UniProtKB - Q03468 (ERCC6_HUMAN)
DNA excision repair protein ERCC-6
ERCC6
Functioni
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 (PubMed:20541997, PubMed:26620705, PubMed:16246722).
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).
It is required for transcription-coupled repair complex formation (PubMed:16916636).
It recruits the CSA complex (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to the sites of RNA polymerase II-blocking lesions (PubMed:16916636).
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).
Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function. 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).
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).
10 PublicationsCatalytic activityi
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 532 – 539 | ATPPROSITE-ProRule annotation | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- ATP-dependent activity, acting on DNA Source: UniProtKB
- ATP-dependent chromatin remodeler activity Source: GO_Central
- ATP hydrolysis activity Source: RHEA
- chromatin binding Source: UniProtKB
- DNA binding Source: UniProtKB
- helicase activity Source: UniProtKB-KW
- protein-containing complex binding Source: UniProtKB
- protein C-terminus binding Source: UniProtKB
- protein N-terminus binding Source: UniProtKB
- protein tyrosine kinase activator activity Source: MGI
- RNA polymerase binding Source: UniProtKB
GO - Biological processi
- base-excision repair Source: UniProtKB
- chromatin remodeling Source: ComplexPortal
- DNA damage checkpoint signaling Source: UniProtKB
- DNA protection Source: Ensembl
- DNA repair Source: UniProtKB
- double-strand break repair via classical nonhomologous end joining Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to DNA damage Source: Ensembl
- JNK cascade Source: Ensembl
- multicellular organism growth Source: Ensembl
- negative regulation of double-strand break repair via nonhomologous end joining Source: UniProtKB
- neurogenesis Source: UniProtKB
- neuron differentiation Source: UniProtKB
- neuron projection development Source: UniProtKB
- photoreceptor cell maintenance Source: Ensembl
- positive regulation of DNA repair Source: UniProtKB
- positive regulation of DNA-templated transcription, elongation Source: UniProtKB
- positive regulation of double-strand break repair via homologous recombination Source: UniProtKB
- positive regulation of histone acetylation Source: ComplexPortal
- positive regulation of transcription by RNA polymerase I Source: ComplexPortal
- positive regulation of transcription by RNA polymerase II Source: ComplexPortal
- positive regulation of transcription by RNA polymerase III Source: ComplexPortal
- positive regulation of transcription initiation from RNA polymerase II promoter Source: Ensembl
- pyrimidine dimer repair Source: Ensembl
- regulation of DNA-templated transcription, elongation Source: UniProtKB
- regulation of transcription elongation from RNA polymerase II promoter Source: Ensembl
- response to gamma radiation Source: Ensembl
- response to oxidative stress Source: UniProtKB
- response to superoxide Source: Ensembl
- response to toxic substance Source: Ensembl
- response to UV Source: UniProtKB
- response to UV-B Source: Ensembl
- response to X-ray Source: Ensembl
- single strand break repair Source: UniProtKB
- transcription by RNA polymerase II Source: UniProtKB
- transcription-coupled nucleotide-excision repair Source: UniProtKB
- transcription elongation from RNA polymerase I promoter Source: Ensembl
Keywordsi
Molecular function | DNA-binding, Helicase, Hydrolase |
Biological process | DNA damage, DNA repair, Neurogenesis, Transcription, Transcription regulation |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q03468 |
Reactomei | R-HSA-427389, ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression R-HSA-5250924, B-WICH complex positively regulates rRNA expression R-HSA-6781823, Formation of TC-NER Pre-Incision Complex R-HSA-6781827, Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-6782135, Dual incision in TC-NER R-HSA-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-73762, RNA Polymerase I Transcription Initiation |
SignaLinki | Q03468 |
SIGNORi | Q03468 |
Names & Taxonomyi
Protein namesi | Recommended name: DNA excision repair protein ERCC-6 (EC:3.6.4.-1 Publication)Alternative name(s): ATP-dependent helicase ERCC6 Cockayne syndrome protein CSB |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3438, ERCC6 |
MIMi | 609413, gene |
neXtProti | NX_Q03468 |
VEuPathDBi | HostDB:ENSG00000225830 |
Subcellular locationi
Nucleus
- Nucleus 1 Publication
Nucleus
- B-WICH complex Source: ComplexPortal
- nucleolus Source: UniProtKB
- nucleoplasm Source: UniProtKB
- nucleus Source: UniProtKB
- transcription elongation factor complex Source: UniProtKB
Other locations
- site of DNA damage Source: UniProtKB
Keywords - Cellular componenti
NucleusPathology & Biotechi
Involvement in diseasei
Cockayne syndrome B (CSB)5 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_001218 | 670 | R → W in CSB. 2 PublicationsCorresponds to variant dbSNP:rs202080674EnsemblClinVar. | 1 | |
Natural variantiVAR_063511 | 680 | N → D in CSB. 1 PublicationCorresponds to variant dbSNP:rs1554788393EnsemblClinVar. | 1 | |
Natural variantiVAR_063512 | 686 | W → C in CSB. 1 PublicationCorresponds to variant dbSNP:rs751292948EnsemblClinVar. | 1 | |
Natural variantiVAR_063513 | 687 | S → L in CSB. 1 PublicationCorresponds to variant dbSNP:rs1026438103EnsemblClinVar. | 1 | |
Natural variantiVAR_001219 | 851 | W → R in CSB; DNA-dependent ATPase-dead mutant; loss of chromatin remodeling activity; loss of its ability to inhibit non-homologous end joining-mediated repair and promote homologous recombination-mediated repair of DNA double-strand breaks; loss of its ability to suppress premature exit from G2/M checkpoint; abrogation of its UV-induced chromatin association. 4 PublicationsCorresponds to variant dbSNP:rs368728467EnsemblClinVar. | 1 | |
Natural variantiVAR_001220 | 957 | V → G in CSB. 2 Publications | 1 | |
Natural variantiVAR_001221 | 1042 | P → L in CSB. 2 Publications | 1 |
Cerebro-oculo-facio-skeletal syndrome 1 (COFS1)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_063514 | 871 | L → P in COFS1. 1 Publication | 1 | |
Natural variantiVAR_063515 | 987 | L → P in COFS1. 1 PublicationCorresponds to variant dbSNP:rs121917905EnsemblClinVar. | 1 |
De Sanctis-Cacchione syndrome (DSC)
Macular degeneration, age-related, 5 (ARMD5)1 Publication
UV-sensitive syndrome 1 (UVSS1)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 10 | 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. 1 Publication | 1 | |
Mutagenesisi | 10 | 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. 1 Publication | 1 | |
Mutagenesisi | 158 | 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. 1 Publication | 1 | |
Mutagenesisi | 158 | 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. 1 Publication | 1 | |
Mutagenesisi | 205 | K → R: Loss of sumoylation and defects in transcription-coupled nucleotide excision repair. 1 Publication | 1 | |
Mutagenesisi | 1427 – 1428 | LL → GG: Fails to bind polyubiquitin chains. 1 Publication | 2 | |
Mutagenesisi | 1457 | K → R: No loss of sumoylation; when associated with R-1487 and R-1489. 1 Publication | 1 | |
Mutagenesisi | 1470 | L → G: Loss of interaction with RIF1; when associated with G-1486 and G-1488. 1 Publication | 1 | |
Mutagenesisi | 1486 | W → G: Loss of interaction with RIF1; when associated with G-1470 and G-1488. 1 Publication | 1 | |
Mutagenesisi | 1487 | K → R: No loss of sumoylation; when associated with R-1457 and R-1489. No loss of sumoylation; when associated with R-1489. 1 Publication | 1 | |
