KSYK_RAT
ID KSYK_RAT Reviewed; 629 AA.
AC Q64725;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Tyrosine-protein kinase SYK;
DE EC=2.7.10.2;
DE AltName: Full=Spleen tyrosine kinase;
DE AltName: Full=p72Syk;
GN Name=Syk;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING (ISOFORMS SYKA AND
RP SYKB).
RX PubMed=7759516; DOI=10.1074/jbc.270.21.12659;
RA Rowley R.B., Bolen J.B., Fargnoli J.;
RT "Molecular cloning of rodent p72Syk. Evidence of alternative mRNA
RT splicing.";
RL J. Biol. Chem. 270:12659-12664(1995).
RN [2]
RP FUNCTION IN PHOSPHORYLATION OF HCLS1.
RX PubMed=8611520; DOI=10.1021/bi9528614;
RA Ruzzene M., Brunati A.M., Marin O., Donella-Deana A., Pinna L.A.;
RT "SH2 domains mediate the sequential phosphorylation of HS1 protein by
RT p72syk and Src-related protein tyrosine kinases.";
RL Biochemistry 35:5327-5332(1996).
RN [3]
RP PHOSPHORYLATION AT TYR-317 BY LYN, AND PHOSPHORYLATION AT TYR-342 AND
RP 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).
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. Assembles into signaling complexes with activated
CC receptors at the plasma membrane via interaction between its SH2
CC domains and the receptor tyrosine-phosphorylated ITAM domains. The
CC association with the receptor can also be indirect and mediated by
CC adapter proteins containing ITAM or partial hemITAM domains. The
CC phosphorylation of the ITAM domains is generally mediated by SRC
CC subfamily kinases upon engagement of the receptor. More rarely signal
CC transduction via SYK could be ITAM-independent. Direct downstream
CC effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2
CC and BLNK. Initially identified as essential in B-cell receptor (BCR)
CC signaling, it is necessary for the maturation of B-cells most probably
CC at the pro-B to pre-B transition. Activated upon BCR engagement, it
CC phosphorylates and activates BLNK an adapter linking the activated BCR
CC to downstream signaling adapters and effectors. It also phosphorylates
CC and activates PLCG1 and the PKC signaling pathway. It also
CC 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 (By similarity). Also functions downstream of receptors mediating cell
CC 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 (By similarity).
CC {ECO:0000250|UniProtKB:P43405, ECO:0000250|UniProtKB:P48025,
CC ECO:0000269|PubMed:8611520}.
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. 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 (By similarity). 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.
CC Interacts with GAB2 (phosphorylated); probably involved in IgE Fc
CC receptor signaling. Interacts (via its SH2 domains) with CD79A (via its
CC 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 (By similarity).
CC Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling.
CC Interacts with ITGB3; upon activation by ITGB3 promotes platelet
CC adhesion. Interacts (via SH2 domains) with TYROBP (via ITAM domain);
CC involved in neutrophils and macrophages integrin-mediated activation.
CC Interacts with MSN and SELPLG; mediates the selectin-dependent
CC activation of SYK by SELPLG. Interacts with BLNK (via SH2 domain).
CC Interacts (via the second SH2 domain) with USP25 (via C-terminus);
CC phosphorylates USP25 and regulates USP25 intracellular levels.
CC Interacts (via SH2 domains) with CLEC1B (dimer). Interacts with CLEC7A;
CC participates in leukocyte activation in presence of fungal pathogens.
CC Interacts (phosphorylated) with SLA; may regulate SYK through CBL
CC recruitment. 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, phosphorylated
CC form of SYK and CEACAM1, which in turn, recruits PTPN6 that
CC dephosphorylates SYK, reducing the production of reactive oxygen
CC species (ROS) and lysosome disruption, leading to a reduction of the
CC inflammasome activity (By similarity). Interacts (via SH2 domains) with
CC CEACAM20 (phosphorylated form); the interaction further enhances
CC CEACAM20 phosphorylation (By similarity). Interacts with IL15RA (By
CC similarity). {ECO:0000250|UniProtKB:P43405,
CC ECO:0000250|UniProtKB:P48025}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}. Cytoplasm, cytosol
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=SykB;
CC IsoId=Q64725-1; Sequence=Displayed;
CC Name=SykA;
CC IsoId=Q64725-2; Sequence=VSP_005011;
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 (By similarity).
CC Phosphorylation at Tyr-342 creates a binding site for VAV1 (By
CC similarity). Phosphorylation on Tyr-342 and Tyr-346 enhances the
CC phosphorylation and activation of phospholipase C-gamma and the early
CC phase of calcium ion mobilization via a phosphoinositide 3-kinase-
CC independent pathway (By similarity). Phosphorylated on tyrosine
CC residues in response to IL15 (By similarity). Phosphorylation on Ser-
CC 291 is very common, it peaks 5 minutes after BCR stimulation, and
CC creates a binding site for YWHAG (By similarity). Phosphorylation at
CC Tyr-624 creates a binding site for BLNK (By similarity).
CC Dephosphorylated by PTPN6 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P43405}.
CC -!- PTM: Ubiquitinated by CBLB after BCR activation; which promotes
CC proteasomal degradation. {ECO:0000250}.
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; U21684; AAA75167.1; -; mRNA.
DR EMBL; U21683; AAA75166.1; -; mRNA.
DR RefSeq; NP_036890.1; NM_012758.1. [Q64725-1]
DR AlphaFoldDB; Q64725; -.
DR SMR; Q64725; -.
DR BioGRID; 247220; 2.
DR IntAct; Q64725; 16.
DR STRING; 10116.ENSRNOP00000016942; -.
DR BindingDB; Q64725; -.
DR ChEMBL; CHEMBL4364; -.
DR iPTMnet; Q64725; -.
DR PhosphoSitePlus; Q64725; -.
DR PaxDb; Q64725; -.
DR PRIDE; Q64725; -.
DR GeneID; 25155; -.
DR KEGG; rno:25155; -.
DR CTD; 6850; -.
DR RGD; 3796; Syk.
DR eggNOG; ENOG502QT06; Eukaryota.
DR InParanoid; Q64725; -.
DR OrthoDB; 796831at2759; -.
DR PhylomeDB; Q64725; -.
DR BRENDA; 2.7.10.2; 5301.
DR Reactome; R-RNO-114604; GPVI-mediated activation cascade.
DR Reactome; R-RNO-2029481; FCGR activation.
DR Reactome; R-RNO-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-RNO-2424491; DAP12 signaling.
DR Reactome; R-RNO-2454202; Fc epsilon receptor (FCERI) signaling.
DR Reactome; R-RNO-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation.
DR Reactome; R-RNO-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-RNO-354192; Integrin signaling.
DR Reactome; R-RNO-5621480; Dectin-2 family.
DR Reactome; R-RNO-9020558; Interleukin-2 signaling.
DR Reactome; R-RNO-912631; Regulation of signaling by CBL.
DR Reactome; R-RNO-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-RNO-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-RNO-9706374; FLT3 signaling through SRC family kinases.
DR Reactome; R-RNO-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
DR PRO; PR:Q64725; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0019815; C:B cell receptor complex; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0042101; C:T cell receptor complex; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; ISO:RGD.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0016170; F:interleukin-15 receptor binding; ISO:RGD.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; ISO:RGD.
DR GO; GO:0043274; F:phospholipase binding; ISO:RGD.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IDA:RGD.
DR GO; GO:0004672; F:protein kinase activity; IDA:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0035325; F:Toll-like receptor binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD.
DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0043366; P:beta selection; ISO:RGD.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
DR GO; GO:0001775; P:cell activation; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD.
DR GO; GO:1990858; P:cellular response to lectin; ISO:RGD.
DR GO; GO:0071396; P:cellular response to lipid; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0002366; P:leukocyte activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0019370; P:leukotriene biosynthetic process; ISO:RGD.
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:0002283; P:neutrophil activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; ISO:RGD.
DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; ISO:RGD.
DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISO:RGD.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:RGD.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; ISO:RGD.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:RGD.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:RGD.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:RGD.
DR GO; GO:0032752; P:positive regulation of interleukin-3 production; ISO:RGD.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:RGD.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IMP:RGD.
DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; ISO:RGD.
DR GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; ISO:RGD.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:RGD.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:RGD.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0050776; P:regulation of immune response; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0001820; P:serotonin secretion; ISO:RGD.
DR GO; GO:0002554; P:serotonin secretion by platelet; ISS:UniProtKB.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; ISO:RGD.
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 Adaptive immunity; Alternative splicing; Angiogenesis; ATP-binding;
KW Cell membrane; Cytoplasm; Immunity; Innate immunity; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; SH2 domain;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..629
FT /note="Tyrosine-protein kinase SYK"
FT /id="PRO_0000088167"
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 /evidence="ECO:0000250"
FT REGION 259..364
FT /note="Interdomain B"
FT /evidence="ECO:0000250"
FT REGION 289..330
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:0000250|UniProtKB:P48025"
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:0000250|UniProtKB:P43405"
FT MOD_RES 311
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 317
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000269|PubMed:12077122"
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:12077122"
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 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:0000250|UniProtKB:P43405"
FT MOD_RES 520
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 524
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 540
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P48025"
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:0000250|UniProtKB:P43405"
FT MOD_RES 624
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 625
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT VAR_SEQ 277..299
FT /note="Missing (in isoform SykA)"
FT /evidence="ECO:0000305"
FT /id="VSP_005011"
SQ SEQUENCE 629 AA; 71529 MW; 81169A643EC6A6FE CRC64;
MAGNAVDNAN HLTYFFGNIT REEAEDYLVQ GGMTDGLYLL RQSRNYLGGF ALSVAHNRKA
HHYTIERELN GTYAISGGRA HASPADLCHY HSQEPEGLVC LLKKPFNRPP GVQPKTGPFE
DLKENLIREY VKQTWNLQGQ ALEQAIISQK PQLEKLIATT AHEKMPWFHG NISRDESEQT
VLIGSKTNGK FLIRARDNNG SFALCLLHEG KVLHYRIDRD KTGKLSIPEG KKFDTLWQLV
EHYSYKPDGL LRVLTVPCQK IGVQMGHPGS SNAHPVTWSP GGIISRIKSY SFPKPGHKKP
PPPQGSRPES TVSFNPYEPT GGAWGPDRGL QREALPMDTE VYESPYADPE EIRPKEVYLD
RKLLTLEDNE LGSGNFGTVK KGYYQMKKVV KTVAVKILKN EANDPALKDE LLAEANVMQQ
LDNPYIVRMI GICEAESWML VMEMAAWGPL NKYLQQNRHI KDKNIIELVH QVSMGMKYLE
ESNFVHRDLA ARNVLLVTQH YAKISDFGLS KALRADENYY KAQTHGKWPV KWYAPECINY
FKFSSKSDVW SFGVLMWEAF SYGQKPYRGM KGSEVTAMLE KGERMGCPPG CPREMYDLMF
LCWTYDVENR PGFAAVELRL RNYYYDVVN
