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FLASH GENE

Symbol

ANGPT1

contributors: mct/npt/pgu - updated : 22-12-2015

HGNC name	angiopoietin 1
HGNC id	484

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	248.54 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	binding sites for ETS and AP-1 transcription factor family members (only the ETS factor ELF3 was capable of transactivating its promoter)

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D8S1977 - D8S1610 - D8S1176 - D8S545 - D8S1844 - DPYS DPYS - D8S1496 - D8S556 - D8S207 - D8S1580 - D8S1780 - D8S1703 - D8S1768 - D8S1975 - D8S1588 - D8S200 - D8S85 - D8S1830 - ANGPT1 - TRHR - D8S1940 ,EBAG9 - D8S1594 - D8S1122 - D8S1960 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed variant 1 9 - 4338 isoform 1 57.4 498 - 2009 19223473

EXPRESSION

Type

widely

constitutive of

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 Cardiovascular vessels         Digestive salivary gland       highly Respiratory respiratory tract trachea     highly Urinary kidney nephron renal capsule glomerulus

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Connective cartilage       Muscular

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell not specific synoviocyte Urinary podocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a 15 aa signal peptide
	a N terminal region lacking homology to any known structure
	an alpha-helical rich coiled-coil segment
	a fibrinogen-like domain at the C terminus
	five consensus motifs for N-glycosylation calcium binding motif

conjugated

GlycoP

isoforms

Precursor

a 483 aa mature peptide

HOMOLOGY

interspecies	homolog to C.elegans D1009.3
	ortholog to rattus Angpt1
	ortholog to murine Angpt1

Homologene

FAMILY	vascular endothelial growth factor family
	angiopoietin family

CATEGORY

regulatory , signaling growth factor

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	secreted ligand for the vascular endothelial restricted receptor tyrosine kinase TEK, inducing phosphorylation of TEK producing activation of TEK
	with ANGPT2 may play an important role in the pathophysiology of septic shock in children
	involved in late stages of angiogenesis, in the regulation of luteal angiogenesis
	promoting angiogenic remodeling as well as vessel maturation and stabilization
	playing a role in the heart early development and in blood vessel formation
	mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme
	may be an important regulator of angiogenesis in inflammatory arthritis
	modulating endothelial cell function and gene expression via the transcription factor FOXO1 and acting as a regulator of endothelial cell survival and blood vessel stability
	inducing lymphatic vessels growth in adult tissues
	shows anti-permeability activity through up-regulation of TJP2
	may have a unique role in neurogenesis independent of its role in angiogenesis
	endothelial growth factor with a critical role in division, survival, and adhesion of endothelial cells via TEK receptor activity
	is a proneurogenic peptide on subventricular zone stem/progenitor cells
	may play an important role in the pathogenesis of Behcet disease
	antileakage action of ANGPT1 requires PDGF-dependent actions of pericytes in maintaining endothelial stability
	plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor TEK
	promotes endothelial differentiation from embryonic stem cells and induced pluripotent stem cells
	decreases endothelial cell permeability and increases vascular stabilization via recruitment of pericytes and smooth muscle cells to growing blood vessels
	balance between the pro-leakage effects of VEGFA and anti-leakage effects of the angiopoietins (ANGPT1, ANGPT2), in part, modulates vascular integrity and oxygen delivery
	ANGPT1 signaling via the TEK receptor regulates vascular and hematopoietic systems
	ANGPT1 and ANGPT2 are secreted factors that bind to the endothelial cell-specific receptor tyrosine kinase TEK (TEK) and regulate angiogenesis
	can induce distinctive vascular remodeling through highly organized angiogenesis and tightening of endothelial cell (EC) junctions
	VEGFA and ANGPT1 regulate endothelial cell (EC) junctions by determining the localization of the RHOA-specific guanine nucleotide exchange factor PLEKHG5
	ANGPT1 and ANGPT2, ligands for TEK, play essential roles in balancing vessel stability and regression during both developmental and tumor-induced angiogenesis

CELLULAR PROCESS	cell life, differentiation
	cell life, proliferation/growth
	cell life, antiapoptosis

PHYSIOLOGICAL PROCESS

development

text	embryogenesis
	morphogenesis
	angiogenesis

PATHWAY

metabolism

signaling

signal transduction

	ANGPT1/TEK signaling has a pivotal role in embryonic stem cell- endothelial cell differentiation
	ANGPT1-TEK signaling affects the differentiation capacity of hematopoietic lineages during development and increases the stem cell activity of hematopoietic stem and progenitor cell (HSPC) (

a component	ANGPT1/TEK axis modulates the expression and function of ABC transporters in glioma cells and brain tumor stem cells
	ANGPT1/TEK signal potentiates basal Notch signal controlling vascular quiescence by up-regulating DLL4 through AKT-mediated activation of CTNNB1

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	TIE2 (TEK) receptor tyrosine kinase (significant correlation between ANGPT1 gene expression and TEK gene expression in normal ovary with corpus luteum)
	negatively regulating HNF1A in endothelial cells
	activating intracellular PI.3' kinase
	interacting with PLD1 (a new mediator of ANGPT1/TEK-induced signaling pathway, that participates in MAPK activation and endothelial cell migration)
	interacting with ANGPT1 (ANGPT2 functions as an agonist when ANGPT1 is absent but as a dose-dependent antagonist when ANGPT1 is present)
	TIE1-TEK interactions are dynamic, inhibitory, and differentially modulated by ANGPT1 and ANGPT2
	regulates both vascular quiescence and angiogenesis through the receptor tyrosine kinase TEK
	ANGPT2 antagonizes ANGPT1 function, leading to excessive vessel sprouting with impaired pericyte recruitment and vessel stabilization
	requires IQGAP1 as an indispensable activator of RAC1
	maintained PLEKHG5 at the junctions, inducing junction stabilization
	under hypoxic conditions, TIE1 is critical for reducing ANGPT1-induced TEK activity and angiogenesis
	KDM3B represses transcription of the angiogenesis regulatory gene, ANGPT1
	ANGPT1 requires oxidant signaling through NCF1 to promote endothelial barrier defense
	overexpression of CASP5 can promote the angiogenesis significantly, possibly by inhibiting the ANGPT1/Tie2 pathway and promoting VEGFA pathway

cell & other

REGULATION

induced by

induced with ELF3 in synovial fibroblasts in response to inflammatory cytokines

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in hepatocellular carcinoma in progression and in synovial fibroblasts of rheumatoid arthritis (RA) constitutional     --low   in menorrhagia constitutional     --other   ectopic expression of Ang1 promotes neuronal differentiation and neurite outgrowth in neural progenitor cells constitutional     --over   in Behçet disease patients compared to controls

Susceptibility

to pregnancy complications

Variant & Polymorphism other	ANGPT1 rs2507800 polymorphism may have a potential role in screening women to predict the risk of these pregnancy complications

Candidate gene
Marker	a single measurement of serum ANGPT1 and ANGPT2 at 6-8 weeks of gestation designate the outcome of a pregnancy, as their levels are significantly decreased in failed than normal pregnancies
	serum ANGPT1 showed potential to discriminate missed abortions (MA) from ectopic pregnancies (EP)
Therapy target
	System Type Disorder Pubmed miscelleaneous vascular   candidate for therapeutic neovascularization and vascular protection

ANIMAL & CELL MODELS

	mice overexpressing Angpt1
	in mice variant COMP-Angpt1 ameliorates leukocyte adhesion and reinforces endothelial tight junctions during endotoxemia