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FLASH GENE
Symbol FAN1 contributors: mct - updated : 25-11-2014
HGNC name FANCD2/FANCI-associated nuclease 1
HGNC id 29170
Corresponding disease
KMIN interstitial nephritis, karyomegalic
Location 15q13.2      Physical location : 31.196.054 - 31.235.307
Synonym name
  • myotubularin related protein 15
  • KIAA1018
  • related to C elegans Cos C01G5
  • coiled-coil domain-containing protein MTMR15
  • Synonym symbol(s) KIAA1018, DKFZp686K16147, DKFZp451H236, MTMR15, KMIN
    EC.number 3.1.4.1
    DNA
    TYPE functioning gene
    STRUCTURE 39.18 kb     15 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 4901 114 1017 - 2010 20603073
    - - 2851 - 533 - 2010 20603073
    - - 2748 - 533 - 2010 20603073
    - - 2864 - 533 - 2010 20603073
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal UBZ-type ubiquitin-binding domain domain, RAD18-like CCHC zinc finger, that is one of many ubiquitin recognition motifs
  • a SAP-type DNA binding domain
  • a putative nuclease domain termed the “VRR_nuc” domain
  • C-terminal nuclease domain
  • HOMOLOGY
    interspecies homolog to C.elegans cosmid C01G5
    Homologene
    FAMILY
  • MTMR15 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • FA-associated nuclease, that binds directly to monoubiquitinated FANCD2, resolving a decade-long puzzle regarding the function of this FANCD2 modification
  • nuclease involved in the processing of mitomycin C (MMC)- and cisplatin-induced DNA damage, to which it is recruited by ubiquitylated FANCD2
  • promotes interstrand cross-linking (ICL)repair in a manner strictly dependent on its ability to accumulate at or near sites of DNA damage and that relies on mono-ubiquitylation of the ID complex
  • repair nuclease that is recruited to sites of crosslink damage in part through binding the ubiquitinated ID complex through its UBZ domain
  • required for the late stages of ICL repair
  • required for the processing of recombination intermediates that arise predominantly during the metabolism of damage induced by ICL-generating agents
  • endonuclease that may act together with other repair proteins to mediate endonucleolytic digestion of cross-linked DNA structures and, thus, generate ends that can serve as substrates for HR repair
  • might be involved in homologous recombination and in the maintenance of chromosomal stability
  • it is possible that FAN1 is functionally at least partially redundant with other, as yet unidentified, nucleases
  • displays both endonuclease and exonuclease activity and this ubiquitin-mediated recruitment focuses the nuclease activity of FAN1 to the site of the ICL
  • structure-selective DNA repair nuclease with 5prime flap endonuclease activity, involved in the repair of interstrand DNA crosslinks
  • its activity on asymmetric repair intermediates is mediated by an atypical monomeric virus-type replication-repair nuclease domain
  • is a new crucial replication fork recovery factor
  • FAN1 nuclease activity at stalled replication forks requires tight regulation: too little inhibits fork restart, whereas too much causes fork degradation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with MLH1, FANCD2 and FANCI
  • nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking (ICL) agents
  • joins the BLM-FANCD2 complex following APH-mediated fork stalling in a manner dependent on MRE11A and FANCD2, followed by FAN1 nuclease-mediated fork restart
  • cell & other
    REGULATION
    Other recruited to sites of DNA damage by monoubiquitinated FANCD2
    ASSOCIATED DISORDERS
    corresponding disease(s) KMIN
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    sensitizes cells to cisplatin and mitomycin C
    Susceptibility to Fanconi anemia (FA)
    Variant & Polymorphism other associates with mono-ubiquitylated FANCI-FANCD2, mutations that may be responsible for FA in a subset of human patients
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS