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 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:60,169,659-60,240,905)mRNA (may differ from genome)Protein (396 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
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H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  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

-  MalaCards Disease Associations
  MalaCards Gene Search: ERCC8
Diseases sorted by gene-association score: uv-sensitive syndrome 2* (1229), cockayne syndrome, type a* (1220), cockayne syndrome type i* (750), ercc8-related cockayne syndrome* (500), cockayne syndrome type iii* (350), cockayne syndrome type ii* (247), uv-sensitive syndrome* (229), cockayne syndrome* (106), cockayne syndrome, type b (13), xeroderma pigmentosum, group c (9), xeroderma pigmentosum, variant type (3)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 3.07 RPKM in Testis
Total median expression: 73.84 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -24.4070-0.349 Picture PostScript Text
3' UTR -185.55783-0.237 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR020472 - G-protein_beta_WD-40_rep
IPR015943 - WD40/YVTN_repeat-like_dom
IPR001680 - WD40_repeat
IPR019775 - WD40_repeat_CS
IPR017986 - WD40_repeat_dom

Pfam Domains:
PF00400 - WD domain, G-beta repeat

SCOP Domains:
50952 - Soluble quinoprotein glucose dehydrogenase
50960 - TolB, C-terminal domain
63825 - YWTD domain
63829 - Calcium-dependent phosphotriesterase
69304 - Tricorn protease N-terminal domain
101898 - NHL repeat
50965 - Galactose oxidase, central domain
75011 - 3-carboxy-cis,cis-mucoante lactonizing enzyme
101908 - Putative isomerase YbhE
50969 - YVTN repeat-like/Quinoprotein amine dehydrogenase
50974 - Nitrous oxide reductase, N-terminal domain
50978 - WD40 repeat-like
50993 - Prolyl oligopeptidase, N-terminal domain
69322 - Tricorn protease domain 2
50998 - Quinoprotein alcohol dehydrogenase-like
51004 - C-terminal (heme d1) domain of cytochrome cd1-nitrite reductase
82171 - Dipeptidyl peptidase IV/CD26, N-terminal domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

4A11
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q13216
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0044877 macromolecular complex binding
GO:0004842 ubiquitin-protein transferase activity
GO:0003678 DNA helicase activity
GO:0008094 DNA-dependent ATPase activity

Biological Process:
GO:0000209 protein polyubiquitination
GO:0006281 DNA repair
GO:0006283 transcription-coupled nucleotide-excision repair
GO:0006289 nucleotide-excision repair
GO:0006974 cellular response to DNA damage stimulus
GO:0006979 response to oxidative stress
GO:0009411 response to UV
GO:0010165 response to X-ray
GO:0010996 response to auditory stimulus
GO:0014070 response to organic cyclic compound
GO:0016567 protein ubiquitination
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043687 post-translational protein modification
GO:0045739 positive regulation of DNA repair
GO:0051865 protein autoubiquitination

Cellular Component:
GO:0000109 nucleotide-excision repair complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0016363 nuclear matrix
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
GO:0032991 macromolecular complex
GO:0043204 perikaryon
GO:0080008 Cul4-RING E3 ubiquitin ligase complex


-  Descriptions from all associated GenBank mRNAs
  AK056931 - Homo sapiens cDNA FLJ32369 fis, clone PUAEN1000276, highly similar to DNA excision repair protein ERCC-8.
U28413 - Human Cockayne syndrome complementation group A CSA protein (CSA) mRNA, complete cds.
AK226129 - Homo sapiens mRNA for excision repair cross-complementing rodent repair deficiency, complementation group 8 isoform 2 variant, clone: fk00939.
JD086548 - Sequence 67572 from Patent EP1572962.
JD226232 - Sequence 207256 from Patent EP1572962.
JD434129 - Sequence 415153 from Patent EP1572962.
JD547995 - Sequence 529019 from Patent EP1572962.
JD297406 - Sequence 278430 from Patent EP1572962.
AK294856 - Homo sapiens cDNA FLJ52883 complete cds, highly similar to DNA excision repair protein ERCC-8.
JD153778 - Sequence 134802 from Patent EP1572962.
JD091793 - Sequence 72817 from Patent EP1572962.
JD345015 - Sequence 326039 from Patent EP1572962.
AK304610 - Homo sapiens cDNA FLJ56290 complete cds, highly similar to DNA excision repair protein ERCC-8.
JD536287 - Sequence 517311 from Patent EP1572962.
AK290726 - Homo sapiens cDNA FLJ78558 complete cds, highly similar to Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 8 (ERCC8), transcript variant 1, mRNA.
JD049048 - Sequence 30072 from Patent EP1572962.
JD205489 - Sequence 186513 from Patent EP1572962.
CR536563 - Homo sapiens full open reading frame cDNA clone RZPDo834A1022D for gene CKN1, Cockayne syndrome 1 (classical); complete cds, incl. stopcodon.
AK314511 - Homo sapiens cDNA, FLJ95329, Homo sapiens Cockayne syndrome 1 (classical) (CKN1), mRNA.
BT020021 - Homo sapiens Cockayne syndrome 1 (classical) mRNA, complete cds.
AB527753 - Synthetic construct DNA, clone: pF1KB7958, Homo sapiens ERCC8 gene for excision repair cross-complementing rodent repair deficiency, complementation group 8, without stop codon, in Flexi system.
BC009793 - Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 8, mRNA (cDNA clone MGC:13580 IMAGE:3683434), complete cds.
KJ901341 - Synthetic construct Homo sapiens clone ccsbBroadEn_10735 ERCC8 gene, encodes complete protein.
KR710326 - Synthetic construct Homo sapiens clone CCSBHm_00011495 ERCC8 (ERCC8) mRNA, encodes complete protein.
KR710327 - Synthetic construct Homo sapiens clone CCSBHm_00011496 ERCC8 (ERCC8) mRNA, encodes complete protein.
KU177979 - Homo sapiens excision repair cross-complementing rodent repair deficiency complementation group 8 isoform 1 (ERCC8) mRNA, partial cds, alternatively spliced.
KU177980 - Homo sapiens excision repair cross-complementing rodent repair deficiency complementation group 8 isoform 3 (ERCC8) mRNA, complete cds, alternatively spliced.
JD104925 - Sequence 85949 from Patent EP1572962.
JD137831 - Sequence 118855 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03420 - Nucleotide excision repair
hsa04120 - Ubiquitin mediated proteolysis

Reactome (by CSHL, EBI, and GO)

Protein Q13216 (Reactome details) participates in the following event(s):

R-HSA-6781867 ERCC8:DDB1:CUL4:RBX1 ubiquitinates ERCC6 and RNA Pol II
R-HSA-6781833 ERCC8 (CSA) binds stalled RNA Pol II
R-HSA-6782004 Assembly of the pre-incision complex in TC-NER
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-HSA-8955245 CAND1 binds CRL4 E3 ubiquitin ligase in the nucleus
R-HSA-6782069 UVSSA:USP7 deubiquitinates ERCC6
R-HSA-6782131 RNA Pol II backtracking in TC-NER
R-HSA-6782138 ERCC5 and RPA bind TC-NER site
R-HSA-8955285 COMMDs displace CAND1 from CRL4 E3 ubiquitin ligase complex
R-HSA-8952639 NEDD8:AcM-UBE2M binds CRL4 E3 ubiquitin ligase complex
R-HSA-8956045 COP9 signalosome deneddylates nuclear CRL4 E3 ubiquitin ligase complex
R-HSA-8952638 AcM-UBE2M transfers NEDD8 to CRL4 E3 ubiquitin ligase complex
R-HSA-6782141 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex
R-HSA-6782135 Dual incision in TC-NER
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-5696398 Nucleotide Excision Repair
R-HSA-8951664 Neddylation
R-HSA-73894 DNA Repair
R-HSA-597592 Post-translational protein modification
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: B2RB64, CKN1, CSA, ERCC8_HUMAN, NM_000082, NP_000073, Q13216, Q6FHX5, Q96GB9
UCSC ID: uc003jsm.3
RefSeq Accession: NM_000082
Protein: Q13216 (aka ERCC8_HUMAN)
CCDS: CCDS3978.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ERCC8:
cockayne (Cockayne Syndrome)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000082.3
exon count: 12CDS single in 3' UTR: no RNA size: 2044
ORF size: 1191CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2494.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.