KSYK_HUMAN
ID KSYK_HUMAN Reviewed; 635 AA.
AC P43405;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 239.
DE RecName: Full=Tyrosine-protein kinase SYK;
DE EC=2.7.10.2 {ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:33782605};
DE AltName: Full=Spleen tyrosine kinase;
DE AltName: Full=p72-Syk;
GN Name=SYK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7513161; DOI=10.1006/bbrc.1994.1409;
RA Yagi S., Suzuki K., Hasegawa A., Okumura K., Ra C.;
RT "Cloning of the cDNA for the deleted syk kinase homologous to ZAP-70 from
RT human basophilic leukemia cell line (KU812).";
RL Biochem. Biophys. Res. Commun. 200:28-34(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND AUTOPHOSPHORYLATION.
RX PubMed=8163536; DOI=10.1016/s0021-9258(17)32717-5;
RA Law C.-L., Sidorenko S.P., Chandran K.A., Draves K.E., Chan A.C., Weiss A.,
RA Edelhoff S., Disteche C.M., Clark E.A.;
RT "Molecular cloning of human Syk. A B cell protein-tyrosine kinase
RT associated with the surface immunoglobulin M-B cell receptor complex.";
RL J. Biol. Chem. 269:12310-12319(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Eye, and Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-635.
RC TISSUE=Tonsil;
RX PubMed=8168854; DOI=10.1007/bf00189234;
RA Mueller B., Cooper L., Terhorst C.;
RT "Molecular cloning of the human homologue to the pig protein-tyrosine
RT kinase syk.";
RL Immunogenetics 39:359-362(1994).
RN [6]
RP INTERACTION WITH EPSTEIN-BARR VIRUS LMP2A (MICROBIAL INFECTION).
RX PubMed=7895172; DOI=10.1016/s1074-7613(95)80040-9;
RA Miller C.L., Burkhardt A.L., Lee J.H., Stealey B., Longnecker R.,
RA Bolen J.B., Kieff E.;
RT "Integral membrane protein 2 of Epstein-Barr virus regulates reactivation
RT from latency through dominant negative effects on protein-tyrosine
RT kinases.";
RL Immunity 2:155-166(1995).
RN [7]
RP INTERACTION WITH VAV1.
RX PubMed=8986718; DOI=10.1016/s1074-7613(00)80273-3;
RA Deckert M., Tartare-Deckert S., Couture C., Mustelin T., Altman A.;
RT "Functional and physical interactions of Syk family kinases with the Vav
RT proto-oncogene product.";
RL Immunity 5:591-604(1996).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF PLCG1, AND INTERACTION WITH PLCG1.
RX PubMed=8657103; DOI=10.1128/mcb.16.4.1305;
RA Law C.L., Chandran K.A., Sidorenko S.P., Clark E.A.;
RT "Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in
RT the linker region of Syk and is a substrate for Syk.";
RL Mol. Cell. Biol. 16:1305-1315(1996).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF CBL, AND INTERACTION WITH CBL.
RX PubMed=9535867; DOI=10.1074/jbc.273.15.8867;
RA Deckert M., Elly C., Altman A., Liu Y.C.;
RT "Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and
RT Syk tyrosine kinases.";
RL J. Biol. Chem. 273:8867-8874(1998).
RN [10]
RP ACTIVITY REGULATION, AND INTERACTION WITH CBL.
RX PubMed=9857068; DOI=10.1074/jbc.273.52.35273;
RA Lupher M.L. Jr., Rao N., Lill N.L., Andoniou C.E., Miyake S., Clark E.A.,
RA Druker B., Band H.;
RT "Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical
RT role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine
RT 323.";
RL J. Biol. Chem. 273:35273-35281(1998).
RN [11]
RP PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN6, AND ACTIVITY REGULATION.
RX PubMed=10458769;
RX DOI=10.1002/(sici)1521-4141(199908)29:08<2539::aid-immu2539>3.0.co;2-m;
RA Brockdorff J., Williams S., Couture C., Mustelin T.;
RT "Dephosphorylation of ZAP-70 and inhibition of T cell activation by
RT activated SHP1.";
RL Eur. J. Immunol. 29:2539-2550(1999).
RN [12]
RP INTERACTION WITH SLA.
RX PubMed=10449770; DOI=10.1073/pnas.96.17.9775;
RA Tang J., Sawasdikosol S., Chang J.-H., Burakoff S.J.;
RT "SLAP, a dimeric adapter protein, plays a functional role in T cell
RT receptor signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:9775-9780(1999).
RN [13]
RP INTERACTION WITH FCRL3.
RX PubMed=11162587; DOI=10.1006/bbrc.2000.4213;
RA Xu M.-J., Zhao R., Zhao Z.J.;
RT "Molecular cloning and characterization of SPAP1, an inhibitory receptor.";
RL Biochem. Biophys. Res. Commun. 280:768-775(2001).
RN [14]
RP FUNCTION IN B-CELL RECEPTOR SIGNALING PATHWAY, AND FUNCTION IN
RP PHOSPHORYLATION OF BLNK.
RX PubMed=12456653; DOI=10.1093/emboj/cdf658;
RA Chiu C.W., Dalton M., Ishiai M., Kurosaki T., Chan A.C.;
RT "BLNK: molecular scaffolding through 'cis'-mediated organization of
RT signaling proteins.";
RL EMBO J. 21:6461-6472(2002).
RN [15]
RP FUNCTION IN CELL ADHESION, AND INTERACTION WITH SELPLG AND MSN.
RX PubMed=12387735; DOI=10.1016/s1074-7613(02)00420-x;
RA Urzainqui A., Serrador J.M., Viedma F., Yanez-Mo M., Rodriguez A.,
RA Corbi A.L., Alonso-Lebrero J.L., Luque A., Deckert M., Vazquez J.,
RA Sanchez-Madrid F.;
RT "ITAM-based interaction of ERM proteins with Syk mediates signaling by the
RT leukocyte adhesion receptor PSGL-1.";
RL Immunity 17:401-412(2002).
RN [16]
RP INTERACTION WITH ITGB3.
RX PubMed=11940607; DOI=10.1083/jcb.200112113;
RA Obergfell A., Eto K., Mocsai A., Buensuceso C., Moores S.L., Brugge J.S.,
RA Lowell C.A., Shattil S.J.;
RT "Coordinate interactions of Csk, Src, and Syk kinases with
RT [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton.";
RL J. Cell Biol. 157:265-275(2002).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF LCP2.
RX PubMed=15388330; DOI=10.1016/j.febslet.2004.07.090;
RA Shim E.K., Moon C.S., Lee G.Y., Ha Y.J., Chae S.K., Lee J.R.;
RT "Association of the Src homology 2 domain-containing leukocyte
RT phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide
RT 3-kinase.";
RL FEBS Lett. 575:35-40(2004).
RN [18]
RP FUNCTION, INTERACTION WITH IL15RA, TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=15123770; DOI=10.1189/jlb.0605298;
RA Ratthe C., Girard D.;
RT "Interleukin-15 enhances human neutrophil phagocytosis by a Syk-dependent
RT mechanism: importance of the IL-15Ralpha chain.";
RL J. Leukoc. Biol. 76:162-168(2004).
RN [19]
RP INTERACTION WITH BLNK, ACTIVITY REGULATION, MUTAGENESIS OF TYR-630, AND
RP PHOSPHORYLATION AT TYR-630.
RX PubMed=18369315; DOI=10.1038/emboj.2008.62;
RA Kulathu Y., Hobeika E., Turchinovich G., Reth M.;
RT "The kinase Syk as an adaptor controlling sustained calcium signalling and
RT B-cell development.";
RL EMBO J. 27:1333-1344(2008).
RN [20]
RP ACTIVITY REGULATION.
RX PubMed=18818202; DOI=10.1074/jbc.m806340200;
RA Tsang E., Giannetti A.M., Shaw D., Dinh M., Tse J.K., Gandhi S., Ho H.,
RA Wang S., Papp E., Bradshaw J.M.;
RT "Molecular mechanism of the Syk activation switch.";
RL J. Biol. Chem. 283:32650-32659(2008).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [22]
RP INTERACTION WITH FCRL3.
RX PubMed=19843936; DOI=10.4049/jimmunol.0901982;
RA Kochi Y., Myouzen K., Yamada R., Suzuki A., Kurosaki T., Nakamura Y.,
RA Yamamoto K.;
RT "FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-
RT cell receptor-mediated signaling.";
RL J. Immunol. 183:5502-5510(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-323, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [25]
RP INTERACTION WITH CLEC1B.
RX PubMed=20154219; DOI=10.1182/blood-2009-08-237834;
RA Hughes C.E., Pollitt A.Y., Mori J., Eble J.A., Tomlinson M.G.,
RA Hartwig J.H., O'Callaghan C.A., Fuetterer K., Watson S.P.;
RT "CLEC-2 activates Syk through dimerization.";
RL Blood 115:2947-2955(2010).
RN [26]
RP INTERACTION WITH USP25, AND FUNCTION.
RX PubMed=19909739; DOI=10.1016/j.yexcr.2009.10.023;
RA Cholay M., Reverdy C., Benarous R., Colland F., Daviet L.;
RT "Functional interaction between the ubiquitin-specific protease 25 and the
RT SYK tyrosine kinase.";
RL Exp. Cell Res. 316:667-675(2010).
RN [27]
RP INTERACTION WITH FLNA.
RX PubMed=20713593; DOI=10.1084/jem.20100222;
RA Falet H., Pollitt A.Y., Begonja A.J., Weber S.E., Duerschmied D.,
RA Wagner D.D., Watson S.P., Hartwig J.H.;
RT "A novel interaction between FlnA and Syk regulates platelet ITAM-mediated
RT receptor signaling and function.";
RL J. Exp. Med. 207:1967-1979(2010).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [29]
RP PHOSPHORYLATION AT TYR-28; SER-44; TYR-47; TYR-131; SER-202; THR-256;
RP SER-295; TYR-296; SER-297; SER-316; THR-317; SER-319; TYR-323; THR-345;
RP TYR-348; SER-350; TYR-352; TYR-364; SER-379; THR-384; TYR-484; TYR-507;
RP TYR-525; TYR-526; THR-530; SER-579; THR-582; TYR-629; TYR-630 AND TYR-631,
RP INTERACTION WITH YWHAG, AND MUTAGENESIS OF SER-297.
RC TISSUE=B-cell;
RX PubMed=21469132; DOI=10.1002/eji.201041326;
RA Bohnenberger H., Oellerich T., Engelke M., Hsiao H.H., Urlaub H.,
RA Wienands J.;
RT "Complex phosphorylation dynamics control the composition of the Syk
RT interactome in B cells.";
RL Eur. J. Immunol. 41:1550-1562(2011).
RN [30]
RP INTERACTION WITH TNS2.
RX PubMed=22019427; DOI=10.1016/j.bbamcr.2011.10.001;
RA Moon K.D., Zhang X., Zhou Q., Geahlen R.L.;
RT "The protein-tyrosine kinase Syk interacts with the C-terminal region of
RT tensin2.";
RL Biochim. Biophys. Acta 1823:199-205(2012).
RN [31]
RP INTERACTION WITH GCSAM.
RX PubMed=23299888; DOI=10.1038/ncomms2334;
RA Romero-Camarero I., Jiang X., Natkunam Y., Lu X., Vicente-Duenas C.,
RA Gonzalez-Herrero I., Flores T., Garcia J.L., McNamara G., Kunder C.,
RA Zhao S., Segura V., Fontan L., Martinez-Climent J.A., Garcia-Criado F.J.,
RA Theis J.D., Dogan A., Campos-Sanchez E., Green M.R., Alizadeh A.A.,
RA Cobaleda C., Sanchez-Garcia I., Lossos I.S.;
RT "Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis
RT via BCR-mediated Syk activation.";
RL Nat. Commun. 4:1338-1338(2013).
RN [32]
RP INVOLVEMENT IN IMD82, VARIANTS IMD82 THR-342; THR-353; ILE-450; PHE-550 AND
RP TYR-550, CHARACTERIZATION OF VARIANTS IMD82 THR-342; THR-353; ILE-450;
RP PHE-550 AND TYR-550, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=33782605; DOI=10.1038/s41588-021-00803-4;
RG Genomics England Research Consortium;
RA Wang L., Aschenbrenner D., Zeng Z., Cao X., Mayr D., Mehta M., Capitani M.,
RA Warner N., Pan J., Wang L., Li Q., Zuo T., Cohen-Kedar S., Lu J.,
RA Ardy R.C., Mulder D.J., Dissanayake D., Peng K., Huang Z., Li X., Wang Y.,
RA Wang X., Li S., Bullers S., Gammage A.N., Warnatz K., Schiefer A.I.,
RA Krivan G., Goda V., Kahr W.H.A., Lemaire M., Lu C.Y., Siddiqui I.,
RA Surette M.G., Kotlarz D., Engelhardt K.R., Griffin H.R., Rottapel R.,
RA Decaluwe H., Laxer R.M., Proietti M., Hambleton S., Elcombe S., Guo C.H.,
RA Grimbacher B., Dotan I., Ng S.C., Freeman S.A., Snapper S.B., Klein C.,
RA Boztug K., Huang Y., Li D., Uhlig H.H., Muise A.M.;
RT "Gain-of-function variants in SYK cause immune dysregulation and systemic
RT inflammation in humans and mice.";
RL Nat. Genet. 53:500-510(2021).
RN [33]
RP STRUCTURE BY NMR OF 163-265.
RX PubMed=8590001; DOI=10.1016/s0969-2126(01)00242-8;
RA Narula S.S., Yuan R.W., Adams S.E., Green O.M., Green J., Philips T.B.,
RA Zydowsky L.D., Botfield M.C., Hatada M., Laird E.R., Zoller M.J.,
RA Karas J.L., Dalgarno D.C.;
RT "Solution structure of the C-terminal SH2 domain of the human tyrosine
RT kinase Syk complexed with a phosphotyrosine pentapeptide.";
RL Structure 3:1061-1073(1995).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF SH2 DOMAINS IN COMPLEX WITH CD3E
RP PHOSPHORYLATED ITAM DOMAIN.
RX PubMed=9698567; DOI=10.1006/jmbi.1998.1964;
RA Fuetterer K., Wong J., Grucza R.A., Chan A.C., Waksman G.;
RT "Structural basis for Syk tyrosine kinase ubiquity in signal transduction
RT pathways revealed by the crystal structure of its regulatory SH2 domains
RT bound to a dually phosphorylated ITAM peptide.";
RL J. Mol. Biol. 281:523-537(1998).
CC -!- FUNCTION: Non-receptor tyrosine kinase which mediates signal
CC transduction downstream of a variety of transmembrane receptors
CC including classical immunoreceptors like the B-cell receptor (BCR).
CC Regulates several biological processes including innate and adaptive
CC immunity, cell adhesion, osteoclast maturation, platelet activation and
CC vascular development (PubMed:33782605). Assembles into signaling
CC complexes with activated receptors at the plasma membrane via
CC interaction between its SH2 domains and the receptor tyrosine-
CC phosphorylated ITAM domains. The association with the receptor can also
CC be indirect and mediated by adapter proteins containing ITAM or partial
CC hemITAM domains. The phosphorylation of the ITAM domains is generally
CC mediated by SRC subfamily kinases upon engagement of the receptor. More
CC rarely signal transduction via SYK could be ITAM-independent. Direct
CC downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-
CC kinase, LCP2 and BLNK. Initially identified as essential in B-cell
CC receptor (BCR) signaling, it is necessary for the maturation of B-cells
CC most probably at the pro-B to pre-B transition. Activated upon BCR
CC engagement, it phosphorylates and activates BLNK an adapter linking the
CC activated BCR to downstream signaling adapters and effectors. It also
CC phosphorylates and activates PLCG1 and the PKC signaling pathway. It
CC also phosphorylates BTK and regulates its activity in B-cell antigen
CC receptor (BCR)-coupled signaling. In addition to its function
CC downstream of BCR also plays a role in T-cell receptor signaling. Plays
CC also a crucial role in the innate immune response to fungal, bacterial
CC and viral pathogens. It is for instance activated by the membrane
CC lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together
CC with SYK activates immune cells inducing the production of ROS. Also
CC activates the inflammasome and NF-kappa-B-mediated transcription of
CC chemokines and cytokines in presence of pathogens. Regulates neutrophil
CC degranulation and phagocytosis through activation of the MAPK signaling
CC cascade (By similarity). Required for the stimulation of neutrophil
CC phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of
CC dendritic cells by cell necrosis stimuli. Also involved in mast cells
CC activation. Involved in interleukin-3/IL3-mediated signaling pathway in
CC basophils (By similarity). Also functions downstream of receptors
CC mediating cell adhesion. Relays for instance, integrin-mediated
CC neutrophils and macrophages activation and P-selectin receptor/SELPG-
CC mediated recruitment of leukocytes to inflammatory loci. Also plays a
CC role in non-immune processes. It is for instance involved in vascular
CC development where it may regulate blood and lymphatic vascular
CC separation. It is also required for osteoclast development and
CC function. Functions in the activation of platelets by collagen,
CC mediating PLCG2 phosphorylation and activation. May be coupled to the
CC collagen receptor by the ITAM domain-containing FCER1G. Also activated
CC by the membrane lectin CLEC1B that is required for activation of
CC platelets by PDPN/podoplanin. Involved in platelet adhesion being
CC activated by ITGB3 engaged by fibrinogen. Together with CEACAM20,
CC enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and
CC may thus have a role in the intestinal immune response (By similarity).
CC {ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:12387735,
CC ECO:0000269|PubMed:12456653, ECO:0000269|PubMed:15123770,
CC ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:19909739,
CC ECO:0000269|PubMed:33782605, ECO:0000269|PubMed:8657103,
CC ECO:0000269|PubMed:9535867}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:33782605};
CC -!- ACTIVITY REGULATION: Autoinhibited. Intramolecular binding of the
CC interdomains A and B (also called linker region) to parts of the
CC catalytic domain keep the catalytic center in an inactive conformation.
CC The phosphorylation of the interdomains or the binding of the SH2
CC domains with dually phosphorylated ITAM domains on transmembrane
CC proteins disrupt those intramolecular interactions allowing the kinase
CC domain to adopt an active conformation. The phosphorylation of SYK and
CC of the ITAM domains which is responsible for SYK activation is
CC essentially mediated by SRC subfamily kinases, like LYN, upon
CC transmembrane receptors engagement. May also be negatively regulated by
CC PTPN6 through dephosphorylation. Downstream signaling adapters and
CC intermediates like BLNK or RHOH may mediate positive and/or negative
CC feedback regulation. Negatively regulated by CBL and CBLB through
CC ubiquitination and probable degradation. Phosphorylates SH3BP2 which in
CC turn may regulate SYK through LYN (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with LYN; phosphorylates SYK (By similarity).
CC Interacts with RHOH (phosphorylated); regulates mast cells activation
CC (By similarity). Interacts with NFAM1 (phosphorylated); probably
CC involved in BCR signaling (By similarity). Interacts with VAV1 (via SH2
CC domain); phosphorylates VAV1 upon BCR activation. Interacts with GAB2
CC (phosphorylated); probably involved in IgE Fc receptor signaling (By
CC similarity). Interacts (via its SH2 domains) with CD79A (via its
CC phosphorylated ITAM domain); the interaction stimulates SYK
CC autophosphorylation and activation (By similarity). Interacts with
CC FCRL3 (PubMed:19843936, PubMed:11162587). Interacts (via SH2 domains)
CC with FCER1G (via ITAM domain); activates SYK and mediates neutrophils
CC and macrophages integrin-mediated activation (By similarity).
CC Interaction with FCER1G in basophils triggers IL3-induced IL4
CC production (By similarity). Interacts with ITGB2 and FGR; involved in
CC ITGB2 downstream signaling (By similarity). Interacts with ITGB3; upon
CC activation by ITGB3 promotes platelet adhesion. Interacts (via SH2
CC domains) with TYROBP (via ITAM domain); involved in neutrophils and
CC macrophages integrin-mediated activation (By similarity). Interacts
CC with MSN and SELPLG; mediates the selectin-dependent activation of SYK
CC by SELPLG. Interacts with BLNK (via SH2 domain). Interacts (via the
CC second SH2 domain) with USP25 (via C-terminus); phosphorylates USP25
CC and regulates USP25 intracellular levels. Interacts (via SH2 domains)
CC with CLEC1B (dimer). Interacts with CLEC7A; participates in leukocyte
CC activation in presence of fungal pathogens. Interacts (phosphorylated)
CC with SLA; may regulate SYK through CBL recruitment. Interacts with
CC YWHAG; attenuates BCR-induced membrane translocation and activation of
CC SYK. Interacts (via SH2 domains) with GCSAM; the interaction increases
CC after B-cell receptor stimulation, resulting in enhanced SYK
CC autophosphorylation and activity. Interacts with TNS2; leading to the
CC phosphorylation of SYK (PubMed:22019427). Interacts with FLNA (via
CC filamin repeat 5); docks SYK to the plasma membrane (PubMed:20713593).
CC Interacts with CEACAM1; lipopolysaccharide activated neutrophils induce
CC phosphorylation of SYK resulting in the formation of a complex
CC including TLR4 and the phosphorylated form of SYK and CEACAM1, which in
CC turn, recruits PTPN6 that dephosphorylates SYK, reducing the production
CC of reactive oxygen species (ROS) and lysosome disruption, leading to a
CC reduction of the inflammasome activity (By similarity). Interacts (via
CC SH2 domains) with CEACAM20 (phosphorylated form); the interaction
CC further enhances CEACAM20 phosphorylation (By similarity). Interacts
CC with IL15RA (PubMed:15123770). {ECO:0000250,
CC ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:10449770,
CC ECO:0000269|PubMed:11162587, ECO:0000269|PubMed:11940607,
CC ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:15123770,
CC ECO:0000269|PubMed:18369315, ECO:0000269|PubMed:19843936,
CC ECO:0000269|PubMed:19909739, ECO:0000269|PubMed:20154219,
CC ECO:0000269|PubMed:20713593, ECO:0000269|PubMed:21469132,
CC ECO:0000269|PubMed:22019427, ECO:0000269|PubMed:23299888,
CC ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:8986718,
CC ECO:0000269|PubMed:9535867, ECO:0000269|PubMed:9698567,
CC ECO:0000269|PubMed:9857068}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus LMP2A.
CC {ECO:0000269|PubMed:7895172}.
CC -!- INTERACTION:
CC P43405; P05067: APP; NbExp=3; IntAct=EBI-78302, EBI-77613;
CC P43405; P22681: CBL; NbExp=2; IntAct=EBI-78302, EBI-518228;
CC P43405; P20273: CD22; NbExp=4; IntAct=EBI-78302, EBI-78277;
CC P43405; P11049: CD37; NbExp=3; IntAct=EBI-78302, EBI-6139068;
CC P43405; P07766: CD3E; NbExp=6; IntAct=EBI-78302, EBI-1211297;
CC P43405; P00533: EGFR; NbExp=6; IntAct=EBI-78302, EBI-297353;
CC P43405; P04626: ERBB2; NbExp=7; IntAct=EBI-78302, EBI-641062;
CC P43405; P21860: ERBB3; NbExp=6; IntAct=EBI-78302, EBI-720706;
CC P43405; P30273: FCER1G; NbExp=2; IntAct=EBI-78302, EBI-515289;
CC P43405; P36888: FLT3; NbExp=22; IntAct=EBI-78302, EBI-3946257;
CC P43405; Q13480: GAB1; NbExp=4; IntAct=EBI-78302, EBI-517684;
CC P43405; P06239: LCK; NbExp=7; IntAct=EBI-78302, EBI-1348;
CC P43405; P08581: MET; NbExp=3; IntAct=EBI-78302, EBI-1039152;
CC P43405; P19174: PLCG1; NbExp=4; IntAct=EBI-78302, EBI-79387;
CC P43405; Q9ULZ3: PYCARD; NbExp=4; IntAct=EBI-78302, EBI-751215;
CC P43405; Q9NP31: SH2D2A; NbExp=3; IntAct=EBI-78302, EBI-490630;
CC P43405; P40763: STAT3; NbExp=10; IntAct=EBI-78302, EBI-518675;
CC P43405; Q96IP4: TENT5A; NbExp=3; IntAct=EBI-78302, EBI-954084;
CC P43405; P54274: TERF1; NbExp=2; IntAct=EBI-78302, EBI-710997;
CC P43405; Q8TF42: UBASH3B; NbExp=2; IntAct=EBI-78302, EBI-1380492;
CC P43405; Q9UHP3: USP25; NbExp=8; IntAct=EBI-78302, EBI-2513462;
CC P43405-2; P01023: A2M; NbExp=3; IntAct=EBI-25892332, EBI-640741;
CC P43405-2; Q06481-5: APLP2; NbExp=3; IntAct=EBI-25892332, EBI-25646567;
CC P43405-2; P05067: APP; NbExp=3; IntAct=EBI-25892332, EBI-77613;
CC P43405-2; Q13867: BLMH; NbExp=3; IntAct=EBI-25892332, EBI-718504;
CC P43405-2; P27824-2: CANX; NbExp=3; IntAct=EBI-25892332, EBI-25890990;
CC P43405-2; Q86YQ8-2: CPNE8; NbExp=3; IntAct=EBI-25892332, EBI-25891175;
CC P43405-2; Q9UGL9: CRCT1; NbExp=3; IntAct=EBI-25892332, EBI-713677;
CC P43405-2; O14576-2: DYNC1I1; NbExp=3; IntAct=EBI-25892332, EBI-25840445;
CC P43405-2; P0DMV8: HSPA1A; NbExp=3; IntAct=EBI-25892332, EBI-11052499;
CC P43405-2; Q07954-2: LRP1; NbExp=3; IntAct=EBI-25892332, EBI-25833471;
CC P43405-2; P41271-2: NBL1; NbExp=3; IntAct=EBI-25892332, EBI-12135485;
CC P43405-2; P62136: PPP1CA; NbExp=3; IntAct=EBI-25892332, EBI-357253;
CC P43405-2; P63000: RAC1; NbExp=3; IntAct=EBI-25892332, EBI-413628;
CC P43405-2; P29353-7: SHC1; NbExp=3; IntAct=EBI-25892332, EBI-9691288;
CC P43405-2; Q9Y4K3: TRAF6; NbExp=3; IntAct=EBI-25892332, EBI-359276;
CC P43405-2; A0A024RC47: ZNF24; NbExp=3; IntAct=EBI-25892332, EBI-25830832;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}. Cytoplasm, cytosol
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P43405-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P43405-2; Sequence=VSP_005010;
CC -!- TISSUE SPECIFICITY: Widely expressed in hematopoietic cells (at protein
CC level) (PubMed:8163536). Expressed in neutrophils (at protein level)
CC (PubMed:15123770). Within the B-cell compartment, expressed from
CC pro- and pre-B cells to plasma cells (PubMed:8163536).
CC {ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:8163536}.
CC -!- DOMAIN: The SH2 domains mediate the interaction of SYK with the
CC phosphorylated ITAM domains of transmembrane proteins. Some proteins
CC like CLEC1B have a partial ITAM domain (also called hemITAM) containing
CC a single YxxL motif. The interaction with SYK requires CLEC1B
CC homodimerization.
CC -!- PTM: Ubiquitinated by CBLB after BCR activation; which promotes
CC proteasomal degradation. {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues by LYN
CC following receptors engagement. Phosphorylation on Tyr-323 creates a
CC binding site for CBL, an adapter protein that serves as a negative
CC regulator of BCR-stimulated calcium ion signaling. Phosphorylation at
CC Tyr-348 creates a binding site for VAV1. Phosphorylation on Tyr-348 and
CC Tyr-352 enhances the phosphorylation and activation of phospholipase C-
CC gamma and the early phase of calcium ion mobilization via a
CC phosphoinositide 3-kinase-independent pathway (By similarity).
CC Phosphorylated on tyrosine residues in response to IL15
CC (PubMed:15123770). Phosphorylation on Ser-297 is very common, it peaks
CC 5 minutes after BCR stimulation, and creates a binding site for YWHAG.
CC Phosphorylation at Tyr-630 creates a binding site for BLNK.
CC Dephosphorylated by PTPN6. {ECO:0000250, ECO:0000269|PubMed:10458769,
CC ECO:0000269|PubMed:15123770, ECO:0000269|PubMed:18369315,
CC ECO:0000269|PubMed:21469132}.
CC -!- DISEASE: Immunodeficiency 82 with systemic inflammation (IMD82)
CC [MIM:619381]: An autosomal dominant immunologic disorder with onset in
CC early childhood. It is characterized by recurrent infections with
CC various organisms, and multi-organ inflammation that manifests as
CC colitis, hepatitis, arthritis and dermatitis. Patients have a
CC propensity for the development of lymphoma, usually in adulthood.
CC Disease severity is variable. {ECO:0000269|PubMed:33782605}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SYK/ZAP-70 subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SYKID394.html";
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DR EMBL; Z29630; CAA82737.1; -; mRNA.
DR EMBL; L28824; AAA36526.1; -; mRNA.
DR EMBL; AL354862; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001645; AAH01645.1; -; mRNA.
DR EMBL; BC011399; AAH11399.1; -; mRNA.
DR EMBL; BC002962; AAH02962.1; -; mRNA.
DR EMBL; X73568; CAA51970.1; -; mRNA.
DR CCDS; CCDS47992.1; -. [P43405-2]
DR CCDS; CCDS6688.1; -. [P43405-1]
DR PIR; A53596; A53596.
DR RefSeq; NP_001128524.1; NM_001135052.3. [P43405-2]
DR RefSeq; NP_001167638.1; NM_001174167.2. [P43405-1]
DR RefSeq; NP_001167639.1; NM_001174168.2. [P43405-2]
DR RefSeq; NP_003168.2; NM_003177.6. [P43405-1]
DR RefSeq; XP_005252204.1; XM_005252147.3. [P43405-1]
DR RefSeq; XP_011517248.1; XM_011518946.2. [P43405-1]
DR PDB; 1A81; X-ray; 3.00 A; A/C/E/G/I/K=9-262.
DR PDB; 1CSY; NMR; -; A=163-265.
DR PDB; 1CSZ; NMR; -; A=163-265.
DR PDB; 1XBA; X-ray; 2.00 A; A=356-635.
DR PDB; 1XBB; X-ray; 1.57 A; A=356-635.
DR PDB; 1XBC; X-ray; 2.00 A; A=356-635.
DR PDB; 3BUW; X-ray; 1.45 A; A/C=317-329.
DR PDB; 3EMG; X-ray; 2.60 A; A=349-635.
DR PDB; 3FQE; X-ray; 2.50 A; A=356-635.
DR PDB; 3FQH; X-ray; 2.26 A; A/B=356-635.
DR PDB; 3FQS; X-ray; 2.10 A; A=356-635.
DR PDB; 3SRV; X-ray; 1.95 A; A/B=360-635.
DR PDB; 3TUB; X-ray; 2.23 A; A=343-635.
DR PDB; 3TUC; X-ray; 2.10 A; A=343-635.
DR PDB; 3TUD; X-ray; 2.33 A; A=343-635.
DR PDB; 3VF8; X-ray; 2.08 A; A=343-635.
DR PDB; 3VF9; X-ray; 2.30 A; A=343-635.
DR PDB; 4DFL; X-ray; 1.98 A; A=363-635.
DR PDB; 4DFN; X-ray; 2.48 A; A=363-635.
DR PDB; 4F4P; X-ray; 2.37 A; A=365-635.
DR PDB; 4FL1; X-ray; 1.79 A; A=356-635.
DR PDB; 4FL2; X-ray; 2.19 A; A=1-635.
DR PDB; 4FL3; X-ray; 1.90 A; A=1-635.
DR PDB; 4FYN; X-ray; 2.32 A; A=356-635.
DR PDB; 4FYO; X-ray; 1.40 A; A=356-635.
DR PDB; 4FZ6; X-ray; 1.85 A; A=356-635.
DR PDB; 4FZ7; X-ray; 1.75 A; A=356-635.
DR PDB; 4GFG; X-ray; 2.35 A; A=356-635.
DR PDB; 4I0R; X-ray; 2.10 A; A=356-635.
DR PDB; 4I0S; X-ray; 1.98 A; A=356-635.
DR PDB; 4I0T; X-ray; 1.70 A; A=356-635.
DR PDB; 4PUZ; X-ray; 2.08 A; A/B=356-635.
DR PDB; 4PV0; X-ray; 2.00 A; A=363-635.
DR PDB; 4PX6; X-ray; 1.60 A; A=356-635.
DR PDB; 4RSS; X-ray; 1.83 A; A=356-635.
DR PDB; 4RX7; X-ray; 1.80 A; A=356-635.
DR PDB; 4RX8; X-ray; 1.59 A; A=356-635.
DR PDB; 4RX9; X-ray; 1.75 A; A=356-635.
DR PDB; 4WNM; X-ray; 2.50 A; A=343-635.
DR PDB; 4XG2; X-ray; 2.21 A; A=356-635.
DR PDB; 4XG3; X-ray; 2.30 A; A/B=356-635.
DR PDB; 4XG4; X-ray; 2.30 A; A=356-635.
DR PDB; 4XG6; X-ray; 2.40 A; A=356-635.
DR PDB; 4XG7; X-ray; 1.76 A; A=356-635.
DR PDB; 4XG8; X-ray; 2.40 A; A/C=356-635.
DR PDB; 4XG9; X-ray; 2.91 A; A/B=356-635.
DR PDB; 4YJO; X-ray; 1.60 A; A=355-635.
DR PDB; 4YJP; X-ray; 1.83 A; A=355-635.
DR PDB; 4YJQ; X-ray; 1.34 A; A=355-635.
DR PDB; 4YJR; X-ray; 1.32 A; A=355-635.
DR PDB; 4YJS; X-ray; 2.22 A; A=355-635.
DR PDB; 4YJT; X-ray; 1.52 A; A=355-635.
DR PDB; 4YJU; X-ray; 1.67 A; A=355-635.
DR PDB; 4YJV; X-ray; 1.65 A; A=355-635.
DR PDB; 5C26; X-ray; 1.95 A; A=343-635.
DR PDB; 5C27; X-ray; 2.15 A; A=343-635.
DR PDB; 5CXH; X-ray; 1.90 A; A=356-635.
DR PDB; 5CXZ; X-ray; 1.70 A; A=356-635.
DR PDB; 5CY3; X-ray; 1.76 A; A=356-635.
DR PDB; 5GHV; X-ray; 2.80 A; A/B=356-635.
DR PDB; 5LMA; X-ray; 1.43 A; A=360-635.
DR PDB; 5LMB; X-ray; 1.95 A; A/B=360-635.
DR PDB; 5T68; X-ray; 2.93 A; A/B=356-635.
DR PDB; 5TIU; X-ray; 1.49 A; A=356-635.
DR PDB; 5TR6; X-ray; 1.93 A; A=356-635.
DR PDB; 5TT7; X-ray; 1.77 A; A=356-635.
DR PDB; 5Y5T; X-ray; 1.80 A; A=356-635.
DR PDB; 5Y5U; X-ray; 2.14 A; A/B=356-635.
DR PDB; 6HM6; X-ray; 2.10 A; A=360-635.
DR PDB; 6HM7; X-ray; 1.64 A; A=360-635.
DR PDB; 6SSB; X-ray; 2.08 A; A=343-635.
DR PDB; 6VOV; X-ray; 1.95 A; A/B=363-635.
DR PDB; 6ZC0; X-ray; 1.97 A; A=343-635.
DR PDB; 6ZCP; X-ray; 2.20 A; A=343-635.
DR PDB; 6ZCQ; X-ray; 2.32 A; A=343-635.
DR PDB; 6ZCR; X-ray; 1.73 A; A=343-635.
DR PDB; 6ZCS; X-ray; 1.47 A; A=343-635.
DR PDB; 6ZCU; X-ray; 1.73 A; A=343-635.
DR PDB; 6ZCX; X-ray; 1.66 A; A=343-635.
DR PDB; 6ZCY; X-ray; 1.81 A; A=343-635.
DR PDB; 7Q5T; X-ray; 2.20 A; AAA/BBB/CCC/DDD/EEE/FFF=6-269.
DR PDB; 7Q5U; X-ray; 2.40 A; AAA/BBB/CCC/DDD/EEE/FFF=6-269.
DR PDB; 7Q5W; X-ray; 2.20 A; AAA/BBB/CCC/DDD/EEE/FFF=6-269.
DR PDB; 7Q63; X-ray; 1.90 A; AAA/BBB/CCC=6-269.
DR PDB; 7SA7; X-ray; 3.20 A; A/B/C/D/E/F=6-269.
DR PDBsum; 1A81; -.
DR PDBsum; 1CSY; -.
DR PDBsum; 1CSZ; -.
DR PDBsum; 1XBA; -.
DR PDBsum; 1XBB; -.
DR PDBsum; 1XBC; -.
DR PDBsum; 3BUW; -.
DR PDBsum; 3EMG; -.
DR PDBsum; 3FQE; -.
DR PDBsum; 3FQH; -.
DR PDBsum; 3FQS; -.
DR PDBsum; 3SRV; -.
DR PDBsum; 3TUB; -.
DR PDBsum; 3TUC; -.
DR PDBsum; 3TUD; -.
DR PDBsum; 3VF8; -.
DR PDBsum; 3VF9; -.
DR PDBsum; 4DFL; -.
DR PDBsum; 4DFN; -.
DR PDBsum; 4F4P; -.
DR PDBsum; 4FL1; -.
DR PDBsum; 4FL2; -.
DR PDBsum; 4FL3; -.
DR PDBsum; 4FYN; -.
DR PDBsum; 4FYO; -.
DR PDBsum; 4FZ6; -.
DR PDBsum; 4FZ7; -.
DR PDBsum; 4GFG; -.
DR PDBsum; 4I0R; -.
DR PDBsum; 4I0S; -.
DR PDBsum; 4I0T; -.
DR PDBsum; 4PUZ; -.
DR PDBsum; 4PV0; -.
DR PDBsum; 4PX6; -.
DR PDBsum; 4RSS; -.
DR PDBsum; 4RX7; -.
DR PDBsum; 4RX8; -.
DR PDBsum; 4RX9; -.
DR PDBsum; 4WNM; -.
DR PDBsum; 4XG2; -.
DR PDBsum; 4XG3; -.
DR PDBsum; 4XG4; -.
DR PDBsum; 4XG6; -.
DR PDBsum; 4XG7; -.
DR PDBsum; 4XG8; -.
DR PDBsum; 4XG9; -.
DR PDBsum; 4YJO; -.
DR PDBsum; 4YJP; -.
DR PDBsum; 4YJQ; -.
DR PDBsum; 4YJR; -.
DR PDBsum; 4YJS; -.
DR PDBsum; 4YJT; -.
DR PDBsum; 4YJU; -.
DR PDBsum; 4YJV; -.
DR PDBsum; 5C26; -.
DR PDBsum; 5C27; -.
DR PDBsum; 5CXH; -.
DR PDBsum; 5CXZ; -.
DR PDBsum; 5CY3; -.
DR PDBsum; 5GHV; -.
DR PDBsum; 5LMA; -.
DR PDBsum; 5LMB; -.
DR PDBsum; 5T68; -.
DR PDBsum; 5TIU; -.
DR PDBsum; 5TR6; -.
DR PDBsum; 5TT7; -.
DR PDBsum; 5Y5T; -.
DR PDBsum; 5Y5U; -.
DR PDBsum; 6HM6; -.
DR PDBsum; 6HM7; -.
DR PDBsum; 6SSB; -.
DR PDBsum; 6VOV; -.
DR PDBsum; 6ZC0; -.
DR PDBsum; 6ZCP; -.
DR PDBsum; 6ZCQ; -.
DR PDBsum; 6ZCR; -.
DR PDBsum; 6ZCS; -.
DR PDBsum; 6ZCU; -.
DR PDBsum; 6ZCX; -.
DR PDBsum; 6ZCY; -.
DR PDBsum; 7Q5T; -.
DR PDBsum; 7Q5U; -.
DR PDBsum; 7Q5W; -.
DR PDBsum; 7Q63; -.
DR PDBsum; 7SA7; -.
DR AlphaFoldDB; P43405; -.
DR SMR; P43405; -.
DR BioGRID; 112717; 130.
DR CORUM; P43405; -.
DR DIP; DIP-253N; -.
DR ELM; P43405; -.
DR IntAct; P43405; 154.
DR MINT; P43405; -.
DR STRING; 9606.ENSP00000364907; -.
DR BindingDB; P43405; -.
DR ChEMBL; CHEMBL2599; -.
DR DrugBank; DB07194; 2-{2-[(3,5-dimethylphenyl)amino]pyrimidin-4-yl}-N-[(1S)-2-hydroxy-1-methylethyl]-4-methyl-1,3-thiazole-5-carboxamide.
DR DrugBank; DB08361; 2-{[(1R,2S)-2-aminocyclohexyl]amino}-4-[(3-methylphenyl)amino]pyrimidine-5-carboxamide.
DR DrugBank; DB08846; Ellagic acid.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB06834; N-(2-hydroxy-1,1-dimethylethyl)-1-methyl-3-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-indole-5-carboxamide.
DR DrugBank; DB02010; Staurosporine.
DR DrugBank; DB07159; Tamatinib.
DR DrugCentral; P43405; -.
DR GuidetoPHARMACOLOGY; 2230; -.
DR MoonDB; P43405; Predicted.
DR GlyGen; P43405; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P43405; -.
DR PhosphoSitePlus; P43405; -.
DR BioMuta; SYK; -.
DR DMDM; 1174527; -.
DR CPTAC; CPTAC-1173; -.
DR CPTAC; CPTAC-1174; -.
DR EPD; P43405; -.
DR jPOST; P43405; -.
DR MassIVE; P43405; -.
DR MaxQB; P43405; -.
DR PaxDb; P43405; -.
DR PeptideAtlas; P43405; -.
DR PRIDE; P43405; -.
DR ProteomicsDB; 55634; -. [P43405-1]
DR ProteomicsDB; 55635; -. [P43405-2]
DR Antibodypedia; 733; 1589 antibodies from 51 providers.
DR DNASU; 6850; -.
DR Ensembl; ENST00000375746.1; ENSP00000364898.1; ENSG00000165025.15. [P43405-1]
DR Ensembl; ENST00000375747.5; ENSP00000364899.1; ENSG00000165025.15. [P43405-2]
DR Ensembl; ENST00000375751.8; ENSP00000364904.4; ENSG00000165025.15. [P43405-2]
DR Ensembl; ENST00000375754.9; ENSP00000364907.4; ENSG00000165025.15. [P43405-1]
DR GeneID; 6850; -.
DR KEGG; hsa:6850; -.
DR MANE-Select; ENST00000375754.9; ENSP00000364907.4; NM_003177.7; NP_003168.2.
DR UCSC; uc004aqz.4; human. [P43405-1]
DR CTD; 6850; -.
DR DisGeNET; 6850; -.
DR GeneCards; SYK; -.
DR HGNC; HGNC:11491; SYK.
DR HPA; ENSG00000165025; Tissue enhanced (lymphoid tissue, parathyroid gland).
DR MalaCards; SYK; -.
DR MIM; 600085; gene.
DR MIM; 619381; phenotype.
DR neXtProt; NX_P43405; -.
DR OpenTargets; ENSG00000165025; -.
DR PharmGKB; PA36273; -.
DR VEuPathDB; HostDB:ENSG00000165025; -.
DR eggNOG; ENOG502QT06; Eukaryota.
DR GeneTree; ENSGT00940000159053; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P43405; -.
DR OMA; RPEVCPT; -.
DR PhylomeDB; P43405; -.
DR TreeFam; TF351629; -.
DR BRENDA; 2.7.10.2; 2681.
DR BRENDA; 2.7.12.1; 2681.
DR PathwayCommons; P43405; -.
DR Reactome; R-HSA-114604; GPVI-mediated activation cascade.
DR Reactome; R-HSA-2029481; FCGR activation.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-HSA-2424491; DAP12 signaling.
DR Reactome; R-HSA-2454202; Fc epsilon receptor (FCERI) signaling.
DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-HSA-354192; Integrin signaling.
DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-HSA-5621480; Dectin-2 family.
DR Reactome; R-HSA-9020558; Interleukin-2 signaling.
DR Reactome; R-HSA-912631; Regulation of signaling by CBL.
DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-HSA-9706374; FLT3 signaling through SRC family kinases.
DR Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR SignaLink; P43405; -.
DR SIGNOR; P43405; -.
DR BioGRID-ORCS; 6850; 20 hits in 1115 CRISPR screens.
DR ChiTaRS; SYK; human.
DR EvolutionaryTrace; P43405; -.
DR GeneWiki; Syk; -.
DR GenomeRNAi; 6850; -.
DR Pharos; P43405; Tclin.
DR PRO; PR:P43405; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P43405; protein.
DR Bgee; ENSG00000165025; Expressed in monocyte and 165 other tissues.
DR ExpressionAtlas; P43405; baseline and differential.
DR Genevisible; P43405; HS.
DR GO; GO:0019815; C:B cell receptor complex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0042101; C:T cell receptor complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0016170; F:interleukin-15 receptor binding; IPI:UniProtKB.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; IEA:Ensembl.
DR GO; GO:0043274; F:phospholipase binding; IPI:ARUK-UCL.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IMP:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:CACAO.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IMP:UniProtKB.
DR GO; GO:0097110; F:scaffold protein binding; IPI:ARUK-UCL.
DR GO; GO:0042169; F:SH2 domain binding; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL.
DR GO; GO:0035325; F:Toll-like receptor binding; IEA:Ensembl.
DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IMP:ARUK-UCL.
DR GO; GO:0043366; P:beta selection; IEA:Ensembl.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0001775; P:cell activation; ISS:ARUK-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:1990858; P:cellular response to lectin; ISS:ARUK-UCL.
DR GO; GO:0071396; P:cellular response to lipid; IMP:ARUK-UCL.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB.
DR GO; GO:0071226; P:cellular response to molecule of fungal origin; ISS:UniProtKB.
DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0042492; P:gamma-delta T cell differentiation; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0038156; P:interleukin-3-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:ARUK-UCL.
DR GO; GO:0002366; P:leukocyte activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0019370; P:leukotriene biosynthetic process; IEA:Ensembl.
DR GO; GO:0001945; P:lymph vessel development; ISS:UniProtKB.
DR GO; GO:0002281; P:macrophage activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0043303; P:mast cell degranulation; IEA:Ensembl.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome.
DR GO; GO:0002283; P:neutrophil activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:ARUK-UCL.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IEA:Ensembl.
DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IBA:GO_Central.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IMP:CACAO.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Ensembl.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:ARUK-UCL.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IEA:Ensembl.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IEA:Ensembl.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IMP:ARUK-UCL.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IMP:ARUK-UCL.
DR GO; GO:0032752; P:positive regulation of interleukin-3 production; IEA:Ensembl.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:ARUK-UCL.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:ARUK-UCL.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IEA:Ensembl.
DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; IMP:ARUK-UCL.
DR GO; GO:0032765; P:positive regulation of mast cell cytokine production; IEA:Ensembl.
DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IBA:GO_Central.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; IMP:ARUK-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IMP:ARUK-UCL.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IEA:Ensembl.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IMP:ARUK-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:ARUK-UCL.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:CACAO.
DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR GO; GO:0090237; P:regulation of arachidonic acid secretion; ISS:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IMP:MGI.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0043313; P:regulation of neutrophil degranulation; ISS:UniProtKB.
DR GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0010543; P:regulation of platelet activation; ISS:UniProtKB.
DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0032928; P:regulation of superoxide anion generation; ISS:UniProtKB.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IMP:CACAO.
DR GO; GO:0002554; P:serotonin secretion by platelet; ISS:UniProtKB.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd09938; SH2_N-SH2_Zap70_Syk_like; 1.
DR Gene3D; 1.10.930.10; -; 1.
DR Gene3D; 3.30.505.10; -; 2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR023420; Kinase_SYK/ZAP-70_inter-SH2_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR035838; SYK/ZAP-70_N_SH2.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR012234; Tyr_kinase_non-rcpt_SYK/ZAP70.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 2.
DR PIRSF; PIRSF000604; TyrPK_SYK; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF55550; SSF55550; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Angiogenesis;
KW ATP-binding; Cell membrane; Cytoplasm; Disease variant;
KW Host-virus interaction; Immunity; Innate immunity; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; SH2 domain;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..635
FT /note="Tyrosine-protein kinase SYK"
FT /id="PRO_0000088165"
FT DOMAIN 15..107
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 168..259
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 371..631
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 108..167
FT /note="Interdomain A"
FT REGION 260..370
FT /note="Interdomain B"
FT ACT_SITE 494
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 377..385
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 402
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 28
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 47
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 131
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 256
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 296
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 317
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 323
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000269|PubMed:21469132,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 345
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 348
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 352
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 364
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 379
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 384
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 484
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 507
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 525
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 526
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 530
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 546
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P48025"
FT MOD_RES 579
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 582
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 629
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT MOD_RES 630
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18369315,
FT ECO:0000269|PubMed:21469132"
FT MOD_RES 631
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21469132"
FT VAR_SEQ 283..305
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_005010"
FT VARIANT 45
FT /note="R -> H (in dbSNP:rs16906862)"
FT /id="VAR_033838"
FT VARIANT 342
FT /note="P -> T (in IMD82; constitutively active protein
FT tyrosine kinase activity)"
FT /evidence="ECO:0000269|PubMed:33782605"
FT /id="VAR_085995"
FT VARIANT 353
FT /note="A -> T (in IMD82; constitutively active protein
FT tyrosine kinase activity)"
FT /evidence="ECO:0000269|PubMed:33782605"
FT /id="VAR_085996"
FT VARIANT 450
FT /note="M -> I (in IMD82; constitutively active protein
FT tyrosine kinase activity)"
FT /evidence="ECO:0000269|PubMed:33782605"
FT /id="VAR_085997"
FT VARIANT 550
FT /note="S -> F (in IMD82; constitutively active protein
FT tyrosine kinase activity)"
FT /evidence="ECO:0000269|PubMed:33782605"
FT /id="VAR_085998"
FT VARIANT 550
FT /note="S -> Y (in IMD82; constitutively active protein
FT tyrosine kinase activity)"
FT /evidence="ECO:0000269|PubMed:33782605"
FT /id="VAR_085999"
FT MUTAGEN 297
FT /note="S->A: Abolishes YWHAG binding."
FT /evidence="ECO:0000269|PubMed:21469132"
FT MUTAGEN 630
FT /note="Y->F: Loss of interaction with BLNK."
FT /evidence="ECO:0000269|PubMed:18369315"
FT CONFLICT 119
FT /note="P -> A (in Ref. 5; CAA51970)"
FT /evidence="ECO:0000305"
FT CONFLICT 250
FT /note="G -> P (in Ref. 5; CAA51970)"
FT /evidence="ECO:0000305"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:7SA7"
FT HELIX 22..31
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 51..57
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 60..68
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:4FL3"
FT HELIX 85..92
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:4FL3"
FT HELIX 119..136
FT /evidence="ECO:0007829|PDB:4FL3"
FT HELIX 140..158
FT /evidence="ECO:0007829|PDB:4FL3"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 169..172
FT /evidence="ECO:0007829|PDB:1A81"
FT HELIX 175..183
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:1CSY"
FT STRAND 192..201
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 203..209
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 212..220
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:1CSY"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:1CSY"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:4FL3"
FT HELIX 237..244
FT /evidence="ECO:0007829|PDB:4FL3"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:4FL3"
FT HELIX 342..344
FT /evidence="ECO:0007829|PDB:4FL3"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:4FL2"
FT HELIX 351..353
FT /evidence="ECO:0007829|PDB:4FL2"
FT HELIX 360..363
FT /evidence="ECO:0007829|PDB:5TT7"
FT HELIX 367..369
FT /evidence="ECO:0007829|PDB:4YJR"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:4YJR"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:6ZCS"
FT STRAND 384..391
FT /evidence="ECO:0007829|PDB:4YJR"
FT STRAND 393..409
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 411..424
FT /evidence="ECO:0007829|PDB:4YJR"
FT STRAND 435..449
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 456..462
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 468..487
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 497..499
FT /evidence="ECO:0007829|PDB:4YJR"
FT STRAND 500..504
FT /evidence="ECO:0007829|PDB:4YJR"
FT STRAND 507..510
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:4RX7"
FT STRAND 524..527
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 536..538
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 541..546
FT /evidence="ECO:0007829|PDB:4YJR"
FT STRAND 548..550
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 551..566
FT /evidence="ECO:0007829|PDB:4YJR"
FT TURN 567..569
FT /evidence="ECO:0007829|PDB:4YJR"
FT TURN 572..575
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 578..586
FT /evidence="ECO:0007829|PDB:4YJR"
FT STRAND 589..591
FT /evidence="ECO:0007829|PDB:3SRV"
FT HELIX 599..608
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 613..615
FT /evidence="ECO:0007829|PDB:4YJR"
FT HELIX 619..624
FT /evidence="ECO:0007829|PDB:4YJR"
SQ SEQUENCE 635 AA; 72066 MW; EAA6BDE65881FC68 CRC64;
MASSGMADSA NHLPFFFGNI TREEAEDYLV QGGMSDGLYL LRQSRNYLGG FALSVAHGRK
AHHYTIEREL NGTYAIAGGR THASPADLCH YHSQESDGLV CLLKKPFNRP QGVQPKTGPF
EDLKENLIRE YVKQTWNLQG QALEQAIISQ KPQLEKLIAT TAHEKMPWFH GKISREESEQ
IVLIGSKTNG KFLIRARDNN GSYALCLLHE GKVLHYRIDK DKTGKLSIPE GKKFDTLWQL
VEHYSYKADG LLRVLTVPCQ KIGTQGNVNF GGRPQLPGSH PATWSAGGII SRIKSYSFPK
PGHRKSSPAQ GNRQESTVSF NPYEPELAPW AADKGPQREA LPMDTEVYES PYADPEEIRP
KEVYLDRKLL TLEDKELGSG NFGTVKKGYY QMKKVVKTVA VKILKNEAND PALKDELLAE
ANVMQQLDNP YIVRMIGICE AESWMLVMEM AELGPLNKYL QQNRHVKDKN IIELVHQVSM
GMKYLEESNF VHRDLAARNV LLVTQHYAKI SDFGLSKALR ADENYYKAQT HGKWPVKWYA
PECINYYKFS SKSDVWSFGV LMWEAFSYGQ KPYRGMKGSE VTAMLEKGER MGCPAGCPRE
MYDLMNLCWT YDVENRPGFA AVELRLRNYY YDVVN
