EKS-MUM-00112

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00112

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Tec	475.9	6.2E-143	362	612	251

Status

Reviewed

Ensembl Protein

ENSMUSP00000020664

UniProt Accession

Q03526;

Protein Name

Tyrosine-protein kinase ITK/TSK

Protein Synonyms/Alias

IL-2-inducible T-cell kinase; Kinase EMT; Kinase TLK; T-cell-specific kinase;

Gene Name

Itk

Gene Synonyms/Alias

Itk; Emt, Tlk, Tsk;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000020395	ENSMUSP00000104860	ENSMUST00000109237
ENSMUSG00000020395	ENSMUSP00000098864	ENSMUST00000101306
ENSMUSG00000020395	ENSMUSP00000020664	ENSMUST00000020664

Organism

Mus musculus

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

619

Protein Sequence
(FASTA)

MNNFILLEEQ LIKKSQQKRR TSPSNFKVRF FVLTKASLAY FEDRHGKKRT LKGSIELSRI 60

KCVEIVKSDI SIPCHYKYPF QVVHDNYLLY VFAPDCESRQ RWVLTLKEET RNNNSLVSKY 120

HPNFWMDGRW RCCSQLEKPA VGCAPYDPSK NASKKPLPPT PEDNRRSFQE PEETLVIALY 180

DYQTNDPQEL ALRCDEEYYL LDSSEIHWWR VQDKNGHEGY APSSYLVEKS PNNLETYEWY 240

NKSISRDKAE KLLLDTGKEG AFMVRDSRTP GTYTVSVFTK AIISENPCIK HYHIKETNDS 300

PKRYYVAEKY VFDSIPLLIQ YHQYNGGGLV TRLRYPVCSW RQKAPVTAGL RYGKWVIQPS 360

ELTFVQEIGS GQFGLVHLGY WLNKDKVAIK TIQEGAMSEE DFIEEAEVMM KLSHPKLVQL 420

YGVCLEQAPI CLVFEFMEHG CLSDYLRSQR GLFAAETLLG MCLDVCEGMA YLEKACVIHR 480

DLAARNCLVG ENQVIKVSDF GMTRFVLDDQ YTSSTGTKFP VKWASPEVFS FSRYSSKSDV 540

WSFGVLMWEV FSEGKIPYEN RSNSEVVEDI STGFRLYKPR LASCHVYQIM NHCWKEKPED 600

RPPFSQLLSQ LAEIAEAGL 619

Nucleotide Sequence
(FASTA)

