EKS-HOS-00111

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00111

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Tec	485.9	1.1E-145	271	521	251

Status

Reviewed

Ensembl Protein

ENSP00000264316

UniProt Accession

P42681; Q14220;

Protein Name

Tyrosine-protein kinase TXK

Protein Synonyms/Alias

Protein-tyrosine kinase 4; Resting lymphocyte kinase;

Gene Name

TXK

Gene Synonyms/Alias

TXK; PTK4, RLK;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000074966	ENSP00000424070	ENST00000509681
ENSG00000074966	ENSP00000264316	ENST00000264316
ENSG00000074966	ENSP00000422139	ENST00000514937
ENSG00000074966	ENSP00000423481	ENST00000507351
ENSG00000074966	ENSP00000422798	ENST00000506073

Organism

Homo sapiens

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)

MILSSYNTIQ SVFCCCCCCS VQKRQMRTQI SLSTDEELPE KYTQRRRPWL SQLSNKKQSN 60

TGRVQPSKRK PLPPLPPSEV AEEKIQVKAL YDFLPREPCN LALRRAEEYL ILEKYNPHWW 120

KARDRLGNEG LIPSNYVTEN KITNLEIYEW YHRNITRNQA EHLLRQESKE GAFIVRDSRH 180

LGSYTISVFM GARRSTEAAI KHYQIKKNDS GQWYVAERHA FQSIPELIWY HQHNAAGLMT 240

RLRYPVGLMG SCLPATAGFS YEKWEIDPSE LAFIKEIGSG QFGVVHLGEW RSHIQVAIKA 300

INEGSMSEED FIEEAKVMMK LSHSKLVQLY GVCIQRKPLY IVTEFMENGC LLNYLRENKG 360

KLRKEMLLSV CQDICEGMEY LERNGYIHRD LAARNCLVSS TCIVKISDFG MTRYVLDDEY 420

VSSFGAKFPI KWSPPEVFLF NKYSSKSDVW SFGVLMWEVF TEGKMPFENK SNLQVVEAIS 480

EGFRLYRPHL APMSIYEVMY SCWHEKPEGR PTFAELLRAV TEIAETW 527

Nucleotide Sequence
(FASTA)

ATGATCCTTT CCTCCTATAA CACCATCCAG TCGGTTTTCT GTTGCTGCTG TTGCTGTTCA 60

GTGCAGAAGC GACAAATGAG AACACAGATA AGCCTGAGCA CAGATGAAGA GCTTCCAGAA 120

AAATACACCC AGCGTCGCAG GCCGTGGCTC AGCCAATTGT CAAATAAGAA GCAATCCAAC 180

ACGGGCCGTG TGCAGCCGTC AAAACGAAAG CCACTGCCTC CCCTCCCACC CTCTGAGGTT 240

GCTGAAGAGA AGATCCAAGT CAAGGCACTT TATGATTTTC TGCCCAGAGA ACCCTGTAAT 300

TTAGCCTTAA GGAGAGCAGA AGAATACCTG ATACTGGAGA AATACAATCC TCACTGGTGG 360

AAGGCAAGAG ACCGTTTGGG GAATGAAGGC TTAATCCCAA GCAACTATGT GACTGAAAAC 420

AAAATAACTA ATTTAGAAAT ATATGAGTGG TACCATAGAA ACATTACCAG AAATCAGGCA 480

GAACATCTAT TGAGACAAGA GTCTAAAGAA GGTGCATTTA TTGTCAGAGA TTCAAGACAT 540

TTAGGATCCT ACACAATTTC CGTATTTATG GGAGCTAGAA GAAGTACGGA GGCTGCCATA 600

AAACATTATC AGATAAAAAA GAATGACTCA GGACAGTGGT ATGTGGCTGA AAGACACGCC 660

TTTCAATCAA TCCCTGAGTT AATCTGGTAT CACCAGCACA ATGCAGCCGG TCTCATGACT 720

CGTCTCCGAT ATCCAGTTGG GCTGATGGGC AGTTGTTTAC CAGCCACAGC TGGGTTTAGC 780

TACGAAAAGT GGGAGATAGA TCCATCTGAG TTGGCTTTTA TAAAGGAGAT TGGAAGCGGT 840

CAGTTTGGAG TGGTCCATTT AGGTGAATGG CGGTCACATA TCCAGGTAGC TATCAAGGCC 900

ATCAATGAAG GCTCCATGTC TGAAGAGGAT TTCATTGAAG AGGCCAAAGT GATGATGAAA 960

TTATCTCATT CAAAGCTAGT GCAACTTTAT GGAGTCTGTA TACAGCGGAA GCCCCTTTAC 1020

ATTGTGACAG AGTTCATGGA AAATGGCTGC CTGCTTAACT ATCTCAGGGA GAATAAAGGA 1080

AAGCTTAGGA AGGAAATGCT ACTGAGTGTA TGCCAGGATA TATGTGAAGG AATGGAATAT 1140

CTGGAGAGGA ATGGCTATAT TCATAGGGAT TTGGCGGCAA GGAATTGTTT GGTCAGTTCA 1200

ACATGCATAG TAAAAATTTC AGACTTTGGA ATGACAAGGT ACGTTTTGGA TGATGAGTAT 1260

GTCAGTTCTT TTGGAGCCAA GTTCCCAATC AAGTGGTCCC CTCCTGAAGT TTTTCTTTTC 1320

AATAAGTACA GCAGTAAATC TGATGTCTGG TCATTTGGAG TTTTAATGTG GGAAGTTTTT 1380

ACAGAAGGAA AAATGCCTTT TGAAAATAAG TCAAATTTGC AAGTCGTGGA AGCTATTTCT 1440

GAAGGCTTCA GGCTATATCG CCCTCACCTG GCACCAATGT CCATATATGA AGTCATGTAC 1500

AGCTGCTGGC ATGAGAAACC TGAAGGCCGC CCTACATTTG CCGAGCTGCT GCGGGCTGTC 1560

ACAGAGATTG CGGAAACCTG GTGA 1584

Domain Profile

S: 1     ltllkelgsgqfgvvklgkwrakidvaikaikegamseedfieeakvmmklshpklvqly  60

         l+++ke+gsgqfgvv+lg+wr++i+vaikai+eg+mseedfieeakvmmklsh+klvqly

Q: 271   LAFIKEIGSGQFGVVHLGEWRSHIQVAIKAINEGSMSEEDFIEEAKVMMKLSHSKLVQLY  330

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

S: 61    gvclkqkpiyivteylengcllnylrekkkklekelllemckdvcegmeylerksfihrd  120

         gvc+++kp+yivte++engcllnylre+k+kl+ke+ll++c+d+cegmeyler+ +ihrd

Q: 331   GVCIQRKPLYIVTEFMENGCLLNYLRENKGKLRKEMLLSVCQDICEGMEYLERNGYIHRD  390

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

S: 121   laarnclvdeelvvkvsdfglaryvlddqyvssvgakfpvkwsppevlsyskyssksdvw  180

         laarnclv+++++vk+sdfg++ryvldd+yvss gakfp+kwsppev+ ++kyssksdvw

Q: 391   LAARNCLVSSTCIVKISDFGMTRYVLDDEYVSSFGAKFPIKWSPPEVFLFNKYSSKSDVW  450

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

S: 181   afgvlmwevfsegklpyekksnsevvekvsrglrlyrpklaskkvyevmkscwkekpeer  240

         +fgvlmwevf+egk+p+e+ksn +vve++s+g+rlyrp+la++++yevm+scw+ekpe+r

Q: 451   SFGVLMWEVFTEGKMPFENKSNLQVVEAISEGFRLYRPHLAPMSIYEVMYSCWHEKPEGR  510

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

S: 241   ptfkellsale  251

         ptf+ell+a++

Q: 511   PTFAELLRAVT  521

         ********986

Domain Sequence
(FASTA)

LAFIKEIGSG QFGVVHLGEW RSHIQVAIKA INEGSMSEED FIEEAKVMMK LSHSKLVQLY 60

GVCIQRKPLY IVTEFMENGC LLNYLRENKG KLRKEMLLSV CQDICEGMEY LERNGYIHRD 120

LAARNCLVSS TCIVKISDFG MTRYVLDDEY VSSFGAKFPI KWSPPEVFLF NKYSSKSDVW 180

SFGVLMWEVF TEGKMPFENK SNLQVVEAIS EGFRLYRPHL APMSIYEVMY SCWHEKPEGR 240

PTFAELLRAV T 251

Keyword

3D-structure; Adaptive immunity; ATP-binding; Cell membrane; Complete proteome; Cytoplasm; DNA-binding; Immunity; Kinase; Lipoprotein; Membrane; Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Polymorphism; 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"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oryctolagus cuniculus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Tursiops truncatus"; ?>

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:0001816	; P:cytokine production
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

hsa:7294

;

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