1. Gene Aliases

HSP90N, HSPC1, HSPCA, Heat Shock Protein 90kDa Alpha (Cytosolic), Class A Member 1, Lipopolysaccharide-Associated Protein 2, Heat Shock 90kDa Protein 1, Alpha, Renal Carcinoma Antigen NY-REN-38, Heat Shock 90kD Protein 1, Alpha, Heat Shock Protein HSP 90-Alpha, LPS-Associated Protein 2, Heat Shock 86 KDa, FLJ31884, HSP90A, HSP 86, Hsp89, Hsp90, HSP86, LAP-2, Heat Shock Protein 90kDa Alpha Family Class A Member 1, Epididymis Secretory Sperm Binding Protein Li 65p, Epididymis Luminal Secretory Protein 52, Heat Shock 90kD Protein 1, Alpha-Like 4, Heat Shock 90kD Protein, Alpha-Like 4, EC 3.6.4.10, HEL-S-65p, HSPCAL1, HSPCAL4, HSP89A, Hsp103, HSP89, HSP90, EL52, HSPN, LAP2

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=HSP90AA1&keywords=Hsp90aa1]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

The interactions list has been truncated to include only interactions with the strongest support from the literature.

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

activation of innate immune response [Any process that initiates an innate immune response. Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. Examples of this process include activation of the hypersensitive response of Arabidopsis thaliana and activation of any NOD or TLR signaling pathway in vertebrate species. GO:0002218]

cardiac muscle cell apoptotic process [A form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases, whose actions dismantle a cardiac muscle cell and result in its death. Cardiac muscle cells are striated muscle cells that are responsible for heart contraction. GO:0010659]

cellular response to heat [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a heat stimulus, a temperature stimulus above the optimal temperature for that organism. GO:0034605]

cellular response to virus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus. GO:0098586]

chaperone-mediated autophagy [The autophagy process which begins when chaperones and co-chaperones recognize a target motif and unfold the substrate protein. The proteins are then transported to the lysosome where they are degraded. GO:0061684]

chaperone-mediated protein complex assembly [The aggregation, arrangement and bonding together of a set of components to form a protein complex, mediated by chaperone molecules that do not form part of the finished complex. GO:0051131]

neuron migration [The characteristic movement of an immature neuron from germinal zones to specific positions where they will reside as they mature. GO:0001764]

positive regulation of cardiac muscle contraction [Any process that increases the frequency, rate or extent of cardiac muscle contraction. GO:0060452]

positive regulation of cell size [Any process that increases cell size. GO:0045793]

positive regulation of defense response to virus by host [Any host process that results in the promotion of antiviral immune response mechanisms, thereby limiting viral replication. GO:0002230]

positive regulation of interferon-beta production [Any process that activates or increases the frequency, rate, or extent of interferon-beta production. GO:0032728]

positive regulation of lamellipodium assembly [Any process that increases the rate, frequency or extent of the formation of a lamellipodium, a thin sheetlike extension of the surface of a migrating cell. GO:0010592]

positive regulation of nitric oxide biosynthetic process [Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of nitric oxide. GO:0045429]

positive regulation of protein catabolic process [Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds. GO:0045732]

positive regulation of protein import into nucleus [Any process that activates or increases the frequency, rate or extent of movement of proteins from the cytoplasm into the nucleus. GO:0042307]

positive regulation of protein phosphorylation [Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein. GO:0001934]

positive regulation of protein polymerization [Any process that activates or increases the frequency, rate or extent of the process of creating protein polymers. GO:0032273]

protein folding [The process of assisting in the covalent and noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure. GO:0006457]

protein insertion into mitochondrial outer membrane [The process comprising the insertion of proteins from outside the organelle into the mitochondrial outer membrane, mediated by large outer membrane translocase complexes. GO:0045040]

protein stabilization [Any process involved in maintaining the structure and integrity of a protein and preventing it from degradation or aggregation. GO:0050821]

regulation of apoptotic process [Any process that modulates the occurrence or rate of cell death by apoptotic process.|This term should only be used when it is not possible to determine which phase or subtype of the apoptotic process is regulated by a gene product. Whenever detailed information is available, the more granular children terms should be used. GO:0042981]

