KSYK_PIG
ID KSYK_PIG Reviewed; 628 AA.
AC Q00655;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Tyrosine-protein kinase SYK;
DE EC=2.7.10.2;
DE AltName: Full=Spleen tyrosine kinase;
DE Contains:
DE RecName: Full=72 kDa tyrosine-protein kinase SYK;
DE Contains:
DE RecName: Full=40 kDa tyrosine-protein kinase SYK;
GN Name=SYK;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 313-333; 346-354 AND
RP 369-379.
RC TISSUE=Spleen;
RX PubMed=1874735; DOI=10.1016/s0021-9258(18)98478-4;
RA Taniguchi T., Kobayashi T., Kondo J., Takahashi K., Nakamura H., Suzuki J.,
RA Nagai K., Yamada T., Nakamura S., Yamamura H.;
RT "Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-
RT tyrosine kinase showing high susceptibility to proteolysis.";
RL J. Biol. Chem. 266:15790-15796(1991).
RN [2]
RP PHOSPHORYLATION BY LYN, INTERACTION WITH LYN, AND AUTOPHOSPHORYLATION.
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 [3]
RP FUNCTION IN TRANSCRIPTION REGULATION, INTERACTION WITH VAV1, MUTAGENESIS OF
RP TYR-341 AND TYR-345, AND PHOSPHORYLATION AT TYR-341.
RX PubMed=8986718; DOI=10.1016/s1074-7613(00)80273-3;
RA Deckert M., Tartare-Deckert S., Couture C., Mustelin T., Altman A.;
RT "Functional and physical interactions of Syk family kinases with the Vav
RT proto-oncogene product.";
RL Immunity 5:591-604(1996).
RN [4]
RP FUNCTION IN PHOSPHORYLATION OF BTK.
RX PubMed=11226282; DOI=10.1073/pnas.051626198;
RA Baba Y., Hashimoto S., Matsushita M., Watanabe D., Kishimoto T.,
RA Kurosaki T., Tsukada S.;
RT "BLNK mediates Syk-dependent Btk activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2582-2586(2001).
RN [5]
RP FUNCTION IN PHOSPHORYLATION OF SH3BP2, MUTAGENESIS OF LYS-395, AND ACTIVITY
RP REGULATION.
RX PubMed=12709437; DOI=10.1074/jbc.m301201200;
RA Maeno K., Sada K., Kyo S., Miah S.M., Kawauchi-Kamata K., Qu X., Shi Y.,
RA Yamamura H.;
RT "Adaptor protein 3BP2 is a potential ligand of Src homology 2 and 3 domains
RT of Lyn protein-tyrosine kinase.";
RL J. Biol. Chem. 278:24912-24920(2003).
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=17936247; DOI=10.1016/j.bbrc.2007.09.100;
RA Adachi T., Wienands J., Tsubata T., Kurosaki T.;
RT "Interdomain A is crucial for ITAM-dependent and -independent regulation of
RT Syk.";
RL Biochem. Biophys. Res. Commun. 364:111-117(2007).
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:11226282, ECO:0000269|PubMed:12709437,
CC ECO:0000269|PubMed:8986718}.
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 (By similarity). May also be
CC negatively regulated by PTPN6 through dephosphorylation (By
CC similarity). Downstream signaling adapters and intermediates like BLNK
CC or RHOH may mediate positive and/or negative feedback regulation (By
CC similarity). 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. {ECO:0000250,
CC ECO:0000269|PubMed:12709437, ECO:0000269|PubMed:17936247}.
CC -!- SUBUNIT: Interacts with LYN; phosphorylates SYK. Interacts with RHOH
CC (phosphorylated); regulates mast cells activation (By similarity).
