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    RFWD3 ring finger and WD repeat domain 3 [ Homo sapiens (human) ]

    Gene ID: 55159, updated on 2-Nov-2024

    Summary

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    Official Symbol
    RFWD3provided by HGNC
    Official Full Name
    ring finger and WD repeat domain 3provided by HGNC
    Primary source
    HGNC:HGNC:25539
    See related
    Ensembl:ENSG00000168411 MIM:614151; AllianceGenome:HGNC:25539
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FANCW; RNF201
    Summary
    Enables MDM2/MDM4 family protein binding activity; p53 binding activity; and ubiquitin protein ligase activity. Involved in several processes, including DNA metabolic process; regulation of cell cycle phase transition; and response to ionizing radiation. Located in nucleoplasm and site of double-strand break. Implicated in Fanconi anemia complementation group W. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Broad expression in testis (RPKM 15.0), bone marrow (RPKM 14.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RFWD3 in Genome Data Viewer
    Location:
    16q23.1
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (74621399..74666877, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (80668129..80713619, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (74655297..74700775, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene golgi glycoprotein 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:74586439-74586940 Neighboring gene MPRA-validated peak2638 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:74599495-74599996 Neighboring gene ribosomal protein S10 pseudogene 23 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:74601639-74602138 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7697 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7698 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:74654659-74655158 Neighboring gene heat shock protein family E (Hsp10) member 1 pseudogene 7 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7699 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:74715965-74716163 Neighboring gene thymopoietin pseudogene 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:74728193-74728362 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11108 Neighboring gene mixed lineage kinase domain like pseudokinase

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Identification of an E3 ligase-encoding gene RFWD3 in non-small cell lung cancer. Zhang Y, et al. Front Med, 2020 Jun. PMID 31571161
    2. Systematic analysis on expression quantitative trait loci identifies a novel regulatory variant in ring finger and WD repeat domain 3 associated with prognosis of pancreatic cancer. Zhu Y, et al. Chin Med J (Engl), 2022 Jun 5. PMID 35830250, Free PMC Article
    3. Down-regulation of RFWD3 inhibits cancer cells proliferation and migration in gastric carcinoma. Jia J, et al. Gen Physiol Biophys, 2020 Jul. PMID 32902405
    4. E3 ligase RFWD3 is a novel modulator of stalled fork stability in BRCA2-deficient cells. Duan H, et al. J Cell Biol, 2020 Jun 1. PMID 32391871, Free PMC Article
    5. PCNA-mediated stabilization of E3 ligase RFWD3 at the replication fork is essential for DNA replication. Lin YC, et al. Proc Natl Acad Sci U S A, 2018 Dec 26. PMID 30530694, Free PMC Article

    See all (56) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. RFWD3 promotes ZRANB3 recruitment to regulate the remodeling of stalled replication forks.
      Title: RFWD3 promotes ZRANB3 recruitment to regulate the remodeling of stalled replication forks.
    2. Systematic analysis on expression quantitative trait loci identifies a novel regulatory variant in ring finger and WD repeat domain 3 associated with prognosis of pancreatic cancer.
      Title: Systematic analysis on expression quantitative trait loci identifies a novel regulatory variant in ring finger and WD repeat domain 3 associated with prognosis of pancreatic cancer.
    3. The E3 ligase RFWD3 stabilizes ORC in a p53-dependent manner.
      Title: The E3 ligase RFWD3 stabilizes ORC in a p53-dependent manner.
    4. E3 ligase RFWD3 is a novel modulator of stalled fork stability in BRCA2-deficient cells.
      Title: E3 ligase RFWD3 is a novel modulator of stalled fork stability in BRCA2-deficient cells.
    5. Identification of an E3 ligase-encoding gene RFWD3 in non-small cell lung cancer.
      Title: Identification of an E3 ligase-encoding gene RFWD3 in non-small cell lung cancer.
    6. The ubiquitin ligase RFWD3 is required for translesion DNA synthesis.
      Title: The ubiquitin ligase RFWD3 is required for translesion DNA synthesis.
    7. Down-regulation of RFWD3 inhibits cancer cells proliferation and migration in gastric carcinoma.
      Title: Down-regulation of RFWD3 inhibits cancer cells proliferation and migration in gastric carcinoma.
    8. The results suggest that RPA phosphorylation enhances the recruitment of PRP19 to RPA-ssDNA and stimulates RPA ubiquitylation through a process requiring both PRP19 and RFWD3, thereby triggering a phosphorylation-ubiquitylation circuitry that promotes ATR activation and homologous recombination.
      Title: A phosphorylation-and-ubiquitylation circuitry driving ATR activation and homologous recombination.
    9. E3 ligase RFWD3 functions in timely removal and degradation of RPA and RAD51 to allow homologous recombination progression to subsequent steps following mitomycin C damage.
      Title: RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination.
    10. Single point mutations in the RPA32 subunit of RPA that abolish interaction with RFWD3 also inhibit interstrand crossling repair, demonstrating that RPA-mediated RFWD3 recruitment to stalled replication forks is important for ICL repair.
      Title: RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for Interstrand Crosslink Repair and Human Health.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Fanconi anemia, complementation group W
    MedGen: C4521564 OMIM: 617784 GeneReviews: Fanconi Anemia
    		Compare labs

    EBI GWAS Catalog

    Description
    Meta-analysis identifies four new loci associated with testicular germ cell tumor.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ10520

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables MDM2/MDM4 family protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables p53 binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin protein ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in double-strand break repair via homologous recombination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in double-strand break repair via homologous recombination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in interstrand cross-link repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in interstrand cross-link repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitotic G1 DNA damage checkpoint signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of DNA damage checkpoint IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in replication fork processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in replication fork processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to ionizing radiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in PML body IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    is_active_in site of DNA damage IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in site of DNA damage IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    colocalizes_with site of double-strand break IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase RFWD3
    Names
    RING finger and WD repeat domain-containing protein 3
    RING finger protein 201
    RING-type E3 ubiquitin transferase RFWD3
    NP_001357463.1
    NP_001357464.1
    NP_001357465.1
    NP_001357466.1
    NP_001357468.1
    NP_001357469.1
    NP_001357471.1
    NP_001357472.1
    NP_060594.3
    XP_005256079.1
    XP_006721291.1
    XP_011521493.1
    XP_016878880.1
    XP_047290279.1
    XP_047290280.1
    XP_054236617.1
    XP_054236618.1
    XP_054236619.1
    XP_054236620.1
    XP_054236621.1
    XP_054236622.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001370534.1 → NP_001357463.1  E3 ubiquitin-protein ligase RFWD3 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC109599
      Consensus CDS
      CCDS32486.1
      UniProtKB/Swiss-Prot
      A8K585, B2RE35, D3DUJ8, Q5XKR3, Q6PCD5, Q9H9Q3, Q9NVT4
      Conserved Domains (3) summary
      COG2319
      Location:486 → 774
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:500 → 537
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:283 → 331
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    2. NM_001370535.1 → NP_001357464.1  E3 ubiquitin-protein ligase RFWD3 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC109599
      Consensus CDS
      CCDS32486.1
      UniProtKB/Swiss-Prot
      A8K585, B2RE35, D3DUJ8, Q5XKR3, Q6PCD5, Q9H9Q3, Q9NVT4
      Related
      ENSP00000460049.1, ENST00000571750.5
      Conserved Domains (3) summary
      COG2319
      Location:486 → 774
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:500 → 537
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:283 → 331
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    3. NM_001370536.1 → NP_001357465.1  E3 ubiquitin-protein ligase RFWD3 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC109599
      Conserved Domains (2) summary
      COG2319
      Location:479 → 715
      WD40; WD40 repeat [General function prediction only]
      cd16450
      Location:283 → 331
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    4. NM_001370537.1 → NP_001357466.1  E3 ubiquitin-protein ligase RFWD3 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC109599
      Conserved Domains (3) summary
      COG2319
      Location:208 → 496
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:264 → 302
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:5 → 65
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    5. NM_001370539.1 → NP_001357468.1  E3 ubiquitin-protein ligase RFWD3 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC109599
      Conserved Domains (3) summary
      COG2319
      Location:208 → 496
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:264 → 302
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:5 → 65
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    6. NM_001370540.1 → NP_001357469.1  E3 ubiquitin-protein ligase RFWD3 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC109599
      Conserved Domains (3) summary
      COG2319
      Location:208 → 496
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:264 → 302
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:5 → 65
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    7. NM_001370542.1 → NP_001357471.1  E3 ubiquitin-protein ligase RFWD3 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC109599
      Conserved Domains (3) summary
      COG2319
      Location:208 → 496
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:264 → 302
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:5 → 65
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    8. NM_001370543.1 → NP_001357472.1  E3 ubiquitin-protein ligase RFWD3 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC109599
      Conserved Domains (3) summary
      COG2319
      Location:208 → 496
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:264 → 302
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:5 → 65
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    9. NM_018124.4 → NP_060594.3  E3 ubiquitin-protein ligase RFWD3 isoform 1

