EKS-MUM-00110

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00110

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Tec	487.5	1.8E-146	271	521	251

Status

Reviewed

Ensembl Protein

ENSMUSP00000109234

UniProt Accession

P42682;

Protein Name

Tyrosine-protein kinase TXK

Protein Synonyms/Alias

PTK-RL-18; Resting lymphocyte kinase;

Gene Name

Txk

Gene Synonyms/Alias

Txk; Rlk;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000054892	ENSMUSP00000129397	ENSMUST00000169534
ENSMUSG00000054892	ENSMUSP00000109234	ENSMUST00000113604

Organism

Mus musculus

Functional Description

Non-receptor tyrosine kinase that plays a redundant rolewith ITK 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 TXK to the cell membrane, where it is phosphorylated at Tyr-420. Phosphorylation leads to TXK full activation. Contributes also to signaling from many receptors and participates in multiple downstream pathways, including regulation of the actin cytoskekleton. Like ITK, can phosphorylate PLCG1, leading to its localization in lipid rafts and activation, followed by 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. With PARP1 and EEF1A1, TXK forms a complex that acts as a T-helper 1 (Th1) cell- specific transcription factor and binds the promoter of IFNG to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production. Phosphorylates both PARP1 and EEF1A1. Phosphorylates also key sites in LCP2 leading to the up-regulation of Th1 preferred cytokine IL-2. Phosphorylates 'Tyr- 201' of CTLA4 which leads to the association of PI-3 kinase with the CTLA4 receptor.

Protein Length

527

Protein Sequence
(FASTA)

MILSSYSSFQ SVLCCCCCRC SVQKRQVRTQ ISLSREEELS EKHSQRQRPW FAKLMGKTQS 60

NRGGVQPSKR KPLPPLPQEP PDERIQVKAL YDFLPREPGN LALKRAEEYL ILERCDPHWW 120

KARDRFGNEG LIPSNYVTEN RLANLEIYEW YHKNITRNQT ERLLRQEAKE GAFIVRDSRH 180

LGSYTISVFT RARRHTQSSI KHYQIKKNDS GQWYITERHL FPSVPELIQY HQYNAAGLIS 240

RLRYPIGLLG SCLPATSGFS YEKWEIDPSE LAFVKEIGSG QFGVVHLGEW RAHIPVAIKA 300

INEGSMSEED FIEEAKVMMK LSHSRLVQLY GVCIQQKPLY IVTEFMENGC LLDYLRERKG 360

QLQKALLLSM CQDICEGMAY LERSCYIHRD LAARNCLVSS ACVVKISDFG MARYVLDDEY 420

ISSSGAKFPV KWCPPEVFHF NKYSSKSDVW SFGVLMWEVF TEGKMPFENK SNLQVVEAIS 480

QGFRLYRPHL APMTIYRVMY SCWHESPKGR PTFAELLQVL TEIAETW 527

Nucleotide Sequence
(FASTA)

