KSYK_MOUSE
ID KSYK_MOUSE Reviewed; 629 AA.
AC P48025;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Tyrosine-protein kinase SYK;
DE EC=2.7.10.2;
DE AltName: Full=Spleen tyrosine kinase;
GN Name=Syk; Synonyms=ptk72, Sykb;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DISRUPTION PHENOTYPE.
RX PubMed=7477352; DOI=10.1038/378298a0;
RA Turner M., Mee P.J., Costello P.S., Williams O., Price A.A., Duddy L.P.,
RA Furlong M.T., Geahlen R.L., Tybulewicz V.L.;
RT "Perinatal lethality and blocked B-cell development in mice lacking the
RT tyrosine kinase Syk.";
RL Nature 378:298-302(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RX PubMed=7639745; DOI=10.1006/bbrc.1995.2126;
RA Flueck M., Zuercher G., Andres A., Ziemiecki A.;
RT "Molecular characterization of the murine syk protein tyrosine kinase cDNA,
RT transcripts and protein.";
RL Biochem. Biophys. Res. Commun. 213:273-281(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Richards J.D., Gold M.R., Hourihane S.L., Defranco A.L., Matsuuchi L.;
RL Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PHOSPHORYLATION BY LYN.
RX PubMed=7513017; DOI=10.1084/jem.179.5.1725;
RA Kurosaki T., Takata M., Yamanashi Y., Inazu T., Taniguchi T., Yamamoto T.,
RA Yamamura H.;
RT "Syk activation by the Src-family tyrosine kinase in the B cell receptor
RT signaling.";
RL J. Exp. Med. 179:1725-1729(1994).
RN [5]
RP INTERACTION WITH CD79A.
RX PubMed=7538118; DOI=10.1074/jbc.270.19.11590;
RA Rowley R.B., Burkhardt A.L., Chao H.-G., Matsueda G.R., Bolen J.B.;
RT "Syk protein-tyrosine kinase is regulated by tyrosine-phosphorylated Ig
RT alpha/Ig beta immunoreceptor tyrosine activation motif binding and
RT autophosphorylation.";
RL J. Biol. Chem. 270:11590-11594(1995).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=7477353; DOI=10.1038/378303a0;
RA Cheng A.M., Rowley B., Pao W., Hayday A., Bolen J.B., Pawson T.;
RT "Syk tyrosine kinase required for mouse viability and B-cell development.";
RL Nature 378:303-306(1995).
RN [7]
RP FUNCTION IN ACTIVATION OF PLATELETS BY COLLAGEN, AND FUNCTION IN PLCG2
RP PHOSPHORYLATION.
RX PubMed=9171347; DOI=10.1093/emboj/16.9.2333;
RA Poole A., Gibbins J.M., Turner M., van Vugt M.J., van de Winkel J.G.,
RA Saito T., Tybulewicz V.L., Watson S.P.;
RT "The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for
RT activation of mouse platelets by collagen.";
RL EMBO J. 16:2333-2341(1997).
RN [8]
RP FUNCTION IN INTEGRIN SIGNALING, PHOSPHORYLATION AT TYR-342; TYR-519 AND
RP TYR-520, AND INTERACTION WITH ITGB2 AND FGR.
RX PubMed=11672534; DOI=10.1016/s1074-7613(01)00221-7;
RA Vines C.M., Potter J.W., Xu Y., Geahlen R.L., Costello P.S.,
RA Tybulewicz V.L., Lowell C.A., Chang P.W., Gresham H.D., Willman C.L.;
RT "Inhibition of beta 2 integrin receptor and Syk kinase signaling in
RT monocytes by the Src family kinase Fgr.";
RL Immunity 15:507-519(2001).
RN [9]
RP PHOSPHORYLATION AT TYR-317; TYR-342 AND TYR-346.
RX PubMed=12077122; DOI=10.1074/jbc.m201362200;
RA Hong J.J., Yankee T.M., Harrison M.L., Geahlen R.L.;
RT "Regulation of signaling in B cells through the phosphorylation of Syk on
RT linker region tyrosines. A mechanism for negative signaling by the Lyn
RT tyrosine kinase.";
RL J. Biol. Chem. 277:31703-31714(2002).
RN [10]
RP FUNCTION IN INTEGRIN-MEDIATED PLATELET ADHESION.
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 [11]
RP UBIQUITINATION BY CBLB, AND ACTIVITY REGULATION.
RX PubMed=12771181; DOI=10.1084/jem.20021686;
RA Sohn H.W., Gu H., Pierce S.K.;
RT "Cbl-b negatively regulates B cell antigen receptor signaling in mature B
RT cells through ubiquitination of the tyrosine kinase Syk.";
RL J. Exp. Med. 197:1511-1524(2003).
RN [12]
RP FUNCTION IN VASCULAR DEVELOPMENT.
RX PubMed=12522250; DOI=10.1126/science.1079477;
RA Abtahian F., Guerriero A., Sebzda E., Lu M.M., Zhou R., Mocsai A.,
RA Myers E.E., Huang B., Jackson D.G., Ferrari V.A., Tybulewicz V.,
RA Lowell C.A., Lepore J.J., Koretzky G.A., Kahn M.L.;
RT "Regulation of blood and lymphatic vascular separation by signaling
RT proteins SLP-76 and Syk.";
RL Science 299:247-251(2003).
RN [13]
RP INTERACTION WITH NFAM1.
RX PubMed=15143214; DOI=10.1073/pnas.0401119101;
RA Ohtsuka M., Arase H., Takeuchi A., Yamasaki S., Shiina R., Suenaga T.,
RA Sakurai D., Yokosuka T., Arase N., Iwashima M., Kitamura T., Moriya H.,
RA Saito T.;
RT "NFAM1, an immunoreceptor tyrosine-based activation motif-bearing molecule
RT that regulates B cell development and signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8126-8131(2004).
RN [14]
RP FUNCTION IN ROS PRODUCTION, AND FUNCTION IN RESPONSE TO FUNGAL PATHOGEN.
RX PubMed=15956283; DOI=10.1182/blood-2005-03-1239;
RA Underhill D.M., Rossnagle E., Lowell C.A., Simmons R.M.;
RT "Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages
RT for reactive oxygen production.";
RL Blood 106:2543-2550(2005).
RN [15]
RP FUNCTION IN RESPONSE TO FUNGAL PATHOGEN, INTERACTION WITH CLEC7A, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15845454; DOI=10.1016/j.immuni.2005.03.004;
RA Rogers N.C., Slack E.C., Edwards A.D., Nolte M.A., Schulz O.,
RA Schweighoffer E., Williams D.L., Gordon S., Tybulewicz V.L., Brown G.D.,
RA Reis e Sousa C.;
RT "Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern
RT recognition pathway for C type lectins.";
RL Immunity 22:507-517(2005).
RN [16]
RP FUNCTION IN ACTIVATION OF PLATELETS BY CLEC1B.
RX PubMed=16174766; DOI=10.1182/blood-2005-05-1994;
RA Suzuki-Inoue K., Fuller G.L.J., Garcia A., Eble J.A., Poehlmann S.,
RA Inoue O., Gartner T.K., Hughan S.C., Pearce A.C., Laing G.D.,
RA Theakston R.D.G., Schweighoffer E., Zitzmann N., Morita T.,
RA Tybulewicz V.L.J., Ozaki Y., Watson S.P.;
RT "A novel Syk-dependent mechanism of platelet activation by the C-type
RT lectin receptor CLEC-2.";
RL Blood 107:542-549(2006).
RN [17]
RP INTERACTION WITH GAB2.
RX PubMed=16456001; DOI=10.4049/jimmunol.176.4.2421;
RA Yu M., Lowell C.A., Neel B.G., Gu H.;
RT "Scaffolding adapter Grb2-associated binder 2 requires Syk to transmit
RT signals from FcepsilonRI.";
RL J. Immunol. 176:2421-2429(2006).
RN [18]
RP FUNCTION IN INTEGRIN-MEDIATED NEUTROPHIL ACTIVATION, INTERACTION WITH
RP FCER1G AND TYROBP, AND MUTAGENESIS OF ARG-41 AND ARG-194.
RX PubMed=17086186; DOI=10.1038/ni1407;
RA Mocsai A., Abram C.L., Jakus Z., Hu Y., Lanier L.L., Lowell C.A.;
RT "Integrin signaling in neutrophils and macrophages uses adapters containing
RT immunoreceptor tyrosine-based activation motifs.";
RL Nat. Immunol. 7:1326-1333(2006).
RN [19]
RP FUNCTION IN OSTEOCLASTIC BONE RESORPTION.
RX PubMed=17353363; DOI=10.1083/jcb.200611083;
RA Zou W., Kitaura H., Reeve J., Long F., Tybulewicz V.L., Shattil S.J.,
RA Ginsberg M.H., Ross F.P., Teitelbaum S.L.;
RT "Syk, c-Src, the alphavbeta3 integrin, and ITAM immunoreceptors, in
RT concert, regulate osteoclastic bone resorption.";
RL J. Cell Biol. 176:877-888(2007).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310; SER-313; TYR-317;
RP TYR-342; TYR-346; TYR-519; TYR-520; TYR-540; TYR-623 AND TYR-624, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [21]
RP INTERACTION WITH BLNK.
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 [22]
RP FUNCTION IN RESPONSE TO BACTERIA.
RX PubMed=19797524; DOI=10.1182/blood-2009-05-220806;
RA Van Ziffle J.A., Lowell C.A.;
RT "Neutrophil-specific deletion of Syk kinase results in reduced host defense
RT to bacterial infection.";
RL Blood 114:4871-4882(2009).
RN [23]
RP FUNCTION IN MAST CELL ACTIVATION, INTERACTION WITH RHOH, AND ACTIVITY
RP REGULATION.
RX PubMed=19124738; DOI=10.4049/jimmunol.182.2.957;
RA Oda H., Fujimoto M., Patrick M.S., Chida D., Sato Y., Azuma Y., Aoki H.,
RA Abe T., Suzuki H., Shirai M.;
RT "RhoH plays critical roles in Fc epsilon RI-dependent signal transduction
RT in mast cells.";
RL J. Immunol. 182:957-962(2009).
RN [24]
RP FUNCTION IN RESPONSE TO FUNGAL PATHOGEN, FUNCTION IN INFLAMMASOME
RP ACTIVATION, AND FUNCTION IN REGULATION OF TRANSCRIPTION.
RX PubMed=19339971; DOI=10.1038/nature07965;
RA Gross O., Poeck H., Bscheider M., Dostert C., Hannesschlaeger N.,
RA Endres S., Hartmann G., Tardivel A., Schweighoffer E., Tybulewicz V.,
RA Mocsai A., Tschopp J., Ruland J.;
RT "Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal
RT host defence.";
RL Nature 459:433-436(2009).
RN [25]
RP FUNCTION IN IMMUNE SYSTEM STIMULATION BY CELL NECROSIS.
RX PubMed=19219027; DOI=10.1038/nature07750;
RA Sancho D., Joffre O.P., Keller A.M., Rogers N.C., Martinez D.,
RA Hernanz-Falcon P., Rosewell I., Reis e Sousa C.;
RT "Identification of a dendritic cell receptor that couples sensing of
RT necrosis to immunity.";
RL Nature 458:899-903(2009).
RN [26]
RP INTERACTION WITH FCER1G, AND FUNCTION.
RX PubMed=19098920; DOI=10.1038/ni.1686;
RA Hida S., Yamasaki S., Sakamoto Y., Takamoto M., Obata K., Takai T.,
RA Karasuyama H., Sugane K., Saito T., Taki S.;
RT "Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is
RT required for IL-3-induced IL-4 production in basophils.";
RL Nat. Immunol. 10:214-222(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-270, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [28]
RP INTERACTION WITH CEACAM1.
RX PubMed=22496641; DOI=10.1371/journal.ppat.1002597;
RA Lu R., Pan H., Shively J.E.;
RT "CEACAM1 negatively regulates IL-1beta production in LPS activated
RT neutrophils by recruiting SHP-1 to a SYK-TLR4-CEACAM1 complex.";
RL PLoS Pathog. 8:E1002597-E1002597(2012).
RN [29]
RP FUNCTION, AND INTERACTION WITH CEACAM20.
RX PubMed=26195794; DOI=10.1073/pnas.1510167112;
RA Murata Y., Kotani T., Supriatna Y., Kitamura Y., Imada S., Kawahara K.,
RA Nishio M., Daniwijaya E.W., Sadakata H., Kusakari S., Mori M., Kanazawa Y.,
RA Saito Y., Okawa K., Takeda-Morishita M., Okazawa H., Ohnishi H., Azuma T.,
RA Suzuki A., Matozaki T.;
RT "Protein tyrosine phosphatase SAP-1 protects against colitis through
RT regulation of CEACAM20 in the intestinal epithelium.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E4264-E4271(2015).
RN [30]
RP FUNCTION, AND MUTAGENESIS OF SER-544.
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).
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. Required for the stimulation of neutrophil phagocytosis by
CC IL15 (By similarity). Also mediates the activation of dendritic cells
CC by cell necrosis stimuli. Also involved in mast cells activation.
CC Involved in interleukin-3/IL3-mediated signaling pathway in basophils
CC (PubMed:19098920). Also functions downstream of receptors mediating
CC cell adhesion. Relays for instance, integrin-mediated neutrophils and
CC macrophages activation and P-selectin receptor/SELPG-mediated
CC recruitment of leukocytes to inflammatory loci. Also plays a role in
CC 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
CC (PubMed:26195794). {ECO:0000250|UniProtKB:P43405,
CC ECO:0000269|PubMed:11672534, ECO:0000269|PubMed:11940607,
CC ECO:0000269|PubMed:12522250, ECO:0000269|PubMed:15845454,
CC ECO:0000269|PubMed:15956283, ECO:0000269|PubMed:16174766,
CC ECO:0000269|PubMed:17086186, ECO:0000269|PubMed:17353363,
CC ECO:0000269|PubMed:19098920, ECO:0000269|PubMed:19124738,
CC ECO:0000269|PubMed:19219027, ECO:0000269|PubMed:19339971,
CC ECO:0000269|PubMed:19797524, ECO:0000269|PubMed:26195794,
CC ECO:0000269|PubMed:33782605, ECO:0000269|PubMed:9171347}.
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 -!- 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 (By similarity). Downstream signaling
CC adapters and intermediates like BLNK or RHOH may mediate positive
CC and/or negative feedback regulation. Negatively regulated by CBL and
CC CBLB through ubiquitination and probable degradation. Phosphorylates
CC SH3BP2 which in turn may regulate SYK through LYN (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with LYN; phosphorylates SYK. Interacts with RHOH
CC (phosphorylated); regulates mast cells activation. Interacts with NFAM1
CC (phosphorylated); probably involved in BCR signaling. Interacts with
CC VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation (By
CC similarity). Interacts with GAB2 (phosphorylated); probably involved in
CC IgE Fc receptor signaling. Interacts (via its SH2 domains) with CD79A
CC (via its phosphorylated ITAM domain); the interaction stimulates SYK
CC autophosphorylation and activation. Interacts (via SH2 domains) with
CC FCER1G (via ITAM domain); activates SYK and mediates neutrophils and
CC macrophages integrin-mediated activation. Interaction with FCER1G in
CC basophils triggers IL3-induced IL4 production (PubMed:19098920).
CC Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling.
CC Interacts with ITGB3; upon activation by ITGB3 promotes platelet
CC adhesion (By similarity). Interacts (via SH2 domains) with TYROBP (via
CC ITAM domain); involved in neutrophils and macrophages integrin-mediated
CC activation. Interacts with MSN and SELPLG; mediates the selectin-
CC dependent activation of SYK by SELPLG (By similarity). Interacts with
CC BLNK (via SH2 domain). Interacts (via the second SH2 domain) with USP25
CC (via C-terminus); phosphorylates USP25 and regulates USP25
CC intracellular levels (By similarity). Interacts (via SH2 domains) with
CC CLEC1B (dimer) (By similarity). Interacts with CLEC7A; participates in
CC leukocyte activation in presence of fungal pathogens. Interacts
CC (phosphorylated) with SLA; may regulate SYK through CBL recruitment (By
CC similarity). Interacts with YWHAG; attenuates BCR-induced membrane
CC translocation and activation of SYK (By similarity). Interacts (via SH2
CC domains) with GCSAM; the interaction increases after B-cell receptor
CC stimulation, resulting in enhanced SYK autophosphorylation and activity
CC (By similarity). Interacts with TNS2; leading to the phosphorylation of
CC SYK (By similarity). Interacts with FLNA (via filamin repeat 5); docks
CC SYK to the plasma membrane (By similarity). Interacts with CEACAM1;
CC lipopolysaccharide activated neutrophils induce phosphorylation of SYK
CC resulting in the formation of a complex including TLR4 and the
CC phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6
CC that dephosphorylates SYK, reducing the production of reactive oxygen
CC species (ROS) and lysosome disruption, leading to a reduction of the
CC inflammasome activity (PubMed:22496641). Interacts (via SH2 domains)
CC with CEACAM20 (phosphorylated form); the interaction further enhances
CC CEACAM20 phosphorylation (PubMed:26195794). Interacts with IL15RA (By
CC similarity). {ECO:0000250|UniProtKB:P43405,
CC ECO:0000269|PubMed:19098920, ECO:0000269|PubMed:22496641,
CC ECO:0000269|PubMed:26195794}.
CC -!- INTERACTION:
CC P48025; Q64693: Pou2af1; NbExp=2; IntAct=EBI-300116, EBI-943530;
CC P48025; P42227: Stat3; NbExp=5; IntAct=EBI-300116, EBI-602878;
CC P48025; P08487: PLCG1; Xeno; NbExp=4; IntAct=EBI-300116, EBI-8013886;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:15845454}.
CC Cytoplasm, cytosol {ECO:0000305|PubMed:15845454}. Cytoplasmic vesicle,
CC phagosome {ECO:0000269|PubMed:15845454}.
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 (By similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues by LYN
CC following receptors engagement. Phosphorylation on Tyr-317 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-342 creates a binding site for VAV1 (By similarity).
CC Phosphorylation on Tyr-342 and Tyr-346 enhances the phosphorylation and
CC activation of phospholipase C-gamma and the early phase of calcium ion
CC mobilization via a phosphoinositide 3-kinase-independent pathway (By
CC similarity). Phosphorylated on tyrosine residues in response to IL15
CC (By similarity). Phosphorylation on Ser-291 is very common, it peaks 5
CC minutes after BCR stimulation, and creates a binding site for YWHAG (By
CC similarity). Phosphorylation at Tyr-624 creates a binding site for BLNK
CC (By similarity). Dephosphorylated by PTPN6 (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P43405}.
CC -!- PTM: Ubiquitinated by CBLB after BCR activation; which promotes
CC proteasomal degradation. {ECO:0000269|PubMed:12771181}.
CC -!- DISRUPTION PHENOTYPE: Embryos display severe systemic hemorrhage and
CC mice are not viable dying perinatally. While T-cells development is not
CC affected, the development of B-cells is impaired most probably at the
CC pro-B to pre-B transition and mice lack mature B-cells.
CC {ECO:0000269|PubMed:7477352, ECO:0000269|PubMed:7477353}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SYK/ZAP-70 subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; U25685; AAA87462.1; -; mRNA.
DR EMBL; Z49877; CAA90034.1; -; mRNA.
DR EMBL; U36776; AAA79996.1; -; mRNA.
DR CCDS; CCDS26517.1; -.
DR PIR; I48781; I48781.
DR RefSeq; NP_001185906.1; NM_001198977.1.
DR RefSeq; NP_035648.2; NM_011518.2.
DR RefSeq; XP_006516958.1; XM_006516895.3.
DR PDB; 2LCT; NMR; -; B=338-350.
DR PDB; 2MC1; NMR; -; B=338-350.
DR PDBsum; 2LCT; -.
DR PDBsum; 2MC1; -.
DR AlphaFoldDB; P48025; -.
DR BMRB; P48025; -.
DR SMR; P48025; -.
DR BioGRID; 203599; 18.
DR DIP; DIP-32621N; -.
DR IntAct; P48025; 13.
DR MINT; P48025; -.
DR STRING; 10090.ENSMUSP00000113852; -.
DR iPTMnet; P48025; -.
DR PhosphoSitePlus; P48025; -.
DR jPOST; P48025; -.
DR PaxDb; P48025; -.
DR PeptideAtlas; P48025; -.
DR PRIDE; P48025; -.
DR ProteomicsDB; 263570; -.
DR Antibodypedia; 733; 1589 antibodies from 51 providers.
DR DNASU; 20963; -.
DR Ensembl; ENSMUST00000055087; ENSMUSP00000060828; ENSMUSG00000021457.
DR Ensembl; ENSMUST00000120135; ENSMUSP00000113852; ENSMUSG00000021457.
DR GeneID; 20963; -.
DR KEGG; mmu:20963; -.
DR UCSC; uc007qmz.1; mouse.
DR CTD; 6850; -.
DR MGI; MGI:99515; Syk.
DR VEuPathDB; HostDB:ENSMUSG00000021457; -.
DR eggNOG; ENOG502QT06; Eukaryota.
DR GeneTree; ENSGT00940000159053; -.
DR InParanoid; P48025; -.
DR OMA; RPEVCPT; -.
DR OrthoDB; 796831at2759; -.
DR PhylomeDB; P48025; -.
DR TreeFam; TF351629; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-114604; GPVI-mediated activation cascade.
DR Reactome; R-MMU-2029481; FCGR activation.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-2454202; Fc epsilon receptor (FCERI) signaling.
DR Reactome; R-MMU-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-MMU-354192; Integrin signaling.
DR Reactome; R-MMU-5621480; Dectin-2 family.
DR Reactome; R-MMU-9020558; Interleukin-2 signaling.
DR Reactome; R-MMU-912631; Regulation of signaling by CBL.
DR Reactome; R-MMU-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-MMU-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-MMU-9706374; FLT3 signaling through SRC family kinases.
DR Reactome; R-MMU-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR BioGRID-ORCS; 20963; 8 hits in 74 CRISPR screens.
DR ChiTaRS; Syk; mouse.
DR PRO; PR:P48025; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P48025; protein.
DR Bgee; ENSMUSG00000021457; Expressed in granulocyte and 171 other tissues.
DR ExpressionAtlas; P48025; baseline and differential.
DR Genevisible; P48025; MM.
DR GO; GO:0019815; C:B cell receptor complex; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032009; C:early phagosome; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0042101; C:T cell receptor complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0005178; F:integrin binding; ISO:MGI.
DR GO; GO:0016170; F:interleukin-15 receptor binding; ISO:MGI.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:0043274; F:phospholipase binding; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0042169; F:SH2 domain binding; IDA:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0035325; F:Toll-like receptor binding; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030183; P:B cell differentiation; IMP:MGI.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IDA:MGI.
DR GO; GO:0043366; P:beta selection; IGI:MGI.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:MGI.
DR GO; GO:0001775; P:cell activation; IMP:ARUK-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:1990858; P:cellular response to lectin; IMP:ARUK-UCL.
DR GO; GO:0071396; P:cellular response to lipid; ISO:MGI.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; IDA:UniProtKB.
DR GO; GO:0071226; P:cellular response to molecule of fungal origin; IMP:UniProtKB.
DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; IMP:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; IDA:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:MGI.
DR GO; GO:0042492; P:gamma-delta T cell differentiation; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0038156; P:interleukin-3-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:0002366; P:leukocyte activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0019370; P:leukotriene biosynthetic process; IMP:MGI.
DR GO; GO:0001945; P:lymph vessel development; IMP:UniProtKB.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0043303; P:mast cell degranulation; IMP:MGI.
DR GO; GO:0002283; P:neutrophil activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IGI:MGI.
DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IGI:MGI.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; IMP:MGI.
DR GO; GO:0045780; P:positive regulation of bone resorption; IMP:UniProtKB.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IMP:MGI.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; IGI:MGI.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IMP:MGI.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IMP:MGI.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:MGI.
DR GO; GO:0032752; P:positive regulation of interleukin-3 production; IMP:MGI.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IMP:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IMP:MGI.
DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:MGI.
DR GO; GO:0032765; P:positive regulation of mast cell cytokine production; IMP:MGI.
DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IMP:MGI.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; ISO:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IMP:CACAO.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISO:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IMP:CACAO.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006606; P:protein import into nucleus; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0031623; P:receptor internalization; IDA:UniProtKB.
DR GO; GO:0090237; P:regulation of arachidonic acid secretion; IMP:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0050776; P:regulation of immune response; ISO:MGI.
DR GO; GO:0043313; P:regulation of neutrophil degranulation; IMP:UniProtKB.
DR GO; GO:0050764; P:regulation of phagocytosis; IMP:UniProtKB.
DR GO; GO:0010543; P:regulation of platelet activation; IMP:UniProtKB.
DR GO; GO:0090330; P:regulation of platelet aggregation; IMP:UniProtKB.
DR GO; GO:0032928; P:regulation of superoxide anion generation; IMP:UniProtKB.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR GO; GO:0001820; P:serotonin secretion; IMP:MGI.
DR GO; GO:0002554; P:serotonin secretion by platelet; IMP:UniProtKB.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; IMP: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 IDEAL; IID50282; -.
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; Angiogenesis; ATP-binding; Cell membrane;
KW Cytoplasm; Cytoplasmic vesicle; Immunity; Innate immunity; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW SH2 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..629
FT /note="Tyrosine-protein kinase SYK"
FT /id="PRO_0000088166"
FT DOMAIN 14..106
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 167..258
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 365..625
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 107..166
FT /note="Interdomain A"
FT REGION 259..364
FT /note="Interdomain B"
FT REGION 293..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 488
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 371..379
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 396
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 27
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 46
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 130
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 201
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 255
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 270
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 289
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 290
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 311
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 317
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000269|PubMed:12077122,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 339
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 342
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11672534,
FT ECO:0000269|PubMed:12077122, ECO:0007744|PubMed:17947660"
FT MOD_RES 344
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 346
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12077122,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 358
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 378
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 478
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 501
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 519
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11672534,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 520
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11672534,
FT ECO:0007744|PubMed:17947660"
FT MOD_RES 524
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 540
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 573
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 576
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 623
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 624
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 625
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MUTAGEN 41
FT /note="R->A: Loss of interaction with FCER1G and TYROBP;
FT when associated with A-194."
FT /evidence="ECO:0000269|PubMed:17086186"
FT MUTAGEN 194
FT /note="R->A: Loss of interaction with FCER1G and TYROBP;
FT when associated with A-41."
FT /evidence="ECO:0000269|PubMed:17086186"
FT MUTAGEN 544
FT /note="S->Y: Constitutively active protein tyrosine kinase
FT activity. Causes an immune dysregulation disorder.
FT Treatment with SYK-specific inhibitor ameliorates the
FT disease phenotype."
FT /evidence="ECO:0000269|PubMed:33782605"
FT CONFLICT 326
FT /note="Missing (in Ref. 2; CAA90034)"
FT /evidence="ECO:0000305"
FT CONFLICT 446..447
FT /note="EL -> DV (in Ref. 2; CAA90034)"
FT /evidence="ECO:0000305"
FT STRAND 346..348
FT /evidence="ECO:0007829|PDB:2LCT"
SQ SEQUENCE 629 AA; 71376 MW; 2F98D21601F8224E CRC64;
MAGSAVDSAN HLTYFFGNIT REEAEDYLVQ GGMTDGLYLL RQSRNYLGGF ALSVAHNRKA
HHYTIERELN GTYAISGGRA HASPADLCHY HSQEPDGLIC LLKKPFNRPP GVQPKTGPFE
DLKENLIREY VKQTWNLQGQ ALEQAIISQK PQLEKLIATT AHEKMPWFHG NISRDESEQT
VLIGSKTNGK FLIRARDNSG SYALCLLHEG KVLHYRIDRD KTGKLSIPEG KKFDTLWQLV
EHYSYKPDGL LRVLTVPCQK IGAQMGHPGS PNAHPVTWSP GGIISRIKSY SFPKPGHKKP
APPQGSRPES TVSFNPYEPT GGPWGPDRGL QREALPMDTE VYESPYADPE EIRPKEVYLD
RSLLTLEDNE LGSGNFGTVK KGYYQMKKVV KTVAVKILKN EANDPALKDE LLAEANVMQQ
LDNPYIVRMI GICEAESWML VMEMAELGPL NKYLQQNRHI KDKNIIELVH QVSMGMKYLE
ESNFVHRDLA ARNVLLVTQH YAKISDFGLS KALRADENYY KAQTHGKWPV KWYAPECINY
YKFSSKSDVW SFGVLMWEAF SYGQKPYRGM KGSEVTAMLE KGERMGCPAG CPREMYDLMN
LCWTYDVENR PGFTAVELRL RNYYYDVVN