regulation of postsynaptic membrane neurotransmitter receptor levels [Any process that regulates the local concentration of neurotransmitter receptor at the postsynaptic membrane. GO:0099072]

regulation of protein complex stability [Any process that affects the structure and integrity of a protein complex by altering the likelihood of its assembly or disassembly. GO:0061635]

regulation of protein localization [Any process that modulates the frequency, rate or extent of any process in which a protein is transported to, or maintained in, a specific location. GO:0032880]

regulation of protein ubiquitination [Any process that modulates the frequency, rate or extent of the addition of ubiquitin groups to a protein. GO:0031396]

response to antibiotic [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an antibiotic stimulus. An antibiotic is a chemical substance produced by a microorganism which has the capacity to inhibit the growth of or to kill other microorganisms. GO:0046677]

response to cocaine [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cocaine stimulus. Cocaine is a crystalline alkaloid obtained from the leaves of the coca plant. GO:0042220]

response to cold [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cold stimulus, a temperature stimulus below the optimal temperature for that organism. GO:0009409]

response to estrogen [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of stimulus by an estrogen, C18 steroid hormones that can stimulate the development of female sexual characteristics. GO:0043627]

response to heat [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a heat stimulus, a temperature stimulus above the optimal temperature for that organism. GO:0009408]

response to salt stress [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating an increase or decrease in the concentration of salt (particularly but not exclusively sodium and chloride ions) in the environment. GO:0009651]

response to xenobiotic stimulus [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organism exposed to it. It may be synthesized by another organism (like ampicillin) or it can be a synthetic chemical. GO:0009410]

skeletal muscle contraction [A process in which force is generated within skeletal muscle tissue, resulting in a change in muscle geometry. Force generation involves a chemo-mechanical energy conversion step that is carried out by the actin/myosin complex activity, which generates force through ATP hydrolysis. In the skeletal muscle, the muscle contraction takes advantage of an ordered sarcomeric structure and in most cases it is under voluntary control. GO:0003009]

telomerase holoenzyme complex assembly [The aggregation, arrangement and bonding together of a set of components to form a telomerase holoenzyme complex. GO:1905323]

telomere maintenance via telomerase [The maintenance of proper telomeric length by the addition of telomeric repeats by telomerase. GO:0007004]

MSigDB Signatures:

REACTOME_CELLULAR_RESPONSES_TO_STIMULI: Cellular responses to stimuli [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELLULAR_RESPONSES_TO_STIMULI.html]

REACTOME_CELLULAR_RESPONSE_TO_HEAT_STRESS: Cellular response to heat stress [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELLULAR_RESPONSE_TO_HEAT_STRESS.html]

REACTOME_INNATE_IMMUNE_SYSTEM: Innate Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INNATE_IMMUNE_SYSTEM.html]

REACTOME_CELL_CYCLE: Cell Cycle [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELL_CYCLE.html]

REACTOME_INFECTIOUS_DISEASE: Infectious disease [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INFECTIOUS_DISEASE.html]

WP_TH17_CELL_DIFFERENTIATION_PATHWAY: Th17 cell differentiation pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_TH17_CELL_DIFFERENTIATION_PATHWAY.html]

REACTOME_CELL_CYCLE_MITOTIC: Cell Cycle, Mitotic [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELL_CYCLE_MITOTIC.html]

REACTOME_SIGNALING_BY_NUCLEAR_RECEPTORS: Signaling by Nuclear Receptors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_NUCLEAR_RECEPTORS.html]

REACTOME_M_PHASE: M Phase [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_M_PHASE.html]

REACTOME_SIGNALING_BY_VEGF: Signaling by VEGF [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_VEGF.html]

WP_FOCAL_ADHESION_PI3K_AKT_MTOR_SIGNALING_PATHWAY: Focal adhesion PI3K Akt mTOR signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_FOCAL_ADHESION_PI3K_AKT_MTOR_SIGNALING_PATHWAY.html]

REACTOME_INFLUENZA_INFECTION: Influenza Infection [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INFLUENZA_INFECTION.html]

REACTOME_HSF1_ACTIVATION: HSF1 activation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_HSF1_ACTIVATION.html]

REACTOME_ANCHORING_OF_THE_BASAL_BODY_TO_THE_PLASMA_MEMBRANE: Anchoring of the basal body to the plasma membrane [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ANCHORING_OF_THE_BASAL_BODY_TO_THE_PLASMA_MEMBRANE.html]

KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION: Antigen processing and presentation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION.html]

REACTOME_SIGNALING_BY_ERBB2: Signaling by ERBB2 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_ERBB2.html]

REACTOME_VEGFR2_MEDIATED_VASCULAR_PERMEABILITY: VEGFR2 mediated vascular permeability [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_VEGFR2_MEDIATED_VASCULAR_PERMEABILITY.html]

KEGG_PATHWAYS_IN_CANCER: Pathways in cancer [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PATHWAYS_IN_CANCER.html]

WP_NUCLEAR_RECEPTORS_META_PATHWAY: Nuclear receptors meta pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_NUCLEAR_RECEPTORS_META_PATHWAY.html]

WP_CONSTITUTIVE_ANDROSTANE_RECEPTOR_PATHWAY: Constitutive androstane receptor pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CONSTITUTIVE_ANDROSTANE_RECEPTOR_PATHWAY.html]

BIOCARTA_AKT_PATHWAY: AKT Signaling Pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BIOCARTA_AKT_PATHWAY.html]

WP_PI3K_AKT_SIGNALING_PATHWAY: PI3K Akt signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PI3K_AKT_SIGNALING_PATHWAY.html]

REACTOME_ATTENUATION_PHASE: Attenuation phase [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ATTENUATION_PHASE.html]

REACTOME_MITOTIC_G2_G2_M_PHASES: Mitotic G2-G2/M phases [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_MITOTIC_G2_G2_M_PHASES.html]

REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS: Diseases of signal transduction by growth factor receptors and second messengers [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DISEASES_OF_SIGNAL_TRANSDUCTION_BY_GROWTH_FACTOR_RECEPTORS_AND_SECOND_MESSENGERS.html]

REACTOME_CILIUM_ASSEMBLY: Cilium Assembly [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CILIUM_ASSEMBLY.html]

REACTOME_NEUTROPHIL_DEGRANULATION: Neutrophil degranulation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NEUTROPHIL_DEGRANULATION.html]

KEGG_NOD_LIKE_RECEPTOR_SIGNALING_PATHWAY: NOD-like receptor signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_NOD_LIKE_RECEPTOR_SIGNALING_PATHWAY.html]

REACTOME_DEVELOPMENTAL_BIOLOGY: Developmental Biology [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DEVELOPMENTAL_BIOLOGY.html]

REACTOME_REGULATED_NECROSIS: Regulated Necrosis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_REGULATED_NECROSIS.html]

REACTOME_VIRAL_INFECTION_PATHWAYS: Viral Infection Pathways [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_VIRAL_INFECTION_PATHWAYS.html]

KEGG_PROSTATE_CANCER: Prostate cancer [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PROSTATE_CANCER.html]

REACTOME_SEMAPHORIN_INTERACTIONS: Semaphorin interactions [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SEMAPHORIN_INTERACTIONS.html]

REACTOME_AUTOPHAGY: Autophagy [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_AUTOPHAGY.html]

WP_TNF_ALPHA_SIGNALING_PATHWAY: TNF alpha signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_TNF_ALPHA_SIGNALING_PATHWAY.html]

REACTOME_NERVOUS_SYSTEM_DEVELOPMENT: Nervous system development [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NERVOUS_SYSTEM_DEVELOPMENT.html]

REACTOME_SIGNALING_BY_INTERLEUKINS: Signaling by Interleukins [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_INTERLEUKINS.html]

BIOCARTA_TEL_PATHWAY: Telomeres, Telomerase, Cellular Aging, and Immortality [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BIOCARTA_TEL_PATHWAY.html]

REACTOME_SARS_COV_2_INFECTION: SARS-CoV-2 Infection [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SARS_COV_2_INFECTION.html]

REACTOME_BACTERIAL_INFECTION_PATHWAYS: Bacterial Infection Pathways [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_BACTERIAL_INFECTION_PATHWAYS.html]

REACTOME_DOWNREGULATION_OF_ERBB2_SIGNALING: Downregulation of ERBB2 signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DOWNREGULATION_OF_ERBB2_SIGNALING.html]

WP_VEGFA_VEGFR2_SIGNALING: VEGFA VEGFR2 signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_VEGFA_VEGFR2_SIGNALING.html]

REACTOME_VESICLE_MEDIATED_TRANSPORT: Vesicle-mediated transport [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_VESICLE_MEDIATED_TRANSPORT.html]

REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM: Cytokine Signaling in Immune system [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM.html]

WP_EBSTEIN_BARR_VIRUS_LMP1_SIGNALING: Ebstein Barr virus LMP1 signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_EBSTEIN_BARR_VIRUS_LMP1_SIGNALING.html]

REACTOME_SCAVENGING_BY_CLASS_F_RECEPTORS: Scavenging by Class F Receptors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SCAVENGING_BY_CLASS_F_RECEPTORS.html]

REACTOME_INTERLEUKIN_4_AND_INTERLEUKIN_13_SIGNALING: Interleukin-4 and Interleukin-13 signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INTERLEUKIN_4_AND_INTERLEUKIN_13_SIGNALING.html]

REACTOME_CONSTITUTIVE_SIGNALING_BY_OVEREXPRESSED_ERBB2: Constitutive Signaling by Overexpressed ERBB2 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CONSTITUTIVE_SIGNALING_BY_OVEREXPRESSED_ERBB2.html]

REACTOME_SIGNALING_BY_RECEPTOR_TYROSINE_KINASES: Signaling by Receptor Tyrosine Kinases [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_RECEPTOR_TYROSINE_KINASES.html]

MA_RAT_AGING_DN: Genes down-regulated across multiple cell types from nine tissues during rat aging. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MA_RAT_AGING_DN.html]

REACTOME_EXTRA_NUCLEAR_ESTROGEN_SIGNALING: Extra-nuclear estrogen signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_EXTRA_NUCLEAR_ESTROGEN_SIGNALING.html]

WP_IL_24_SIGNALING_PATHWAY: IL 24 Signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_IL_24_SIGNALING_PATHWAY.html]

WP_PREGNANE_X_RECEPTOR_PATHWAY: Pregnane X receptor pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PREGNANE_X_RECEPTOR_PATHWAY.html]

REACTOME_MITOTIC_PROMETAPHASE: Mitotic Prometaphase [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_MITOTIC_PROMETAPHASE.html]

REACTOME_CONSTITUTIVE_SIGNALING_BY_EGFRVIII: Constitutive Signaling by EGFRvIII [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CONSTITUTIVE_SIGNALING_BY_EGFRVIII.html]

WP_ARYL_HYDROCARBON_RECEPTOR_PATHWAY_WP2586: Aryl hydrocarbon receptor pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_ARYL_HYDROCARBON_RECEPTOR_PATHWAY_WP2586.html]

WP_ARYL_HYDROCARBON_RECEPTOR_PATHWAY_WP2873: Aryl hydrocarbon receptor pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_ARYL_HYDROCARBON_RECEPTOR_PATHWAY_WP2873.html]

REACTOME_ENOS_ACTIVATION: eNOS activation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ENOS_ACTIVATION.html]

REACTOME_HSF1_DEPENDENT_TRANSACTIVATION: HSF1-dependent transactivation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_HSF1_DEPENDENT_TRANSACTIVATION.html]

REACTOME_SIGNALING_BY_ERBB2_IN_CANCER: Signaling by ERBB2 in Cancer [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_ERBB2_IN_CANCER.html]

REACTOME_AURKA_ACTIVATION_BY_TPX2: AURKA Activation by TPX2 [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_AURKA_ACTIVATION_BY_TPX2.html]

REACTOME_SIGNALING_BY_ERBB2_ECD_MUTANTS: Signaling by ERBB2 ECD mutants [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_ERBB2_ECD_MUTANTS.html]

REACTOME_ESTROGEN_DEPENDENT_GENE_EXPRESSION: Estrogen-dependent gene expression [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ESTROGEN_DEPENDENT_GENE_EXPRESSION.html]

REACTOME_ESR_MEDIATED_SIGNALING: ESR-mediated signaling [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ESR_MEDIATED_SIGNALING.html]

REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE: Organelle biogenesis and maintenance [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ORGANELLE_BIOGENESIS_AND_MAINTENANCE.html]

REACTOME_PROGRAMMED_CELL_DEATH: Programmed Cell Death [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_PROGRAMMED_CELL_DEATH.html]

WP_GLUCOCORTICOID_RECEPTOR_PATHWAY: Glucocorticoid receptor pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_GLUCOCORTICOID_RECEPTOR_PATHWAY.html]

REACTOME_AGGREPHAGY: Aggrephagy [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_AGGREPHAGY.html]

REACTOME_SARS_COV_INFECTIONS: SARS-CoV Infections [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SARS_COV_INFECTIONS.html]

REACTOME_SIGNALING_BY_EGFR_IN_CANCER: Signaling by EGFR in Cancer [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_SIGNALING_BY_EGFR_IN_CANCER.html]

REACTOME_BINDING_AND_UPTAKE_OF_LIGANDS_BY_SCAVENGER_RECEPTORS: Binding and Uptake of Ligands by Scavenger Receptors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_BINDING_AND_UPTAKE_OF_LIGANDS_BY_SCAVENGER_RECEPTORS.html]

WP_CORTICOTROPIN_RELEASING_HORMONE_SIGNALING_PATHWAY: Corticotropin releasing hormone signaling pathway [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_CORTICOTROPIN_RELEASING_HORMONE_SIGNALING_PATHWAY.html]

7. Gene Descriptions

NCBI Gene Summary: The protein encoded by this gene is an inducible molecular chaperone that functions as a homodimer. The encoded protein aids in the proper folding of specific target proteins by use of an ATPase activity that is modulated by co-chaperones. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GeneCards Summary: HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1) is a Protein Coding gene. Diseases associated with HSP90AA1 include Hepatocellular Carcinoma and Candidiasis. Among its related pathways are Resistance of ERBB2 KD mutants to osimertinib and Loss of proteins required for interphase microtubule organization from the centrosome. Gene Ontology (GO) annotations related to this gene include RNA binding and identical protein binding. An important paralog of this gene is HSP90AB1.

UniProtKB/Swiss-Prot Summary: Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function [PMID: 11274138, PMID: 15577939, PMID: 15937123, PMID: 27353360, PMID: 29127155, PMID: 12526792]. Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself [PMID: 29127155]. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle [PMID: 27295069, PMID: 26991466]. Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 [PMID: 12526792]. Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels [PMID: 25973397]. In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues[PMID: 25973397]. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment [PMID: 25973397]. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression [PMID: 25973397]. Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes [PMID: 11276205]. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation [PMID: 24613385]. Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response [PMID: 20628368, PMID: 25609812]. Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion.

8. Cellular Location of Gene Product

Cytoplasmic expression in several tissues. Mainly localized to the cytosol. Predicted location: Intracellular [https://www.proteinatlas.org/ENSG00000080824/subcellular]

9. Mechanistic Information

Summary

Hsp90aa1, as a molecular chaperone, is crucial in responding to skin diseases and toxicities due to its role in maintaining protein structure and function [CS: 9]. In the context of skin diseases like melanoma or psoriasis, the upregulation of Hsp90aa1 can be mechanistically linked to its function in stabilizing proteins that are vital for cell survival and proliferation [CS: 8]. For instance, in melanoma, the gene's overexpression is associated with stabilizing proteins in the telomerase complex, crucial for chromosomal integrity in proliferating cells [CS: 6]. This response could be a cellular attempt to manage aberrant cell growth and DNA damage, typical in cancerous conditions [CS: 7].

In response to thermal stress or toxicities, such as exposure to high temperatures, Hsp90aa1 expression increases, possibly to counteract the denaturing effect of heat on proteins [CS: 8]. This upregulation aids in refolding or stabilizing proteins that may have lost their structure due to heat shock [CS: 8]. In psoriasis, an exacerbated immune response leads to inflammation and skin cell proliferation [CS: 8]. The increased expression of Hsp90aa1 in this context might serve to stabilize key signaling proteins involved in these inflammatory and proliferative pathways, thus attempting to restore cellular homeostasis [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: low tissue specificity [https://www.proteinatlas.org/ENSG00000080824/tissue]

Cell type enchanced: low cell type specificity [https://www.proteinatlas.org/ENSG00000080824/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: