EKS-HOS-00113

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00113

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Tec	475.7	1.4E-142	363	613	251

Status

Reviewed

Ensembl Protein

ENSP00000398655

UniProt Accession

Q08881; B2R752; Q32ML7;

Protein Name

Tyrosine-protein kinase ITK/TSK

Protein Synonyms/Alias

Interleukin-2-inducible T-cell kinase; IL-2-inducible T-cell kinase; Kinase EMT; T-cell-specific kinase; Tyrosine-protein kinase Lyk;

Gene Name

ITK

Gene Synonyms/Alias

ITK; EMT, LYK;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000113263	ENSP00000398655	ENST00000422843
ENSG00000113263	ENSP00000430327	ENST00000521769
ENSG00000113263	ENSP00000431054	ENST00000517779

Organism

Homo sapiens

Functional Description

Tyrosine kinase that plays an essential role inregulation 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.

Protein Length

620

Protein Sequence
(FASTA)

MNNFILLEEQ LIKKSQQKRR TSPSNFKVRF FVLTKASLAY FEDRHGKKRT LKGSIELSRI 60

KCVEIVKSDI SIPCHYKYPF QVVHDNYLLY VFAPDRESRQ RWVLALKEET RNNNSLVPKY 120

HPNFWMDGKW RCCSQLEKLA TGCAQYDPTK NASKKPLPPT PEDNRRPLWE PEETVVIALY 180

DYQTNDPQEL ALRRNEEYCL LDSSEIHWWR VQDRNGHEGY VPSSYLVEKS PNNLETYEWY 240

NKSISRDKAE KLLLDTGKEG AFMVRDSRTA GTYTVSVFTK AVVSENNPCI KHYHIKETND 300

NPKRYYVAEK YVFDSIPLLI NYHQHNGGGL VTRLRYPVCF GRQKAPVTAG LRYGKWVIDP 360

SELTFVQEIG SGQFGLVHLG YWLNKDKVAI KTIREGAMSE EDFIEEAEVM MKLSHPKLVQ 420

LYGVCLEQAP ICLVFEFMEH GCLSDYLRTQ RGLFAAETLL GMCLDVCEGM AYLEEACVIH 480

RDLAARNCLV GENQVIKVSD FGMTRFVLDD QYTSSTGTKF PVKWASPEVF SFSRYSSKSD 540

VWSFGVLMWE VFSEGKIPYE NRSNSEVVED ISTGFRLYKP RLASTHVYQI MNHCWKERPE 600

DRPAFSRLLR QLAEIAESGL 620

Nucleotide Sequence
(FASTA)

