P42682 (TXK_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	527 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Adaptive immunity Immunity Transcription Transcription regulation
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative initiation
Domain	SH2 domain SH3 domain
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NK 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 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-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm 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_function	ATP 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: 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 527	527	Tyrosine-protein kinase TXK		PRO_0000088176
Regions
	Domain	82 – 142	61	SH3
	Domain	150 – 246	97	SH2
	Domain	271 – 527	257	Protein kinase
	Nucleotide binding	277 – 285	9	ATP By similarity
	Compositional bias	14 – 20	7	Poly-Cys
Sites
	Active site	390	1	Proton acceptor By similarity
	Binding site	299	1	ATP By similarity
Amino acid modifications
	Modified residue	91	1	Phosphotyrosine; by autocatalysis Ref.10
	Modified residue	420	1	Phosphotyrosine; by FYN and autocatalysis Ref.9 Ref.10
Natural variations
	Alternative sequence	1 – 54	54	Missing in isoform 2.		VSP_041923
Experimental info
	Mutagenesis	16 – 18	3	CCC → SLA: Reduces palmitoylation and leads to nuclear localization. Ref.7
	Sequence conflict	3 – 4	2	LS → SF in BAA07900. Ref.4
	Sequence conflict	6	1	Y → D in BAA07900. Ref.4
	Sequence conflict	272	1	A → T in BAA07900. Ref.4
	Sequence conflict	497	1	R → S in BAA07900. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: D3A32C09B3A201FA	FASTA	527	61,108
	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
	Isoform 2 [UniParc]. Checksum: AA6C96FBDB8C5AF9	FASTA	473	54,741
	10 20 30 40 50 60 MGKTQSNRGG VQPSKRKPLP PLPQEPPDER IQVKALYDFL PREPGNLALK RAEEYLILER 70 80 90 100 110 120 CDPHWWKARD RFGNEGLIPS NYVTENRLAN LEIYEWYHKN ITRNQTERLL RQEAKEGAFI 130 140 150 160 170 180 VRDSRHLGSY TISVFTRARR HTQSSIKHYQ IKKNDSGQWY ITERHLFPSV PELIQYHQYN 190 200 210 220 230 240 AAGLISRLRY PIGLLGSCLP ATSGFSYEKW EIDPSELAFV KEIGSGQFGV VHLGEWRAHI 250 260 270 280 290 300 PVAIKAINEG SMSEEDFIEE AKVMMKLSHS RLVQLYGVCI QQKPLYIVTE FMENGCLLDY 310 320 330 340 350 360 LRERKGQLQK ALLLSMCQDI CEGMAYLERS CYIHRDLAAR NCLVSSACVV KISDFGMARY 370 380 390 400 410 420 VLDDEYISSS GAKFPVKWCP PEVFHFNKYS SKSDVWSFGV LMWEVFTEGK MPFENKSNLQ 430 440 450 460 470 VVEAISQGFR LYRPHLAPMT IYRVMYSCWH ESPKGRPTFA ELLQVLTEIA ETW

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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.
IPI	IPI00118515.
PIR	I49133.
RefSeq	NP_001116226.1. NM_001122754.1. NP_038726.2. NM_013698.2.
UniGene	Mm.3264.
3D structure databases
ProteinModelPortal	P42682.
SMR	P42682. Positions 87-526.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4138781.
STRING	10090.ENSMUSP00000109234.
PTM databases
PhosphoSite	P42682.
Proteomic databases
PaxDb	P42682.
PRIDE	P42682.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000113604; ENSMUSP00000109234; ENSMUSG00000054892.
GeneID	22165.
KEGG	mmu:22165.
UCSC	uc008xrx.2. mouse.
Organism-specific databases
CTD	7294.
MGI	MGI:102960. Txk.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00640000091251.
HOGENOM	HOG000233859.
HOVERGEN	HBG008761.
InParanoid	P42682.
KO	K08016.
OrthoDB	EOG4KSPJK.
Enzyme and pathway databases
BRENDA	2.7.10.2. 3474.
Gene expression databases
ArrayExpress	P42682.
Bgee	P42682.
CleanEx	MM_TXK.
Genevestigator	P42682.
GermOnline	ENSMUSG00000054892. Mus musculus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00109. TYRKINASE.
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	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]
ProtoNet	Search...
Other
NextBio	302102.
SOURCE	Search...

Entry information

Entry name

TXK_MOUSE

Accession

Primary (citable) accession number: P42682

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 29, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program