ERCC4 (xeroderma pigmentosum, complementation group F)

2001-05-01   Anne Stary , Alain Sarasin 

Laboratory of Genetic Instability, Cancer, UPR2169 CNRS, Institut de Recherches sur le Cancer, 7, rue guy Moquet, BP 8, 94801 VILLEJUIF, France

Identity

HGNC
ERCC4
LOCATION
16p13.12
IMAGE
Atlas Image
LEGEND
XPF (16p13) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
2072
ALIAS
ERCC11,FANCQ,RAD1,XFEPS,XPF
FUSION GENES
Show Gene Fusions

DNA/RNA

Description

28.2 kb

Transcription

2881 bp =D0 11 exons

Proteins

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

    Bibliography

    Pubmed IDLast YearTitleAuthors

    Other Information

    Locus ID:

    NCBI: 2072
    MIM: 133520
    HGNC: 3436
    Ensembl: ENSG00000175595

    Variants:

    dbSNP: 2072
    ClinVar: 2072
    TCGA: ENSG00000175595
    COSMIC: ERCC4

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000175595ENST00000311895Q92889
    ENSG00000175595ENST00000311895A0A1W1GSK9
    ENSG00000175595ENST00000462862I3L4K0
    ENSG00000175595ENST00000574194I3NI48
    ENSG00000175595ENST00000575156Q92889
    ENSG00000175595ENST00000575156A0A1W1GSP5

    Expression (GTEx)

    0
    5
    10
    15
    Adipose - Subcutaneous
    Adipose - Visceral
    Adrenal Gland
    Artery - Aorta
    Artery - Tibial
    Bladder
    Brain - Amygdala
    Brain - Anterior cingulate cortex
    Brain - Caudate
    Brain - Cerebellar Hemisphere
    Brain - Cerebellum
    Brain - Cortex
    Brain - Frontal Cortex
    Brain - Hippocampus
    Brain - Hypothalamus
    Brain - Nucleus accumbens
    Brain - Putamen
    Brain - Spinal cord
    Brain - Substantia nigra
    Breast - Mammary Tissue
    Cells - Cultured fibroblasts
    Cells - EBV - transformed lymphocytes
    Cervix - Ectocervix
    Cervix - Endocervix
    Colon - Sigmoid
    Colon - Transverse
    Esophagus - Gastroesophageal Junction
    Esophagus - Mucosa
    Esophagus - Muscularis
    Fallopian Tube
    Heart - Atrial Appendage
    Heart - Left Ventricle
    Kidney - Cortex
    Kidney - Medulla
    Liver
    Lung
    Minor Salivary Gland
    Muscle - Skeletal
    Nerve - Tibial
    Ovary
    Pancreas
    Pituitary
    Prostate
    Skin - Not Sun Exposed
    Skin - Sun Exposed
    Small Intestine - Terminal Ileum
    Spleen
    Stomach
    Testis
    Thyroid
    Uterus
    Vagina
    Whole Blood

    Pathways

    PathwaySourceExternal ID
    Nucleotide excision repairKEGGko03420
    Nucleotide excision repairKEGGhsa03420
    Fanconi anemia pathwayKEGGko03460
    Fanconi anemia pathwayKEGGhsa03460
    DNA RepairREACTOMER-HSA-73894
    DNA Double-Strand Break RepairREACTOMER-HSA-5693532
    Homology Directed RepairREACTOMER-HSA-5693538
    HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA)REACTOMER-HSA-5693567
    HDR through Single Strand Annealing (SSA)REACTOMER-HSA-5685938
    Nucleotide Excision RepairREACTOMER-HSA-5696398
    Global Genome Nucleotide Excision Repair (GG-NER)REACTOMER-HSA-5696399
    Formation of Incision Complex in GG-NERREACTOMER-HSA-5696395
    Dual Incision in GG-NERREACTOMER-HSA-5696400
    Transcription-Coupled Nucleotide Excision Repair (TC-NER)REACTOMER-HSA-6781827
    Dual incision in TC-NERREACTOMER-HSA-6782135
    Fanconi Anemia PathwayREACTOMER-HSA-6783310

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High
    cerebral cortex
    cerebellum
    hippocampus
    caudate
    thyroid gland
    parathyroid gland
    adrenal gland
    bronchus
    lung
    oral mucosa
    salivary gland
    esophagus
    stomach 1
    stomach 2
    duodenum
    small intestine
    colon
    rectum
    liver
    gallbladder
    pancreas
    kidney
    urinary bladder
    testis
    epididymis
    seminal vesicle
    prostate
    vagina
    ovary
    fallopian tube
    endometrium 1
    endometrium 2
    cervix, uterine
    placenta
    breast
    heart muscle
    smooth muscle
    skeletal muscle
    soft tissue 1
    soft tissue 2
    adipose tissue
    skin 1
    skin 2
    appendix
    spleen
    lymph node
    tonsil
    bone marrow

    PharmGKB

    Entity IDNameTypeEvidenceAssociationPKPDPMIDs
    PA164713176Platinum compoundsChemicalClinicalAnnotationassociatedPD25069034
    PA443622Carcinoma, Non-Small-Cell LungDiseaseClinicalAnnotationassociatedPD25069034

    References

    Pubmed IDYearTitleCitations
    146906022003ERCC1/XPF removes the 3' overhang from uncapped telomeres and represses formation of telomeric DNA-containing double minute chromosomes.139
    161952372006Polymorphisms of DNA repair genes and risk of non-small cell lung cancer.112
    166090222006Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer.71
    218966582011Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair.71
    187014352008Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk.63
    191163882009A field synopsis on low-penetrance variants in DNA repair genes and cancer susceptibility.63
    150952992004Reduced levels of XPA, ERCC1 and XPF DNA repair proteins in testis tumor cell lines.60
    172995782007Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis.58
    160769552005Crystal structure and DNA binding functions of ERCC1, a subunit of the DNA structure-specific endonuclease XPF-ERCC1.57
    183961112008ERCC1/XPF limits L1 retrotransposition.51

    Citation

    Anne Stary ; Alain Sarasin

    ERCC4 (xeroderma pigmentosum, complementation group F)

    Atlas Genet Cytogenet Oncol Haematol. 2001-05-01

    Online version: http://atlasgeneticsoncology.org/gene/299/gene-fusions/deep-insight-explorer/