SIAH1 [The Human Chemical-Genetic Interaction Map Project]

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======= SIAH1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SIAH1
  * **<color #00a2e8>Official Name</color>**: siah E3 ubiquitin protein ligase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6477|6477]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q8IUQ4|Q8IUQ4]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SIAH1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SIAH1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602212|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in the development of certain forms of Parkinson's disease, the regulation of the cellular response to hypoxia and induction of apoptosis. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]. 
  * **<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 (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S- nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins. {ECO:0000269|PubMed:10747903, ECO:0000269|PubMed:11146551, ECO:0000269|PubMed:11389839, ECO:0000269|PubMed:11389840, ECO:0000269|PubMed:11483517, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:11752454, ECO:0000269|PubMed:12072443, ECO:0000269|PubMed:14506261, ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14654780, ECO:0000269|PubMed:15064394, ECO:0000269|PubMed:16085652, ECO:0000269|PubMed:18536714, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:20508617, ECO:0000269|PubMed:22483617, ECO:0000269|PubMed:9334332, ECO:0000269|PubMed:9858595}.

<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'>
|regulation of netrin-activated signaling pathway|
|negative regulation of netrin-activated signaling pathway|
|beta-catenin destruction complex|
|ubiquitin conjugating enzyme binding|
|neuron apoptotic process|
|protein destabilization|
|neuron death|
|positive regulation of intrinsic apoptotic signaling pathway|
|regulation of intrinsic apoptotic signaling pathway|
|positive regulation of apoptotic signaling pathway|
|protein C-terminus binding|
|ubiquitin protein ligase activity|
|ubiquitin-protein transferase activity|
|early endosome|
|axon guidance|
|neuron projection guidance|
|regulation of protein stability|
|protein polyubiquitination|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|proteasomal protein catabolic process|
|axonogenesis|
|regulation of apoptotic signaling pathway|
|axon development|
|cell morphogenesis involved in neuron differentiation|
|neuron projection morphogenesis|
|plasma membrane bounded cell projection morphogenesis|
|cell projection morphogenesis|
|cell part morphogenesis|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|spermatogenesis|
|chemotaxis|
|taxis|
|cell morphogenesis involved in differentiation|
|male gamete generation|
|proteolysis involved in cellular protein catabolic process|
|cellular protein catabolic process|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|neuron projection development|
|protein catabolic process|
|protein ubiquitination|
|gamete generation|
|positive regulation of cell death|
|cell morphogenesis|
|protein modification by small protein conjugation|
|neuron development|
|cellular component morphogenesis|
|multicellular organismal reproductive process|
|sexual reproduction|
|zinc ion binding|
|multicellular organism reproduction|
|cellular macromolecule catabolic process|
|apoptotic process|
|protein modification by small protein conjugation or removal|
|multi-organism reproductive process|
|neuron differentiation|
|positive regulation of intracellular signal transduction|
|macromolecule catabolic process|
|programmed cell death|
|organonitrogen compound catabolic process|
|identical protein binding|
|cell death|
|plasma membrane bounded cell projection organization|
|cell projection organization|
|negative regulation of signal transduction|
|proteolysis|
|locomotion|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|reproductive process|
|reproduction|
|generation of neurons|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|regulation of programmed cell death|
|negative regulation of response to stimulus|
|neurogenesis|
|cell development|
|positive regulation of signal transduction|
|regulation of cell death|
|organic substance catabolic process|
|cellular catabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
</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:exp498|Lead acetate 2000μM R08 exp498 no dilution day6]]|-2.36|
|[[:results:exp216|Erlotinib 10μM R05 exp216]]|-1.94|
|[[:results:exp49|NFN1 0.1μM R01 exp49]]|1.72|
|[[:results:exp90|WYE-354 6μM R02 exp90]]|1.76|
|[[:results:exp261|ABT-702 5μM R06 exp261]]|1.84|
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|1.87|
</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: 1/739
^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|1/33|
|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>**: 15318
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.43 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SIAH1 Expression in NALM6 Cells: 4.43'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>