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    RNF216 ring finger protein 216 [ Homo sapiens (human) ]

    Gene ID: 54476, updated on 28-Oct-2024

    Summary

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    Official Symbol
    RNF216provided by HGNC
    Official Full Name
    ring finger protein 216provided by HGNC
    Primary source
    HGNC:HGNC:21698
    See related
    Ensembl:ENSG00000011275 MIM:609948; AllianceGenome:HGNC:21698
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ZIN; CAHH; U7I1; TRIAD3; UBCE7IP1
    Summary
    This gene encodes a cytoplasmic protein which specifically colocalizes and interacts with the serine/threonine protein kinase, receptor-interacting protein (RIP). Zinc finger domains of the encoded protein are required for its interaction with RIP and for inhibition of TNF- and IL1-induced NF-kappa B activation pathways. The encoded protein may also function as an E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes and transfers it to substrates. Several alternatively spliced transcript variants have been described for this locus but the full-length natures of only some are known. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 16.3), lymph node (RPKM 10.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See RNF216 in Genome Data Viewer
    Location:
    7p22.1
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (5620047..5781663, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (5737579..5899098, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (5659678..5821294, complement)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene S100 calcium binding protein A11 pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5601490-5602016 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5602542-5603067 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5602017-5602541 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:5609174-5610162 Neighboring gene CRISPRi-validated cis-regulatory element chr7.769 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25602 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17924 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5626381-5626880 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25603 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25604 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17925 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17926 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:5633617-5634192 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17928 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:5634770-5635345 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:5636965-5637180 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5642390-5643243 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5643244-5644096 Neighboring gene Sharpr-MPRA regulatory region 1133 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5648079-5648632 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5655393-5656132 Neighboring gene fascin actin-bundling protein 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5666829-5667500 Neighboring gene VISTA enhancer hs1623 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:5678992-5679856 Neighboring gene RNF216 intronic transcript 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25605 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25606 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25607 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25608 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17929 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25609 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5735716-5736216 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5736217-5736717 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25610 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr7:5741581-5742780 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25611 Neighboring gene microRNA 6874 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5775501-5776002 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5776003-5776502 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17930 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25612 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:5871051-5871551 Neighboring gene zinc finger protein 815, pseudogene Neighboring gene Sharpr-MPRA regulatory region 1711 Neighboring gene RNA, 7SL, cytoplasmic 556, pseudogene Neighboring gene oncomodulin

    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. Ring finger protein 216 loss-of-function induces white matter hyperintensities by inhibiting oligodendroglia proliferation. Xu W, et al. Cell Biochem Funct, 2024 Jun. PMID 38853469
    2. Clinical and genetic spectrum of RNF216-related disorder: a new case and literature review. Wu C, et al. J Med Genet, 2024 Apr 19. PMID 38050071
    3. RNF216 mutations as a novel cause of autosomal recessive Huntington-like disorder. Santens P, et al. Neurology, 2015 Apr 28. PMID 25841028
    4. Whole-Exome Sequencing Identified a Novel Mutation in RNF216 in a Family with Gordon Holmes Syndrome. Chen KL, et al. J Mol Neurosci, 2022 Apr. PMID 35088240
    5. Structural basis of K63-ubiquitin chain formation by the Gordon-Holmes syndrome RBR E3 ubiquitin ligase RNF216. Cotton TR, et al. Mol Cell, 2022 Feb 3. PMID 34998453

    See all (66) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Ring finger protein 216 loss-of-function induces white matter hyperintensities by inhibiting oligodendroglia proliferation.
      Title: Ring finger protein 216 loss-of-function induces white matter hyperintensities by inhibiting oligodendroglia proliferation.
    2. Clinical and genetic spectrum of RNF216-related disorder: a new case and literature review.
      Title: Clinical and genetic spectrum of RNF216-related disorder: a new case and literature review.
    3. RNF216 affects the stability of STAU2 in the hypothalamus.
      Title: RNF216 affects the stability of STAU2 in the hypothalamus.
    4. Whole-Exome Sequencing Identified a Novel Mutation in RNF216 in a Family with Gordon Holmes Syndrome.
      Title: Whole-Exome Sequencing Identified a Novel Mutation in RNF216 in a Family with Gordon Holmes Syndrome.
    5. Structural basis of K63-ubiquitin chain formation by the Gordon-Holmes syndrome RBR E3 ubiquitin ligase RNF216.
      Title: Structural basis of K63-ubiquitin chain formation by the Gordon-Holmes syndrome RBR E3 ubiquitin ligase RNF216.
    6. [Screening of interacting proteins of idiopathic gonadotropin-releasing hormone deficiency pathogenic gene RNF216].
      Title: [Screening of interacting proteins of idiopathic gonadotropin-releasing hormone deficiency pathogenic gene RNF216].
    7. RNF216 regulates meiosis and PKA stability in the testes.
      Title: RNF216 regulates meiosis and PKA stability in the testes.
    8. An essential function of RNF216 in spermatogenesis and male fertility and suggest a critical role for RNF216 in human gonadal development.
      Title: RNF216 is essential for spermatogenesis and male fertility†.
    9. that TLR8 proteasomal disposal through RNF216 in response to RNA ligands regulates TLR8 cellular concentrations
      Title: Toll-like Receptor 8 Stability Is Regulated by Ring Finger 216 in Response to Circulating MicroRNAs.
    10. ICM inhibited autophagy by inhibiting nucleocytoplasmic translocation of HMGB1 and by increasing Beclin 1 ubiquitylation for degradation by enhancing the interaction between Beclin 1 and E3 ubiquitin ligase RNF216
      Title: Inflachromene inhibits autophagy through modulation of Beclin 1 activity.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    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
    Cerebellar ataxia-hypogonadism syndrome
    MedGen: C1859305 OMIM: 212840 GeneReviews: PNPLA6 Disorders
    		Compare labs

    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

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of ring finger protein 216 (RNF216; TRIAD3) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif Triad 3/ZIN binds to purified HIV-1 Vif in vitro, interacts with HIV-1 Vif in transfected human 293T cells, and can impair viral DNA synthesis by two-fold when overexpressed in cells69 PubMed
    vif Triad3 is proposed to act as a linker protein between HIV-1 Vif and other cellular or viral proteins PubMed
    vif HIV-1 Vif mutants with amino acid substitutions in residues 105-107 are specifically unable to bind to Triad3 PubMed
    vif Binding of HIV-1 Vif to Triad3 was identified using a yeast two-hybrid screen PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of type I interferon production TAS
    Traceable Author Statement
    more info
    		  
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein K48-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of defense response to virus by host IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of interferon-beta production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in clathrin-coated vesicle IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase RNF216
    Names
    RING-type E3 ubiquitin transferase RNF216
    triad domain-containing protein 3
    ubiquitin-conjugating enzyme 7-interacting protein 1
    zinc finger protein inhibiting NF-kappa-B
    NP_001364085.1
    NP_996994.1
    NP_996999.1
    XP_005249842.1
    XP_047276480.1
    XP_047276481.1
    XP_047276482.1
    XP_047276483.1
    XP_047276484.1
    XP_047276485.1
    XP_054214467.1
    XP_054214468.1
    XP_054214469.1
    XP_054214470.1
    XP_054214471.1
    XP_054214472.1
    XP_054214473.1
    XP_054214474.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_029374.2 RefSeqGene

      Range
      5000..166616
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001377156.1 → NP_001364085.1  E3 ubiquitin-protein ligase RNF216 isoform b

      Status: REVIEWED

      Source sequence(s)
      AC006483, AC008167
      Consensus CDS
      CCDS34595.1
      UniProtKB/Swiss-Prot
      Q6Y691, Q75ML7, Q7Z2H7, Q7Z7C1, Q8NHW7, Q9NWF9, Q9NYT1
      UniProtKB/TrEMBL
      A8K8N1
      Conserved Domains (2) summary
      cd16630
      Location:513 → 569
      RING-HC_RBR_RNF216; RING finger, HC subclass, found in RING finger protein 216 (RNF216) and similar proteins
      pfam01485
      Location:655 → 705
      IBR; IBR domain, a half RING-finger domain

    2. NM_207111.4 → NP_996994.1  E3 ubiquitin-protein ligase RNF216 isoform a

      See identical proteins and their annotated locations for NP_996994.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as TRIAD3B) represents the longer transcript and it encodes the longer isoform (a).
      Source sequence(s)
      AC006483, AC008167
      Consensus CDS
      CCDS34594.1
      UniProtKB/TrEMBL
      A8K8N1
      Related
      ENSP00000374552.3, ENST00000389902.8
      Conserved Domains (2) summary
      pfam01485
      Location:712 → 762
      IBR; IBR domain, a half RING-finger domain
      cd16630
      Location:570 → 626
      RING-HC_RBR_RNF216; RING finger, HC subclass, found in RING finger protein 216 (RNF216) and similar proteins

    3. NM_207116.3 → NP_996999.1  E3 ubiquitin-protein ligase RNF216 isoform b

      See identical proteins and their annotated locations for NP_996999.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as TRIAD3A) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. It encodes isoform b which is shorter than isoform a.
      Source sequence(s)
      AC006483, AC008167
      Consensus CDS
      CCDS34595.1
      UniProtKB/Swiss-Prot
      Q6Y691, Q75ML7, Q7Z2H7, Q7Z7C1, Q8NHW7, Q9NWF9, Q9NYT1
      UniProtKB/TrEMBL
      A8K8N1
      Related
      ENSP00000404602.2, ENST00000425013.6
      Conserved Domains (2) summary
      cd16630
      Location:513 → 569
      RING-HC_RBR_RNF216; RING finger, HC subclass, found in RING finger protein 216 (RNF216) and similar proteins
      pfam01485
      Location:655 → 705
      IBR; IBR domain, a half RING-finger domain

    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_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      5620047..5781663 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047420525.1 → XP_047276481.1  E3 ubiquitin-protein ligase RNF216 isoform X1

    2. XM_005249785.3 → XP_005249842.1  E3 ubiquitin-protein ligase RNF216 isoform X1

      See identical proteins and their annotated locations for XP_005249842.1

      UniProtKB/TrEMBL
      A8K8N1
      Conserved Domains (2) summary
      pfam01485
      Location:712 → 762
      IBR; IBR domain, a half RING-finger domain
      cd16630
      Location:570 → 626
      RING-HC_RBR_RNF216; RING finger, HC subclass, found in RING finger protein 216 (RNF216) and similar proteins

    3. XM_047420524.1 → XP_047276480.1  E3 ubiquitin-protein ligase RNF216 isoform X1

    4. XM_047420526.1 → XP_047276482.1  E3 ubiquitin-protein ligase RNF216 isoform X2

      UniProtKB/Swiss-Prot
      Q6Y691, Q75ML7, Q7Z2H7, Q7Z7C1, Q8NHW7, Q9NWF9, Q9NYT1

    5. XM_047420529.1 → XP_047276485.1  E3 ubiquitin-protein ligase RNF216 isoform X5

    6. XM_047420528.1 → XP_047276484.1  E3 ubiquitin-protein ligase RNF216 isoform X4

    7. XM_047420527.1 → XP_047276483.1  E3 ubiquitin-protein ligase RNF216 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      5737579..5899098 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054358493.1 → XP_054214468.1  E3 ubiquitin-protein ligase RNF216 isoform X1

    2. XM_054358495.1 → XP_054214470.1  E3 ubiquitin-protein ligase RNF216 isoform X1

    3. XM_054358494.1 → XP_054214469.1  E3 ubiquitin-protein ligase RNF216 isoform X1

    4. XM_054358492.1 → XP_054214467.1  E3 ubiquitin-protein ligase RNF216 isoform X1

    5. XM_054358496.1 → XP_054214471.1  E3 ubiquitin-protein ligase RNF216 isoform X2

      UniProtKB/Swiss-Prot
      Q6Y691, Q75ML7, Q7Z2H7, Q7Z7C1, Q8NHW7, Q9NWF9, Q9NYT1

    6. XM_054358499.1 → XP_054214474.1  E3 ubiquitin-protein ligase RNF216 isoform X5

    7. XM_054358498.1 → XP_054214473.1  E3 ubiquitin-protein ligase RNF216 isoform X4

    8. XM_054358497.1 → XP_054214472.1  E3 ubiquitin-protein ligase RNF216 isoform X3

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_019011.4: Suppressed sequence

      Description
      NM_019011.4: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NWF9.3 GenPept UniProtKB/Swiss-Prot:Q9NWF9

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