SIAH2 [The Human Chemical-Genetic Interaction Map Project]

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======= SIAH2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SIAH2
  * **<color #00a2e8>Official Name</color>**: siah E3 ubiquitin protein ligase 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6478|6478]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O43255|O43255]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SIAH2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SIAH2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602213|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin- conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes. Has some overlapping function with SIAH1. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not. Promotes monoubiquitination of SNCA. {ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:12411493, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:9334332}.

<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'>
|Sina|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of netrin-activated signaling pathway|
|regulation of netrin-activated signaling pathway|
|ubiquitin conjugating enzyme binding|
|negative regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|negative regulation of cysteine-type endopeptidase activity|
|negative regulation of extrinsic apoptotic signaling pathway|
|regulation of circadian rhythm|
|regulation of extrinsic apoptotic signaling pathway|
|negative regulation of canonical Wnt signaling pathway|
|regulation of protein ubiquitination|
|negative regulation of Wnt signaling pathway|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|ubiquitin protein ligase activity|
|negative regulation of apoptotic signaling pathway|
|regulation of protein modification by small protein conjugation or removal|
|transcription corepressor activity|
|regulation of cysteine-type endopeptidase activity|
|negative regulation of endopeptidase activity|
|ubiquitin-protein transferase activity|
|negative regulation of peptidase activity|
|early endosome|
|rhythmic process|
|regulation of canonical Wnt signaling pathway|
|protein deubiquitination|
|protein modification by small protein removal|
|protein polyubiquitination|
|small GTPase mediated signal transduction|
|neuron projection|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|proteasomal protein catabolic process|
|negative regulation of proteolysis|
|regulation of Wnt signaling pathway|
|neuronal cell body|
|regulation of apoptotic signaling pathway|
|regulation of endopeptidase activity|
|regulation of peptidase activity|
|negative regulation of hydrolase activity|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|proteolysis involved in cellular protein catabolic process|
|cellular protein catabolic process|
|protein catabolic process|
|intracellular membrane-bounded organelle|
|protein ubiquitination|
|regulation of proteolysis|
|protein modification by small protein conjugation|
|negative regulation of catalytic activity|
|zinc ion binding|
|negative regulation of apoptotic process|
|cellular macromolecule catabolic process|
|negative regulation of programmed cell death|
|apoptotic process|
|protein modification by small protein conjugation or removal|
|negative regulation of cell death|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|programmed cell death|
|organonitrogen compound catabolic process|
|cell death|
|negative regulation of protein metabolic process|
|negative regulation of molecular function|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|proteolysis|
|regulation of hydrolase activity|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|regulation of programmed cell death|
|negative regulation of response to stimulus|
|regulation of cell death|
|intracellular signal transduction|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of protein modification process|
</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:exp6|Bortezomib 0.005μM R00 exp6]]|-2.03|
|[[:results:exp54|Taxol 0.002μM R01 exp54]]|-1.97|
|[[:results:exp101|Nicotinamide 1000μM R03 exp101]]|-1.95|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|-1.73|
|[[:results:exp413|THZ531 0.11 to 0.175μM on day4 R07 exp413]]|1.74|
</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: 1/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|1/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 12760
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.51 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SIAH2 Expression in NALM6 Cells: 5.51'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>