InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ERCC2

Summary

InnateDB Protein

IDBP-246664.6

Last Modified

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

Gene Symbol

ERCC2

Protein Name

excision repair cross-complementing rodent repair deficiency, complementation group 2

Synonyms

COFS2; EM9; TFIIH; TTD; XPD;

Species

Homo sapiens

Ensembl Protein

ENSP00000375809

InnateDB Gene

IDBG-57385 (ERCC2)

Protein Structure

UniProt Annotation

Function

ATP-dependent 5'-3' DNA helicase, component of the core- TFIIH basal transcription factor. Involved in nucleotide excision repair (NER) of DNA by opening DNA around the damage, and in RNA transcription by RNA polymerase II by anchoring the CDK-activating kinase (CAK) complex, composed of CDK7, cyclin H and MAT1, to the core-TFIIH complex. Involved in the regulation of vitamin-D receptor activity. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation. Might have a role in aging process and could play a causative role in the generation of skin cancers. {ECO:0000269PubMed:10024882, ECO:0000269PubMed:15494306, ECO:0000269PubMed:20797633, ECO:0000269PubMed:8413672}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:20797633}. Cytoplasm, cytoskeleton, spindle {ECO:0000269PubMed:20797633}.

Disease Associations

Xeroderma pigmentosum complementation group D (XP-D) [MIM:278730]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Some XP-D patients present features of Cockayne syndrome, including cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex. {ECO:0000269PubMed:11709541, ECO:0000269PubMed:7585650, ECO:0000269PubMed:7825573, ECO:0000269PubMed:7849702, ECO:0000269PubMed:9101292}. Note=The disease is caused by mutations affecting the gene represented in this entry.Trichothiodystrophy photosensitive (TTDP) [MIM:601675]: TTDP is an autosomal recessive disease characterized by sulfur- deficient brittle hair and nails, ichthyosis, mental retardation, impaired sexual development, abnormal facies and cutaneous photosensitivity correlated with a nucleotide excision repair (NER) defect. Neonates with trichothiodystrophy and ichthyosis are usually born with a collodion membrane. The severity of the ichthyosis after the membrane is shed is variable, ranging from a mild to severe lamellar ichthyotic phenotype. There are no reports of skin cancer associated with TTDP. {ECO:0000269PubMed:11242112, ECO:0000269PubMed:7920640, ECO:0000269PubMed:8571952, ECO:0000269PubMed:9195225, ECO:0000269PubMed:9238033, ECO:0000269PubMed:9758621}. Note=The disease is caused by mutations affecting the gene represented in this entry.Cerebro-oculo-facio-skeletal syndrome 2 (COFS2) [MIM:610756]: 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:11443545}. 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.

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

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003676	nucleic acid binding
GO:0003677	DNA binding
GO:0004003	ATP-dependent DNA helicase activity
GO:0004672	protein kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008022	protein C-terminus binding
GO:0008026	ATP-dependent helicase activity
GO:0008094	DNA-dependent ATPase activity
GO:0008353	RNA polymerase II carboxy-terminal domain kinase activity
GO:0016818	hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
GO:0043139	5'-3' DNA helicase activity
GO:0046872	metal ion binding
GO:0047485	protein N-terminus binding
GO:0051539	4 iron, 4 sulfur cluster binding

Biological Process

GO:0000718	nucleotide-excision repair, DNA damage removal
GO:0001666	response to hypoxia
GO:0001701	in utero embryonic development
GO:0006139	nucleobase-containing compound metabolic process
GO:0006200	ATP catabolic process
GO:0006281	DNA repair
GO:0006283	transcription-coupled nucleotide-excision repair
GO:0006289	nucleotide-excision repair
GO:0006360	transcription from RNA polymerase I promoter
GO:0006361	transcription initiation from RNA polymerase I promoter
GO:0006362	transcription elongation from RNA polymerase I promoter
GO:0006363	termination of RNA polymerase I transcription
GO:0006366	transcription from RNA polymerase II promoter
GO:0006367	transcription initiation from RNA polymerase II promoter
GO:0006368	transcription elongation from RNA polymerase II promoter
GO:0006370	7-methylguanosine mRNA capping
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0006979	response to oxidative stress
GO:0007059	chromosome segregation
GO:0007568	aging
GO:0008283	cell proliferation
GO:0009411	response to UV
GO:0009650	UV protection
GO:0009791	post-embryonic development
GO:0010467	gene expression
GO:0016032	viral process
GO:0021510	spinal cord development
GO:0022405	hair cycle process
GO:0030198	extracellular matrix organization
GO:0030282	bone mineralization
GO:0032289	central nervous system myelin formation
GO:0032508	DNA duplex unwinding
GO:0033683	nucleotide-excision repair, DNA incision
GO:0035264	multicellular organism growth
GO:0035315	hair cell differentiation
GO:0040016	embryonic cleavage
GO:0043249	erythrocyte maturation
GO:0043388	positive regulation of DNA binding
GO:0043588	skin development
GO:0044281	small molecule metabolic process
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048820	hair follicle maturation
GO:0050434	positive regulation of viral transcription
GO:0060218	hematopoietic stem cell differentiation
GO:1901990	regulation of mitotic cell cycle phase transition

Cellular Component

GO:0000439	core TFIIH complex
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005675	holo TFIIH complex
GO:0005737	cytoplasm
GO:0005819	spindle
GO:0019907	cyclin-dependent protein kinase activating kinase holoenzyme complex
GO:0071817	MMXD complex

Protein Structure and Domains

PDB ID

InterPro

IPR001945 Xeroderma pigmentosum group D protein
IPR006554 Helicase-like, DEXD box c2 type
IPR006555 ATP-dependent helicase, C-terminal
IPR010614 DEAD2
IPR010643 Domain of unknown function DUF1227
IPR013020 DNA helicase (DNA repair), Rad3 type
IPR014013 Helicase, superfamily 1/2, ATP-binding domain, DinG/Rad3-type
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF13307
PF06733
PF06777

PRINTS

PR00852

PIRSF

SMART

SM00488
SM00491

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt