UniProtKB - Q03526 (ITK_MOUSE)
Tyrosine-protein kinase ITK/TSK
Itk
Functioni
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells (PubMed:23562159).
Phosphorylates TBX21 at 'Tyr-525' and mediates its interaction with GATA3 (PubMed:15662016).
3 PublicationsCatalytic activityi
- EC:2.7.10.2PROSITE-ProRule annotation
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 127 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 138 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 139 | ZincPROSITE-ProRule annotation | 1 | |
Metal bindingi | 149 | ZincPROSITE-ProRule annotation | 1 | |
Binding sitei | 396 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 487 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 119 – 155 | Btk-typePROSITE-ProRule annotationAdd BLAST | 37 | |
Nucleotide bindingi | 374 – 382 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein tyrosine kinase activity Source: GO_Central
GO - Biological processi
- activation of phospholipase C activity Source: UniProtKB
- adaptive immune response Source: UniProtKB
- B cell receptor signaling pathway Source: GO_Central
- gamma-delta T cell activation Source: UniProtKB
- intracellular signal transduction Source: InterPro
- NK T cell differentiation Source: MGI
- peptidyl-tyrosine autophosphorylation Source: GO_Central
- positive regulation of cytokine production Source: UniProtKB
- protein phosphorylation Source: UniProtKB
- T cell receptor signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Kinase, Transferase, Tyrosine-protein kinase |
Biological process | Adaptive immunity, Immunity |
Ligand | ATP-binding, Metal-binding, Nucleotide-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 3474 2.7.10.2, 3474 |
Reactomei | R-MMU-202433, Generation of second messenger molecules R-MMU-2871809, FCERI mediated Ca+2 mobilization |
Names & Taxonomyi
Protein namesi | Recommended name: Tyrosine-protein kinase ITK/TSK (EC:2.7.10.2)Alternative name(s): IL-2-inducible T-cell kinase Kinase EMT Kinase TLK T-cell-specific kinase |
Gene namesi | Name:Itk Synonyms:Emt, Tlk, Tsk |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:96621, Itk |
VEuPathDBi | HostDB:ENSMUSG00000020395 |
Subcellular locationi
Cytosol
- cytosol Source: MGI
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: MGI
Other locations
- cell-cell junction Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000088107 | 1 – 625 | Tyrosine-protein kinase ITK/TSKAdd BLAST | 625 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 186 | Phosphotyrosine; by autocatalysisBy similarity | 1 | |
Modified residuei | 517 | Phosphotyrosine; by LCKBy similarity | 1 | |
Modified residuei | 570 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q03526 |
jPOSTi | Q03526 |
MaxQBi | Q03526 |
PaxDbi | Q03526 |
PRIDEi | Q03526 |
ProteomicsDBi | 269110 |
PTM databases
iPTMneti | Q03526 |
PhosphoSitePlusi | Q03526 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000020395, Expressed in thymus and 116 other tissues |
ExpressionAtlasi | Q03526, baseline and differential |
Genevisiblei | Q03526, MM |
Interactioni
Subunit structurei
Homooligomerizes; this association negatively regulates kinase activity.
Interacts with PPIA/CYPA; this interaction regulates TCR signal strength via a proline-directed conformational switch in ITK.
Interacts with THEMIS (By similarity).
Interacts with FASLG.
Interacts with VAV1; this interaction is important for VAV1 localization and TCR-induced actin polarization.
Interacts with TBX21 (PubMed:15662016).