Mutagenesisi | 1488 | L → G: Loss of interaction with RIF1; when associated with G-1470 and G-1486. 1 Publication | 1 | |
Mutagenesisi | 1489 | K → R: No loss of sumoylation; when associated with R-1457 and R-1487. No loss of sumoylation; when associated with R-1487. 1 Publication | 1 |
Keywords - Diseasei
Age-related macular degeneration, Cataract, Cockayne syndrome, Deafness, Disease variant, Dwarfism, Mental retardation, Xeroderma pigmentosumOrganism-specific databases
DisGeNETi | 2074 |
GeneReviewsi | ERCC6 |
MalaCardsi | ERCC6 |
MIMi | 133540, phenotype 214150, phenotype 278800, phenotype 600630, phenotype 613761, phenotype |
OpenTargetsi | ENSG00000225830 |
Orphaneti | 90321, Cockayne syndrome type 1 90322, Cockayne syndrome type 2 90324, Cockayne syndrome type 3 1466, COFS syndrome 619, NON RARE IN EUROPE: Primary ovarian failure 178338, UV-sensitive syndrome |
PharmGKBi | PA27852 |
Miscellaneous databases
Pharosi | Q03468, Tbio |
Genetic variation databases
BioMutai | ERCC6 |
DMDMi | 416959 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000074314 | 1 – 1493 | DNA excision repair protein ERCC-6Add BLAST | 1493 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 10 | Phosphoserine; by ATM1 Publication | 1 | |
Modified residuei | 158 | Phosphoserine; by CDK2Combined sources1 Publication | 1 | |
Modified residuei | 170 | N6-methylated lysine; by EHMT21 Publication | 1 | |
Cross-linki | 205 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO3)1 Publication | ||
Cross-linki | 255 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 297 | N6-methylated lysine; by EHMT21 Publication | 1 | |
Modified residuei | 429 | PhosphoserineCombined sources | 1 | |
Modified residuei | 430 | PhosphoserineCombined sources | 1 | |
Modified residuei | 448 | N6-methylated lysine; by EHMT21 Publication | 1 | |
Modified residuei | 486 | PhosphoserineCombined sources | 1 | |
Modified residuei | 489 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1054 | N6-methylated lysine; by EHMT21 Publication | 1 | |
Modified residuei | 1142 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1348 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q03468 |
jPOSTi | Q03468 |
MassIVEi | Q03468 |
MaxQBi | Q03468 |
PaxDbi | Q03468 |
PeptideAtlasi | Q03468 |
PRIDEi | Q03468 |
ProteomicsDBi | 18566 58213 |
PTM databases
iPTMneti | Q03468 |
PhosphoSitePlusi | Q03468 |
Expressioni
Gene expression databases
Bgeei | ENSG00000258838, Expressed in sural nerve and 116 other tissues |
ExpressionAtlasi | Q03468, baseline and differential |
Genevisiblei | Q03468, HS |
Organism-specific databases
HPAi | ENSG00000225830, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer (PubMed:16128801, PubMed:15548521). Binds DNA (PubMed:15548521).
Interacts with ERCC8 (PubMed:16751180).
Interacts with RNA polymerase II; interaction is enhanced by UV irradiation (PubMed:26620705).
Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 (PubMed:16603771).
Interacts with KIAA1530/UVSSA (PubMed:22466612).
Interacts with ELOA and CUL5; the interaction is induced by DNA damaging agents or by inhibitors of RNA polymerase II elongation (PubMed:28292928).
Interacts (via WHD region) with RIF1 (PubMed:29203878).
Interacts with SMARCC2/BAF170, SMARCB1/BAF47 and the neuron-specific chromatin remodeling complex (nBAF complex)(PubMed:24874740).
Interacts with ERCC5/XPG (via C-terminus); the interaction stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity (PubMed:16246722). May form a complex composed of RNA polymerase II, ERCC6/CSB and ERCC5/XPG which associates with the DNA repair bubble during transcription-coupled nucleotide excision repair (PubMed:16246722).
Interacts with CAND1, CSTF1, DDX3X, DDX5, DDX17, DDX23, DHX36, HDAC1, HNRNPU, MTA2, PRPF3, PSMD3, RBBP4, SFPQ, SMARCA1, SMARCA2, TOP1, USP7, XRCC5, COPS3, COPS4, COPS6, DDX1, DDX41, GATAD2A, GATAD2B, PRPF4, PSMC5, SF3B2, CTR9, NONO, PSMD12 and TOP2A (PubMed:26030138).
