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FLASH GENE
Symbol FANCM contributors: mct/npt/pgu - updated : 26-10-2018
HGNC name Fanconi anemia, complementation group M
HGNC id 23168
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
23 - 7143 232 2048 - 2005 16116422
22 - 7060 - 2022 - 2005 16116422
15 - 2139 - 669 - 2005 16116422
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunelymph node    
Nervousnerve   highly
Reproductivefemale systemuterus   
 male systemtestis  highly Homo sapiens
 male systemtestisseminiferous tubule   Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
Nervousperipherous   
cells
SystemCellPubmedSpeciesStageRna symbol
ReproductiveSertoli cell Homo sapiens
Reproductivesperm cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal helicase domain which has both ATP dependent and independent activities, and required for monoubiquitination (for FANCD2 monoubiquitination)
  • two DNA processing domains: a DEAH box helicase domain and an XPF/ERCC4-like endonuclease domain
  • C-terminal endonuclease domains, ERCC4 nuclease domain
  • conjugated RiboP
    HOMOLOGY
    interspecies homolog to murine Fancm
    ortholog to yeast Fml1
    Homologene
    FAMILY
  • DEAD box helicase, XPF family
  • DEAH subfamily
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text localizes to chromatin
    basic FUNCTION
  • playing an essential role for monoubiquitination of FANCD2
  • required to prevent accumulation of replication-associated DNA double-strand breaks
  • having an ATP-independent binding activity and an
  • ATP-dependent DNA translocase property
  • having additional activities that suggest its direct participation in DNA repair
  • may could utilize its ATP-dependent DNA-processing activity to work coordinately with BRCA2 and FANCJ in DNA repair, ultimately leading to the removal of the damaged DNA
  • could promote DNA damage tolerance in S phase
  • can specifically bind to model replication forks and Holliday junctions and move their junction points in an ATPase-dependent manner
  • could counteract the advancement of replication forks and prevent them from running into lesions and collapsing
  • playing a vital role during replication
  • might be involved in DNA processing at stalled replication forks
  • functions both inside and outside the FA core complex to maintain genome stability and to prevent tumorigenesis
  • can promote branch migration of Holliday junctions and DNA replication structure), suggesting that FANCM may provide a link between the FA pathway and DNA repair
  • can catalyze the regression or unwinding of replication forks, which can potentially lead to recombination
  • displaying DNA-dependent ATPase activity and promoting the dissociation of DNA triplexes
  • potent DNA translocase that can remodel replication fork structures to promote fork regression
  • role in DNA processing, consistent with the current view that FA proteins coordinate DNA repair at stalled replication forks
  • role of FANCM in controlling replisome progression and fork dynamics in response to replication stress
  • controls DNA chain elongation in an ATPase-dependent manner, and is may be a ringmaster in the response to replication stress by physically altering replication fork structures and by providing a tight link to S-phase checkpoint signalling
  • promotes replication through damaged DNA and the integrity of its ATPase domain is necessary for the reactivation of stalled forks after DNA damage
  • early role for FANCM in ATR-mediated checkpoint signalling by promoting chromatin retention of TOPBP1
  • required for efficient activation of ATR by promoting TOPBP1 loading on chromatin
  • FANCM/FAAP24 complex is specifically required for the recruitment of replication protein A (RPA) to interstrand crosslinking (ICL)-stalled replication forks
  • important for resistance to interstrand crosslinks but not at the step of monoubiquitylation of the ID complex
  • FANCM translocase activity is essential for promoting replication fork stability
  • plays an essential role in maintaining chromosomal integrity by promoting the recovery of stalled replication forks and hence preventing tumourigenesis
  • UBE2T and FANCM are functionally linked to nucleotide excision repair
  • key factor imposing an upper limit on the number of meiotic crossovers
  • FANCM and FAAP24 play multiple, while not fully epistatic, roles in maintaining genomic integrity
  • histone-fold complex MHF is remodeled by FANCM to recognize branched DNA and protect genome stability
  • FANCM and BLM complex work together at stalled forks to promote both Fanconi anemia repair and replication traverse pathways of interstrand crosslinks (ICLs)
  • is a breast cancer-predisposing gene
  • CENPS and FANCM were found to prevent gross chromosomal rearrangements mediated by centromere repeats (PMID
  • role in maintaining genomic stability in meiosis and mitosis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • forms a heterodimer with FAAP24 through its C-terminal-conserved region
  • member of the Group I Fanconi anemia proteins including also FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL
  • INTERACTION
    DNA binding
    RNA
    small molecule
  • ATP
  • protein
  • interacting with FANCD2 (FANCM and FANCD2 are functionally interdependent)
  • stabilizes CHEK1 and CHEK1 activity is required for FANCM stability in the presence of replication inhibitors and DNA-damaging agents
  • FANCM-APID1/STRA13 is an essential DNA-remodeling complex that protects replication forks
  • binds to both RMI proteins through a hydrophobic “knobs-into-holes” packing arrangement
  • interaction between FANCM and the RMI core complex depends heavily upon docking of conserved hydrophobic side chains from FANCM into hydrophobic pockets on the RMI1/RMI2 surface
  • FANCM and its DNA-binding partner, FAAP24, constitute a complex involved in the activation of Fanconi anemia (FA) DNA damage response mechanism
  • ATR-FANCM feedback loop is present in the FA and replication stress response pathways and that it is required for both efficient ATR/CHEK1 checkpoint activation and FANCM function
  • cell & other
    REGULATION
    Other phosphorylated during both the M and S phases and in response to DNA-damaging agents
    ASSOCIATED DISORDERS
    corresponding disease(s) FANCM , SPGF28 , POF15
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    cause a cancer predisposition syndrome clinically distinct from bona fide Fanconi anemia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Fancm-deficient mice having hypogonadism and hypersensitivity to cross-linking agents in mouse embryonic fibroblasts (MEFs), thus phenocopying other FA mouse models
  • Fancm-deficient male mice display reduced testis size and abnormal morphology of spermatogonia and seminiferous tubules, including completely missing germ cells in a subset of tubules