HSPA8 [The Human Chemical-Genetic Interaction Map Project]

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======= HSPA8 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: HSPA8
  * **<color #00a2e8>Official Name</color>**: heat shock protein family A (Hsp70) member 8
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3312|3312]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P11142|P11142]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=HSPA8&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20HSPA8|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600816|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J- domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP- bound state thereby promoting substrate release), and the TPR domain chaperones such as HOPX and STUB1 (PubMed:24318877, PubMed:27474739, PubMed:24121476, PubMed:26865365). Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:10722728, PubMed:11276205). Participates in the ER- associated degradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUB1 (PubMed:23990462). {ECO:0000269|PubMed:10722728, ECO:0000269|PubMed:11276205, ECO:0000269|PubMed:21148293, ECO:0000269|PubMed:21150129, ECO:0000269|PubMed:23018488, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24732912, ECO:0000269|PubMed:27474739, ECO:0000269|PubMed:27916661, ECO:0000303|PubMed:24121476, ECO:0000303|PubMed:26865365}.

<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'>
|MreB Mbl|
|HSP70|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|clathrin-uncoating ATPase activity|
|chaperone-mediated autophagy translocation complex disassembly|
|slow axonal transport|
|lumenal side of lysosomal membrane|
|chaperone-mediated protein transport involved in chaperone-mediated autophagy|
|late endosomal microautophagy|
|protein targeting to lysosome involved in chaperone-mediated autophagy|
|protein targeting to vacuole involved in autophagy|
|C3HC4-type RING finger domain binding|
|clathrin coat disassembly|
|vesicle uncoating|
|chaperone-mediated autophagy|
|clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane|
|chaperone complex|
|regulation of protein complex stability|
|chaperone-mediated protein transport|
|Prp19 complex|
|presynaptic cytosol|
|MHC class II protein complex binding|
|postsynaptic cytosol|
|protein targeting to lysosome|
|ATPase activity, coupled|
|protein folding chaperone|
|misfolded protein binding|
|chaperone cofactor-dependent protein refolding|
|protein depolymerization|
|protein targeting to vacuole|
|de novo posttranslational protein folding|
|protein refolding|
|protein localization to lysosome|
|de novo protein folding|
|establishment of protein localization to vacuole|
|terminal bouton|
|heat shock protein binding|
|regulation of protein import|
|chaperone-mediated protein folding|
|protein transmembrane transport|
|protein localization to vacuole|
|axo-dendritic transport|
|G protein-coupled receptor binding|
|autophagosome|
|cellular response to heat|
|protein binding, bridging|
|regulation of cellular response to heat|
|spliceosomal complex|
|lysosomal lumen|
|melanosome|
|signal release from synapse|
|neurotransmitter secretion|
|chaperone binding|
|lysosomal transport|
|response to heat|
|secretory granule lumen|
|ficolin-1-rich granule lumen|
|cellular response to unfolded protein|
|negative regulation of supramolecular fiber organization|
|unfolded protein binding|
|cellular protein complex disassembly|
|blood microparticle|
|vacuolar transport|
|cellular response to topologically incorrect protein|
|cellular response to starvation|
|ribonucleoprotein complex|
|transport along microtubule|
|response to unfolded protein|
|signal release|
|cytoskeleton-dependent intracellular transport|
|response to temperature stimulus|
|neurotransmitter transport|
|regulation of mRNA stability|
|microtubule-based transport|
|regulation of RNA stability|
|response to topologically incorrect protein|
|response to starvation|
|regulation of mRNA catabolic process|
|ATP metabolic process|
|protein folding|
|cellular response to nutrient levels|
|ATPase activity|
|protein-containing complex disassembly|
|lysosome|
|autophagy|
|process utilizing autophagic mechanism|
|cellular response to extracellular stimulus|
|microtubule-based movement|
|regulation of protein stability|
|ubiquitin protein ligase binding|
|axon|
|RNA splicing, via transesterification reactions with bulged adenosine as nucleophile|
|mRNA splicing, via spliceosome|
|lysosomal membrane|
|RNA splicing, via transesterification reactions|
|cadherin binding|
|regulation of mRNA metabolic process|
|cellular response to external stimulus|
|enzyme binding|
|regulation of supramolecular fiber organization|
|regulation of neurotransmitter levels|
|protein targeting|
|RNA splicing|
|cellular component disassembly|
|focal adhesion|
|anterograde trans-synaptic signaling|
|chemical synaptic transmission|
|dendrite|
|establishment of protein localization to organelle|
|trans-synaptic signaling|
|regulation of protein complex assembly|
|synaptic signaling|
|mRNA processing|
|neutrophil degranulation|
|neutrophil activation involved in immune response|
|response to nutrient levels|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|leukocyte degranulation|
|myeloid leukocyte mediated immunity|
|myeloid cell activation involved in immune response|
|posttranscriptional regulation of gene expression|
|response to extracellular stimulus|
|myeloid leukocyte activation|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|microtubule-based process|
|cytokine-mediated signaling pathway|
|protein catabolic process|
|mRNA metabolic process|
|viral process|
|regulated exocytosis|
|negative regulation of cellular component organization|
|regulation of protein transport|
|regulation of cellular response to stress|
|protein localization to organelle|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|leukocyte mediated immunity|
|symbiotic process|
|exocytosis|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|membrane organization|
|nucleolus|
|RNA processing|
|leukocyte activation|
|regulation of cellular component biogenesis|
|regulation of catabolic process|
|intracellular protein transport|
|secretion by cell|
|cellular response to cytokine stimulus|
|regulation of protein localization|
|export from cell|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|cell activation|
|immune effector process|
|response to cytokine|
|cell-cell signaling|
|secretion|
|response to abiotic stimulus|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|transmembrane transport|
|negative regulation of RNA metabolic process|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|ATP binding|
|protein transport|
|negative regulation of cellular biosynthetic process|
|intracellular transport|
|peptide transport|
|negative regulation of biosynthetic process|
|movement of cell or subcellular component|
|amide transport|
|cellular protein localization|
|cellular macromolecule localization|
|extracellular space|
|establishment of protein localization|
|RNA metabolic process|
|cellular response to stress|
|negative regulation of gene expression|
|organic substance catabolic process|
|cellular catabolic process|
|establishment of localization in cell|
|nitrogen compound transport|
|protein-containing complex subunit organization|
|regulation of transport|
|immune response|
|extracellular region|
|vesicle-mediated transport|
|membrane|
|gene expression|
</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:exp354|Diepoxybutane 3μM R07 exp354]]|1.73|
|[[:results:exp316|Geldanamycin 0.015 to 0.025μM on day4 R07 exp316]]|1.75|
|[[:results:exp210|LB-100 2μM R05 exp210]]|1.77|
|[[:results:exp426|FBS-Wisent 0.1 R07 exp426]]|1.79|
|[[:results:exp440|Aphidicolin 0.4μM R08 exp440]]|1.82|
|[[:results:exp37|Wortmannin 0.5μM R00 exp37]]|1.91|
|[[:results:exp16|DABN 2μM R00 exp16]]|1.92|
|[[:results:exp211|AICAR 240μM R05 exp211]]|1.94|
|[[:results:exp261|ABT-702 5μM R06 exp261]]|2|
|[[:results:exp259|6-Thio-2-deoxyguanosine 2μM R06 exp259]]|2.26|
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|2.5|
</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: 18/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|3/28|
|bone|1/26|
|breast|0/33|
|central nervous system|1/56|
|cervix|0/4|
|colorectal|1/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|1/20|
|lung|2/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|2/16|
|plasma cell|1/15|
|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>**: 348
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 11.22 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='HSPA8 Expression in NALM6 Cells: 11.22'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>