InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ERCC8

Summary

InnateDB Protein

IDBP-22961.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ERCC8

Protein Name

excision repair cross-complementing rodent repair deficiency, complementation group 8

Synonyms

CKN1; CSA; UVSS2;

Species

Homo sapiens

Ensembl Protein

ENSP00000265038

InnateDB Gene

IDBG-22959 (ERCC8)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:16751180, ECO:0000269PubMed:16916636, ECO:0000269PubMed:16964240}.

Subcellular Localization

Nucleus {ECO:0000305}.

Disease Associations

Cockayne syndrome A (CSA) [MIM:216400]: 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. {ECO:0000269PubMed:14661080, ECO:0000269PubMed:15744458, ECO:0000269PubMed:19894250}. Note=The disease is caused by mutations affecting the gene represented in this entry.UV-sensitive syndrome 2 (UVSS2) [MIM:614621]: An autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors. {ECO:0000269PubMed:19329487}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 43 experimentally validated interaction(s) in this database.
They are also associated with 10 interaction(s) predicted by orthology.

Experimentally validated
Total	43 [view]
Protein-Protein	42 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	10 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0032403	protein complex binding

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:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
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:0016363	nuclear matrix
GO:0031464	Cul4A-RING E3 ubiquitin ligase complex
GO:0043234	protein complex