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FLASH GENE

Symbol

EPAS1

contributors: mct/npt/pgu - updated : 08-09-2018

HGNC name	endothelial PAS domain protein 1
HGNC id	3374

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ECYT4 erythrocytosis/polycythemia, familial, 4
Location	2p21      Physical location : 46.524.540 - 46.613.842
Synonym name	hypoxia inducible factor 2 alpha subunit
	HIF-1 alpha-like factor
	HIF2 alpha
Synonym symbol(s)	MOP2, HIF2A, PASD2, HLF, bHLHe73, EPAS-1

DNA

TYPE	functioning gene
STRUCTURE	89.30 kb     16 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001430 16 - 5184 NP_001421 96.3 870 - 2000 10823831

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 Cardiovascular heart         Homo sapiens Digestive intestine small intestine       Homo sapiens Respiratory lung       highly Homo sapiens   respiratory tract trachea     highly Urinary kidney         Homo sapiens

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 Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	endothelial cells, placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two PAS (per-arnt-sim) dimerization domains
	C-terminal PAS domains form heterodimer with ARNT subunits of the HIF2 transcription factor

HOMOLOGY

intraspecies

homolog to HIF1A

Homologene

FAMILY

basic helix-loop-helix (BHLH) family of transcription factors

CATEGORY

RNA associated , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus

basic FUNCTION	involved in the induction of oxygen regulated genes and may be implicated in the development of blood vessels and the tubular system of lung
	playing a role in the adaptation of the cardiac myocytes during heart failure as well as in the regulation of gene expression by hypoxia
	involved in complex oxygen sensing, and influencing the relative contribution of aerobic and anaerobic metabolism and hence the maximum sustainable metabolic power for a given event duration
	differentially binds and regulates transcription under hypoxia
	EPAS1 acts downstream of PPARGC1A as a key regulator of a muscle fiber-type program and the adaptive response to exercise
	regulated CD82 gene expression by binding to its HRE consensus sequence located within its first intron
	is required to induce CD82 expression under hypoxia
	HIF1A and EPAS1 play a critical role in cellular response to hypoxia
	important role in the regulation of tumor progression under chronic hypoxia
	opposite roles of HIF1A and EPAS1 in the regulation of IL8 expression in endothelial cells
	key regulator in alveolar maturation and the production of phospholipids by Type II cells
	role for the EPAS1/ITPR1 axis in regulating Clear cell renal carcinomas cell survival

CELLULAR PROCESS

cell organization/biogenesis

PHYSIOLOGICAL PROCESS

text	vascular remodeling

PATHWAY

metabolism

aminoacid

signaling

catecholamine homeostasis

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting with SOX9 (hypoxia, and more specifically EPAS1, promotes both SOX9-dependent and -independent factors important for cartilage homeostasis)
	interacting with RICTOR (dependent only on the CRTC2 constituent Rictor)
	regulating intronic hypoxia response elements of TWIST1
	VHL appears to specifically repress EPAS1 in renal epithelia
	EPAS1, but not HIF1A, interacted with KLHL20
	KLHL20 as a EPAS1-interacting protein that increases the expression level of EPAS1 protein
	potent and functional inducer of CEBPB expression in chondrocytes by the CEBPB promoter assay
	critical role for CDCP1 as a unique EPAS1 target gene involved in the regulation of cancer metastasis
	FOXO4 interacts with SREBF2 and EPAS1 to modulate CYP51A1 promoter activity
	EPAS1 plays an indispensible role in SP1 transcription factor-mediated ZBTB7A induction, and participated in tumor cell survival and proliferation
	positive correlation of EGLN3 and EPAS1 mRNA expression in clear cell renal cell carcinomas (ccRCCs)
	TSGA10 could bind EPAS1

cell & other

REGULATION

activated by	hypoxia
	KLHL20, that increases EPAS1 activity through a VHL-independent pathway

induced by

IL-1beta at the transcriptional level

Other	regulated via SUMOylation, reducing its transcriptional activity
	regulated by VHL (regulate HIF-alpha proteolysis by acting as the recognition component of a ubiquitin ligase complex)
	VHL and RNF4 control the levels of sumoylated EPAS1

ASSOCIATED DISORDERS

corresponding disease(s)

ECYT4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in renal cell carcinoma

Susceptibility

to the endurance phenotype in elite endurance athletes to the development of retinopathy of prematurity (ROP)

Variant & Polymorphism SNP	influencing the relative contribution of aerobic and anaerobic metabolism and hence the maximum sustainable metabolic power for a given event duration
	association between SNPs in the EPAS1 gene and the development of ROP

Candidate gene
Marker
Therapy target	new and promising therapeutic target for cartilage repair
	System Type Disorder Pubmed osteoarticular     new and promising therapeutic target for cartilage repair

ANIMAL & CELL MODELS