11 PublicationsBinary interactionsi
Q03468
With | #Exp. | IntAct |
---|---|---|
ABL1 [P00519] | 8 | EBI-295284,EBI-375543 |
ERCC8 - isoform 1 [Q13216-1] | 2 | EBI-295284,EBI-596556 |
GO - Molecular functioni
- protein C-terminus binding Source: UniProtKB
- protein N-terminus binding Source: UniProtKB
- RNA polymerase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 108386, 214 interactors |
ComplexPortali | CPX-1099, B-WICH chromatin remodelling complex |
CORUMi | Q03468 |
DIPi | DIP-193N |
IntActi | Q03468, 26 interactors |
MINTi | Q03468 |
STRINGi | 9606.ENSP00000348089 |
Miscellaneous databases
RNActi | Q03468, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q03468 |
SMRi | Q03468 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 519 – 695 | Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST | 177 | |
Domaini | 843 – 1002 | Helicase C-terminalPROSITE-ProRule annotationAdd BLAST | 160 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 510 | N-terminal domain; essential for its chromatin remodeling activity1 PublicationAdd BLAST | 510 | |
Regioni | 1 – 39 | DisorderedSequence analysisAdd BLAST | 39 | |
Regioni | 287 – 323 | DisorderedSequence analysisAdd BLAST | 37 | |
Regioni | 344 – 453 | DisorderedSequence analysisAdd BLAST | 110 | |
Regioni | 1042 – 1147 | DisorderedSequence analysisAdd BLAST | 106 | |
Regioni | 1181 – 1247 | DisorderedSequence analysisAdd BLAST | 67 | |
Regioni | 1318 – 1384 | DisorderedSequence analysisAdd BLAST | 67 | |
Regioni | 1400 – 1428 | Ubiquitin-binding domain (UBD)1 PublicationAdd BLAST | 29 | |
Regioni | 1429 – 1493 | Winged-helix domain (WHD)1 PublicationAdd BLAST | 65 | |
Regioni | 1446 – 1493 | Essential for its interaction with RNA polymerase II, transcription-coupled nucleotide excision repair activity, association with chromatin after UV irradiation and for mediating the UV-induced translocation of ERRC8 to the nuclear matrix1 PublicationAdd BLAST | 48 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 646 – 649 | DEAH boxPROSITE-ProRule annotation | 4 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 1 – 31 | Polar residuesSequence analysisAdd BLAST | 31 | |
Compositional biasi | 363 – 396 | Acidic residuesSequence analysisAdd BLAST | 34 | |
Compositional biasi | 405 – 422 | Basic and acidic residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 1095 – 1110 | Polar residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 1124 – 1142 | Polar residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 1181 – 1202 | Basic and acidic residuesSequence analysisAdd BLAST | 22 | |
Compositional biasi | 1211 – 1247 | Basic and acidic residuesSequence analysisAdd BLAST | 37 | |
Compositional biasi | 1335 – 1353 | Polar residuesSequence analysisAdd BLAST | 19 | |
Compositional biasi | 1354 – 1375 | Basic and acidic residuesSequence analysisAdd BLAST | 22 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0387, Eukaryota |
GeneTreei | ENSGT00940000158057 |
HOGENOMi | CLU_000315_7_2_1 |
InParanoidi | Q03468 |
OMAi | HSVVKHD |
OrthoDBi | 372069at2759 |
PhylomeDBi | Q03468 |
TreeFami | TF101236 TF328011 |
Family and domain databases
Gene3Di | 3.40.50.10810, 1 hit 3.40.50.300, 1 hit |
InterProi | View protein in InterPro IPR014001, Helicase_ATP-bd IPR001650, Helicase_C IPR027417, P-loop_NTPase IPR038718, SNF2-like_sf IPR000330, SNF2_N |
Pfami | View protein in Pfam PF00271, Helicase_C, 1 hit PF00176, SNF2-rel_dom, 1 hit |
SMARTi | View protein in SMART SM00487, DEXDc, 1 hit SM00490, HELICc, 1 hit |
SUPFAMi | SSF52540, SSF52540, 2 hits |
PROSITEi | View protein in PROSITE PS51192, HELICASE_ATP_BIND_1, 1 hit PS51194, HELICASE_CTER, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPNEGIPHSS QTQEQDCLQS QPVSNNEEMA IKQESGGDGE VEEYLSFRSV
60 70 80 90 100
GDGLSTSAVG CASAAPRRGP ALLHIDRHQI QAVEPSAQAL ELQGLGVDVY
110 120 130 140 150
DQDVLEQGVL QQVDNAIHEA SRASQLVDVE KEYRSVLDDL TSCTTSLRQI
160 170 180 190 200
NKIIEQLSPQ AATSRDINRK LDSVKRQKYN KEQQLKKITA KQKHLQAILG
210 220 230 240 250
GAEVKIELDH ASLEEDAEPG PSSLGSMLMP VQETAWEELI RTGQMTPFGT
260 270 280 290 300
QIPQKQEKKP RKIMLNEASG FEKYLADQAK LSFERKKQGC NKRAARKAPA
310 320 330 340 350
PVTPPAPVQN KNKPNKKARV LSKKEERLKK HIKKLQKRAL QFQGKVGLPK
360 370 380 390 400
ARRPWESDMR PEAEGDSEGE ESEYFPTEEE EEEEDDEVEG AEADLSGDGT
410 420 430 440 450
DYELKPLPKG GKRQKKVPVQ EIDDDFFPSS GEEAEAASVG EGGGGGRKVG
460 470 480 490 500
RYRDDGDEDY YKQRLRRWNK LRLQDKEKRL KLEDDSEESD AEFDEGFKVP
510 520 530 540 550
GFLFKKLFKY QQTGVRWLWE LHCQQAGGIL GDEMGLGKTI QIIAFLAGLS
560 570 580 590 600
YSKIRTRGSN YRFEGLGPTV IVCPTTVMHQ WVKEFHTWWP PFRVAILHET
610 620 630 640 650
GSYTHKKEKL IRDVAHCHGI LITSYSYIRL MQDDISRYDW HYVILDEGHK
660 670 680 690 700
IRNPNAAVTL ACKQFRTPHR IILSGSPMQN NLRELWSLFD FIFPGKLGTL
710 720 730 740 750
PVFMEQFSVP ITMGGYSNAS PVQVKTAYKC ACVLRDTINP YLLRRMKSDV
760 770 780 790 800
KMSLSLPDKN EQVLFCRLTD EQHKVYQNFV DSKEVYRILN GEMQIFSGLI
810 820 830 840 850
ALRKICNHPD LFSGGPKNLK GLPDDELEED QFGYWKRSGK MIVVESLLKI
860 870 880 890 900
WHKQGQRVLL FSQSRQMLDI LEVFLRAQKY TYLKMDGTTT IASRQPLITR
910 920 930 940 950
YNEDTSIFVF LLTTRVGGLG VNLTGANRVV IYDPDWNPST DTQARERAWR
960 970 980 990 1000
IGQKKQVTVY RLLTAGTIEE KIYHRQIFKQ FLTNRVLKDP KQRRFFKSND
1010 1020 1030 1040 1050
LYELFTLTSP DASQSTETSA IFAGTGSDVQ TPKCHLKRRI QPAFGADHDV
1060 1070 1080 1090 1100
PKRKKFPASN ISVNDATSSE EKSEAKGAEV NAVTSNRSDP LKDDPHMSSN
1110 1120 1130 1140 1150
VTSNDRLGEE TNAVSGPEEL SVISGNGECS NSSGTGKTSM PSGDESIDEK
1160 1170 1180 1190 1200
LGLSYKRERP SQAQTEAFWE NKQMENNFYK HKSKTKHHSV AEEETLEKHL
1210 1220 1230 1240 1250
RPKQKPKNSK HCRDAKFEGT RIPHLVKKRR YQKQDSENKS EAKEQSNDDY
1260 1270 1280 1290 1300
VLEKLFKKSV GVHSVMKHDA IMDGASPDYV LVEAEANRVA QDALKALRLS
1310 1320 1330 1340 1350
RQRCLGAVSG VPTWTGHRGI SGAPAGKKSR FGKKRNSNFS VQHPSSTSPT
1360 1370 1380 1390 1400
EKCQDGIMKK EGKDNVPEHF SGRAEDADSS SGPLASSSLL AKMRARNHLI
1410 1420 1430 1440 1450
LPERLESESG HLQEASALLP TTEHDDLLVE MRNFIAFQAH TDGQASTREI
1460 1470 1480 1490
LQEFESKLSA SQSCVFRELL RNLCTFHRTS GGEGIWKLKP EYC
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A7P0T9G4 | A0A7P0T9G4_HUMAN | Chimeric ERCC6-PGBD3 protein | ERCC6 | 1,440 | Annotation score: | ||
A0A7P0TA32 | A0A7P0TA32_HUMAN | Chimeric ERCC6-PGBD3 protein | ERCC6 | 224 | Annotation score: | ||
D6R9X7 | D6R9X7_HUMAN | Chimeric ERCC6-PGBD3 protein | ERCC6 | 179 | Annotation score: | ||
A0A096LNQ7 | A0A096LNQ7_HUMAN | Chimeric ERCC6-PGBD3 protein | ERCC6 | 77 | Annotation score: | ||
A0A7P0T7Y4 | A0A7P0T7Y4_HUMAN | Chimeric ERCC6-PGBD3 protein | ERCC6 | 80 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_054153 | 134 | R → W1 PublicationCorresponds to variant dbSNP:rs148095899EnsemblClinVar. | 1 | |
Natural variantiVAR_001216 | 255 | K → T1 Publication | 1 | |
Natural variantiVAR_001217 | 399 | G → D2 PublicationsCorresponds to variant dbSNP:rs2228528EnsemblClinVar. | 1 | |
Natural variantiVAR_016301 | 425 | D → A1 PublicationCorresponds to variant dbSNP:rs4253046EnsemblClinVar. | 1 | |
Natural variantiVAR_016302 | 446 | G → D1 PublicationCorresponds to variant dbSNP:rs4253047EnsemblClinVar. | 1 | |
Natural variantiVAR_036021 | 591 | P → A in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1184760254Ensembl. | 1 | |
Natural variantiVAR_036022 | 652 | R → L in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1365187961Ensembl. | 1 | |
Natural variantiVAR_001218 | 670 | R → W in CSB. 2 PublicationsCorresponds to variant dbSNP:rs202080674EnsemblClinVar. | 1 | |
Natural variantiVAR_063511 | 680 | N → D in CSB. 1 PublicationCorresponds to variant dbSNP:rs1554788393EnsemblClinVar. | 1 | |
Natural variantiVAR_063512 | 686 | W → C in CSB. 1 PublicationCorresponds to variant dbSNP:rs751292948EnsemblClinVar. | 1 | |
Natural variantiVAR_063513 | 687 | S → L in CSB. 1 PublicationCorresponds to variant dbSNP:rs1026438103EnsemblClinVar. | 1 | |
Natural variantiVAR_001219 | 851 | W → R in CSB; DNA-dependent ATPase-dead mutant; loss of chromatin remodeling activity; loss of its ability to inhibit non-homologous end joining-mediated repair and promote homologous recombination-mediated repair of DNA double-strand breaks; loss of its ability to suppress premature exit from G2/M checkpoint; abrogation of its UV-induced chromatin association. 4 PublicationsCorresponds to variant dbSNP:rs368728467EnsemblClinVar. | 1 | |
Natural variantiVAR_063514 | 871 | L → P in COFS1. 1 Publication | 1 | |
Natural variantiVAR_016303 | 942 | T → M1 PublicationCorresponds to variant dbSNP:rs2228525EnsemblClinVar. | 1 | |
Natural variantiVAR_001220 | 957 | V → G in CSB. 2 Publications | 1 | |
Natural variantiVAR_063515 | 987 | L → P in COFS1. 1 PublicationCorresponds to variant dbSNP:rs121917905EnsemblClinVar. | 1 | |
Natural variantiVAR_016304 | 1002 | Y → C1 PublicationCorresponds to variant dbSNP:rs4253206Ensembl. | 1 | |
Natural variantiVAR_036023 | 1038 | R → T in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_001221 | 1042 | P → L in CSB. 2 Publications | 1 | |
Natural variantiVAR_001222 | 1095 | P → R3 PublicationsCorresponds to variant dbSNP:rs4253208EnsemblClinVar. | 1 | |
Natural variantiVAR_001223 | 1097 | M → V2 PublicationsCorresponds to variant dbSNP:rs2228526EnsemblClinVar. | 1 | |
Natural variantiVAR_036024 | 1119 | E → Q in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_036025 | 1119 | E → V in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_001224 | 1213 | R → G3 PublicationsCorresponds to variant dbSNP:rs2228527EnsemblClinVar. | 1 | |
Natural variantiVAR_037436 | 1220 | T → I. Corresponds to variant dbSNP:rs34704611EnsemblClinVar. | 1 | |
