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Protein

Tyrosine-protein kinase TXK

Gene

Txk

Organism
Mus musculus (Mouse)
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.4 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei299 – 2991ATPPROSITE-ProRule annotation
Active sitei390 – 3901Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi277 – 2859ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  3. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI
  4. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: MGI
  5. RNA polymerase II regulatory region DNA binding Source: MGI

GO - Biological processi

  1. activation of phospholipase C activity Source: UniProtKB
  2. adaptive immune response Source: UniProtKB
  3. cytokine production Source: UniProtKB
  4. innate immune response Source: GO_Central
  5. interferon-gamma production Source: MGI
  6. interleukin-4 production Source: MGI
  7. NK T cell differentiation Source: MGI
  8. peptidyl-tyrosine autophosphorylation Source: GO_Central
  9. positive regulation of interferon-gamma-mediated signaling pathway Source: MGI
  10. positive regulation of interferon-gamma production Source: MGI
  11. positive regulation of transcription from RNA polymerase II promoter Source: MGI
  12. protein autophosphorylation Source: MGI
  13. regulation of cell proliferation Source: GO_Central
  14. regulation of transcription from RNA polymerase II promoter Source: MGI
  15. T cell receptor signaling pathway Source: UniProtKB
  16. transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
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. 3474.
ReactomeiREACT_188202. FCERI mediated Ca+2 mobilization.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase TXK (EC:2.7.10.2)
Alternative name(s):
PTK-RL-18
Resting lymphocyte kinase
Gene namesi
Name:Txk
Synonyms:Rlk
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 5

Organism-specific databases

MGIiMGI:102960. Txk.

Subcellular locationi

Cytoplasm By similarity. Nucleus By similarity. 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.By similarity

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  3. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi16 – 183CCC → SLA: Reduces palmitoylation and leads to nuclear localization. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 527527Tyrosine-protein kinase TXKPRO_0000088176Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei91 – 911Phosphotyrosine; by autocatalysis1 Publication
Modified residuei420 – 4201Phosphotyrosine; by FYN and autocatalysis2 Publications

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.By similarity
The cysteine string at the N-terminus is palmitoylated and required for the proper subcellular location.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP42682.
PRIDEiP42682.

PTM databases

PhosphoSiteiP42682.

Expressioni

Tissue specificityi

Expressed in early thymocytes, T-cells and mast cells.

Gene expression databases

BgeeiP42682.
CleanExiMM_TXK.
ExpressionAtlasiP42682. baseline and differential.
GenevestigatoriP42682.

Interactioni

Subunit structurei

Interacts with PARP1 and EEF1A1 (By similarity). Interacts with SH2D2A.By similarity2 Publications

Protein-protein interaction databases

IntActiP42682. 1 interaction.
MINTiMINT-4138781.
STRINGi10090.ENSMUSP00000109234.

Structurei

3D structure databases

ProteinModelPortaliP42682.
SMRiP42682. Positions 87-526.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini82 – 14261SH3PROSITE-ProRule annotationAdd
BLAST
Domaini150 – 24697SH2PROSITE-ProRule annotationAdd
BLAST
Domaini271 – 527257Protein kinasePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi14 – 207Poly-Cys

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

eggNOGiCOG0515.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233859.
HOVERGENiHBG008761.
InParanoidiP42682.
KOiK08016.
OrthoDBiEOG7KM5SC.
PhylomeDBiP42682.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P42682-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MILSSYSSFQ SVLCCCCCRC SVQKRQVRTQ ISLSREEELS EKHSQRQRPW
60 70 80 90 100
FAKLMGKTQS NRGGVQPSKR KPLPPLPQEP PDERIQVKAL YDFLPREPGN
110 120 130 140 150
LALKRAEEYL ILERCDPHWW KARDRFGNEG LIPSNYVTEN RLANLEIYEW
160 170 180 190 200
YHKNITRNQT ERLLRQEAKE GAFIVRDSRH LGSYTISVFT RARRHTQSSI
210 220 230 240 250
KHYQIKKNDS GQWYITERHL FPSVPELIQY HQYNAAGLIS RLRYPIGLLG
260 270 280 290 300
SCLPATSGFS YEKWEIDPSE LAFVKEIGSG QFGVVHLGEW RAHIPVAIKA
310 320 330 340 350
INEGSMSEED FIEEAKVMMK LSHSRLVQLY GVCIQQKPLY IVTEFMENGC
360 370 380 390 400
LLDYLRERKG QLQKALLLSM CQDICEGMAY LERSCYIHRD LAARNCLVSS
410 420 430 440 450
ACVVKISDFG MARYVLDDEY ISSSGAKFPV KWCPPEVFHF NKYSSKSDVW
460 470 480 490 500
SFGVLMWEVF TEGKMPFENK SNLQVVEAIS QGFRLYRPHL APMTIYRVMY
510 520
SCWHESPKGR PTFAELLQVL TEIAETW
Length:527
Mass (Da):61,108
Last modified:November 1, 1995 - v1
Checksum:iD3A32C09B3A201FA
GO
Isoform 2 (identifier: P42682-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: Missing.

Note: Produced by alternative initiation at Met-55 of isoform 1.

Show »
Length:473
Mass (Da):54,741
Checksum:iAA6C96FBDB8C5AF9
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 42LS → SF in BAA07900 (Ref. 4) Curated
Sequence conflicti6 – 61Y → D in BAA07900 (Ref. 4) Curated
Sequence conflicti272 – 2721A → T in BAA07900 (Ref. 4) Curated
Sequence conflicti497 – 4971R → S in BAA07900 (Ref. 4) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5454Missing in isoform 2. CuratedVSP_041923Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16145 mRNA. Translation: AAC52264.1.
U19607 mRNA. Translation: AAA86698.1.
L35268 mRNA. Translation: AAA67039.1.
D43964 mRNA. Translation: BAA07900.1.
CCDSiCCDS51514.1. [P42682-1]
PIRiI49133.
RefSeqiNP_001116226.1. NM_001122754.2. [P42682-1]
NP_001276424.1. NM_001289495.1. [P42682-2]
UniGeneiMm.3264.

