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Protein

Tyrosine-protein kinase TXK

Gene

TXK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Non-receptor tyrosine kinase that plays a redundant role with 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 cytoskeleton. 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.5 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

Activated by phosphorylation by FYN.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei299ATPPROSITE-ProRule annotation1
Active sitei390Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi277 – 285ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: ProtInc
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II regulatory region DNA binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Adaptive immunity, Immunity, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01155-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-2871809. FCERI mediated Ca+2 mobilization.
SignaLinkiP42681.
SIGNORiP42681.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase TXK (EC:2.7.10.2)
Alternative name(s):
Protein-tyrosine kinase 4
Resting lymphocyte kinase
Gene namesi
Name:TXK
Synonyms:PTK4, RLK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:12434. TXK.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication
  • Cell membrane 1 Publication; Peripheral membrane protein 1 Publication

  • Note: Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation. Translocates into the nucleus and enhances IFN-gamma gene transcription in T-cells.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi91Y → A: Reduces expression levels if IFN-gamma. 1 Publication1
Mutagenesisi299K → A: Impairs kinase activity. 1 Publication1

Organism-specific databases

DisGeNETi7294.
OpenTargetsiENSG00000074966.
PharmGKBiPA37090.

Chemistry databases

ChEMBLiCHEMBL4367.
GuidetoPHARMACOLOGYi2268.

Polymorphism and mutation databases

BioMutaiTXK.
DMDMi116242835.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881751 – 527Tyrosine-protein kinase TXKAdd BLAST527

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei91Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei420Phosphotyrosine; by FYN and autocatalysis1 Publication1

Post-translational modificationi

Phosphorylated at Tyr-420 by FYN. Autophosphorylation at Tyr-91 is critical for the activation of TXK, leading to the up-regulation of IFN-gamma gene transcription.1 Publication
The cysteine string at the N-terminus is palmitoylated and required for the proper subcellular location.By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP42681.
PeptideAtlasiP42681.
PRIDEiP42681.

PTM databases

iPTMnetiP42681.
PhosphoSitePlusiP42681.

Expressioni

Tissue specificityi

Expressed in T-cells and some myeloid cell lines. Expressed in Th1/Th0 cells with IFN-gamma-producing potential.2 Publications

Gene expression databases

BgeeiENSG00000074966.
CleanExiHS_TXK.
ExpressionAtlasiP42681. baseline and differential.
GenevisibleiP42681. HS.

Organism-specific databases

HPAiHPA043769.

Interactioni

Subunit structurei

Interacts with PARP1 and EEF1A1. Interacts with SH2D2A (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
KITP107213EBI-7877438,EBI-1379503

Protein-protein interaction databases

BioGridi113145. 4 interactors.
IntActiP42681. 13 interactors.
MINTiMINT-1493369.
STRINGi9606.ENSP00000264316.

Chemistry databases

BindingDBiP42681.

Structurei

Secondary structure

1527
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi148 – 151Combined sources4
Helixi157 – 167Combined sources11
Beta strandi175 – 178Combined sources4
Beta strandi181 – 189Combined sources9
Beta strandi193 – 197Combined sources5
Beta strandi200 – 207Combined sources8
Beta strandi213 – 218Combined sources6
Helixi224 – 231Combined sources8
Beta strandi237 – 239Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DM0NMR-A140-251[»]
ProteinModelPortaliP42681.
SMRiP42681.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42681.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini82 – 142SH3PROSITE-ProRule annotationAdd BLAST61
Domaini150 – 246SH2PROSITE-ProRule annotationAdd BLAST97
Domaini271 – 527Protein kinasePROSITE-ProRule annotationAdd BLAST257

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi68 – 73Nuclear localization signalSequence analysis6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi14 – 19Poly-Cys6

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233859.
HOVERGENiHBG008761.
InParanoidiP42681.
KOiK08016.
OMAiPIKWSPP.
OrthoDBiEOG091G0D46.
PhylomeDBiP42681.
TreeFamiTF351634.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P42681-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MILSSYNTIQ SVFCCCCCCS VQKRQMRTQI SLSTDEELPE KYTQRRRPWL
60 70 80 90 100
SQLSNKKQSN TGRVQPSKRK PLPPLPPSEV AEEKIQVKAL YDFLPREPCN
110 120 130 140 150
LALRRAEEYL ILEKYNPHWW KARDRLGNEG LIPSNYVTEN KITNLEIYEW
160 170 180 190 200
YHRNITRNQA EHLLRQESKE GAFIVRDSRH LGSYTISVFM GARRSTEAAI
210 220 230 240 250
KHYQIKKNDS GQWYVAERHA FQSIPELIWY HQHNAAGLMT RLRYPVGLMG
260 270 280 290 300
SCLPATAGFS YEKWEIDPSE LAFIKEIGSG QFGVVHLGEW RSHIQVAIKA
310 320 330 340 350
INEGSMSEED FIEEAKVMMK LSHSKLVQLY GVCIQRKPLY IVTEFMENGC
360 370 380 390 400
LLNYLRENKG KLRKEMLLSV CQDICEGMEY LERNGYIHRD LAARNCLVSS
410 420 430 440 450
TCIVKISDFG MTRYVLDDEY VSSFGAKFPI KWSPPEVFLF NKYSSKSDVW
460 470 480 490 500
SFGVLMWEVF TEGKMPFENK SNLQVVEAIS EGFRLYRPHL APMSIYEVMY
510 520
SCWHEKPEGR PTFAELLRAV TEIAETW
Length:527
Mass (Da):61,258
Last modified:October 17, 2006 - v3
Checksum:iBCCA081F4155CAA6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02836845R → H.2 PublicationsCorresponds to variant rs7658300dbSNPEnsembl.1
Natural variantiVAR_04186963R → C.1 PublicationCorresponds to variant rs41265727dbSNPEnsembl.1
Natural variantiVAR_028369336R → Q.1 PublicationCorresponds to variant rs11724347dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27071 mRNA. Translation: AAA74557.1.
U34379
, U34367, U34368, U34369, U34370, U34371, U34372, U34373, U34374, U34375, U34376, U34377, U34378 Genomic DNA. Translation: AAB60412.1.
CCDSiCCDS3480.1.
PIRiI84483.
RefSeqiNP_003319.2. NM_003328.2.
UniGeneiHs.479669.

Genome annotation databases

EnsembliENST00000264316; ENSP00000264316; ENSG00000074966.
GeneIDi7294.
KEGGihsa:7294.
UCSCiuc003gxx.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L27071 mRNA. Translation: AAA74557.1.
U34379
, U34367, U34368, U34369, U34370, U34371, U34372, U34373, U34374, U34375, U34376, U34377, U34378 Genomic DNA. Translation: AAB60412.1.
CCDSiCCDS3480.1.
PIRiI84483.
RefSeqiNP_003319.2. NM_003328.2.
UniGeneiHs.479669.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DM0NMR-A140-251[»]
ProteinModelPortaliP42681.
SMRiP42681.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113145. 4 interactors.
IntActiP42681. 13 interactors.
MINTiMINT-1493369.
STRINGi9606.ENSP00000264316.

Chemistry databases

BindingDBiP42681.
ChEMBLiCHEMBL4367.
GuidetoPHARMACOLOGYi2268.

PTM databases

iPTMnetiP42681.
PhosphoSitePlusiP42681.

Polymorphism and mutation databases

BioMutaiTXK.
DMDMi116242835.

Proteomic databases

PaxDbiP42681.
PeptideAtlasiP42681.
PRIDEiP42681.

Protocols and materials databases

DNASUi7294.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264316; ENSP00000264316; ENSG00000074966.
GeneIDi7294.
KEGGihsa:7294.
UCSCiuc003gxx.4. human.

Organism-specific databases

CTDi7294.
DisGeNETi7294.
GeneCardsiTXK.
H-InvDBHIX0031512.
HGNCiHGNC:12434. TXK.
HPAiHPA043769.
MIMi600058. gene.
neXtProtiNX_P42681.
OpenTargetsiENSG00000074966.
PharmGKBiPA37090.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233859.
HOVERGENiHBG008761.
InParanoidiP42681.
KOiK08016.
OMAiPIKWSPP.
OrthoDBiEOG091G0D46.
PhylomeDBiP42681.
TreeFamiTF351634.

Enzyme and pathway databases

BioCyciZFISH:HS01155-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-2871809. FCERI mediated Ca+2 mobilization.
SignaLinkiP42681.
SIGNORiP42681.

Miscellaneous databases

ChiTaRSiTXK. human.
EvolutionaryTraceiP42681.
GeneWikiiTXK_(gene).
GenomeRNAii7294.
PROiP42681.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000074966.
CleanExiHS_TXK.
ExpressionAtlasiP42681. baseline and differential.
GenevisibleiP42681. HS.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTXK_HUMAN
AccessioniPrimary (citable) accession number: P42681
Secondary accession number(s): Q14220
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 166 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Unlike the other TEC subfamily members, TXK is activated independently of the activity of phosphatidylinositol 3-kinase, consistent with its lack of a PH domain. Membrane association is performed through palmitoylation at the N-terminus.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.