======= HSPA1A =======
== Gene Information ==
* **Official Symbol**: HSPA1A
* **Official Name**: heat shock protein family A (Hsp70) member 1A
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=3303|3303]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P0DMV8|P0DMV8]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=HSPA1A&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20HSPA1A|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/140550|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: N/A
* **UniProt Summary**: 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. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. The affinity 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. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release. The co-chaperones are of three types: J-domain co-chaperones such as 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:24012426, PubMed:26865365, PubMed:24318877). Maintains protein homeostasis during cellular stress through two opposing mechanisms: protein refolding and degradation. Its acetylation/deacetylation state determines whether it functions in protein refolding or protein degradation by controlling the competitive binding of co-chaperones HOPX and STUB1. During the early stress response, the acetylated form binds to HOPX which assists in chaperone-mediated protein refolding, thereafter, it is deacetylated and binds to ubiquitin ligase STUB1 that promotes ubiquitin-mediated protein degradation (PubMed:27708256). Regulates centrosome integrity during mitosis, and is required for the maintenance of a functional mitotic centrosome that supports the assembly of a bipolar mitotic spindle (PubMed:27137183). Enhances STUB1-mediated SMAD3 ubiquitination and degradation and facilitates STUB1-mediated inhibition of TGF-beta signaling (PubMed:24613385). Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223). Negatively regulates heat shock- induced HSF1 transcriptional activity during the attenuation and recovery phase period of the heat shock response (PubMed:9499401). {ECO:0000269|PubMed:22528486, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:24318877, ECO:0000269|PubMed:24613385, ECO:0000269|PubMed:27137183, ECO:0000269|PubMed:27708256, ECO:0000269|PubMed:9499401, ECO:0000303|PubMed:24012426, ECO:0000303|PubMed:26865365}.
|MreB Mbl|
|HSP70|
|denatured protein binding|
|positive regulation of endoribonuclease activity|
|positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway|
|positive regulation of nucleotide-binding oligomerization domain containing signaling pathway|
|regulation of endoribonuclease activity|
|positive regulation of microtubule nucleation|
|C3HC4-type RING finger domain binding|
|regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway|
|cellular heat acclimation|
|heat acclimation|
|regulation of microtubule nucleation|
|negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway|
|positive regulation of nuclease activity|
|regulation of nucleotide-binding oligomerization domain containing signaling pathway|
|regulation of ribonuclease activity|
|positive regulation of tumor necrosis factor-mediated signaling pathway|
|negative regulation of inclusion body assembly|
|negative regulation of transcription from RNA polymerase II promoter in response to stress|
|regulation of inclusion body assembly|
|chaperone-mediated protein complex assembly|
|inclusion body|
|negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway|
|ATPase activity, coupled|
|regulation of nuclease activity|
|regulation of mitotic spindle assembly|
|protein folding chaperone|
|misfolded protein binding|
|regulation of spindle assembly|
|positive regulation of erythrocyte differentiation|
|positive regulation of microtubule polymerization|
|chaperone cofactor-dependent protein refolding|
|regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway|
|disordered domain specific binding|
|positive regulation of RNA splicing|
|positive regulation of microtubule polymerization or depolymerization|
|negative regulation of signal transduction in absence of ligand|
|negative regulation of extrinsic apoptotic signaling pathway in absence of ligand|
|COP9 signalosome|
|protein refolding|
|de novo posttranslational protein folding|
|regulation of mitotic spindle organization|
|de novo protein folding|
|regulation of spindle organization|
|aggresome|
|negative regulation of response to endoplasmic reticulum stress|
|regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway|
|regulation of erythrocyte differentiation|
|regulation of extrinsic apoptotic signaling pathway in absence of ligand|
|positive regulation of interleukin-8 production|
|positive regulation of cytokine-mediated signaling pathway|
|regulation of microtubule polymerization|
|negative regulation of mitochondrion organization|
|positive regulation of response to cytokine stimulus|
|heat shock protein binding|
|regulation of tumor necrosis factor-mediated signaling pathway|
|chaperone-mediated protein folding|
|G protein-coupled receptor binding|
|regulation of interleukin-8 production|
|cellular response to heat|
|regulation of mitochondrial membrane permeability|
|negative regulation of transforming growth factor beta receptor signaling pathway|
|negative regulation of protein ubiquitination|
|negative regulation of cellular response to transforming growth factor beta stimulus|
|virus receptor activity|
|regulation of cellular response to heat|
|regulation of microtubule polymerization or depolymerization|
|regulation of membrane permeability|
|positive regulation of proteasomal ubiquitin-dependent protein catabolic process|
|regulation of response to endoplasmic reticulum stress|
|negative regulation of protein modification by small protein conjugation or removal|
|positive regulation of myeloid cell differentiation|
|viral entry into host cell|
|negative regulation of intrinsic apoptotic signaling pathway|
|positive regulation of ubiquitin-dependent protein catabolic process|
|negative regulation of extrinsic apoptotic signaling pathway|
|entry into host|
|entry into host cell|
|positive regulation of proteasomal protein catabolic process|
|lysosomal transport|
|protein N-terminus binding|
|response to heat|
|histone deacetylase binding|
|regulation of transforming growth factor beta receptor signaling pathway|
|regulation of cellular response to transforming growth factor beta stimulus|
|negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|regulation of transcription from RNA polymerase II promoter in response to stress|
|positive regulation of proteolysis involved in cellular protein catabolic process|
|regulation of proteasomal ubiquitin-dependent protein catabolic process|
|ficolin-1-rich granule lumen|
|regulation of DNA-templated transcription in response to stress|
|cellular response to unfolded protein|
|mitochondrial membrane organization|
|positive regulation of protein polymerization|
|unfolded protein binding|
|regulation of RNA splicing|
|positive regulation of cellular protein catabolic process|
|vesicle|
|blood microparticle|
|vacuolar transport|
|centriole|
|negative regulation of cellular response to growth factor stimulus|
|cellular response to topologically incorrect protein|
|positive regulation of NF-kappaB transcription factor activity|
|regulation of ubiquitin-dependent protein catabolic process|
|regulation of extrinsic apoptotic signaling pathway|
|ribonucleoprotein complex|
|interaction with host|
|regulation of intrinsic apoptotic signaling pathway|
|response to unfolded protein|
|regulation of cytokine-mediated signaling pathway|
|regulation of mitotic nuclear division|
|regulation of response to cytokine stimulus|
|response to temperature stimulus|
|protein stabilization|
|regulation of mRNA stability|
|regulation of mitochondrion organization|
|negative regulation of cell growth|
|regulation of proteasomal protein catabolic process|
|regulation of RNA stability|
|response to topologically incorrect protein|
|positive regulation of hemopoiesis|
|regulation of microtubule cytoskeleton organization|
|regulation of nuclear division|
|positive regulation of supramolecular fiber organization|
|regulation of protein ubiquitination|
|regulation of mRNA catabolic process|
|viral life cycle|
|ATP metabolic process|
|mitochondrial transport|
|mRNA catabolic process|
|regulation of proteolysis involved in cellular protein catabolic process|
|positive regulation of protein catabolic process|
|positive regulation of cytoskeleton organization|
|regulation of organelle assembly|
|regulation of microtubule-based process|
|regulation of protein polymerization|
|regulation of myeloid cell differentiation|
|negative regulation of apoptotic signaling pathway|
|regulation of protein modification by small protein conjugation or removal|
|protein folding|
|regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|ATPase activity|
|cellular response to oxidative stress|
|transcription corepressor activity|
|negative regulation of growth|
|RNA catabolic process|
|positive regulation of protein complex assembly|
|regulation of cellular protein catabolic process|
|positive regulation of DNA-binding transcription factor activity|
|regulation of cellular response to growth factor stimulus|
|regulation of protein stability|
|ubiquitin protein ligase binding|
|cadherin binding|
|regulation of mRNA metabolic process|
|signaling receptor binding|
|positive regulation of innate immune response|
|enzyme binding|
|regulation of supramolecular fiber organization|
|positive regulation of proteolysis|
|positive regulation of response to biotic stimulus|
|positive regulation of cellular catabolic process|
|negative regulation of organelle organization|
|nucleobase-containing compound catabolic process|
|regulation of protein catabolic process|
|response to oxidative stress|
|regulation of apoptotic signaling pathway|
|nuclear speck|
|focal adhesion|
|regulation of cell growth|
|regulation of DNA-binding transcription factor activity|
|positive regulation of catabolic process|
|heterocycle catabolic process|
|cellular nitrogen compound catabolic process|
|mitochondrion organization|
|aromatic compound catabolic process|
|positive regulation of cytokine production|
|regulation of protein complex assembly|
|regulation of hemopoiesis|
|regulation of innate immune response|
|positive regulation of defense response|
|organic cyclic compound catabolic process|
|negative regulation of transport|
|neutrophil degranulation|
|centrosome|
|neutrophil activation involved in immune response|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|negative regulation of intracellular signal transduction|
|positive regulation of multi-organism process|
|leukocyte degranulation|
|myeloid leukocyte mediated immunity|
|positive regulation of cellular component biogenesis|
|myeloid cell activation involved in immune response|
|regulation of response to biotic stimulus|
|posttranscriptional regulation of gene expression|
|regulation of cytoskeleton organization|
|myeloid leukocyte activation|
|negative regulation of protein modification process|
|protein-containing complex|
|positive regulation of response to external stimulus|
|positive regulation of organelle organization|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|regulation of mitotic cell cycle|
|regulation of growth|
|negative regulation of cell population proliferation|
|regulation of cytokine production|
|mRNA metabolic process|
|perinuclear region of cytoplasm|
|viral process|
|regulated exocytosis|
|negative regulation of cellular component organization|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of cell cycle process|
|regulation of defense response|
|leukocyte mediated immunity|
|positive regulation of hydrolase activity|
|regulation of multi-organism process|
|symbiotic process|
|exocytosis|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|cellular protein-containing complex assembly|
|membrane organization|
|negative regulation of transcription by RNA polymerase II|
|positive regulation of immune response|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|cellular macromolecule catabolic process|
|leukocyte activation|
|regulation of cellular component biogenesis|
|positive regulation of cell differentiation|
|regulation of catabolic process|
|negative regulation of cell death|
|secretion by cell|
|endoplasmic reticulum|
|positive regulation of intracellular signal transduction|
|negative regulation of cellular protein metabolic process|
|export from cell|
|macromolecule catabolic process|
|cell activation|
|immune effector process|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|secretion|
|positive regulation of immune system process|
|regulation of immune response|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|positive regulation of cellular component organization|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|mitochondrion|
|negative regulation of signal transduction|
|regulation of hydrolase activity|
|regulation of organelle organization|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|protein-containing complex assembly|
|regulation of programmed cell death|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|regulation of immune system process|
|positive regulation of signal transduction|
|RNA metabolic process|
|regulation of cell death|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|organic substance catabolic process|
|positive regulation of molecular function|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|extracellular region|
|vesicle-mediated transport|
|positive regulation of gene expression|
\\
=== CRISPR Data ===
No hits were found.
No correlation found to any other genes in chemogenomics.
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|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|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 5183
* **Expression level (log2 read counts)**: 3.71
{{:chemogenomics:nalm6 dist.png?nolink |}}