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Aliases for RNF168 Gene

Aliases for RNF168 Gene

  • Ring Finger Protein 168 2 3
  • Ring Finger Protein 168, E3 Ubiquitin Protein Ligase 2 3
  • RING Finger Protein 168 4 5
  • HRNF168 3 4
  • E3 Ubiquitin-Protein Ligase RNF168 3
  • EC 6.3.2.- 4
  • EC 6.3.2 61

External Ids for RNF168 Gene

Previous GeneCards Identifiers for RNF168 Gene

  • GC03M197687
  • GC03M196195
  • GC03M193493

Summaries for RNF168 Gene

Entrez Gene Summary for RNF168 Gene

  • This gene encodes an E3 ubiquitin ligase protein that contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The protein is involved in DNA double-strand break (DSB) repair. Mutations in this gene result in Riddle syndrome. [provided by RefSeq, Sep 2011]

GeneCards Summary for RNF168 Gene

RNF168 (Ring Finger Protein 168) is a Protein Coding gene. Diseases associated with RNF168 include Riddle Syndrome and Embryonal Testis Carcinoma. Among its related pathways are DNA Double-Strand Break Repair and Transport to the Golgi and subsequent modification. GO annotations related to this gene include chromatin binding and ubiquitin-protein transferase activity.

UniProtKB/Swiss-Prot for RNF168 Gene

  • E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of Lys-63-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 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. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate Lys-63-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of Lys-13 and Lys-15 of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RNF168 Gene

Genomics for RNF168 Gene

Regulatory Elements for RNF168 Gene

Enhancers for RNF168 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
- Elite enhancer/Elite enhancer-gene association

Enhancers around RNF168 on UCSC Golden Path with GeneCards custom track

Promoters for RNF168 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around RNF168 on UCSC Golden Path with GeneCards custom track

Genomic Location for RNF168 Gene

Chromosome:
3
Start:
196,468,783 bp from pter
End:
196,503,768 bp from pter
Size:
34,986 bases
Orientation:
Minus strand

Genomic View for RNF168 Gene

Genes around RNF168 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RNF168 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RNF168 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RNF168 Gene

Proteins for RNF168 Gene

  • Protein details for RNF168 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IYW5-RN168_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase RNF168
    Protein Accession:
    Q8IYW5
    Secondary Accessions:
    • Q8NA67
    • Q96NS4

    Protein attributes for RNF168 Gene

    Size:
    571 amino acids
    Molecular mass:
    65020 Da
    Quaternary structure:
    • Monomer. Interacts with UBE2N/UBC13.
    SequenceCaution:
    • Sequence=BAC04060.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RNF168 Gene

neXtProt entry for RNF168 Gene

Selected DME Specific Peptides for RNF168 Gene

Post-translational modifications for RNF168 Gene

  • Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs).
  • Ubiquitinated.
  • Ubiquitination at Lys 158, Lys 227, Lys 232, Lys 334, Lys 341, Lys 389, Lys 399, Lys 406, Lys 441, Lys 455, Lys 468, Lys 485, Lys 524, Lys 528, Lys 548, and Lys 560
  • Modification sites at PhosphoSitePlus

Other Protein References for RNF168 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for RNF168 Gene

Gene Families for RNF168 Gene

Protein Domains for RNF168 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for RNF168 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8IYW5

UniProtKB/Swiss-Prot:

RN168_HUMAN :
  • The MIU motif (motif interacting with ubiquitin) mediates the interaction with both Lys-48- and Lys-63-linked ubiquitin chains (PubMed:19500350). The UMI motif mediates interaction with ubiquitin with a preference for Lys-63-linked ubiquitin (PubMed:21041483). The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs) (PubMed:22742833).
  • Belongs to the RNF168 family.
  • Contains 1 RING-type zinc finger.
Domain:
  • The MIU motif (motif interacting with ubiquitin) mediates the interaction with both Lys-48- and Lys-63-linked ubiquitin chains (PubMed:19500350). The UMI motif mediates interaction with ubiquitin with a preference for Lys-63-linked ubiquitin (PubMed:21041483). The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs) (PubMed:22742833).
Family:
  • Belongs to the RNF168 family.
Similarity:
  • Contains 1 RING-type zinc finger.
genes like me logo Genes that share domains with RNF168: view

Function for RNF168 Gene

Molecular function for RNF168 Gene

UniProtKB/Swiss-Prot Function:
E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and H2AX and amplifies the RNF8-dependent H2A ubiquitination, promoting the formation of Lys-63-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 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. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate Lys-63-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of Lys-13 and Lys-15 of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).

Enzyme Numbers (IUBMB) for RNF168 Gene

Gene Ontology (GO) - Molecular Function for RNF168 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003682 chromatin binding IDA 19203578
GO:0004842 ubiquitin-protein transferase activity IDA 19203578
GO:0005515 protein binding IPI 19203578
GO:0008270 zinc ion binding IEA --
GO:0016874 ligase activity IEA --
genes like me logo Genes that share ontologies with RNF168: view
genes like me logo Genes that share phenotypes with RNF168: view

Human Phenotype Ontology for RNF168 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for RNF168 Gene

Localization for RNF168 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RNF168 Gene

Nucleus. Note=Localizes to double-strand breaks (DSBs) sites of DNA damage.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RNF168 Gene COMPARTMENTS Subcellular localization image for RNF168 gene
Compartment Confidence
nucleus 5
cytosol 3
extracellular 1
plasma membrane 1

Gene Ontology (GO) - Cellular Components for RNF168 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000151 ubiquitin ligase complex IDA 19203578
GO:0005634 nucleus IDA 19203578
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IDA --
GO:0035861 site of double-strand break IDA 19500350
genes like me logo Genes that share ontologies with RNF168: view

Pathways & Interactions for RNF168 Gene

genes like me logo Genes that share pathways with RNF168: view

Pathways by source for RNF168 Gene

UniProtKB/Swiss-Prot Q8IYW5-RN168_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for RNF168 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for RNF168 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006302 double-strand break repair IDA 19203578
GO:0006303 double-strand break repair via nonhomologous end joining TAS --
GO:0006511 ubiquitin-dependent protein catabolic process IDA 22373579
GO:0006974 cellular response to DNA damage stimulus IDA 19500350
GO:0010212 response to ionizing radiation IDA 19203578
genes like me logo Genes that share ontologies with RNF168: view

Drugs & Compounds for RNF168 Gene

No Compound Related Data Available

Transcripts for RNF168 Gene

mRNA/cDNA for RNF168 Gene

Unigene Clusters for RNF168 Gene

Ring finger protein 168, E3 ubiquitin protein ligase:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for RNF168 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b
SP1:
SP2: -

Relevant External Links for RNF168 Gene

GeneLoc Exon Structure for
RNF168
ECgene alternative splicing isoforms for
RNF168

Expression for RNF168 Gene

mRNA expression in normal human tissues for RNF168 Gene

Protein differential expression in normal tissues from HIPED for RNF168 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (56.1) and Blymphocyte (12.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for RNF168 Gene



Protein tissue co-expression partners for RNF168 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of RNF168 Gene:

RNF168

SOURCE GeneReport for Unigene cluster for RNF168 Gene:

Hs.250648
genes like me logo Genes that share expression patterns with RNF168: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for RNF168 Gene

Orthologs for RNF168 Gene

This gene was present in the common ancestor of chordates.

Orthologs for RNF168 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia RNF168 34
  • 82.16 (n)
  • 75.96 (a)
-- 35
  • 62 (a)
OneToMany
RNF168 35
  • 75 (a)
OneToMany
dog
(Canis familiaris)
Mammalia RNF168 34
  • 83.48 (n)
  • 76.8 (a)
RNF168 35
  • 77 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rnf168 34
  • 75.07 (n)
  • 65.19 (a)
Rnf168 16
Rnf168 35
  • 63 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia RNF168 34
  • 99.36 (n)
  • 99.12 (a)
RNF168 35
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Rnf168 34
  • 74.21 (n)
  • 65.78 (a)
oppossum
(Monodelphis domestica)
Mammalia -- 35
  • 51 (a)
OneToMany
-- 35
  • 44 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 35
  • 42 (a)
OneToMany
-- 35
  • 69 (a)
OneToMany
chicken
(Gallus gallus)
Aves RNF168 34
  • 55.56 (n)
  • 47.1 (a)
RNF168 35
  • 43 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RNF168 35
  • 40 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rnf168 34
  • 51.9 (n)
  • 46.26 (a)
Str.18706 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.6274 34
zebrafish
(Danio rerio)
Actinopterygii rnf168 35
  • 31 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3447 35
  • 30 (a)
OneToOne
Species where no ortholog for RNF168 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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 RNF168 Gene

ENSEMBL:
Gene Tree for RNF168 (if available)
TreeFam:
Gene Tree for RNF168 (if available)

Paralogs for RNF168 Gene

(3) SIMAP similar genes for RNF168 Gene using alignment to 2 proteins:

Pseudogenes.org Pseudogenes for RNF168 Gene

genes like me logo Genes that share paralogs with RNF168: view

No data available for Paralogs for RNF168 Gene

Variants for RNF168 Gene

Sequence variations from dbSNP and Humsavar for RNF168 Gene

SNP ID Clin Chr 03 pos Sequence Context AA Info Type
rs3796129 - 196,472,333(+) AGCAT(G/T)GATCC reference, missense
rs35774921 - 196,472,375(-) TTCCA(A/G)AAGAA reference, missense
rs6790173 - 196,472,298(+) AGATT(C/T)GGGGG reference, missense
rs1471771 -- 196,503,291(-) TGATA(C/G)GCTTC utr-variant-5-prime
rs2341336 -- 196,493,928(-) ctgca(A/G)tgagc intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RNF168 Gene

Variant ID Type Subtype PubMed ID
esv2677146 CNV deletion 23128226
esv3599286 CNV loss 21293372
nsv1003066 CNV gain 25217958
nsv10389 CNV loss 18304495
nsv469831 CNV gain 16826518
nsv822416 CNV loss 20364138
nsv997797 CNV gain 25217958

Variation tolerance for RNF168 Gene

Residual Variation Intolerance Score: 71.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 7.27; 81.26% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for RNF168 Gene

Human Gene Mutation Database (HGMD)
RNF168
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RNF168

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RNF168 Gene

Disorders for RNF168 Gene

MalaCards: The human disease database

(3) MalaCards diseases for RNF168 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
riddle syndrome
  • radiosensitivity, immunodeficiency, dysmorphic features, and learning difficulties
embryonal testis carcinoma
  • embryonal carcinoma of testis
chromosome 3q29 microdeletion syndrome
  • chromosome 3q29 deletion syndrome
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

RN168_HUMAN
  • Riddle syndrome (RIDDLES) [MIM:611943]: Characterized by increased radiosensitivity, immunodeficiency, mild motor control and learning difficulties, facial dysmorphism, and short stature. Defects are probably due to impaired localization of TP53BP1 and BRCA1 at DNA lesions. {ECO:0000269 PubMed:19203578}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for RNF168

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RNF168
genes like me logo Genes that share disorders with RNF168: view

No data available for Genatlas for RNF168 Gene

Publications for RNF168 Gene

  1. RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites. (PMID: 22373579) Mallette F.A. … Richard S. (EMBO J. 2012) 3 4 65
  2. DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. (PMID: 22508508) Danielsen J.R. … Mailand N. (J. Cell Biol. 2012) 3 4 65
  3. Molecular insights into the function of RING Finger (RNF)-containing proteins hRNF8 and hRNF168 in Ubc13/Mms2-dependent ubiquitylation. (PMID: 22589545) Campbell S.J. … Glover J.N. (J. Biol. Chem. 2012) 3 4 65
  4. A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network. (PMID: 22705371) Yan Z. … Wang W. (Mol. Cell 2012) 3 4 65
  5. A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase. (PMID: 22713238) Gatti M. … Penengo L. (Cell Cycle 2012) 3 4 65

Products for RNF168 Gene

Sources for RNF168 Gene

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