dbPTM

TXK_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	TXK_HUMAN
UniProt AC	P42681
Protein Name	Tyrosine-protein kinase TXK
Gene Name	TXK
Organism	Homo sapiens (Human).
Sequence Length	527
Subcellular Localization	Cytoplasm . Nucleus . Cell membrane Peripheral membrane protein . 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-ce
Protein Description	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..
Protein Sequence	MILSSYNTIQSVFCCCCCCSVQKRQMRTQISLSTDEELPEKYTQRRRPWLSQLSNKKQSNTGRVQPSKRKPLPPLPPSEVAEEKIQVKALYDFLPREPCNLALRRAEEYLILEKYNPHWWKARDRLGNEGLIPSNYVTENKITNLEIYEWYHRNITRNQAEHLLRQESKEGAFIVRDSRHLGSYTISVFMGARRSTEAAIKHYQIKKNDSGQWYVAERHAFQSIPELIWYHQHNAAGLMTRLRYPVGLMGSCLPATAGFSYEKWEIDPSELAFIKEIGSGQFGVVHLGEWRSHIQVAIKAINEGSMSEEDFIEEAKVMMKLSHSKLVQLYGVCIQRKPLYIVTEFMENGCLLNYLRENKGKLRKEMLLSVCQDICEGMEYLERNGYIHRDLAARNCLVSSTCIVKISDFGMTRYVLDDEYVSSFGAKFPIKWSPPEVFLFNKYSSKSDVWSFGVLMWEVFTEGKMPFENKSNLQVVEAISEGFRLYRPHLAPMSIYEVMYSCWHEKPEGRPTFAELLRAVTEIAETW

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
31	Phosphorylation	RQMRTQISLSTDEEL HHHHHEECCCCCCCC	13.37	28152594
33	Phosphorylation	MRTQISLSTDEELPE HHHEECCCCCCCCCH	27.33	28152594
34	Phosphorylation	RTQISLSTDEELPEK HHEECCCCCCCCCHH	53.36	28152594
42	Phosphorylation	DEELPEKYTQRRRPW CCCCCHHHHHHCCHH	13.37	28152594
43	Phosphorylation	EELPEKYTQRRRPWL CCCCHHHHHHCCHHH	27.02	28152594
91	Phosphorylation	KIQVKALYDFLPREP HHHHHHHHHHCCCCC	14.98	12081135
307	Phosphorylation	AINEGSMSEEDFIEE HHHCCCCCHHHHHHH	39.26	-
400	Phosphorylation	ARNCLVSSTCIVKIS HHCCEEECEEEEEEH	21.59	22210691
412	Phosphorylation	KISDFGMTRYVLDDE EEHHCCCCEEEECHH	21.16	22210691
420	Phosphorylation	RYVLDDEYVSSFGAK EEEECHHHHHCCCCC	16.78	12081135
422	Phosphorylation	VLDDEYVSSFGAKFP EECHHHHHCCCCCCC	21.03	22210691
423	Phosphorylation	LDDEYVSSFGAKFPI ECHHHHHCCCCCCCC	20.04	29978859

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
91	Y	Phosphorylation	Kinase	TXK	P42681	PSP
420	Y	Phosphorylation	Kinase	FYN	P06241	Uniprot
420	Y	Phosphorylation	Kinase	TXK	P42681	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of TXK_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of TXK_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
Oops, there are no PPI records of TXK_HUMAN !!

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of TXK_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Evidence of autophosphorylation in Txk: Y91 is an autophosphorylationsite."; Kashiwakura J., Suzuki N., Takeno M., Itoh S., Oku T., Sakane T.,Nakajin S., Toyoshima S.; Biol. Pharm. Bull. 25:718-721(2002). Cited for: AUTOPHOSPHORYLATION, PHOSPHORYLATION AT TYR-91 AND TYR-420, ENZYMEREGULATION, AND MUTAGENESIS OF TYR-91.	12081135 [Abstract]