InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ERCC6

Summary

InnateDB Protein

IDBP-73925.6

Last Modified

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

Gene Symbol

ERCC6

Protein Name

excision repair cross-complementing rodent repair deficiency, complementation group 6

Synonyms

ARMD5; CKN2; COFS; COFS1; CSB; RAD26; UVSS1;

Species

Homo sapiens

Ensembl Protein

ENSP00000348089

InnateDB Gene

IDBG-304121 (ERCC6)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:15548521, ECO:0000269PubMed:16916636, ECO:0000269PubMed:20541997}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:16128801}.

Disease Associations

Cockayne syndrome B (CSB) [MIM:133540]: 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:19894250, ECO:0000269PubMed:9443879}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cerebro-oculo-facio-skeletal syndrome 1 (COFS1) [MIM:214150]: A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome. {ECO:0000269PubMed:19894250}. Note=The disease is caused by mutations affecting the gene represented in this entry.De Sanctis-Cacchione syndrome (DSC) [MIM:278800]: An autosomal recessive syndrome consisting of xeroderma pigmentosum associated with severe neurological and developmental involvement. In addition to the clinical signs of xeroderma pigmentosum, patients present with mental retardation, dwarfism, gonadal hypoplasia, microcephaly and various neurologic complications of early onset. Note=The disease is caused by mutations affecting the gene represented in this entry.Macular degeneration, age-related, 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. {ECO:0000269PubMed:16754848}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.UV-sensitive syndrome 1 (UVSS1) [MIM:600630]: An autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors. {ECO:0000269PubMed:15486090}. 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 50 experimentally validated interaction(s) in this database.

Experimentally validated
Total	50 [view]
Protein-Protein	49 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0003676	nucleic acid binding
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003711	transcription elongation regulator activity
GO:0004386	helicase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008022	protein C-terminus binding
GO:0008094	DNA-dependent ATPase activity
GO:0016787	hydrolase activity
GO:0032403	protein complex binding
GO:0047485	protein N-terminus binding

Biological Process

GO:0000303	response to superoxide
GO:0006200	ATP catabolic process
GO:0006281	DNA repair
GO:0006283	transcription-coupled nucleotide-excision repair
GO:0006284	base-excision repair
GO:0006289	nucleotide-excision repair
GO:0006290	pyrimidine dimer repair
GO:0006350	transcription
GO:0006355	regulation of transcription, DNA-templated
GO:0006362	transcription elongation from RNA polymerase I promoter
GO:0006366	transcription from RNA polymerase II promoter
GO:0006974	cellular response to DNA damage stimulus
GO:0006979	response to oxidative stress
GO:0007256	activation of JNKK activity
GO:0007257	activation of JUN kinase activity
GO:0007605	sensory perception of sound
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009411	response to UV
GO:0009636	response to toxic substance
GO:0010165	response to X-ray
GO:0010224	response to UV-B
GO:0010332	response to gamma radiation
GO:0032784	regulation of DNA-templated transcription, elongation
GO:0032786	positive regulation of DNA-templated transcription, elongation
GO:0035264	multicellular organism growth
GO:0045494	photoreceptor cell maintenance

Cellular Component

GO:0005625	soluble fraction
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005730	nucleolus
GO:0008023	transcription elongation factor complex

Protein Structure and Domains

PDB ID

InterPro

IPR000330 SNF2-related
IPR001650 Helicase, C-terminal
IPR014001 Helicase, superfamily 1/2, ATP-binding domain
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00176
PF00271

PRINTS

PIRSF

SMART

SM00490
SM00487

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q03468