Natural variantiVAR_016305 | 1230 | R → P1 PublicationCorresponds to variant dbSNP:rs4253211EnsemblClinVar. | 1 | |
Natural variantiVAR_016306 | 1308 | V → L1 PublicationCorresponds to variant dbSNP:rs2229761EnsemblClinVar. | 1 | |
Natural variantiVAR_016307 | 1322 | G → V1 PublicationCorresponds to variant dbSNP:rs4253219EnsemblClinVar. | 1 | |
Natural variantiVAR_037437 | 1355 | D → E. Corresponds to variant dbSNP:rs34917815EnsemblClinVar. | 1 | |
Natural variantiVAR_016308 | 1372 | G → R1 PublicationCorresponds to variant dbSNP:rs4253227EnsemblClinVar. | 1 | |
Natural variantiVAR_016309 | 1382 | G → R1 PublicationCorresponds to variant dbSNP:rs4253228Ensembl. | 1 | |
Natural variantiVAR_016310 | 1410 | G → R1 PublicationCorresponds to variant dbSNP:rs4253229Ensembl. | 1 | |
Natural variantiVAR_001225 | 1413 | Q → R2 PublicationsCorresponds to variant dbSNP:rs2228529EnsemblClinVar. | 1 | |
Natural variantiVAR_016311 | 1441 | T → I1 PublicationCorresponds to variant dbSNP:rs4253230EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L04791 mRNA Translation: AAA52397.1 AY204752 Genomic DNA Translation: AAO13487.1 AC073366 Genomic DNA No translation available. AL138760 Genomic DNA No translation available. CH471187 Genomic DNA Translation: EAW93094.1 CH471187 Genomic DNA Translation: EAW93097.1 |
CCDSi | CCDS7229.1 [Q03468-1] |
PIRi | A44224 |
RefSeqi | NP_000115.1, NM_000124.3 [Q03468-1] NP_001333369.1, NM_001346440.1 [Q03468-1] |
Genome annotation databases
Ensembli | ENST00000355832.10; ENSP00000348089.5; ENSG00000225830.16 |
GeneIDi | 2074 |
KEGGi | hsa:2074 |
MANE-Selecti | ENST00000355832.10; ENSP00000348089.5; NM_000124.4; NP_000115.1 |
UCSCi | uc001jhs.6, human [Q03468-1] uc001jhu.4, human |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L04791 mRNA Translation: AAA52397.1 AY204752 Genomic DNA Translation: AAO13487.1 AC073366 Genomic DNA No translation available. AL138760 Genomic DNA No translation available. CH471187 Genomic DNA Translation: EAW93094.1 CH471187 Genomic DNA Translation: EAW93097.1 |
CCDSi | CCDS7229.1 [Q03468-1] |
PIRi | A44224 |
RefSeqi | NP_000115.1, NM_000124.3 [Q03468-1] NP_001333369.1, NM_001346440.1 [Q03468-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4CVO | X-ray | 1.85 | A | 84-160 | [»] | |
7OO3 | electron microscopy | 2.80 | b | 1-1493 | [»] | |
7OOB | electron microscopy | 2.70 | b | 1-1493 | [»] | |
7OOP | electron microscopy | 2.90 | b | 1-1493 | [»] | |
7OPC | electron microscopy | 3.00 | b | 1-1493 | [»] | |
7OPD | electron microscopy | 3.00 | b | 1-1493 | [»] | |
AlphaFoldDBi | Q03468 | |||||
SMRi | Q03468 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108386, 214 interactors |
ComplexPortali | CPX-1099, B-WICH chromatin remodelling complex |
CORUMi | Q03468 |
DIPi | DIP-193N |
IntActi | Q03468, 26 interactors |
MINTi | Q03468 |
STRINGi | 9606.ENSP00000348089 |
PTM databases
iPTMneti | Q03468 |
PhosphoSitePlusi | Q03468 |
Genetic variation databases
BioMutai | ERCC6 |
DMDMi | 416959 |
Proteomic databases
EPDi | Q03468 |
jPOSTi | Q03468 |
MassIVEi | Q03468 |
MaxQBi | Q03468 |
PaxDbi | Q03468 |
PeptideAtlasi | Q03468 |
PRIDEi | Q03468 |
ProteomicsDBi | 18566 58213 |
Protocols and materials databases
