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P42681

- TXK_HUMAN

UniProt

P42681 - TXK_HUMAN

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Protein

Tyrosine-protein kinase TXK

Gene
TXK, PTK4, RLK
Organism
Homo sapiens (Human)
Status
Reviewed - 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.

Enzyme regulationi

Activated by phosphorylation by FYN.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei299 – 2991ATP By similarity
Active sitei390 – 3901Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi277 – 2859ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. non-membrane spanning protein tyrosine kinase activity Source: ProtInc
  3. protein binding Source: IntAct
  4. RNA polymerase II regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  1. activation of phospholipase C activity Source: UniProtKB
  2. adaptive immune response Source: UniProtKB
  3. cytokine production Source: UniProtKB
  4. interferon-gamma production Source: Ensembl
  5. interleukin-4 production Source: Ensembl
  6. NK T cell differentiation Source: Ensembl
  7. peptidyl-tyrosine phosphorylation Source: GOC
  8. positive regulation of interferon-gamma-mediated signaling pathway Source: UniProtKB
  9. positive regulation of interferon-gamma production Source: UniProtKB
  10. protein autophosphorylation Source: UniProtKB
  11. protein phosphorylation Source: ProtInc
  12. regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  13. T cell receptor signaling pathway Source: UniProtKB
  14. transcription, DNA-templated Source: UniProtKB-KW
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

BRENDAi2.7.10.2. 2681.
ReactomeiREACT_163834. FCERI mediated Ca+2 mobilization.
SignaLinkiP42681.

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
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:12434. TXK.

Subcellular locationi

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.1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
  3. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi91 – 911Y → A: Reduces expression levels if IFN-gamma. 1 Publication
Mutagenesisi299 – 2991K → A: Impairs kinase activity. 1 Publication

Organism-specific databases

PharmGKBiPA37090.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 527527Tyrosine-protein kinase TXKPRO_0000088175Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei91 – 911Phosphotyrosine; by autocatalysis1 Publication
Modified residuei420 – 4201Phosphotyrosine; by FYN and autocatalysis1 Publication

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.
PRIDEiP42681.

PTM databases

PhosphoSiteiP42681.

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

ArrayExpressiP42681.
BgeeiP42681.
CleanExiHS_TXK.
GenevestigatoriP42681.

Organism-specific databases

HPAiHPA043769.

Interactioni

Subunit structurei

Interacts with PARP1 and EEF1A1. Interacts with SH2D2A By similarity.1 Publication

Binary interactionsi

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

Protein-protein interaction databases

BioGridi113145. 4 interactions.
IntActiP42681. 4 interactions.
MINTiMINT-1493369.
STRINGi9606.ENSP00000264316.

Structurei

Secondary structure

1
527
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi148 – 1514
Helixi157 – 16711
Beta strandi175 – 1784
Beta strandi181 – 1899
Beta strandi193 – 1975
Beta strandi200 – 2078
Beta strandi213 – 2186
Helixi224 – 2318
Beta strandi237 – 2393

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2DM0NMR-A140-251[»]
ProteinModelPortaliP42681.
SMRiP42681. Positions 86-526.

Miscellaneous databases

EvolutionaryTraceiP42681.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini82 – 14261SH3Add
BLAST
Domaini150 – 24697SH2Add
BLAST
Domaini271 – 527257Protein kinaseAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi68 – 736Nuclear localization signal Reviewed prediction

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi14 – 196Poly-Cys

Sequence similaritiesi

Contains 1 SH2 domain.
Contains 1 SH3 domain.

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233859.
HOVERGENiHBG008761.
InParanoidiP42681.
KOiK08016.
OMAiPIKWSPP.
OrthoDBiEOG7KM5SC.
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

MILSSYNTIQ SVFCCCCCCS VQKRQMRTQI SLSTDEELPE KYTQRRRPWL    50
SQLSNKKQSN TGRVQPSKRK PLPPLPPSEV AEEKIQVKAL YDFLPREPCN 100
LALRRAEEYL ILEKYNPHWW KARDRLGNEG LIPSNYVTEN KITNLEIYEW 150
YHRNITRNQA EHLLRQESKE GAFIVRDSRH LGSYTISVFM GARRSTEAAI 200
KHYQIKKNDS GQWYVAERHA FQSIPELIWY HQHNAAGLMT RLRYPVGLMG 250
SCLPATAGFS YEKWEIDPSE LAFIKEIGSG QFGVVHLGEW RSHIQVAIKA 300
INEGSMSEED FIEEAKVMMK LSHSKLVQLY GVCIQRKPLY IVTEFMENGC 350
LLNYLRENKG KLRKEMLLSV CQDICEGMEY LERNGYIHRD LAARNCLVSS 400
TCIVKISDFG MTRYVLDDEY VSSFGAKFPI KWSPPEVFLF NKYSSKSDVW 450
SFGVLMWEVF TEGKMPFENK SNLQVVEAIS EGFRLYRPHL APMSIYEVMY 500
SCWHEKPEGR PTFAELLRAV TEIAETW 527
Length:527
Mass (Da):61,258
Last modified:October 17, 2006 - v3
Checksum:iBCCA081F4155CAA6
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti45 – 451R → H.2 Publications
Corresponds to variant rs7658300 [ dbSNP | Ensembl ].
VAR_028368
Natural varianti63 – 631R → C.1 Publication
Corresponds to variant rs41265727 [ dbSNP | Ensembl ].
VAR_041869
Natural varianti336 – 3361R → Q.1 Publication
Corresponds to variant rs11724347 [ dbSNP | Ensembl ].
VAR_028369

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi116242835.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS3480.1.
PIRi I84483.
RefSeqi NP_003319.2. NM_003328.2.
UniGenei Hs.479669.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2DM0 NMR - A 140-251 [» ]
ProteinModelPortali P42681.
SMRi P42681. Positions 86-526.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113145. 4 interactions.
IntActi P42681. 4 interactions.
MINTi MINT-1493369.
STRINGi 9606.ENSP00000264316.

Chemistry

BindingDBi P42681.
ChEMBLi CHEMBL4367.
GuidetoPHARMACOLOGYi 2268.

PTM databases

PhosphoSitei P42681.

Polymorphism databases

DMDMi 116242835.

Proteomic databases

PaxDbi P42681.
PRIDEi P42681.

Protocols and materials databases

DNASUi 7294.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264316 ; ENSP00000264316 ; ENSG00000074966 .
GeneIDi 7294.
KEGGi hsa:7294.
UCSCi uc003gxx.4. human.

Organism-specific databases

CTDi 7294.
GeneCardsi GC04M047984.
H-InvDB HIX0031512.
HGNCi HGNC:12434. TXK.
HPAi HPA043769.
MIMi 600058. gene.
neXtProti NX_P42681.
PharmGKBi PA37090.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233859.
HOVERGENi HBG008761.
InParanoidi P42681.
KOi K08016.
OMAi PIKWSPP.
OrthoDBi EOG7KM5SC.
PhylomeDBi P42681.
TreeFami TF351634.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 2681.
Reactomei REACT_163834. FCERI mediated Ca+2 mobilization.
SignaLinki P42681.

Miscellaneous databases

ChiTaRSi TXK. human.
EvolutionaryTracei P42681.
GeneWikii TXK_(gene).
GenomeRNAii 7294.
NextBioi 28519.
PROi P42681.
SOURCEi Search...

Gene expression databases

ArrayExpressi P42681.
Bgeei P42681.
CleanExi HS_TXK.
Genevestigatori P42681.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR011009. 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 ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTi SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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.

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: September 3, 2014
This is version 143 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.

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

External Data

Dasty 3

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