By similarity3 PublicationsBinary interactionsi
Q03526
With | #Exp. | IntAct |
---|---|---|
PLCG1 [P08487] from Bos taurus. | 4 | EBI-647969,EBI-8013886 |
Protein-protein interaction databases
BioGRIDi | 200840, 5 interactors |
DIPi | DIP-29283N |
IntActi | Q03526, 9 interactors |
MINTi | Q03526 |
STRINGi | 10090.ENSMUSP00000104860 |
Miscellaneous databases
RNActi | Q03526, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q03526 |
BMRBi | Q03526 |
SMRi | Q03526 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q03526 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 4 – 117 | PHPROSITE-ProRule annotationAdd BLAST | 114 | |
Domaini | 177 – 237 | SH3PROSITE-ProRule annotationAdd BLAST | 61 | |
Domaini | 245 – 343 | SH2PROSITE-ProRule annotationAdd BLAST | 99 | |
Domaini | 368 – 620 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 253 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 153 – 174 | DisorderedSequence analysisAdd BLAST | 22 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 119 – 155 | Btk-typePROSITE-ProRule annotationAdd BLAST | 37 |
Keywords - Domaini
SH2 domain, SH3 domain, Zinc-fingerPhylogenomic databases
eggNOGi | KOG0197, Eukaryota |
GeneTreei | ENSGT00940000158850 |
InParanoidi | Q03526 |
OrthoDBi | 1047190at2759 |
PhylomeDBi | Q03526 |
TreeFami | TF351634 |
Family and domain databases
CDDi | cd05112, PTKc_Itk, 1 hit cd11908, SH3_ITK, 1 hit |
Gene3Di | 2.30.29.30, 1 hit 3.30.505.10, 1 hit |
IDEALi | IID50118 |
InterProi | View protein in InterPro IPR042785, ITK_PTKc IPR035583, ITK_SH3 IPR011009, Kinase-like_dom_sf IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR000980, SH2 IPR036860, SH2_dom_sf IPR036028, SH3-like_dom_sf IPR001452, SH3_domain IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom IPR001562, Znf_Btk_motif |
Pfami | View protein in Pfam PF00779, BTK, 1 hit PF00169, PH, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit PF00017, SH2, 1 hit PF00018, SH3_1, 1 hit |
PRINTSi | PR00401, SH2DOMAIN PR00402, TECBTKDOMAIN PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00107, BTK, 1 hit SM00233, PH, 1 hit SM00252, SH2, 1 hit SM00326, SH3, 1 hit SM00219, TyrKc, 1 hit |
SUPFAMi | SSF50044, SSF50044, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50003, PH_DOMAIN, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00109, PROTEIN_KINASE_TYR, 1 hit PS50001, SH2, 1 hit PS50002, SH3, 1 hit PS51113, ZF_BTK, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MNNFILLEEQ LIKKSQQKRR TSPSNFKVRF FVLTKASLAY FEDRHGKKRT
60 70 80 90 100
LKGSIELSRI KCVEIVKSDI SIPCHYKYPF QTLVYLQVVH DNYLLYVFAP
110 120 130 140 150
DCESRQRWVL TLKEETRNNN SLVSKYHPNF WMDGRWRCCS QLEKPAVGCA
160 170 180 190 200
PYDPSKNASK KPLPPTPEDN RRSFQEPEET LVIALYDYQT NDPQELALRC
210 220 230 240 250
DEEYYLLDSS EIHWWRVQDK NGHEGYAPSS YLVEKSPNNL ETYEWYNKSI
260 270 280 290 300
SRDKAEKLLL DTGKEGAFMV RDSRTPGTYT VSVFTKAIIS ENPCIKHYHI
310 320 330 340 350
KETNDSPKRY YVAEKYVFDS IPLLIQYHQY NGGGLVTRLR YPVCSWRQKA
360 370 380 390 400
PVTAGLRYGK WVIQPSELTF VQEIGSGQFG LVHLGYWLNK DKVAIKTIQE
410 420 430 440 450
GAMSEEDFIE EAEVMMKLSH PKLVQLYGVC LEQAPICLVF EFMEHGCLSD
460 470 480 490 500
YLRSQRGLFA AETLLGMCLD VCEGMAYLEK ACVIHRDLAA RNCLVGENQV
510 520 530 540 550
IKVSDFGMTR FVLDDQYTSS TGTKFPVKWA SPEVFSFSRY SSKSDVWSFG
560 570 580 590 600
VLMWEVFSEG KIPYENRSNS EVVEDISTGF RLYKPRLASC HVYQIMNHCW
610 620
KEKPEDRPPF SQLLSQLAEI AEAGL
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5STT8 | Q5STT8_MOUSE | Tyrosine-protein kinase | Itk | 619 | Annotation score: | ||
Q5STT7 | Q5STT7_MOUSE | Tyrosine-protein kinase ITK/TSK | Itk | 264 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 82 – 87 | Missing (PubMed:8421704).Curated | 6 | |
Sequence conflicti | 82 – 87 | Missing (PubMed:8476425).Curated | 6 | |
Sequence conflicti | 82 – 87 | Missing (Ref. 4) Curated | 6 | |
Sequence conflicti | 535 | F → S in L10628 (PubMed:8476425).Curated | 1 | |
Sequence conflicti | 540 | Y → C in L10628 (PubMed:8476425).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L00619 mRNA Translation: AAA39337.1 L05631 mRNA Translation: AAA40518.1 L10628 mRNA No translation available. D14042 mRNA Translation: BAA03129.1 |
CCDSi | CCDS70169.1 |
PIRi | A43030 |
RefSeqi | NP_001268894.1, NM_001281965.1 NP_001268895.1, NM_001281966.1 NP_001268897.1, NM_001281968.1 NP_034713.2, NM_010583.3 |
Genome annotation databases
Ensembli | ENSMUST00000109237; ENSMUSP00000104860; ENSMUSG00000020395 |
GeneIDi | 16428 |
KEGGi | mmu:16428 |
UCSCi | uc011xtn.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L00619 mRNA Translation: AAA39337.1 L05631 mRNA Translation: AAA40518.1 L10628 mRNA No translation available. D14042 mRNA Translation: BAA03129.1 |
CCDSi | CCDS70169.1 |
PIRi | A43030 |
RefSeqi | NP_001268894.1, NM_001281965.1 NP_001268895.1, NM_001281966.1 NP_001268897.1, NM_001281968.1 NP_034713.2, NM_010583.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1AWJ | NMR | - | A | 160-236 | [»] | |
1LUI | NMR | - | A | 238-344 | [»] | |
1LUK | NMR | - | A | 238-344 | [»] | |
1LUM | NMR | - | A | 238-344 | [»] | |
1LUN | NMR | - | A | 238-344 | [»] | |
2ETZ | NMR | - | A | 238-344 | [»] | |
2EU0 | NMR | - | A | 238-344 | [»] | |
2K79 | NMR | - | A | 177-237 | [»] | |
B | 238-344 | [»] | ||||
2K7A | NMR | - | A | 177-237 | [»] | |
B | 238-344 | [»] | ||||
2RN8 | NMR | - | A | 177-238 | [»] | |
2RNA | NMR | - | A | 177-238 | [»] | |
3S9K | X-ray | 2.35 | A | 236-344 | [»] | |
AlphaFoldDBi | Q03526 | |||||
BMRBi | Q03526 | |||||
SMRi | Q03526 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 200840, 5 interactors |
DIPi | DIP-29283N |
IntActi | Q03526, 9 interactors |
MINTi | Q03526 |
STRINGi | 10090.ENSMUSP00000104860 |
PTM databases
iPTMneti | Q03526 |
PhosphoSitePlusi | Q03526 |
Proteomic databases
EPDi | Q03526 |
jPOSTi | Q03526 |
MaxQBi | Q03526 |
PaxDbi | Q03526 |
PRIDEi | Q03526 |
ProteomicsDBi | 269110 |
Protocols and materials databases
Antibodypediai | 16533, 503 antibodies from 42 providers |
DNASUi | 16428 |
Genome annotation databases
Ensembli | ENSMUST00000109237; ENSMUSP00000104860; ENSMUSG00000020395 |
GeneIDi | 16428 |
KEGGi | mmu:16428 |
UCSCi | uc011xtn.2, mouse |
Organism-specific databases
CTDi | 3702 |
MGIi | MGI:96621, Itk |
VEuPathDBi | HostDB:ENSMUSG00000020395 |
Phylogenomic databases
eggNOGi | KOG0197, Eukaryota |
GeneTreei | ENSGT00940000158850 |
InParanoidi | Q03526 |
OrthoDBi | 1047190at2759 |
PhylomeDBi | Q03526 |
TreeFami | TF351634 |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 3474 2.7.10.2, 3474 |
Reactomei | R-MMU-202433, Generation of second messenger molecules R-MMU-2871809, FCERI mediated Ca+2 mobilization |
Miscellaneous databases
BioGRID-ORCSi | 16428, 1 hit in 73 CRISPR screens |
ChiTaRSi | Itk, mouse |
EvolutionaryTracei | Q03526 |
PROi | PR:Q03526 |
RNActi | Q03526, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000020395, Expressed in thymus and 116 other tissues |
ExpressionAtlasi | Q03526, baseline and differential |
Genevisiblei | Q03526, MM |
Family and domain databases
CDDi | cd05112, PTKc_Itk, 1 hit cd11908, SH3_ITK, 1 hit |
Gene3Di | 2.30.29.30, 1 hit 3.30.505.10, 1 hit |
IDEALi | IID50118 |
InterProi | View protein in InterPro IPR042785, ITK_PTKc IPR035583, ITK_SH3 IPR011009, Kinase-like_dom_sf IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR001245, Ser-Thr/Tyr_kinase_cat_dom IPR000980, SH2 IPR036860, SH2_dom_sf IPR036028, SH3-like_dom_sf IPR001452, SH3_domain IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom IPR001562, Znf_Btk_motif |
Pfami | View protein in Pfam PF00779, BTK, 1 hit PF00169, PH, 1 hit PF07714, PK_Tyr_Ser-Thr, 1 hit PF00017, SH2, 1 hit PF00018, SH3_1, 1 hit |
PRINTSi | PR00401, SH2DOMAIN PR00402, TECBTKDOMAIN PR00109, TYRKINASE |
SMARTi | View protein in SMART SM00107, BTK, 1 hit SM00233, PH, 1 hit SM00252, SH2, 1 hit SM00326, SH3, 1 hit SM00219, TyrKc, 1 hit |
SUPFAMi | SSF50044, SSF50044, 1 hit SSF55550, SSF55550, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS50003, PH_DOMAIN, 1 hit PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00109, PROTEIN_KINASE_TYR, 1 hit PS50001, SH2, 1 hit PS50002, SH3, 1 hit PS51113, ZF_BTK, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ITK_MOUSE | |
Accessioni | Q03526Primary (citable) accession number: Q03526 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | February 1, 1995 | |
Last modified: | May 25, 2022 | |
This is version 210 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families