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FLASH GENE
Symbol FANCI contributors: mct/pgu - updated : 04-01-2015
HGNC name Fanconi anemia, complementation group I
HGNC id 25568
DNA
TYPE functioning gene
STRUCTURE 73.17 kb     37 Exon(s)
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
38 splicing 4749 149 1328 - 2009 19561358
  • isoform 1
  • 37 splicing 4569 - 1268 - 2009 19561358
  • isoform 2
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Lymphoid/Immunelymph node   highly
    Respiratoryrespiratory tractlarynx  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminus, with a leucine zipper domain (AA 130–151) that could be involved in mediating protein-protein or protein-DNA interactions
  • three nuclear localization signals
  • three ATM/ATR phosphorylation motifs
  • a monoubiquitination site
  • ten S/TQ motifs, with multiple phosphorylation sites that are functionally important for inducing monoubiquitination of FANCD2, a crucial event in the Fanconi anemia pathway and interstrand cross-links repair
  • an EDGE motif that is critical for the ability of FANCI to properly monoubiquitinate FANCD2 and promote DNA crosslink resistance
  • C-terminus may be involved in the regulation of DNA binding activity, but dispensable for direct DNA binding
  • conjugated Other
    mono polymer heteromer , trimer
    HOMOLOGY
    interspecies homolog to murine Fanci (75.7 pc)
    intraspecies paralog to FANCD2
    Homologene
    FAMILY
  • DNA polymerase type-a family
  • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text concentrated in nuclear foci upon genotoxic stress
    basic FUNCTION
  • involved in the replication of mitochondrial DNA
  • DNA damage-responsive protein that functions similarly to FANCD2
  • having a monoubiquitination-independent role in DNA repair, such as in the regulation of FANCD2 protein stability
  • required to prevent accumulation of replication-associated DNA double-strand breaks
  • required for maintenance of chromosomal stability
  • involved in the repair of DNA double-strand breaks by homologous recombination and in the repair of DNA cross-links
  • participating in S phase and G2 phase checkpoint activation upon DNA damage
  • promoting FANCD2 ubiquitination and recruitment to DNA repair sites
  • ATR-dependent phosphorylation of FANCI is a molecular switch for the Fanconi anemia pathway
  • monoubiquitination of FANCI is largely dispensable for the DNA repair function of the Fanconi anemia pathway
  • 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
  • FANCD2 and FANCI function together in the Fanconi anemia network of deoxyribonucleic acid (DNA) crosslink repair
  • CELLULAR PROCESS cell cycle, checkpoint
    nucleotide, repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterotrimer composed of a catalytic subunit and an homodimer of accessory subunits
  • member of the group II Fanconi anemia proteins
  • 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 binding branched DNA
    RNA
    small molecule cofactor,
  • Mg2+
  • protein
  • interacting directly with FANCD2 (FANCI–FANCD2 (ID) complex) and phosphorylation of FANCI may recruit FANCD2 to the core complex by interacting with a member of the complex
  • interacts with FANCD2 through its C-terminal amino acid 1001–1328 fragment
  • FANCI-FANCD2 complex may participate in repair of damaged replication forks through its preferential recognition of branched structures
  • RAD18 binds FANCD2 and is required for efficient monoubiquitylation and chromatin localization of both FANCD2 and FANCI
  • FANCD2 and FANCI have been identified as targets of FANCL monoubiquitylation
  • binding of FANCL with its partners, UBE2T, FANCD2, and FANCI
  • FANCD2-FANCI may regulate chromatin dynamics during DNA repair
  • N-terminus of USP1 is sufficient to engineer specificity in a more promiscuous USP, but is not required for direct PCNA or FANCI deubiquitination
  • cell & other
    REGULATION
    activated by site-specific monoubiquitination upon DNA damage, which then enables it to localize to DNA damage nuclear foci
    Phosphorylated by ATR (ATR phosphorylates many FA proteins including FANCI, and this phosphorylation acts as a molecular switch in the FA pathway)
    Other monoubiquitinated on Lys-523 during S phase and upon genotoxic stress
    deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed
    ubiquitination required for binding to chromatin, DNA repair, and normal cell cycle progression
    phosphorylated in response to DNA damage by ATM and/or ATR
    monoubiquitinated by UBE2T-FANCL
    ASSOCIATED DISORDERS
    corresponding disease(s) FANCI
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS