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P42682 (TXK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·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):
PTK-RL-18
Resting lymphocyte kinase
Gene names
Name:Txk
Synonyms:Rlk
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

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.5 Ref.6 Ref.8 Ref.11

Catalytic activity

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

Enzyme regulation

Activated by phosphorylation by FYN. Ref.7

Subunit structure

Interacts with PARP1 and EEF1A1 By similarity. Interacts with SH2D2A. Ref.5 Ref.9

Subcellular location

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 By similarity. Translocates into the nucleus and enhances IFN-gamma gene transcription in T-cells By similarity. Ref.7 Ref.9

Tissue specificity

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

Post-translational modification

Phosphorylated at Tyr-420 by FYN By similarity. Autophosphorylation at Tyr-91 is critical for the activation of TXK, leading to the up-regulation of IFN-gamma gene transcription By similarity. Ref.9

The cysteine string at the N-terminus is palmitoylated and required for the proper subcellular location. Ref.7

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 diversityAlternative initiation
   DomainSH2 domain
SH3 domain
   LigandATP-binding
DNA-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMLipoprotein
Palmitate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNK T cell differentiation

Inferred from genetic interaction PubMed 18292523. Source: MGI

T cell receptor signaling pathway

Inferred from mutant phenotype PubMed 10213685. Source: UniProtKB

activation of phospholipase C activity

Inferred from mutant phenotype PubMed 10213685. Source: UniProtKB

adaptive immune response

Inferred from mutant phenotype PubMed 10213685. Source: UniProtKB

cytokine production

Inferred from mutant phenotype PubMed 10213685. Source: UniProtKB

interferon-gamma production

Inferred from genetic interaction PubMed 18292523. Source: MGI

interleukin-4 production

Inferred from genetic interaction PubMed 18292523. Source: MGI

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform 1 (identifier: P42682-1)

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.
Isoform 2 (identifier: P42682-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 527527Tyrosine-protein kinase TXK
PRO_0000088176

Regions

Domain82 – 14261SH3
Domain150 – 24697SH2
Domain271 – 527257Protein kinase
Nucleotide binding277 – 2859ATP By similarity
Compositional bias14 – 207Poly-Cys

Sites

Active site3901Proton acceptor By similarity
Binding site2991ATP By similarity

Amino acid modifications

Modified residue911Phosphotyrosine; by autocatalysis Ref.10
Modified residue4201Phosphotyrosine; by FYN and autocatalysis Ref.9 Ref.10

Natural variations

Alternative sequence1 – 5454Missing in isoform 2.
VSP_041923

Experimental info

Mutagenesis16 – 183CCC → SLA: Reduces palmitoylation and leads to nuclear localization. Ref.7
Sequence conflict3 – 42LS → SF in BAA07900. Ref.4
Sequence conflict61Y → D in BAA07900. Ref.4
Sequence conflict2721A → T in BAA07900. Ref.4
Sequence conflict4971R → S in BAA07900. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: D3A32C09B3A201FA

FASTA52761,108
        10         20         30         40         50         60 
MILSSYSSFQ SVLCCCCCRC SVQKRQVRTQ ISLSREEELS EKHSQRQRPW FAKLMGKTQS 

        70         80         90        100        110        120 
NRGGVQPSKR KPLPPLPQEP PDERIQVKAL YDFLPREPGN LALKRAEEYL ILERCDPHWW 

       130        140        150        160        170        180 
KARDRFGNEG LIPSNYVTEN RLANLEIYEW YHKNITRNQT ERLLRQEAKE GAFIVRDSRH 

       190        200        210        220        230        240 
LGSYTISVFT RARRHTQSSI KHYQIKKNDS GQWYITERHL FPSVPELIQY HQYNAAGLIS 

       250        260        270        280        290        300 
RLRYPIGLLG SCLPATSGFS YEKWEIDPSE LAFVKEIGSG QFGVVHLGEW RAHIPVAIKA 

       310        320        330        340        350        360 
INEGSMSEED FIEEAKVMMK LSHSRLVQLY GVCIQQKPLY IVTEFMENGC LLDYLRERKG 

       370        380        390        400        410        420 
QLQKALLLSM CQDICEGMAY LERSCYIHRD LAARNCLVSS ACVVKISDFG MARYVLDDEY 

       430        440        450        460        470        480 
ISSSGAKFPV KWCPPEVFHF NKYSSKSDVW SFGVLMWEVF TEGKMPFENK SNLQVVEAIS 

       490        500        510        520 
QGFRLYRPHL APMTIYRVMY SCWHESPKGR PTFAELLQVL TEIAETW 

« Hide

Isoform 2 [UniParc].

Checksum: AA6C96FBDB8C5AF9
Show »

FASTA47354,741

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U16145 mRNA. Translation: AAC52264.1.
U19607 mRNA. Translation: AAA86698.1.
L35268 mRNA. Translation: AAA67039.1.
D43964 mRNA. Translation: BAA07900.1.
CCDSCCDS51514.1. [P42682-1]
PIRI49133.
RefSeqNP_001116226.1. NM_001122754.2. [P42682-1]
NP_001276424.1. NM_001289495.1. [P42682-2]
UniGeneMm.3264.

3D structure databases

ProteinModelPortalP42682.
SMRP42682. Positions 87-526.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP42682. 1 interaction.
MINTMINT-4138781.
STRING10090.ENSMUSP00000109234.

PTM databases

PhosphoSiteP42682.

Proteomic databases

PaxDbP42682.
PRIDEP42682.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000113604; ENSMUSP00000109234; ENSMUSG00000054892. [P42682-1]
GeneID22165.
KEGGmmu:22165.
UCSCuc008xrx.2. mouse. [P42682-1]

Organism-specific databases

CTD7294.
MGIMGI:102960. Txk.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00640000091251.
HOGENOMHOG000233859.
HOVERGENHBG008761.
InParanoidP42682.
KOK08016.
OrthoDBEOG7KM5SC.
PhylomeDBP42682.
TreeFamTF351634.

Enzyme and pathway databases

BRENDA2.7.10.2. 3474.

Gene expression databases

ArrayExpressP42682.
BgeeP42682.
CleanExMM_TXK.
GenevestigatorP42682.

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

NextBio302102.
PROP42682.
SOURCESearch...

Entry information

Entry nameTXK_MOUSE
AccessionPrimary (citable) accession number: P42682
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot