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Aliases for RFWD3 Gene

Aliases for RFWD3 Gene

  • Ring Finger And WD Repeat Domain 3 2 3 5
  • RING Finger And WD Repeat Domain-Containing Protein 3 3 4
  • RING Finger Protein 201 3 4
  • RNF201 3 4
  • RING-Type E3 Ubiquitin Transferase RFWD3 3
  • E3 Ubiquitin-Protein Ligase RFWD3 3
  • EC 2.3.2.27 4
  • FANCW 3

External Ids for RFWD3 Gene

Previous GeneCards Identifiers for RFWD3 Gene

  • GC16M073214
  • GC16M060404

Summaries for RFWD3 Gene

GeneCards Summary for RFWD3 Gene

RFWD3 (Ring Finger And WD Repeat Domain 3) is a Protein Coding gene. Diseases associated with RFWD3 include Fanconi Anemia, Complementation Group W and Fanconi Anemia, Complementation Group A. Gene Ontology (GO) annotations related to this gene include ligase activity and p53 binding.

UniProtKB/Swiss-Prot for RFWD3 Gene

  • E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658). Plays a key role in RPA-mediated DNA damage signaling and repair (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658). Acts by mediating ubiquitination of the RPA complex (RPA1, RPA2 and RPA3 subunits) and RAD51 at stalled replication forks, leading to remove them from DNA damage sites and promote homologous recombination (PubMed:26474068, PubMed:28575657, PubMed:28575658). Also mediates the ubiquitination of p53/TP53 in the late response to DNA damage, and acts as a positive regulator of p53/TP53 stability, thereby regulating the G1/S DNA damage checkpoint (PubMed:20173098). May act by catalyzing the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome (PubMed:20173098). In response to ionizing radiation, interacts with MDM2 and enhances p53/TP53 ubiquitination, possibly by restricting MDM2 from extending polyubiquitin chains on ubiquitinated p53/TP53 (PubMed:20173098).

Additional gene information for RFWD3 Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RFWD3 Gene

Genomics for RFWD3 Gene

GeneHancer (GH) Regulatory Elements for RFWD3 Gene

Promoters and enhancers for RFWD3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH16I074666 Promoter/Enhancer 2.3 EPDnew FANTOM5 Ensembl ENCODE 629.1 -0.1 -103 2.4 HDGF PKNOX1 SMAD1 ZFP64 ARID4B NEUROD1 SIN3A DMAP1 ZNF2 YY1 RFWD3 TMPOP2 ENSG00000214331 ADAT1 KARS ENSG00000261079 GLG1 NPIPB15
GH16I074665 Promoter 0.5 EPDnew 550.8 +1.7 1667 0.1 RFWD3 HSPE1P7
GH16I074605 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 47.5 +59.5 59534 4.3 HDGF PKNOX1 SMAD1 MLX ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 GLG1 RFWD3 ENSG00000259972 RPL21P118 ENSG00000260884 ENSG00000214331 BCAR1 TMEM231 WDR59 CLEC18B
GH16I075564 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE 37.2 -899.4 -899354 3.2 HDGF PKNOX1 CLOCK SMAD1 ARNT ARID4B SIN3A FEZF1 DMAP1 ZBTB7B GABARAPL2 RFWD3 ADAT1 KARS WDR59 TMEM231 TMEM170A ENSG00000276408 ENSG00000259992
GH16I075432 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 25.6 -766.9 -766862 2.5 CLOCK MLX ZFP64 DMAP1 YY1 SLC30A9 ZNF213 E2F8 ZNF143 SP3 CFDP1 ENSG00000274220 ENSG00000261783 RFWD3 ADAT1 GLG1 TMEM231 ENSG00000261717
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around RFWD3 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the RFWD3 gene promoter:

Genomic Locations for RFWD3 Gene

Genomic Locations for RFWD3 Gene
chr16:74,621,394-74,666,892
(GRCh38/hg38)
Size:
45,499 bases
Orientation:
Minus strand
chr16:74,655,292-74,700,779
(GRCh37/hg19)

Genomic View for RFWD3 Gene

Genes around RFWD3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RFWD3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RFWD3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RFWD3 Gene

Proteins for RFWD3 Gene

  • Protein details for RFWD3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6PCD5-RFWD3_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase RFWD3
    Protein Accession:
    Q6PCD5
    Secondary Accessions:
    • A8K585
    • B2RE35
    • D3DUJ8
    • Q5XKR3
    • Q9H9Q3
    • Q9NVT4

    Protein attributes for RFWD3 Gene

    Size:
    774 amino acids
    Molecular mass:
    85094 Da
    Quaternary structure:
    • Interacts with MDM2 and p53/TP53 (PubMed:20173098). Binds to the RPA complex via direct interaction with RPA2 (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575658). Interacts with RAD51 (PubMed:28575658).
    SequenceCaution:
    • Sequence=BAA91662.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAF83889.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAG38132.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

neXtProt entry for RFWD3 Gene

Post-translational modifications for RFWD3 Gene

  • Phosphorylated at Ser-46 and Ser-63 upon DNA damage by ATM or ATR. ATM phosphorylation occurs at early times upon DNA damage, while ATR is the major kinase at later times. Phosphorylation by ATM and ATR is required to stabilize p53/TP53. Part of the phosphorylation depends upon RPA2 presence.
  • Ubiquitination at Lys364, isoforms=370, Lys389, Lys402, isoforms=440, isoforms=498, Lys583, Lys658, isoforms=697, and isoforms=766

No data available for DME Specific Peptides for RFWD3 Gene

Domains & Families for RFWD3 Gene

Suggested Antigen Peptide Sequences for RFWD3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q6PCD5

UniProtKB/Swiss-Prot:

RFWD3_HUMAN :
  • The coiled coil domain may be involved in RPA2-binding.
Domain:
  • The coiled coil domain may be involved in RPA2-binding.
genes like me logo Genes that share domains with RFWD3: view

Function for RFWD3 Gene

Molecular function for RFWD3 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
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.
UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658). Plays a key role in RPA-mediated DNA damage signaling and repair (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658). Acts by mediating ubiquitination of the RPA complex (RPA1, RPA2 and RPA3 subunits) and RAD51 at stalled replication forks, leading to remove them from DNA damage sites and promote homologous recombination (PubMed:26474068, PubMed:28575657, PubMed:28575658). Also mediates the ubiquitination of p53/TP53 in the late response to DNA damage, and acts as a positive regulator of p53/TP53 stability, thereby regulating the G1/S DNA damage checkpoint (PubMed:20173098). May act by catalyzing the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome (PubMed:20173098). In response to ionizing radiation, interacts with MDM2 and enhances p53/TP53 ubiquitination, possibly by restricting MDM2 from extending polyubiquitin chains on ubiquitinated p53/TP53 (PubMed:20173098).

Enzyme Numbers (IUBMB) for RFWD3 Gene

Phenotypes From GWAS Catalog for RFWD3 Gene

Gene Ontology (GO) - Molecular Function for RFWD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002039 p53 binding IPI 20173098
GO:0004842 ubiquitin-protein transferase activity IDA 20173098
GO:0005515 protein binding IPI 19549727
GO:0016740 transferase activity IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with RFWD3: view
genes like me logo Genes that share phenotypes with RFWD3: view

Animal Models for RFWD3 Gene

MGI Knock Outs for RFWD3:

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RFWD3 Gene

Localization for RFWD3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RFWD3 Gene

Nucleus. Nucleus, PML body. Cytoplasm. Note=In undamaged cells, found both in the cytoplasm and in the nucleus, partially associated with PML nuclear bodies (PubMed:21558276). In response to replication block, such as that caused by hydroxyurea treatment, or to DNA damage caused by ionizing radiations or doxorubicin, recruited to the nucleus, to stalled replication forks or to sites of DNA repair (PubMed:21504906, PubMed:28575657). This recruitment depends upon RPA2 (PubMed:21504906). {ECO:0000269 PubMed:21504906, ECO:0000269 PubMed:28575657}.

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 RFWD3 gene
Compartment Confidence
nucleus 5
cytosol 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (4)
  • Cytosol (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RFWD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 20173098
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IEA --
GO:0016605 PML body IEA --
GO:0035861 colocalizes_with site of double-strand break IDA 21504906
genes like me logo Genes that share ontologies with RFWD3: view

Pathways & Interactions for RFWD3 Gene

SuperPathways for RFWD3 Gene

No Data Available

UniProtKB/Swiss-Prot Q6PCD5-RFWD3_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for RFWD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000724 double-strand break repair via homologous recombination IDA 26474068
GO:0006281 DNA repair IEA --
GO:0006974 cellular response to DNA damage stimulus IDA,IEA 26474068
GO:0010212 response to ionizing radiation IDA 20173098
GO:0016567 protein ubiquitination IEA --
genes like me logo Genes that share ontologies with RFWD3: view

No data available for Pathways by source and SIGNOR curated interactions for RFWD3 Gene

Drugs & Compounds for RFWD3 Gene

(1) Drugs for RFWD3 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
ATP Investigational Nutra Agonist 0

(1) Additional Compounds for RFWD3 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
genes like me logo Genes that share compounds with RFWD3: view

Transcripts for RFWD3 Gene

Unigene Clusters for RFWD3 Gene

Ring finger and WD repeat domain 3:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for RFWD3 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c · 5d · 5e ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12a · 12b ^
SP1: - - - - - - - -
SP2: -
SP3: - - -
SP4: - -
SP5: - - -
SP6: - -
SP7: -
SP8:
SP9:

ExUns: 13 ^ 14a · 14b ^ 15 ^ 16
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:

Relevant External Links for RFWD3 Gene

GeneLoc Exon Structure for
RFWD3
ECgene alternative splicing isoforms for
RFWD3

Expression for RFWD3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RFWD3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RFWD3 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for RFWD3 Gene



Protein tissue co-expression partners for RFWD3 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of RFWD3 Gene:

RFWD3

SOURCE GeneReport for Unigene cluster for RFWD3 Gene:

Hs.567525

Evidence on tissue expression from TISSUES for RFWD3 Gene

  • Nervous system(4.4)
genes like me logo Genes that share expression patterns with RFWD3: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for RFWD3 Gene

Orthologs for RFWD3 Gene

This gene was present in the common ancestor of animals.

Orthologs for RFWD3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RFWD3 33 34
  • 99.61 (n)
dog
(Canis familiaris)
Mammalia RFWD3 33 34
  • 84.2 (n)
cow
(Bos Taurus)
Mammalia RFWD3 33 34
  • 81.92 (n)
mouse
(Mus musculus)
Mammalia Rfwd3 33 16 34
  • 76.7 (n)
rat
(Rattus norvegicus)
Mammalia Rfwd3 33
  • 74.22 (n)
oppossum
(Monodelphis domestica)
Mammalia RFWD3 34
  • 60 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RFWD3 34
  • 60 (a)
OneToOne
chicken
(Gallus gallus)
Aves RFWD3 33 34
  • 67.27 (n)
lizard
(Anolis carolinensis)
Reptilia RFWD3 34
  • 56 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rfwd3 33
  • 60.66 (n)
Str.818 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.29638 33
zebrafish
(Danio rerio)
Actinopterygii LOC100329327 33
  • 59.89 (n)
rfwd3 34
  • 49 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005643 33
  • 41.44 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG13025 33 34
  • 41.08 (n)
CG17329 34
  • 27 (a)
OneToMany
CG14983 34
  • 25 (a)
OneToMany
CG13481 34
  • 23 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.787 34
  • 37 (a)
OneToOne
Species where no ortholog for RFWD3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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 (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for RFWD3 Gene

ENSEMBL:
Gene Tree for RFWD3 (if available)
TreeFam:
Gene Tree for RFWD3 (if available)

Paralogs for RFWD3 Gene

No data available for Paralogs for RFWD3 Gene

Variants for RFWD3 Gene

Sequence variations from dbSNP and Humsavar for RFWD3 Gene

SNP ID Clin Chr 16 pos Variation AA Info Type
rs1000039792 -- 74,631,918(-) T/C intron_variant
rs1000070959 -- 74,632,067(-) C/T intron_variant
rs1000174234 -- 74,644,520(-) G/A intron_variant
rs1000186609 -- 74,664,366(-) C/A genic_upstream_transcript_variant, intron_variant, upstream_transcript_variant
rs1000214364 -- 74,626,814(-) A/G intron_variant

Structural Variations from Database of Genomic Variants (DGV) for RFWD3 Gene

Variant ID Type Subtype PubMed ID
nsv833279 CNV loss 17160897
nsv572975 CNV loss 21841781
nsv472098 CNV novel sequence insertion 20440878
esv2760414 CNV gain 21179565
esv275138 CNV gain+loss 21479260

Variation tolerance for RFWD3 Gene

Residual Variation Intolerance Score: 13.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.66; 86.39% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RFWD3 Gene

Human Gene Mutation Database (HGMD)
RFWD3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RFWD3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RFWD3 Gene

Disorders for RFWD3 Gene

MalaCards: The human disease database

(2) MalaCards diseases for RFWD3 Gene - From: HGMD, OMIM, ClinVar, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search RFWD3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

RFWD3_HUMAN
  • Note=Fanconi anemia, complementation group W (FANCW): A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair (PubMed:28575657). The disease is caused by mutations affecting the gene represented in this entry. {ECO:0000269 PubMed:28575657}.

Additional Disease Information for RFWD3

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 RFWD3: view

No data available for Genatlas for RFWD3 Gene

Publications for RFWD3 Gene

  1. E3 ligase RFWD3 participates in replication checkpoint control. (PMID: 21504906) Gong Z … Chen J (The Journal of biological chemistry 2011) 2 3 4 58
  2. RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination. (PMID: 28575658) Inano S … Takata M (Molecular cell 2017) 3 4 58
  3. RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for Interstrand Crosslink Repair and Human Health. (PMID: 28575657) Feeney L … Rouse J (Molecular cell 2017) 3 4 58
  4. Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia. (PMID: 28691929) Knies K … Schindler D (The Journal of clinical investigation 2017) 2 3 58
  5. RFWD3-Dependent Ubiquitination of RPA Regulates Repair at Stalled Replication Forks. (PMID: 26474068) Elia AE … Elledge SJ (Molecular cell 2015) 3 4 58

Products for RFWD3 Gene

Sources for RFWD3 Gene

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