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FLASH GENE
Symbol CHFR contributors: mct - updated : 25-01-2015
HGNC name checkpoint with forkhead and ring finger domains
HGNC id 20455
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver   moderately
Lymphoid/Immunespleen   highly
 thymus   highly
Nervousnervecranial nerve  highly
Reproductivemale systemprostate  moderately
Respiratoryrespiratory tracttrachea  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
cell lineage
cell lines
fluid/secretion
at STAGE
cell cycle     cell cycle, G1, S
Text weakly expressed in G1, higlhy in S phase
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal FHA domain (forkhead associated domain)
  • a C3HC4 type (RING) zinc finger in the N terminus
  • a central RING finger domain
  • a cysteine-rich domain that is the essential domain for the CHFR/MAD2L1 interaction and for promoting interaction between MAD2L1 and CDC20 to inhibit the anaphase-promoting complex
  • a PBZ motif, needed for the interaction with polyADP-ribose
  • C-terminal cysteine-rich (CR) regio
    • HOMOLOGY
    interspecies homolog to murine Chfr (80.7pc)
    homolog to rattus Chfr (81.3pc)
    Homologene
    FAMILY
  • CHFR family
    • CATEGORY tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text colocalizes with TPT1 to the mitotic spindle
    basic FUNCTION
  • mediating protein-protein interactions
  • defining a checkpoint that delays entry into metaphase in response to mitotic stress
  • acting as an ubiquitin ligase (ubiquitinating Plk1)
  • inhibiting Cdc2 at the G2 to M transition
  • tumor suppressor controlling the expression of key mitotic proteins such STK6
  • E3 ubiquitin ligase and early mitotic checkpoint protein implicated in many cancers and in the maintenance of genomic stability
  • role for CHFR regulating chromosome segregation where decreased expression, as seen in cancer cells, contributes to genomic instability by impairing the spindle assembly checkpoint
  • checkpoint protein that plays an important function in cell cycle progression and tumor suppression
  • plays a role in the maintenance of genome integrity
  • promotes the ubiquitination of AURKA and PLK1
  • may also promote the formation of 'Lys-63'-linked polyubiquitins chains and functions with the specific ubiquitin conjugating UBEN2-UBE2V2 heterodimer
  • negative regulator of the NF-KappaB pathway, downregulating IL8 production
  • binding and downregulating HDAC1 by inducing its polyubiquitination
  • functions as a mitotic checkpoint by delaying entry into metaphase in response to mitotic stress
  • plays an important role in regulation of HLTF stability and protects cells against HLTF-mediated cell migration
  • critical role for CHFR in the MAD2L1 spindle checkpoint
  • is one of the E3 ligases, which is known to be a tumor suppressor and play an essential role in cell cycle control and tumorigenesis
  • CHFR and RNF8 may have overlapping targets and/or functions in mitosis
  • RNF8 and CHFR affect chromatin relaxation and modulate ATM activation and DNA damage response pathways
  • RNF8 and CHFR, function together to activate ATM and maintain genomic stability
  • mediates the ubiquitination of the major components of the SWI/SNF complex (PMID;
  • PARP1 is a novel CHFR binding protein and found a functional interaction that regulates the early mitotic checkpoint and tumorigenesis
  • is an important E3 ligase in the early stage of the DNA damage response, which mediates the crosstalk between
  • important role in cell cycle progression and tumorigenesis
  • new regulatory mechanism for CHFR that sequential post-translational modifications of CHFR by SUMO and ubiquitin coordinately regulates its stability
  • ubiquitin ligase CHFR, that is a checkpoint protein involved in G2/M transition, and a new effector involved in the control of insulin-induced cell proliferation
    • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, other,
  • phosphotyrosine
  • ion zinc Zn2+
    • protein
  • interacting with STK6
  • interacting with KIF22 and controling genomic stability
  • interacting with TPT1 (CHFR-TPT1 interaction is stable throughout the cell cycle, but it could be diminished by the complete depolymerization of the microtubules, providing a possible mechanism where CHFR could be the sensor that detects microtubule disruption and then activates the prophase checkpoint)
  • interacts with the mitotic kinase Aurora A to regulate its expression
  • MAD2L1 is a novel CHFR interacting protein
  • interacting with HDAC1
  • interacting with HDAC2, PML
  • HLTF is a CHFR-interacting protein (CHFR binds to and ubiquitinates HLTF, leading to its degradation)
  • interact with MAD2L1, an important component of the spindle assembly checkpoint, where CHFR knockdown resulted in mislocalization of MAD2L1 and disruption of the MAD2L1/CDC20 interaction
  • CHFR interacts with SMARCA4, SMARCB1, and SMARCD1 of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and SMARCC1 stabilizes these components by blocking their interaction with CHFR
  • SMARCA4, SMARCB1, and SMARCD1, but not SMARCC1, are the substrates of CHFR for ubiquitination
  • tumor suppressor, regulating the ubiquitination and degradation of the SWI/SNF chromatin remodeling proteins
  • PARP1 is a novel CHFR binding protein suggesting a functional interaction that regulates the early mitotic checkpoint and tumorigenesis (CHFR polyubiquitinates PARP1 and caused cell cycle arrest via PARP1 degradation)
  • aggregated LDL (agLDL) prolongs the half life of LRP1 by preventing the receptor ubiquitinylation, at least in part, through CHFR targeting
  • ubiquitinates and regulates PBK levels, which is essential for its checkpoint function
  • PBK and PTEN are new players in CHFR mediated mitotic checkpoint
  • CHFR is a partner of the molecular adapter GRB14, an inhibitor of insulin signalling
    • cell & other
    REGULATION
    inhibited by phosphorylation
    Other CpG methylation-dependent silencing of CHFR expression in cancers
    polyADPribosylated
    autoubiquitinated
    is covalently modified by SUMO-1 at lysine 663 and subsequently destabilized by ubiquitin-proteasome system (emerging role of SUMOylation in modulating protein stability)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    3 of 8 human cancer cell lines examined did not contain CHFR mRNA
    tumoral     --low  
    by aberrant methylation associated with gene silencing in primary hepatocellular carcinomas, oral squamous cell carcinomas , gastric cancer , and ovarian cancer
    constitutional     --low  
    led to disorganized multipolar mitotic spindles
    Susceptibility
    Variant & Polymorphism
    Candidate gene molecular marker to estimate the malignancy of hepatocellular carcinoma
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    CHFR-mediated downregulation of HLTF may help protect against cancer
    ANIMAL & CELL MODELS