      See identical proteins and their annotated locations for NP_060594.3

      Status: VALIDATED

      Source sequence(s)
      BC002574, BC059371, BM467919, BP872110
      Consensus CDS
      CCDS32486.1
      UniProtKB/Swiss-Prot
      A8K585, B2RE35, D3DUJ8, Q5XKR3, Q6PCD5, Q9H9Q3, Q9NVT4
      Related
      ENSP00000354361.4, ENST00000361070.9
      Conserved Domains (3) summary
      COG2319
      Location:486 → 774
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:500 → 537
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:283 → 331
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      74621399..74666877 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011523191.4 → XP_011521493.1  E3 ubiquitin-protein ligase RFWD3 isoform X1

      See identical proteins and their annotated locations for XP_011521493.1

      UniProtKB/Swiss-Prot
      A8K585, B2RE35, D3DUJ8, Q5XKR3, Q6PCD5, Q9H9Q3, Q9NVT4
      Conserved Domains (3) summary
      COG2319
      Location:486 → 774
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:500 → 537
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:283 → 331
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    2. XM_047434323.1 → XP_047290279.1  E3 ubiquitin-protein ligase RFWD3 isoform X2

    3. XM_017023391.2 → XP_016878880.1  E3 ubiquitin-protein ligase RFWD3 isoform X1

      UniProtKB/Swiss-Prot
      A8K585, B2RE35, D3DUJ8, Q5XKR3, Q6PCD5, Q9H9Q3, Q9NVT4
      Conserved Domains (3) summary
      COG2319
      Location:486 → 774
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:500 → 537
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:283 → 331
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    4. XM_006721228.4 → XP_006721291.1  E3 ubiquitin-protein ligase RFWD3 isoform X2

      Conserved Domains (2) summary
      COG2319
      Location:479 → 715
      WD40; WD40 repeat [General function prediction only]
      cd16450
      Location:283 → 331
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    5. XM_005256022.5 → XP_005256079.1  E3 ubiquitin-protein ligase RFWD3 isoform X1

      See identical proteins and their annotated locations for XP_005256079.1

      UniProtKB/Swiss-Prot
      A8K585, B2RE35, D3DUJ8, Q5XKR3, Q6PCD5, Q9H9Q3, Q9NVT4
      Conserved Domains (3) summary
      COG2319
      Location:486 → 774
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:500 → 537
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:283 → 331
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    6. XM_047434324.1 → XP_047290280.1  E3 ubiquitin-protein ligase RFWD3 isoform X3

      Conserved Domains (3) summary
      COG2319
      Location:208 → 496
      WD40; WD40 repeat [General function prediction only]
      sd00039
      Location:264 → 302
      7WD40; WD40 repeat [structural motif]
      cd16450
      Location:5 → 65
      mRING-C3HGC3_RFWD3; Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      80668129..80713619 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054380644.1 → XP_054236619.1  E3 ubiquitin-protein ligase RFWD3 isoform X2

    2. XM_054380642.1 → XP_054236617.1  E3 ubiquitin-protein ligase RFWD3 isoform X1

      UniProtKB/Swiss-Prot
      A8K585, B2RE35, D3DUJ8, Q5XKR3, Q6PCD5, Q9H9Q3, Q9NVT4

    3. XM_054380643.1 → XP_054236618.1  E3 ubiquitin-protein ligase RFWD3 isoform X2

    4. XM_054380646.1 → XP_054236621.1  E3 ubiquitin-protein ligase RFWD3 isoform X1

      UniProtKB/Swiss-Prot
      A8K585, B2RE35, D3DUJ8, Q5XKR3, Q6PCD5, Q9H9Q3, Q9NVT4

    5. XM_054380645.1 → XP_054236620.1  E3 ubiquitin-protein ligase RFWD3 isoform X1

      UniProtKB/Swiss-Prot
      A8K585, B2RE35, D3DUJ8, Q5XKR3, Q6PCD5, Q9H9Q3, Q9NVT4

    6. XM_054380647.1 → XP_054236622.1  E3 ubiquitin-protein ligase RFWD3 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6PCD5.3 GenPept UniProtKB/Swiss-Prot:Q6PCD5

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