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Entry version 205 (03 Jul 2019)
Sequence version 1 (01 Oct 1994)
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Protein

Tyrosine-protein kinase ITK/TSK

Gene

ITK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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 (PubMed:12186560, PubMed:12682224, PubMed:21725281). Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3 (By similarity).By similarity3 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi121ZincBy similarity1
Metal bindingi132ZincBy similarity1
Metal bindingi133ZincBy similarity1
Metal bindingi143ZincBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei391ATPPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei482Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section specifies the position(s) and type(s) of zinc fingers within the protein.<p><a href='/help/zn_fing' target='_top'>More...</a></p>Zinc fingeri113 – 149Btk-typePROSITE-ProRule annotationAdd BLAST37
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi369 – 377ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processAdaptive immunity, Immunity
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.10.2 2681

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-202433 Generation of second messenger molecules
R-HSA-2871809 FCERI mediated Ca+2 mobilization

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
Q08881

SIGNOR Signaling Network Open Resource

More...
SIGNORi
Q08881

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
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
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ITK
Synonyms:EMT, LYK
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 5

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:6171 ITK

Online Mendelian Inheritance in Man (OMIM)

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MIMi
186973 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_Q08881

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Lymphoproliferative syndrome 1 (LPFS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_063424335R → W in LPFS1; shows nearly undetectable mutant ITK protein consistent with severe protein instability. 1 PublicationCorresponds to variant dbSNP:rs121908191EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi288P → G: Complete loss of interaction with PPIA/CYPA. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
3702

MalaCards human disease database

More...
MalaCardsi
ITK
MIMi613011 phenotype

Open Targets

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OpenTargetsi
ENSG00000113263

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
238505 Combined immunodeficiency due to CD27 deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA29968

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL2959

Drug and drug target database

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DrugBanki
DB06589 Pazopanib
DB02010 Staurosporine

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
2046

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
ITK

Domain mapping of disease mutations (DMDM)

More...
DMDMi
585361

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000881061 – 620Tyrosine-protein kinase ITK/TSKAdd BLAST620

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei180Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei512Phosphotyrosine; by LCKCombined sources1
Modified residuei565PhosphoserineCombined sources1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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.2 Publications
Ubiquitinated.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
Q08881

MaxQB - The MaxQuant DataBase

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MaxQBi
Q08881

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q08881

PeptideAtlas

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PeptideAtlasi
Q08881

PRoteomics IDEntifications database

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PRIDEi
Q08881

ProteomicsDB human proteome resource

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ProteomicsDBi
58650

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q08881

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q08881

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

T-cell lines and natural killer cell lines.

<p>This subsection of the ‘Expression’ section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Through a myriad of surface receptors including the TCR/CD3 signaling complex, coreceptors, or chemokine receptors.2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000113263 Expressed in 134 organ(s), highest expression level in mononuclear cell

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q08881 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q08881 HS

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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.

Interacts with TBX21 (By similarity).

By similarity3 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
109907, 35 interactors

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
Q08881

Database of interacting proteins

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DIPi
DIP-29974N

Protein interaction database and analysis system

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IntActi
Q08881, 14 interactors

Molecular INTeraction database

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MINTi
Q08881

STRING: functional protein association networks

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STRINGi
9606.ENSP00000398655

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
Q08881

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1620
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q08881

Database of comparative protein structure models

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ModBasei
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
Q08881

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini4 – 111PHPROSITE-ProRule annotationAdd BLAST108
Domaini171 – 231SH3PROSITE-ProRule annotationAdd BLAST61
Domaini239 – 338SH2PROSITE-ProRule annotationAdd BLAST100
Domaini363 – 615Protein kinasePROSITE-ProRule annotationAdd BLAST253

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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.1 Publication

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri113 – 149Btk-typePROSITE-ProRule annotationAdd BLAST37

Keywords - Domaini

SH2 domain, SH3 domain, Zinc-finger

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG0197 Eukaryota
COG0515 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000158850

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000233859

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q08881

KEGG Orthology (KO)

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KOi
K07363

Identification of Orthologs from Complete Genome Data

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OMAi
GRWRCCA

Database of Orthologous Groups

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OrthoDBi
933071at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q08881

TreeFam database of animal gene trees

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TreeFami
TF351634

Family and domain databases

Conserved Domains Database

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CDDi
cd11908 SH3_ITK, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.30.29.30, 1 hit
3.30.505.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR035583 ITK_SH3
IPR011009 Kinase-like_dom_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR001562 Znf_Btk_motif

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00779 BTK, 1 hit
PF00169 PH, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit

Protein Motif fingerprint database; a protein domain database

More...
PRINTSi
PR00401 SH2DOMAIN
PR00109 TYRKINASE

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00107 BTK, 1 hit
SM00233 PH, 1 hit
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in 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

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q08881-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNNFILLEEQ LIKKSQQKRR TSPSNFKVRF FVLTKASLAY FEDRHGKKRT
60 70 80 90 100
LKGSIELSRI KCVEIVKSDI SIPCHYKYPF QVVHDNYLLY VFAPDRESRQ
110 120 130 140 150
RWVLALKEET RNNNSLVPKY HPNFWMDGKW RCCSQLEKLA TGCAQYDPTK
160 170 180 190 200
NASKKPLPPT PEDNRRPLWE PEETVVIALY DYQTNDPQEL ALRRNEEYCL
210 220 230 240 250
LDSSEIHWWR VQDRNGHEGY VPSSYLVEKS PNNLETYEWY NKSISRDKAE
260 270 280 290 300
KLLLDTGKEG AFMVRDSRTA GTYTVSVFTK AVVSENNPCI KHYHIKETND
310 320 330 340 350
NPKRYYVAEK YVFDSIPLLI NYHQHNGGGL VTRLRYPVCF GRQKAPVTAG
360 370 380 390 400
LRYGKWVIDP SELTFVQEIG SGQFGLVHLG YWLNKDKVAI KTIREGAMSE
410 420 430 440 450
EDFIEEAEVM MKLSHPKLVQ LYGVCLEQAP ICLVFEFMEH GCLSDYLRTQ
460 470 480 490 500
RGLFAAETLL GMCLDVCEGM AYLEEACVIH RDLAARNCLV GENQVIKVSD
510 520 530 540 550
FGMTRFVLDD QYTSSTGTKF PVKWASPEVF SFSRYSSKSD VWSFGVLMWE
560 570 580 590 600
VFSEGKIPYE NRSNSEVVED ISTGFRLYKP RLASTHVYQI MNHCWKERPE
610 620
DRPAFSRLLR QLAEIAESGL
Length:620
Mass (Da):71,831
Last modified:October 1, 1994 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iDAE396BD2309319D
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RFR5E5RFR5_HUMAN
Tyrosine-protein kinase ITK/TSK
ITK
73Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E5RJY4E5RJY4_HUMAN
Tyrosine-protein kinase ITK/TSK
ITK
116Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti171 – 172PE → GS AA sequence (PubMed:12573241).Curated2
Sequence conflicti331V → W in AAB28072 (PubMed:8364206).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04171019R → K in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_04171123P → L in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_051696193R → Q. Corresponds to variant dbSNP:rs17054374EnsemblClinVar.1
Natural variantiVAR_063424335R → W in LPFS1; shows nearly undetectable mutant ITK protein consistent with severe protein instability. 1 PublicationCorresponds to variant dbSNP:rs121908191EnsemblClinVar.1
Natural variantiVAR_041712451R → Q in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs779372373Ensembl.1
Natural variantiVAR_041713581R → W1 PublicationCorresponds to variant dbSNP:rs34482255EnsemblClinVar.1
Natural variantiVAR_041714587V → I1 PublicationCorresponds to variant dbSNP:rs56005928EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
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

The Consensus CDS (CCDS) project

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CCDSi
CCDS4336.1

Protein sequence database of the Protein Information Resource

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PIRi
S33253

NCBI Reference Sequences

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RefSeqi
NP_005537.3, NM_005546.3

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENST00000422843; ENSP00000398655; ENSG00000113263

Database of genes from NCBI RefSeq genomes

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GeneIDi
3702

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:3702

UCSC genome browser

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UCSCi
uc003lwo.2 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS4336.1
PIRiS33253
RefSeqiNP_005537.3, NM_005546.3

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SM2X-ray2.30A/B357-620[»]
1SNUX-ray2.50A/B357-620[»]
1SNXX-ray3.20A/B357-620[»]
2E6INMR-A113-169[»]
2LMJNMR-A171-231[»]
2YUQNMR-A162-239[»]
3MIYX-ray1.67A/B357-620[»]
3MJ1X-ray1.72A357-620[»]
3MJ2X-ray1.90A357-620[»]
3QGWX-ray2.10A/B357-620[»]
3QGYX-ray2.10A/B357-620[»]
3T9TX-ray1.65A354-620[»]
3V5JX-ray2.59A/B357-620[»]
3V5LX-ray1.86A/B/C/D357-620[»]
3V8TX-ray2.00A/B357-620[»]
3V8WX-ray2.27A/B357-620[»]
4HCTX-ray1.48A354-620[»]
4HCUX-ray1.43A354-620[»]
4HCVX-ray1.48A354-620[»]
4KIOX-ray2.18A/B/C/D357-620[»]
4L7SX-ray2.03A/B357-620[»]
4M0YX-ray1.70A354-620[»]
4M0ZX-ray2.00A354-620[»]
4M12X-ray2.15A354-620[»]
4M13X-ray1.85A354-620[»]
4M14X-ray1.55A354-620[»]
4M15X-ray1.52A354-620[»]
4MF0X-ray2.67A/B357-620[»]
4MF1X-ray2.11A/B357-620[»]
4PP9X-ray2.58A/B357-620[»]
4PPAX-ray2.67A/B357-620[»]
4PPBX-ray2.82A/B357-620[»]
4PPCX-ray2.95A/B357-620[»]
4PQNX-ray1.71A357-620[»]
4QD6X-ray2.45A/B357-620[»]
4RFMX-ray2.10A357-620[»]
SMRiQ08881
ModBaseiSearch...

Protein-protein interaction databases

BioGridi109907, 35 interactors
CORUMiQ08881
DIPiDIP-29974N
IntActiQ08881, 14 interactors
MINTiQ08881
STRINGi9606.ENSP00000398655

Chemistry databases

BindingDBiQ08881
ChEMBLiCHEMBL2959
DrugBankiDB06589 Pazopanib
DB02010 Staurosporine
GuidetoPHARMACOLOGYi2046

PTM databases

iPTMnetiQ08881
PhosphoSitePlusiQ08881

Polymorphism and mutation databases

BioMutaiITK
DMDMi585361

Proteomic databases

jPOSTiQ08881
MaxQBiQ08881
PaxDbiQ08881
PeptideAtlasiQ08881
PRIDEiQ08881
ProteomicsDBi58650

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
3702
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000422843; ENSP00000398655; ENSG00000113263
GeneIDi3702
KEGGihsa:3702
UCSCiuc003lwo.2 human

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
3702
DisGeNETi3702

GeneCards: human genes, protein and diseases

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GeneCardsi
ITK
HGNCiHGNC:6171 ITK
MalaCardsiITK
MIMi186973 gene
613011 phenotype
neXtProtiNX_Q08881
OpenTargetsiENSG00000113263
Orphaneti238505 Combined immunodeficiency due to CD27 deficiency
PharmGKBiPA29968

GenAtlas: human gene database

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GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00940000158850
HOGENOMiHOG000233859
InParanoidiQ08881
KOiK07363
OMAiGRWRCCA
OrthoDBi933071at2759
PhylomeDBiQ08881
TreeFamiTF351634

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-202433 Generation of second messenger molecules
R-HSA-2871809 FCERI mediated Ca+2 mobilization
SignaLinkiQ08881
SIGNORiQ08881

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
ITK human
EvolutionaryTraceiQ08881

The Gene Wiki collection of pages on human genes and proteins

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GeneWikii
ITK_(gene)

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

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GenomeRNAii
3702

Protein Ontology

More...
PROi
PR:Q08881

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000113263 Expressed in 134 organ(s), highest expression level in mononuclear cell
ExpressionAtlasiQ08881 baseline and differential
GenevisibleiQ08881 HS

Family and domain databases

CDDicd11908 SH3_ITK, 1 hit
Gene3Di2.30.29.30, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR035583 ITK_SH3
IPR011009 Kinase-like_dom_sf
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR001562 Znf_Btk_motif
PfamiView protein in Pfam
PF00779 BTK, 1 hit
PF00169 PH, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PF00018 SH3_1, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00107 BTK, 1 hit
SM00233 PH, 1 hit
SM00252 SH2, 1 hit
SM00326 SH3, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF50044 SSF50044, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiITK_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q08881
Secondary accession number(s): B2R752, Q32ML7
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: July 3, 2019
This is version 205 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  7. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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