ERCC6
entrez
2074
canonical
uniprot
P0DP91
canonical
uniprot
Q03468
canonical
ensembl
ENSG00000225830
resolver
ensp
ENSP00000348089
resolver
ensp
ENSP00000387966
resolver
ensp
ENSP00000423550
resolver
ensp
ENSP00000568314
resolver
enst
ENST00000355832
resolver
enst
ENST00000447839
resolver
enst
ENST00000515869
resolver
enst
ENST00000898255
resolver
genesymbol
ERCC6
resolver
genesymbol_syn
CSB
resolver
hgnc
HGNC:3438
resolver
uniprot
D3DX94
resolver
uniprot
E7EV46
resolver
uniprot
Q59FF6
resolver
uniprot
Q5W0L9
resolver
uniprot_entry
ERCC6_HUMAN
resolver
uniprot_entry
ERPG3_HUMAN
resolver
uniprot_entry
Q59FF6_HUMAN
resolver
uniprot_sec
D3DX94
resolver
uniprot_sec
E7EV46
resolver
uniprot_sec
Q5W0L9
resolver
amino_acid_sequence
MPNEGIPHSSQTQEQDCLQSQPVSNNEEMAIKQESGGDGEVEEYLSFRSVGDGLSTSAVGCASAAPRRGPALLHIDRHQIQAVEPSAQALELQGLGVDVYDQDVLEQGVLQQVDNAIHEASRASQLVDVEKEYRSVLDDLTSCTTSLRQINKIIEQLSPQAATSRDINRKLDSVKRQKYNKEQQLKKITAKQKHLQAILGGAEVKIELDHASLEEDAEPGPSSLGSMLMPVQETAWEELIRTGQMTPFGTQIPQKQEKKPRKIMLNEASGFEKYLADQAKLSFERKKQGCNKRAARKAPAPVTPPAPVQNKNKPNKKARVLSKKEERLKKHIKKLQKRALQFQGKVGLPKARRPWESDMRPEAEGDSEGEESEYFPTEEEEEEEDDEVEGAEADLSGDGTDYELKPLPKGGKRQKKVPVQEIDDDFFPSSGEEAEAASVGEGGGGGRKVGRYRDDGDEDYYKQRLRRWNKLRLQDKEKRLKLEDDSEESDAEFDEGFKVPGFLFKKLFKYQQTGVRWLWELHCQQAGGILGDEMGLGKTIQIIAFLAGLSYSKIRTRGSNYRFEGLGPTVIVCPTTVMHQWVKEFHTWWPPFRVAILHETGSYTHKKEKLIRDVAHCHGILITSYSYIRLMQDDISRYDWHYVILDEGHKIRNPNAAVTLACKQFRTPHRIILSGSPMQNNLRELWSLFDFIFPGKLGTLPVFMEQFSVPITMGGYSNASPVQVKTAYKCACVLRDTINPYLLRRMKSDVKMSLSLPDKNEQVLFCRLTDEQHKVYQNFVDSKEVYRILNGEMQIFSGLIALRKICNHPDLFSGGPKNLKGLPDDELEEDQFGYWKRSGKMIVVESLLKIWHKQGQRVLLFSQSRQMLDILEVFLRAQKYTYLKMDGTTTIASRQPLITRYNEDTSIFVFLLTTRVGGLGVNLTGANRVVIYDPDWNPSTDTQARERAWRIGQKKQVTVYRLLTAGTIEEKIYHRQIFKQFLTNRVLKDPKQRRFFKSNDLYELFTLTSPDASQSTETSAIFAGTGSDVQTPKCHLKRRIQPAFGADHDVPKRKKFPASNISVNDATSSEEKSEAKGAEVNAVTSNRSDPLKDDPHMSSNVTSNDRLGEETNAVSGPEELSVISGNGECSNSSGTGKTSMPSGDESIDEKLGLSYKRERPSQAQTEAFWENKQMENNFYKHKSKTKHHSVAEEETLEKHLRPKQKPKNSKHCRDAKFEGTRIPHLVKKRRYQKQDSENKSEAKEQSNDDYVLEKLFKKSVGVHSVMKHDAIMDGASPDYVLVEAEANRVAQDALKALRLSRQRCLGAVSGVPTWTGHRGISGAPAGKKSRFGKKRNSNFSVQHPSSTSPTEKCQDGIMKKEGKDNVPEHFSGRAEDADSSSGPLASSSLLAKMRARNHLILPERLESESGHLQEASALLPTTEHDDLLVEMRNFIAFQAHTDGQASTREILQEFESKLSASQSCVFRELLRNLCTFHRTSGGEGIWKLKPEYC
uniprot
proteins
amino_acid_sequence
