======= RNF168 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: RNF168
  * **<color #00a2e8>Official Name</color>**: ring finger protein 168
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=165918|165918]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q8IYW5|Q8IYW5]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=RNF168&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RNF168|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/612688|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000255|HAMAP- Rule:MF_03066, ECO:0000269|PubMed:19203578, ECO:0000269|PubMed:19203579, ECO:0000269|PubMed:20550933, ECO:0000269|PubMed:22373579, ECO:0000269|PubMed:22705371, ECO:0000269|PubMed:22713238, ECO:0000269|PubMed:22742833, ECO:0000269|PubMed:22980979, ECO:0000269|PubMed:23760478}.

<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|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|histone H2A-K13 ubiquitination|
|histone H2A-K15 ubiquitination|
|histone H2A K63-linked ubiquitination|
|negative regulation of transcription elongation from RNA polymerase II promoter|
|negative regulation of DNA-templated transcription, elongation|
|histone H2A monoubiquitination|
|somatic recombination of immunoglobulin genes involved in immune response|
|isotype switching|
|somatic diversification of immunoglobulins involved in immune response|
|K63-linked polyubiquitin modification-dependent protein binding|
|histone H2A ubiquitination|
|somatic recombination of immunoglobulin gene segments|
|immunoglobulin production involved in immunoglobulin mediated immune response|
|nucleosome binding|
|histone monoubiquitination|
|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|
|somatic diversification of immune receptors|
|regulation of DNA-templated transcription, elongation|
|interstrand cross-link repair|
|double-strand break repair via nonhomologous end joining|
|site of double-strand break|
|protein monoubiquitination|
|non-recombinational repair|
|positive regulation of DNA repair|
|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|
|response to ionizing radiation|
|B cell activation|
|immunoglobulin production|
|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|
|DNA recombination|
|ubiquitin-protein transferase activity|
|lymphocyte mediated immunity|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|protein polyubiquitination|
|regulation of DNA metabolic process|
|histone modification|
|covalent chromatin modification|
|lymphocyte activation|
|chromatin binding|
|response to radiation|
|DNA repair|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|proteolysis involved in cellular protein catabolic process|
|protein-containing complex|
|adaptive immune response|
|cellular protein catabolic process|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|immune system development|
|protein catabolic process|
|protein ubiquitination|
|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|
|negative regulation of transcription by RNA polymerase II|
|cellular macromolecule catabolic process|
|leukocyte activation|
|protein modification by small protein conjugation or removal|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|chromosome organization|
|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|
|negative regulation of cellular macromolecule biosynthetic process|
|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|
|cellular response to stress|
|negative regulation of gene expression|
|organic substance catabolic process|
|cellular catabolic process|
|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:exp520|Rucaparib 6.5μM R08 exp520]]|-3.3|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|-2.67|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|-2.42|
|[[:results:exp299|Talazoparib 0.006μM R06 exp299]]|-2.39|
|[[:results:exp270|Campthothecin 0.001μM R06 exp270]]|-1.77|
|[[:results:exp58|UM131593 0.1μM R01 exp58]]|1.75|
|[[:results:exp501|Methotrexate 0.01μM R08 exp501]]|1.88|
|[[:results:exp15|Cycloheximide 0.2μM R00 exp15]]|2.02|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:h2afx|H2AFX]]|0.515|
|[[:human genes:s:spidr|SPIDR]]|0.47|
|[[:human genes:c:c1orf112|C1orf112]]|0.457|
|[[:human genes:s:swsap1|SWSAP1]]|0.441|
|[[:human genes:s:sfr1|SFR1]]|0.426|
|[[:human genes:r:rnf8|RNF8]]|0.418|
|[[:human genes:z:zswim7|ZSWIM7]]|0.402|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 61/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|1/28|
|bone|3/25|
|breast|3/33|
|central nervous system|4/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|3/13|
|fibroblast|0/1|
|gastric|4/15|
|kidney|1/21|
|liver|3/20|
|lung|7/75|
|lymphocyte|0/14|
|ovary|4/26|
|pancreas|1/24|
|peripheral nervous system|2/16|
|plasma cell|1/15|
|prostate|0/1|
|skin|3/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|3/29|
|uterus|1/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 703
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.42 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='RNF168 Expression in NALM6 Cells: 6.42'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>