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

Gene ID: 54476, updated on 3-Apr-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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Location:
7p22.1
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (5620047..5781663, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (5737579..5899098, complement)
105.20220307 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
  • 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. 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
  2. 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
  3. RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy. Wang H, et al. Oncotarget, 2016 Aug 9. PMID 27203674, Free PMC Article
  4. RNF216 mutations as a novel cause of autosomal recessive Huntington-like disorder. Santens P, et al. Neurology, 2015 Apr 28. PMID 25841028
  5. [Screening of interacting proteins of idiopathic gonadotropin-releasing hormone deficiency pathogenic gene RNF216]. Dai W, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2021 Jul 10. PMID 34247365

See all (57) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. RNF216 affects the stability of STAU2 in the hypothalamus.
    Title: RNF216 affects the stability of STAU2 in the hypothalamus.
  2. 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.
  3. 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.
  4. [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].
  5. RNF216 regulates meiosis and PKA stability in the testes.
    Title: RNF216 regulates meiosis and PKA stability in the testes.
  6. 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†.
  7. 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.
  8. 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.
  9. RNF216 is a potential biomarker and novel therapeutic target for inhibiting colorectal carcinoma development and progression.
    Title: RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy.
  10. missense mutations in TRIAD3 abolished the interaction of TRIAD3A with Arc, disrupting Arc ubiquitination, and consequently Arc degradation.
    Title: TRIAD3/RNF216 mutations associated with Gordon Holmes syndrome lead to synaptic and cognitive impairments via Arc misregulation.
Submit: New GeneRIF Correction See all GeneRIFs (21)

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
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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_2023_10

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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