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FLASH GENE
Symbol FAN1 contributors: mct - updated : 03-09-2020
HGNC name FANCD2/FANCI-associated nuclease 1
HGNC id 29170
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
  • a PCNA interacting peptide (PIP) motif that, together with its ubiquitin-binding zinc finger (UBZ) domain, helps recruit FAN1 to ubiquitylated PCNA accumulated at stalled forks
  • C-terminal nuclease domain
  • HOMOLOGY
    interspecies homolog to C.elegans cosmid C01G5
    Homologene
    FAMILY
  • MTMR15 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    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
  • is a DNA structure-specific endonuclease that is considered to be involved in DNA incision at the stalled replication fork
  • FAN1 recruitment enables processing of stalled forks that is essential for genome stability and health
  • FAN1 is likely protective in the context of an expanded HTT CAG repeat
  • encodes a protein that participates in DNA interstrand cross-link (ICL) repair
  • FAN1 normally functions to stabilize the expanded CAG repeat
  • 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
  • FAN1 possesses the ability to promote the ICL repair of 5'-flapped DNA covered by RPA1
  • 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
    constitutional     --over  
    increased FAN1 expression is significantly associated with delayed age at onset (AAO) and slower progression of HD
    tumoral germinal mutation      
    cause hereditary colorectal cancer by impairing DNA repair
    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