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FLASH GENE
Symbol ERCC6 contributors: mct/npt/pgu - updated : 31-08-2015
HGNC name excision repair cross-complementing rodent repair deficiency, complementation group 6
HGNC id 3438
Corresponding disease
COFS1 cerebro-oculo-facio-skeletal syndrome 1
CSB Cockayne syndrome, type B
UVS UV-sensitive syndrome
XPV2 xeroderma pigmentosum variant
Location 10q11.23      Physical location : 50.664.491 - 50.747.147
Synonym name
  • Cockayne syndrome protein CSB
  • ATP-dependent helicase ERCC6
  • DNA excision repair protein ERCC-6
  • Rad26 (yeast) homolog
  • Synonym symbol(s) CSB, RAD26, CKN2, COFS, COFS1, ARMD5, UVSS1
    EC.number 3.6.1.-
    DNA
    TYPE functioning gene
    STRUCTURE 84.64 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC387669 10 LOC387669 LOC387670 10 hypothetical gene supported by NM_133446 ZNF488 10q11.22 zinc finger protein 488 RBP3 10q11.2 retinol binding protein 3, interstitial GDF2 10q11.22 growth differentiation factor 2 GDF10 10q21.1 growth differentiation factor 10 DKFZP566K0524 10q11.22 DKFZP566K0524 protein LOC387671 10 similar to ARF GTPase-activating protein LOC387672 10 similar to Ribosome biogenesis protein BMS1 homolog LOC387673 10 similar to Glutamate dehydrogenase, mitochondrial precursor (GDH) LOC338598 10q11.22 similar to hypothetical protein MGC5560 LOC118706 10q11.22 similar to ARF GTPase-activating protein LOC387674 10 similar to Ribosome biogenesis protein BMS1 homolog MGC35285 10q11.22 hypothetical protein MGC35285 MAPK8 10q11.2 mitogen-activated protein kinase 8 RhoGAP2 LOC387675 10 LOC387675 LOC159491 LOC389964 10 similar to ribosomal protein L13a; 60S ribosomal protein L13a; 23 kD highly basic protein KIAA1607 FLJ31737 LOC170370 10q11.23 hypothetical LOC170370 LOC170371 10q11.23 hypothetical protein LOC170371 LOC118461 DRG11 ERCC6 10q11 excision repair cross-complementing rodent repair deficiency, complementation group 6 PGBD3 10q11 piggyBac transposable element derived 3 CHAT 10q11.2 choline acetyltransferase SLC18A3 10q11.2 solute carrier family 18 (vesicular acetylcholine), member 3 LOC282966 10q11.23 hypothetical protein LOC282966 FLJ10851 10q11.23 hypothetical protein FLJ10851 MAPK6PS6 10q11.21 hypothetical protein FLJ10851 PARG 10q11.23 poly (ADP-ribose) glycohydrolase LOC387676 10 similar to KIAA0592 protein LOC387677 10 hypothetical gene supported by BC051717; NM_133446 LOC255319 10q11.23 similar to ARF GTPase-activating protein MSMB 10q11.2 microseminoprotein, beta- NCOA4 10q11.2 nuclear receptor coactivator 4 TIMM23 10q11.21-q11.23 translocase of inner mitochondrial membrane 23 homolog (yeast) LOC387678 10 similar to ARF GTPase-activating protein LOC389965 10 similar to Sodium/hydrogen exchanger 3 (Na(+)/H(+) exchanger 3) (NHE-3) LOC387679 10 similar to KIAA0592 protein LOC387680 10 similar to KIAA0592 protein LOC389966 10 similar to Sodium/hydrogen exchanger 3 (Na(+)/H(+) exchanger 3) (NHE-3) ASAH2 10q11.21 N-acylsphingosine amidohydrolase (non-lysosomal ceramidase) 2 LOC387681 10 hypothetical gene supported by BT007130; NM_001378 MOB 10q11.2 mob protein LOC340858 10q21.1 similar to hypothetical protein FLJ10539 FLJ31958 10q21.1 hypothetical protein FLJ31958 LOC389967 10 similar to bA182L21.1 (novel protein similar to hypothetical proteins) LOC389968 10 similar to Cathepsin L preproprotein LOC283023 10q21.1 similar to Geranylgeranyl transferase type I beta subunit (Type I protein geranyl-geranyltransferase beta subunit) (GGTase-I-beta) ACF 10q21,1 similar to Geranylgeranyl transferase type I beta subunit (Type I protein geranyl-geranyltransferase beta subunit) (GGTase-I-beta) PRKG1 10q11.2 protein kinase, cGMP-dependent, type I
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 8993 168 1493 - 1992 1339317
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     mouthtongue  highly
    Hearing/Equilibriumear   highly
    Reproductivemale systemtestis  highly
    Respiratorylung   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • SNF2 N-terminal domain
  • N-terminal region interacting with the SH3 domain of ABL1, with a conserved protein motif, termed the "leucine latch," at the N terminus
  • acidic domain and glycine-rich stretch
  • bipartite nuclear localization signal
  • helicase conserved C-terminal domain
  • mono polymer dimer
    HOMOLOGY
    interspecies homolog to yeast RAD26 (see CKN2)
    Homologene
    FAMILY
  • DEAD-like helicase superfamily
  • SNF2/RAD54 helicase family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • accumulates at sites of DNA double-strand breaks (DSBs) in a transcription-dependent manner
  • basic FUNCTION
  • playing an important roles in transcription, transcription-coupled nucleotide excision repair and base excision DNA repair
  • Swi/Snf-like RNA/DNA helicase homolog without active helicase activity
  • involved in transcription-coupled and global genome-DNA repair, as well as in general transcription
