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Identification
HMDB Protein ID HMDBP01458
Secondary Accession Numbers
  • 6754
Name Tyrosine-protein kinase SYK
Synonyms
  1. Spleen tyrosine kinase
Gene Name SYK
Protein Type Unknown
Biological Properties
General Function Involved in protein kinase activity
Specific Function Positive effector of BCR-stimulated responses. Couples the B-cell antigen receptor (BCR) to the mobilization of calcium ion either through a phosphoinositide 3-kinase-dependent pathway, when not phosphorylated on tyrosines of the linker region, or through a phospholipase C-gamma-dependent pathway, when phosphorylated on Tyr-348 and Tyr-352. Thus the differential phosphorylation of Syk can determine the pathway by which BCR is coupled to the regulation of intracellular calcium ion. Phosphorylates USP25 and regulates its intracellular levels
Pathways
  • Fc Epsilon Receptor I Signaling in Mast Cells
Reactions Not Available
GO Classification
Component
cell part
intracellular part
cytoplasm
Function
protein tyrosine kinase activity
non-membrane spanning protein tyrosine kinase activity
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein binding
protein kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
protein amino acid autophosphorylation
cellular metabolic process
protein amino acid phosphorylation
intracellular signaling pathway
signaling
signaling pathway
phosphorylation
Cellular Location Not Available
Gene Properties
Chromosome Location Chromosome:9
Locus 9q22
SNPs SYK
Gene Sequence
>1908 bp
ATGGCCAGCAGCGGCATGGCTGACAGCGCCAACCACCTGCCCTTCTTTTTCGGCAACATC
ACCCGGGAGGAGGCAGAAGATTACCTGGTCCAGGGGGGCATGAGTGATGGGCTTTATTTG
CTGCGCCAGAGCCGCAACTACCTGGGTGGCTTCGCCCTGTCCGTGGCCCACGGGAGGAAG
GCACACCACTACACCATCGAGCGGGAGCTGAATGGCACCTACGCCATCGCCGGTGGCAGG
ACCCATGCCAGCCCCGCCGACCTCTGCCACTACCACTCCCAGGAGTCTGATGGCCTGGTC
TGCCTCCTCAAGAAGCCCTTCAACCGGCCCCAAGGGGTGCAGCCCAAGACTGGGCCCTTT
GAGGATTTGAAGGAAAACCTCATCAGGGAATATGTGAAGCAGACATGGAACCTGCAGGGT
CAGGCTCTGGAGCAGGCCATCATCAGTCAGAAGCCTCAGCTGGAGAAGCTGATCGCTACC
ACAGCCCATGAAAAAATGCCTTGGTTCCATGGAAAAATCTCTCGGGAAGAATCTGAGCAA
ATTGTCCTGATAGGATCAAAGACAAATGGAAAGTTCCTGATCCGAGCCAGAGACAACAAC
GGCTCCTACGCCCTGTGCCTGCTGCACGAAGGGAAGGTGCTGCACTATCGCATCGACAAA
GACAAGACAGGGAAGCTCTCCATCCCCGAGGGAAAGAAGTTCGACACGCTCTGGCAGCTA
GTCGAGCATTATTCTTATAAAGCAGATGGTTTGTTAAGAGTTCTTACTGTCCCATGTCAA
AAAATCGGCACACAGGGAAATGTTAATTTTGGAGGCCGTCCACAACTTCCAGGTTCCCAT
CCTGCGACTTGGTCAGCGGGTGGAATAATCTCAAGAATCAAATCATACTCCTTCCCAAAG
CCTGGCCACAGAAAGTCCTCCCCTGCCCAAGGGAACCGGCAAGAGAGTACTGTGTCATTC
AATCCGTATGAGCCAGAACTTGCACCCTGGGCTGCAGACAAAGGCCCCCAGAGAGAAGCC
CTACCCATGGACACAGAGGTGTACGAGAGCCCCTACGCGGACCCTGAGGAGATCAGGCCC
AAGGAGGTTTACCTGGACCGAAAGCTGCTGACGCTGGAAGACAAAGAACTGGGCTCTGGT
AATTTTGGAACTGTGAAAAAGGGCTACTACCAAATGAAAAAAGTTGTGAAAACCGTGGCT
GTGAAAATACTGAAAAACGAGGCCAATGACCCCGCTCTTAAAGATGAGTTATTAGCAGAA
GCAAATGTCATGCAGCAGCTGGACAACCCGTACATCGTGCGCATGATCGGGATATGCGAG
GCCGAGTCCTGGATGCTAGTTATGGAGATGGCAGAACTTGGTCCCCTCAATAAGTATTTG
CAGCAGAACAGACATGTCAAGGATAAGAACATCATAGAACTGGTTCATCAGGTTTCCATG
GGCATGAAGTACTTGGAGGAGAGCAATTTTGTGCACAGAGATCTGGCTGCAAGAAATGTG
TTGCTAGTTACCCAACATTATGCCAAGATCAGTGATTTCGGACTCTCCAAAGCACTGCGT
GCTGATGAAAACTACTACAAGGCCCAGACCCATGGAAAGTGGCCTGTCAAGTGGTACGCT
CCGGAATGCATCAACTACTACAAGTTCTCCAGCAAAAGCGATGTCTGGAGCTTTGGAGTG
TTGATGTGGGAAGCATTCTCCTATGGGCAGAAGCCATATCGAGGGATGAAAGGAAGTGAA
GTCACCGCTATGTTAGAGAAAGGAGAGCGGATGGGGTGCCCTGCAGGGTGTCCAAGAGAG
ATGTACGATCTCATGAATCTGTGCTGGACATACGATGTGGAAAACAGGCCCGGATTCGCA
GCAGTGGAACTGCGGCTGCGCAATTACTACTATGACGTGGTGAACTAA
Protein Properties
Number of Residues 635
Molecular Weight 72065.8
Theoretical pI 8.4
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Tyrosine-protein kinase SYK
