======= ISG15 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: ISG15
  * **<color #00a2e8>Official Name</color>**: ISG15 ubiquitin like modifier
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9636|9636]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P05161|P05161]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=ISG15&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20ISG15|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/147571|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a ubiquitin-like protein that is conjugated to intracellular target proteins upon activation by interferon-alpha and interferon-beta. Several functions have been ascribed to the encoded protein, including chemotactic activity towards neutrophils, direction of ligated target proteins to intermediate filaments, cell-to-cell signaling, and antiviral activity during viral infections. While conjugates of this protein have been found to be noncovalently attached to intermediate filaments, this protein is sometimes secreted. [provided by RefSeq, Dec 2012]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation- inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade therby inhibiting IFNA- induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. {ECO:0000269|PubMed:1373138, ECO:0000269|PubMed:16009940, ECO:0000269|PubMed:16112642, ECO:0000269|PubMed:16428300, ECO:0000269|PubMed:16434471, ECO:0000269|PubMed:16872604, ECO:0000269|PubMed:18305167, ECO:0000269|PubMed:19270716, ECO:0000269|PubMed:19357168, ECO:0000269|PubMed:2005397, ECO:0000269|PubMed:20133869, ECO:0000269|PubMed:20308324, ECO:0000269|PubMed:20639253, ECO:0000269|PubMed:21543490, ECO:0000269|PubMed:22693631, ECO:0000269|PubMed:22859821, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:7526157, ECO:0000269|PubMed:8550581}.

<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'>
|ubiquitin|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|interleukin-10 secretion|
|interleukin-10 production|
|ISG15-protein conjugation|
|interferon-gamma secretion|
|protein tag|
|interferon-gamma production|
|positive regulation of erythrocyte differentiation|
|positive regulation of bone mineralization|
|translesion synthesis|
|negative regulation of type I interferon production|
|regulation of erythrocyte differentiation|
|positive regulation of biomineralization|
|positive regulation of biomineral tissue development|
|cytokine secretion|
|DNA synthesis involved in DNA repair|
|postreplication repair|
|negative regulation of viral genome replication|
|cellular response to type I interferon|
|type I interferon signaling pathway|
|response to type I interferon|
|negative regulation of protein ubiquitination|
|regulation of bone mineralization|
|negative regulation of viral life cycle|
|negative regulation of protein modification by small protein conjugation or removal|
|positive regulation of ossification|
|positive regulation of myeloid cell differentiation|
|regulation of biomineral tissue development|
|regulation of biomineralization|
|integrin-mediated signaling pathway|
|regulation of viral genome replication|
|negative regulation of viral process|
|regulation of interferon-gamma production|
|DNA biosynthetic process|
|regulation of type I interferon production|
|integrin binding|
|regulation of viral life cycle|
|cytokine production|
|protein secretion|
|establishment of protein localization to extracellular region|
|protein localization to extracellular region|
|peptide secretion|
|positive regulation of hemopoiesis|
|regulation of ossification|
|defense response to virus|
|regulation of protein ubiquitination|
|regulation of viral process|
|negative regulation of multi-organism process|
|regulation of symbiosis, encompassing mutualism through parasitism|
|regulation of myeloid cell differentiation|
|regulation of protein modification by small protein conjugation or removal|
|negative regulation of cytokine production|
|response to virus|
|defense response to bacterium|
|regulation of hemopoiesis|
|DNA repair|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|proteolysis involved in cellular protein catabolic process|
|negative regulation of protein modification process|
|cellular protein catabolic process|
|cytokine-mediated signaling pathway|
|protein catabolic process|
|response to bacterium|
|regulation of cytokine production|
|viral process|
|DNA metabolic process|
|innate immune response|
|regulation of multi-organism process|
|cellular response to DNA damage stimulus|
|symbiotic process|
|interspecies interaction between organisms|
|cellular macromolecule catabolic process|
|defense response to other organism|
|positive regulation of cell differentiation|
|secretion by cell|
|cellular response to cytokine stimulus|
|negative regulation of cellular protein metabolic process|
|export from cell|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|immune effector process|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|negative regulation of protein metabolic process|
|secretion|
|positive regulation of immune system process|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|negative regulation of multicellular organismal process|
|proteolysis|
|response to other organism|
|organic cyclic compound biosynthetic process|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|positive regulation of developmental process|
|protein transport|
|peptide transport|
|amide transport|
|establishment of protein localization|
|cellular nitrogen compound biosynthetic process|
|regulation of immune system process|
|cellular response to stress|
|cellular macromolecule biosynthetic process|
|positive regulation of multicellular organismal process|
|macromolecule biosynthetic process|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|nitrogen compound transport|
|regulation of protein modification process|
|immune response|
|extracellular region|
</modal>
\\

 === CRISPR Data ===
<button type='default' 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'>
No hits were found.
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:polr2j3|POLR2J3]]|0.435|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 5/739
^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|1/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|1/75|
|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|1/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 2891
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 2.59 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='ISG15 Expression in NALM6 Cells: 2.59'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>