ATGAACAACT TTATCCTCCT GGAAGAACAG CTCATCAAGA AATCCCAACA AAAGAGAAGA 60

ACTTCTCCCT CGAACTTTAA AGTCCGCTTC TTTGTGTTAA CCAAAGCCAG CCTGGCATAC 120

TTTGAAGATC GTCATGGGAA GAAGCGCACG CTGAAGGGGT CCATTGAGCT CTCCCGAATC 180

AAATGTGTTG AGATTGTGAA AAGTGACATC AGCATCCCAT GCCACTATAA ATACCCGTTT 240

CAGGTGGTGC ATGACAACTA CCTCCTATAT GTGTTTGCTC CAGATCGTGA GAGCCGGCAG 300

CGCTGGGTGC TGGCCCTTAA AGAAGAAACG AGGAATAATA ACAGTTTGGT GCCTAAATAT 360

CATCCTAATT TCTGGATGGA TGGGAAGTGG AGGTGCTGTT CTCAGCTGGA GAAGCTTGCA 420

ACAGGCTGTG CCCAATATGA TCCAACCAAG AATGCTTCAA AGAAGCCTCT TCCTCCTACT 480

CCTGAAGACA ACAGGCGACC ACTTTGGGAA CCTGAAGAAA CTGTGGTCAT TGCCTTATAT 540

GACTACCAAA CCAATGATCC TCAGGAACTC GCACTGCGGC GCAACGAAGA GTACTGCCTG 600

CTGGACAGTT CTGAGATTCA CTGGTGGAGA GTCCAGGACA GGAATGGGCA TGAAGGATAT 660

GTACCAAGCA GTTATCTGGT GGAAAAATCT CCAAATAATC TGGAAACCTA TGAGTGGTAC 720

AATAAGAGTA TCAGCCGAGA CAAAGCTGAA AAACTTCTTT TGGACACAGG CAAAGAAGGA 780

GCCTTCATGG TAAGGGATTC CAGGACTGCA GGAACATACA CCGTGTCTGT TTTCACCAAG 840

GCTGTTGTAA GTGAGAACAA TCCCTGTATA AAGCATTATC ACATCAAGGA AACAAATGAC 900

AATCCTAAGC GATACTATGT GGCTGAAAAG TATGTGTTCG ATTCCATCCC TCTTCTCATC 960

AACTATCACC AACATAATGG AGGAGGCCTG GTGACTCGAC TCCGGTATCC AGTTTGTTTT 1020

GGGAGGCAGA AAGCCCCAGT TACAGCAGGG CTGAGATACG GGAAATGGGT GATCGACCCC 1080

TCAGAGCTCA CTTTTGTGCA AGAGATTGGC AGTGGGCAAT TTGGGTTGGT GCATCTGGGC 1140

TACTGGCTCA ACAAGGACAA GGTGGCTATC AAAACCATTC GGGAAGGGGC TATGTCAGAA 1200

GAGGACTTCA TAGAGGAGGC TGAAGTAATG ATGAAACTCT CTCATCCCAA ACTGGTGCAG 1260

CTGTATGGGG TGTGCCTGGA GCAGGCCCCC ATCTGCCTGG TGTTTGAGTT CATGGAGCAC 1320

GGCTGCCTGT CAGATTATCT ACGCACCCAG CGGGGACTTT TTGCTGCAGA GACCCTGCTG 1380

GGCATGTGTC TGGATGTGTG TGAGGGCATG GCCTACCTGG AAGAGGCATG TGTCATCCAC 1440

AGAGACTTGG CTGCCAGAAA TTGTTTGGTG GGAGAAAACC AAGTCATCAA GGTGTCTGAC 1500

TTTGGGATGA CAAGGTTCGT TCTGGATGAT CAGTACACCA GTTCCACAGG CACCAAATTC 1560

CCGGTGAAGT GGGCATCCCC AGAGGTTTTC TCTTTCAGTC GCTATAGCAG CAAGTCCGAT 1620

GTGTGGTCAT TTGGTGTGCT GATGTGGGAA GTTTTCAGTG AAGGCAAAAT CCCGTATGAA 1680

AACCGAAGCA ACTCAGAGGT GGTGGAAGAC ATCAGTACCG GATTTCGGTT GTACAAGCCC 1740

CGGCTGGCCT CCACACACGT CTACCAGATT ATGAATCACT GCTGGAAAGA GAGACCAGAA 1800

GATCGGCCAG CCTTCTCCAG ACTGCTGCGT CAACTGGCTG AAATTGCAGA ATCAGGACTT 1860

TAG 1863

Domain Profile

S: 1     ltllkelgsgqfgvvklgkwrakidvaikaikegamseedfieeakvmmklshpklvqly  60

         lt+++e+gsgqfg+v+lg+w +k++vaik+i+egamseedfieea+vmmklshpklvqly

Q: 363   LTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLY  422

         79**********************************************************

S: 61    gvclkqkpiyivteylengcllnylrekkkklekelllemckdvcegmeylerksfihrd  120

         gvcl+q+pi++v+e++e+gcl++ylr++++ +++e+ll mc dvcegm+yle++++ihrd

Q: 423   GVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRD  482

         ************************************************************

S: 121   laarnclvdeelvvkvsdfglaryvlddqyvssvgakfpvkwsppevlsyskyssksdvw  180

         laarnclv+e++v+kvsdfg++r+vlddqy+ss+g+kfpvkw++pev+s+s+yssksdvw

Q: 483   LAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVW  542

         ************************************************************

S: 181   afgvlmwevfsegklpyekksnsevvekvsrglrlyrpklaskkvyevmkscwkekpeer  240

         +fgvlmwevfsegk+pye++snsevve++s+g+rly+p+las++vy++m++cwke+pe+r

Q: 543   SFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDR  602

         ************************************************************

S: 241   ptfkellsale  251

         p+f++ll++l+

Q: 603   PAFSRLLRQLA  613

         ********996

Domain Sequence
(FASTA)

LTFVQEIGSG QFGLVHLGYW LNKDKVAIKT IREGAMSEED FIEEAEVMMK LSHPKLVQLY 60

GVCLEQAPIC LVFEFMEHGC LSDYLRTQRG LFAAETLLGM CLDVCEGMAY LEEACVIHRD 120

LAARNCLVGE NQVIKVSDFG MTRFVLDDQY TSSTGTKFPV KWASPEVFSF SRYSSKSDVW 180

SFGVLMWEVF SEGKIPYENR SNSEVVEDIS TGFRLYKPRL ASTHVYQIMN HCWKERPEDR 240

PAFSRLLRQL A 251

Keyword

3D-structure; Acetylation; Adaptive immunity; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Immunity; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase; Zinc; Zinc-finger.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0005524	; F:ATP binding
GO:0046872	; F:metal ion binding
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0005543	; F:phospholipid binding
GO:0007202	; P:activation of phospholipase C activity
GO:0002250	; P:adaptive immune response
GO:0006968	; P:cellular defense response
GO:0001816	; P:cytokine production
GO:0032609	; P:interferon-gamma production
GO:0032633	; P:interleukin-4 production
GO:0035556	; P:intracellular signal transduction
GO:0001865	; P:NK T cell differentiation
GO:0042110	; P:T cell activation
GO:0050852	; P:T cell receptor signaling pathway

KEGG

hsa:3702

;

InterPros

IPR011009	; Kinase-like_dom.
IPR011993	; PH_like_dom.
IPR001849	; Pleckstrin_homology.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR001245	; Ser-Thr/Tyr_kinase_cat_dom.
IPR000980	; SH2.
IPR001452	; SH3_domain.
IPR008266	; Tyr_kinase_AS.
IPR020635	; Tyr_kinase_cat_dom.
IPR001562	; Znf_Btk_motif.

Pfam

PF00779	; BTK; 1.
PF00169	; PH; 1.
PF07714	; Pkinase_Tyr; 1.
PF00017	; SH2; 1.
PF00018	; SH3_1; 1.

SMARTs

SM00107	; BTK; 1.
SM00233	; PH; 1.
SM00252	; SH2; 1.
SM00326	; SH3; 1.
SM00219	; TyrKc; 1.

Prosites

PS50003	; PH_DOMAIN; 1.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS50001	; SH2; 1.
PS50002	; SH3; 1.
PS51113	; ZF_BTK; 1.

Prints

PR00401	; SH2DOMAIN.
PR00109	; TYRKINASE.

Created Date

20-Feb-2013