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Protein

DNA excision repair protein ERCC-8

Gene

ERCC8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair. The CSA complex (DCX(ERCC8) complex) promotes the ubiquitination and subsequent proteasomal degradation of ERCC6 in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair. It is required for the recruitment of XAB2, HMGN1 and TCEA1/TFIIS to a transcription-coupled repair complex which removes RNA polymerase II-blocking lesions from the transcribed strand of active genes.3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • protein-containing complex binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processDNA damage, DNA repair, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-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-8951664 Neddylation
SignaLinkiQ13216
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
DNA excision repair protein ERCC-8
Alternative name(s):
Cockayne syndrome WD repeat protein CSA
Gene namesi
Name:ERCC8
Synonyms:CKN1, CSA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000049167.13
HGNCiHGNC:3439 ERCC8
MIMi609412 gene
neXtProtiNX_Q13216

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Cockayne syndrome A (CSA)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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 mental retardation. 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.
See also OMIM:216400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063507160A → T in CSA. 1 PublicationCorresponds to variant dbSNP:rs281875222EnsemblClinVar.1
Natural variantiVAR_025380160A → V in CSA. 1 PublicationCorresponds to variant dbSNP:rs121434325EnsemblClinVar.1
Natural variantiVAR_063508194W → C in CSA. 1 PublicationCorresponds to variant dbSNP:rs281875223EnsemblClinVar.1
Natural variantiVAR_063509202L → S in CSA. 1 PublicationCorresponds to variant dbSNP:rs281875224EnsemblClinVar.1
Natural variantiVAR_025381205A → P in CSA. 1 PublicationCorresponds to variant dbSNP:rs121434326EnsemblClinVar.1
Natural variantiVAR_063510266D → G in CSA. 1 PublicationCorresponds to variant dbSNP:rs281875225EnsemblClinVar.1
UV-sensitive syndrome 2 (UVSS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors.
See also OMIM:614621
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068177361W → C in UVSS2. 1 PublicationCorresponds to variant dbSNP:rs281875221EnsemblClinVar.1

Keywords - Diseasei

Cockayne syndrome, Deafness, Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi1161
GeneReviewsiERCC8
MalaCardsiERCC8
MIMi216400 phenotype
614621 phenotype
OpenTargetsiENSG00000049167
Orphaneti90321 Cockayne syndrome type 1
90322 Cockayne syndrome type 2
90324 Cockayne syndrome type 3
178338 UV-sensitive syndrome
PharmGKBiPA27853

Polymorphism and mutation databases

BioMutaiERCC8
DMDMi3121917

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000509701 – 396DNA excision repair protein ERCC-8Add BLAST396

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei390PhosphoserineCombined sources1
Modified residuei391PhosphoserineCombined sources1
Modified residuei392PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ13216
MaxQBiQ13216
PaxDbiQ13216
PeptideAtlasiQ13216
PRIDEiQ13216
ProteomicsDBi59228
59229 [Q13216-2]

PTM databases

iPTMnetiQ13216
PhosphoSitePlusiQ13216

Expressioni

Gene expression databases

BgeeiENSG00000049167 Expressed in 171 organ(s), highest expression level in kidney
CleanExiHS_ERCC8
ExpressionAtlasiQ13216 baseline and differential
GenevisibleiQ13216 HS

Organism-specific databases

HPAiHPA029328

Interactioni

Subunit structurei

Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Interacts with ERCC6 and KIAA1530/UVSSA. Interacts with a subunit of RNA polymerase II TFIIH. Interacts directly with DDB1 (PubMed:22118460).4 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi107581, 45 interactors
CORUMiQ13216
DIPiDIP-291N
IntActiQ13216, 10 interactors
MINTiQ13216
STRINGi9606.ENSP00000265038

Structurei

Secondary structure

1396
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ13216
SMRiQ13216
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati33 – 73WD 1Add BLAST41
Repeati88 – 129WD 2Add BLAST42
Repeati133 – 173WD 3Add BLAST41
Repeati177 – 216WD 4Add BLAST40
Repeati235 – 274WD 5Add BLAST40
Repeati281 – 321WD 6Add BLAST41
Repeati325 – 363WD 7Add BLAST39

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG4283 Eukaryota
ENOG410Z0MQ LUCA
GeneTreeiENSGT00390000009065
HOGENOMiHOG000248233
HOVERGENiHBG005409
InParanoidiQ13216
KOiK10570
OMAiTMLRGHY
OrthoDBiEOG091G09HW
PhylomeDBiQ13216
TreeFamiTF101237

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR020472 G-protein_beta_WD-40_rep
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF00400 WD40, 4 hits
PRINTSiPR00320 GPROTEINBRPT
SMARTiView protein in SMART
SM00320 WD40, 5 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 2 hits
PS50082 WD_REPEATS_2, 5 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q13216-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MLGFLSARQT GLEDPLRLRR AESTRRVLGL ELNKDRDVER IHGGGINTLD
60 70 80 90 100
IEPVEGRYML SGGSDGVIVL YDLENSSRQS YYTCKAVCSI GRDHPDVHRY
110 120 130 140 150
SVETVQWYPH DTGMFTSSSF DKTLKVWDTN TLQTADVFNF EETVYSHHMS
160 170 180 190 200
PVSTKHCLVA VGTRGPKVQL CDLKSGSCSH ILQGHRQEIL AVSWSPRYDY
210 220 230 240 250
ILATASADSR VKLWDVRRAS GCLITLDQHN GKKSQAVESA NTAHNGKVNG
260 270 280 290 300
LCFTSDGLHL LTVGTDNRMR LWNSSNGENT LVNYGKVCNN SKKGLKFTVS
310 320 330 340 350
CGCSSEFVFV PYGSTIAVYT VYSGEQITML KGHYKTVDCC VFQSNFQELY
360 370 380 390
SGSRDCNILA WVPSLYEPVP DDDETTTKSQ LNPAFEDAWS SSDEEG
Length:396
Mass (Da):44,055
Last modified:November 1, 1996 - v1
Checksum:iEC962D56226D717B
GO
Isoform 2 (identifier: Q13216-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     185-205: HRQEILAVSWSPRYDYILATA → IFILFQTATTLSKRFNKKKRY
     206-396: Missing.

Note: No experimental confirmation available.
Show »
Length:205
Mass (Da):23,182
Checksum:i6553CE607A392576
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JNT2C9JNT2_HUMAN
DNA excision repair protein ERCC-8
ERCC8
134Annotation score:
A0A2R8YD24A0A2R8YD24_HUMAN
DNA excision repair protein ERCC-8
ERCC8
159Annotation score:
A0A2R8YEZ3A0A2R8YEZ3_HUMAN
DNA excision repair protein ERCC-8
ERCC8
137Annotation score:
A0A2R8Y5I1A0A2R8Y5I1_HUMAN
DNA excision repair protein ERCC-8
ERCC8
189Annotation score:
G3XAG7G3XAG7_HUMAN
DNA excision repair protein ERCC-8
ERCC8 hCG_2003063
57Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053392150S → C. Corresponds to variant dbSNP:rs167037Ensembl.1
Natural variantiVAR_063507160A → T in CSA. 1 PublicationCorresponds to variant dbSNP:rs281875222EnsemblClinVar.1
Natural variantiVAR_025380160A → V in CSA. 1 PublicationCorresponds to variant dbSNP:rs121434325EnsemblClinVar.1
Natural variantiVAR_063508194W → C in CSA. 1 PublicationCorresponds to variant dbSNP:rs281875223EnsemblClinVar.1
Natural variantiVAR_016319200Y → C1 PublicationCorresponds to variant dbSNP:rs4647105Ensembl.1
Natural variantiVAR_063509202L → S in CSA. 1 PublicationCorresponds to variant dbSNP:rs281875224EnsemblClinVar.1
Natural variantiVAR_025381205A → P in CSA. 1 PublicationCorresponds to variant dbSNP:rs121434326EnsemblClinVar.1
Natural variantiVAR_063510266D → G in CSA. 1 PublicationCorresponds to variant dbSNP:rs281875225EnsemblClinVar.1
Natural variantiVAR_068177361W → C in UVSS2. 1 PublicationCorresponds to variant dbSNP:rs281875221EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013914185 – 205HRQEI…ILATA → IFILFQTATTLSKRFNKKKR Y in isoform 2. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_013915206 – 396Missing in isoform 2. 1 PublicationAdd BLAST191

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28413 mRNA Translation: AAA82605.1
CR536563 mRNA Translation: CAG38800.1
BT020021 mRNA Translation: AAV38824.1
AY213194 Genomic DNA Translation: AAO21128.1
AK314511 mRNA Translation: BAG37111.1
CH471123 Genomic DNA Translation: EAW55004.1
BC009793 mRNA Translation: AAH09793.1
CCDSiCCDS3978.1 [Q13216-1]
PIRiA57090
RefSeqiNP_000073.1, NM_000082.3 [Q13216-1]
NP_001007235.1, NM_001007234.2 [Q13216-2]
UniGeneiHs.435237

Genome annotation databases

EnsembliENST00000265038; ENSP00000265038; ENSG00000049167 [Q13216-1]
GeneIDi1161
KEGGihsa:1161
UCSCiuc003jsm.4 human [Q13216-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
Mendelian genes excision repair cross-complementing rodent repair deficiency, complementation group 8 (ERCC8)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28413 mRNA Translation: AAA82605.1
CR536563 mRNA Translation: CAG38800.1
BT020021 mRNA Translation: AAV38824.1
AY213194 Genomic DNA Translation: AAO21128.1
AK314511 mRNA Translation: BAG37111.1
CH471123 Genomic DNA Translation: EAW55004.1
BC009793 mRNA Translation: AAH09793.1
CCDSiCCDS3978.1 [Q13216-1]
PIRiA57090
RefSeqiNP_000073.1, NM_000082.3 [Q13216-1]
NP_001007235.1, NM_001007234.2 [Q13216-2]
UniGeneiHs.435237

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4A11X-ray3.31B1-396[»]
ProteinModelPortaliQ13216
SMRiQ13216
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107581, 45 interactors
CORUMiQ13216
DIPiDIP-291N
IntActiQ13216, 10 interactors
MINTiQ13216
STRINGi9606.ENSP00000265038

PTM databases

iPTMnetiQ13216
PhosphoSitePlusiQ13216

Polymorphism and mutation databases

BioMutaiERCC8
DMDMi3121917

Proteomic databases

EPDiQ13216
MaxQBiQ13216
PaxDbiQ13216
PeptideAtlasiQ13216
PRIDEiQ13216
ProteomicsDBi59228
59229 [Q13216-2]

Protocols and materials databases

DNASUi1161
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265038; ENSP00000265038; ENSG00000049167 [Q13216-1]
GeneIDi1161
KEGGihsa:1161
UCSCiuc003jsm.4 human [Q13216-1]

Organism-specific databases

CTDi1161
DisGeNETi1161
EuPathDBiHostDB:ENSG00000049167.13
GeneCardsiERCC8
GeneReviewsiERCC8
H-InvDBiHIX0004887
HGNCiHGNC:3439 ERCC8
HPAiHPA029328
MalaCardsiERCC8
MIMi216400 phenotype
609412 gene
614621 phenotype
neXtProtiNX_Q13216
OpenTargetsiENSG00000049167
Orphaneti90321 Cockayne syndrome type 1
90322 Cockayne syndrome type 2
90324 Cockayne syndrome type 3
178338 UV-sensitive syndrome
PharmGKBiPA27853
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4283 Eukaryota
ENOG410Z0MQ LUCA
GeneTreeiENSGT00390000009065
HOGENOMiHOG000248233
HOVERGENiHBG005409
InParanoidiQ13216
KOiK10570
OMAiTMLRGHY
OrthoDBiEOG091G09HW
PhylomeDBiQ13216
TreeFamiTF101237

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-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-8951664 Neddylation
SignaLinkiQ13216

Miscellaneous databases

ChiTaRSiERCC8 human
GeneWikiiERCC8_(gene)
GenomeRNAii1161
PROiPR:Q13216
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000049167 Expressed in 171 organ(s), highest expression level in kidney
CleanExiHS_ERCC8
ExpressionAtlasiQ13216 baseline and differential
GenevisibleiQ13216 HS

Family and domain databases

Gene3Di2.130.10.10, 1 hit
InterProiView protein in InterPro
IPR020472 G-protein_beta_WD-40_rep
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PfamiView protein in Pfam
PF00400 WD40, 4 hits
PRINTSiPR00320 GPROTEINBRPT
SMARTiView protein in SMART
SM00320 WD40, 5 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 2 hits
PS50082 WD_REPEATS_2, 5 hits
PS50294 WD_REPEATS_REGION, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiERCC8_HUMAN
AccessioniPrimary (citable) accession number: Q13216
Secondary accession number(s): B2RB64, Q6FHX5, Q96GB9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 178 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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