MASSGMADSANHLPFFFGNITREEAEDYLVQGGMSDGLYLLRQSRNYLGGFALSVAHGRK
AHHYTIERELNGTYAIAGGRTHASPADLCHYHSQESDGLVCLLKKPFNRPQGVQPKTGPF
EDLKENLIREYVKQTWNLQGQALEQAIISQKPQLEKLIATTAHEKMPWFHGKISREESEQ
IVLIGSKTNGKFLIRARDNNGSYALCLLHEGKVLHYRIDKDKTGKLSIPEGKKFDTLWQL
VEHYSYKADGLLRVLTVPCQKIGTQGNVNFGGRPQLPGSHPATWSAGGIISRIKSYSFPK
PGHRKSSPAQGNRQESTVSFNPYEPELAPWAADKGPQREALPMDTEVYESPYADPEEIRP
KEVYLDRKLLTLEDKELGSGNFGTVKKGYYQMKKVVKTVAVKILKNEANDPALKDELLAE
ANVMQQLDNPYIVRMIGICEAESWMLVMEMAELGPLNKYLQQNRHVKDKNIIELVHQVSM
GMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQTHGKWPVKWYA
PECINYYKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPAGCPRE
MYDLMNLCWTYDVENRPGFAAVELRLRNYYYDVVN
GenBank ID Protein 12804475
UniProtKB/Swiss-Prot ID P43405
UniProtKB/Swiss-Prot Entry Name KSYK_HUMAN
PDB IDs
GenBank Gene ID BC001645
GeneCard ID SYK
GenAtlas ID SYK
HGNC ID HGNC:11491
References
General References
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  2. 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 ]
  3. 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 ]
  4. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [PubMed:18088087 ]
  5. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  6. Wolf-Yadlin A, Hautaniemi S, Lauffenburger DA, White FM: Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5860-5. Epub 2007 Mar 26. [PubMed:17389395 ]
  7. Miller CL, Burkhardt AL, Lee JH, Stealey B, Longnecker R, Bolen JB, Kieff E: Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Immunity. 1995 Feb;2(2):155-66. [PubMed:7895172 ]
  8. Salomon AR, Ficarro SB, Brill LM, Brinker A, Phung QT, Ericson C, Sauer K, Brock A, Horn DM, Schultz PG, Peters EC: Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):443-8. Epub 2003 Jan 9. [PubMed:12522270 ]
  9. Yagi S, Suzuki K, Hasegawa A, Okumura K, Ra C: Cloning of the cDNA for the deleted syk kinase homologous to ZAP-70 from human basophilic leukemia cell line (KU812). Biochem Biophys Res Commun. 1994 Apr 15;200(1):28-34. [PubMed:7513161 ]
  10. Law CL, Sidorenko SP, Chandran KA, Draves KE, Chan AC, Weiss A, Edelhoff S, Disteche CM, Clark EA: Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex. J Biol Chem. 1994 Apr 22;269(16):12310-9. [PubMed:8163536 ]
  11. Muller B, Cooper L, Terhorst C: Molecular cloning of the human homologue to the pig protein-tyrosine kinase syk. Immunogenetics. 1994;39(5):359-62. [PubMed:8168854 ]
  12. Deckert M, Elly C, Altman A, Liu YC: Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases. J Biol Chem. 1998 Apr 10;273(15):8867-74. [PubMed:9535867 ]
  13. Tang J, Sawasdikosol S, Chang JH, Burakoff SJ: SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling. Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9775-80. [PubMed:10449770 ]
  14. Xu MJ, Zhao R, Zhao ZJ: Molecular cloning and characterization of SPAP1, an inhibitory receptor. Biochem Biophys Res Commun. 2001 Jan 26;280(3):768-75. [PubMed:11162587 ]
  15. Cholay M, Reverdy C, Benarous R, Colland F, Daviet L: Functional interaction between the ubiquitin-specific protease 25 and the SYK tyrosine kinase. Exp Cell Res. 2010 Feb 15;316(4):667-75. doi: 10.1016/j.yexcr.2009.10.023. Epub 2009 Nov 10. [PubMed:19909739 ]
  16. Narula SS, Yuan RW, Adams SE, Green OM, Green J, Philips TB, Zydowsky LD, Botfield MC, Hatada M, Laird ER, et al.: Solution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide. Structure. 1995 Oct 15;3(10):1061-73. [PubMed:8590001 ]
  17. Futterer K, Wong J, Grucza RA, Chan AC, Waksman G: Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide. J Mol Biol. 1998 Aug 21;281(3):523-37. [PubMed:9698567 ]