Reviewed, UniProtKB/Swiss-Prot Q08881 (ITK_HUMAN)

Names and origin

Protein names

Recommended name:
    Tyrosine-protein kinase ITK/TSK
    EC=2.7.10.2
Alternative name(s):
    T-cell-specific kinase
    Tyrosine-protein kinase Lyk
    Kinase EMT

Gene names

Name:	ITK
Synonyms:	EMT, LYK

Organism

Homo sapiens (Human) [Complete proteome]

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	Plays a role in T-cell proliferation and differentiation.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Ligation of CD2, TCR or CD28 induces activation and tyrosine phosphorylation of ITK. Interacts with THEMIS By similarity.
Subcellular location	Cell membrane By similarity. Note: Localizes to cell surface receptors in the plasma membrane after stimulation with respective receptors (TCR, CD28, CD2) in T-cells By similarity.
Tissue specificity	T-cell lines and natural killer cell lines.
Induction	By interleukin-2.
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
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
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
Gene Ontology (GO)
Biological process	cellular defense response Ref.2 Traceable author statement. Source: ProtInc intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from Experiment. Source: Reactome plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Ref.2 Traceable author statement. Source: ProtInc protein binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FASLG	P48023	2	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.9

Modified residue

512

1

Phosphotyrosine; by autocatalysis Ref.7 Ref.8

Modified residue

565

1

Phosphoserine Ref.7 Ref.8

Natural variations

Natural variant

19

1

R → K in a metastatic melanoma sample; somatic mutation. Ref.11

VAR_041710

Natural variant

23

1

P → L in a metastatic melanoma sample; somatic mutation. Ref.11

VAR_041711

Natural variant

193

1

R → Q: dbSNP rs17054374.

VAR_051696

Natural variant

451

1

R → Q in a gastric adenocarcinoma sample; somatic mutation. Ref.11

VAR_041712

Natural variant

581

1

R → W: dbSNP rs34482255. Ref.11

VAR_041713

Natural variant

587

1

V → I: dbSNP rs56005928. Ref.11

VAR_041714

Experimental info

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)
	Q08881-1 [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].
[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]	"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.
[8]	"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: T-cell.
[9]	"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.
[10]	"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.
[11]	"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.
+	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.

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	[»]

SMR

Q08881. Positions 5-146, 232-339.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29974N.

IntAct

Q08881. 2 interactions.

STRING

Q08881.

PTM databases

PhosphoSite

Q08881.

Proteomic databases

PeptideAtlas

Q08881.

PRIDE

Q08881.

Genome annotation databases

Ensembl

ENST00000422843; ENSP00000398655; ENSG00000113263; Homo sapiens. [Genome view]

GeneID

3702.

KEGG

hsa:3702.

UCSC

uc003lwo.1. human.

Organism-specific databases

CTD

3702.

GeneCards

GC05P156540.

H-InvDB

HIX0024849.

HGNC

HGNC:6171. ITK.

MIM

186973. gene.

PharmGKB

PA29968.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16075.

HOGENOM

HBG755340.

HOVERGEN

Q08881.

InParanoid

Q08881.

OMA

FEFMEHG.

OrthoDB

EOG92JRBF.

PhylomeDB

Q08881.

Enzyme and pathway databases

BRENDA

2.7.10.2. 247.

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. Signaling in 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.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR020635. Tyr_Pkinase_cat_dom.
IPR020685. Tyr_prot_kinase.
IPR008266. Tyr_prot_kinase_AS.
IPR001562. Znf_Btk_motif.
[Graphical view]

Gene3D

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

PANTHER

PTHR23256. Tyr_prot_kinase. 1 hit.

Pfam

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

PRINTS

PR00401. SH2DOMAIN.

SMART

SM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]

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

Search...

Other Resources

NextBio

14507.

SOURCE

Search...

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:	February 9, 2010
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.