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P42681 (TXK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase TXK

EC=2.7.10.2
Alternative name(s):
Protein-tyrosine kinase 4
Resting lymphocyte kinase
Gene names
Name:TXK
Synonyms:PTK4, RLK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length527 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.4 Ref.5 Ref.7 Ref.8

Catalytic activity

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

Enzyme regulation

Activated by phosphorylation by FYN. Ref.6

Subunit structure

Interacts with PARP1 and EEF1A1. Interacts with SH2D2A By similarity. Ref.8

Subcellular location

Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. 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. Ref.8

Tissue specificity

Expressed in T-cells and some myeloid cell lines. Expressed in Th1/Th0 cells with IFN-gamma-producing potential. Ref.1 Ref.4

Post-translational modification

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. Ref.6

The cysteine string at the N-terminus is palmitoylated and required for the proper subcellular location By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

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.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
Transcription
Transcription regulation
   Cellular componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DomainSH2 domain
SH3 domain
   LigandATP-binding
DNA-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMLipoprotein
Palmitate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNK T cell differentiation

Inferred from electronic annotation. Source: Ensembl

T cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

activation of phospholipase C activity

Inferred from sequence or structural similarity. Source: UniProtKB

adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

cytokine production

Inferred from sequence or structural similarity. Source: UniProtKB

interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

interleukin-4 production

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Traceable author statement Ref.1. Source: GOC

positive regulation of interferon-gamma production

Inferred from direct assay Ref.4Ref.7. Source: UniProtKB

positive regulation of interferon-gamma-mediated signaling pathway

Inferred from direct assay Ref.7. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.6. Source: UniProtKB

protein phosphorylation

Traceable author statement Ref.1. Source: ProtInc

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.7. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.4. Source: UniProtKB

nucleus

Inferred from direct assay Ref.4. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA polymerase II regulatory region DNA binding

Inferred from direct assay Ref.7. Source: UniProtKB

non-membrane spanning protein tyrosine kinase activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 24728074. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

KITP107213EBI-7877438,EBI-1379503

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 527527Tyrosine-protein kinase TXK
PRO_0000088175

Regions

Domain82 – 14261SH3
Domain150 – 24697SH2
Domain271 – 527257Protein kinase
Nucleotide binding277 – 2859ATP By similarity
Motif68 – 736Nuclear localization signal Potential
Compositional bias14 – 196Poly-Cys

Sites

Active site3901Proton acceptor By similarity
Binding site2991ATP By similarity

Amino acid modifications

Modified residue911Phosphotyrosine; by autocatalysis Ref.6
Modified residue4201Phosphotyrosine; by FYN and autocatalysis Ref.6

Natural variations

Natural variant451R → H. Ref.1 Ref.11
Corresponds to variant rs7658300 [ dbSNP | Ensembl ].
VAR_028368
Natural variant631R → C. Ref.11
Corresponds to variant rs41265727 [ dbSNP | Ensembl ].
VAR_041869
Natural variant3361R → Q. Ref.11
Corresponds to variant rs11724347 [ dbSNP | Ensembl ].
VAR_028369

Experimental info

Mutagenesis911Y → A: Reduces expression levels if IFN-gamma. Ref.6
Mutagenesis2991K → A: Impairs kinase activity. Ref.3

Secondary structure

................... 527
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42681 [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: BCCA081F4155CAA6

FASTA52761,258
        10         20         30         40         50         60 
MILSSYNTIQ SVFCCCCCCS VQKRQMRTQI SLSTDEELPE KYTQRRRPWL SQLSNKKQSN 

        70         80         90        100        110        120 
TGRVQPSKRK PLPPLPPSEV AEEKIQVKAL YDFLPREPCN LALRRAEEYL ILEKYNPHWW 

       130        140        150        160        170        180 
KARDRLGNEG LIPSNYVTEN KITNLEIYEW YHRNITRNQA EHLLRQESKE GAFIVRDSRH 

       190        200        210        220        230        240 
LGSYTISVFM GARRSTEAAI KHYQIKKNDS GQWYVAERHA FQSIPELIWY HQHNAAGLMT 

       250        260        270        280        290        300 
RLRYPVGLMG SCLPATAGFS YEKWEIDPSE LAFIKEIGSG QFGVVHLGEW RSHIQVAIKA 

       310        320        330        340        350        360 
INEGSMSEED FIEEAKVMMK LSHSKLVQLY GVCIQRKPLY IVTEFMENGC LLNYLRENKG 

       370        380        390        400        410        420 
KLRKEMLLSV CQDICEGMEY LERNGYIHRD LAARNCLVSS TCIVKISDFG MTRYVLDDEY 

       430        440        450        460        470        480 
VSSFGAKFPI KWSPPEVFLF NKYSSKSDVW SFGVLMWEVF TEGKMPFENK SNLQVVEAIS 

