This gene encodes an E3 ubiquitin-protein ligase required for the maintenance of the antephase checkpoint that regulates cell cycle entry into mitosis and, therefore, may play a key role in cell cycle progression and tumorigenesis. The encoded protein has an N-terminal forkhead-associated domain, a central RING-finger domain, and a cysteine-rich C-terminal region. Alternatively... See more...

Aliases for CHFR Gene

Aliases for CHFR Gene

  • Checkpoint With Forkhead And Ring Finger Domains 2 3 5
  • RING-Type E3 Ubiquitin Transferase CHFR 3 4
  • E3 Ubiquitin-Protein Ligase CHFR 3 4
  • RING Finger Protein 196 3 4
  • RNF196 3 4
  • Checkpoint With Forkhead And Ring Finger Domains, E3 Ubiquitin Protein Ligase 3
  • Checkpoint With Forkhead And RING Finger Domains Protein 4
  • EC 2.3.2.27 4
  • RNF116 3

External Ids for CHFR Gene

Previous GeneCards Identifiers for CHFR Gene

  • GC12M130925
  • GC12M132970
  • GC12M133041
  • GC12M131655
  • GC12M132027
  • GC12M131927
  • GC12M133416
  • GC12M130193
  • GC12M133399

Summaries for CHFR Gene

Entrez Gene Summary for CHFR Gene

  • This gene encodes an E3 ubiquitin-protein ligase required for the maintenance of the antephase checkpoint that regulates cell cycle entry into mitosis and, therefore, may play a key role in cell cycle progression and tumorigenesis. The encoded protein has an N-terminal forkhead-associated domain, a central RING-finger domain, and a cysteine-rich C-terminal region. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Mar 2014]

GeneCards Summary for CHFR Gene

CHFR (Checkpoint With Forkhead And Ring Finger Domains) is a Protein Coding gene. Diseases associated with CHFR include Hypertrichosis Universalis Congenita, Ambras Type. Among its related pathways are DNA Damage. Gene Ontology (GO) annotations related to this gene include nucleotide binding and ubiquitin-protein transferase activity.

UniProtKB/Swiss-Prot Summary for CHFR Gene

  • E3 ubiquitin-protein ligase that functions in the antephase checkpoint by actively delaying passage into mitosis in response to microtubule poisons. Acts in early prophase before chromosome condensation, when the centrosome move apart from each other along the periphery of the nucleus. Probably involved in signaling the presence of mitotic stress caused by microtubule poisons by mediating the 'Lys-48'-linked ubiquitination of target proteins, leading to their degradation by the proteasome. Promotes the ubiquitination and subsequent degradation of AURKA and PLK1. Probably acts as a tumor suppressor, possibly by mediating the polyubiquitination of HDAC1, leading to its degradation. May also promote the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation, but are rather involved in signaling cellular stress.

Gene Wiki entry for CHFR Gene

Additional gene information for CHFR Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CHFR Gene

Genomics for CHFR Gene

GeneHancer (GH) Regulatory Elements for CHFR Gene

Promoters and enhancers for CHFR Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CHFR on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CHFR

Top Transcription factor binding sites by QIAGEN in the CHFR gene promoter:
  • ATF6
  • COMP1
  • FAC1
  • Hlf
  • NF-1
  • NF-Y
  • NF-YA
  • NF-YB
  • NF-YC
  • Pax-5

Genomic Locations for CHFR Gene

Genomic Locations for CHFR Gene
chr12:132,822,187-132,956,304
(GRCh38/hg38)
Size:
134,118 bases
Orientation:
Minus strand
chr12:133,398,773-133,532,890
(GRCh37/hg19)
Size:
134,118 bases
Orientation:
Minus strand

Genomic View for CHFR Gene

Genes around CHFR on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CHFR Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CHFR Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CHFR Gene

Proteins for CHFR Gene

  • Protein details for CHFR Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96EP1-CHFR_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase CHFR
    Protein Accession:
    Q96EP1
    Secondary Accessions:
    • A6NEN5
    • B4DZ77
    • B4E2L6
    • Q96SL3
    • Q9NRT4
    • Q9NT32
    • Q9NVD5

    Protein attributes for CHFR Gene

    Size:
    664 amino acids
    Molecular mass:
    73386 Da
    Quaternary structure:
    • Interacts with HDAC1 and HDAC2. Interacts with PML (with sumoylated form of PML).
    Miscellaneous:
    • CHFR is silenced in many primary cancers because of CpG methylation and deacetylated histones on its promoter region. This however raises the question of whether CHFR silencing is a consequence or a cause of primary cancers.

    Three dimensional structures from OCA and Proteopedia for CHFR Gene

    Alternative splice isoforms for CHFR Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CHFR Gene

Post-translational modifications for CHFR Gene

  • Poly-ADP-ribosylated. In addition to binding non covalently poly(ADP-ribose) via its PBZ-type zinc finger, the protein is also covalently poly-ADP-ribosylated by PARP1.
  • Autoubiquitinated; may regulate its cellular level.
  • Phosphorylated by PKB. Phosphorylation may affect its E3 ligase activity.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for CHFR Gene

Domains & Families for CHFR Gene

Gene Families for CHFR Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for CHFR Gene

Blocks:
  • Forkhead-associated (FHA)
  • Zn-finger, RING
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CHFR Gene

GenScript: Design optimal peptide antigens:
  • RING finger protein 196 (CHFR_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96EP1

UniProtKB/Swiss-Prot:

CHFR_HUMAN :
  • The PBZ-type zinc finger (also named CYR) mediates non-covalent poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is dependent on the presence of zinc and is required for its function in antephase checkpoint.
  • Belongs to the CHFR family.
Domain:
  • The PBZ-type zinc finger (also named CYR) mediates non-covalent poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is dependent on the presence of zinc and is required for its function in antephase checkpoint.
  • The FHA domain plays a key role in the anti-proliferative properties of the protein and is involved in initiating a cell cycle arrest at G2/M. The FHA domain may be required to interact with phosphorylated proteins.
Family:
  • Belongs to the CHFR family.
genes like me logo Genes that share domains with CHFR: view

Function for CHFR Gene

Molecular function for CHFR Gene

UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase that functions in the antephase checkpoint by actively delaying passage into mitosis in response to microtubule poisons. Acts in early prophase before chromosome condensation, when the centrosome move apart from each other along the periphery of the nucleus. Probably involved in signaling the presence of mitotic stress caused by microtubule poisons by mediating the 'Lys-48'-linked ubiquitination of target proteins, leading to their degradation by the proteasome. Promotes the ubiquitination and subsequent degradation of AURKA and PLK1. Probably acts as a tumor suppressor, possibly by mediating the polyubiquitination of HDAC1, leading to its degradation. May also promote the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation, but are rather involved in signaling cellular stress.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; Evidence={ECO:0000269 PubMed:11807090, ECO:0000269 PubMed:11912157, ECO:0000269 PubMed:14562038, ECO:0000269 PubMed:18172500, ECO:0000269 PubMed:19182791};.

Enzyme Numbers (IUBMB) for CHFR Gene

Phenotypes From GWAS Catalog for CHFR Gene

Gene Ontology (GO) - Molecular Function for CHFR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IDA 18172500
GO:0004842 ubiquitin-protein transferase activity IBA,IDA 18172500
GO:0005515 protein binding IPI,IEA 15467728
GO:0016740 transferase activity IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with CHFR: view
genes like me logo Genes that share phenotypes with CHFR: view

Animal Models for CHFR Gene

MGI Knock Outs for CHFR:

Animal Model Products

  • Taconic Biosciences Mouse Models for CHFR

CRISPR Products

miRNA for CHFR Gene

miRTarBase miRNAs that target CHFR

Clone Products

  • Addgene plasmids for CHFR

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CHFR Gene

Localization for CHFR Gene

Subcellular locations from UniProtKB/Swiss-Prot for CHFR Gene

Nucleus, PML body.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CHFR gene
Compartment Confidence
nucleus 5
cytoskeleton 2
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Microtubules (1)
  • Nuclear bodies (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CHFR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA,IBA 18172500
GO:0016605 PML body IDA,IEA 15467728
genes like me logo Genes that share ontologies with CHFR: view

Pathways & Interactions for CHFR Gene

PathCards logo

SuperPathways for CHFR Gene

SuperPathway Contained pathways
1 DNA Damage
genes like me logo Genes that share pathways with CHFR: view

Pathways by source for CHFR Gene

1 Cell Signaling Technology pathway for CHFR Gene

UniProtKB/Swiss-Prot Q96EP1-CHFR_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for CHFR Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination IEA,IDA 19182791
GO:0000278 mitotic cell cycle IEA --
GO:0006511 ubiquitin-dependent protein catabolic process IBA,IEA 21873635
GO:0007049 cell cycle IEA --
GO:0007093 mitotic cell cycle checkpoint IBA,TAS 10935642
genes like me logo Genes that share ontologies with CHFR: view

No data available for SIGNOR curated interactions for CHFR Gene

Drugs & Compounds for CHFR Gene

(4) Drugs for CHFR Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoric acid Approved Pharma 0
Adenosine monophosphate Approved, Investigational Nutra 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Pore Blocker, Potentiation 0

(1) Additional Compounds for CHFR Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
pyrophosphate
  • [(ho)2P(O)OP(O)(OH)2]
  • Acide diphosphorique
  • Diphosphorsaeure
  • H4P2O7
  • PYROphosphATE
14000-31-8
genes like me logo Genes that share compounds with CHFR: view

Transcripts for CHFR Gene

mRNA/cDNA for CHFR Gene

5 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
24 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for CHFR

Alternative Splicing Database (ASD) splice patterns (SP) for CHFR Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b · 16c ^
SP1: - - - - - - - - -
SP2: - - - - - - - -
SP3: - - - - - - - - -
SP4: - - - - - - - - -
SP5: - - - -
SP6:
SP7: -
SP8: - - - -
SP9:
SP10: -
SP11:
SP12: -
SP13:
SP14:

ExUns: 17a · 17b ^ 18a · 18b ^ 19a · 19b ^ 20 ^ 21 ^ 22a · 22b · 22c · 22d · 22e · 22f
SP1: - - -
SP2: - - -
SP3: - - -
SP4: - -
SP5: - - -
SP6: - - -
SP7:
SP8:
SP9: -
SP10:
SP11:
SP12:
SP13:
SP14:

Relevant External Links for CHFR Gene

GeneLoc Exon Structure for
CHFR

Expression for CHFR Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CHFR Gene

Protein differential expression in normal tissues from HIPED for CHFR Gene

This gene is overexpressed in Urine (66.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CHFR Gene



Protein tissue co-expression partners for CHFR Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CHFR

SOURCE GeneReport for Unigene cluster for CHFR Gene:

Hs.720197

mRNA Expression by UniProt/SwissProt for CHFR Gene:

Q96EP1-CHFR_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for CHFR Gene

  • Nervous system(3.4)
  • Intestine(2.3)
genes like me logo Genes that share expression patterns with CHFR: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for CHFR Gene

Orthologs for CHFR Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CHFR Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CHFR 31 30
  • 99.41 (n)
OneToOne
dog
(Canis familiaris)
Mammalia CHFR 31 30
  • 84.82 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CHFR 31 30
  • 84.54 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Chfr 17 31 30
  • 82.95 (n)
rat
(Rattus norvegicus)
Mammalia Chfr 30
  • 82.42 (n)
oppossum
(Monodelphis domestica)
Mammalia CHFR 31
  • 75 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CHFR 31
  • 72 (a)
OneToOne
chicken
(Gallus gallus)
Aves CHFR 31 30
  • 70.15 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CHFR 31
  • 66 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia chfr 30
  • 66.18 (n)
MGC75959 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.25667 30
zebrafish
(Danio rerio)
Actinopterygii chfr 31 30
  • 62.17 (n)
OneToOne
thale cress
(Arabidopsis thaliana)
eudicotyledons AT1G47570 30
  • 41.12 (n)
rice
(Oryza sativa)
Liliopsida Os11g0175500 30
  • 43.18 (n)
Species where no ortholog for CHFR was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CHFR Gene

