAGGAGAAGGTTCATCGGGTTTTAGGCATTAT
CATATAAAGGAAACAACAACATCTCCAAAGAAGTATTACCTAGCTGAAAAACATGCTTTT
GGCTCCATTCCTGAGATTATTGAATATCATAAGCACAATGCAGCAGGACTTGTCACCAGG
CTTCGGTACCCAGTTAGTGTGAAAGGGAAGAATGCACCCACCACTGCAGGATTCAGCTAT
GAGAAATGGGAGATTAACCCTTCAGAACTGACCTTTATGAGGGAATTGGGAAGTGGACTG
TTTGGAGTGGTGAGGCTTGGCAAATGGCGAGCCCAGTACAAAGTCGCAATCAAAGCTATT
CGGGAAGGTGCAATGTGCGAGGAGGACTTTATAGAAGAAGCTAAAGTGATGATGAAACTG
ACACACCCGAAGTTAGTGCAGCTTTATGGTGTGTGCACCCAGCAGAAACCAATATACATT
GTTACTGAGTTCATGGAAAGGGGCTGCCTTCTGAATTTCCTCCGACAGAGACAAGGTCAT
TTCAGTAGAGACGTACTGCTGAGCATGTGTCAGGATGTGTGTGAAGGGATGGAGTATCTG
GAGAGAAACAGCTTCATCCACAGAGATCTGGCTGCCAGAAATTGTCTAGTAAGTGAGGCG
GGAGTTGTAAAAGTATCTGATTTTGGAATGGCCAGGTATGTTCTGGATGATCAGTACACA
AGTTCTTCTGGTGCTAAGTTTCCTGTGAAGTGGTGTCCACCTGAAGTGTTTAATTACAGC
CGCTTCAGCAGCAAATCAGATGTCTGGTCATTTGGTGTTTTAATGTGGGAAGTATTCACG
GAAGGCAGAATGCCTTTTGAAAAATACACCAATTATGAAGTGGTAACCATGGTTACTCGA
GGCCACCGACTCTACCAGCCGAAGTTGGCGTCCAACTATGTGTATGAGGTGATGCTGAGA
TGTTGGCAGGAGAAACCAGAGGGAAGGCCTTCTTTCGAAGATCTGCTGCGCACAATAGAT
GAACTAGTTGAATGTGAAGAAACTTTTGGAAGATAA
Chromosome Location
4
Locus
4p12-p11
External Identifiers
ResourceLink
UniProtKB IDP42680
UniProtKB Entry NameTEC_HUMAN
HGNC IDHGNC:11719
General References
  1. Sato K, Mano H, Ariyama T, Inazawa J, Yazaki Y, Hirai H: Molecular cloning and analysis of the human Tec protein-tyrosine kinase. Leukemia. 1994 Oct;8(10):1663-72. [PubMed:7934162]
  2. 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]
  3. Nore BF, Mattsson PT, Antonsson P, Backesjo CM, Westlund A, Lennartsson J, Hansson H, Low P, Ronnstrand L, Smith CI: Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases. Biochim Biophys Acta. 2003 Feb 21;1645(2):123-32. [PubMed:12573241]
  4. Tang B, Mano H, Yi T, Ihle JN: Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding. Mol Cell Biol. 1994 Dec;14(12):8432-7. [PubMed:7526158]
  5. Laffargue M, Monnereau L, Tuech J, Ragab A, Ragab-Thomas J, Payrastre B, Raynal P, Chap H: Integrin-dependent tyrosine phoshorylation and cytoskeletal translocation of Tec in thrombin-activated platelets. Biochem Biophys Res Commun. 1997 Sep 8;238(1):247-51. [PubMed:9299487]
  6. Ohya Ki, Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H: SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase. J Biol Chem. 1997 Oct 24;272(43):27178-82. [PubMed:9341160]
  7. Mano H, Ohya K, Miyazato A, Yamashita Y, Ogawa W, Inazawa J, Ikeda U, Shimada K, Hatake K, Kasuga M, Ozawa K, Kajigaya S: Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase. Genes Cells. 1998 Jul;3(7):431-41. [PubMed:9753425]
  8. Hamazaki Y, Kojima H, Mano H, Nagata Y, Todokoro K, Abe T, Nagasawa T: Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets. Oncogene. 1998 May 28;16(21):2773-9. [PubMed:9652744]
  9. Ohya K, Kajigaya S, Kitanaka A, Yoshida K, Miyazato A, Yamashita Y, Yamanaka T, Ikeda U, Shimada K, Ozawa K, Mano H: Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11976-81. [PubMed:10518561]
  10. Tomlinson MG, Heath VL, Turck CW, Watson SP, Weiss A: SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase. J Biol Chem. 2004 Dec 31;279(53):55089-96. Epub 2004 Oct 18. [PubMed:15492005]
  11. Voss M, Lettau M, Janssen O: Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. BMC Immunol. 2009 Oct 6;10:53. doi: 10.1186/1471-2172-10-53. [PubMed:19807924]
  12. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195]
  13. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332]
  14. Susaki K, Kitanaka A, Dobashi H, Kubota Y, Kittaka K, Kameda T, Yamaoka G, Mano H, Mihara K, Ishida T: Tec protein tyrosine kinase inhibits CD25 expression in human T-lymphocyte. Immunol Lett. 2010 Jan 4;127(2):135-42. doi: 10.1016/j.imlet.2009.10.009. Epub 2009 Oct 31. [PubMed:19883687]
  15. Ebert AD, Laussmann M, Wegehingel S, Kaderali L, Erfle H, Reichert J, Lechner J, Beer HD, Pepperkok R, Nickel W: Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion. Traffic. 2010 Jun;11(6):813-26. doi: 10.1111/j.1600-0854.2010.01059.x. Epub 2010 Mar 10. [PubMed:20230531]
  16. 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. [PubMed:17344846]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB15035Zanubrutinibapproved, investigationalunknowninhibitorDetails