LIG4 [The Human Chemical-Genetic Interaction Map Project]

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======= LIG4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: LIG4
  * **<color #00a2e8>Official Name</color>**: DNA ligase 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3981|3981]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P49917|P49917]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=LIG4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20LIG4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/601837|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Efficiently joins single-strand breaks in a double- stranded polydeoxynucleotide in an ATP-dependent reaction. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA- dependent protein kinase complex DNA-PK to these DNA ends. {ECO:0000269|PubMed:10854421, ECO:0000269|PubMed:9809069}.

<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'>
|BRCT|
|DNA ligase A M|
|DNA ligase A N|
|DNA ligase IV|
|DNA ligase A C|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|DNA ligation involved in DNA recombination|
|DNA ligase activity|
|DNA ligase IV complex|
|DNA ligase (ATP) activity|
|DNA-dependent protein kinase-DNA ligase 4 complex|
|pro-B cell differentiation|
|double-strand break repair via classical nonhomologous end joining|
|somatic diversification of T cell receptor genes|
|immunoglobulin V(D)J recombination|
|somatic recombination of T cell receptor gene segments|
|T cell receptor V(D)J recombination|
|single strand break repair|
|nonhomologous end joining complex|
|establishment of integrated proviral latency|
|DNA ligation involved in DNA repair|
|establishment of viral latency|
|viral latency|
|lymphoid progenitor cell differentiation|
|cellular response to lithium ion|
|DNA ligation|
|ligase activity|
|V(D)J recombination|
|somatic diversification of immunoglobulins involved in immune response|
|isotype switching|
|somatic recombination of immunoglobulin genes involved in immune response|
|response to lithium ion|
|nucleotide-excision repair, DNA gap filling|
|somatic recombination of immunoglobulin gene segments|
|immunoglobulin production involved in immunoglobulin mediated immune response|
|condensed chromosome|
|response to X-ray|
|somatic diversification of immunoglobulins|
|somatic diversification of immune receptors via germline recombination within a single locus|
|somatic cell DNA recombination|
|B cell activation involved in immune response|
|neuron apoptotic process|
|T cell differentiation in thymus|
|somatic diversification of immune receptors|
|positive regulation of fibroblast proliferation|
|neuron death|
|response to gamma radiation|
|double-strand break repair via nonhomologous end joining|
|non-recombinational repair|
|somatic stem cell population maintenance|
|cytoplasmic ribonucleoprotein granule|
|cellular response to ionizing radiation|
|regulation of fibroblast proliferation|
|hematopoietic progenitor cell differentiation|
|DNA biosynthetic process|
|nuclear chromosome, telomeric region|
|nucleotide-excision repair|
|lymphocyte activation involved in immune response|
|stem cell population maintenance|
|T cell differentiation|
|maintenance of cell number|
|negative regulation of neuron apoptotic process|
|response to ionizing radiation|
|B cell activation|
|immunoglobulin production|
|positive regulation of chromosome organization|
|cellular response to radiation|
|production of molecular mediator of immune response|
|double-strand break repair|
|protein C-terminus binding|
|cellular response to metal ion|
|regulation of neuron apoptotic process|
|negative regulation of neuron death|
|immunoglobulin mediated immune response|
|B cell mediated immunity|
|DNA replication|
|cellular response to inorganic substance|
|DNA recombination|
|T cell activation|
|lymphocyte differentiation|
|lymphocyte mediated immunity|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|regulation of neuron death|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|leukocyte differentiation|
|regulation of chromosome organization|
|response to metal ion|
|in utero embryonic development|
|lymphocyte activation|
|response to radiation|
|positive regulation of neurogenesis|
|cell division|
|DNA repair|
|response to inorganic substance|
|positive regulation of nervous system development|
|positive regulation of cell development|
|cell population proliferation|
|hemopoiesis|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|positive regulation of organelle organization|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|chordate embryonic development|
|immune system development|
|embryo development ending in birth or egg hatching|
|viral process|
|DNA metabolic process|
|leukocyte mediated immunity|
|cellular response to DNA damage stimulus|
|symbiotic process|
|regulation of neurogenesis|
|interspecies interaction between organisms|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|positive regulation of cell population proliferation|
|apoptotic process|
|regulation of nervous system development|
|leukocyte activation|
|regulation of cell development|
|positive regulation of cell differentiation|
|embryo development|
|central nervous system development|
|negative regulation of cell death|
|programmed cell death|
|chromosome organization|
|cell activation|
|immune effector process|
|cell death|
|nucleobase-containing compound biosynthetic process|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|positive regulation of cellular component organization|
|regulation of organelle organization|
|organic cyclic compound biosynthetic process|
|cell cycle|
|positive regulation of developmental process|
|DNA binding|
|ATP binding|
|generation of neurons|
|regulation of apoptotic process|
|regulation of programmed cell death|
|regulation of cell population proliferation|
|neurogenesis|
|cellular nitrogen compound biosynthetic process|
|regulation of cell death|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|positive regulation of multicellular organismal process|
|macromolecule biosynthetic process|
|regulation of cell differentiation|
|immune response|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' 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:exp360|Genistein 15μM R07 exp360]]|-3.06|
|[[:results:exp45|Docetaxel 0.002μM R01 exp45]]|-2.84|
|[[:results:exp357|Dorsomorphin 5μM R07 exp357]]|-2.73|
|[[:results:exp478|Doxorubicin 0.02μM R08 exp478]]|-2.61|
|[[:results:exp240|Pyridostatin 4μM R05 exp240]]|-2.49|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|-2.47|
|[[:results:exp256|HMS-I1 10μM R06 exp256]]|-2.41|
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|-2.25|
|[[:results:exp299|Talazoparib 0.006μM R06 exp299]]|-2.2|
|[[:results:exp464|Calcipotriol 5μM R08 exp464]]|-2.16|
|[[:results:exp379|MSC2530818 10μM R07 exp379]]|-2.07|
|[[:results:exp444|THZ531 0.225μM R08 exp444]]|-2.01|
|[[:results:exp226|Cerivastatin 0.15μM R05 exp226]]|-1.97|
|[[:results:exp291|LLY-284 2.6μM R06 exp291]]|-1.95|
|[[:results:exp512|Olaparib 4μM R08 exp512]]|-1.95|
|[[:results:exp447|Amiloride 100μM R08 exp447]]|-1.92|
|[[:results:exp417|Tubastatin-A 2.5μM R07 exp417]]|-1.92|
|[[:results:exp372|Ibrutinib 1μM R07 exp372]]|-1.88|
|[[:results:exp527|Tanespimycin 14μM R08 exp527]]|-1.86|
|[[:results:exp340|BN82002 4μM R07 exp340]]|-1.85|
|[[:results:exp517|Quercetin 20μM R08 exp517]]|-1.85|
|[[:results:exp485|GSK626616 14μM R08 exp485]]|-1.82|
|[[:results:exp317|Geldanamycin 0.015 to 0.05μM on day4 R07 exp317]]|-1.78|
|[[:results:exp148|SB202190 10μM R03 exp148]]|-1.75|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 16762
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 8.17 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='LIG4 Expression in NALM6 Cells: 8.17'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>