ATGATCCTGT CCTCTTATAG CTCCTTCCAG TCTGTTCTCT GCTGCTGCTG TTGCCGCTGC 60

TCAGTACAGA AGAGACAGGT GAGAACTCAG ATAAGCCTGA GCAGAGAGGA AGAACTCTCA 120

GAAAAACATT CCCAGCGTCA GAGGCCGTGG TTCGCCAAAC TGATGGGCAA AACTCAATCC 180

AACAGAGGCG GGGTGCAACC CTCGAAGCGC AAGCCGCTGC CCCCCCTCCC GCAGGAGCCT 240

CCAGATGAGA GAATCCAGGT CAAGGCTCTT TATGACTTCC TGCCTCGGGA GCCTGGTAAT 300

TTGGCACTGA AGAGAGCGGA GGAATATCTG ATATTGGAGA GGTGTGATCC TCACTGGTGG 360

AAGGCCAGAG ACCGCTTCGG GAATGAAGGC TTAATCCCAA GCAACTATGT GACAGAAAAC 420

AGACTCGCCA ACTTAGAAAT CTATGAATGG TACCACAAGA ACATTACGAG AAACCAGACC 480

GAACGCCTAT TGAGGCAAGA GGCTAAAGAA GGTGCCTTTA TCGTGAGAGA TTCGAGACAC 540

TTGGGGTCTT ACACAATCTC TGTGTTTACA AGAGCTCGAA GGCATACACA GTCTTCAATA 600

AAACATTATC AGATAAAAAA GAATGACTCC GGACAGTGGT ACATCACCGA AAGACATCTC 660

TTCCCCTCAG TCCCCGAGTT GATCCAGTAT CACCAGTACA ATGCAGCTGG TCTCATATCT 720

CGTCTCCGCT ATCCCATTGG GCTCCTGGGC AGCTGTTTAC CAGCCACATC TGGTTTTAGC 780

TATGAAAAGT GGGAGATAGA TCCATCAGAG TTGGCTTTTG TCAAGGAGAT CGGAAGTGGT 840

CAGTTTGGGG TTGTCCACTT AGGAGAATGG AGAGCACATA TCCCGGTCGC CATCAAGGCC 900

ATCAATGAAG GTTCCATGTC TGAAGAAGAC TTCATTGAGG AAGCCAAGGT GATGATGAAA 960

CTGTCACATT CGAGGTTAGT TCAACTTTAC GGGGTGTGTA TACAGCAGAA GCCCCTGTAC 1020

ATAGTGACGG AGTTCATGGA GAACGGCTGC CTGCTTGACT ATCTCAGGGA GAGGAAAGGC 1080

CAGCTTCAGA AGGCGCTGCT CTTGAGCATG TGCCAAGACA TATGTGAAGG GATGGCGTAC 1140

CTGGAGAGGA GCTGCTATAT TCACAGGGAT CTGGCTGCCA GGAACTGTTT GGTCAGTTCT 1200

GCCTGCGTAG TAAAGATCTC AGACTTCGGC ATGGCGAGGT ATGTTTTGGA CGATGAATAT 1260

ATCAGTTCTT CTGGAGCTAA GTTCCCAGTC AAGTGGTGCC CACCTGAAGT CTTTCATTTC 1320

AACAAATACA GTAGCAAGTC TGATGTCTGG TCGTTCGGAG TTTTAATGTG GGAAGTTTTT 1380

ACAGAAGGAA AAATGCCTTT TGAAAATAAG TCAAATTTGC AAGTGGTGGA AGCCATTTCT 1440

CAAGGTTTCC GGCTGTATCG TCCTCACCTG GCCCCCATGA CCATATACAG AGTGATGTAC 1500

AGTTGCTGGC ATGAGAGCCC TAAAGGCCGT CCGACATTTG CTGAGCTGCT TCAGGTTCTC 1560

ACGGAGATCG CAGAAACGTG GTGA 1584

Domain Profile

S: 1     ltllkelgsgqfgvvklgkwrakidvaikaikegamseedfieeakvmmklshpklvqly  60

         l+++ke+gsgqfgvv+lg+wra+i vaikai+eg+mseedfieeakvmmklsh++lvqly

Q: 271   LAFVKEIGSGQFGVVHLGEWRAHIPVAIKAINEGSMSEEDFIEEAKVMMKLSHSRLVQLY  330

         68**********************************************************

S: 61    gvclkqkpiyivteylengcllnylrekkkklekelllemckdvcegmeylerksfihrd  120

         gvc++qkp+yivte++engcll+ylre+k++l+k+lll+mc+d+cegm+yler+++ihrd

Q: 331   GVCIQQKPLYIVTEFMENGCLLDYLRERKGQLQKALLLSMCQDICEGMAYLERSCYIHRD  390

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

S: 121   laarnclvdeelvvkvsdfglaryvlddqyvssvgakfpvkwsppevlsyskyssksdvw  180

         laarnclv++++vvk+sdfg+aryvldd+y+ss+gakfpvkw+ppev++++kyssksdvw

Q: 391   LAARNCLVSSACVVKISDFGMARYVLDDEYISSSGAKFPVKWCPPEVFHFNKYSSKSDVW  450

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

S: 181   afgvlmwevfsegklpyekksnsevvekvsrglrlyrpklaskkvyevmkscwkekpeer  240

         +fgvlmwevf+egk+p+e+ksn +vve++s+g+rlyrp+la++++y+vm+scw+e+p++r

Q: 451   SFGVLMWEVFTEGKMPFENKSNLQVVEAISQGFRLYRPHLAPMTIYRVMYSCWHESPKGR  510

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

S: 241   ptfkellsale  251

         ptf+ell+ l+

Q: 511   PTFAELLQVLT  521

         *******9986

Domain Sequence
(FASTA)

LAFVKEIGSG QFGVVHLGEW RAHIPVAIKA INEGSMSEED FIEEAKVMMK LSHSRLVQLY 60

GVCIQQKPLY IVTEFMENGC LLDYLRERKG QLQKALLLSM CQDICEGMAY LERSCYIHRD 120

LAARNCLVSS ACVVKISDFG MARYVLDDEY ISSSGAKFPV KWCPPEVFHF NKYSSKSDVW 180

SFGVLMWEVF TEGKMPFENK SNLQVVEAIS QGFRLYRPHL APMTIYRVMY SCWHESPKGR 240

PTFAELLQVL T 251

Keyword

Adaptive immunity; Alternative initiation; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; DNA-binding; Immunity; Kinase; Lipoprotein; Membrane; Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Reference proteome; SH2 domain; SH3 domain; Transcription; Transcription regulation; Transferase; Tyrosine-protein kinase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Equus caballus"; ?>Erinaceus europaeus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Tursiops truncatus"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005634	; C:nucleus
GO:0005886	; C:plasma membrane
GO:0005524	; F:ATP binding
GO:0004715	; F:non-membrane spanning protein tyrosine kinase activity
GO:0001012	; F:RNA polymerase II regulatory region DNA 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:0001865	; P:NK T cell differentiation
GO:0032729	; P:positive regulation of interferon-gamma production
GO:0060335	; P:positive regulation of interferon-gamma-mediated signaling pathway
GO:0046777	; P:protein autophosphorylation
GO:0006357	; P:regulation of transcription from RNA polymerase II promoter
GO:0050852	; P:T cell receptor signaling pathway
GO:0006351	; P:transcription, DNA-dependent

KEGG

mmu:22165

;

InterPros

IPR011009	; Kinase-like_dom.
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.

Pfam

PF07714	; Pkinase_Tyr; 1.
PF00017	; SH2; 1.
PF00018	; SH3_1; 1.

SMARTs

SM00252	; SH2; 1.
SM00326	; SH3; 1.
SM00219	; TyrKc; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS50001	; SH2; 1.
PS50002	; SH3; 1.

Prints

PR00401	; SH2DOMAIN.
PR00109	; TYRKINASE.

Created Date

20-Feb-2013