ID:ERCC6_HUMAN DESCRIPTION: RecName: Full=DNA excision repair protein ERCC-6; EC=3.6.4.-; AltName: Full=ATP-dependent helicase ERCC6; AltName: Full=Cockayne syndrome protein CSB; FUNCTION: Essential factor involved in transcription-coupled nucleotide excision repair which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Upon DNA-binding, it locally modifies DNA conformation by wrapping the DNA around itself, thereby modifying the interface between stalled RNA polymerase II and DNA. It is required for transcription-coupled repair complex formation. It recruits the CSA complex (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to the at sites of RNA polymerase II- blocking lesions. SUBUNIT: Homodimer. Binds DNA. Interacts with ERCC8. Interacts with a subunit of RNA polymerase II TFIIH. Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21. Interacts with KIAA1530/UVSSA. INTERACTION: Q13216-1:ERCC8; NbExp=2; IntAct=EBI-295284, EBI-596556; SUBCELLULAR LOCATION: Nucleus. DOMAIN: A C-terminal ubiquitin-binding domain (UBD) is essential for transcription-coupled nucleotide excision repair to proceed. PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. PTM: Ubiquitinated at the C-terminus. Ubiquitination by the CSA complex leads to ERCC6 proteasomal degradation in a UV-dependent manner. Stabilized following interaction with KIAA1530/UVSSA, which promotes recruitment of deubiquitinating enzyme USP7, leading to deubiquitination of ERCC6 thereby preventing UV-induced degradation of ERCC6 by the proteasome. DISEASE: Defects in ERCC6 are the cause of Cockayne syndrome type B (CSB) [MIM:133540]. Cockayne syndrome is a rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer. DISEASE: Defects in ERCC6 are the cause of cerebro-oculo-facio- skeletal syndrome type 1 (COFS1) [MIM:214150]; also known as COFS syndrome or Pena-Shokeir syndrome type 2. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur. DISEASE: Defects in ERCC6 are a cause of De Sanctis-Cacchione syndrome (DSC) [MIM:278800]; also known as xerodermic idiocy. DSC is an autosomal recessive syndrome consisting of xeroderma pigmentosum associated with mental retardation, retarded growth, gonadal hypoplasia and sometimes neurologic complications. DISEASE: Defects in ERCC6 are the cause of susceptibility to age- related macular degeneration type 5 (ARMD5) [MIM:613761]. A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. DISEASE: Defects in ERCC6 are a cause of UV-sensitive syndrome type 1 (UVSS1) [MIM:600630]. A rare autosomal recessive disorder characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors. Patient exhibit a number of freckles, hypopigmented spots, telangiectases, and slightly dried skin in sun-exposed areas. SIMILARITY: Belongs to the SNF2/RAD54 helicase family. SIMILARITY: Contains 1 helicase ATP-binding domain. SIMILARITY: Contains 1 helicase C-terminal domain. WEB RESOURCE: Name=Allelic variations of the XP genes; URL="http://www.xpmutations.org/"; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CSBID302.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ERCC6"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ercc6/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q03468
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
L04791 - Human excision repair protein ERCC6 mRNA, complete cds. BC127104 - Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 6, mRNA (cDNA clone MGC:150685 IMAGE:40124639), complete cds. BC028954 - Homo sapiens piggyBac transposable element derived 3, mRNA (cDNA clone MGC:30025 IMAGE:4479639), complete cds. BC063690 - Homo sapiens piggyBac transposable element derived 3, mRNA (cDNA clone MGC:70395 IMAGE:4450811), complete cds. BC034479 - Homo sapiens piggyBac transposable element derived 3, mRNA (cDNA clone MGC:26346 IMAGE:4822982), complete cds. AK074682 - Homo sapiens cDNA FLJ90201 fis, clone MAMMA1001623, weakly similar to Homo sapiens piggyBac transposable element derived 1 (PGBD1), mRNA. AK291018 - Homo sapiens cDNA FLJ77465 complete cds, highly similar to Homo sapiens piggyBac transposable element derived 3, mRNA. CR749388 - Homo sapiens mRNA; cDNA DKFZp781P1019 (from clone DKFZp781P1019). AK094670 - Homo sapiens cDNA FLJ37351 fis, clone BRAMY2021867. JD090084 - Sequence 71108 from Patent EP1572962. JD386326 - Sequence 367350 from Patent EP1572962. JD123276 - Sequence 104300 from Patent EP1572962. AB209504 - Homo sapiens mRNA for excision repair cross-complementing rodent repair deficiency, complementation group 6 variant protein. JD147934 - Sequence 128958 from Patent EP1572962. JD524928 - Sequence 505952 from Patent EP1572962. JD220149 - Sequence 201173 from Patent EP1572962. JD490391 - Sequence 471415 from Patent EP1572962. JD270043 - Sequence 251067 from Patent EP1572962. JD239319 - Sequence 220343 from Patent EP1572962. JD090314 - Sequence 71338 from Patent EP1572962. JD398354 - Sequence 379378 from Patent EP1572962. JD399617 - Sequence 380641 from Patent EP1572962. JD290388 - Sequence 271412 from Patent EP1572962. JD052672 - Sequence 33696 from Patent EP1572962. JD097351 - Sequence 78375 from Patent EP1572962. JD082134 - Sequence 63158 from Patent EP1572962. JD224274 - Sequence 205298 from Patent EP1572962. JD345817 - Sequence 326841 from Patent EP1572962. JD166302 - Sequence 147326 from Patent EP1572962. JD109701 - Sequence 90725 from Patent EP1572962. JD078835 - Sequence 59859 from Patent EP1572962. JD343118 - Sequence 324142 from Patent EP1572962. JD321529 - Sequence 302553 from Patent EP1572962. JD234649 - Sequence 215673 from Patent EP1572962. JD491740 - Sequence 472764 from Patent EP1572962. AK130100 - Homo sapiens cDNA FLJ26590 fis, clone LNF07869, highly similar to Excision repair protein ERCC-6. JD410416 - Sequence 391440 from Patent EP1572962. AK303022 - Homo sapiens cDNA FLJ57242 complete cds, highly similar to DNA excision repair protein ERCC-6 (EC 3.6.1.-). JD062606 - Sequence 43630 from Patent EP1572962. JD339493 - Sequence 320517 from Patent EP1572962. JD241568 - Sequence 222592 from Patent EP1572962. JD160496 - Sequence 141520 from Patent EP1572962. JD165066 - Sequence 146090 from Patent EP1572962. JD434495 - Sequence 415519 from Patent EP1572962. JD450051 - Sequence 431075 from Patent EP1572962. JD034257 - Sequence 15281 from Patent EP1572962. JD024908 - Sequence 5932 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q03468 (Reactome details) participates in the following event(s):
R-NUL-573385 Recruitment of CSB, G9a, and NuRD to the rRNA promoter R-HSA-6781840 ERCC6 binds stalled RNA Pol II R-HSA-427404 Recruitment of ERCC6 (CSB), EHMT2 (G9a), and NuRD to the promoter of rRNA gene R-HSA-5250947 B-WICH complex binds rDNA promoter R-HSA-6781833 ERCC8 (CSA) binds stalled RNA Pol II R-HSA-6782211 DNA polymerases delta, epsilon or kappa bind the TC-NER site R-HSA-6782204 5' incision of damaged DNA strand by ERCC1:ERCC4 in TC-NER R-HSA-6782224 3' incision by ERCC5 (XPG) in TC-NER R-HSA-6782227 Ligation of newly synthesized repair patch to incised DNA in TC-NER R-HSA-6782208 Repair DNA synthesis of ~27-30 bases long patch by POLD, POLE or POLK in TC-NER R-NUL-573373 Ttf-I:rRNA Promoter:Ercc6:Ehmt2 complex dimethylates histone H3 at lysine-9 R-HSA-6781867 ERCC8:DDB1:CUL4:RBX1 ubiquitinates ERCC6 and RNA Pol II R-HSA-427336 TTF1:rRNA promoter:ERCC6:EHMT2 complex dimethylates histone H3 at lysine-9. R-HSA-5250930 B-WICH recruits histone acetyltransferases R-HSA-6782131 RNA Pol II backtracking in TC-NER R-HSA-6782069 UVSSA:USP7 deubiquitinates ERCC6 R-HSA-6782138 ERCC5 and RPA bind TC-NER site R-HSA-6782004 Assembly of the pre-incision complex in TC-NER R-HSA-6782141 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER R-HSA-5250938 B-WICH:histone acetyltransferase acetylates histone H3 at lysine-9 R-HSA-6781823 Formation of TC-NER Pre-Incision Complex R-HSA-427389 ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression R-HSA-5250924 B-WICH complex positively regulates rRNA expression R-HSA-6782135 Dual incision in TC-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-5250913 Positive epigenetic regulation of rRNA expression R-HSA-5696398 Nucleotide Excision Repair R-HSA-212165 Epigenetic regulation of gene expression R-HSA-73894 DNA Repair R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