  • contributing to base excision repair (BER) of 8-hydroxyguanine (OGG1) through motifs V and VI of the putative helicase domains
  • playing a role in the transcriptionnal bypass of some oxidative DNA damage, and implicated in transcription-coupled repair, transcriptional elongation, and restoration of RNA synthesis after DNA damage
  • stimulates elongation of RNA Pol I in an ATP-independent manner
  • recruits nucleotide excision repair factors to the DNA damage site and plays an important role in the repair process
  • playing a general role in maintenance and remodeling of chromatin structure
  • positively cooperates in ATP hydrolysis as a function of protein concentration
  • playing a role in the repair of base excision repair substrates/intermediates, and a specific functional interaction with the predominant AP site repair enzyme, APEX1
  • playing a role in the processing of base excision repair specific DNA substrates, potentially in regions of the genome that take on complex structures
  • has novel strand annealing and exchange activities
  • having a possible role as a signaling molecule in response to oxidative damage (tyrosine-phosphorylated ERCC6 may serve as a signal for repair proteins to localize to DNA damage and may help maintain active transcription in the nucleolus)
  • fulfills a key role as a coupling factor to attract histone acetyltransferase p300, nucleotide excision repair (NER) proteins
  • plays a role in repair of formamidopyrimidines, possibly by interacting with and stimulating NEIL1, and accumulation of such modifications may have a causal role in the pathogenesis of CS
  • ERCC6, ERCC8 are the key elements of a regulatory mechanism that equilibrate beneficial and detrimental effects of TP53 activity upon cellular stress
  • is a multifunctional protein regulating both repair and the transcriptional response to reactive oxygen through its interaction with EP300 and the HIF1 pathway
  • likely modulates cell viability in pluripotent stem cells, regulating the expression of TP53 and TXNIP and ROS production
  • function for ERCC6 in neural precursors
  • role of ERCC6 and ERCC8 protein in the oxidative stress response
  • ERCC6, ERCC8, in addition to their established role in transcription-coupled nucleotide excision repair, can modulate the base excision repair (BER) of oxidized DNA bases both directly (by interaction with BER proteins) and indirectly (by modulating the expression of the DNA repair genes)
  • biological role for ERCC6 and NEIL2 in transcription associated base excision repair
  • has a crucial role in coordinated regulation of transcription and chromatin remodeling activities that are required during neurogenesis
  • appears to behave as an electron scavenger in the mitochondria whose absence leads to increased oxidative stress
  • plays crucial roles in gene expression and the maintenance of genome integrity
  • critical for transcription-coupled-Nucleotide excision repair
  • CELLULAR PROCESS nucleotide, repair, nucleotide excision repair
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of a complex with RNA pol1, TFIIH (GTF2H*) and XPG (ERCC5)
  • forms a dimer in solution, enzymatically active CSB has an apparent molecular mass of approximately 360 kDa, consistent with dimerization of CSB
  • INTERACTION
    DNA DNA binding domain
    RNA
    small molecule
    protein
  • ERCC3
  • regulating expression of OGG1
  • interacting with PARP1, BRCA1, BRCA2, and TCEB3
  • functional interaction of CSB with the predominant AP site repair enzyme, APEX1
  • interacting with ABL1 (may regulate each other in a reciprocal manner in response to oxidative stress)
  • protects CAG repeats from expansion by either active reduction of the tract length during parent-child transmission, or by antagonizing the action of OGG1, which tends to promote expansion in somatic cells
  • NR2C2 directly regulates ERCC6 at the transcriptional level
  • UVSSA forms a complex with USP7, stabilizes ERCC6 and restores the hypophosphorylated form of RNA polymerase II after UV irradiation
  • ERCC6, and NEIL2 were found to physically interact independently of DNA
  • coordinates the resolution of interstrand crosslink , possibly in a transcription-associated repair mechanism involving DCLRE1A, and defects in the process could contribute to the post-mitotic degenerative pathologies associated with Cockayne syndrome
  • DGCR8 physically interacted with ERCC6 and RNA polymerase II
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CSB , XPV2 , COFS1 , UVS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in sqamous cell carcinoma of the head and neck
    Susceptibility
  • to macular degeneration
  • to smoking-related lung cancer
  • Variant & Polymorphism SNP increasing the risk of macular degeneration (in association with CFH SNPs)
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS