UniProt Accession

 ITK_HUMAN; Q08881; B2R752; Q32ML7 

Genbank Protein ID

 D13720; L10717; S65186; AK312846; CH471062; BC109077; BC109078 

Genbank Nucleotide ID

 BAA02873.1; AAA36748.1; AAB28072.2; BAG35699.1; EAW61608.1; AAI09078.1; AAI09079.1 

Protein Name

 Tyrosine-protein kinase ITK/TSK 

Protein Synonyms/Alias

 Interleukin-2-inducible T-cell kinase; IL-2-inducible T-cell kinase; Kinase EMT; T-cell-specific kinase; Tyrosine-protein kinase Lyk 

Gene Name

 ITK 

Gene Synonyms/Alias

 EMT; LYK 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
13	LLEEQLIKKSQQKRR	ubiquitination	[1]
14	LEEQLIKKSQQKRRT	ubiquitination	[2]
52	HGKKRTLKGSIELSR	ubiquitination	[2]
61	SIELSRIKCVEIVKS	ubiquitination	[2]
107	QRWVLALKEETRNNN	ubiquitination	[2, 3]
119	NNNSLVPKYHPNFWM	ubiquitination	[2, 3]
129	PNFWMDGKWRCCSQL	ubiquitination	[1, 2]
138	RCCSQLEKLATGCAQ	ubiquitination	[1, 2]
150	CAQYDPTKNASKKPL	ubiquitination	[1, 2]
154	DPTKNASKKPLPPTP	ubiquitination	[2]
229	PSSYLVEKSPNNLET	ubiquitination	[1, 2]
242	ETYEWYNKSISRDKA	ubiquitination	[1, 2, 3]
251	ISRDKAEKLLLDTGK	ubiquitination	[1, 2]
258	KLLLDTGKEGAFMVR	ubiquitination	[1, 2, 3]
291	SENNPCIKHYHIKET	ubiquitination	[1, 2, 3]
296	CIKHYHIKETNDNPK	acetylation	[4]
296	CIKHYHIKETNDNPK	ubiquitination	[2]
344	PVCFGRQKAPVTAGL	ubiquitination	[2]
391	NKDKVAIKTIREGAM	ubiquitination	[2, 3]
412	EEAEVMMKLSHPKLV	ubiquitination	[2]
497	VGENQVIKVSDFGMT	ubiquitination	[1, 2]
519	YTSSTGTKFPVKWAS	ubiquitination	[1, 2, 3]
523	TGTKFPVKWASPEVF	ubiquitination	[1, 2]

Reference

 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 

Functional Description

 Tyrosine kinase that plays an essential role 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 ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and 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. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. 

Sequence Annotation

 DOMAIN 4 111 PH.
 DOMAIN 171 231 SH3.
 DOMAIN 239 338 SH2.
 DOMAIN 363 615 Protein kinase.
 ZN_FING 113 149 Btk-type.
 NP_BIND 369 377 ATP (By similarity).
 ACT_SITE 482 482 Proton acceptor (By similarity).
 METAL 121 121 Zinc (By similarity).
 METAL 132 132 Zinc (By similarity).
 METAL 133 133 Zinc (By similarity).
 METAL 143 143 Zinc (By similarity).
 BINDING 391 391 ATP (By similarity).
 MOD_RES 180 180 Phosphotyrosine; by autocatalysis.
 MOD_RES 512 512 Phosphotyrosine; by LCK.
 MOD_RES 565 565 Phosphoserine.  

Keyword

 3D-structure; Adaptive immunity; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Immunity; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 620 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0005543; F:phospholipid binding; IEA:InterPro.
 GO:0007202; P:activation of phospholipase C activity; ISS:UniProtKB.
 GO:0002250; P:adaptive immune response; ISS:UniProtKB.
 GO:0006968; P:cellular defense response; TAS:ProtInc.
 GO:0001816; P:cytokine production; ISS:UniProtKB.
 GO:0032609; P:interferon-gamma production; IEA:Compara.
 GO:0032633; P:interleukin-4 production; IEA:Compara.
 GO:0035556; P:intracellular signal transduction; IEA:InterPro.
 GO:0001865; P:NK T cell differentiation; IEA:Compara.
 GO:0042110; P:T cell activation; TAS:UniProtKB.
 GO:0050852; P:T cell receptor signaling pathway; ISS:UniProtKB. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR011993; PH_like_dom.
 IPR001849; Pleckstrin_homology.
 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.
 IPR001562; Znf_Btk_motif. 

Pfam

 PF00779; BTK
 PF00169; PH
 PF07714; Pkinase_Tyr
 PF00017; SH2
 PF00018; SH3_1 

SMART

 SM00107; BTK
 SM00233; PH
 SM00252; SH2
 SM00326; SH3
 SM00219; TyrKc 

PROSITE

 PS50003; PH_DOMAIN
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2
 PS50002; SH3
 PS51113; ZF_BTK 

PRINTS

 PR00401; SH2DOMAIN.
 PR00109; TYRKINASE.