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Protein

Tyrosine-protein kinase Tec

Gene

TEC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

Caution

It is uncertain whether Met-1 is the initiator.Curated

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Cofactori

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

Activity regulationi

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.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi121ZincBy similarity1
Metal bindingi132ZincBy similarity1
Metal bindingi133ZincBy similarity1
Metal bindingi143ZincBy similarity1
Binding sitei398ATPPROSITE-ProRule annotation1
Active sitei489Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri113 – 149Btk-typePROSITE-ProRule annotationAdd BLAST37
Nucleotide bindingi376 – 384ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  • phospholipid binding Source: BHF-UCL

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-1433557 Signaling by SCF-KIT
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling
SignaLinkiP42680
SIGNORiP42680

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase Tec (EC:2.7.10.2)
Gene namesi
Name:TEC
Synonyms:PSCTK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000135605.12
HGNCiHGNC:11719 TEC
MIMi600583 gene
neXtProtiNX_P42680

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; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi7006
MalaCardsiTEC
OpenTargetsiENSG00000135605
PharmGKBiPA36436

Chemistry databases

ChEMBLiCHEMBL4246
GuidetoPHARMACOLOGYi2238

Polymorphism and mutation databases

BioMutaiTEC
DMDMi158518392

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000881701 – 631Tyrosine-protein kinase TecAdd BLAST631

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei206Phosphotyrosine; by autocatalysisCombined sources1 Publication1
Modified residuei228PhosphotyrosineCombined sources1
Modified residuei519Phosphotyrosine; by autocatalysis, LYN and JAK2Combined sources1

Post-translational modificationi

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.4 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP42680
MaxQBiP42680
PaxDbiP42680
PeptideAtlasiP42680
PRIDEiP42680
ProteomicsDBi55526

PTM databases

iPTMnetiP42680
PhosphoSitePlusiP42680

Expressioni

Tissue specificityi

Expressed in a wide range of cells, including hematopoietic cell lines like myeloid, B-, and T-cell lineages.

Gene expression databases

BgeeiENSG00000135605 Expressed in 92 organ(s), highest expression level in lower esophagus mucosa
CleanExiHS_TEC
ExpressionAtlasiP42680 baseline and differential
GenevisibleiP42680 HS

Organism-specific databases

HPAiHPA005733
HPA024657

Interactioni

Subunit structurei

Interacts with INPP5D/SHIP1 and INPPL1/SHIP2. Interacts with CD28, FASLG, FGF2, GRB10, LYN and KIT. Interacts with VAV1 and JAK2 (By similarity).By similarity

Binary interactionsi

Protein-protein interaction databases

BioGridi112865, 23 interactors
IntActiP42680, 18 interactors
MINTiP42680
STRINGi9606.ENSP00000370912

Chemistry databases

BindingDBiP42680

Structurei

Secondary structure

1631
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP42680
SMRiP42680
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 111PHPROSITE-ProRule annotationAdd BLAST108
Domaini179 – 239SH3PROSITE-ProRule annotationAdd BLAST61
Domaini247 – 345SH2PROSITE-ProRule annotationAdd BLAST99
Domaini370 – 623Protein kinasePROSITE-ProRule annotationAdd BLAST254

Domaini

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

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

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000119011
HOGENOMiHOG000233859
HOVERGENiHBG008761
InParanoidiP42680
KOiK07364
OMAiEWYCRNM
OrthoDBiEOG091G0D46
PhylomeDBiP42680
TreeFamiTF351634

Family and domain databases

CDDicd11905 SH3_Tec, 1 hit
Gene3Di2.30.29.30, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
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
IPR035572 Tec_SH3
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
PR00452 SH3DOMAIN
PR00402 TECBTKDOMAIN
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

Sequence (1+)i

Sequence statusi: Complete.

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

P42680-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNFNTILEEI LIKRSQQKKK TSPLNYKERL FVLTKSMLTY YEGRAEKKYR
60 70 80 90 100
KGFIDVSKIK CVEIVKNDDG VIPCQNKYPF QVVHDANTLY IFAPSPQSRD
110 120 130 140 150
LWVKKLKEEI KNNNNIMIKY HPKFWTDGSY QCCRQTEKLA PGCEKYNLFE
160 170 180 190 200
SSIRKALPPA PETKKRRPPP PIPLEEEDNS EEIVVAMYDF QAAEGHDLRL
210 220 230 240 250
ERGQEYLILE KNDVHWWRAR DKYGNEGYIP SNYVTGKKSN NLDQYEWYCR
260 270 280 290 300
NMNRSKAEQL LRSEDKEGGF MVRDSSQPGL YTVSLYTKFG GEGSSGFRHY
310 320 330 340 350
HIKETTTSPK KYYLAEKHAF GSIPEIIEYH KHNAAGLVTR LRYPVSVKGK
360 370 380 390 400
NAPTTAGFSY EKWEINPSEL TFMRELGSGL FGVVRLGKWR AQYKVAIKAI
410 420 430 440 450
REGAMCEEDF IEEAKVMMKL THPKLVQLYG VCTQQKPIYI VTEFMERGCL
460 470 480 490 500
LNFLRQRQGH FSRDVLLSMC QDVCEGMEYL ERNSFIHRDL AARNCLVSEA
510 520 530 540 550
GVVKVSDFGM ARYVLDDQYT SSSGAKFPVK WCPPEVFNYS RFSSKSDVWS
560 570 580 590 600
FGVLMWEVFT EGRMPFEKYT NYEVVTMVTR GHRLYQPKLA SNYVYEVMLR
610 620 630
CWQEKPEGRP SFEDLLRTID ELVECEETFG R
Length:631
Mass (Da):73,581
Last modified:September 11, 2007 - v2
Checksum:iF55DECBF9916E1F9
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RB75D6RB75_HUMAN
Tyrosine-protein kinase Tec
TEC
51Annotation score:
D6RB05D6RB05_HUMAN
Tyrosine-protein kinase Tec
TEC
100Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti514V → F in BAA06171 (PubMed:7934162).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04185044R → Q1 PublicationCorresponds to variant dbSNP:rs35374286Ensembl.1
Natural variantiVAR_041851563R → K in a lung adenocarcinoma sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS3481.1
PIRiI38268
I56997
RefSeqiNP_003206.2, NM_003215.2
UniGeneiHs.479670

Genome annotation databases

EnsembliENST00000381501; ENSP00000370912; ENSG00000135605
GeneIDi7006
KEGGihsa:7006
UCSCiuc003gxz.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS3481.1
PIRiI38268
I56997
RefSeqiNP_003206.2, NM_003215.2
UniGeneiHs.479670

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LULNMR-A1-154[»]
ProteinModelPortaliP42680
SMRiP42680
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112865, 23 interactors
IntActiP42680, 18 interactors
MINTiP42680
STRINGi9606.ENSP00000370912

Chemistry databases

BindingDBiP42680
ChEMBLiCHEMBL4246
GuidetoPHARMACOLOGYi2238

PTM databases

iPTMnetiP42680
PhosphoSitePlusiP42680

Polymorphism and mutation databases

BioMutaiTEC
DMDMi158518392

Proteomic databases

EPDiP42680
MaxQBiP42680
PaxDbiP42680
PeptideAtlasiP42680
PRIDEiP42680
ProteomicsDBi55526

Protocols and materials databases

DNASUi7006
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381501; ENSP00000370912; ENSG00000135605
GeneIDi7006
KEGGihsa:7006
UCSCiuc003gxz.4 human

Organism-specific databases

CTDi7006
DisGeNETi7006
EuPathDBiHostDB:ENSG00000135605.12
GeneCardsiTEC
HGNCiHGNC:11719 TEC
HPAiHPA005733
HPA024657
MalaCardsiTEC
MIMi600583 gene
neXtProtiNX_P42680
OpenTargetsiENSG00000135605
PharmGKBiPA36436
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000119011
HOGENOMiHOG000233859
HOVERGENiHBG008761
InParanoidiP42680
KOiK07364
OMAiEWYCRNM
OrthoDBiEOG091G0D46
PhylomeDBiP42680
TreeFamiTF351634

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-1433557 Signaling by SCF-KIT
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-512988 Interleukin-3, Interleukin-5 and GM-CSF signaling
SignaLinkiP42680
SIGNORiP42680

Miscellaneous databases

ChiTaRSiTEC human
GeneWikiiTEC_(gene)
GenomeRNAii7006
PROiPR:P42680
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135605 Expressed in 92 organ(s), highest expression level in lower esophagus mucosa
CleanExiHS_TEC
ExpressionAtlasiP42680 baseline and differential
GenevisibleiP42680 HS

Family and domain databases

CDDicd11905 SH3_Tec, 1 hit
Gene3Di2.30.29.30, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
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
IPR035572 Tec_SH3
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
PR00452 SH3DOMAIN
PR00402 TECBTKDOMAIN
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
ProtoNetiSearch...

Entry informationi

Entry nameiTEC_HUMAN
AccessioniPrimary (citable) accession number: P42680
Secondary accession number(s): B7ZKZ6, Q3MIS5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: September 11, 2007
Last modified: November 7, 2018
This is version 184 of the entry and version 2 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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