MPNEGIPHSSQTQEQDCLQSQPVSNNEEMAIKQESGGDGEVEEYLSFRSVGDGLSTSAVGCASAAPRRGPALLHIDRHQIQAVEPSAQALELQGLGVDVYDQDVLEQGVLQQVDNAIHEASRASQLVDVEKEYRSVLDDLTSCTTSLRQINKIIEQLSPQAATSRDINRKLDSVKRQKYNKEQQLKKITAKQKHLQAILGGAEVKIELDHASLEEDAEPGPSSLGSMLMPVQETAWEELIRTGQMTPFGTQIPQKQEKKPRKIMLNEASGFEKYLADQAKLSFERKKQGCNKRAARKAPAPVTPPAPVQNKNKPNKKARVLSKKEERLKKHIKKLQKRALQFQGKVGLPKARRPWESDMRPEAEGDSEGEESEYFPTEEEEEEEDDEVEGAEADLSGDGTDYELKPLPKGGKRQKKVPVQEIDDDFFPSSGEEAEAASVGEGGGGGRKVGRYRDDGDEDYYKQRLSPKMPRTLSLHEITDLLETDDSIEASAIVIQPPENATAPVSDEESGDEEGGTINNLPGSLLHTAAYLIQDGSDAESDSDDPSYAPKDDSPDEVPSTFTVQQPPPSRRRKMTKILCKWKKADLTVQPVAGRVTAPPNDFFTVMRTPTEILELFLDDEVIELIVKYSNLYACSKGVHLGLTSSEFKCFLGIIFLSGYVSVPRRRMFWEQRTDVHNVLVSAAMRRDRFETIFSNLHVADNANLDPVDKFSKLRPLISKLNERCMKFVPNETYFSFDEFMVPYFGRHGCKQFIRGKPIRFGYKFWCGATCLGYICWFQPYQGKNPNTKHEEYGVGASLVLQFSEALTEAHPGQYHFVFNNFFTSIALLDKLSSMGHQATGTVRKDHIDRVPLESDVALKKKERGTFDYRIDGKGNIVCRWNDNSVVTVASSGAGIHPLCLVSRYSQKLKKKIQVQQPNMIKVYNQFMGGVDRADENIDKYRASIRGKKWYSSPLLFCFELVLQNAWQLHKTYDEKPVDFLEFRRRVVCHYLETHGHPPEPGQKGRPQKRNIDSRYDGINHVIVKQGKQTRCAECHKNTTFRCEKCDVALHVKCSVEYHTE
uniprot
proteins
disease_involvement
DISEASE: 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 intellectual disability. 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:0000269|PubMed:10447254, ECO:0000269|PubMed:19894250, ECO:0000269|PubMed:25820262, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:9443879}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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:0000269|PubMed:19894250}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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 intellectual disability, dwarfism, gonadal hypoplasia, microcephaly and various neurologic complications of early onset. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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:0000269|PubMed:16754848}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: 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:0000269|PubMed:15486090}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
disease_involvement
DISEASE: Premature ovarian failure 11 (POF11) [MIM:616946]: An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. {ECO:0000269|PubMed:26218421}. Note=The protein represented in this entry is involved in disease pathogenesis. Disease-causing variants affect isoform CSB-PGBD3, which is a chimeric protein between ERCC6 N-terminus and the entire PGBD3 sequence. {ECO:0000269|PubMed:26218421}.
uniprot
proteins
ec_number
3.6.4.-
uniprot
proteins
function
FUNCTION: Essential factor involved in transcription-coupled nucleotide excision repair (TC-NER), a process during which RNA polymerase II-blocking lesions are rapidly removed from the transcribed strand of active genes (PubMed:16246722, PubMed:20541997, PubMed:22483866, PubMed:26620705, PubMed:32355176, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). Plays a central role in the initiation of the TC-NER process: specifically recognizes and binds RNA polymerase II stalled at a lesion, and mediates recruitment of ERCC8/CSA, initiating DNA damage excision by TFIIH recruitment (PubMed:32355176, PubMed:34526721, PubMed:38600235, PubMed:38600236). 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 (PubMed:15548521). Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function (PubMed:16246722, PubMed:9565609). Plays an important role in regulating the choice of the DNA double-strand breaks (DSBs) repair pathway and G2/M checkpoint activation; DNA-dependent ATPase activity is essential for this function (PubMed:25820262). Regulates the DNA repair pathway choice by inhibiting non-homologous end joining (NHEJ), thereby promoting the homologous recombination (HR)-mediated repair of DSBs during the S/G2 phases of the cell cycle (PubMed:25820262). Mediates the activation of the ATM- and CHEK2-dependent DNA damage responses thus preventing premature entry of cells into mitosis following the induction of DNA DSBs (PubMed:25820262). Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR (PubMed:29203878). Required for stable recruitment of ELOA and CUL5 to DNA damage sites (PubMed:28292928). Also involved in UV-induced translocation of ERCC8 to the nuclear matrix (PubMed:26620705). Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis (PubMed:24874740). {ECO:0000269|PubMed:15548521, ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:22483866, ECO:0000269|PubMed:24874740, ECO:0000269|PubMed:25820262, ECO:0000269|PubMed:26620705, ECO:0000269|PubMed:28292928, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:32355176, ECO:0000269|PubMed:34526721, ECO:0000269|PubMed:38316879, ECO:0000269|PubMed:38600235, ECO:0000269|PubMed:38600236, ECO:0000269|PubMed:9565609}.
uniprot
proteins
function
FUNCTION: Involved in repair of DNA damage following UV irradiation, acting either in the absence of ERCC6 or synergistically with ERCC6. Involved in the regulation of gene expression. In the absence of ERCC6, induces the expression of genes characteristic of interferon-like antiviral responses. This response is almost completely suppressed in the presence of ERCC6. In the presence of ERCC6, regulates the expression of genes involved in metabolism regulation, including IGFBP5 and IGFBP7. In vitro binds to PGBD3-related transposable elements, called MER85s; these non-autonomous 140 bp elements are characterized by the presence of PGBD3 terminal inverted repeats and the absence of internal transposase ORF. {ECO:0000269|PubMed:22483866}.
uniprot
proteins
mass_dalton
119487
uniprot
proteins
mass_dalton
168416
uniprot
proteins
mutagenesis
MUTAGEN 10; /note="S->A: Non-phosphorylatable by ATM. Loss of chromatin remodeling activity and its ability to promote the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain."; /evidence="ECO:0000269|PubMed:29203878"; MUTAGEN 10; /note="S->D: Phosphomimetic mutant. No loss of chromatin remodeling activity and its ability to promote the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain."; /evidence="ECO:0000269|PubMed:29203878"; MUTAGEN 158; /note="S->A: Non-phosphorylatable by CDK2. Loss of chromatin remodeling activity and its ability to promote the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain."; /evidence="ECO:0000269|PubMed:29203878"; MUTAGEN 158; /note="S->D: Phosphomimetic mutant. No loss of chromatin remodeling activity and its ability to promote the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain."; /evidence="ECO:0000269|PubMed:29203878"; MUTAGEN 205; /note="K->R: Loss of sumoylation and defects in transcription-coupled nucleotide excision repair."; /evidence="ECO:0000269|PubMed:26620705"; MUTAGEN 538; /note="K->R: Abolished ATPase activity without abolishing ability to promote transcription-coupled nucleotide excision repair (TC-NER)."; /evidence="ECO:0000269|PubMed:9565609"; MUTAGEN 1385..1399; /note="Missing: Abolished interaction with ERCC8/CSA and ERCC8/CSA recruitmentto DNA damage sites."; /evidence="ECO:0000269|PubMed:32355176"; MUTAGEN 1427..1428; /note="LL->GG: Fails to bind polyubiquitin chains."; /evidence="ECO:0000269|PubMed:20541997"; MUTAGEN 1457; /note="K->R: No loss of sumoylation; when associated with R-1487 and R-1489."; /evidence="ECO:0000269|PubMed:26620705"; MUTAGEN 1470; /note="L->G: Loss of interaction with RIF1; when associated with G-1486 and G-1488."; /evidence="ECO:0000269|PubMed:29203878"; MUTAGEN 1486; /note="W->G: Loss of interaction with RIF1; when associated with G-1470 and G-1488."; /evidence="ECO:0000269|PubMed:29203878"; MUTAGEN 1487; /note="K->R: No loss of sumoylation; when associated with R-1457 and R-1489. No loss of sumoylation; when associated with R-1489."; /evidence="ECO:0000269|PubMed:26620705"; MUTAGEN 1488; /note="L->G: Loss of interaction with RIF1; when associated with G-1470 and G-1486."; /evidence="ECO:0000269|PubMed:29203878"; MUTAGEN 1489; /note="K->R: No loss of sumoylation; when associated with R-1457 and R-1487. No loss of sumoylation; when associated with R-1487."; /evidence="ECO:0000269|PubMed:26620705
uniprot
proteins
post_translational_modification
PTM: Phosphorylated in a cell cycle-dependent manner at Ser-158 by cyclin A-CDK2 and at Ser-10 by ATM in response to DNA damage (PubMed:29203878). Phosphorylation at these two sites promotes the intramolecular interaction of the N-terminal domain with the helicase ATP-binding domain, thereby probably releasing the inhibitory effect of the N-terminal domain on its ATPase activity (PubMed:29203878). Phosphorylation is essential for its chromatin remodeling activity (PubMed:29203878). {ECO:0000269|PubMed:29203878}.; PTM: Ubiquitinated at the C-terminus. Ubiquitination by the CSA complex leads to ERCC6 proteasomal degradation in a UV-dependent manner. Stabilized following interaction with KIAA1530/UVSSA, which promotes recruitment of deubiquitinating enzyme USP7, leading to deubiquitination of ERCC6 thereby preventing UV-induced degradation of ERCC6 by the proteasome. {ECO:0000269|PubMed:16751180, ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:22466610, ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612}.; PTM: Sumoylation at Lys-205 in an UV-radiation-dependent manner is essential for its transcription-coupled nucleotide excision repair activity. {ECO:0000269|PubMed:26620705}.
uniprot
proteins
protein_family
SNF2/RAD54 helicase family
uniprot
proteins
pubmed
10447254
uniprot
proteins
pubmed
10739753
uniprot
proteins
pubmed
10767341
uniprot
proteins
pubmed
1339317
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15486090
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15548521
uniprot
proteins
pubmed
16128801
uniprot
proteins
pubmed
16246722
uniprot
proteins
pubmed
16603771
uniprot
proteins
pubmed
16751180
uniprot
proteins
pubmed
16754848
uniprot
proteins
pubmed
16916636
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18369450
uniprot
proteins
pubmed
18438403
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18987736
uniprot
proteins
pubmed
19894250
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20541997
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22466610
uniprot
proteins
pubmed
22466611
uniprot
proteins
pubmed
22466612
uniprot
proteins
pubmed
22483866
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24874740
uniprot
proteins
pubmed
25820262
uniprot
proteins
pubmed
26030138
uniprot
proteins
pubmed
26218421
uniprot
proteins
pubmed
26620705
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28292928
uniprot
proteins
pubmed
29203878
uniprot
proteins
pubmed
29545921
uniprot
proteins
pubmed
32142649
uniprot
proteins
pubmed
32355176
uniprot
proteins
pubmed
34526721
uniprot
proteins
pubmed
34919821
uniprot
proteins
pubmed
38316879
uniprot
proteins
pubmed
38600235
uniprot
proteins
pubmed
38600236
uniprot
proteins
pubmed
8382798
uniprot
proteins
pubmed
9443879
uniprot
proteins
pubmed
9565609
uniprot
proteins
sequence_length
1061
uniprot
proteins
sequence_length
1493
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16128801}. Chromosome {ECO:0000269|PubMed:26620705, ECO:0000269|PubMed:32355176}. Note=Recognizes and binds RNA polymerase II stalled at DNA damage sites. {ECO:0000269|PubMed:32355176}.
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26218421}.
uniprot
proteins