       490        500        510        520 
EGFRLYRPHL APMSIYEVMY SCWHEKPEGR PTFAELLRAV TEIAETW 

« Hide

References

« Hide 'large scale' references
[1]"TXK, a novel human tyrosine kinase expressed in T cells shares sequence identity with Tec family kinases and maps to 4p12."
Haire R.N., Ohta Y., Lewis J.E., Fu S.M., Kroisel P.M., Litman G.W.
Hum. Mol. Genet. 3:897-901(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-45, TISSUE SPECIFICITY.
Tissue: Blood.
[2]"Human Txk: genomic organization, structure and contiguous physical linkage with the Tec gene."
Ohta Y., Haire R.N., Amemiya C.T., Litman R.T., Trager T., Riess O., Litman G.W.
Oncogene 12:937-942(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Blood.
[3]"Resting lymphocyte kinase (Rlk/Txk) phosphorylates the YVKM motif and regulates PI 3-kinase binding to T-cell antigen CTLA-4."
Schneider H., Schwartzberg P.L., Rudd C.E.
Biochem. Biophys. Res. Commun. 252:14-19(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CTLA4, MUTAGENESIS OF LYS-299.
[4]"Txk, a nonreceptor tyrosine kinase of the Tec family, is expressed in T helper type 1 cells and regulates interferon gamma production in human T lymphocytes."
Kashiwakura J., Suzuki N., Nagafuchi H., Takeno M., Takeba Y., Shimoyama Y., Sakane T.
J. Exp. Med. 190:1147-1154(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, FUNCTION.
[5]"Membrane raft-dependent regulation of phospholipase Cgamma-1 activation in T lymphocytes."
Veri M.C., DeBell K.E., Seminario M.C., DiBaldassarre A., Reischl I., Rawat R., Graham L., Noviello C., Rellahan B.L., Miscia S., Wange R.L., Bonvini E.
Mol. Cell. Biol. 21:6939-6950(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PLCG1.
[6]"Evidence of autophosphorylation in Txk: Y91 is an autophosphorylation site."
Kashiwakura J., Suzuki N., Takeno M., Itoh S., Oku T., Sakane T., Nakajin S., Toyoshima S.
Biol. Pharm. Bull. 25:718-721(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-91 AND TYR-420, ENZYME REGULATION, MUTAGENESIS OF TYR-91.
[7]"Txk, a member of nonreceptor tyrosine kinase of Tec family, acts as a Th1 cell-specific transcription factor and regulates IFN-gamma gene transcription."
Takeba Y., Nagafuchi H., Takeno M., Kashiwakura J., Suzuki N.
J. Immunol. 168:2365-2370(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, FUNCTION.
[8]"Txk, a member of the non-receptor tyrosine kinase of the Tec family, forms a complex with poly(ADP-ribose) polymerase 1 and elongation factor 1alpha and regulates interferon-gamma gene transcription in Th1 cells."
Maruyama T., Nara K., Yoshikawa H., Suzuki N.
Clin. Exp. Immunol. 147:164-175(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PARP1 AND EEF1A1, FUNCTION IN PHOSPHORYLATION OF PARP1 AND EEF1A1, SUBCELLULAR LOCATION, FUNCTION AS A TRANSCRIPTION FACTOR.
[9]"Tec kinases regulate T-lymphocyte development and function: new insights into the roles of Itk and Rlk/Txk."
Readinger J.A., Mueller K.L., Venegas A.M., Horai R., Schwartzberg P.L.
Immunol. Rev. 228:93-114(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[10]"Solution structure of the SH2 domain of human tyrosine-protein kinase TXK."
RIKEN structural genomics initiative (RSGI)
Submitted (OCT-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 140-251.
[11]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-45; CYS-63 AND GLN-336.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L27071 mRNA. Translation: AAA74557.1.
U34379 expand/collapse EMBL AC list , U34367, U34368, U34369, U34370, U34371, U34372, U34373, U34374, U34375, U34376, U34377, U34378 Genomic DNA. Translation: AAB60412.1.
CCDSCCDS3480.1.
PIRI84483.
RefSeqNP_003319.2. NM_003328.2.
UniGeneHs.479669.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DM0NMR-A140-251[»]
ProteinModelPortalP42681.
SMRP42681. Positions 86-526.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113145. 4 interactions.
IntActP42681. 4 interactions.
MINTMINT-1493369.
STRING9606.ENSP00000264316.

Chemistry

BindingDBP42681.
ChEMBLCHEMBL4367.
GuidetoPHARMACOLOGY2268.

PTM databases

PhosphoSiteP42681.

Polymorphism databases

DMDM116242835.

Proteomic databases

PaxDbP42681.
PRIDEP42681.

Protocols and materials databases

DNASU7294.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264316; ENSP00000264316; ENSG00000074966.
GeneID7294.
KEGGhsa:7294.
UCSCuc003gxx.4. human.

Organism-specific databases

CTD7294.
GeneCardsGC04M047984.
H-InvDBHIX0031512.
HGNCHGNC:12434. TXK.
HPAHPA043769.
MIM600058. gene.
neXtProtNX_P42681.
PharmGKBPA37090.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233859.
HOVERGENHBG008761.
InParanoidP42681.
KOK08016.
OMAPIKWSPP.
OrthoDBEOG7KM5SC.
PhylomeDBP42681.
TreeFamTF351634.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_6900. Immune System.
SignaLinkP42681.

Gene expression databases

ArrayExpressP42681.
BgeeP42681.
CleanExHS_TXK.
GenevestigatorP42681.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR011009. 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]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. 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]
ProtoNetSearch...

Other

ChiTaRSTXK. human.
EvolutionaryTraceP42681.
GeneWikiTXK_(gene).
GenomeRNAi7294.
NextBio28519.
PROP42681.
SOURCESearch...

Entry information

Entry nameTXK_HUMAN
AccessionPrimary (citable) accession number: P42681
Secondary accession number(s): Q14220
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM