Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol FANCD2 contributors: mct/npt/pgu - updated : 25-11-2016
HGNC name Fanconi anemia, complementation group D2
HGNC id 3585
Corresponding disease
FANCD2 Fanconi anemia, complementation group D
Location 3p25.3      Physical location : 10.068.112 - 10.143.614
Synonym name protein FACD2
Synonym symbol(s) FAD, FACD, FANCD, FA4, FAD2, FA-D2, FLJ23826, DKFZp762A223
DNA
TYPE functioning gene
STRUCTURE 75.50 kb     43 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map pter - D3S3891 - D3S18 - OXTR - D3S1597 - CAMK1 - OGG1 - VHL VHL - FANCD2 FANCD2 - D3S1317 - IRAK2 - ATP2B2 - cen
Physical map
FLJ10707 3p25.3 hypothetical protein FLJ10707 LOC375323 3p25.3 lipoma HMGIC fusion partner-like protein 4 FLJ22405 3p26 hypothetical protein FLJ22405 LOC151835 3p25.3 copine family member BRPF1 3p26-p25 bromodomain and PHD finger containing, 1 OGG1 3p26.2 8-oxoguanine DNA glycosylase CAMK1 3p25.2 calcium/calmodulin-dependent protein kinase I TADA3L 3p25.3 transcriptional adaptor 3 (NGG1 homolog, yeast)-like ARPC4 3p25.3-p24.1 actin related protein 2/3 complex, subunit 4, 20kDa LOC389093 3 similar to RIKEN cDNA 4833441J24 DKFZP434B103 MGC29784 3p25.3 hypothetical protein MGC29784 CIDE-3 3p25.3 cell death activator CIDE-3 GL009 3p25.2 hypothetical protein GL009 IL17RE 3p25.3 interleukin 17 receptor E IL17RC 3p25.3 interleukin 17 receptor C CRELD1 3p25.3 cysteine-rich with EGF-like domains 1 FLJ33674 3p25.3 hypothetical protein FLJ33674 LOC55831 3p25.3 30 kDa protein HCP10 3p25.3 cytochrome c, somatic pseudogene LOC389094 3 LOC389094 CICE 3p25.3 cell death-inducing CIDE-like effector pseudogene FANCD2 3p25.3 Fanconi anemia, complementation group D2 HCP11 3p25.3 cytochrome c, somatic pseudogene MGC40179 3p25.3 hypothetical protein MGC40179 MDS027 3p25.3 uncharacterized hematopoietic stem/progenitor cells protein MDS027 VHL 3p26-p25 von Hippel-Lindau syndrome IRAK2 3p25.3 interleukin-1 receptor-associated kinase 2 KIAA0218 3p25.3 interleukin-1 receptor-associated kinase 2 NAG73 3p26-p25 NPC-related protein NAG73 GHRL 3p26-p25 NPC-related protein NAG73 SEC13L1 3p25-p24 SEC13-like 1 (S. cerevisiae) ATP2B2 3p25-p24 ATPase, Ca++ transporting, plasma membrane 2
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
43 splicing 5204 164 1471 - 2001 11239453
43 - 5134 - 1451 - 2001 11239453
differing by the C terminal end
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain   moderately
Reproductivemale systemprostate  moderately
Respiratorylung   moderately
Urinarykidney   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone   
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text stem cells
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a CUE (coupling of ubiquitin conjugation to endoplasmic reticulum degradation) ubiquitin-binding domain (UBD), mediating noncovalent binding to ubiquitin, and required for interaction with FANCI, retention of monoubiquitinated FANCD2, and FANCI in chromatin, and for efficient ICL repair
  • HOMOLOGY
    interspecies homolog to C.elegans
    homolog to Drosophila
    intraspecies paralog to FANCI
    Homologene
    FAMILY
  • member of the group II Fanconi anemia proteins
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,nucleoplasm
    text
  • targeted to nuclear face in response to DNA damage and colocalizing with BRCA1 in ionizing radiation induced face and in synaptonemal complexes
  • localizes to discrete spots on mitotic chromosomes
  • nuclear import of FANCD2 is a regulated step in the DNA damage response
  • CEBPD and IPO4 play important roles in the nuclear import of FANCD2
  • basic FUNCTION
  • involved in cellular decision - making in response to DNA damage and in the arrest of DNA synthese after ionizing radiation
  • playing an early role in homologous double-strand breaks repair pathway choice
  • may be having a role in the cellular response to stalled replication forks or in the repair of replication-associated double-strand breaks, irrespective of the type of primary DNA lesion
  • FANCD2 deubiquitination required for efficient DNA crosslink repair
  • functioning in a double strand break repair pathway that is distinct from non-homologous end joining
  • required to maintain the G2 checkpoint
  • mediating double strand DNA break repair independently of RAD51-associated homologous recombination
  • required to prevent accumulation of replication-associated DNA double-strand breaks
  • DNA structure-induced recruitment and activation of the Fanconi anemia pathway protein FANCD2
  • independent prognostic value in sporadic breast cancer
  • chromosomal localization is responsive to replicative stress and specifically targets APH-induced chromatid gaps and breaks
  • bind to double strand DNA ends and Holliday junctions
  • ubiquitylated FANCI-FANCD2 controls interstrand cross-links repair in S phase
  • upon the occurrence of DNA damage, FANCI becomes monoubiquitinated on Lys-523 and relocalizes to chromatin, where it functions with monoubiquitinated FANCD2 to facilitate DNA repair
  • requires an active nuclear import mechanism to participate in DNA repair
  • key factor in the FANC-BRCA1 pathway and is monoubiquitinated and targeted to discrete nuclear foci following DNA damage
  • FANCI-FANCD2 acts upstream of homologous recombination in the context of replication-coupled interstrand cross-link repair, but it is not required for RAD51 recruitment to chromatin
  • is an effector of ATR signaling implicated in a general replisome surveillance mechanism that is necessary for sustaining cell proliferation and attenuating carcinogenesis
  • HELQ and FANCD2 act in parallel ICL repair pathways
  • FANCD2 and FANCI function together in the Fanconi anemia network of deoxyribonucleic acid (DNA) crosslink repair
  • not only FANCD2 regulates BRIP1 chromatin localization but also BRIP1 is necessary for efficient loading of FANCD2 onto chromatin following DNA damage caused by mitomycin C treatment
  • BRCA1, FANCD2 and CHEK1 are potential targets for the modulation of radiation response in bystander cells
  • CELLULAR PROCESS nucleotide, repair
    nucleotide, genomic integrity
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    chromosome instability pathway
    a component
  • FANCI-FANCD2 complex preferentially binds to the branched DNA structures when compared with either FANCI or FANCD2 alone
  • FANCI and FANCD2, form a heterodimer and play essential roles in DNA interstrand crosslink (ICL) repair
  • INTERACTION
    DNA
  • may be binding to ssDNA arising from MRE11-processed DNA double strand breaks
  • RNA
    small molecule
    protein
  • with ATM (phosphorylation of FANCD2 for regulating discrete cellular signaling pathway)
  • with BRCA2 and FANCG in DNA damage response pathway
  • complexing with BRCA1 and RAD51
  • interacting with menin (MEN1)for critical role in repair of DNA damage
  • interaction with BRCA2 (monoubiquitination of FANCD2, which is regulated by the FA pathway, promotes BRCA2 loading into chromatin complexes)
  • associating with USP1
  • FANCE-mediated association of FANCC with FANCD2
  • interacting with FANCM (FANCM and FANCD2 are functionally interdependent)
  • FANCI-FANCD2 complex preferentially binds to the branched DNA structures when compared with either FANCI or FANCD2 alone
  • interacting with UBE2T (with Fanconi anemia (FA) nuclear core complex, are required for the S phase and DNA damage-restricted monoubiquitination of FANCD2)
  • upon the occurrence of DNA damage, FANCI becomes monoubiquitinated on Lys-523 and relocalizes to chromatin, where it functions with monoubiquitinated FANCD2 to facilitate DNA repair
  • interaction with FAN1 (recruitment of FAN1 to mitomycin C-induced foci is dependent on FANCD2 ubiquitylation, and this interaction represent strong evidence in support of an involvement of this nuclease in the FA-dependent pathway of ICL repair)
  • recruited in response to replication stress and BRIP1 may serve to link FANCD2 to BRCA1
