Description: Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 2 (ERCC2), transcript variant 1, mRNA. RefSeq Summary (NM_000400): The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]. Transcript (Including UTRs) Position: hg19 chr19:45,854,649-45,873,845 Size: 19,197 Total Exon Count: 23 Strand: - Coding Region Position: hg19 chr19:45,854,887-45,873,798 Size: 18,912 Coding Exon Count: 23
ID:ERCC2_HUMAN DESCRIPTION: RecName: Full=TFIIH basal transcription factor complex helicase XPD subunit; EC=3.6.4.12; AltName: Full=Basic transcription factor 2 80 kDa subunit; Short=BTF2 p80; AltName: Full=CXPD; AltName: Full=DNA excision repair protein ERCC-2; AltName: Full=DNA repair protein complementing XP-D cells; AltName: Full=TFIIH basal transcription factor complex 80 kDa subunit; Short=TFIIH 80 kDa subunit; Short=TFIIH p80; AltName: Full=Xeroderma pigmentosum group D-complementing protein; 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. CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. COFACTOR: Magnesium. COFACTOR: Binds 1 4Fe-4S cluster. SUBUNIT: One of the six subunits forming the core-TFIIH basal transcription factor which associates with the CAK complex composed of CDK7, CCNH/cyclin H and MNAT1 to form the TFIIH basal transcription factor. The interaction with GTF2H2 results in the stimulation of the 5'-->3' helicase activity. Component of the MMXD complex, which includes CIAO1, ERCC2, FAM96B, MMS19 and SLC25A5. Interacts with FAM196B; the interaction is direct. Interacts with ATF7IP. Interacts with Epstein-Barr virus EBNA2. SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton, spindle. PTM: ISGylated (Probable). DISEASE: Defects in ERCC2 are the cause of xeroderma pigmentosum complementation group D (XP-D) [MIM:278730]; also known as XP group D (XPD). Xeroderma pigmentosum is 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. Some XP-D patients present features of Cockayne syndrome, including dwarfism, sensorineural deafness, microcephaly, mental retardation, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. DISEASE: Defects in ERCC2 are a cause of 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. DISEASE: Defects in ERCC2 are the cause of cerebro-oculo-facio- skeletal syndrome type 2 (COFS2) [MIM:610756]. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur. SIMILARITY: Belongs to the helicase family. RAD3/XPD subfamily. SIMILARITY: Contains 1 helicase ATP-binding domain. SEQUENCE CAUTION: Sequence=AAM45142.1; Type=Erroneous gene model prediction; 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/XPDID297.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ERCC2"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/ercc2/";
benzene toxicity Huang, H. L. et al. 2006, Association between polymorphisms of XPD gene and susceptibility to chronic benzene poisoning., Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2006 24(7) 390-3.
[PubMed 16889696]
The subjects with XPD 751Gln variant allele are more susceptive to benzene.
brain cancer Yang, P. et al. 2005, Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas., Cancer. 2005 Jun;103(11):2363-72.
[PubMed 15834925]
These results suggested that alterations in GLTSCR1 (or a closely linked gene) were associated with the development and progression of oligodendroglioma.
Carcinoma, Hepatocellular|Hepatitis B|Hepatitis C|Liver Neoplasms Xi Dai Long , et al. BMC cancer 2010 9():400, XPD codon 312 and 751 polymorphisms, and AFB1 exposure, and hepatocellular carcinoma risk., BMC cancer 2010 9():400.
[PubMed 19919686]
XPD codon 751 polymorphism modifies the risk of hepatocellular carcinoma
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 P18074
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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.
X52222 - H.sapiens genomic sequence for ERCC2 gene 3'region involved in DNA excision repair. BC108255 - Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 2, mRNA (cDNA clone MGC:102762 IMAGE:6044425), complete cds. AK092872 - Homo sapiens cDNA FLJ35553 fis, clone SPLEN2004368, highly similar to DNA-REPAIR PROTEIN COMPLEMENTING XP-D CELLS. AX747782 - Sequence 1307 from Patent EP1308459. AK130849 - Homo sapiens cDNA FLJ27339 fis, clone TMS09615, highly similar to TFIIH basal transcription factor complex helicase subunit (EC 3.6.1.-). BC110522 - Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 2, mRNA (cDNA clone MGC:126218 IMAGE:40034047), complete cds. BC110523 - Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 2, mRNA (cDNA clone MGC:126219 IMAGE:40034048), complete cds. JD414249 - Sequence 395273 from Patent EP1572962. JD184021 - Sequence 165045 from Patent EP1572962. AB590942 - Synthetic construct DNA, clone: pFN21AE2086, Homo sapiens ERCC2 gene for excision repair cross-complementing rodent repair deficiency, complementation group 2, without stop codon, in Flexi system. X52221 - H.sapiens ERCC2 gene, exons 1 & 2 (partial). BC008346 - Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 2 (xeroderma pigmentosum D), mRNA (cDNA clone IMAGE:3531867). KJ905740 - Synthetic construct Homo sapiens clone ccsbBroadEn_15410 ERCC2 gene, encodes complete protein. BT006883 - Homo sapiens excision repair cross-complementing rodent repair deficiency, complementation group 2 (xeroderma pigmentosum D) mRNA, complete cds. AK303358 - Homo sapiens cDNA FLJ57462 complete cds, highly similar to TFIIH basal transcription factor complex helicase subunit (EC 3.6.1.-).
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa03420 - Nucleotide excision repair
Reactome (by CSHL, EBI, and GO)
Protein P18074 (Reactome details) participates in the following event(s):
R-HSA-73758 Recruitment of Active RNA Polymerase I to SL1:phos.UBF-1:rDNA Promoter R-HSA-109639 Formation of the closed pre-initiation complex R-HSA-112379 Recruitment of elongation factors to form elongation complex R-HSA-112383 Hypophosphorylation of RNA Pol II CTD by FCP1P protein R-HSA-167072 Hypophosphorylation of RNA Pol II CTD by FCP1P protein R-HSA-167077 Recruitment of elongation factors to form HIV-1 elongation complex R-HSA-167196 Recruitment of elongation factors to form HIV-1 elongation complex R-HSA-5691000 TFIIH binds GG-NER site to form a verification complex R-HSA-73946 Abortive initiation R-HSA-75856 Abortive Initiation Before Second Transition R-HSA-75891 Abortive Initiation After Second Transition R-HSA-77090 Methylation of GMP-cap by RNA Methyltransferase R-HSA-112385 Addition of nucleotides leads to transcript elongation R-HSA-167181 Addition of nucleotides leads to HIV-1 transcript elongation R-HSA-167468 Abortive HIV-1 Initiation After Second Transition R-HSA-167474 Abortive HIV-1 Initiation Before Second Transition R-HSA-167477 Abortive HIV-1 initiation after formation of the first phosphodiester bond R-HSA-5690988 3'-incision of DNA by ERCC5 (XPG) in GG-NER R-HSA-73769 Loss of Rrn3 from RNA Polymerase I promoter escape complex R-HSA-74994 Polymerase I Transcription Complex/Nascent Pre rRNA Complex pauses at the TTF-I:Sal Box R-HSA-74992 Dissociation of PTRF:Polymerase I/Nascent Pre rRNA Complex:TTF-I:Sal Box R-HSA-75873 Addition of Nucleotides 5 through 9 on the growing Transcript R-HSA-76576 Addition of nucleotides 10 and 11 on the growing transcript: Third Transition R-HSA-111264 Addition of nucleotides between position +11 and +30 R-HSA-77068 Activation of GT R-HSA-77069 RNA Polymerase II CTD (phosphorylated) binds to CE R-HSA-77073 SPT5 subunit of Pol II binds the RNA triphosphatase (RTP) R-HSA-77077 Capping complex formation R-HSA-75864 Newly Formed Phosphodiester Bond Stabilized and PPi Released R-HSA-75866 Nucleophillic Attack by 3'-hydroxyl Oxygen of nascent transcript on the Alpha Phosphate of NTP R-HSA-75949 RNA Polymerase II Promoter Opening: First Transition R-HSA-75862 Fall Back to Closed Pre-initiation Complex R-HSA-75861 NTP Binds Active Site of RNA Polymerase II R-HSA-113430 Extrusion of 5'-end of 30 nt long transcript through the pore in Pol II complex R-HSA-77071 Phosphorylation (Ser5) of RNA pol II CTD R-HSA-167117 Addition of nucleotides 10 and 11 on the growing HIV-1 transcript: Third Transition R-HSA-167136 Addition of nucleotides 5 through 9 on the growing HIV-1 transcript R-HSA-167134 Newly formed phosphodiester bond stabilized and PPi released R-HSA-167098 Phosphorylation (Ser5) of RNA pol II CTD R-HSA-167111 Extrusion of 5'-end of 30 nt long HIV-1 transcript through the pore in Pol II complex R-HSA-167130 Nucleophillic attack by 3'-hydroxyl oxygen of nascent HIV-1 transcript on the Alpha phosphate of NTP R-HSA-167133 Activation of GT R-HSA-167128 RNA Polymerase II CTD (phosphorylated) binds to CE R-HSA-167115 Addition of nucleotides between position +11 and +30 on HIV-1 transcript R-HSA-167153 SPT5 subunit of Pol II binds the RNA triphosphatase (RTP) R-HSA-167097 HIV Promoter Opening: First Transition R-HSA-167484 Fall Back to Closed Pre-initiation Complex R-HSA-167118 NTP binds active site of RNA Polymerase II in HIV-1 open pre-initiation complex R-HSA-5689861 Recruitment of XPA and release of CAK R-HSA-6781840 ERCC6 binds stalled RNA Pol II 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-6797616 CCNK:CDK12 binds RNA Pol II at DNA repair genes R-HSA-5696670 CHD1L is recruited to GG-NER site R-HSA-5690213 DNA polymerases delta, epsilon or kappa bind the GG-NER site R-HSA-6790454 SUMOylation of XPC R-HSA-5690996 ERCC2 and ERCC3 DNA helicases form an open bubble structure in damaged DNA R-HSA-5690990 5'- incision of DNA by ERCC1:ERCC4 in GG-NER R-HSA-6790487 RNF111 ubiquitinates SUMOylated XPC R-HSA-5689317 Formation of the pre-incision complex in GG-NER R-HSA-74993 PTRF Binds the Polymerase I Transcription Complex/Nascent Pre rRNA Complex paused at the TTF-I:Sal Box R-HSA-74986 Elongation of pre-rRNA transcript R-HSA-427366 Transcription of intergenic spacer of the rRNA gene R-HSA-77078 Hydrolysis of the 5'-end of the nascent transcript by the capping enzyme R-HSA-77081 Formation of the CE:GMP intermediate complex R-HSA-77085 Dissociation of transcript with 5'-GMP from GT R-HSA-77083 Transfer of GMP from the capping enzyme GT site to 5'-end of mRNA R-HSA-6781833 ERCC8 (CSA) binds stalled RNA Pol II R-HSA-6797606 CDK12 phosphorylates RNA Pol II CTD at DNA repair genes R-HSA-5690991 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in GG-NER R-HSA-6781867 ERCC8:DDB1:CUL4:RBX1 ubiquitinates ERCC6 and RNA Pol II R-HSA-6782004 Assembly of the pre-incision complex in TC-NER 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-6782141 Binding of ERCC1:ERCC4 (ERCC1:XPF) to pre-incision complex in TC-NER R-HSA-73762 RNA Polymerase I Transcription Initiation R-HSA-73779 RNA Polymerase II Transcription Pre-Initiation And Promoter Opening R-HSA-112382 Formation of RNA Pol II elongation complex R-HSA-113418 Formation of the Early Elongation Complex R-HSA-167158 Formation of the HIV-1 Early Elongation Complex R-HSA-167152 Formation of HIV elongation complex in the absence of HIV Tat R-HSA-167200 Formation of HIV-1 elongation complex containing HIV-1 Tat R-HSA-5696395 Formation of Incision Complex in GG-NER R-HSA-6781823 Formation of TC-NER Pre-Incision Complex R-HSA-674695 RNA Polymerase II Pre-transcription Events R-HSA-72086 mRNA Capping R-HSA-75955 RNA Polymerase II Transcription Elongation R-HSA-167246 Tat-mediated elongation of the HIV-1 transcript R-HSA-167162 RNA Polymerase II HIV Promoter Escape R-HSA-167161 HIV Transcription Initiation R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-5696400 Dual Incision in GG-NER R-HSA-2564830 Cytosolic iron-sulfur cluster assembly R-HSA-73772 RNA Polymerase I Promoter Escape R-HSA-73863 RNA Polymerase I Transcription Termination R-HSA-73776 RNA Polymerase II Promoter Escape R-HSA-77075 RNA Pol II CTD phosphorylation and interaction with CE R-HSA-75953 RNA Polymerase II Transcription Initiation R-HSA-76042 RNA Polymerase II Transcription Initiation And Promoter Clearance R-HSA-167160 RNA Pol II CTD phosphorylation and interaction with CE during HIV infection R-HSA-167172 Transcription of the HIV genome R-HSA-6782135 Dual incision in TC-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes R-HSA-73854 RNA Polymerase I Promoter Clearance R-HSA-73857 RNA Polymerase II Transcription R-HSA-167169 HIV Transcription Elongation R-HSA-5696399 Global Genome Nucleotide Excision Repair (GG-NER) R-HSA-8953854 Metabolism of RNA R-HSA-5696398 Nucleotide Excision Repair R-HSA-1430728 Metabolism R-HSA-73864 RNA Polymerase I Transcription R-HSA-73777 RNA Polymerase I Chain Elongation R-HSA-427413 NoRC negatively regulates rRNA expression R-HSA-162599 Late Phase of HIV Life Cycle R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-74160 Gene expression (Transcription) R-HSA-73894 DNA Repair R-HSA-5250941 Negative epigenetic regulation of rRNA expression R-HSA-162587 HIV Life Cycle R-HSA-212436 Generic Transcription Pathway R-HSA-212165 Epigenetic regulation of gene expression R-HSA-162906 HIV Infection R-HSA-5663205 Infectious disease R-HSA-1643685 Disease
US Server
