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P42682

- TXK_MOUSE

UniProt

P42682 - TXK_MOUSE

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Protein
Tyrosine-protein kinase TXK
Gene
Txk, Rlk
Organism
Mus musculus (Mouse)
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.4 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. DNA binding Source: UniProtKB-KW
  3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. NK T cell differentiation Source: MGI
  2. T cell receptor signaling pathway Source: UniProtKB
  3. activation of phospholipase C activity Source: UniProtKB
  4. adaptive immune response Source: UniProtKB
  5. cytokine production Source: UniProtKB
  6. interferon-gamma production Source: MGI
  7. interleukin-4 production Source: MGI
  8. regulation of transcription, DNA-templated Source: UniProtKB-KW
  9. 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. 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 By similarity. Translocates into the nucleus and enhances IFN-gamma gene transcription in T-cells By similarity.2 Publications

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. nucleus Source: UniProtKB-SubCell
  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
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 TXK
PRO_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 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.1 Publication
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

ArrayExpressiP42682.
BgeeiP42682.
CleanExiMM_TXK.
GenevestigatoriP42682.

Interactioni

Subunit structurei

Interacts with PARP1 and EEF1A1 By similarity. Interacts with SH2D2A.2 Publications

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliP42682.
SMRiP42682. Positions 87-526.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini82 – 14261SH3
Add
BLAST
Domaini150 – 24697SH2
Add
BLAST
Domaini271 – 527257Protein kinase
Add
BLAST

Compositional bias

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

Sequence similaritiesi

Contains 1 SH2 domain.
Contains 1 SH3 domain.

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00640000091251.
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. Align

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

MILSSYSSFQ SVLCCCCCRC SVQKRQVRTQ ISLSREEELS EKHSQRQRPW    50
FAKLMGKTQS NRGGVQPSKR KPLPPLPQEP PDERIQVKAL YDFLPREPGN 100
LALKRAEEYL ILERCDPHWW KARDRFGNEG LIPSNYVTEN RLANLEIYEW 150
YHKNITRNQT ERLLRQEAKE GAFIVRDSRH LGSYTISVFT RARRHTQSSI 200
KHYQIKKNDS GQWYITERHL FPSVPELIQY HQYNAAGLIS RLRYPIGLLG 250
SCLPATSGFS YEKWEIDPSE LAFVKEIGSG QFGVVHLGEW RAHIPVAIKA 300
INEGSMSEED FIEEAKVMMK LSHSRLVQLY GVCIQQKPLY IVTEFMENGC 350
LLDYLRERKG QLQKALLLSM CQDICEGMAY LERSCYIHRD LAARNCLVSS 400
ACVVKISDFG MARYVLDDEY ISSSGAKFPV KWCPPEVFHF NKYSSKSDVW 450
SFGVLMWEVF TEGKMPFENK SNLQVVEAIS QGFRLYRPHL APMTIYRVMY 500
SCWHESPKGR PTFAELLQVL TEIAETW 527
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 5454Missing in isoform 2.
VSP_041923Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 42LS → SF in BAA07900. 1 Publication
Sequence conflicti6 – 61Y → D in BAA07900. 1 Publication
Sequence conflicti272 – 2721A → T in BAA07900. 1 Publication
Sequence conflicti497 – 4971R → S in BAA07900. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
U16145 mRNA. Translation: AAC52264.1 .
U19607 mRNA. Translation: AAA86698.1 .
L35268 mRNA. Translation: AAA67039.1 .
D43964 mRNA. Translation: BAA07900.1 .
CCDSi CCDS51514.1. [P42682-1 ]
PIRi I49133.
RefSeqi NP_001116226.1. NM_001122754.2. [P42682-1 ]
NP_001276424.1. NM_001289495.1. [P42682-2 ]
UniGenei Mm.3264.

3D structure databases

ProteinModelPortali P42682.
SMRi P42682. Positions 87-526.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P42682. 1 interaction.
MINTi MINT-4138781.
STRINGi 10090.ENSMUSP00000109234.

PTM databases

PhosphoSitei P42682.

Proteomic databases

PaxDbi P42682.
PRIDEi P42682.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000113604 ; ENSMUSP00000109234 ; ENSMUSG00000054892 . [P42682-1 ]
GeneIDi 22165.
KEGGi mmu:22165.
UCSCi uc008xrx.2. mouse. [P42682-1 ]

Organism-specific databases

CTDi 7294.
MGIi MGI:102960. Txk.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00640000091251.
HOGENOMi HOG000233859.
HOVERGENi HBG008761.
InParanoidi P42682.
KOi K08016.
OrthoDBi EOG7KM5SC.
PhylomeDBi P42682.
TreeFami TF351634.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 3474.
Reactomei REACT_188202. FCERI mediated Ca+2 mobilization.

Miscellaneous databases

NextBioi 302102.
PROi P42682.
SOURCEi Search...

Gene expression databases

ArrayExpressi P42682.
Bgeei P42682.
CleanExi MM_TXK.
Genevestigatori P42682.

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. "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: September 3, 2014
This is version 134 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

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