Description: Homo sapiens tec protein tyrosine kinase (TEC), mRNA. RefSeq Summary (NM_003215): The protein encoded by this gene belongs to the Tec family of non-receptor protein-tyrosine kinases containing a pleckstrin homology domain. Tec family kinases are involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, heterotrimeric G-protein coupled receptors, and integrin molecules. They are also key players in the regulation of the immune functions. Tec kinase is an integral component of T cell signaling and has a distinct role in T cell activation. This gene may be associated with myelodysplastic syndrome. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr4:48,137,800-48,271,814 Size: 134,015 Total Exon Count: 18 Strand: - Coding Region Position: hg19 chr4:48,139,433-48,230,631 Size: 91,199 Coding Exon Count: 17
ID:TEC_HUMAN DESCRIPTION: RecName: Full=Tyrosine-protein kinase Tec; EC=2.7.10.2; FUNCTION: Non-receptor tyrosine kinase that contributes to signaling from many receptors and participates as a signal transducer in multiple downstream pathways, including regulation of the actin cytoskekleton. Plays a redundant role to ITK in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. Required for TCR-dependent IL2 gene induction. Phosphorylates DOK1, one CD28-specific substrate, and contributes to CD28-signaling. Mediates signals that negatively regulate IL2RA expression induced by TCR cross-linking. Plays a redundant role to BTK in BCR-signaling for B-cell development and activation, especially by phosphorylating STAP1, a BCR-signaling protein. Required in mast cells for efficient cytokine production. Involved in both growth and differentiation mechanisms of myeloid cells through activation by the granulocyte colony-stimulating factor CSF3, a critical cytokine to promoting the growth, differentiation, and functional activation of myeloid cells. Participates in platelet signaling downstream of integrin activation. Cooperates with JAK2 through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. GRB10, a negative modifier of the FOS activation pathway, is another substrate of TEC. TEC is involved in G protein-coupled receptor- and integrin-mediated signalings in blood platelets. Plays a role in hepatocyte proliferation and liver regeneration and is involved in HGF-induced ERK signaling pathway. TEC regulates also FGF2 unconventional secretion (endoplasmic reticulum (ER)/Golgi-independent mechanism) under various physiological conditions through phosphorylation of FGF2 'Tyr-215'. May also be involved in the regulation of osteoclast differentiation. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. COFACTOR: Binds 1 zinc ion per subunit (By similarity). ENZYME REGULATION: Activated by tyrosine phosphorylation by a wide range of cytokine stimulations. When T-cells or B-cells receptors are activated, a series of phosphorylation leads to the recruitment of TEC to the cell membrane, where it is phosphorylated at Tyr-519. Also activated in response to SCF. Integrin engagement induces tyrosine phosphorylation of TEC in platelets. STAP1 participates in a positive feedback loop by increasing the activity of TEC. SOCS1 is an inhibitor of TEC kinase activity. SUBUNIT: Interacts with INPP5D/SHIP1 and INPPL1/SHIP2. Interacts with CD28, FASLG, FGF2, GRB10, LYN and KIT. Interacts with VAV1 and JAK2 (By similarity). SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane protein. Cytoplasm, cytoskeleton. Note=Following B-cell or T-cell receptors activation by antigen, translocates to the plasma membrane through its PH domain. Thrombin and integrin engagement induces translocation of TEC to the cytoskeleton during platelet activation. In cardiac myocytes, assumes a diffuse intracellular localization under basal conditions but is recruited to striated structures upon various stimuli, including ATP (By similarity). TISSUE SPECIFICITY: Expressed in a wide range of cells, including hematopoietic cell lines like myeloid, B-, and T-cell lineages. DOMAIN: The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane. It is extended in the BTK kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain. DOMAIN: The SH3 domain is essential for its targeting to activated CD28 costimulatory molecule (By similarity). PTM: Following B-cell or T-cell receptors engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-519. Undergoes also tyrosine phosphorylation during platelet activation. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. SIMILARITY: Contains 1 Btk-type zinc finger. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. SIMILARITY: Contains 1 SH3 domain. CAUTION: It is uncertain whether Met-1 is the initiator.
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): TEC CDC HuGE Published Literature: TEC Positive Disease Associations: Inflammatory Bowel Diseases Related Studies:
Inflammatory Bowel Diseases Richard H Duerr et al. Science (New York, N.Y.) 2006, A genome-wide association study identifies IL23R as an inflammatory bowel disease gene., Science (New York, N.Y.).
[PubMed 17068223]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P42680
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