ENSEMBL:
Gene Tree for CHFR (if available)
TreeFam:
Gene Tree for CHFR (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CHFR: view image

Paralogs for CHFR Gene

(7) SIMAP similar genes for CHFR Gene using alignment to 9 proteins:

  • CHFR_HUMAN
  • F5GWH4_HUMAN
  • F5H375_HUMAN
  • F5H5P5_HUMAN
  • F5H7R8_HUMAN
  • F5H829_HUMAN
  • J3KN56_HUMAN
  • U3KPU9_HUMAN
  • U3KQ08_HUMAN

Pseudogenes.org Pseudogenes for CHFR Gene

genes like me logo Genes that share paralogs with CHFR: view

No data available for Paralogs for CHFR Gene

Variants for CHFR Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CHFR Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
725004 Benign: not provided 132,848,720(-) C/T SYNONYMOUS_VARIANT
733760 Benign: not provided 132,851,694(-) C/T SYNONYMOUS_VARIANT
rs1176037831 A patient with non small cell lung carcinomas p.Pro166Leu
VAR_017583 A patient with non small cell lung carcinomas p.Arg202Pro
VAR_017586 A patient with non small cell lung carcinomas p.Phe536Ser

Additional dbSNP identifiers (rs#s) for CHFR Gene

Structural Variations from Database of Genomic Variants (DGV) for CHFR Gene

Variant ID Type Subtype PubMed ID
dgv1589n100 CNV gain 25217958
dgv3058n54 CNV gain+loss 21841781
dgv318e214 CNV loss 21293372
esv1097344 CNV insertion 17803354
esv2378478 CNV deletion 18987734
esv2382110 CNV deletion 18987734
esv2463073 CNV deletion 19546169
esv25804 CNV loss 19812545
esv2661448 CNV deletion 23128226
esv2667136 CNV deletion 23128226
esv2674916 CNV deletion 23128226
esv3631320 CNV gain 21293372
esv3631321 CNV loss 21293372
nsv1140126 CNV insertion 24896259
nsv1147078 CNV deletion 26484159
nsv455812 CNV loss 19166990
nsv561133 CNV loss 21841781
nsv561134 CNV loss 21841781
nsv561135 CNV loss 21841781
nsv561136 CNV loss 21841781
nsv561139 CNV gain 21841781
nsv561140 CNV loss 21841781
nsv561141 CNV gain 21841781
nsv952513 CNV deletion 24416366

Variation tolerance for CHFR Gene

Residual Variation Intolerance Score: 19.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 14.70; 96.61% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CHFR Gene

Human Gene Mutation Database (HGMD)
CHFR
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CHFR

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CHFR Gene

Disorders for CHFR Gene

MalaCards: The human disease database

(1) MalaCards diseases for CHFR Gene - From: DISEASES

Disorder Aliases PubMed IDs
hypertrichosis universalis congenita, ambras type
  • htc1
- elite association - COSMIC cancer census association via MalaCards
Search CHFR in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CHFR

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CHFR: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CHFR Gene

Publications for CHFR Gene

  1. The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and inhibits Cdc2 at the G2 to M transition. (PMID: 11807090) Kang D … Fang G (The Journal of cell biology 2002) 2 3 4 23 54
  2. Chfr defines a mitotic stress checkpoint that delays entry into metaphase. (PMID: 10935642) Scolnick DM … Halazonetis TD (Nature 2000) 2 3 4 23 54
  3. The anti-proliferative effects of the CHFR depend on the forkhead associated domain, but not E3 ligase activity mediated by ring finger domain. (PMID: 18335050) Fukuda T … Nakagama H (PloS one 2008) 3 4 23 54
  4. Promotion of mitosis by activated protein kinase B after DNA damage involves polo-like kinase 1 and checkpoint protein CHFR. (PMID: 14638868) Shtivelman E (Molecular cancer research : MCR 2003) 3 4 23 54
  5. The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains. (PMID: 14562038) Bothos J … Halazonetis TD (Oncogene 2003) 3 4 23 54

Products for CHFR Gene

Sources for CHFR Gene