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UniProtKB/Swiss-Prot Q03468 (ERCC6_HUMAN)
Last modified
November 25, 2008.
Version 97.
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90%,
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Names and origin
| Protein names | Recommended name: DNA excision repair protein ERCC-6 EC=3.6.1.- Alternative name(s): ATP-dependent helicase ERCC6 Cockayne syndrome protein CSB | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1493 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Is involved in the preferential repair of active genes. Presumed DNA or RNA unwinding function. Corrects the UV survival and RNA synthesis after UV exposure of Cockayne syndrome complementation group B. |
| Subunit structure | Interacts with the CSA protein and a subunit of RNA polymerase II TFIIH. |
| Subcellular location | NucleusProbable. |
| Post-translational modification | Phosphorylated upon DNA damage, probably by ATM or ATR. |
| Involvement in disease | Defects in ERCC6 are the cause of Cockayne syndrome type B (CSB) [MIM:133540]. Cockayne syndrome is 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 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. Defects in ERCC6 are the cause of cerebro-oculo-facio-skeletal syndrome type 1 (COFS1) [MIM:214150]; also known as COFS syndrome or Pena-Shokeir syndrome type 2. 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. Defects in ERCC6 are a cause of De Sanctis-Cacchione syndrome (DSC) [MIM:278800]; also known as xerodermic idiocy. DSC is an autosomal recessive syndrome consisting of xeroderma pigmentosum associated with mental retardation, retarded growth, gonadal hypoplasia and sometimes neurologic complications. Genetic variation in ERCC6 is associated with susceptibility to age-related macular degeneration type 5 (ARMD5) [MIM:609413]. ARMD is 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 (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Defects in ERCC6 are a cause of UV-sensitive syndrome (UVS) [MIM:600630]. UVS is a rare autosomal recessive disorder characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors. |
| Sequence similarities | Belongs to the SNF2/RAD54 helicase family. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1493 | 1493 | DNA excision repair protein ERCC-6 | PRO_0000074314 | |||||
Regions | |||||||||
| Domain | 519 – 695 | 177 | Helicase ATP-binding | ||||||
| Domain | 843 – 1002 | 160 | Helicase C-terminal | ||||||
| Nucleotide binding | 532 – 539 | 8 | ATP Potential | ||||||
| Motif | 466 – 481 | 16 | Nuclear localization signal Potential | ||||||
| Motif | 646 – 649 | 4 | DEGH box | ||||||
| Motif | 1038 – 1055 | 18 | Nuclear localization signal Potential | ||||||
| Compositional bias | 356 – 394 | 39 | Asp/Glu-rich (acidic) | ||||||
| Compositional bias | 442 – 446 | 5 | Gly-rich | ||||||
Amino acid modifications | |||||||||
| Modified residue | 158 | 1 | Phosphoserine | ||||||
| Modified residue | 429 | 1 | Phosphoserine | ||||||
| Modified residue | 430 | 1 | Phosphoserine | ||||||
| Modified residue | 486 | 1 | Phosphoserine | ||||||
| Modified residue | 489 | 1 | Phosphoserine | ||||||
| Modified residue | 1142 | 1 | Phosphoserine | ||||||
| Modified residue | 1348 | 1 | Phosphoserine | ||||||
| Modified residue | 1461 | 1 | Phosphoserine | ||||||
Natural variations | |||||||||
| Natural variant | 255 | 1 | K → T | VAR_001216 | |||||
| Natural variant | 399 | 1 | G → D: dbSNP rs2228528. | VAR_001217 | |||||
| Natural variant | 425 | 1 | D → A: dbSNP rs4253046. | VAR_016301 | |||||
| Natural variant | 446 | 1 | G → D: dbSNP rs4253047. | VAR_016302 | |||||
| Natural variant | 591 | 1 | P → A in a colorectal cancer sample; somatic mutation. | VAR_036021 | |||||
| Natural variant | 652 | 1 | R → L in a colorectal cancer sample; somatic mutation. | VAR_036022 | |||||
| Natural variant | 670 | 1 | R → W in CSB. | VAR_001218 | |||||
| Natural variant | 851 | 1 | W → R in CSB. | VAR_001219 | |||||
| Natural variant | 942 | 1 | T → M: dbSNP rs2228525. | VAR_016303 | |||||
| Natural variant | 957 | 1 | V → G in CSB. | VAR_001220 | |||||
| Natural variant | 1002 | 1 | Y → C: dbSNP rs4253206. | VAR_016304 | |||||
| Natural variant | 1038 | 1 | R → T in a breast cancer sample; somatic mutation. | VAR_036023 | |||||
| Natural variant | 1042 | 1 | P → L in CSB. | VAR_001221 | |||||
| Natural variant | 1095 | 1 | P → R: dbSNP rs4253208. | VAR_001222 | |||||
| Natural variant | 1097 | 1 | M → V: dbSNP rs2228526. | VAR_001223 | |||||
| Natural variant | 1119 | 1 | E → Q in a breast cancer sample; somatic mutation. | VAR_036024 | |||||
| Natural variant | 1119 | 1 | E → V in a breast cancer sample; somatic mutation. | VAR_036025 | |||||
| Natural variant | 1213 | 1 | R → G: dbSNP rs2228527. | VAR_001224 | |||||
| Natural variant | 1220 | 1 | T → I: dbSNP rs34704611. | VAR_037436 | |||||
| Natural variant | 1230 | 1 | R → P: dbSNP rs4253211. | VAR_016305 | |||||
| Natural variant | 1308 | 1 | V → L: dbSNP rs2229761. | VAR_016306 | |||||
| Natural variant | 1322 | 1 | G → V: dbSNP rs4253219. | VAR_016307 | |||||
| Natural variant | 1355 | 1 | D → E: dbSNP rs34917815. | VAR_037437 | |||||
| Natural variant | 1372 | 1 | G → R: dbSNP rs4253227. | VAR_016308 | |||||
| Natural variant | 1382 | 1 | G → R: dbSNP rs4253228. | VAR_016309 | |||||
| Natural variant | 1410 | 1 | G → R: dbSNP rs4253229. | VAR_016310 | |||||
| Natural variant | 1413 | 1 | Q → R: dbSNP rs2228529. | VAR_001225 | |||||
| Natural variant | 1441 | 1 | T → I: dbSNP rs4253230. | VAR_016311 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes." Troelstra C., van Gool A., de Wit J., Vermeulen W., Bootsma D., Hoeijmakers J.H.J. Cell 71:939-953(1992) [PubMed: 1339317] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. |
| [2] | "Structure and expression of the excision repair gene ERCC6, involved in the human disorder Cockayne's syndrome group B." Troelstra C., Hesen V., Bootsma D., Hoeijmakers J.H.J. Nucleic Acids Res. 21:419-426(1993) [PubMed: 8382798] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Livingston R.J., Daniels M.R., Montoya M.A., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASP-399; ALA-425; ASP-446; MET-942; CYS-1002; ARG-1095; VAL-1097; GLY-1213; PRO-1230; LEU-1308; VAL-1322; ARG-1372; ARG-1382; ARG-1410; ARG-1413 AND ILE-1441. |
| [4] | "The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. Rogers J.Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy." Cleaver J.E., Thompson L.H., Richardson A.S., States J.C. Hum. Mutat. 14:9-22(1999) [PubMed: 10447254] [Abstract] Cited for: REVIEW ON VARIANTS CSB. |
| [6] | "A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158, MASS SPECTROMETRY. Tissue: Epithelium. |
| [7] | "Phosphoproteome analysis of the human mitotic spindle." Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R. Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006) [PubMed: 16565220] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486, MASS SPECTROMETRY. Tissue: Epithelium. |
| [8] | "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158, MASS SPECTROMETRY. Tissue: Epithelium. |
| [9] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1461, MASS SPECTROMETRY. |
| [10] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158; SER-429; SER-430; SER-486; SER-489; SER-1142 AND SER-1348, MASS SPECTROMETRY. |
| [11] | "Molecular analysis of mutations in the CSB (ERCC6) gene in patients with Cockayne syndrome." Mallery D.L., Tanganelli B., Colella S., Steingrimsdottir H., van Gool A.J., Troelstra C., Stefanini M., Lehmann A.R. Am. J. Hum. Genet. 62:77-85(1998) [PubMed: 9443879] [Abstract] Cited for: VARIANTS CSB TRP-670; ARG-851; GLY-957 AND LEU-1042, VARIANTS THR-255; ASP-399; ARG-1095; VAL-1097; GLY-1213 AND ARG-1413. |
| [12] | "Manitoba aboriginal kindred with original cerebro-oculo-facio-skeletal syndrome has a mutation in the Cockayne syndrome group B (CSB) gene." Meira L.B., Graham J.M. Jr., Greenberg C.R., Busch D.B., Doughty A.T.B., Ziffer D.W., Coleman D.M., Savre-Train I., Friedberg E.C. Am. J. Hum. Genet. 66:1221-1228(2000) [PubMed: 10739753] [Abstract] Cited for: DISEASE. |
| [13] | "Identical mutations in the CSB gene associated with either Cockayne syndrome or the DeSanctis-Cacchione variant of xeroderma pigmentosum." Colella S., Nardo T., Botta E., Lehmann A.R., Stefanini M. Hum. Mol. Genet. 9:1171-1175(2000) [PubMed: 10767341] [Abstract] Cited for: DISEASE. |
| [14] | "Complete absence of Cockayne syndrome group B gene product gives rise to UV-sensitive syndrome but not Cockayne syndrome." Horibata K., Iwamoto Y., Kuraoka I., Jaspers N.G.J., Kurimasa A., Oshimura M., Ichihashi M., Tanaka K. Proc. Natl. Acad. Sci. U.S.A. 101:15410-15415(2004) [PubMed: 15486090] [Abstract] Cited for: INVOLVEMENT IN UVS. |
| [15] | "Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition." Tuo J., Ning B., Bojanowski C.M., Lin Z.-N., Ross R.J., Reed G.F., Shen D., Jiao X., Zhou M., Chew E.Y., Kadlubar F.F., Chan C.-C. |

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