CC Interacts with NFAM1 (phosphorylated); probably involved in BCR
CC signaling (By similarity). Interacts with VAV1 (via SH2 domain);
CC phosphorylates VAV1 upon BCR activation. Interacts with GAB2
CC (phosphorylated); probably involved in IgE Fc receptor signaling (By
CC similarity). Interacts (via its SH2 domains) with CD79A (via its
CC phosphorylated ITAM domain); the interaction stimulates SYK
CC autophosphorylation and activation (By similarity). Interacts (via SH2
CC domains) with FCER1G (via ITAM domain); activates SYK and mediates
CC neutrophils and macrophages integrin-mediated activation (By
CC similarity). Interaction with FCER1G in basophils triggers IL3-induced
CC IL4 production (By similarity). Interacts with ITGB2 and FGR; involved
CC in ITGB2 downstream signaling (By similarity). Interacts with ITGB3;
CC upon activation by ITGB3 promotes platelet adhesion (By similarity).
CC Interacts (via SH2 domains) with TYROBP (via ITAM domain); involved in
CC neutrophils and macrophages integrin-mediated activation (By
CC similarity). Interacts with MSN and SELPLG; mediates the selectin-
CC dependent activation of SYK by SELPLG (By similarity). Interacts with
CC BLNK (via SH2 domain) (By similarity). Interacts (via the second SH2
CC domain) with USP25 (via C-terminus); phosphorylates USP25 and regulates
CC USP25 intracellular levels (By similarity). Interacts (via SH2 domains)
CC with CLEC1B (dimer) (By similarity). Interacts with CLEC7A;
CC participates in leukocyte activation in presence of fungal pathogens
CC (By similarity). Interacts (phosphorylated) with SLA; may regulate SYK
CC through CBL recruitment (By similarity). Interacts with YWHAG;
CC attenuates BCR-induced membrane translocation and activation of SYK (By
CC similarity). Interacts (via SH2 domains) with GCSAM; the interaction
CC increases after B-cell receptor stimulation, resulting in enhanced SYK
CC autophosphorylation and activity (By similarity).Interacts with TNS2;
CC leading to the phosphorylation of SYK (By similarity). Interacts with
CC FLNA (via filamin repeat 5); docks SYK to the plasma membrane (By
CC similarity). Interacts CEACAM1; lipopolysaccharide activated
CC neutrophils induce phosphorylation of SYK resulting in the formation of
CC a complex including TLR4 and the phosphorylated form of SYK and
CC CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK,
CC reducing the production of reactive oxygen species (ROS) and lysosome
CC disruption, which in turn, reduces the activity of the inflammasome (By
CC similarity). Interacts (via SH2 domains) with CEACAM20 (phosphorylated
CC form); the interaction further enhances CEACAM20 phosphorylation (By
CC similarity). Interacts with IL15RA (By similarity).
CC {ECO:0000250|UniProtKB:P43405, ECO:0000250|UniProtKB:P48025}.
CC -!- SUBCELLULAR LOCATION: [72 kDa tyrosine-protein kinase SYK]: Cell
CC membrane {ECO:0000305}. Cytoplasm, cytosol. Note=Mainly associated with
CC membranes.
CC -!- SUBCELLULAR LOCATION: [40 kDa tyrosine-protein kinase SYK]: Cell
CC membrane {ECO:0000305}. Cytoplasm, cytosol. Note=Equally distributed
CC between membranes and cytosol.
CC -!- TISSUE SPECIFICITY: Spleen and with lesser amounts in thymus.
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-316 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-341 creates a binding site for VAV1 (By similarity).
CC Phosphorylation on Tyr-341 and Tyr-345 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-290 is very common, it peaks 5
CC minutes after BCR stimulation, and creates a binding site for YWHAG (By
CC similarity). Phosphorylation at Tyr-623 creates a binding site for BLNK
CC (By similarity). Dephosphorylated by PTPN6 (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P43405}.
CC -!- PTM: Shows high susceptibility to proteolysis.
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; M73237; AAA31112.1; -; mRNA.
DR PIR; A40802; A40802.
DR RefSeq; NP_001098422.1; NM_001104952.1.
DR AlphaFoldDB; Q00655; -.
DR SMR; Q00655; -.
DR IntAct; Q00655; 1.
DR MINT; Q00655; -.
DR STRING; 9823.ENSSSCP00000010237; -.
DR iPTMnet; Q00655; -.
DR PaxDb; Q00655; -.
DR PRIDE; Q00655; -.
DR GeneID; 100125540; -.
DR KEGG; ssc:100125540; -.
DR CTD; 6850; -.
DR eggNOG; ENOG502QT06; Eukaryota.
DR InParanoid; Q00655; -.
DR OrthoDB; 796831at2759; -.
DR BRENDA; 2.7.10.2; 6170.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB.
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:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
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:0042742; P:defense response to bacterium; ISS:UniProtKB.
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; IEA:InterPro.
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: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:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR GO; GO:0090237; P:regulation of arachidonic acid secretion; ISS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0043313; P:regulation of neutrophil degranulation; ISS:UniProtKB.
DR GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0010543; P:regulation of platelet activation; ISS:UniProtKB.
DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0032928; P:regulation of superoxide anion generation; ISS:UniProtKB.
DR GO; GO:0002554; P:serotonin secretion by platelet; ISS:UniProtKB.
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; Angiogenesis; ATP-binding; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Immunity; Innate immunity; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; SH2 domain;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..628
FT /note="72 kDa tyrosine-protein kinase SYK"
FT /id="PRO_0000024468"
FT CHAIN 313..628
FT /note="40 kDa tyrosine-protein kinase SYK"
FT /id="PRO_0000024469"
FT DOMAIN 10..102
FT /note="SH2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 163..253
FT /note="SH2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 364..624
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 103..162
FT /note="Interdomain A"
FT /evidence="ECO:0000250"
FT REGION 254..363
FT /note="Interdomain B"
FT /evidence="ECO:0000250"
FT REGION 293..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 487
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 370..378
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 395
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 23
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 42
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 126
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 250
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 289
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 316
FT /note="Phosphotyrosine; by LYN"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 338
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 341
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:8986718"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 345
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 357
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 377
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 477
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 500
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 518
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 519
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 523
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 539
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P48025"
FT MOD_RES 572
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43405"
FT MOD_RES 622
FT /note="Phosphotyrosine"
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 MUTAGEN 341
FT /note="Y->F: Alters interaction with VAV1."
FT /evidence="ECO:0000269|PubMed:8986718"
FT MUTAGEN 345
FT /note="Y->F: Moderately alters interaction with VAV1."
FT /evidence="ECO:0000269|PubMed:8986718"
FT MUTAGEN 395
FT /note="K->R: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12709437"
SQ SEQUENCE 628 AA; 71620 MW; D7C0CEF7EBBEBC1E CRC64;
MADSANHLPF FFGQITREEA EDYLVQGGMS DGLYLLRQSR NYLGGFALSV AYDRKAHHYT
IERELNGTYA ISGGRTHGSP AELCHYHSQE LDGLVCLLKN PFNRPPGVQP KTGPFEDLKE
NLIREYVKQT WNLQGQALEQ AIISQKPQLE KLIATTAHEK MPWFHGKISR DESEQIVLIG
SKTNGKFLIR ARDNGSYALG LLHEGKVLHY RIDKDKTGKL SIPGGKNFDT LWQLVEHYSY
KSDGLLRVLT VPCQKIGGQT GNDSFRPQLP SAHPATWSAG GIISRIKSYS FPKPGHRKAS
SPQGNRPESL VSYNPYESDR GPWANEREAQ REALPMDTEV YESPYADPEE IRPKEVYLDR
KLLTLEDKEL GSGNFGTVKK GYYQMKKVVK TVAVKILKNE ANDPALKDEL LAEANVMQQL
DNPYIVRMIG ICEAESWMLV MEMAELGPLN KYLQQNRHVK DKNIIELVHQ VSMGMKYLEE
CNFVHRDLAA RNVLLVTQHY AKISDFGLSK ALRADENYYK AQTHGKWPVK WYAPECINYY
KFSSKSDVWS FGVLMWEAFS YGQKPYRGMK GSEVSAMLEK GERMGCPPGC PREMYELMTL
CWTYDVENRP GFVAVELRLR NYYYDVVN