  • interacts with CEBPD (CEBPD mediates the indirect association of FANCD2 with IPO4 through its interaction with both of these proteins via separate domains)
  • RAD18 binds FANCD2 and is required for efficient monoubiquitylation and chromatin localization of both FANCD2 and FANCI
  • BTBD12 is recruited to sites of DNA damage by monoubiquitylated FANCD2, and this recruitment requires its UBZ domain
  • DCLRE1B and FANCD2 function epistatically in cellular responses to mitomycin C -induced DNA damage to ensure survival
  • target for caspase-mediated apoptotic pathway, which may be an early indicator for apoptotic cell death
  • binding of FANCL with its partners, UBE2T, FANCD2, and FANCI
  • FANCD2 and FANCI have been identified as targets of FANCL monoubiquitylation
  • C1orf86 binds to FANCA subunit and is required for stability of the complex and monoubiquitination of FANCD2
  • FANCD2-FANCI may regulate chromatin dynamics during DNA repair
  • DNA2 interacts with FANCD2, and cisplatin induces FANCD2 ubiquitylation even in the absence of DNA2
  • in the early phase of DNA damage response, FANCD2 plays crucial roles in recruiting POLH to the sites of DNA damage for repair
  • activates transcription of TP63 and suppresses tumorigenesis
  • DCLRE1B is a nuclease required for efficient localization of the DNA repair proteins, FANCD2 and BRCA1
  • can interact directly with minichromosome maintenance (MCM) proteins
  • ATR signaling promoted the transient association of endogenous FANCD2 with the MCM2-MCM7 replicative helicase independently of FANCD2 monoubiquitination
  • HELQ-deficient cells exhibited constitutive FANCD2 monoubiquitination, indicating that HELQ is dispensable for this modification
  • important regulatory role of the USP1-WDR48 complex in HR (homologous recombination) repair through its regulation of the FANCD2-ubiquitinated (Ub) and PCNA-Ub cellular pools
  • FAN1 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
  • is a novel and specific substrate of CASP3 (cleavage of FANCD2 by CASP3 did not require either the FA core complex or mono-ubiquitylation of FANCD2, and was stimulated by TP53)
  • FANCD2, BRIP1 and BRCA2 cooperate to promote replication fork recovery independently of the Fanconi Anemia core complex
  • USP1-WDR48 complex promotes homologous recombination (HR) repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1
  • RUNX1 and RUNX3 also maintain genomic integrity in a non-transcriptional manner during interstand crosslink repair by promoting the recruitment of FANCD2 to sites of DNA damage
  • N-terminus of USP1 harbours a FANCD2-specific binding sequence required for deubiquitination of K561 on FANCD2
  • cell & other
    REGULATION
    activated by a complex containing FANCA, FANCC, FANCF and FANCD2 to a mono-ubiquitinated form in response to DNA damage
    WDR48
    Other MRN complex is a crucial regulator of FANCD2 stability
    regulated by ATR and ATM (phosphorylate FANCD2 at different sites in response to DNA damage, indicating that important FA pathway functions are controlled by these two cell cycle kinases)
    monoubiquitinated by the FANCL protein and UBE2T
    is regulated by caspase-mediated degradation during apoptosis induced by DNA damage
    ASSOCIATED DISORDERS
    corresponding disease(s) FANCD2
    related resource Fanconi Anaemia Mutation Database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in leukemias
    tumoral somatic mutation     loss of function
    somatic inactivating (epi)genetic events in FANCD2 may be important in both sporadic and hereditary breast carcinogenesis
    constitutional       loss of function
    FANCD2 deficiency promotes transcriptional activity of the TNF promoter and induces overproduction of TNF-which then sustains prolonged inflammatory responses
    Susceptibility to sporadic breast cancer
    Variant & Polymorphism SNP increasing the risk of sporadic breast cancer
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS