Q08881 (ITK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase ITK/TSK
EC=2.7.10.2

Alternative name(s):
Interleukin-2-inducible T cell kinase
Short name=IL-2-inducible T cell kinase
Kinase EMT
T-cell-specific kinase
Tyrosine-protein kinase Lyk

Gene names

Name:	ITK
Synonyms:	EMT, LYK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	620 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.10 Ref.11 Ref.20
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Homooligomerizes; this association negatively regulates kinase activity By similarity. Interacts with PPIA/CYPA; this interaction regulates TCR signal strength via a proline-directed conformational switch in ITK. Interacts with THEMIS By similarity. Interacts with FASLG. Interacts with VAV1; this interaction is important for VAV1 localization and TCR-induced actin polarization. Ref.12 Ref.13 Ref.16
Subcellular location	Cytoplasm. Note: Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation. Ref.14
Tissue specificity	T-cell lines and natural killer cell lines.
Induction	Through a myriad of surface receptors including the TCR/CD3 signaling complex, coreceptors, or chemokine receptors. Ref.1 Ref.8
Domain	The N-terminal PH domain allows ITK to be recruited to the plasma membrane by an activated PI3 kinase. This domain contains also a proline-rich region (PRR). The adjoining domain is a SH3 domain, which binds to PRR (from itself or from other proteins). Next, a SH2 domain is required for binding tyrosine-phosphorylated substrates. In the C-terminal region, the kinase domain is required for tyrosine phosphorylation. Ref.9
Post-translational modification	Phosphorylated at Tyr-512 in the activation loop of the kinase domain by LCK. Subsequent autophosphorylation at Tyr-180 leads to the kinase activation. The autophosphorylated Tyr-180 lies within the substrate binding sequence of the SH3 domain. Ref.6 Ref.7 Ref.10 Ref.15 Ref.17 Ref.18 Ref.20
Involvement in disease	Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:613011]. LPSA1 is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma. Ref.23
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. Contains 1 Btk-type zinc finger. Contains 1 PH domain. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	SH2 domain SH3 domain Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	T cell receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB activation of phospholipase C activity Inferred from sequence or structural similarity. Source: UniProtKB adaptive immune response Inferred from sequence or structural similarity. Source: UniProtKB cellular defense response Traceable author statement. Source: ProtInc intracellular signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from direct assay Ref.10. Source: UniProtKB protein binding Inferred from physical interaction Ref.10. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FASLG	P48023	3	EBI-968552,EBI-495538

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 620

620

Tyrosine-protein kinase ITK/TSK

PRO_0000088106

Regions

Domain

4 – 111

108

PH

Domain

171 – 231

61

SH3

Domain

239 – 338

100

SH2

Domain

363 – 615

253

Protein kinase

Zinc finger

113 – 149

37

Btk-type

Nucleotide binding

369 – 377

9

ATP By similarity

Sites

Active site

482

1

Proton acceptor By similarity

Metal binding

121

1

Zinc By similarity

Metal binding

132

1

Zinc By similarity

Metal binding

133

1

Zinc By similarity

Metal binding

143

1

Zinc By similarity

Binding site

391

1

ATP By similarity

Amino acid modifications

Modified residue

180

1

Phosphotyrosine; by autocatalysis Ref.6

Modified residue

296

1

N6-acetyllysine Ref.19

Modified residue

512

1

Phosphotyrosine; by LCK Ref.15 Ref.18

Modified residue

565

1

Phosphoserine Ref.15 Ref.18

Natural variations

Natural variant

19

1

R → K in a metastatic melanoma sample; somatic mutation. Ref.22

VAR_041710

Natural variant

23

1

P → L in a metastatic melanoma sample; somatic mutation. Ref.22

VAR_041711

Natural variant

193

1

R → Q.
Corresponds to variant rs17054374 [ dbSNP | Ensembl ].

VAR_051696

Natural variant

335

1

R → W in LPSA1; shows nearly undetectable mutant ITK protein consistent with severe protein instability. Ref.23
Corresponds to variant rs121908191 [ dbSNP | Ensembl ].

VAR_063424

Natural variant

451

1

R → Q in a gastric adenocarcinoma sample; somatic mutation. Ref.22

VAR_041712

Natural variant

581

1

R → W. Ref.22
Corresponds to variant rs34482255 [ dbSNP | Ensembl ].

VAR_041713

Natural variant

587

1

V → I. Ref.22
Corresponds to variant rs56005928 [ dbSNP | Ensembl ].

VAR_041714

Experimental info

Mutagenesis

288

1

P → G: Complete loss of interaction with PPIA/CYPA. Ref.12

Sequence conflict

171 – 172

2

PE → GS AA sequence Ref.6

Sequence conflict

331

1

V → W in AAB28072. Ref.2

Secondary structure

1

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620

Helix Strand Turn

Details...

Beta strand

127 – 133

7

Beta strand

148 – 152

5

Beta strand

171 – 173

3

Beta strand

175 – 180

6

Beta strand

187 – 189

3

Beta strand

197 – 202

6

Beta strand

205 – 212

8

Beta strand

214 – 216

3

Beta strand

218 – 222

5

Turn

223 – 225

3

Beta strand

226 – 228

3

Beta strand

363 – 370

8

Beta strand

377 – 382

6

Turn

383 – 385

3

Beta strand

386 – 392

7

Beta strand

395 – 398

4

Helix

400 – 412

13

Beta strand

421 – 425

5

Beta strand

427 – 430

4

Beta strand

432 – 436

5

Helix

443 – 448

6

Turn

449 – 452

4

Helix

456 – 475

20

Helix

485 – 487

3

Beta strand

488 – 490

3

Helix

492 – 494

3

Beta strand

496 – 498

3

Helix

527 – 530

4

Helix

537 – 552

16

Helix

564 – 572

9

Helix

585 – 594

10

Helix

599 – 601

3

Helix

605 – 618

14

Sequences

	Sequence		Length	Mass (Da)
	Q08881 [UniParc]. Last modified October 1, 1994. Version 1. Checksum: DAE396BD2309319D	FASTA	620	71,831
	10 20 30 40 50 60 MNNFILLEEQ LIKKSQQKRR TSPSNFKVRF FVLTKASLAY FEDRHGKKRT LKGSIELSRI 70 80 90 100 110 120 KCVEIVKSDI SIPCHYKYPF QVVHDNYLLY VFAPDRESRQ RWVLALKEET RNNNSLVPKY 130 140 150 160 170 180 HPNFWMDGKW RCCSQLEKLA TGCAQYDPTK NASKKPLPPT PEDNRRPLWE PEETVVIALY 190 200 210 220 230 240 DYQTNDPQEL ALRRNEEYCL LDSSEIHWWR VQDRNGHEGY VPSSYLVEKS PNNLETYEWY 250 260 270 280 290 300 NKSISRDKAE KLLLDTGKEG AFMVRDSRTA GTYTVSVFTK AVVSENNPCI KHYHIKETND 310 320 330 340 350 360 NPKRYYVAEK YVFDSIPLLI NYHQHNGGGL VTRLRYPVCF GRQKAPVTAG LRYGKWVIDP 370 380 390 400 410 420 SELTFVQEIG SGQFGLVHLG YWLNKDKVAI KTIREGAMSE EDFIEEAEVM MKLSHPKLVQ 430 440 450 460 470 480 LYGVCLEQAP ICLVFEFMEH GCLSDYLRTQ RGLFAAETLL GMCLDVCEGM AYLEEACVIH 490 500 510 520 530 540 RDLAARNCLV GENQVIKVSD FGMTRFVLDD QYTSSTGTKF PVKWASPEVF SFSRYSSKSD 550 560 570 580 590 600 VWSFGVLMWE VFSEGKIPYE NRSNSEVVED ISTGFRLYKP RLASTHVYQI MNHCWKERPE 610 620 DRPAFSRLLR QLAEIAESGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel human tyrosine kinase gene inducible in T cells by interleukin 2." Tanaka N., Asao H., Ohtani K., Nakamura M., Sugamura K. FEBS Lett. 324:1-5(1993) [PubMed: 8504851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
[2]	"Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q." Gibson S., Leung B., Squire J.A., Hill M., Arima N., Goss P., Hogg D., Mills G.B. Blood 82:1561-1572(1993) [PubMed: 8364206] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Thymus.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thymus.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases." Nore B.F., Mattsson P.T., Antonsson P., Backesjo C.-M., Westlund A., Lennartsson J., Hansson H., Low P., Ronnstrand L., Smith C.I.E. Biochim. Biophys. Acta 1645:123-132(2003) [PubMed: 12573241] [Abstract] Cited for: PROTEIN SEQUENCE OF 171-192, PHOSPHORYLATION AT TYR-180.
[7]	"Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity." Heyeck S.D., Wilcox H.M., Bunnell S.C., Berg L.J. J. Biol. Chem. 272:25401-25408(1997) [PubMed: 9312162] [Abstract] Cited for: PHOSPHORYLATION BY LCK.
[8]	"CD2-mediated activation of the Tec-family tyrosine kinase ITK is controlled by proline-rich stretch-4 of the CD2 cytoplasmic tail." King P.D., Sadra A., Teng J.M., Bell G.M., Dupont B. Int. Immunol. 10:1009-1016(1998) [PubMed: 9701039] [Abstract] Cited for: INDUCTION.
[9]	"Tec kinases: a family with multiple roles in immunity." Yang W.C., Collette Y., Nunes J.A., Olive D. Immunity 12:373-382(2000) [PubMed: 10795735] [Abstract] Cited for: DOMAIN.
[10]	"Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav." Perez-Villar J.J., Whitney G.S., Sitnick M.T., Dunn R.J., Venkatesan S., O'Day K., Schieven G.L., Lin T.A., Kanner S.B. Biochemistry 41:10732-10740(2002) [PubMed: 12186560] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF LAT.
[11]	"Inducible T cell tyrosine kinase regulates actin-dependent cytoskeletal events induced by the T cell antigen receptor." Grasis J.A., Browne C.D., Tsoukas C.D. J. Immunol. 170:3971-3976(2003) [PubMed: 12682224] [Abstract] Cited for: FUNCTION.
[12]	"Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk." Colgan J., Asmal M., Neagu M., Yu B., Schneidkraut J., Lee Y., Sokolskaja E., Andreotti A., Luban J. Immunity 21:189-201(2004) [PubMed: 15308100] [Abstract] Cited for: INTERACTION WITH PPIA/CYPA, MUTAGENESIS OF PRO-288.
[13]	"Kinase-independent functions for Itk in TCR-induced regulation of Vav and the actin cytoskeleton." Dombroski D., Houghtling R.A., Labno C.M., Precht P., Takesono A., Caplen N.J., Billadeau D.D., Wange R.L., Burkhardt J.K., Schwartzberg P.L. J. Immunol. 174:1385-1392(2005) [PubMed: 15661896] [Abstract] Cited for: INTERACTION WITH VAV1.
[14]	"Tec kinase Itk forms membrane clusters specifically in the vicinity of recruiting receptors." Qi Q., Sahu N., August A. J. Biol. Chem. 281:38529-38534(2006) [PubMed: 17060314] [Abstract] Cited for: SUBCELLULAR LOCATION.
[15]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-512 AND SER-565, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[16]	"Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening." Voss M., Lettau M., Janssen O. BMC Immunol. 10:53-53(2009) [PubMed: 19807924] [Abstract] Cited for: INTERACTION WITH FASLG.
[17]	"SH2-dependent autophosphorylation within the Tec family kinase Itk." Joseph R.E., Severin A., Min L., Fulton D.B., Andreotti A.H. J. Mol. Biol. 391:164-177(2009) [PubMed: 19523959] [Abstract] Cited for: AUTOPHOSPHORYLATION.
[18]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-512 AND SER-565, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[19]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-296, MASS SPECTROMETRY.
[20]	"Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells." Sela M., Bogin Y., Beach D., Oellerich T., Lehne J., Smith-Garvin J.E., Okumura M., Starosvetsky E., Kosoff R., Libman E., Koretzky G., Kambayashi T., Urlaub H., Wienands J., Chernoff J., Yablonski D. EMBO J. 30:3160-3172(2011) [PubMed: 21725281] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF LCP2.
[21]	"Solution structure of the BTK motif and the SH3 domain of tyrosine-protein kinase ITK from human." RIKEN structural genomics initiative (RSGI) Submitted (OCT-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 113-239.
[22]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-19; LEU-23; GLN-451; TRP-581 AND ILE-587.
[23]	"Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation." Huck K., Feyen O., Niehues T., Rueschendorf F., Huebner N., Laws H.-J., Telieps T., Knapp S., Wacker H.-H., Meindl A., Jumaa H., Borkhardt A. J. Clin. Invest. 119:1350-1358(2009) [PubMed: 19425169] [Abstract] Cited for: VARIANT LPSA1 TRP-335, CHARACTERIZATION OF VARIANT LPSA1 TRP-335.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D13720 mRNA. Translation: BAA02873.1.
L10717 mRNA. Translation: AAA36748.1.
S65186 mRNA. Translation: AAB28072.2.
AK312846 mRNA. Translation: BAG35699.1.
CH471062 Genomic DNA. Translation: EAW61608.1.
BC109077 mRNA. Translation: AAI09078.1.
BC109078 mRNA. Translation: AAI09079.1.

IPI

IPI00004566.

PIR

S33253.

RefSeq

NP_005537.3. NM_005546.3.

UniGene

Hs.558348.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SM2	X-ray	2.30	A/B	357-620	[»]
1SNU	X-ray	2.50	A/B	357-620	[»]
1SNX	X-ray	3.20	A/B	357-620	[»]
2E6I	NMR	-	A	113-169	[»]
2YUQ	NMR	-	A	162-239	[»]
3MIY	X-ray	1.67	A/B	357-620	[»]
3MJ1	X-ray	1.72	A	357-620	[»]
3MJ2	X-ray	1.90	A	357-620	[»]
3QGW	X-ray	2.10	A/B	357-620	[»]
3QGY	X-ray	2.10	A/B	357-620	[»]
3T9T	X-ray	1.65	A	354-620	[»]

ProteinModelPortal

Q08881.

SMR

Q08881. Positions 3-617.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29974N.

IntAct

Q08881. 1 interaction.

MINT

MINT-110502.

STRING

Q08881.

PTM databases

PhosphoSite

Q08881.

Polymorphism databases

DMDM

585361.

Proteomic databases

PeptideAtlas

Q08881.

PRIDE

Q08881.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000422843; ENSP00000398655; ENSG00000113263.

GeneID

3702.

KEGG

hsa:3702.

UCSC

uc003lwo.1. human.

Organism-specific databases

CTD

3702.

GeneCards

GC05P156607.

H-InvDB

HIX0024849.

HGNC

HGNC:6171. ITK.

MIM

186973. gene.
613011. phenotype.

neXtProt

NX_Q08881.

Orphanet

238505. Autosomal recessive lymphoproliferative disease.

PharmGKB

PA29968.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16075.

HOGENOM

HBG755340.

HOVERGEN

HBG008761.

InParanoid

Q08881.

OMA

HVYQIMN.

OrthoDB

EOG48WC1S.

PhylomeDB

Q08881.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
tcrpathway. TCR signaling in naive CD4+ T cells.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q08881.

Bgee

Q08881.

CleanEx

HS_ITK.

Genevestigator

Q08881.

GermOnline

ENSG00000113263. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR020697. Tyr_kinase_non-rcpt_ITK/TSK.
IPR001562. Znf_Btk_motif.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:3.30.505.10. SH2. 1 hit.

KO

K07363.

PANTHER

PTHR24418:SF138. PTHR24418:SF138. 1 hit.

Pfam

PF00779. BTK. 1 hit.
PF00169. PH. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]

PRINTS

PR00401. SH2DOMAIN.
PR00109. TYRKINASE.

SMART

SM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
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

PS50003. PH_DOMAIN. 1 hit.
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.
PS51113. ZF_BTK. 1 hit.
[Graphical view]

ProtoNet

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Other

NextBio

14507.

SOURCE

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Entry information

Entry name

ITK_HUMAN

Accession

Primary (citable) accession number: Q08881
Secondary accession number(s): B2R752, Q32ML7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	January 25, 2012
This is version 133 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.