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ERCC4 (xeroderma pigmentosum, complementation group F)

Identity

Other namesXPF (xeroderma pigmentosum, complementation group F)
ERCC4
HGNC (Hugo) ERCC4
LocusID (NCBI) 2072
Location 16p13.12
Location_base_pair Starts at 14014014 and ends at 14046205 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  XPF (16p13) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

DNA/RNA

Description 28.2 kb
Transcription 2881 bp =D0 11 exons

Protein

Description
  • xeroderma pigmentosum group F complementing factor; DNA-repair protein complementing XPF cells 905 amino acids; form a stable complex with the ERCC1 protein; The XPF protein and the ERCC1 protein form a complex that exhibits structure specific endonuclease activity that is responsible for the 5' incision during the NER reaction. XPF-ERCC1 also binds to XPA (through ERCC1) and to RPA (through XPF) but not preferentially to damaged DNA. At the site of a lesion Nucleotide Excision Repair (NER) proteins create a DNA bubble structure over a length of approximately 25 nucleotides and the XPG protein incises the damaged DNA strand 0-2 nucleotides 3' to the ssDNA-dsDNA junction. In most studies the 3'-incision made by the XPG protein appeared to be made prior to and independently of the 5'-incision by XPF-ERCC1. XP-F patients have a relatively mild XP phenotype without neurological abnormalities. Cells from XP-F patients are slightly UV-sensitive and exhibit low levels of repair initially after UV-irradiation.
  • The XPF protein is a single-stranded DNA endonuclease that is also involved in a pathway of recombination repair of DNA interstrand crosslinks.
    • Homology Substantial homology with the eucaryotic DNA repair and recombination proteins MEI-9 (Drosophila melanogaster), Rad16 (Saccharomyces cerevisae) and Rad1 (Schizosaccharomyces pombe).

    Mutations

    Germinal 9 point mutations ; 3 small deletions ; 1 small insertion ; 1 gross deletion

    Implicated in

    Entity xeroderma pigmentosum, XP group F
    Disease Early skin tumours in XPF patients
      

    External links

    Nomenclature
    HGNC (Hugo)ERCC4   3436
    Cards
    AtlasXPFID299
    Entrez_Gene (NCBI)ERCC4  2072  excision repair cross-complementation group 4
    GeneCards (Weizmann)ERCC4
    Ensembl (Hinxton)ENSG00000175595 [Gene_View]  chr16:14014014-14046205 [Contig_View]  ERCC4 [Vega]
    ICGC DataPortalENSG00000175595
    cBioPortalERCC4
    AceView (NCBI)ERCC4
    Genatlas (Paris)ERCC4
    WikiGenes2072
    SOURCE (Princeton)NM_005236
    Genomic and cartography
    GoldenPath (UCSC)ERCC4  -  16p13.12   chr16:14014014-14046205 +  16p13.3   [Description]    (hg19-Feb_2009)
    EnsemblERCC4 - 16p13.3 [CytoView]
    Mapping of homologs : NCBIERCC4 [Mapview]
    OMIM133520   278760   610965   615272   
    Gene and transcription
    Genbank (Entrez)AI470593 AK289726 AK301930 AK308341 BC020741
    RefSeq transcript (Entrez)NM_005236
    RefSeq genomic (Entrez)AC_000148 NC_000016 NC_018927 NG_011442 NT_010393 NW_001838343 NW_004929400
    Consensus coding sequences : CCDS (NCBI)ERCC4
    Cluster EST : UnigeneHs.567265 [ NCBI ]
    CGAP (NCI)Hs.567265
    Alternative Splicing : Fast-db (Paris)GSHG0010969
    Alternative Splicing GalleryENSG00000175595
    Gene ExpressionERCC4 [ NCBI-GEO ]     ERCC4 [ SEEK ]   ERCC4 [ MEM ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ92889 (Uniprot)
    NextProtQ92889  [Medical]
    With graphics : InterProQ92889
    Splice isoforms : SwissVarQ92889 (Swissvar)
    Catalytic activity : Enzyme3.1.-.- [ Enzyme-Expasy ]   3.1.-.-3.1.-.- [ IntEnz-EBI ]   3.1.-.- [ BRENDA ]   3.1.-.- [ KEGG ]   
    Domains : Interpro (EBI)DNA_repair_nuc_XPF/helicase [organisation]   ERCC4_domain [organisation]   Rad1 [organisation]   Restrct_endonuc-II-like [organisation]   RuvA_2-like [organisation]  
    Related proteins : CluSTrQ92889
    Domain families : Pfam (Sanger)ERCC4 (PF02732)   
    Domain families : Pfam (NCBI)pfam02732   
    Domain families : Smart (EMBL)ERCC4 (SM00891)  
    DMDM Disease mutations2072
    Blocks (Seattle)Q92889
    PDB (SRS)1Z00    2A1J    2AQ0    2KN7   
    PDB (PDBSum)1Z00    2A1J    2AQ0    2KN7   
    PDB (IMB)1Z00    2A1J    2AQ0    2KN7   
    PDB (RSDB)1Z00    2A1J    2AQ0    2KN7   
    Human Protein AtlasENSG00000175595 [gene] [tissue] [antibody] [cell] [cancer]
    Peptide AtlasQ92889
    HPRD00594
    IPIIPI00219179   IPI00657932   
    Protein Interaction databases
    DIP (DOE-UCLA)Q92889
    IntAct (EBI)Q92889
    FunCoupENSG00000175595
    BioGRIDERCC4
    InParanoidQ92889
    Interologous Interaction database Q92889
    IntegromeDBERCC4
    STRING (EMBL)ERCC4
    Ontologies - Pathways
    Ontology : AmiGOsingle-stranded DNA endodeoxyribonuclease activity  nucleotide-excision repair complex  nucleotide-excision repair factor 1 complex  resolution of meiotic recombination intermediates  nucleotide-excision repair, DNA damage removal  telomere maintenance  double-strand break repair via homologous recombination  DNA catabolic process, endonucleolytic  DNA catabolic process, endonucleolytic  chromosome, telomeric region  nuclear chromosome, telomeric region  TFIID-class transcription factor binding  damaged DNA binding  single-stranded DNA binding  endodeoxyribonuclease activity  endodeoxyribonuclease activity  protein binding  nucleus  nucleoplasm  transcription factor TFIID complex  DNA repair  DNA repair  transcription-coupled nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair, DNA incision, 3'-to lesion  nucleotide-excision repair, DNA incision, 5'-to lesion  protein C-terminus binding  response to UV  UV protection  telomere maintenance via telomere shortening  negative regulation of telomere maintenance  nucleotide-excision repair, DNA incision  structure-specific DNA binding  protein N-terminus binding  nucleotide-excision repair involved in interstrand cross-link repair  
    Ontology : EGO-EBIsingle-stranded DNA endodeoxyribonuclease activity  nucleotide-excision repair complex  nucleotide-excision repair factor 1 complex  resolution of meiotic recombination intermediates  nucleotide-excision repair, DNA damage removal  telomere maintenance  double-strand break repair via homologous recombination  DNA catabolic process, endonucleolytic  DNA catabolic process, endonucleolytic  chromosome, telomeric region  nuclear chromosome, telomeric region  TFIID-class transcription factor binding  damaged DNA binding  single-stranded DNA binding  endodeoxyribonuclease activity  endodeoxyribonuclease activity  protein binding  nucleus  nucleoplasm  transcription factor TFIID complex  DNA repair  DNA repair  transcription-coupled nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair  nucleotide-excision repair, DNA incision, 3'-to lesion  nucleotide-excision repair, DNA incision, 5'-to lesion  protein C-terminus binding  response to UV  UV protection  telomere maintenance via telomere shortening  negative regulation of telomere maintenance  nucleotide-excision repair, DNA incision  structure-specific DNA binding  protein N-terminus binding  nucleotide-excision repair involved in interstrand cross-link repair  
    Pathways : KEGGNucleotide excision repair    Fanconi anemia pathway   
    Protein Interaction DatabaseERCC4
    Wikipedia pathwaysERCC4
    Gene fusion - rearrangments
    Polymorphisms : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)ERCC4
    snp3D : Map Gene to Disease2072
    SNP (GeneSNP Utah)ERCC4
    SNP : HGBaseERCC4
    Genetic variants : HAPMAPERCC4
    Exome VariantERCC4
    1000_GenomesERCC4 
    ICGC programENSG00000175595 
    Cancer Gene: CensusERCC4 
    Somatic Mutations in Cancer : COSMICERCC4 
    CONAN: Copy Number AnalysisERCC4 
    Mutations and Diseases : HGMDERCC4
    Genomic VariantsERCC4  ERCC4 [DGVbeta]
    dbVarERCC4
    ClinVarERCC4
    Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
    Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
    Diseases
    OMIM133520    278760    610965    615272   
    MedgenERCC4
    GENETestsERCC4
    Disease Genetic AssociationERCC4
    Huge Navigator ERCC4 [HugePedia]  ERCC4 [HugeCancerGEM]
    General knowledge
    Homologs : HomoloGeneERCC4
    Homology/Alignments : Family Browser (UCSC)ERCC4
    Phylogenetic Trees/Animal Genes : TreeFamERCC4
    Chemical/Protein Interactions : CTD2072
    Chemical/Pharm GKB GenePA27850
    Clinical trialERCC4
    Cancer Resource (Charite)ENSG00000175595
    Other databases
    Probes
    ProbeCancer Cytogenetics (Bari)
    Litterature
    PubMed170 Pubmed reference(s) in Entrez
    CoreMineERCC4
    iHOPERCC4
    OncoSearchERCC4

    Bibliography

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    Yang LL, Kouri RE, Curren RD
    Carcinogenesis. 1984 ; 5 (2) : 291-294.
    PMID 6321052
     
    Late onset of skin cancers in 2 xeroderma pigmentosum group F siblings and a review of 30 Japanese xeroderma pigmentosum patients in groups D, E and F.
    Kondo S, Mamada A, Miyamoto C, Keong CH, Satoh Y, Fujiwara Y
    Photo-dermatology. 1989 ; 6 (2) : 89-95.
    PMID 2664729
     
    Human chromosome 15 confers partial complementation of phenotypes to xeroderma pigmentosum group F cells.
    Saxon PJ, Schultz RA, Stanbridge EJ, Friedberg EC
    American journal of human genetics. 1989 ; 44 (4) : 474-485.
    PMID 2929593
     
    Analysis of point mutations in an ultraviolet-irradiated shuttle vector plasmid propagated in cells from Japanese xeroderma pigmentosum patients in complementation groups A and F.
    Yagi T, Tatsumi-Miyajima J, Sato M, Kraemer KH, Takebe H
    Cancer research. 1991 ; 51 (12) : 3177-3182.
    PMID 2039995
     
    Xeroderma pigmentosum patients belonging to complementation group F and efficient liquid-holding recovery of ultraviolet damage.
    Nishigori C, Fujisawa H, Uyeno K, Kawaguchi T, Takebe H
    Photodermatology, photoimmunology & photomedicine. 1991 ; 8 (4) : 146-150.
    PMID 1814424
     
    A case of xeroderma pigmentosum complementation group F with neurological abnormalities.
    Moriwaki S, Nishigori C, Imamura S, Yagi T, Takahashi C, Fujimoto N, Takebe H
    The British journal of dermatology. 1993 ; 128 (1) : 91-94.
    PMID 8427828
     
    Regional mapping of human DNA excision repair gene ERCC4 to chromosome 16p13.13-p13.2.
    Liu P, Siciliano J, White B, Legerski R, Callen D, Reeders S, Siciliano MJ, Thompson LH
    Mutagenesis. 1993 ; 8 (3) : 199-205.
    PMID 8332082
     
    Co-correction of the ERCC1, ERCC4 and xeroderma pigmentosum group F DNA repair defects in vitro.
    Biggerstaff M, Szymkowski DE, Wood RD
    The EMBO journal. 1993 ; 12 (9) : 3685-3692.
    PMID 8253090
     
    Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins.
    Park CH, Sancar A
    Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (11) : 5017-5021.
    PMID 8197175
     
    Molecular cloning of the human nucleotide-excision-repair gene ERCC4.
    Thompson LH, Brookman KW, Weber CA, Salazar EP, Reardon JT, Sancar A, Deng Z, Siciliano MJ
    Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (15) : 6855-6859.
    PMID 8041709
     
    Partial characterization of the DNA repair protein complex, containing the ERCC1, ERCC4, ERCC11 and XPF correcting activities.
    van Vuuren AJ, Appeldoorn E, Odijk H, Humbert S, Moncollin V, Eker AP, Jaspers NG, Egly JM, Hoeijmakers JH
    Mutation research. 1995 ; 337 (1) : 25-39.
    PMID 7596355
     
    Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease.
    Park CH, Bessho T, Matsunaga T, Sancar A
    The Journal of biological chemistry. 1995 ; 270 (39) : 22657-22660.
    PMID 7559382
     
    Human DNA repair excision nuclease. Analysis of the roles of the subunits involved in dual incisions by using anti-XPG and anti-ERCC1 antibodies.
    Matsunaga T, Mu D, Park CH, Reardon JT, Sancar A
    The Journal of biological chemistry. 1995 ; 270 (35) : 20862-20869.
    PMID 7657672
     
    Detection of nucleotide excision repair incisions in human fibroblasts by immunostaining for PCNA.
    Aboussekhra A, Wood RD
    Experimental cell research. 1995 ; 221 (2) : 326-332.
    PMID 7493631
     
    Mammalian DNA nucleotide excision repair reconstituted with purified protein components.
    Aboussekhra A, Biggerstaff M, Shivji MK, Vilpo JA, Moncollin V, Podust VN, ProtiŸá M, Hˆºbscher U, Egly JM, Wood RD
    Cell. 1995 ; 80 (6) : 859-868.
    PMID 7697716
     
    ERCC4 (XPF) encodes a human nucleotide excision repair protein with eukaryotic recombination homologs.
    Brookman KW, Lamerdin JE, Thelen MP, Hwang M, Reardon JT, Sancar A, Zhou ZQ, Walter CA, Parris CN, Thompson LH
    Molecular and cellular biology. 1996 ; 16 (11) : 6553-6562.
    PMID 8887684
     
    Reaction mechanism of human DNA repair excision nuclease.
    Mu D, Hsu DS, Sancar A
    The Journal of biological chemistry. 1996 ; 271 (14) : 8285-8294.
    PMID 8626523
     
    Replication protein A confers structure-specific endonuclease activities to the XPF-ERCC1 and XPG subunits of human DNA repair excision nuclease.
    Matsunaga T, Park CH, Bessho T, Mu D, Sancar A
    The Journal of biological chemistry. 1996 ; 271 (19) : 11047-11050.
    PMID 8626644
     
    ERCC1/ERCC4 5'-endonuclease activity as a determinant of hypoxic cell radiosensitivity.
    Murray D, Macann A, Hanson J, Rosenberg E
    International journal of radiation biology. 1996 ; 69 (3) : 319-327.
    PMID 8613681
     
    Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease.
    Sijbers AM, de Laat WL, Ariza RR, Biggerstaff M, Wei YF, Moggs JG, Carter KC, Shell BK, Evans E, de Jong MC, Rademakers S, de Rooij J, Jaspers NG, Hoeijmakers JH, Wood RD
    Cell. 1996 ; 86 (5) : 811-822.
    PMID 8797827
     
    Mutational analysis of the human nucleotide excision repair gene ERCC1.
    Sijbers AM, van der Spek PJ, Odijk H, van den Berg J, van Duin M, Westerveld A, Jaspers NG, Bootsma D, Hoeijmakers JH
    Nucleic acids research. 1996 ; 24 (17) : 3370-3380.
    PMID 8811092
     
    The non-catalytic function of XPG protein during dual incision in human nucleotide excision repair.
    Wakasugi M, Reardon JT, Sancar A
    The Journal of biological chemistry. 1997 ; 272 (25) : 16030-16034.
    PMID 9188507
     
    Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence.
    Weeda G, Donker I, de Wit J, Morreau H, Janssens R, Vissers CJ, Nigg A, van Steeg H, Bootsma D, Hoeijmakers JH
    Current biology : CB. 1997 ; 7 (6) : 427-439.
    PMID 9197240
     
    Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complex.
    Bessho T, Sancar A, Thompson LH, Thelen MP
    The Journal of biological chemistry. 1997 ; 272 (6) : 3833-3837.
    PMID 9013642
     
    Excision-repair patch lengths are similar for transcription-coupled repair and global genome repair in UV-irradiated human cells.
    Bowman KK, Smith CA, Hanawalt PC
    Mutation research. 1997 ; 385 (2) : 95-105.
    PMID 9447231
     
    Mechanism of open complex and dual incision formation by human nucleotide excision repair factors.
    Evans E, Moggs JG, Hwang JR, Egly JM, Wood RD
    The EMBO journal. 1997 ; 16 (21) : 6559-6573.
    PMID 9351836
     
    A low content of ERCC1 and a 120 kDa protein is a frequent feature of group F xeroderma pigmentosum fibroblast cells.
    Yagi T, Wood RD, Takebe H
    Mutagenesis. 1997 ; 12 (1) : 41-44.
    PMID 9025096
     
    Sensitivity of group F xeroderma pigmentosum cells to UV and mitomycin C relative to levels of XPF and ERCC1 overexpression.
    Yagi T, Katsuya A, Koyano A, Takebe H
    Mutagenesis. 1998 ; 13 (6) : 595-599.
    PMID 9862190
     
    Homozygous R788W point mutation in the XPF gene of a patient with xeroderma pigmentosum and late-onset neurologic disease.
    Sijbers AM, van Voorst Vader PC, Snoek JW, Raams A, Jaspers NG, Kleijer WJ
    The Journal of investigative dermatology. 1998 ; 110 (5) : 832-836.
    PMID 9579555
     
    Complete restoration of normal DNA repair characteristics in group F xeroderma pigmentosum cells by over-expression of transfected XPF cDNA.
    Yagi T, Matsumura Y, Sato M, Nishigori C, Mori T, Sijbers AM, Takebe H
    Carcinogenesis. 1998 ; 19 (1) : 55-60.
    PMID 9472693
     
    Mapping of interaction domains between human repair proteins ERCC1 and XPF.
    de Laat WL, Sijbers AM, Odijk H, Jaspers NG, Hoeijmakers JH
    Nucleic acids research. 1998 ; 26 (18) : 4146-4152.
    PMID 9722633
     
    DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair.
    de Laat WL, Appeldoorn E, Sugasawa K, Weterings E, Jaspers NG, Hoeijmakers JH
    Genes & development. 1998 ; 12 (16) : 2598-2609.
    PMID 9716411
     
    DNA structural elements required for ERCC1-XPF endonuclease activity.
    de Laat WL, Appeldoorn E, Jaspers NG, Hoeijmakers JH
    The Journal of biological chemistry. 1998 ; 273 (14) : 7835-7842.
    PMID 9525876
     
    ERCC1 mutations in UV-sensitive Chinese hamster ovary (CHO) cell lines.
    Hayashi T, Takao M, Tanaka K, Yasui A
    Mutation research. 1998 ; 407 (3) : 269-276.
    PMID 9653453
     
    Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms.
    Matsumura Y, Nishigori C, Yagi T, Imamura S, Takebe H
    Human molecular genetics. 1998 ; 7 (6) : 969-974.
    PMID 9580660
     
    Action of DNA repair endonuclease ERCC1/XPF in living cells.
    Houtsmuller AB, Rademakers S, Nigg AL, Hoogstraten D, Hoeijmakers JH, Vermeulen W
    Science (New York, N.Y.). 1999 ; 284 (5416) : 958-961.
    PMID 10320375
     
    Domain mapping of the DNA binding, endonuclease, and ERCC1 binding properties of the human DNA repair protein XPF.
    McCutchen-Maloney SL, Giannecchini CA, Hwang MH, Thelen MP
    Biochemistry. 1999 ; 38 (29) : 9417-9425.
    PMID 10413517
     
    DNA damage recognition during nucleotide excision repair in mammalian cells.
    Wood RD
    Biochimie. 1999 ; 81 (1-2) : 39-44.
    PMID 10214908
     
    Nucleotide excision repair of DNA with recombinant human proteins: definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK.
    Araˆ†jo SJ, Tirode F, Coin F, Pospiech H, Syvˆ§oja JE, Stucki M, Hˆºbscher U, Egly JM, Wood RD
    Genes & development. 2000 ; 14 (3) : 349-359.
    PMID 10673506
     
    Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression.
    Nouspikel T, Hanawalt PC
    Molecular and cellular biology. 2000 ; 20 (5) : 1562-1570.
    PMID 10669734
     
    Genetic polymorphisms in DNA repair genes and risk of lung cancer.
    Butkiewicz D, Rusin M, Enewold L, Shields PG, Chorazy M, Harris CC
    Carcinogenesis. 2001 ; 22 (4) : 593-597.
    PMID 11285194
     
    Activity of individual ERCC1 and XPF subunits in DNA nucleotide excision repair.
    Gaillard PH, Wood RD
    Nucleic acids research. 2001 ; 29 (4) : 872-879.
    PMID 11160918
     
    Novel functional interactions between nucleotide excision DNA repair proteins influencing the enzymatic activities of TFIIH, XPG, and ERCC1-XPF.
    Winkler GS, Sugasawa K, Eker AP, de Laat WL, Hoeijmakers JH
    Biochemistry. 2001 ; 40 (1) : 160-165.
    PMID 11141066
     
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    Contributor(s)

    Written05-2001Anne Stary and Alain Sarasin

    Citation

    This paper should be referenced as such :
    Stary, A ; Sarasin, A
    XPF (xeroderma pigmentosum, complementation group F)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(3):180-182.
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Genes/XPFID299.html

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