ITK_MOUSE
ID ITK_MOUSE Reviewed; 625 AA.
AC Q03526;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Tyrosine-protein kinase ITK/TSK;
DE EC=2.7.10.2;
DE AltName: Full=IL-2-inducible T-cell kinase;
DE AltName: Full=Kinase EMT;
DE AltName: Full=Kinase TLK;
DE AltName: Full=T-cell-specific kinase;
GN Name=Itk; Synonyms=Emt, Tlk, Tsk;
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].
RC TISSUE=Thymocyte;
RX PubMed=1280821; DOI=10.1073/pnas.89.23.11194;
RA Siliciano J.D., Morrow T.A., Desiderio S.V.;
RT "itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:11194-11198(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thymocyte;
RX PubMed=8421704; DOI=10.1073/pnas.90.2.669;
RA Heyeck S.D., Berg L.J.;
RT "Developmental regulation of a murine T-cell-specific tyrosine kinase gene,
RT Tsk.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:669-673(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CBA/J; TISSUE=Mast cell;
RX PubMed=8476425; DOI=10.1006/bbrc.1993.1404;
RA Yamada N., Kawakami Y., Kimura H., Fukamachi H., Baier G., Altman A.,
RA Kato T., Inagaki Y., Kawakami T.;
RT "Structure and expression of novel protein-tyrosine kinases, Emb and Emt,
RT in hematopoietic cells.";
RL Biochem. Biophys. Res. Commun. 192:231-240(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ogata M., Sawada M., Fujiwara H., Hamaoka T.;
RL Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=8777721; DOI=10.1016/1074-7613(95)90065-9;
RA Liao X.C., Littman D.R.;
RT "Altered T cell receptor signaling and disrupted T cell development in mice
RT lacking Itk.";
RL Immunity 3:757-769(1995).
RN [6]
RP FUNCTION, INTERACTION WITH TBX21, AND SUBCELLULAR LOCATION.
RX PubMed=15662016; DOI=10.1126/science.1103336;
RA Hwang E.S., Szabo S.J., Schwartzberg P.L., Glimcher L.H.;
RT "T helper cell fate specified by kinase-mediated interaction of T-bet with
RT GATA-3.";
RL Science 307:430-433(2005).
RN [7]
RP INTERACTION WITH THEMIS.
RX PubMed=19597499; DOI=10.1038/ni.1766;
RA Fu G., Vallee S., Rybakin V., McGuire M.V., Ampudia J., Brockmeyer C.,
RA Salek M., Fallen P.R., Hoerter J.A.H., Munshi A., Huang Y.H., Hu J.,
RA Fox H.S., Sauer K., Acuto O., Gascoigne N.R.J.;
RT "Themis controls thymocyte selection through regulation of T cell antigen
RT receptor-mediated signaling.";
RL Nat. Immunol. 10:848-856(2009).
RN [8]
RP STRUCTURE BY NMR OF 160-236.
RX PubMed=8985255; DOI=10.1038/385093a0;
RA Andreotti A.H., Bunnell S.C., Feng S., Berg L.J., Schreiber S.L.;
RT "Regulatory intramolecular association in a tyrosine kinase of the Tec
RT family.";
RL Nature 385:93-97(1997).
RN [9]
RP CHARACTERIZATION.
RX PubMed=7524075; DOI=10.1073/pnas.91.20.9347;
RA August A., Gibson S., Kawakami Y., Kawakami T., Mills G.B., Dupont B.;
RT "CD28 is associated with and induces the immediate tyrosine phosphorylation
RT and activation of the Tec family kinase ITK/EMT in the human Jurkat
RT leukemic T-cell line.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:9347-9351(1994).
RN [10]
RP CHARACTERIZATION.
RX PubMed=8943565; DOI=10.1093/intimm/8.11.1707;
RA King P.D., Sadra A., Han A., Liu X.-R., Sunder-Plassmann R., Reinherz E.L.,
RA Dupont B.;
RT "CD2 signaling in T cells involves tyrosine phosphorylation and activation
RT of the Tec family kinase, EMT/ITK/TSK.";
RL Int. Immunol. 8:1707-1714(1996).
RN [11]
RP CHARACTERIZATION.
RX PubMed=10570288;
RA Ching K.A., Kawakami Y., Kawakami T., Tsoukas C.D.;
RT "Emt/Itk associates with activated TCR complexes: role of the pleckstrin
RT homology domain.";
RL J. Immunol. 163:6006-6013(1999).
RN [12]
RP DISRUPTION PHENOTYPE.
RX PubMed=10213685; DOI=10.1126/science.284.5414.638;
RA Schaeffer E.M., Debnath J., Yap G., McVicar D., Liao X.C., Littman D.R.,
RA Sher A., Varmus H.E., Lenardo M.J., Schwartzberg P.L.;
RT "Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and
RT immunity.";
RL Science 284:638-641(1999).
RN [13]
RP DISRUPTION PHENOTYPE.
RX PubMed=16860760; DOI=10.1016/j.immuni.2006.05.011;
RA Broussard C., Fleischacker C., Horai R., Chetana M., Venegas A.M.,
RA Sharp L.L., Hedrick S.M., Fowlkes B.J., Schwartzberg P.L.;
RT "Altered development of CD8+ T cell lineages in mice deficient for the Tec
RT kinases Itk and Rlk.";
RL Immunity 25:93-104(2006).
RN [14]
RP SUBUNIT.
RX PubMed=20237289; DOI=10.4049/jimmunol.0901908;
RA Min L., Wu W., Joseph R.E., Fulton D.B., Berg L., Andreotti A.H.;
RT "Disrupting the intermolecular self-association of Itk enhances T cell
RT signaling.";
RL J. Immunol. 184:4228-4235(2010).
RN [15]
RP FUNCTION IN INVARIANT NKT CELL MATURATION, AND DISRUPTION PHENOTYPE.
RX PubMed=21036902; DOI=10.1074/jbc.m110.148205;
RA Qi Q., Xia M., Bai Y., Yu S., Cantorna M., August A.;
RT "Interleukin-2-inducible T cell kinase (Itk) network edge dependence for
RT the maturation of iNKT cell.";
RL J. Biol. Chem. 286:138-146(2011).
RN [16]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23562159; DOI=10.1016/j.immuni.2013.01.010;
RG Immunological Genome Project Consortium;
RA Malhotra N., Narayan K., Cho O.H., Sylvia K.E., Yin C., Melichar H.,
RA Rashighi M., Lefebvre V., Harris J.E., Berg L.J., Kang J.;
RT "A network of high-mobility group box transcription factors programs innate
RT interleukin-17 production.";
RL Immunity 38:681-693(2013).
CC -!- FUNCTION: Tyrosine kinase that plays an essential role in regulation of
CC the adaptive immune response. Regulates the development, function and
CC differentiation of conventional T-cells and nonconventional NKT-cells.
CC When antigen presenting cells (APC) activate T-cell receptor (TCR), a
CC series of phosphorylation lead to the recruitment of ITK to the cell
CC membrane, in the vicinity of the stimulated TCR receptor, where it is
CC phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation
CC and full activation. Once activated, phosphorylates PLCG1, leading to
CC the activation of this lipase and subsequent cleavage of its
CC substrates. In turn, the endoplasmic reticulum releases calcium in the
CC cytoplasm and the nuclear activator of activated T-cells (NFAT)
CC translocates into the nucleus to perform its transcriptional duty.
CC Phosphorylates 2 essential adapter proteins: the linker for activation
CC of T-cells/LAT protein and LCP2. Then, a large number of signaling
CC molecules such as VAV1 are recruited and ultimately lead to lymphokine
CC production, T-cell proliferation and differentiation. Required for TCR-
CC mediated calcium response in gamma-delta T-cells, may also be involved
CC in the modulation of the transcriptomic signature in the Vgamma2-
CC positive subset of immature gamma-delta T-cells (PubMed:23562159).
CC Phosphorylates TBX21 at 'Tyr-525' and mediates its interaction with
CC GATA3 (PubMed:15662016). {ECO:0000269|PubMed:15662016,
CC ECO:0000269|PubMed:21036902, ECO:0000269|PubMed:23562159}.
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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Homooligomerizes; this association negatively regulates kinase
CC activity. Interacts with PPIA/CYPA; this interaction regulates TCR
CC signal strength via a proline-directed conformational switch in ITK.
CC Interacts with THEMIS (By similarity). Interacts with FASLG. Interacts
CC with VAV1; this interaction is important for VAV1 localization and TCR-
CC induced actin polarization. Interacts with TBX21 (PubMed:15662016).
CC {ECO:0000250|UniProtKB:Q08881, ECO:0000269|PubMed:15662016,
CC ECO:0000269|PubMed:19597499, ECO:0000269|PubMed:20237289}.
CC -!- INTERACTION:
CC Q03526; P08487: PLCG1; Xeno; NbExp=4; IntAct=EBI-647969, EBI-8013886;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:15662016}.
CC Note=Localizes in the vicinity of cell surface receptors in the plasma
CC membrane after receptor stimulation. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Is detected in the thymus, lymph node and very
CC faintly in the spleen, but is not detected in the liver, lung, kidney,
CC heart, brain, intestine or testis. Expressed in T-lymphocytes and mast
CC cells. It may also be expressed in natural killer cells.
CC -!- DEVELOPMENTAL STAGE: Is present in the fetal thymus as early as day 14
CC of gestation. The levels are 5- to 10-fold higher in thymocytes than in
CC peripheral T-cells, and increase in the thymus during development from
CC neonate to adult.
CC -!- INDUCTION: Through a myriad of surface receptors including the TCR/CD3
CC signaling complex, coreceptors, or chemokine receptors.
CC -!- DOMAIN: The N-terminal PH domain allows ITK to be recruited to the
CC plasma membrane by an activated PI3 kinase. This domain contains also a
CC proline-rich region (PRR). The adjoining domain is a SH3 domain, which
CC binds to PRR (from itself or from other proteins). Next, a SH2 domain
CC is required for binding tyrosine-phosphorylated substrates. In the C-
CC terminal region, the kinase domain is required for tyrosine
CC phosphorylation (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated at Tyr-517 in the activation loop of the kinase
CC domain by LCK. Subsequent autophosphorylation at Tyr-186 leads to the
CC kinase activation. The autophosphorylated Tyr-186 lies within the
CC substrate binding sequence of the SH3 domain (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice display decreased mature thymocytes and
CC elicit profound defect in CD4+ and CD8+ T-cell development
CC (PubMed:8777721, PubMed:10213685, PubMed:16860760, PubMed:21036902).
CC Additionally, they show a strong decrease of cytokine production in
CC response to TCR receptor stimulation (PubMed:21036902). Impaired TCR-
CC mediated calcium response in gamma-delta T-cells (PubMed:23562159).
CC Loss of Vgamma2-positive immature thymocyte-specific transcriptomic
CC profile, although there is no change to overall transcription factor
CC expression levels (PubMed:23562159). Not required for the generation of
CC IL17A expressing gamma-delta T-cells (PubMed:23562159).
CC {ECO:0000269|PubMed:10213685, ECO:0000269|PubMed:16860760,
CC ECO:0000269|PubMed:21036902, ECO:0000269|PubMed:23562159,
CC ECO:0000269|PubMed:8777721}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. TEC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; L00619; AAA39337.1; -; mRNA.
DR EMBL; L05631; AAA40518.1; -; mRNA.
DR EMBL; L10628; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; D14042; BAA03129.1; -; mRNA.
DR CCDS; CCDS70169.1; -.
DR PIR; A43030; A43030.
DR RefSeq; NP_001268894.1; NM_001281965.1.
DR RefSeq; NP_001268895.1; NM_001281966.1.
DR RefSeq; NP_001268897.1; NM_001281968.1.
DR RefSeq; NP_034713.2; NM_010583.3.
DR PDB; 1AWJ; NMR; -; A=160-236.
DR PDB; 1LUI; NMR; -; A=238-344.
DR PDB; 1LUK; NMR; -; A=238-344.
DR PDB; 1LUM; NMR; -; A=238-344.
DR PDB; 1LUN; NMR; -; A=238-344.
DR PDB; 2ETZ; NMR; -; A=238-344.
DR PDB; 2EU0; NMR; -; A=238-344.
DR PDB; 2K79; NMR; -; A=177-237, B=238-344.
DR PDB; 2K7A; NMR; -; A=177-237, B=238-344.
DR PDB; 2RN8; NMR; -; A=177-238.
DR PDB; 2RNA; NMR; -; A=177-238.
DR PDB; 3S9K; X-ray; 2.35 A; A=236-344.
DR PDBsum; 1AWJ; -.
DR PDBsum; 1LUI; -.
DR PDBsum; 1LUK; -.
DR PDBsum; 1LUM; -.
DR PDBsum; 1LUN; -.
DR PDBsum; 2ETZ; -.
DR PDBsum; 2EU0; -.
DR PDBsum; 2K79; -.
DR PDBsum; 2K7A; -.
DR PDBsum; 2RN8; -.
DR PDBsum; 2RNA; -.
DR PDBsum; 3S9K; -.
DR AlphaFoldDB; Q03526; -.
DR BMRB; Q03526; -.
DR SMR; Q03526; -.
DR BioGRID; 200840; 5.
DR DIP; DIP-29283N; -.
DR IntAct; Q03526; 9.
DR MINT; Q03526; -.
DR STRING; 10090.ENSMUSP00000104860; -.
DR iPTMnet; Q03526; -.
DR PhosphoSitePlus; Q03526; -.
DR EPD; Q03526; -.
DR jPOST; Q03526; -.
DR MaxQB; Q03526; -.
DR PaxDb; Q03526; -.
DR PRIDE; Q03526; -.
DR ProteomicsDB; 269110; -.
DR Antibodypedia; 16533; 511 antibodies from 42 providers.
DR DNASU; 16428; -.
DR Ensembl; ENSMUST00000109237; ENSMUSP00000104860; ENSMUSG00000020395.
DR GeneID; 16428; -.
DR KEGG; mmu:16428; -.
DR UCSC; uc011xtn.2; mouse.
DR CTD; 3702; -.
DR MGI; MGI:96621; Itk.
DR VEuPathDB; HostDB:ENSMUSG00000020395; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000158850; -.
DR InParanoid; Q03526; -.
DR OrthoDB; 1047190at2759; -.
DR PhylomeDB; Q03526; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.1; 3474.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-202433; Generation of second messenger molecules.
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization.
DR BioGRID-ORCS; 16428; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Itk; mouse.
DR EvolutionaryTrace; Q03526; -.
DR PRO; PR:Q03526; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q03526; protein.
DR Bgee; ENSMUSG00000020395; Expressed in thymus and 62 other tissues.
DR ExpressionAtlas; Q03526; baseline and differential.
DR Genevisible; Q03526; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0007202; P:activation of phospholipase C activity; IMP:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IMP:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0046629; P:gamma-delta T cell activation; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0001865; P:NK T cell differentiation; IMP:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IMP:UniProtKB.
DR CDD; cd05112; PTKc_Itk; 1.
DR CDD; cd11908; SH3_ITK; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR IDEAL; IID50118; -.
DR InterPro; IPR042785; ITK_PTKc.
DR InterPro; IPR035583; ITK_SH3.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
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; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001562; Znf_Btk_motif.
