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FLASH GENE

Symbol

ERG

contributors: mct/npt/pgu - updated : 09-04-2016

HGNC name	v-ets erythroblastosis virus E26 oncogene homolog (avian)
HGNC id	3446

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	294.52 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site   transcription factor
text structure	several potential transcription factor binding sites but there were no Bright or Cart-1 sites

MAPPING

cloned

Y

linked

N

status

confirmed

Map	see AML1 , ETS2

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_182918 10 - 4945 NP_891548 - 479 - 2009 19156837 NM_004449 11 - 5042 NP_004440 - 462 - 2009 19156837 NM_001136154 12 - 5114 NM_001136154 54.5 486 - 2009 19156837 NM_001136155 9 - 4727 NP_001129627 44 387 - 2009 19156837 NM_001243432 12 - 1520 NP_001230361 - 317 - 2009 19156837 NM_001243428 12 - 5139 NP_001230357 - 486 - 2009 19156837 NM_001243429 9 - 4703 NP_001230358 - 363 - 2009 19156837

EXPRESSION

Type	ubiquitous

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 vessel       highly Homo sapiens Endocrine parathyroid       highly Lymphoid/Immune spleen       highly Reproductive male system testis       Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Muscular smooth vessel   highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

perinatal

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

ETS DNA-binding and helix-loop-helix (HLH) domains

HOMOLOGY

intraspecies

homolog to avian erythroblastosis virus E26 (v-ets) oncogene

Homologene

FAMILY

Ets family of transcription factors

CATEGORY

transcription factor , protooncogene

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm
	intracellular,nucleus
text	its protein expression is predominantly found in prostate carcinomas with ERG gene rearrangement and does not occur in benign glands

basic FUNCTION	transcription regulator, through SETDB1-mediated histone methylation
	required for endothelial tube formation
	involved in a new pathway regulating angiogenesis and endothelial survival, via the adhesion molecule VE-cadherin
	is at the center of a distinct regulatory program that is not required for hematopoietic specification or differentiation but is critical for hematopoietic stem cell maintenance during embryonic development
	Ets-transcription factor required for normal blood stem cell development
	promotes T-ALL (T-acute lymphoblastic leukemia) and failure to extinguish activity of stem cell enhancers associated with regulatory transcription factors such as ERG can contribute to the development of leukemia
	plays a pivotal role in regulating endothelial cells (EC) barrier function and this effect is mediated in part through its regulation of CLDN5 gene expression
	role for ERG as a gatekeeper controlling vascular inflammation, thus providing an important barrier to protect against inappropriate endothelial activation
	in primary leukemic cells, ERG may contribute to the dysregulation of kinase signaling, which results in resistance to kinase inhibitors
	is critically important for maintenance of the hematopoietic stem cell population

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	SETDB1
	WNT11 is a direct target of ERG (potent ERG induction promoted morphological transformation through WNT11 signals
	from the fetal period, ERG acts as a direct upstream regulator of GATA2 and RUNX1 gene activity
	CLDN5 is a downstream target of ERG in EC
	TDRD1 is the first identified upregulated direct ERG target gene that is strongly associated with ERG overexpression in primary prostate cancer
	ERG redirects AR to a set of genes including SOX9 that are not normally androgen stimulated, and SOX9 is a critical downstream effector of ERG in TMPRSS2:ERG fusion-positive prostate cancer (PCa)
	LEF1 is a direct target of ERG and LEF1 inhibition fully abolished ERG-induced WNT signaling and target gene expression
	SPOP functions as a tumor suppressor to negatively regulate the stability of the ERG oncoprotein in prostate cancer
	ERG is recruited to mRNAs via interaction with RBPMS, and it promotes mRNA decay by binding CNOT2, a component of the CCR4-NOT deadenylation complex
	role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion translocation     Loss of PTEN and concomitant activation of AKTcould act in partnership with the TMPRSS2-ERG fusion protein to promote progression to prostatecancer tumoral     --over   overexpression in prostate tumor cells may contribute to the neoplastic process by activating MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers tumoral fusion       NDRG1-ERG fusion in prostate carcinoma is predicted to encode a chimeric protein tumoral fusion       TMPRSS2:ERG gene fusion predicts subsequent detection of prostate cancer in patients with high-grade prostatic intraepithelial neoplasia (P tumoral     --over   may deregulate several signaling cascades in acute leukemia tumoral fusion       TMPRSS2-ERG gene fusions were observed in 44p 100 of prostate cancer, and over 90p100 of these fusions occurred in ERG exons 3 or 4

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS