UniProtKB - F8VPZ5 (ERCC6_MOUSE)
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 (By similarity).
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 (By similarity).
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 sites of RNA polymerase II-blocking lesions (By similarity).
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 (By similarity).
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 (By similarity).
Mediates the activation of the ATM- and CHEK2-dependent DNA damage responses thus preventing the premature exit from the G2/M checkpoint (By similarity).
Acts as a chromatin remodeler at DSBs; DNA-dependent ATPase-dependent activity is essential for this function (By similarity).
Remodels chromatin by evicting histones from chromatin flanking DSBs, limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR (By similarity).
Required for stable recruitment of ELOA and CUL5 to DNA damage sites (By similarity).
Involved in UV-induced translocation of ERCC8 to the nuclear matrix (By similarity).
Essential for neuronal differentiation and neuritogenesis; regulates transcription and chromatin remodeling activities required during neurogenesis (By similarity).
By similarityCatalytic activityi
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 528 – 535 | ATPPROSITE-ProRule annotation | 8 |
GO - Molecular functioni
- ATP binding Source: MGI
- ATP-dependent activity, acting on DNA Source: UniProtKB
- ATP-dependent chromatin remodeler activity Source: UniProtKB
- ATP hydrolysis activity Source: RHEA
- chromatin binding Source: UniProtKB
- DNA binding Source: MGI
- helicase activity Source: UniProtKB-KW
- protein-containing complex binding Source: MGI
- protein C-terminus binding Source: MGI
- protein N-terminus binding Source: MGI
- protein tyrosine kinase activator activity Source: MGI
- RNA polymerase binding Source: MGI
- sequence-specific DNA binding Source: MGI
GO - Biological processi
- base-excision repair Source: MGI
- cellular response to DNA damage stimulus Source: MGI
- chromatin remodeling Source: ComplexPortal
- DNA damage checkpoint signaling Source: UniProtKB
- DNA protection Source: MGI
- DNA repair Source: MGI
- double-strand break repair via classical nonhomologous end joining Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
- JNK cascade Source: MGI
- multicellular organism growth Source: MGI
- 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: MGI
- positive regulation of defense response to virus by host Source: MGI
- positive regulation of DNA repair Source: MGI
- positive regulation of DNA-templated transcription, elongation Source: MGI
- positive regulation of double-strand break repair via homologous recombination Source: UniProtKB
- positive regulation of gene expression Source: MGI
- positive regulation of histone acetylation Source: ComplexPortal
- positive regulation of peptidyl-serine phosphorylation of STAT protein Source: MGI
- 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: MGI
- positive regulation of transcription initiation from RNA polymerase II promoter Source: MGI
- pyrimidine dimer repair Source: MGI
- regulation of DNA-templated transcription, elongation Source: MGI
- regulation of transcription elongation from RNA polymerase II promoter Source: MGI
- response to gamma radiation Source: MGI
- response to oxidative stress Source: MGI
- response to superoxide Source: MGI
- response to toxic substance Source: MGI
- response to UV Source: MGI
- response to UV-B Source: MGI
- response to X-ray Source: MGI
- single strand break repair Source: UniProtKB
- transcription-coupled nucleotide-excision repair Source: MGI
- transcription elongation from RNA polymerase I promoter Source: MGI
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
Reactomei | R-MMU-5250924, B-WICH complex positively regulates rRNA expression R-MMU-6781823, Formation of TC-NER Pre-Incision Complex R-MMU-6782135, Dual incision in TC-NER R-MMU-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER R-MMU-73762, RNA Polymerase I Transcription Initiation |
Names & Taxonomyi
Protein namesi | Recommended name: DNA excision repair protein ERCC-6 (EC:3.6.4.-By similarity)Alternative name(s): ATP-dependent helicase ERCC6 Cockayne syndrome protein CSB |
Gene namesi | Name:Ercc6 Synonyms:Csb |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1100494, Ercc6 |
VEuPathDBi | HostDB:ENSMUSG00000054051 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Nucleus
- B-WICH complex Source: MGI
- nuclear body Source: MGI
- nucleolus Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: MGI
- transcription elongation factor complex Source: MGI
Other locations
- site of DNA damage Source: UniProtKB
Keywords - Cellular componenti
NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000448242 | 1 – 1481 | DNA excision repair protein ERCC-6Add BLAST | 1481 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 158 | Phosphoserine; by CDK2By similarity | 1 | |
Modified residuei | 170 | N6-methylated lysine; by EHMT2By similarity | 1 | |
Cross-linki | 256 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity | ||
Modified residuei | 298 | N6-methylated lysine; by EHMT2By similarity | 1 | |
Modified residuei | 428 | PhosphoserineBy similarity | 1 | |
Modified residuei | 429 | PhosphoserineBy similarity | 1 | |
Modified residuei | 444 | N6-methylated lysine; by EHMT2By similarity | 1 | |
Modified residuei | 482 | PhosphoserineBy similarity | 1 | |
Modified residuei | 485 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1047 | N6-methylated lysine; by EHMT2By similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | F8VPZ5 |
MaxQBi | F8VPZ5 |
PaxDbi | F8VPZ5 |
PRIDEi | F8VPZ5 |
ProteomicsDBi | 363699 |
PTM databases
iPTMneti | F8VPZ5 |
PhosphoSitePlusi | F8VPZ5 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000054051, Expressed in dorsal root ganglion and 90 other tissues |
ExpressionAtlasi | F8VPZ5, baseline and differential |
Genevisiblei | F8VPZ5, MM |
Interactioni
Subunit structurei
Homodimer (By similarity). Binds DNA (By similarity).
Interacts with ERCC8 (By similarity).
Interacts with RNA polymerase II; interaction is enhanced by UV irradiation (By similarity).
Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21 (By similarity).
Interacts with KIAA1530/UVSSA (By similarity).
Interacts with ELOA and CUL5; the interaction is induced by DNA damaging agents or by inhibitors of RNA polymerase II elongation (By similarity).
Interacts (via WHD region) with RIF1 (By similarity).
Interacts with SMARCC2/BAF170, SMARCB1/BAF47 and the neuron-specific chromatin remodeling complex (nBAF complex) (By similarity).
Interacts with ERCC5/XPG (via C-terminus); the interaction stimulates ERCC6/CSB binding to DNA repair bubble and ERCC6/CSB ATPase activity (By similarity). 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 (By similarity).
Interacts with CAND1, CSTF1, DDX3X, DDX5, DDX17, DDX23, DHX36, HDAC1, HNRNPU, MTA2, PRPF3, PSMD3, RBBP4, SFPQ, SMARCA1, SMARCA2, TOP1, USP7 and XRCC5 (By similarity).
By similarityGO - Molecular functioni
- protein C-terminus binding Source: MGI
- protein N-terminus binding Source: MGI
- RNA polymerase binding Source: MGI
Protein-protein interaction databases
ComplexPortali | CPX-1133, B-WICH chromatin remodelling complex |
STRINGi | 10090.ENSMUSP00000066256 |
Miscellaneous databases
RNActi | F8VPZ5, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 515 – 691 | Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST | 177 | |
Domaini | 839 – 998 | Helicase C-terminalPROSITE-ProRule annotationAdd BLAST | 160 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 506 | N-terminal domain; essential for its chromatin remodeling activityBy similarityAdd BLAST | 506 | |
Regioni | 309 – 452 | DisorderedSequence analysisAdd BLAST | 144 | |
Regioni | 1040 – 1096 | DisorderedSequence analysisAdd BLAST | 57 | |
Regioni | 1114 – 1238 | DisorderedSequence analysisAdd BLAST | 125 | |
Regioni | 1307 – 1372 | DisorderedSequence analysisAdd BLAST | 66 | |
Regioni | 1387 – 1416 | Ubiquitin-binding domain (UBD)By similarityAdd BLAST | 30 | |
Regioni | 1417 – 1481 | Winged-helix domain (WHD)By similarityAdd BLAST | 65 | |
Regioni | 1434 – 1481 | 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 matrixBy similarityAdd BLAST | 48 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 642 – 645 | DEAH boxPROSITE-ProRule annotation | 4 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 363 – 393 | Acidic residuesSequence analysisAdd BLAST | 31 | |
Compositional biasi | 401 – 421 | Basic and acidic residuesSequence analysisAdd BLAST | 21 | |
Compositional biasi | 432 – 452 | Basic and acidic residuesSequence analysisAdd BLAST | 21 | |
Compositional biasi | 1129 – 1164 | Polar residuesSequence analysisAdd BLAST | 36 | |
Compositional biasi | 1170 – 1238 | Basic and acidic residuesSequence analysisAdd BLAST | 69 | |
Compositional biasi | 1322 – 1343 | Polar residuesSequence analysisAdd BLAST | 22 | |
Compositional biasi | 1344 – 1360 | Basic and acidic residuesSequence analysisAdd BLAST | 17 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0387, Eukaryota |
GeneTreei | ENSGT00940000158057 |
HOGENOMi | CLU_000315_7_2_1 |
InParanoidi | F8VPZ5 |
OMAi | HSVVKHD |
OrthoDBi | 372069at2759 |
PhylomeDBi | F8VPZ5 |
TreeFami | TF101236 |
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 |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
10 20 30 40 50
MFHEEVPNST HPQEQDCLPS QHANAYKDMP VGQENGGVSE AGECLSSTSC
60 70 80 90 100
EYGPSTSAEA CVLAATRRGP TLLHIDRHQI PAVEPSAQAL ELQGLGVDVY
110 120 130 140 150
DQAVLEQGVL QQVDSAMHEA SCVAQLADAE KEYQSVLDDL MSCTTSLRQI
160 170 180 190 200
NKIIEQLSPQ AASNRDINRK LDSVKRQKYN KEQQLKKITA KQKRLQAILG
210 220 230 240 250
GAGVQVELDH ASLEEDDAEP GPSCLGSMLM PAQETAWEEL IRTGQMTPFG
260 270 280 290 300
TPAPQKQEKK PRKIMLNEAS GFEKYLAEQA QLSFERKKQA ATKRTAKKAI
310 320 330 340 350
VISESSRAAI ETKADQRSQV LSQTDKRLKK HSRKLQRRAL QFQGKVGLPS
360 370 380 390 400
GKKPLEPEVR PEAEGDTEGE ESGSSPTDGE EEEEQEEEEG VASLSSDDVS
410 420 430 440 450
YELKPLRKRQ KYQKKVPVQE IDDDFFPSSE EEDEAMEGRG GGRKVARRQD
460 470 480 490 500
DGDEDYYKQR LRRWNRLRLQ DKEKRLKLED DSEESDAEFD EGFKVPGFLF
510 520 530 540 550
KKLFKYQQTG VRWLWELHCQ QAGGILGDEM GLGKTIQIIA FLAGLSYSKI
560 570 580 590 600
RTRGSNYRFE GLGPTIIVCP TTVMHQWVKE FHTWWPPFRV AVLHETGSYT
610 620 630 640 650
HKKERLIRDI VYCHGVLITS YSYIRLMQDD ISRHDWHYVI LDEGHKIRNP
660 670 680 690 700
NAAVTLACKQ FRTPHRIILS GSPMQNNLRE LWSLFDFIFP GKLGTLPVFM
710 720 730 740 750
EQFSVPITMG GYSNASPVQV KTAYKCACVL RDTINPYLLR RMKSDVKMSL
760 770 780 790 800
SLPDKNEQVL FCRLTDEQHK VYQNFIDSKA VYRILNGENQ IFSGLVALRK
810 820 830 840 850
ICNHPDLFSG GPKNASGPPE DELEEEQFGH WRRSGKMIVV ESLLKIWHRQ
860 870 880 890 900
GQRVLLFSQS RQMLHILEVF LRAHKYSYLK MDGTTTIASR QPLITKYNED
910 920 930 940 950
TSIFVFLLTT RVGGLGVNLT GANRVIIYDP DWNPSTDTQA RERAWRIGQK
960 970 980 990 1000
KQVTVYRLLT AGTIEEKIYH RQIFKQFLTN RVLKDPKQRR FFKSNDLYEL
1010 1020 1030 1040 1050
FTLTSPDASQ GTETSAIFAG TGSSIQTPKC QLKKRTSTVL GTDPKCKKPP
1060 1070 1080 1090 1100
VSDTPANAAT LIGEKPKAAG ATGRSVTSGE SGPFKGDHDT NGNRASSVAF
1110 1120 1130 1140 1150
GEETDAGSTL EHLSVMSGDG KHSDSPTVDH TSRPPVEAST SEKQGSSYAG
1160 1170 1180 1190 1200
ARCQAQTEPV PMSEQMEGQF SKYKSKRKHD ASEEETTEKR PQPKQKAKNS
1210 1220 1230 1240 1250
KHCRDAKFEG TRVPHLVKKR RYRQQTSEQE GGAKDRSSDD YVLEKLFKKS
1260 1270 1280 1290 1300
VGVHSVVRHD AIIDGSSPDY VLVEAEANRV AQDALKALRL SRQQCLGAAS
1310 1320 1330 1340 1350
GVPTWTGHRG ISGAPTGVKN RFGQKRDSSL PVQHPSSLTE KTQNNMKKEG
1360 1370 1380 1390 1400
KAHTPEHFSG KEDGASVSGA PSSSSLLARM RARNHMILPE RLESDSEHLA
1410 1420 1430 1440 1450
EAAAVPPCGT EHDDLLVDMR NFIAFQAQVD GQASTQEILQ EFESKLSVAQ
1460 1470 1480
SCVFRELLRN LCNFHRTPGG EGIWKLKPEY C
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A2I3BQP1 | A0A2I3BQP1_MOUSE | DNA excision repair protein ERCC-6 | Ercc6 | 48 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC154412 Genomic DNA No translation available. BC132447 mRNA Translation: AAI32448.1 |
CCDSi | CCDS36868.1 |
RefSeqi | NP_001074690.1, NM_001081221.1 XP_006519183.1, XM_006519120.3 |
Genome annotation databases
Ensembli | ENSMUST00000066807; ENSMUSP00000066256; ENSMUSG00000054051 |
GeneIDi | 319955 |
KEGGi | mmu:319955 |
UCSCi | uc007sze.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AC154412 Genomic DNA No translation available. BC132447 mRNA Translation: AAI32448.1 |
CCDSi | CCDS36868.1 |
RefSeqi | NP_001074690.1, NM_001081221.1 XP_006519183.1, XM_006519120.3 |
3D structure databases
AlphaFoldDBi | F8VPZ5 |
SMRi | F8VPZ5 |
ModBasei | Search... |
Protein-protein interaction databases
ComplexPortali | CPX-1133, B-WICH chromatin remodelling complex |
STRINGi | 10090.ENSMUSP00000066256 |
PTM databases
iPTMneti | F8VPZ5 |
PhosphoSitePlusi | F8VPZ5 |
Proteomic databases
EPDi | F8VPZ5 |
MaxQBi | F8VPZ5 |
PaxDbi | F8VPZ5 |
PRIDEi | F8VPZ5 |
ProteomicsDBi | 363699 |
Protocols and materials databases
Antibodypediai | 34972, 404 antibodies from 35 providers |
DNASUi | 319955 |
Genome annotation databases
Ensembli | ENSMUST00000066807; ENSMUSP00000066256; ENSMUSG00000054051 |
GeneIDi | 319955 |
KEGGi | mmu:319955 |
UCSCi | uc007sze.1, mouse |
Organism-specific databases
CTDi | 2074 |
MGIi | MGI:1100494, Ercc6 |
VEuPathDBi | HostDB:ENSMUSG00000054051 |
Phylogenomic databases
eggNOGi | KOG0387, Eukaryota |
GeneTreei | ENSGT00940000158057 |
HOGENOMi | CLU_000315_7_2_1 |
InParanoidi | F8VPZ5 |
OMAi | HSVVKHD |
OrthoDBi | 372069at2759 |
PhylomeDBi | F8VPZ5 |
TreeFami | TF101236 |
Enzyme and pathway databases
Reactomei | R-MMU-5250924, B-WICH complex positively regulates rRNA expression R-MMU-6781823, Formation of TC-NER Pre-Incision Complex R-MMU-6782135, Dual incision in TC-NER R-MMU-6782210, Gap-filling DNA repair synthesis and ligation in TC-NER R-MMU-73762, RNA Polymerase I Transcription Initiation |
Miscellaneous databases
BioGRID-ORCSi | 319955, 7 hits in 110 CRISPR screens |
PROi | PR:F8VPZ5 |
RNActi | F8VPZ5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000054051, Expressed in dorsal root ganglion and 90 other tissues |
ExpressionAtlasi | F8VPZ5, baseline and differential |
Genevisiblei | F8VPZ5, MM |
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_MOUSE | |
Accessioni | F8VPZ5Primary (citable) accession number: F8VPZ5 Secondary accession number(s): A3KMN2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 16, 2019 |
Last sequence update: | September 21, 2011 | |
Last modified: | May 25, 2022 | |
This is version 86 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families