ATGAACAACT TCATCCTCCT GGAAGAACAG CTGATCAAGA AGTCCCAACA GAAGAGAAGG 60

ACTTCTCCCT CGAATTTTAA AGTTCGTTTC TTTGTCTTAA CGAAAGCCAG CCTGGCCTAC 120

TTTGAGGACC GCCACGGGAA GAAGCGCACG TTGAAGGGCT CCATTGAACT CTCCAGAATC 180

AAGTGTGTGG AGATTGTCAA GAGTGACATT AGCATCCCGT GCCACTATAA ATACCCTTTT 240

CAGGTCGTGC ATGACAACTA TCTCCTGTAT GTGTTTGCTC CAGACTGTGA GAGTCGGCAG 300

CGCTGGGTGC TGACCCTTAA AGAAGAAACG AGGAATAACA ACAGCCTGGT ATCCAAGTAT 360

CACCCTAATT TCTGGATGGA TGGGCGGTGG AGGTGCTGCT CCCAGCTGGA GAAGCCTGCT 420

GTAGGCTGTG CTCCCTACGA CCCATCCAAG AATGCTTCAA AGAAGCCTCT TCCTCCTACT 480

CCTGAAGACA ACAGGCGGTC ATTTCAGGAA CCTGAAGAAA CCCTGGTCAT TGCCTTGTAC 540

GACTACCAAA CCAACGACCC TCAGGAGCTC GCACTGCGGT GTGATGAAGA GTACTACCTG 600

CTGGACAGCT CCGAGATCCA CTGGTGGAGG GTTCAAGACA AAAATGGGCA TGAAGGATAT 660

GCACCAAGCA GTTACCTGGT AGAAAAATCT CCAAATAACC TTGAAACCTA TGAGTGGTAC 720

AATAAAAGCA TCAGCCGCGA CAAAGCTGAA AAACTTCTTT TGGACACAGG TAAAGAAGGA 780

GCTTTCATGG TCCGAGATTC CAGGACACCC GGGACATACA CAGTCTCTGT TTTCACCAAG 840

GCCATCATAA GTGAGAACCC CTGTATAAAA CATTATCACA TCAAAGAAAC AAATGACAGC 900

CCCAAGCGCT ACTACGTGGC TGAGAAGTAT GTGTTTGACT CCATCCCTCT CCTCATCCAG 960

TATCACCAGT ACAATGGAGG AGGTTTGGTC ACTCGACTCC GCTATCCAGT TTGCTCCTGG 1020

AGACAAAAAG CCCCTGTCAC AGCAGGGCTA AGATATGGGA AGTGGGTGAT CCAACCCTCA 1080

GAGCTAACGT TCGTGCAGGA GATTGGCAGC GGGCAGTTTG GGCTGGTGCA TCTCGGCTAC 1140

TGGCTCAACA AGGACAAGGT GGCCATCAAG ACCATTCAGG AAGGGGCGAT GTCAGAAGAA 1200

GACTTTATCG AGGAGGCGGA AGTCATGATG AAACTCTCTC ACCCCAAACT GGTGCAGCTC 1260

TATGGGGTGT GCCTGGAGCA AGCCCCCATC TGCCTGGTGT TTGAGTTCAT GGAGCACGGC 1320

TGCCTGTCGG ATTACCTTCG AAGTCAGCGG GGTCTCTTTG CTGCGGAGAC CCTGCTGGGC 1380

ATGTGCCTGG ATGTGTGTGA GGGCATGGCC TACCTGGAAA AAGCTTGTGT CATCCACAGA 1440

GACCTGGCAG CCAGAAACTG TTTGGTGGGA GAAAACCAGG TCATCAAGGT GTCCGACTTT 1500

GGGATGACAA GATTTGTCCT TGATGATCAA TATACCAGCT CCACGGGCAC CAAATTCCCA 1560

GTGAAGTGGG CATCCCCAGA GGTGTTCTCC TTTAGTCGCT ATAGCAGCAA GTCAGATGTG 1620

TGGTCGTTTG GTGTACTGAT GTGGGAAGTC TTCAGTGAAG GCAAAATCCC ATACGAAAAC 1680

CGAAGCAATT CCGAGGTCGT GGAAGATATC AGCACTGGCT TTCGGTTATA CAAGCCCCGC 1740

CTGGCCTCCT GTCATGTCTA CCAGATCATG AATCATTGCT GGAAAGAGAA ACCAGAAGAC 1800

CGGCCACCCT TCTCCCAGCT GTTAAGCCAG CTGGCTGAAA TCGCAGAAGC TGGGCTTTAG 1860

Domain Profile

S: 1     ltllkelgsgqfgvvklgkwrakidvaikaikegamseedfieeakvmmklshpklvqly  60

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

Q: 362   LTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIQEGAMSEEDFIEEAEVMMKLSHPKLVQLY  421

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

S: 61    gvclkqkpiyivteylengcllnylrekkkklekelllemckdvcegmeylerksfihrd  120

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

Q: 422   GVCLEQAPICLVFEFMEHGCLSDYLRSQRGLFAAETLLGMCLDVCEGMAYLEKACVIHRD  481

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

S: 121   laarnclvdeelvvkvsdfglaryvlddqyvssvgakfpvkwsppevlsyskyssksdvw  180

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

Q: 482   LAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVW  541

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

S: 181   afgvlmwevfsegklpyekksnsevvekvsrglrlyrpklaskkvyevmkscwkekpeer  240

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

Q: 542   SFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASCHVYQIMNHCWKEKPEDR  601

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

S: 241   ptfkellsale  251

         p f++lls+l+

Q: 602   PPFSQLLSQLA  612

         ********996

Domain Sequence
(FASTA)

LTFVQEIGSG QFGLVHLGYW LNKDKVAIKT IQEGAMSEED FIEEAEVMMK LSHPKLVQLY 60

GVCLEQAPIC LVFEFMEHGC LSDYLRSQRG LFAAETLLGM CLDVCEGMAY LEKACVIHRD 120

LAARNCLVGE NQVIKVSDFG MTRFVLDDQY TSSTGTKFPV KWASPEVFSF SRYSSKSDVW 180

SFGVLMWEVF SEGKIPYENR SNSEVVEDIS TGFRLYKPRL ASCHVYQIMN HCWKEKPEDR 240

PPFSQLLSQL A 251

Keyword

3D-structure; Acetylation; Adaptive immunity; ATP-binding; Complete proteome; Cytoplasm; Immunity; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; 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"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>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:0005737	; C:cytoplasm
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: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:0050852	; P:T cell receptor signaling pathway

KEGG

mmu:16428

;

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.
PR00402	; TECBTKDOMAIN.
PR00109	; TYRKINASE.

Created Date

20-Feb-2013