Human Gene ERCC8 (uc003jsm.3) Description and Page Index
Description: Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 8 (ERCC8), mRNA. RefSeq Summary (NM_000082): This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]. Transcript (Including UTRs) Position: hg19 chr5:60,169,659-60,240,905 Size: 71,247 Total Exon Count: 12 Strand: - Coding Region Position: hg19 chr5:60,170,442-60,240,835 Size: 70,394 Coding Exon Count: 12
ID:ERCC8_HUMAN DESCRIPTION: RecName: Full=DNA excision repair protein ERCC-8; AltName: Full=Cockayne syndrome WD repeat protein CSA; FUNCTION: Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair. The CSA complex (DCX(ERCC8) complex) promotes the ubiquitination and subsequent proteasomal degradation of ERCC6 in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair. It is required for the recruitment of XAB2, HMGN1 and TCEA1/TFIIS to a transcription- coupled repair complex which removes RNA polymerase II-blocking lesions from the transcribed strand of active genes. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Interacts with ERCC6 and KIAA1530/UVSSA. Interacts with a subunit of RNA polymerase II TFIIH. Interacts with DDB1. INTERACTION: Q03468:ERCC6; NbExp=2; IntAct=EBI-596556, EBI-295284; Q9HCS7:XAB2; NbExp=3; IntAct=EBI-295260, EBI-295232; SUBCELLULAR LOCATION: Nucleus (Probable). DISEASE: Defects in ERCC8 are the cause of Cockayne syndrome type A (CSA) [MIM:216400]. 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 ERCC8 are the cause of UV-sensitive syndrome type 2 (UVSS2) [MIM:614621]. An autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors. SIMILARITY: Contains 5 WD repeats. 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/CSAID301.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ERCC8"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ckn1/"; WEB RESOURCE: Name=Mendelian genes excision repair cross- complementing rodent repair deficiency, complementation group 8 (ERCC8); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/ERCC8";
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): ERCC8 CDC HuGE Published Literature: ERCC8
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 Q13216
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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.