Free for academic non-profit institutions. Other users need a Commercial license

Aliases for RNF8 Gene

Aliases for RNF8 Gene

  • Ring Finger Protein 8, E3 Ubiquitin Protein Ligase 2 3
  • Ring Finger Protein (C3HC4 Type) 8 2 3
  • KIAA0646 4 6
  • HRNF8 3 4
  • UBC13/UEV-Interacting Ring Finger Protein 3
  • E3 Ubiquitin-Protein Ligase RNF8 3
  • C3HC4-Type Zinc Finger Protein 3
  • Ring Finger Protein 8 2
  • RING Finger Protein 8 4
  • EC 6.3.2.- 4
  • EC 6.3.2 63

External Ids for RNF8 Gene

Summaries for RNF8 Gene

Entrez Gene Summary for RNF8 Gene

  • The protein encoded by this gene contains a RING finger motif and an FHA domain. This protein has been shown to interact with several class II ubiquitin-conjugating enzymes (E2), including UBE2E1/UBCH6, UBE2E2, and UBE2E3, and may act as an ubiquitin ligase (E3) in the ubiquitination of certain nuclear proteins. This protein is also known to play a role in the DNA damage response and depletion of this protein causes cell growth inhibition and cell cycle arrest. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

GeneCards Summary for RNF8 Gene

RNF8 (Ring Finger Protein 8, E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Diseases associated with RNF8 include morgagni cataract. Among its related pathways are Ubiquitin-Proteasome Dependent Proteolysis and SMAD Signaling Network. GO annotations related to this gene include protein homodimerization activity and ubiquitin-protein transferase activity.

UniProtKB/Swiss-Prot for RNF8 Gene

  • E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the Lys-63-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing Lys-48-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the Lys-63-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes Lys-63-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of Lys-63-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at Lys-63 are usually not targeted for degradation. Also catalyzes the formation of Lys-48-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward Lys-48- versus Lys-63-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of Lys-63-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the Lys-48-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 Lys-16 acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggravating telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.

Gene Wiki entry for RNF8 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RNF8 Gene

Genomics for RNF8 Gene

Genomic Location for RNF8 Gene

Start:
37,353,972 bp from pter
End:
37,394,738 bp from pter
Size:
40,767 bases
Orientation:
Plus strand

Genomic View for RNF8 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for RNF8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RNF8 Gene

Regulatory Elements for RNF8 Gene

Proteins for RNF8 Gene

  • Protein details for RNF8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O76064-RNF8_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase RNF8
    Protein Accession:
    O76064
    Secondary Accessions:
    • A6NN24
    • A8MYC0
    • B4DPG0
    • Q53H16
    • Q5NKW5

    Protein attributes for RNF8 Gene

    Size:
    485 amino acids
    Molecular mass:
    55518 Da
    Quaternary structure:
    • Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of the RNF8 homodimer and a E2 heterodimer of UBE2N and UBE2V2. Interacts with class III E2s, including UBE2E1, UBE2E2, and UBE2E3 and with UBE2N. Interacts with RXRA. Interacts (via FHA domain) with ATM-phosphorylated MDC1. Interacts (via FHA domain) with Thr-4827 phosphorylated HERC2 (via C-terminus). Interacts (via FHA domain) with phosphorylated human herpesvirus 1 ICP0 protein; leading to RNF8 degradation by the proteasome.
    SequenceCaution:
    • Sequence=BAA31621.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAG60572.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305}; Sequence=EAX03945.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RNF8 Gene

    Alternative splice isoforms for RNF8 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RNF8 Gene

Proteomics data for RNF8 Gene at MOPED

Selected DME Specific Peptides for RNF8 Gene

Post-translational modifications for RNF8 Gene

  • Autoubiquitinated through Lys-48 and Lys-63 of ubiquitin. Lys-63 polyubiquitination is mediated by UBE2N. Lys-29-type polyubiquitination is also observed, but it doesnt require its own functional RING-type zinc finger.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains for RNF8 Gene

Gene Families for RNF8 Gene

HGNC:
  • RNF :RING-type (C3HC4) zinc fingers

Protein Domains for RNF8 Gene

Suggested Antigen Peptide Sequences for RNF8 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O76064

UniProtKB/Swiss-Prot:

RNF8_HUMAN
Domain:
  • The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and Thr-4827 phosphorylated HERC2.:
    • O76064
  • Contains 1 FHA domain.:
    • O76064
Family:
  • Belongs to the RNF8 family.:
    • O76064
Similarity:
  • Contains 1 RING-type zinc finger.:
    • O76064
genes like me logo Genes that share domains with RNF8: view

Function for RNF8 Gene

Molecular function for RNF8 Gene

GENATLAS Biochemistry: RING finger protein 8,same ? as RING1
UniProtKB/Swiss-Prot Function: E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the Lys-63-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing Lys-48-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the Lys-63-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes Lys-63-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of Lys-63-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at Lys-63 are usually not targeted for degradation. Also catalyzes the formation of Lys-48-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward Lys-48- versus Lys-63-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of Lys-63-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the Lys-48-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 Lys-16 acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggravating telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.

Enzyme Numbers (IUBMB) for RNF8 Gene

Gene Ontology (GO) - Molecular Function for RNF8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003682 chromatin binding IDA 18001824
GO:0004842 ubiquitin-protein transferase activity IDA 18001824
GO:0005515 protein binding IPI 18001824
GO:0008270 zinc ion binding IDA 22980979
GO:0016874 ligase activity IEA --
genes like me logo Genes that share ontologies with RNF8: view
genes like me logo Genes that share phenotypes with RNF8: view

No data available for Animal Models , miRNA , Transcription Factor Targeting and HOMER Transcription for RNF8 Gene

Localization for RNF8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RNF8 Gene

Nucleus. Midbody. Chromosome, telomere. Note=Recruited at uncapped telomeres (By similarity). Following DNA double-strand breaks, recruited to the sites of damage. During prophase, concomitant with nuclear envelope breakdown, localizes throughout the cell, with a dotted pattern. In telophase, again in the nucleus and also with a discrete dotted pattern in the cytoplasm. In late telophase and during cytokinesis, localizes in the midbody of the tubulin bridge joining the daughter cells. Does not seem to be associated with condensed chromosomes at any time during the cell cycle. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RNF8 Gene COMPARTMENTS Subcellular localization image for RNF8 gene
Compartment Confidence
nucleus 5
cytosol 2

Gene Ontology (GO) - Cellular Components for RNF8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000151 ubiquitin ligase complex IDA 18001824
GO:0000781 chromosome, telomeric region ISS --
GO:0005634 nucleus IDA --
GO:0005730 nucleolus IDA --
GO:0030496 midbody IEA --
genes like me logo Genes that share ontologies with RNF8: view

Pathways for RNF8 Gene

genes like me logo Genes that share pathways with RNF8: view

Pathways by source for RNF8 Gene

UniProtKB/Swiss-Prot O76064-RNF8_HUMAN

  • Pathway: Protein modification; protein ubiquitination

Gene Ontology (GO) - Biological Process for RNF8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006302 double-strand break repair IDA 18001824
GO:0006303 double-strand break repair via nonhomologous end joining ISS --
GO:0006511 ubiquitin-dependent protein catabolic process IDA 22266820
GO:0006974 cellular response to DNA damage stimulus IDA 20550933
GO:0007067 mitotic nuclear division IEA --
genes like me logo Genes that share ontologies with RNF8: view

Compounds for RNF8 Gene

(4) HMDB Compounds for RNF8 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine monophosphate
  • 5'-AMP
61-19-8
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
Phosphoric acid
  • acide phosphorique (FRENCH)
7664-38-2
Pyrophosphate
  • (4-)Diphosphoric acid ion
14000-31-8
genes like me logo Genes that share compounds with RNF8: view

Transcripts for RNF8 Gene

Unigene Clusters for RNF8 Gene

Ring finger protein 8, E3 ubiquitin protein ligase:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for RNF8 Gene

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

Relevant External Links for RNF8 Gene

GeneLoc Exon Structure for
RNF8
ECgene alternative splicing isoforms for
RNF8

Expression for RNF8 Gene

mRNA expression in normal human tissues for RNF8 Gene

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for RNF8 Gene

SOURCE GeneReport for Unigene cluster for RNF8 Gene Hs.485278

mRNA Expression by UniProt/SwissProt for RNF8 Gene

O76064-RNF8_HUMAN
Tissue specificity: Ubiquitous. In fetal tissues, highest expression in brain, thymus and liver. In adult tissues, highest levels in brain and testis, lowest levels in peripheral blood cells.
genes like me logo Genes that share expressions with RNF8: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for RNF8 Gene

Orthologs for RNF8 Gene

This gene was present in the common ancestor of chordates.

Orthologs for RNF8 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RNF8 35
  • 98.93 (n)
  • 98.77 (a)
RNF8 36
  • 98 (a)
OneToOne
cow
(Bos Taurus)
Mammalia RNF8 35
  • 88.25 (n)
  • 83.71 (a)
RNF8 36
  • 83 (a)
OneToOne
dog
(Canis familiaris)
Mammalia RNF8 35
  • 89.6 (n)
  • 85.95 (a)
RNF8 36
  • 85 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rnf8 35
  • 78.03 (n)
  • 71.49 (a)
Rnf8 16
Rnf8 36
  • 71 (a)
OneToMany
RNF8 36
  • 48 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 66 (a)
OneToMany
-- 36
  • 60 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Rnf8 35
  • 78.76 (n)
  • 73.2 (a)
chicken
(Gallus gallus)
Aves RNF8 35
  • 66.16 (n)
  • 59.7 (a)
RNF8 36
  • 52 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RNF8 36
  • 54 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rnf8 35
  • 67.68 (n)
  • 66.41 (a)
zebrafish
(Danio rerio)
Actinopterygii rnf8 35
  • 54.84 (n)
  • 46.68 (a)
rnf8 36
  • 36 (a)
OneToOne
Species with no ortholog for RNF8:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • oppossum (Monodelphis domestica)
  • 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 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)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for RNF8 Gene

ENSEMBL:
Gene Tree for RNF8 (if available)
TreeFam:
Gene Tree for RNF8 (if available)

Paralogs for RNF8 Gene

No data available for Paralogs for RNF8 Gene

Variants for RNF8 Gene

Sequence variations from dbSNP and Humsavar for RNF8 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs104669 -- 37,386,283(-) CTAGG(A/T)CTTCC intron-variant
rs169005 -- 37,374,144(+) TGACT(A/G)TCTAA intron-variant
rs169006 -- 37,379,763(+) ATGAT(A/G)TCTTA intron-variant
rs195374 -- 37,373,025(+) CCACT(C/G)TCATG intron-variant
rs195375 -- 37,373,553(+) aggcg(C/T)gcgcc intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RNF8 Gene

Variant ID Type Subtype PubMed ID
esv2498217 CNV Deletion 19546169
esv2731933 CNV Deletion 23290073
nsv520294 CNV Gain 19592680

Relevant External Links for RNF8 Gene

HapMap Linkage Disequilibrium report
RNF8

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RNF8 Gene

Disorders for RNF8 Gene

(1) MalaCards Diseases for RNF8 Gene

Search for RNF8 Gene in MalaCards »

(1) University of Copenhagen DISEASES for RNF8 Gene

Relevant External Links for RNF8

Genetic Association Database (GAD)
RNF8
Human Genome Epidemiology (HuGE) Navigator
RNF8
genes like me logo Genes that share disorders with RNF8: view

No data available for UniProtKB/Swiss-Prot for RNF8 Gene

Publications for RNF8 Gene

  1. N-terminally extended human ubiquitin-conjugating enzymes (E2s) mediate the ubiquitination of RING-finger proteins, ARA54 and RNF8. (PMID: 11322894) Ito K. … Okano Y. (Eur. J. Biochem. 2001) 3 4 23
  2. HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. (PMID: 20023648) Bekker-Jensen S. … Mailand N. (Nat. Cell Biol. 2010) 3 4 23
  3. Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. (PMID: 9734811) Ishikawa K. … Ohara O. (DNA Res. 1998) 2 3 4
  4. Isolation, tissue expression, and chromosomal assignment of a novel human gene which encodes a protein with RING finger motif. (PMID: 9852682) Seki N. … Saito T. (J. Hum. Genet. 1998) 2 3 4
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard D.S. … Malek J. (Genome Res. 2004) 3 4

Products for RNF8 Gene

Sources for RNF8 Gene

Back to Top

Content