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Protein

Tyrosine-protein kinase TXK

Gene

TXK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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

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

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Kinase, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Immunity, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000074966.10
HGNCiHGNC:12434 TXK
MIMi600058 gene
neXtProtiNX_P42681

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi55527

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

HPAiHPA062482

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, 19 interactors
MINTiP42681
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

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

CDDicd10398 SH2_Tec_Txk, 1 hit
cd11907 SH3_TXK, 1 hit
Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR035870 Txk_SH2
IPR035579 TXK_SH3
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 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

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 → H2 PublicationsCorresponds to variant dbSNP:rs7658300Ensembl.1
Natural variantiVAR_04186963R → C1 PublicationCorresponds to variant dbSNP:rs41265727Ensembl.1
Natural variantiVAR_028369336R → Q1 PublicationCorresponds to variant dbSNP:rs11724347Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiTXK_HUMAN
AccessioniPrimary (citable) accession number: P42681
Secondary accession number(s): Q14220
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 17, 2006
Last modified: June 20, 2018
This is version 176 of the entry and version 3 of the sequence. See 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

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

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