Genome annotation databases

EnsembliENSMUST00000113604; ENSMUSP00000109234; ENSMUSG00000054892. [P42682-1]
GeneIDi22165.
KEGGimmu:22165.
UCSCiuc008xrx.2. mouse. [P42682-1]

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U16145 mRNA. Translation: AAC52264.1.
U19607 mRNA. Translation: AAA86698.1.
L35268 mRNA. Translation: AAA67039.1.
D43964 mRNA. Translation: BAA07900.1.
CCDSiCCDS51514.1. [P42682-1]
PIRiI49133.
RefSeqiNP_001116226.1. NM_001122754.2. [P42682-1]
NP_001276424.1. NM_001289495.1. [P42682-2]
UniGeneiMm.3264.

3D structure databases

ProteinModelPortaliP42682.
SMRiP42682. Positions 87-526.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP42682. 1 interaction.
MINTiMINT-4138781.
STRINGi10090.ENSMUSP00000109234.

PTM databases

PhosphoSiteiP42682.

Proteomic databases

PaxDbiP42682.
PRIDEiP42682.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000113604; ENSMUSP00000109234; ENSMUSG00000054892. [P42682-1]
GeneIDi22165.
KEGGimmu:22165.
UCSCiuc008xrx.2. mouse. [P42682-1]

Organism-specific databases

CTDi7294.
MGIiMGI:102960. Txk.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119011.
HOGENOMiHOG000233859.
HOVERGENiHBG008761.
InParanoidiP42682.
KOiK08016.
OrthoDBiEOG7KM5SC.
PhylomeDBiP42682.
TreeFamiTF351634.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiREACT_188202. FCERI mediated Ca+2 mobilization.

Miscellaneous databases

NextBioi302102.
PROiP42682.
SOURCEiSearch...

Gene expression databases

BgeeiP42682.
CleanExiMM_TXK.
ExpressionAtlasiP42682. baseline and differential.
GenevestigatoriP42682.

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...

Publicationsi

« Hide 'large scale' publications
  1. "The murine form of TXK, a novel TEC kinase expressed in thymus maps to chromosome 5."
    Haire R.N., Litman G.W.
    Mamm. Genome 6:476-480(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
    Tissue: Thymus.
  2. "Murine txk: a protein tyrosine kinase gene regulated by T cell activation."
    Sommers C.L., Huang K., Shores E.W., Grinberg A., Charlick D.A., Kozak C.A., Love P.E.
    Oncogene 11:245-251(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: FVB/N.
    Tissue: Thymus.
  3. "Identification of Rlk, a novel protein tyrosine kinase with predominant expression in the T cell lineage."
    Hu Q., Davidson D., Schwartzberg P.L., Macchiarini F., Lenardo M.J., Bluestone J.A., Matis L.A.
    J. Biol. Chem. 270:1928-1934(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Thymus.
  4. Higashitsuji H., Nonoguchi K., Arii S., Furutani M., Kaneko Y., Nakayama H., Fujita J.
    Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6.
    Tissue: Liver.
  5. "RIBP, a novel Rlk/Txk- and Itk-binding adaptor protein that regulates T cell activation."
    Rajagopal K., Sommers C.L., Decker D.C., Mitchell E.O., Korthauer U., Sperling A.I., Kozak C.A., Love P.E., Bluestone J.A.
    J. Exp. Med. 190:1657-1668(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SH2D2A.
  6. "A role for the Tec family tyrosine kinase Txk in T cell activation and thymocyte selection."
    Sommers C.L., Rabin R.L., Grinberg A., Tsay H.C., Farber J., Love P.E.
    J. Exp. Med. 190:1427-1438(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "rlk/TXK encodes two forms of a novel cysteine string tyrosine kinase activated by Src family kinases."
    Debnath J., Chamorro M., Czar M.J., Schaeffer E.M., Lenardo M.J., Varmus H.E., Schwartzberg P.L.
    Mol. Cell. Biol. 19:1498-1507(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE INITIATION (ISOFORM 2), SUBCELLULAR LOCATION, PALMITOYLATION, MUTAGENESIS OF 16-CYS--CYS-18, ENZYME REGULATION.
  8. "Resting lymphocyte kinase (Rlk/Txk) targets lymphoid adaptor SLP-76 in the cooperative activation of interleukin-2 transcription in T-cells."
    Schneider H., Guerette B., Guntermann C., Rudd C.E.
    J. Biol. Chem. 275:3835-3840(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF LCP2.
  9. "Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk."
    Chamorro M., Czar M.J., Debnath J., Cheng G., Lenardo M.J., Varmus H.E., Schwartzberg P.L.
    BMC Immunol. 2:3-3(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FYN, PHOSPHORYLATION AT TYR-420, SUBCELLULAR LOCATION.
  10. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
    Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
    J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-91 AND TYR-420, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Mast cell.
  11. "Selective expression rather than specific function of Txk and Itk regulate Th1 and Th2 responses."
    Sahu N., Venegas A.M., Jankovic D., Mitzner W., Gomez-Rodriguez J., Cannons J.L., Sommers C., Love P., Sher A., Schwartzberg P.L., August A.
    J. Immunol. 181:6125-6131(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "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.

Entry informationi

Entry nameiTXK_MOUSE
AccessioniPrimary (citable) accession number: P42682
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: March 4, 2015
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.