P42680 (TEC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase Tec
EC=2.7.10.2

Gene names

Name:	TEC
Synonyms:	PSCTK4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	631 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 cytoskeleton. 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. Ref.8 Ref.10 Ref.15 Ref.16
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. Ref.5 Ref.7 Ref.9 Ref.10
Subunit structure	Interacts with INPP5D/SHIP1 and INPPL1/SHIP2. Interacts with CD28, FASLG, FGF2, GRB10, LYN and KIT. Interacts with VAV1 and JAK2 By similarity. Ref.5 Ref.8 Ref.11 Ref.12 Ref.16
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. Ref.6 Ref.9
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. The SH3 domain is essential for its targeting to activated CD28 costimulatory molecule By similarity.
Post-translational modification	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. Ref.4 Ref.5 Ref.6 Ref.9
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.
Caution	It is uncertain whether Met-1 is the initiator.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Polymorphism
Domain	SH2 domain SH3 domain Zinc-finger
Ligand	ATP-binding Lipid-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	B cell receptor signaling pathway Inferred from direct assay Ref.10. Source: UniProtKB integrin-mediated signaling pathway Inferred from direct assay Ref.9. Source: UniProtKB intracellular protein kinase cascade Traceable author statement Ref.1. Source: ProtInc regulation of platelet activation Inferred from direct assay Ref.6Ref.9. Source: UniProtKB
Cellular_component	cytoskeleton Inferred from direct assay Ref.6Ref.9. Source: UniProtKB cytosol Traceable author statement. Source: Reactome plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
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 phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 631

631

Tyrosine-protein kinase Tec

PRO_0000088170

Regions

Domain

4 – 111

108

PH

Domain

179 – 239

61

SH3

Domain

247 – 345

99

SH2

Domain

370 – 623

254

Protein kinase

Zinc finger

113 – 149

37

Btk-type

Nucleotide binding

376 – 384

9

ATP By similarity

Sites

Active site

489

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

398

1

ATP By similarity

Amino acid modifications

Modified residue

206

1

Phosphotyrosine; by autocatalysis Ref.4 Ref.13

Modified residue

228

1

Phosphotyrosine Ref.13

Modified residue

519

1

Phosphotyrosine; by autocatalysis, LYN and JAK2 Ref.14

Natural variations

Natural variant

44

1

R → Q. Ref.17
Corresponds to variant rs35374286 [ dbSNP | Ensembl ].

VAR_041850

Natural variant

563

1

R → K in a lung adenocarcinoma sample; somatic mutation. Ref.17

VAR_041851

Experimental info

Sequence conflict

514

1

V → F in BAA06171. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

631

Helix Strand Turn

Details...

Beta strand

3 – 14

12

Beta strand

19 – 21

3

Beta strand

26 – 41

16

Beta strand

45 – 47

3

Beta strand

53 – 55

3

Helix

56 – 58

3

Beta strand

61 – 64

4

Beta strand

69 – 71

3

Beta strand

74 – 76

3

Beta strand

78 – 83

6

Beta strand

88 – 92

5

Helix

96 – 110

15

Beta strand

118 – 120

3

Beta strand

132 – 134

3

Beta strand

143 – 145

3

Sequences

	Sequence		Length	Mass (Da)
	P42680 [UniParc]. Last modified September 11, 2007. Version 2. Checksum: F55DECBF9916E1F9	FASTA	631	73,581
	10 20 30 40 50 60 MNFNTILEEI LIKRSQQKKK TSPLNYKERL FVLTKSMLTY YEGRAEKKYR KGFIDVSKIK 70 80 90 100 110 120 CVEIVKNDDG VIPCQNKYPF QVVHDANTLY IFAPSPQSRD LWVKKLKEEI KNNNNIMIKY 130 140 150 160 170 180 HPKFWTDGSY QCCRQTEKLA PGCEKYNLFE SSIRKALPPA PETKKRRPPP PIPLEEEDNS 190 200 210 220 230 240 EEIVVAMYDF QAAEGHDLRL ERGQEYLILE KNDVHWWRAR DKYGNEGYIP SNYVTGKKSN 250 260 270 280 290 300 NLDQYEWYCR NMNRSKAEQL LRSEDKEGGF MVRDSSQPGL YTVSLYTKFG GEGSSGFRHY 310 320 330 340 350 360 HIKETTTSPK KYYLAEKHAF GSIPEIIEYH KHNAAGLVTR LRYPVSVKGK NAPTTAGFSY 370 380 390 400 410 420 EKWEINPSEL TFMRELGSGL FGVVRLGKWR AQYKVAIKAI REGAMCEEDF IEEAKVMMKL 430 440 450 460 470 480 THPKLVQLYG VCTQQKPIYI VTEFMERGCL LNFLRQRQGH FSRDVLLSMC QDVCEGMEYL 490 500 510 520 530 540 ERNSFIHRDL AARNCLVSEA GVVKVSDFGM ARYVLDDQYT SSSGAKFPVK WCPPEVFNYS 550 560 570 580 590 600 RFSSKSDVWS FGVLMWEVFT EGRMPFEKYT NYEVVTMVTR GHRLYQPKLA SNYVYEVMLR 610 620 630 CWQEKPEGRP SFEDLLRTID ELVECEETFG R

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and analysis of the human Tec protein-tyrosine kinase." Sato K., Mano H., Ariyama T., Inazawa J., Yazaki Y., Hirai H. Leukemia 8:1663-1672(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[2]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[4]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 203-206, PHOSPHORYLATION AT TYR-206.
[5]	"Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding." Tang B., Mano H., Yi T., Ihle J.N. Mol. Cell. Biol. 14:8432-8437(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH KIT, ENZYME REGULATION.
[6]	"Integrin-dependent tyrosine phosphorylation and cytoskeletal translocation of Tec in thrombin-activated platelets." Laffargue M., Monnereau L., Tuech J., Ragab A., Ragab-Thomas J., Payrastre B., Raynal P., Chap H. Biochem. Biophys. Res. Commun. 238:247-251(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
[7]	"SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase." Ohya K., Kajigaya S., Yamashita Y., Miyazato A., Hatake K., Miura Y., Ikeda U., Shimada K., Ozawa K., Mano H. J. Biol. Chem. 272:27178-27182(1997) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[8]	"Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase." Mano H., Ohya K., Miyazato A., Yamashita Y., Ogawa W., Inazawa J., Ikeda U., Shimada K., Hatake K., Kasuga M., Ozawa K., Kajigaya S. Genes Cells 3:431-441(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRB10, FUNCTION IN PHOSPHORYLATION OF GRB10.
[9]	"Tec is involved in G protein-coupled receptor- and integrin-mediated signalings in human blood platelets." Hamazaki Y., Kojima H., Mano H., Nagata Y., Todokoro K., Abe T., Nagasawa T. Oncogene 16:2773-2779(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION, ENZYME REGULATION, SUBCELLULAR LOCATION.
[10]	"Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase." Ohya K., Kajigaya S., Kitanaka A., Yoshida K., Miyazato A., Yamashita Y., Yamanaka T., Ikeda U., Shimada K., Ozawa K., Mano H. Proc. Natl. Acad. Sci. U.S.A. 96:11976-11981(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF STAP1, ENZYME REGULATION.
[11]	"SHIP family inositol phosphatases interact with and negatively regulate the Tec tyrosine kinase." Tomlinson M.G., Heath V.L., Turck C.W., Watson S.P., Weiss A. J. Biol. Chem. 279:55089-55096(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH INPP5D AND INPPL1.
[12]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FASLG.
[13]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-206 AND TYR-228, MASS SPECTROMETRY.
[14]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-519, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"Tec protein tyrosine kinase inhibits CD25 expression in human T-lymphocyte." Susaki K., Kitanaka A., Dobashi H., Kubota Y., Kittaka K., Kameda T., Yamaoka G., Mano H., Mihara K., Ishida T. Immunol. Lett. 127:135-142(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"Tec-kinase-mediated phosphorylation of fibroblast growth factor 2 is essential for unconventional secretion." Ebert A.D., Laussmann M., Wegehingel S., Kaderali L., Erfle H., Reichert J., Lechner J., Beer H.D., Pepperkok R., Nickel W. Traffic 11:813-826(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF FGF2, INTERACTION WITH FGF2.
[17]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLN-44 AND LYS-563.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D29767 mRNA. Translation: BAA06171.1.
CH471069 Genomic DNA. Translation: EAW93055.1.
BC101711 mRNA. Translation: AAI01712.1.
BC101713 mRNA. Translation: AAI01714.1.
BC143487 mRNA. Translation: AAI43488.1.

IPI

IPI00000878.

PIR

I38268.
I56997.

RefSeq

NP_003206.2. NM_003215.2.

UniGene

Hs.479670.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LUL	NMR	-	A	1-154	[»]

ProteinModelPortal

P42680.

ModBase

Search...

Protein-protein interaction databases

IntAct

P42680. 9 interactions.

MINT

MINT-1498364.

STRING

9606.ENSP00000370912.

PTM databases

PhosphoSite

P42680.

Polymorphism databases

DMDM

158518392.

Proteomic databases

PaxDb

P42680.

PRIDE

P42680.

Protocols and materials databases

DNASU

7006.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000381501; ENSP00000370912; ENSG00000135605.

GeneID

7006.

KEGG

hsa:7006.

UCSC

uc003gxz.3. human.

Organism-specific databases

CTD

7006.

GeneCards

GC04M048137.

HGNC

HGNC:11719. TEC.

HPA

HPA005733.

MIM

600583. gene.

neXtProt

NX_P42680.

PharmGKB

PA36436.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233859.

HOVERGEN

HBG008761.

InParanoid

P42680.

KO

K07364.

OMA

MERGCLL.

OrthoDB

EOG4XKV6H.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

epopathway. EPO signaling pathway.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Reactome

REACT_111102. Signal Transduction.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P42680.

Bgee

P42680.

CleanEx

HS_TEC.

Genevestigator

P42680.

GermOnline

ENSG00000135605. Homo sapiens.

Family and domain databases

Gene3D

2.30.29.30. 1 hit.
3.30.505.10. 1 hit.

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.
[Graphical view]

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.
PR00452. SH3DOMAIN.
PR00402. TECBTKDOMAIN.
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

Search...

Other

BindingDB

P42680.

ChEMBL

CHEMBL4246.

GenomeRNAi

7006.

NextBio

27366.

SOURCE

Search...

Entry information

Entry name

TEC_HUMAN

Accession

Primary (citable) accession number: P42680
Secondary accession number(s): B7ZKZ6, Q3MIS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	September 11, 2007
Last modified:	May 1, 2013
This is version 132 of the entry and version 2 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.