DR Pfam; PF00779; BTK; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00402; TECBTKDOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00107; BTK; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50003; PH_DOMAIN; 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; 1.
DR PROSITE; PS50002; SH3; 1.
DR PROSITE; PS51113; ZF_BTK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; ATP-binding; Cytoplasm; Immunity; Kinase;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..625
FT /note="Tyrosine-protein kinase ITK/TSK"
FT /id="PRO_0000088107"
FT DOMAIN 4..117
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 177..237
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 245..343
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 368..620
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 119..155
FT /note="Btk-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT REGION 153..174
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 127
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 138
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 149
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00432"
FT BINDING 374..382
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 186
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q08881"
FT MOD_RES 517
FT /note="Phosphotyrosine; by LCK"
FT /evidence="ECO:0000250|UniProtKB:Q08881"
FT MOD_RES 570
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q08881"
FT CONFLICT 82..87
FT /note="Missing (in Ref. 2, 3 and 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 535
FT /note="F -> S (in Ref. 3; L10628)"
FT /evidence="ECO:0000305"
FT CONFLICT 540
FT /note="Y -> C (in Ref. 3; L10628)"
FT /evidence="ECO:0000305"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:1AWJ"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:2K79"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:2K79"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:1AWJ"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:2K79"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:1AWJ"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:2RN8"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:1AWJ"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:2K79"
FT STRAND 229..234
FT /evidence="ECO:0007829|PDB:2K79"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:3S9K"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:2ETZ"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:2K79"
FT HELIX 252..262
FT /evidence="ECO:0007829|PDB:3S9K"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:3S9K"
FT TURN 275..277
FT /evidence="ECO:0007829|PDB:1LUI"
FT STRAND 279..285
FT /evidence="ECO:0007829|PDB:3S9K"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:3S9K"
FT STRAND 294..302
FT /evidence="ECO:0007829|PDB:3S9K"
FT STRAND 305..307
FT /evidence="ECO:0007829|PDB:1LUM"
FT STRAND 310..313
FT /evidence="ECO:0007829|PDB:3S9K"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:1LUI"
FT HELIX 321..330
FT /evidence="ECO:0007829|PDB:3S9K"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:3S9K"
FT STRAND 338..342
FT /evidence="ECO:0007829|PDB:1LUK"
SQ SEQUENCE 625 AA; 72292 MW; F7A4A18A8A1AADDC CRC64;
MNNFILLEEQ LIKKSQQKRR TSPSNFKVRF FVLTKASLAY FEDRHGKKRT LKGSIELSRI
KCVEIVKSDI SIPCHYKYPF QTLVYLQVVH DNYLLYVFAP DCESRQRWVL TLKEETRNNN
SLVSKYHPNF WMDGRWRCCS QLEKPAVGCA PYDPSKNASK KPLPPTPEDN RRSFQEPEET
LVIALYDYQT NDPQELALRC DEEYYLLDSS EIHWWRVQDK NGHEGYAPSS YLVEKSPNNL
ETYEWYNKSI SRDKAEKLLL DTGKEGAFMV RDSRTPGTYT VSVFTKAIIS ENPCIKHYHI
KETNDSPKRY YVAEKYVFDS IPLLIQYHQY NGGGLVTRLR YPVCSWRQKA PVTAGLRYGK
WVIQPSELTF VQEIGSGQFG LVHLGYWLNK DKVAIKTIQE GAMSEEDFIE EAEVMMKLSH
PKLVQLYGVC LEQAPICLVF EFMEHGCLSD YLRSQRGLFA AETLLGMCLD VCEGMAYLEK
ACVIHRDLAA RNCLVGENQV IKVSDFGMTR FVLDDQYTSS TGTKFPVKWA SPEVFSFSRY
SSKSDVWSFG VLMWEVFSEG KIPYENRSNS EVVEDISTGF RLYKPRLASC HVYQIMNHCW
KEKPEDRPPF SQLLSQLAEI AEAGL