Antibodypediai | 34972, 404 antibodies from 35 providers |
DNASUi | 2074 |
Genome annotation databases
Ensembli | ENST00000355832.10; ENSP00000348089.5; ENSG00000225830.16 |
GeneIDi | 2074 |
KEGGi | hsa:2074 |
MANE-Selecti | ENST00000355832.10; ENSP00000348089.5; NM_000124.4; NP_000115.1 |
UCSCi | uc001jhs.6, human [Q03468-1] uc001jhu.4, human |
Organism-specific databases
CTDi | 2074 |
DisGeNETi | 2074 |
GeneCardsi | ERCC6 |
GeneReviewsi | ERCC6 |
HGNCi | HGNC:3438, ERCC6 |
HPAi | ENSG00000225830, Low tissue specificity |
MalaCardsi | ERCC6 |
MIMi | 133540, phenotype 214150, phenotype 278800, phenotype 600630, phenotype 609413, gene 613761, phenotype |
neXtProti | NX_Q03468 |
OpenTargetsi | ENSG00000225830 |
Orphaneti | 90321, Cockayne syndrome type 1 90322, Cockayne syndrome type 2 90324, Cockayne syndrome type 3 1466, COFS syndrome 619, NON RARE IN EUROPE: Primary ovarian failure 178338, UV-sensitive syndrome |
PharmGKBi | PA27852 |
VEuPathDBi | HostDB:ENSG00000225830 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0387, Eukaryota |
GeneTreei | ENSGT00940000158057 |
HOGENOMi | CLU_000315_7_2_1 |
InParanoidi | Q03468 |
OMAi | HSVVKHD |
OrthoDBi | 372069at2759 |
PhylomeDBi | Q03468 |
TreeFami | TF101236 TF328011 |
Enzyme and pathway databases
PathwayCommonsi | Q03468 |
Reactomei | R-HSA-427389, ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression R-HSA-5250924, B-WICH complex positively regulates rRNA expression R-HSA-6781823, Formation of TC-NER Pre-Incision Complex R-HSA-6781827, Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-6782135, Dual incision in TC-NER R-HSA-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-73762, RNA Polymerase I Transcription Initiation |
SignaLinki | Q03468 |
SIGNORi | Q03468 |
Miscellaneous databases
BioGRID-ORCSi | 2074, 26 hits in 1068 CRISPR screens |
ChiTaRSi | ERCC6, human |
GeneWikii | ERCC6 |
GenomeRNAii | 2074 |
Pharosi | Q03468, Tbio |
PROi | PR:Q03468 |
RNActi | Q03468, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000258838, Expressed in sural nerve and 116 other tissues |
ExpressionAtlasi | Q03468, baseline and differential |
Genevisiblei | Q03468, HS |
Family and domain databases
Gene3Di | 3.40.50.10810, 1 hit 3.40.50.300, 1 hit |
InterProi | View protein in InterPro IPR014001, Helicase_ATP-bd IPR001650, Helicase_C IPR027417, P-loop_NTPase IPR038718, SNF2-like_sf IPR000330, SNF2_N |
Pfami | View protein in Pfam PF00271, Helicase_C, 1 hit PF00176, SNF2-rel_dom, 1 hit |
SMARTi | View protein in SMART SM00487, DEXDc, 1 hit SM00490, HELICc, 1 hit |
SUPFAMi | SSF52540, SSF52540, 2 hits |
PROSITEi | View protein in PROSITE PS51192, HELICASE_ATP_BIND_1, 1 hit PS51194, HELICASE_CTER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ERCC6_HUMAN | |
Accessioni | Q03468Primary (citable) accession number: Q03468 Secondary accession number(s): D3DX94, E7EV46, Q5W0L9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1993 |
Last sequence update: | October 1, 1993 | |
Last modified: | May 25, 2022 | |
This is version 221 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 10
Human chromosome 10: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families