RNF8 [The Human Chemical-Genetic Interaction Map Project]

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======= RNF8 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: RNF8
  * **<color #00a2e8>Official Name</color>**: ring finger protein 8
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9025|9025]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O76064|O76064]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=RNF8&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RNF8|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/611685|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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 (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001824, PubMed:18001825, PubMed:18006705, PubMed:18077395, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19202061, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22865450, PubMed:22980979). Following DNA damage, mediates the ubiquitination and degradation of POLD4/p12, a subunit of DNA polymerase delta. In the absence of POLD4, DNA polymerase delta complex exhibits higher proofreading activity (PubMed:23233665). 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 (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001824, PubMed:18001825, PubMed:18006705, PubMed:18077395, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19202061, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22865450, PubMed:22980979). {ECO:0000269|PubMed:11322894, ECO:0000269|PubMed:14981089, ECO:0000269|PubMed:17724460, ECO:0000269|PubMed:18001824, ECO:0000269|PubMed:18001825, ECO:0000269|PubMed:18006705, ECO:0000269|PubMed:18077395, ECO:0000269|PubMed:18337245, ECO:0000269|PubMed:18948756, ECO:0000269|PubMed:19015238, ECO:0000269|PubMed:19124460, ECO:0000269|PubMed:19202061, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:20550933, ECO:0000269|PubMed:21558560, ECO:0000269|PubMed:21857671, ECO:0000269|PubMed:21911360, ECO:0000269|PubMed:22266820, ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22531782, ECO:0000269|PubMed:22705371, ECO:0000269|PubMed:22865450, ECO:0000269|PubMed:22980979, ECO:0000269|PubMed:23233665}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|zf-C3HC4|
|FHA|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|histone H2A K63-linked ubiquitination|
|spermatogenesis, exchange of chromosomal proteins|
|histone H2B ubiquitination|
|negative regulation of transcription elongation from RNA polymerase II promoter|
|sperm chromatin condensation|
|negative regulation of DNA-templated transcription, elongation|
|somatic recombination of immunoglobulin genes involved in immune response|
|isotype switching|
|somatic diversification of immunoglobulins involved in immune response|
|spermatid nucleus differentiation|
|histone H2A ubiquitination|
|somatic recombination of immunoglobulin gene segments|
|immunoglobulin production involved in immunoglobulin mediated immune response|
|regulation of transcription elongation from RNA polymerase II promoter|
|somatic diversification of immunoglobulins|
|somatic diversification of immune receptors via germline recombination within a single locus|
|somatic cell DNA recombination|
|protein K63-linked ubiquitination|
|histone ubiquitination|
|B cell activation involved in immune response|
|histone exchange|
|somatic diversification of immune receptors|
|chromosome, telomeric region|
|regulation of DNA-templated transcription, elongation|
|interstrand cross-link repair|
|protein K48-linked ubiquitination|
|double-strand break repair via nonhomologous end joining|
|site of double-strand break|
|non-recombinational repair|
|protein autoubiquitination|
|positive regulation of DNA repair|
|ATP-dependent chromatin remodeling|
|ubiquitin binding|
|positive regulation of response to DNA damage stimulus|
|ubiquitin ligase complex|
|lymphocyte activation involved in immune response|
|regulation of DNA repair|
|histone binding|
|nucleus organization|
|response to ionizing radiation|
|spermatid development|
|B cell activation|
|immunoglobulin production|
|spermatid differentiation|
|nucleosome organization|
|midbody|
|chromatin remodeling|
|DNA packaging|
|production of molecular mediator of immune response|
|double-strand break repair|
|positive regulation of DNA metabolic process|
|immunoglobulin mediated immune response|
|B cell mediated immunity|
|regulation of response to DNA damage stimulus|
|ubiquitin protein ligase activity|
|DNA recombination|
|protein-DNA complex subunit organization|
|ubiquitin-protein transferase activity|
|germ cell development|
|lymphocyte mediated immunity|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|ubiquitin protein ligase binding|
|DNA conformation change|
|protein polyubiquitination|
|cellular process involved in reproduction in multicellular organism|
|regulation of DNA metabolic process|
|histone modification|
|covalent chromatin modification|
|lymphocyte activation|
|chromatin binding|
|response to radiation|
|cell division|
|DNA repair|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|spermatogenesis|
|modification-dependent macromolecule catabolic process|
|male gamete generation|
|proteolysis involved in cellular protein catabolic process|
|adaptive immune response|
|cellular protein catabolic process|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|immune system development|
|developmental process involved in reproduction|
|protein catabolic process|
|protein ubiquitination|
|gamete generation|
|chromatin organization|
|regulation of cellular response to stress|
|DNA metabolic process|
|leukocyte mediated immunity|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|multicellular organismal reproductive process|
|sexual reproduction|
|zinc ion binding|
|multicellular organism reproduction|
|negative regulation of transcription by RNA polymerase II|
|protein homodimerization activity|
|cellular macromolecule catabolic process|
|leukocyte activation|
|protein modification by small protein conjugation or removal|
|multi-organism reproductive process|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|chromosome organization|
|identical protein binding|
|cell activation|
|immune effector process|
|response to abiotic stimulus|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|proteolysis|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|reproductive process|
|reproduction|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|negative regulation of biosynthetic process|
|cell development|
|cellular response to stress|
|negative regulation of gene expression|
|organic substance catabolic process|
|cellular catabolic process|
|protein-containing complex subunit organization|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp512|Olaparib 4μM R08 exp512]]|-2.46|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|-2.34|
|[[:results:exp270|Campthothecin 0.001μM R06 exp270]]|-2.31|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:s:swsap1|SWSAP1]]|0.421|
|[[:human genes:r:rnf168|RNF168]]|0.418|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 68/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|1/28|
|blood|1/28|
|bone|2/25|
|breast|3/33|
|central nervous system|7/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|2/13|
|fibroblast|0/1|
|gastric|4/15|
|kidney|1/21|
|liver|3/20|
|lung|9/75|
|lymphocyte|0/14|
|ovary|2/26|
|pancreas|1/24|
|peripheral nervous system|1/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|2/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|4/22|
|urinary tract|3/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 2470
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 3.71 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='RNF8 Expression in NALM6 Cells: 3.71'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>