Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Tyrosine-protein kinase SYK (EC 2.7.10.2) (Spleen tyrosine kinase) (p72-Syk)

 KSYK_HUMAN              Reviewed;         635 AA.
P43405;
01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
01-NOV-1995, sequence version 1.
22-NOV-2017, entry version 205.
RecName: Full=Tyrosine-protein kinase SYK;
EC=2.7.10.2;
AltName: Full=Spleen tyrosine kinase;
AltName: Full=p72-Syk;
Name=SYK;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=7513161; DOI=10.1006/bbrc.1994.1409;
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. 200:28-34(1994).
[2]
NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND
AUTOPHOSPHORYLATION.
PubMed=8163536;
Law C.-L., Sidorenko S.P., Chandran K.A., Draves K.E., Chan A.C.,
Weiss A., Edelhoff S., Disteche C.M., Clark E.A.;
"Molecular cloning of human Syk. A B cell protein-tyrosine kinase
associated with the surface immunoglobulin M-B cell receptor
complex.";
J. Biol. Chem. 269:12310-12319(1994).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15164053; DOI=10.1038/nature02465;
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
Rogers J., Dunham I.;
"DNA sequence and analysis of human chromosome 9.";
Nature 429:369-374(2004).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT).
TISSUE=Eye, and Lymph;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
NUCLEOTIDE SEQUENCE [MRNA] OF 6-635.
TISSUE=Tonsil;
PubMed=8168854; DOI=10.1007/BF00189234;
Mueller B., Cooper L., Terhorst C.;
"Molecular cloning of the human homologue to the pig protein-tyrosine
kinase syk.";
Immunogenetics 39:359-362(1994).
[6]
INTERACTION WITH EPSTEIN-BARR VIRUS LMP2A.
PubMed=7895172; DOI=10.1016/S1074-7613(95)80040-9;
Miller C.L., Burkhardt A.L., Lee J.H., Stealey B., Longnecker R.,
Bolen J.B., Kieff E.;
"Integral membrane protein 2 of Epstein-Barr virus regulates
reactivation from latency through dominant negative effects on
protein-tyrosine kinases.";
Immunity 2:155-166(1995).
[7]
INTERACTION WITH VAV1.
PubMed=8986718; DOI=10.1016/S1074-7613(00)80273-3;
Deckert M., Tartare-Deckert S., Couture C., Mustelin T., Altman A.;
"Functional and physical interactions of Syk family kinases with the
Vav proto-oncogene product.";
Immunity 5:591-604(1996).
[8]
FUNCTION IN PHOSPHORYLATION OF PLCG1, AND INTERACTION WITH PLCG1.
PubMed=8657103; DOI=10.1128/MCB.16.4.1305;
Law C.L., Chandran K.A., Sidorenko S.P., Clark E.A.;
"Phospholipase C-gamma1 interacts with conserved phosphotyrosyl
residues in the linker region of Syk and is a substrate for Syk.";
Mol. Cell. Biol. 16:1305-1315(1996).
[9]
FUNCTION IN PHOSPHORYLATION OF CBL, AND INTERACTION WITH CBL.
PubMed=9535867; DOI=10.1074/jbc.273.15.8867;
Deckert M., Elly C., Altman A., Liu Y.C.;
"Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn
and Syk tyrosine kinases.";
J. Biol. Chem. 273:8867-8874(1998).
[10]
ENZYME REGULATION, AND INTERACTION WITH CBL.
PubMed=9857068; DOI=10.1074/jbc.273.52.35273;
Lupher M.L. Jr., Rao N., Lill N.L., Andoniou C.E., Miyake S.,
Clark E.A., Druker B., Band H.;
"Cbl-mediated negative regulation of the Syk tyrosine kinase. A
critical role for Cbl phosphotyrosine-binding domain binding to Syk
phosphotyrosine 323.";
J. Biol. Chem. 273:35273-35281(1998).
[11]
PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN6, AND ENZYME REGULATION.
PubMed=10458769;
DOI=10.1002/(SICI)1521-4141(199908)29:08<2539::AID-IMMU2539>3.0.CO;2-M;
Brockdorff J., Williams S., Couture C., Mustelin T.;
"Dephosphorylation of ZAP-70 and inhibition of T cell activation by
activated SHP1.";
Eur. J. Immunol. 29:2539-2550(1999).
[12]
INTERACTION WITH SLA.
PubMed=10449770; DOI=10.1073/pnas.96.17.9775;
Tang J., Sawasdikosol S., Chang J.-H., Burakoff S.J.;
"SLAP, a dimeric adapter protein, plays a functional role in T cell
receptor signaling.";
Proc. Natl. Acad. Sci. U.S.A. 96:9775-9780(1999).
[13]
INTERACTION WITH FCRL3.
PubMed=11162587; DOI=10.1006/bbrc.2000.4213;
Xu M.-J., Zhao R., Zhao Z.J.;
"Molecular cloning and characterization of SPAP1, an inhibitory
receptor.";
Biochem. Biophys. Res. Commun. 280:768-775(2001).
[14]
FUNCTION IN B-CELL RECEPTOR SIGNALING PATHWAY, AND FUNCTION IN
PHOSPHORYLATION OF BLNK.
PubMed=12456653; DOI=10.1093/emboj/cdf658;
Chiu C.W., Dalton M., Ishiai M., Kurosaki T., Chan A.C.;
"BLNK: molecular scaffolding through 'cis'-mediated organization of
signaling proteins.";
EMBO J. 21:6461-6472(2002).
[15]
FUNCTION IN CELL ADHESION, AND INTERACTION WITH SELPLG AND MSN.
PubMed=12387735; DOI=10.1016/S1074-7613(02)00420-X;
Urzainqui A., Serrador J.M., Viedma F., Yanez-Mo M., Rodriguez A.,
Corbi A.L., Alonso-Lebrero J.L., Luque A., Deckert M., Vazquez J.,
Sanchez-Madrid F.;
"ITAM-based interaction of ERM proteins with Syk mediates signaling by
the leukocyte adhesion receptor PSGL-1.";
Immunity 17:401-412(2002).
[16]
INTERACTION WITH ITGB3.
PubMed=11940607; DOI=10.1083/jcb.200112113;
Obergfell A., Eto K., Mocsai A., Buensuceso C., Moores S.L.,
Brugge J.S., Lowell C.A., Shattil S.J.;
"Coordinate interactions of Csk, Src, and Syk kinases with
[alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton.";
J. Cell Biol. 157:265-275(2002).
[17]
FUNCTION IN PHOSPHORYLATION OF LCP2.
PubMed=15388330; DOI=10.1016/j.febslet.2004.07.090;
Shim E.K., Moon C.S., Lee G.Y., Ha Y.J., Chae S.K., Lee J.R.;
"Association of the Src homology 2 domain-containing leukocyte
phosphoprotein of 76 kD (SLP-76) with the p85 subunit of
phosphoinositide 3-kinase.";
FEBS Lett. 575:35-40(2004).
[18]
INTERACTION WITH BLNK, ENZYME REGULATION, MUTAGENESIS OF TYR-630, AND
PHOSPHORYLATION AT TYR-630.
PubMed=18369315; DOI=10.1038/emboj.2008.62;
Kulathu Y., Hobeika E., Turchinovich G., Reth M.;
"The kinase Syk as an adaptor controlling sustained calcium signalling
and B-cell development.";
EMBO J. 27:1333-1344(2008).
[19]
ENZYME REGULATION.
PubMed=18818202; DOI=10.1074/jbc.M806340200;
Tsang E., Giannetti A.M., Shaw D., Dinh M., Tse J.K., Gandhi S.,
Ho H., Wang S., Papp E., Bradshaw J.M.;
"Molecular mechanism of the Syk activation switch.";
J. Biol. Chem. 283:32650-32659(2008).
[20]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Platelet;
PubMed=18088087; DOI=10.1021/pr0704130;
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
Schuetz C., Walter U., Gambaryan S., Sickmann A.;
"Phosphoproteome of resting human platelets.";
J. Proteome Res. 7:526-534(2008).
[21]
INTERACTION WITH FCRL3.
PubMed=19843936; DOI=10.4049/jimmunol.0901982;
Kochi Y., Myouzen K., Yamada R., Suzuki A., Kurosaki T., Nakamura Y.,
Yamamoto K.;
"FCRL3, an autoimmune susceptibility gene, has inhibitory potential on
B-cell receptor-mediated signaling.";
J. Immunol. 183:5502-5510(2009).
[22]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-323, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
Mann M., Daub H.;
"Large-scale proteomics analysis of the human kinome.";
Mol. Cell. Proteomics 8:1751-1764(2009).
[23]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-28, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Leukemic T-cell;
PubMed=19690332; DOI=10.1126/scisignal.2000007;
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
Rodionov V., Han D.K.;
"Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions.";
Sci. Signal. 2:RA46-RA46(2009).
[24]
INTERACTION WITH CLEC1B.
PubMed=20154219; DOI=10.1182/blood-2009-08-237834;
Hughes C.E., Pollitt A.Y., Mori J., Eble J.A., Tomlinson M.G.,
Hartwig J.H., O'Callaghan C.A., Fuetterer K., Watson S.P.;
"CLEC-2 activates Syk through dimerization.";
Blood 115:2947-2955(2010).
[25]
INTERACTION WITH USP25, AND FUNCTION.
PubMed=19909739; DOI=10.1016/j.yexcr.2009.10.023;
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. 316:667-675(2010).
[26]
INTERACTION WITH FLNA.
PubMed=20713593; DOI=10.1084/jem.20100222;
Falet H., Pollitt A.Y., Begonja A.J., Weber S.E., Duerschmied D.,
Wagner D.D., Watson S.P., Hartwig J.H.;
"A novel interaction between FlnA and Syk regulates platelet ITAM-
mediated receptor signaling and function.";
J. Exp. Med. 207:1967-1979(2010).
[27]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[28]
PHOSPHORYLATION AT TYR-28; SER-44; TYR-47; TYR-131; SER-202; THR-256;
SER-295; TYR-296; SER-297; SER-316; THR-317; SER-319; TYR-323;
THR-345; TYR-348; SER-350; TYR-352; TYR-364; SER-379; THR-384;
TYR-484; TYR-507; TYR-525; TYR-526; THR-530; SER-579; THR-582;
TYR-629; TYR-630 AND TYR-631, INTERACTION WITH YWHAG, AND MUTAGENESIS
OF SER-297.
TISSUE=B-cell;
PubMed=21469132; DOI=10.1002/eji.201041326;
Bohnenberger H., Oellerich T., Engelke M., Hsiao H.H., Urlaub H.,
Wienands J.;
"Complex phosphorylation dynamics control the composition of the Syk
interactome in B cells.";
Eur. J. Immunol. 41:1550-1562(2011).
[29]
INTERACTION WITH TNS2.
PubMed=22019427; DOI=10.1016/j.bbamcr.2011.10.001;
Moon K.D., Zhang X., Zhou Q., Geahlen R.L.;
"The protein-tyrosine kinase Syk interacts with the C-terminal region
of tensin2.";
Biochim. Biophys. Acta 1823:199-205(2012).
[30]
INTERACTION WITH GCSAM.
PubMed=23299888; DOI=10.1038/ncomms2334;
Romero-Camarero I., Jiang X., Natkunam Y., Lu X., Vicente-Duenas C.,
Gonzalez-Herrero I., Flores T., Garcia J.L., McNamara G., Kunder C.,
Zhao S., Segura V., Fontan L., Martinez-Climent J.A.,
Garcia-Criado F.J., Theis J.D., Dogan A., Campos-Sanchez E.,
Green M.R., Alizadeh A.A., Cobaleda C., Sanchez-Garcia I.,
Lossos I.S.;
"Germinal centre protein HGAL promotes lymphoid hyperplasia and
amyloidosis via BCR-mediated Syk activation.";
Nat. Commun. 4:1338-1338(2013).
[31]
STRUCTURE BY NMR OF 163-265.
PubMed=8590001; DOI=10.1016/S0969-2126(01)00242-8;
Narula S.S., Yuan R.W., Adams S.E., Green O.M., Green J.,
Philips T.B., Zydowsky L.D., Botfield M.C., Hatada M., Laird E.R.,
Zoller M.J., Karas J.L., Dalgarno D.C.;
"Solution structure of the C-terminal SH2 domain of the human tyrosine
kinase Syk complexed with a phosphotyrosine pentapeptide.";
Structure 3:1061-1073(1995).
[32]
X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF SH2 DOMAINS IN COMPLEX WITH
CD3E PHOSPHORYLATED ITAM DOMAIN.
PubMed=9698567; DOI=10.1006/jmbi.1998.1964;
Fuetterer K., Wong J., Grucza R.A., Chan A.C., 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. 281:523-537(1998).
-!- FUNCTION: Non-receptor tyrosine kinase which mediates signal
transduction downstream of a variety of transmembrane receptors
including classical immunoreceptors like the B-cell receptor
(BCR). Regulates several biological processes including innate and
adaptive immunity, cell adhesion, osteoclast maturation, platelet
activation and vascular development. Assembles into signaling
complexes with activated receptors at the plasma membrane via
interaction between its SH2 domains and the receptor tyrosine-
phosphorylated ITAM domains. The association with the receptor can
also be indirect and mediated by adapter proteins containing ITAM
or partial hemITAM domains. The phosphorylation of the ITAM
domains is generally mediated by SRC subfamily kinases upon
engagement of the receptor. More rarely signal transduction via
SYK could be ITAM-independent. Direct downstream effectors
phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and
BLNK. Initially identified as essential in B-cell receptor (BCR)
signaling, it is necessary for the maturation of B-cells most
probably at the pro-B to pre-B transition. Activated upon BCR
engagement, it phosphorylates and activates BLNK an adapter
linking the activated BCR to downstream signaling adapters and
effectors. It also phosphorylates and activates PLCG1 and the PKC
signaling pathway. It also phosphorylates BTK and regulates its
activity in B-cell antigen receptor (BCR)-coupled signaling. In
addition to its function downstream of BCR plays also a role in T-
cell receptor signaling. Plays also a crucial role in the innate
immune response to fungal, bacterial and viral pathogens. It is
for instance activated by the membrane lectin CLEC7A. Upon
stimulation by fungal proteins, CLEC7A together with SYK activates
immune cells inducing the production of ROS. Also activates the
inflammasome and NF-kappa-B-mediated transcription of chemokines
and cytokines in presence of pathogens. Regulates neutrophil
degranulation and phagocytosis through activation of the MAPK
signaling cascade. Also mediates the activation of dendritic cells
by cell necrosis stimuli. Also involved in mast cells activation.
Also functions downstream of receptors mediating cell adhesion.
Relays for instance, integrin-mediated neutrophils and macrophages
activation and P-selectin receptor/SELPG-mediated recruitment of
leukocytes to inflammatory loci. Plays also a role in non-immune
processes. It is for instance involved in vascular development
where it may regulate blood and lymphatic vascular separation. It
is also required for osteoclast development and function.
Functions in the activation of platelets by collagen, mediating
PLCG2 phosphorylation and activation. May be coupled to the
collagen receptor by the ITAM domain-containing FCER1G. Also
activated by the membrane lectin CLEC1B that is required for
activation of platelets by PDPN/podoplanin. Involved in platelet
adhesion being activated by ITGB3 engaged by fibrinogen. Together
with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via
the NFKB pathway and may thus have a role in the intestinal immune
response (By similarity). {ECO:0000250|UniProtKB:P48025,
ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:12456653,
ECO:0000269|PubMed:15388330, ECO:0000269|PubMed:19909739,
ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:9535867}.
-!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
[protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE-
ProRule:PRU10028}.
-!- ENZYME REGULATION: Autoinhibited. Intramolecular binding of the
interdomains A and B (also called linker region) to parts of the
catalytic domain keep the catalytic center in an inactive
conformation. The phosphorylation of the interdomains or the
binding of the SH2 domains with dually phosphorylated ITAM domains
on transmembrane proteins disrupt those intramolecular
interactions allowing the kinase domain to adopt an active
conformation. The phosphorylation of SYK and of the ITAM domains
which is responsible for SYK activation is essentially mediated by
SRC subfamily kinases, like LYN, upon transmembrane receptors
engagement. May also be negatively regulated by PTPN6 through
dephosphorylation. Downstream signaling adapters and intermediates
like BLNK or RHOH may mediate positive and/or negative feedback
regulation. Negatively regulated by CBL and CBLB through
ubiquitination and probable degradation. Phosphorylates SH3BP2
which in turn may regulate SYK through LYN (By similarity).
{ECO:0000250}.
-!- SUBUNIT: Interacts with LYN; phosphorylates SYK (By similarity).
Interacts with RHOH (phosphorylated); regulates mast cells
activation (By similarity). Interacts with NFAM1 (phosphorylated);
probably involved in BCR signaling (By similarity). Interacts with
VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation.
Interacts with GAB2 (phosphorylated); probably involved in IgE Fc
receptor signaling (By similarity). Interacts (via its SH2
domains) with CD79A (via its phosphorylated ITAM domain); the
interaction stimulates SYK autophosphorylation and activation (By
similarity). Interacts with FCRL3 (PubMed:19843936,
PubMed:11162587). Interacts (via SH2 domains) with FCER1G (via
ITAM domain); activates SYK and mediates neutrophils and
macrophages integrin-mediated activation (By similarity).
Interacts with ITGB2 and FGR; involved in ITGB2 downstream
signaling (By similarity). Interacts with ITGB3; upon activation
by ITGB3 promotes platelet adhesion. Interacts (via SH2 domains)
with TYROBP (via ITAM domain); involved in neutrophils and
macrophages integrin-mediated activation (By similarity).
Interacts with MSN and SELPLG; mediates the selectin-dependent
activation of SYK by SELPLG. Interacts with BLNK (via SH2 domain).
Interacts (via the second SH2 domain) with USP25 (via C-terminus);
phosphorylates USP25 and regulates USP25 intracellular levels.
Interacts (via SH2 domains) with CLEC1B (dimer). Interacts with
CLEC7A; participates in leukocyte activation in presence of fungal
pathogens. Interacts (phosphorylated) with SLA; may regulate SYK
through CBL recruitment. Interacts with YWHAG; attenuates BCR-
induced membrane translocation and activation of SYK. Interacts
with Epstein-Barr virus LMP2A. Interacts (via SH2 domains) with
GCSAM; the interaction increases after B-cell receptor
stimulation, resulting in enhanced SYK autophosphorylation and
activity. Interacts with TNS2; leading to the phosphorylation of
SYK (PubMed:22019427). Interacts with FLNA (via filamin repeat 5);
docks SYK to the plasma membrane (PubMed:20713593). Interacts with
CEACAM1; lipopolysaccharide activated neutrophils induce
phosphorylation of SYK resulting in the formation of a complex
including TLR4 and the phosphorylated form of SYK and CEACAM1,
which in turn, recruits PTPN6 that dephosphorylates SYK, reducing
the production of reactive oxygen species (ROS) and lysosome
disruption, leading to a reduction of the inflammasome activity
(By similarity). Interacts (via SH2 domains) with CEACAM20
(phosphorylated form); the interaction further enhances CEACAM20
phosphorylation (By similarity). {ECO:0000250,
ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:10449770,
ECO:0000269|PubMed:11162587, ECO:0000269|PubMed:11940607,
ECO:0000269|PubMed:12387735, ECO:0000269|PubMed:18369315,
ECO:0000269|PubMed:19843936, ECO:0000269|PubMed:19909739,
ECO:0000269|PubMed:20154219, ECO:0000269|PubMed:20713593,
ECO:0000269|PubMed:21469132, ECO:0000269|PubMed:22019427,
ECO:0000269|PubMed:23299888, ECO:0000269|PubMed:7895172,
ECO:0000269|PubMed:8657103, ECO:0000269|PubMed:8986718,
ECO:0000269|PubMed:9535867, ECO:0000269|PubMed:9698567,
ECO:0000269|PubMed:9857068}.
-!- INTERACTION:
P22681:CBL; NbExp=2; IntAct=EBI-78302, EBI-518228;
P20273:CD22; NbExp=4; IntAct=EBI-78302, EBI-78277;
P11049:CD37; NbExp=3; IntAct=EBI-78302, EBI-6139068;
P07766:CD3E; NbExp=6; IntAct=EBI-78302, EBI-1211297;
P00533:EGFR; NbExp=6; IntAct=EBI-78302, EBI-297353;
P04626:ERBB2; NbExp=7; IntAct=EBI-78302, EBI-641062;
P21860:ERBB3; NbExp=6; IntAct=EBI-78302, EBI-720706;
Q96IP4:FAM46A; NbExp=3; IntAct=EBI-78302, EBI-954084;
P30273:FCER1G; NbExp=2; IntAct=EBI-78302, EBI-515289;
P36888:FLT3; NbExp=21; IntAct=EBI-78302, EBI-3946257;
Q13480:GAB1; NbExp=4; IntAct=EBI-78302, EBI-517684;
P06239:LCK; NbExp=7; IntAct=EBI-78302, EBI-1348;
P08581:MET; NbExp=3; IntAct=EBI-78302, EBI-1039152;
P19174:PLCG1; NbExp=4; IntAct=EBI-78302, EBI-79387;
Q9ULZ3:PYCARD; NbExp=4; IntAct=EBI-78302, EBI-751215;
Q9NP31:SH2D2A; NbExp=3; IntAct=EBI-78302, EBI-490630;
P40763:STAT3; NbExp=8; IntAct=EBI-78302, EBI-518675;
P54274:TERF1; NbExp=2; IntAct=EBI-78302, EBI-710997;
Q8TF42:UBASH3B; NbExp=2; IntAct=EBI-78302, EBI-1380492;
Q9UHP3:USP25; NbExp=6; IntAct=EBI-78302, EBI-2513462;
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}. Cytoplasm,
cytosol {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=Long;
IsoId=P43405-1; Sequence=Displayed;
Name=Short;
IsoId=P43405-2; Sequence=VSP_005010;
-!- TISSUE SPECIFICITY: Widely expressed in hematopoietic cells (at
protein level). Within the B-cells compartment it is for instance
expressed for pro-B-cells to plasma cells.
{ECO:0000269|PubMed:8163536}.
-!- DOMAIN: The SH2 domains mediate the interaction of SYK with the
phosphorylated ITAM domains of transmembrane proteins. Some
proteins like CLEC1B have a partial ITAM domain (also called
hemITAM) containing a single YxxL motif. The interaction with SYK
requires CLEC1B homodimerization.
-!- PTM: Ubiquitinated by CBLB after BCR activation; which promotes
proteasomal degradation. {ECO:0000250}.
-!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues by
LYN following receptors engagement. Phosphorylation on Tyr-323
creates a binding site for CBL, an adapter protein that serves as
a negative regulator of BCR-stimulated calcium ion signaling.
Phosphorylation at Tyr-348 creates a binding site for VAV1.
Phosphorylation on Tyr-348 and Tyr-352 enhances the
phosphorylation and activation of phospholipase C-gamma and the
early phase of calcium ion mobilization via a phosphoinositide 3-
kinase-independent pathway (By similarity). Phosphorylation on
Ser-297 is very common, it peaks 5 minutes after BCR stimulation,
and creates a binding site for YWHAG. Phosphorylation at Tyr-630
creates a binding site for BLNK. Dephosphorylated by PTPN6.
{ECO:0000250, ECO:0000269|PubMed:10458769,
ECO:0000269|PubMed:18369315, ECO:0000269|PubMed:21469132}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
kinase family. SYK/ZAP-70 subfamily. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/SYKID394.html";
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; Z29630; CAA82737.1; -; mRNA.
EMBL; L28824; AAA36526.1; -; mRNA.
EMBL; AL354862; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC001645; AAH01645.1; -; mRNA.
EMBL; BC011399; AAH11399.1; -; mRNA.
EMBL; BC002962; AAH02962.1; -; mRNA.
EMBL; X73568; CAA51970.1; -; mRNA.
CCDS; CCDS47992.1; -. [P43405-2]
CCDS; CCDS6688.1; -. [P43405-1]
PIR; A53596; A53596.
RefSeq; NP_001128524.1; NM_001135052.3. [P43405-2]
RefSeq; NP_001167638.1; NM_001174167.2. [P43405-1]
RefSeq; NP_001167639.1; NM_001174168.2. [P43405-2]
RefSeq; NP_003168.2; NM_003177.6. [P43405-1]
RefSeq; XP_005252204.1; XM_005252147.3. [P43405-1]
RefSeq; XP_011517248.1; XM_011518946.2. [P43405-1]
UniGene; Hs.371720; -.
PDB; 1A81; X-ray; 3.00 A; A/C/E/G/I/K=9-262.
PDB; 1CSY; NMR; -; A=163-265.
PDB; 1CSZ; NMR; -; A=163-265.
PDB; 1XBA; X-ray; 2.00 A; A=356-635.
PDB; 1XBB; X-ray; 1.57 A; A=356-635.
PDB; 1XBC; X-ray; 2.00 A; A=356-635.
PDB; 3BUW; X-ray; 1.45 A; A/C=317-329.
PDB; 3EMG; X-ray; 2.60 A; A=349-635.
PDB; 3FQE; X-ray; 2.50 A; A=356-635.
PDB; 3FQH; X-ray; 2.26 A; A/B=356-635.
PDB; 3FQS; X-ray; 2.10 A; A=356-635.
PDB; 3SRV; X-ray; 1.95 A; A/B=360-635.
PDB; 3TUB; X-ray; 2.23 A; A=343-635.
PDB; 3TUC; X-ray; 2.10 A; A=343-635.
PDB; 3TUD; X-ray; 2.33 A; A=343-635.
PDB; 3VF8; X-ray; 2.08 A; A=343-635.
PDB; 3VF9; X-ray; 2.30 A; A=343-635.
PDB; 4DFL; X-ray; 1.98 A; A=363-635.
PDB; 4DFN; X-ray; 2.48 A; A=363-635.
PDB; 4F4P; X-ray; 2.37 A; A=365-635.
PDB; 4FL1; X-ray; 1.79 A; A=356-635.
PDB; 4FL2; X-ray; 2.19 A; A=1-635.
PDB; 4FL3; X-ray; 1.90 A; A=1-635.
PDB; 4FYN; X-ray; 2.32 A; A=356-635.
PDB; 4FYO; X-ray; 1.40 A; A=356-635.
PDB; 4FZ6; X-ray; 1.85 A; A=356-635.
PDB; 4FZ7; X-ray; 1.75 A; A=356-635.
PDB; 4GFG; X-ray; 2.35 A; A=356-635.
PDB; 4I0R; X-ray; 2.10 A; A=356-635.
PDB; 4I0S; X-ray; 1.98 A; A=356-635.
PDB; 4I0T; X-ray; 1.70 A; A=356-635.
PDB; 4PUZ; X-ray; 2.08 A; A/B=356-635.
PDB; 4PV0; X-ray; 2.00 A; A=363-635.
PDB; 4PX6; X-ray; 1.60 A; A=356-635.
PDB; 4RSS; X-ray; 1.83 A; A=356-635.
PDB; 4RX7; X-ray; 1.80 A; A=356-635.
PDB; 4RX8; X-ray; 1.59 A; A=356-635.
PDB; 4RX9; X-ray; 1.75 A; A=356-635.
PDB; 4WNM; X-ray; 2.50 A; A=343-635.
PDB; 4XG2; X-ray; 2.21 A; A=356-635.
PDB; 4XG3; X-ray; 2.30 A; A/B=356-635.
PDB; 4XG4; X-ray; 2.30 A; A=356-635.
PDB; 4XG6; X-ray; 2.40 A; A=356-635.
PDB; 4XG7; X-ray; 1.76 A; A=356-635.
PDB; 4XG8; X-ray; 2.40 A; A/C=356-635.
PDB; 4XG9; X-ray; 2.91 A; A/B=356-635.
PDB; 4YJO; X-ray; 1.60 A; A=355-635.
PDB; 4YJP; X-ray; 1.83 A; A=355-635.
PDB; 4YJQ; X-ray; 1.34 A; A=355-635.
PDB; 4YJR; X-ray; 1.32 A; A=355-635.
PDB; 4YJS; X-ray; 2.22 A; A=355-635.
PDB; 4YJT; X-ray; 1.52 A; A=355-635.
PDB; 4YJU; X-ray; 1.67 A; A=355-635.
PDB; 4YJV; X-ray; 1.65 A; A=355-635.
PDB; 5C26; X-ray; 1.95 A; A=343-635.
PDB; 5C27; X-ray; 2.15 A; A=343-635.
PDB; 5CXH; X-ray; 1.90 A; A=356-635.
PDB; 5CXZ; X-ray; 1.70 A; A=356-635.
PDB; 5CY3; X-ray; 1.76 A; A=356-635.
PDB; 5GHV; X-ray; 2.80 A; A/B=356-635.
PDB; 5LMA; X-ray; 1.43 A; A=360-635.
PDB; 5LMB; X-ray; 1.95 A; A/B=360-635.
PDB; 5T68; X-ray; 2.93 A; A/B=356-635.
PDB; 5TIU; X-ray; 1.49 A; A=356-635.
PDB; 5TR6; X-ray; 1.93 A; A=356-635.
PDB; 5TT7; X-ray; 1.77 A; A=356-635.
PDBsum; 1A81; -.
PDBsum; 1CSY; -.
PDBsum; 1CSZ; -.
PDBsum; 1XBA; -.
PDBsum; 1XBB; -.
PDBsum; 1XBC; -.
PDBsum; 3BUW; -.
PDBsum; 3EMG; -.
PDBsum; 3FQE; -.
PDBsum; 3FQH; -.
PDBsum; 3FQS; -.
PDBsum; 3SRV; -.
PDBsum; 3TUB; -.
PDBsum; 3TUC; -.
PDBsum; 3TUD; -.
PDBsum; 3VF8; -.
PDBsum; 3VF9; -.
PDBsum; 4DFL; -.
PDBsum; 4DFN; -.
PDBsum; 4F4P; -.
PDBsum; 4FL1; -.
PDBsum; 4FL2; -.
PDBsum; 4FL3; -.
PDBsum; 4FYN; -.
PDBsum; 4FYO; -.
PDBsum; 4FZ6; -.
PDBsum; 4FZ7; -.
PDBsum; 4GFG; -.
PDBsum; 4I0R; -.
PDBsum; 4I0S; -.
PDBsum; 4I0T; -.
PDBsum; 4PUZ; -.
PDBsum; 4PV0; -.
PDBsum; 4PX6; -.
PDBsum; 4RSS; -.
PDBsum; 4RX7; -.
PDBsum; 4RX8; -.
PDBsum; 4RX9; -.
PDBsum; 4WNM; -.
PDBsum; 4XG2; -.
PDBsum; 4XG3; -.
PDBsum; 4XG4; -.
PDBsum; 4XG6; -.
PDBsum; 4XG7; -.
PDBsum; 4XG8; -.
PDBsum; 4XG9; -.
PDBsum; 4YJO; -.
PDBsum; 4YJP; -.
PDBsum; 4YJQ; -.
PDBsum; 4YJR; -.
PDBsum; 4YJS; -.
PDBsum; 4YJT; -.
PDBsum; 4YJU; -.
PDBsum; 4YJV; -.
PDBsum; 5C26; -.
PDBsum; 5C27; -.
PDBsum; 5CXH; -.
PDBsum; 5CXZ; -.
PDBsum; 5CY3; -.
PDBsum; 5GHV; -.
PDBsum; 5LMA; -.
PDBsum; 5LMB; -.
PDBsum; 5T68; -.
PDBsum; 5TIU; -.
PDBsum; 5TR6; -.
PDBsum; 5TT7; -.
ProteinModelPortal; P43405; -.
SMR; P43405; -.
BioGrid; 112717; 110.
CORUM; P43405; -.
DIP; DIP-253N; -.
ELM; P43405; -.
IntAct; P43405; 46.
MINT; MINT-148486; -.
STRING; 9606.ENSP00000364898; -.
BindingDB; P43405; -.
ChEMBL; CHEMBL2599; -.
DrugBank; DB08846; Ellagic Acid.
DrugBank; DB02010; Staurosporine.
GuidetoPHARMACOLOGY; 2230; -.
iPTMnet; P43405; -.
PhosphoSitePlus; P43405; -.
BioMuta; SYK; -.
DMDM; 1174527; -.
EPD; P43405; -.
MaxQB; P43405; -.
PaxDb; P43405; -.
PeptideAtlas; P43405; -.
PRIDE; P43405; -.
DNASU; 6850; -.
Ensembl; ENST00000375746; ENSP00000364898; ENSG00000165025. [P43405-1]
Ensembl; ENST00000375747; ENSP00000364899; ENSG00000165025. [P43405-2]
Ensembl; ENST00000375751; ENSP00000364904; ENSG00000165025. [P43405-2]
Ensembl; ENST00000375754; ENSP00000364907; ENSG00000165025. [P43405-1]
GeneID; 6850; -.
KEGG; hsa:6850; -.
UCSC; uc004aqz.4; human. [P43405-1]
CTD; 6850; -.
DisGeNET; 6850; -.
EuPathDB; HostDB:ENSG00000165025.14; -.
GeneCards; SYK; -.
HGNC; HGNC:11491; SYK.
HPA; CAB007773; -.
HPA; HPA001384; -.
MIM; 600085; gene.
neXtProt; NX_P43405; -.
OpenTargets; ENSG00000165025; -.
PharmGKB; PA36273; -.
eggNOG; ENOG410IH0T; Eukaryota.
eggNOG; COG0515; LUCA.
GeneTree; ENSGT00760000118799; -.
HOGENOM; HOG000113264; -.
HOVERGEN; HBG001540; -.
InParanoid; P43405; -.
KO; K05855; -.
OMA; KPFNRPP; -.
OrthoDB; EOG091G07KU; -.
PhylomeDB; P43405; -.
TreeFam; TF351629; -.
BRENDA; 2.7.10.2; 2681.
Reactome; R-HSA-114604; GPVI-mediated activation cascade.
Reactome; R-HSA-2029481; FCGR activation.
Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
Reactome; R-HSA-2029485; Role of phospholipids in phagocytosis.
Reactome; R-HSA-2424491; DAP12 signaling.
Reactome; R-HSA-2454202; Fc epsilon receptor (FCERI) signaling.
Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
Reactome; R-HSA-354192; Integrin alphaIIb beta3 signaling.
Reactome; R-HSA-451927; Interleukin-2 family signaling.
Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
Reactome; R-HSA-5621480; Dectin-2 family.
Reactome; R-HSA-912631; Regulation of signaling by CBL.
Reactome; R-HSA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
SignaLink; P43405; -.
SIGNOR; P43405; -.
ChiTaRS; SYK; human.
EvolutionaryTrace; P43405; -.
GeneWiki; Syk; -.
GenomeRNAi; 6850; -.
PRO; PR:P43405; -.
Proteomes; UP000005640; Chromosome 9.
Bgee; ENSG00000165025; -.
CleanEx; HS_SYK; -.
ExpressionAtlas; P43405; baseline and differential.
Genevisible; P43405; HS.
GO; GO:0019815; C:B cell receptor complex; IEA:Ensembl.
GO; GO:0005737; C:cytoplasm; IDA:MGI.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0005886; C:plasma membrane; TAS:Reactome.
GO; GO:0043234; C:protein complex; IDA:MGI.
GO; GO:0042101; C:T cell receptor complex; IDA:MGI.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
GO; GO:0019902; F:phosphatase binding; IEA:Ensembl.
GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA.
GO; GO:0004672; F:protein kinase activity; IDA:CACAO.
GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome.
GO; GO:0042169; F:SH2 domain binding; IEA:Ensembl.
GO; GO:0004716; F:signal transducer, downstream of receptor, with protein tyrosine kinase activity; IEA:Ensembl.
GO; GO:0035325; F:Toll-like receptor binding; IEA:Ensembl.
GO; GO:0007257; P:activation of JUN kinase activity; IEA:Ensembl.
GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB.
GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc.
GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB.
GO; GO:0043366; P:beta selection; IEA:Ensembl.
GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB.
GO; GO:0071226; P:cellular response to molecule of fungal origin; ISS:UniProtKB.
GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IEA:Ensembl.
GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
GO; GO:0002366; P:leukocyte activation involved in immune response; ISS:UniProtKB.
GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:UniProtKB.
GO; GO:0019370; P:leukotriene biosynthetic process; IEA:Ensembl.
GO; GO:0001945; P:lymph vessel development; ISS:UniProtKB.
GO; GO:0002281; P:macrophage activation involved in immune response; ISS:UniProtKB.
GO; GO:0002283; P:neutrophil activation involved in immune response; ISS:UniProtKB.
GO; GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IBA:GO_Central.
GO; GO:0030168; P:platelet activation; TAS:Reactome.
GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IEA:Ensembl.
GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IBA:GO_Central.
GO; GO:0045579; P:positive regulation of B cell differentiation; IMP:CACAO.
GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB.
GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Ensembl.
GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
GO; GO:0050715; P:positive regulation of cytokine secretion; IEA:Ensembl.
GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IEA:Ensembl.
GO; GO:0045425; P:positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process; IEA:Ensembl.
GO; GO:0045401; P:positive regulation of interleukin-3 biosynthetic process; IEA:Ensembl.
GO; GO:0043306; P:positive regulation of mast cell degranulation; IBA:GO_Central.
GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; IEA:Ensembl.
GO; GO:0002092; P:positive regulation of receptor internalization; IEA:Ensembl.
GO; GO:0032481; P:positive regulation of type I interferon production; IEA:Ensembl.
GO; GO:0006468; P:protein phosphorylation; IDA:CACAO.
GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
GO; GO:0090237; P:regulation of arachidonic acid secretion; ISS:UniProtKB.
GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
GO; GO:0043313; P:regulation of neutrophil degranulation; ISS:UniProtKB.
GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB.
GO; GO:0010543; P:regulation of platelet activation; ISS:UniProtKB.
GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
GO; GO:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; IMP:MGI.
GO; GO:0032928; P:regulation of superoxide anion generation; ISS:UniProtKB.
GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IMP:CACAO.
GO; GO:0002554; P:serotonin secretion by platelet; ISS:UniProtKB.
GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; TAS:Reactome.
GO; GO:0042991; P:transcription factor import into nucleus; IMP:MGI.
GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
CDD; cd09938; SH2_N-SH2_Zap70_Syk_like; 1.
Gene3D; 1.10.930.10; -; 1.
Gene3D; 3.30.505.10; -; 2.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR023420; Kinase_SYK/ZAP-70_inter-SH2_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR000980; SH2.
InterPro; IPR036860; SH2_dom_sf.
InterPro; IPR035838; SYK/ZAP-70_N_SH2.
InterPro; IPR008266; Tyr_kinase_AS.
InterPro; IPR020635; Tyr_kinase_cat_dom.
InterPro; IPR012234; Tyr_kinase_non-rcpt_SYK/ZAP70.
Pfam; PF07714; Pkinase_Tyr; 1.
Pfam; PF00017; SH2; 2.
PIRSF; PIRSF000604; TyrPK_SYK; 1.
PRINTS; PR00401; SH2DOMAIN.
PRINTS; PR00109; TYRKINASE.
SMART; SM00252; SH2; 2.
SMART; SM00219; TyrKc; 1.
SUPFAM; SSF55550; SSF55550; 2.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PROSITE; PS50001; SH2; 2.
1: Evidence at protein level;
3D-structure; Adaptive immunity; Alternative splicing; Angiogenesis;
ATP-binding; Cell membrane; Complete proteome; Cytoplasm;
Host-virus interaction; Immunity; Innate immunity; Kinase; Membrane;
Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome;
Repeat; SH2 domain; Transferase; Tyrosine-protein kinase;
Ubl conjugation.
CHAIN 1 635 Tyrosine-protein kinase SYK.
/FTId=PRO_0000088165.
DOMAIN 15 107 SH2 1. {ECO:0000255|PROSITE-
ProRule:PRU00191}.
DOMAIN 168 259 SH2 2. {ECO:0000255|PROSITE-
ProRule:PRU00191}.
DOMAIN 371 631 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 377 385 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
REGION 108 167 Interdomain A.
REGION 260 370 Interdomain B.
ACT_SITE 494 494 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10028}.
BINDING 402 402 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 28 28 Phosphotyrosine.
{ECO:0000244|PubMed:19690332,
ECO:0000269|PubMed:21469132}.
MOD_RES 44 44 Phosphoserine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 47 47 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 131 131 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 202 202 Phosphoserine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 256 256 Phosphothreonine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 295 295 Phosphoserine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 296 296 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 297 297 Phosphoserine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 316 316 Phosphoserine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 317 317 Phosphothreonine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 319 319 Phosphoserine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 323 323 Phosphotyrosine; by LYN.
{ECO:0000244|PubMed:19369195,
ECO:0000269|PubMed:21469132}.
MOD_RES 345 345 Phosphothreonine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 348 348 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 350 350 Phosphoserine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 352 352 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 364 364 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 379 379 Phosphoserine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 384 384 Phosphothreonine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 484 484 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 507 507 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 525 525 Phosphotyrosine; by autocatalysis.
{ECO:0000269|PubMed:21469132}.
MOD_RES 526 526 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 530 530 Phosphothreonine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 546 546 Phosphotyrosine.
{ECO:0000250|UniProtKB:P48025}.
MOD_RES 579 579 Phosphoserine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 582 582 Phosphothreonine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 629 629 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
MOD_RES 630 630 Phosphotyrosine.
{ECO:0000269|PubMed:18369315,
ECO:0000269|PubMed:21469132}.
MOD_RES 631 631 Phosphotyrosine.
{ECO:0000269|PubMed:21469132}.
VAR_SEQ 283 305 Missing (in isoform Short).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_005010.
VARIANT 45 45 R -> H (in dbSNP:rs16906862).
/FTId=VAR_033838.
MUTAGEN 297 297 S->A: Abolishes YWHAG binding.
{ECO:0000269|PubMed:21469132}.
MUTAGEN 630 630 Y->F: Loss of interaction with BLNK.
{ECO:0000269|PubMed:18369315}.
CONFLICT 119 119 P -> A (in Ref. 5; CAA51970).
{ECO:0000305}.
CONFLICT 250 250 G -> P (in Ref. 5; CAA51970).
{ECO:0000305}.
HELIX 22 31 {ECO:0000244|PDB:4FL3}.
STRAND 38 43 {ECO:0000244|PDB:4FL3}.
STRAND 47 49 {ECO:0000244|PDB:4FL3}.
STRAND 51 57 {ECO:0000244|PDB:4FL3}.
STRAND 60 68 {ECO:0000244|PDB:4FL3}.
STRAND 74 76 {ECO:0000244|PDB:4FL3}.
STRAND 82 84 {ECO:0000244|PDB:4FL3}.
HELIX 85 92 {ECO:0000244|PDB:4FL3}.
STRAND 99 101 {ECO:0000244|PDB:4FL3}.
HELIX 119 136 {ECO:0000244|PDB:4FL3}.
HELIX 140 158 {ECO:0000244|PDB:4FL3}.
HELIX 163 165 {ECO:0000244|PDB:4FL3}.
STRAND 169 172 {ECO:0000244|PDB:1A81}.
HELIX 175 183 {ECO:0000244|PDB:4FL3}.
STRAND 184 186 {ECO:0000244|PDB:4FL3}.
STRAND 187 189 {ECO:0000244|PDB:1CSY}.
STRAND 192 201 {ECO:0000244|PDB:4FL3}.
STRAND 203 209 {ECO:0000244|PDB:4FL3}.
STRAND 212 220 {ECO:0000244|PDB:4FL3}.
STRAND 221 224 {ECO:0000244|PDB:1CSY}.
STRAND 226 228 {ECO:0000244|PDB:4FL3}.
STRAND 229 231 {ECO:0000244|PDB:1CSY}.
STRAND 234 236 {ECO:0000244|PDB:4FL3}.
HELIX 237 244 {ECO:0000244|PDB:4FL3}.
STRAND 251 253 {ECO:0000244|PDB:4FL3}.
HELIX 342 344 {ECO:0000244|PDB:4FL3}.
HELIX 346 348 {ECO:0000244|PDB:4FL2}.
HELIX 351 353 {ECO:0000244|PDB:4FL2}.
HELIX 360 363 {ECO:0000244|PDB:5TT7}.
HELIX 367 369 {ECO:0000244|PDB:4YJR}.
STRAND 370 372 {ECO:0000244|PDB:4YJR}.
STRAND 377 380 {ECO:0000244|PDB:4YJT}.
STRAND 384 391 {ECO:0000244|PDB:4YJR}.
STRAND 393 409 {ECO:0000244|PDB:4YJR}.
HELIX 411 424 {ECO:0000244|PDB:4YJR}.
STRAND 435 449 {ECO:0000244|PDB:4YJR}.
HELIX 456 462 {ECO:0000244|PDB:4YJR}.
HELIX 468 487 {ECO:0000244|PDB:4YJR}.
HELIX 497 499 {ECO:0000244|PDB:4YJR}.
STRAND 500 504 {ECO:0000244|PDB:4YJR}.
STRAND 507 510 {ECO:0000244|PDB:4YJR}.
HELIX 513 515 {ECO:0000244|PDB:4RX7}.
STRAND 524 527 {ECO:0000244|PDB:4YJR}.
HELIX 536 538 {ECO:0000244|PDB:4YJR}.
HELIX 541 546 {ECO:0000244|PDB:4YJR}.
STRAND 548 550 {ECO:0000244|PDB:4YJR}.
HELIX 551 566 {ECO:0000244|PDB:4YJR}.
TURN 567 569 {ECO:0000244|PDB:4YJR}.
TURN 572 575 {ECO:0000244|PDB:4YJR}.
HELIX 578 586 {ECO:0000244|PDB:4YJR}.
STRAND 589 591 {ECO:0000244|PDB:3SRV}.
HELIX 599 608 {ECO:0000244|PDB:4YJR}.
HELIX 613 615 {ECO:0000244|PDB:4YJR}.
HELIX 619 624 {ECO:0000244|PDB:4YJR}.
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


Related products :

Catalog number Product name Quantity
EIAAB33008 CCK4,CCK-4,Colon carcinoma kinase 4,Homo sapiens,Human,Inactive tyrosine-protein kinase 7,Protein-tyrosine kinase 7,Pseudo tyrosine kinase receptor 7,PTK7,Tyrosine-protein kinase-like 7
E1915m ELISA kit Agammaglobulinaemia tyrosine kinase,ATK,B-cell progenitor kinase,BPK,Bpk,Bruton tyrosine kinase,Btk,Kinase EMB,Mouse,Mus musculus,Tyrosine-protein kinase BTK 96T
U1915m CLIA kit Agammaglobulinaemia tyrosine kinase,ATK,B-cell progenitor kinase,BPK,Bpk,Bruton tyrosine kinase,Btk,Kinase EMB,Mouse,Mus musculus,Tyrosine-protein kinase BTK 96T
U1915m CLIA Agammaglobulinaemia tyrosine kinase,ATK,B-cell progenitor kinase,BPK,Bpk,Bruton tyrosine kinase,Btk,Kinase EMB,Mouse,Mus musculus,Tyrosine-protein kinase BTK 96T
E1915m ELISA Agammaglobulinaemia tyrosine kinase,ATK,B-cell progenitor kinase,BPK,Bpk,Bruton tyrosine kinase,Btk,Kinase EMB,Mouse,Mus musculus,Tyrosine-protein kinase BTK 96T
EIAAB33010 Inactive tyrosine-protein kinase 7,Mouse,Mus musculus,Protein chuzhoi,Protein-tyrosine kinase 7,Pseudo tyrosine kinase receptor 7,Ptk7,Tyrosine-protein kinase-like 7
E1915h ELISA Agammaglobulinaemia tyrosine kinase,AGMX1,ATK,ATK,B-cell progenitor kinase,BPK,BPK,Bruton tyrosine kinase,BTK,Homo sapiens,Human,Tyrosine-protein kinase BTK 96T
U1915h CLIA kit Agammaglobulinaemia tyrosine kinase,AGMX1,ATK,ATK,B-cell progenitor kinase,BPK,BPK,Bruton tyrosine kinase,BTK,Homo sapiens,Human,Tyrosine-protein kinase BTK 96T
U1915h CLIA Agammaglobulinaemia tyrosine kinase,AGMX1,ATK,ATK,B-cell progenitor kinase,BPK,BPK,Bruton tyrosine kinase,BTK,Homo sapiens,Human,Tyrosine-protein kinase BTK 96T
E1915h ELISA kit Agammaglobulinaemia tyrosine kinase,AGMX1,ATK,ATK,B-cell progenitor kinase,BPK,BPK,Bruton tyrosine kinase,BTK,Homo sapiens,Human,Tyrosine-protein kinase BTK 96T
E1520m ELISA Mouse,Mus musculus,Spleen tyrosine kinase,Syk,Sykb,Tyrosine-protein kinase SYK 96T
E1520h ELISA Homo sapiens,Human,Spleen tyrosine kinase,SYK,Tyrosine-protein kinase SYK 96T
E1520m ELISA kit Mouse,Mus musculus,Spleen tyrosine kinase,Syk,Sykb,Tyrosine-protein kinase SYK 96T
U1520h CLIA Homo sapiens,Human,Spleen tyrosine kinase,SYK,Tyrosine-protein kinase SYK 96T
U1520m CLIA Mouse,Mus musculus,Spleen tyrosine kinase,Syk,Sykb,Tyrosine-protein kinase SYK 96T
E1520h ELISA kit Homo sapiens,Human,Spleen tyrosine kinase,SYK,Tyrosine-protein kinase SYK 96T
U1520r CLIA Rat,Rattus norvegicus,Spleen tyrosine kinase,Syk,Tyrosine-protein kinase SYK 96T
E1520r ELISA Rat,Rattus norvegicus,Spleen tyrosine kinase,Syk,Tyrosine-protein kinase SYK 96T
E1520r ELISA kit Rat,Rattus norvegicus,Spleen tyrosine kinase,Syk,Tyrosine-protein kinase SYK 96T
E1520p ELISA Pig,Spleen tyrosine kinase,Sus scrofa,SYK,Tyrosine-protein kinase SYK 96T
E1520p ELISA kit Pig,Spleen tyrosine kinase,Sus scrofa,SYK,Tyrosine-protein kinase SYK 96T
U1520p CLIA Pig,Spleen tyrosine kinase,Sus scrofa,SYK,Tyrosine-protein kinase SYK 96T
18-661-15209 Tyrosine-protein kinase BTK - EC 2.7.10.2; Bruton tyrosine kinase; Agammaglobulinaemia tyrosine kinase; ATK; B cell progenitor kinase; BPK Polyclonal 0.1 mg
EIAAB13100 EK6,ELK,ELK,EPH tyrosine kinase 2,EPHB1,EPH-like kinase 6,Ephrin type-B receptor 1,EPHT2,hEK6,HEK6,Homo sapiens,Human,NET,NET,Neuronally-expressed EPH-related tyrosine kinase,Tyrosine-protein kinase r
U2227h CLIA kit BMX,Bone marrow tyrosine kinase gene in chromosome X protein,Cytoplasmic tyrosine-protein kinase BMX,Epithelial and endothelial tyrosine kinase,ETK,Homo sapiens,Human,NTK38 96T


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur





GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017

BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG

france@gentaur.com | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur