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FLASH GENE

Symbol

TEK

contributors: mct/pgu - updated : 09-12-2013

HGNC name	TEK tyrosine kinase, endothelial
HGNC id	11724

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	VMCM familial venous malformation, multiple cutaneous and mucosal
Location	9p21.2      Physical location : 27.109.146 - 27.230.171
Synonym name	endothelial-specific receptor for angiopoietin-1
	venous malformations, multiple cutaneous and mucosal
	CD202b antigen
	tunica interna endothelial cell kinase
	soluble TIE2 variant 2
	angiopoietin-1 receptor
Synonym symbol(s)	TIE2, CD202B, TIE-2, VMCM1
EC.number	2.7.10.1

DNA

TYPE	functioning gene
STRUCTURE	121.03 kb     23 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	promoter contains closely aligned clusters of three GATA sites and six Ets-binding sites in the first exon

MAPPING

cloned

Y

linked

N

status

confirmed

Physical map

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000459 23 - 1124 NP_000450 12.4 1124 - 1999 10521483

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Hearing/Equilibrium ear inner cochlea   highly Lymphoid/Immune lymphatic vessel         Nervous brain       lowly Reproductive female system placenta     highly Homo sapiens Respiratory respiratory tract trachea     highly Urinary kidney nephron renal capsule glomerulus lowly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text	in chorionic villi tree during early pregnancy

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two immunoglobulin like C2-type domains
	three epidermal growth factor 3 -like domains
	three fibronectin-type III homology domains
	a protein kinase domain

HOMOLOGY

interspecies	homolog to rattus Tek (93.74 pc)
	homolog to murine Tek (90.61 pc)

Homologene

FAMILY	protein kinase superfamily
	Tyr protein kinase family

CATEGORY

enzyme , signaling , receptor membrane tyrosine kinase

SUBCELLULAR LOCALIZATION	plasma membrane
text	localized with PLD1 in caveolae

basic FUNCTION	required for blood vessel formation and maintenance
	involved in angiogenesis (in maintenance and/or remodeling of the adult vasculature and regulation during luteinization, luteolysis and rescue)
	protein-tyrosine kinase receptor that is specifically expressed in endothelial cells
	has dual roles in promoting angiogenesis and stabilizing blood vessels ligand-independent dimerization of TEK

CELLULAR PROCESS

cell communication

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

ANGPT1/TEK signaling has a pivotal role in embryonic stem cell- endothelial cell differentiation

a component

ANGPT1/TEK axis modulates the expression and function of ABC transporters in glioma cells and brain tumor stem cells

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	receptor of ANGPT1
	HOXA13 directly regulates TEK and FOXF1 in the placental labyrinth endothelia
	interacting with ABCG2, ABCC2 (downmodulation of ABCG2 or ABCC2 resulted in the inability of TEK activation to induce a chemoresistant phenotype)
	bind to GATA3
	TIE1-TEK interactions are dynamic, inhibitory, and differentially modulated by ANGPT1 and ANGPT2
	ST14 interacts with TEK and degrades the TEK extracellular portion that contains the ligand-binding domain
	molecular balance between receptor tyrosine kinases TIE1 and TEK is dynamically controlled by VEGF and TNF and regulates angiopoietin signalling
	expression level of TIE1 and its physical interaction with TEK defines whether ANGPT2 functions as a TEK2 agonist or antagonist, thereby determining the context-dependent differential endothelial sensitivity to ANGPT2
	ANGPT1 signaling via the TEK receptor regulates vascular and hematopoietic systems
	ligand-independent dimerization of TEK is essential for a strong response upon stimulation with high dose ANGPT1
	under hypoxic conditions, TIE1 is critical for reducing ANGPT1-induced TEK activity and angiogenesis

cell & other

REGULATION

activated by

by its ligand, angiopoietin ANGPT1

Other

regulated by shear stress

ASSOCIATED DISORDERS

corresponding disease(s)

VMCM

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       gain of function in pulmonary hypertension constitutional somatic mutation       cause solitary and multiple sporadic venous malformations tumoral       gain of function may be important in modifying the evolution of gliomas during conventional chemotherapy regimens, and open new avenues for the search of more effective therapies to avoid the inevitable brain tumor recurrence constitutional somatic mutation       in venous malformations (VM)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed miscelleaneous vascular   potential therapeutic targets for venous malformations

ANIMAL & CELL MODELS