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FLASH GENE

Symbol

ERCC5

contributors: mct - updated : 09-09-2016

HGNC name	excision repair cross-complementing rodent repair deficiency, complementation group 5
HGNC id	3437

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	COFS3 cerebro-oculo-facio-skeletal syndrome 3 XPG xeroderma pigmentosum, complementation group G
Location	13q33.1      Physical location : 103.498.173 - 103.528.347
Synonym name	excision repair cross-complementing rodent repair defect in CHO cells
	DNA-repair protein complementing XP-G cells
	XPG-complementing protein
Synonym symbol(s)	ERCM2, XPGC, COFS3, XPG

DNA

TYPE	functioning gene
STRUCTURE	30.16 kb     15 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type

text	multiple splice sites with low information content

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000123 15 - 4091 NP_000114 133 1186 - 2001 11266544 also called ERCC5-I cryptic exon in intron 1 variant 2 - - - isoform 2 - - - 2001 11266544 also called ERCC5-II intron 3 retention variant 3 - - - isoform 3 - - - 2001 11266544 also called ERCC5-III cryptic exon in intron 6 variant 4 - - - isoform 4 - - - 2001 11266544 also called ERCC5-IV 5' end of exon 8, cryptic acceptor potential exon skipping variant 5 - - - isoform 5 - - - 2001 11266544 also called ERCC5-V cryptic donor partial retention of intron 8 variant 6 - - - isoform 6 - - - 2001 11266544 also called ERCC5-VI intron 9 retention

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 heart         Homo sapiens Digestive mouth tongue       Homo sapiens Endocrine adrenal gland         Homo sapiens   thyroid         Homo sapiens Reproductive female system breast       Homo sapiens Urinary kidney         Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	XPG N terminal domain
	helix-hairpin-helix class 2 motifs
	C-terminal region interacts with WRN and also interacts with TFIIH to activate transcription

HOMOLOGY

interspecies

homolog to yeast RAD2

Homologene

FAMILY	XPG/RAD2 endonuclease family
	XPG subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome
text	predominantly nuclear

basic FUNCTION	endonuclease,making a excision 5'- 3' on a single strand of DNA (nucleotide excision repair)
	required non enzymatically for subsequent 5' incision by the XPF/ERCC1 heterodimer
	involved in transcription-coupled repair (TCR) of oxidative DNA lesions
	ERCC5 and EXO1 may have an analogous disorder-to-order transition promoted by ssDNA or a partner
	FEN1, EXO1, ERCC5, and GEN1 are junction specific enzymes that require three separate binding sites for DNA and that incise one base pair into the duplex region of the substrate
	novel function in S phase that is, at least in part, performed coordinately with WRN, and which may contribute to the severity of the phenotypes that occur upon loss of ERCC5
	NER factors ERCC5 and ERCC4 are essential for establishing CTCF-dependent chromatin looping between the promoter and terminator of the activated RARB2 gene
	ERCC5 endonuclease promotes DNA breaks and DNA demethylation at promoters allowing the recruitment of CTCF and gene looping, which is further stabilized by ERCC4
	is a structure-specific endonuclease required for nucleotide excision repair
	is an homologous recombination (HRR) protein with important roles in genome stability, suggesting how ERCC5 defects produce severe clinical consequences including cancer and accelerated aging

CELLULAR PROCESS

nucleotide, repair, nucleotide excision repair

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	component of a complex with RNA POL1, TFII alpha, ERCC6
	EXO1, ERCC5, and GEN1, whose activities span multiple DNA repair pathways, are members of the 5 prime nuclease superfamily with FEN1

INTERACTION

DNA	single stranded DNA binding

RNA

small molecule

protein	interacts directly with WRN, which is defective in the premature aging disorder Werner syndrome, and the two proteins undergo similar subnuclear redistribution in S phase and colocalize in nuclear foci
	interacts directly and functionally with the WRN helicase (stimulates the helicase activity of WRN, and XPG and WRN work cooperatively to anneal two DNA single strands)
	ERCC4, ERCC5 are essential for establishing CTCF-dependent chromatin looping between the promoter and terminator of the activated RARB2 gene
	is a partner of BRCA1 and BRCA2 in maintaining genomic stability through homologous recombination (HRR)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

XPG , COFS3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in metastatic prostate carcinoma tumoral     --low   in sqamous cell carcinoma of the head and neck tumoral somatic mutation       frameshift mutation in gastric carcinomas with microsatellite instability constitutional     --low   causes DNA double-strand breaks, chromosomal abnormalities, cell-cycle delays, defective HRR, inability to overcome replication fork stalling, and replication stress (pMID: 26833090)

Susceptibility

to cervical carcinoma to melanoma

Variant & Polymorphism SNP	His1104Asp or His1104His genotypes associated with increased risk of cervical carcinoma
	XPG Asp1104His polymorphism was a risk factor for melanoma susceptibility

Candidate gene
Marker	biomarker of ovarian cancer prognosis
	EIF4B, DAXX and ERCC5 are identified as novel prognostic markers for poor survival in diffuse large B-cell lymphoma (DLBCL)
Therapy target
	System Type Disorder Pubmed cancer reproductive ovary potential therapeutic target of ovarian cancer response to platinum chemotherapy

ANIMAL & CELL MODELS