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FLASH GENE
Symbol HSP90AA1 contributors: shn/npt/pgu - updated : 22-10-2018
HGNC name heat shock protein 90kDa alpha (cytosolic), class A member 1
HGNC id 5253
DNA
TYPE like-sequence
STRUCTURE 59.01 kb     12 Exon(s)
MAPPING cloned Y linked N status provisional
Map cent - D14S985 - D14S1051 - HSP90AA1 - D14S272 - D14S293 - qter
RNA
TRANSCRIPTS type messenger
text
  • composed of 17 exons with multiple alternative splicing sites (PMID: 21256126)
    • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3887 85 854 - 2008 18270269
    11 - 3366 - 732 - 2008 18270269
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Endocrinepancreas    
    Lymphoid/Immunetonsils   highly
    Nervousnerve   highly
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousglia
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text pancreas
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a highly conserved N-terminal domain
  • two charged domains
  • a middle domain involved in ATPase activity
  • a 4 helical cytokine motif and a glutamin-rich region
  • a C-terminal MEEVD motif
    • mono polymer dimer , tetramer , hexamer , oligo
    HOMOLOGY
    interspecies ortholog to hsp90a.1, Danio rerio
    ortholog to Hsp90aa1, Mus musculus
    ortholog to Hsp90aa1, Rattus norvegicus
    Homologene
    FAMILY
  • heat shock protein 90 family
    • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm
    text
  • also found in mitochondria of tumor cells
  • Shuttling of the chaperones UNC45B and HSPAA1 between the A band and the Z line of the myofibril
  • found in almost every compartment of eukaryotic cells
  • clustered at the periciliary base
    • basic FUNCTION
  • molecular chaperone that have key roles in the protein signaling pathway, protein folding, protein degradation, and morphologic evolution
  • plays a key role in the conformational maturation of oncogenic signaling proteins
  • helps a variety of proteins to adopt their native conformation
  • has a role in cancer cell invasion
  • play important roles in folding newly synthesized proteins or stabilizing and refolding denatured proteins after stress
  • having ATPase activity
  • mediating the targeting of a subset of mitochondrial preproteins to the TOM70 receptor
  • playing important roles in maintaining and facilitating the degenerative phenotype in degenerative diseases and provide a common principle governing cancer and neurodegenerative diseases
  • playing an active role in the targeting and outer membrane translocation steps of TOMM70A-mediated mitochondrial import
  • a crucial role of Hsp90 for growth and/or survival of tumor cells
  • plays a key role in the conformational maturation of various transcription factors and protein kinases in signal transduction
  • role in protein sorting, pointing to a central role for this molecular chaperone in the cell
  • a critical role in TGFbeta signaling
  • HSP90AA1, HSP90AB1 differentially modulate NO and O(2)(-) generation by eNOS (endothelial nitric oxide synthase) through promoting changes in endothelial nitric oxide synthase conformation and phosphorylation state 3)
  • HSP90AA1 promotes folding of REV1 into a stable and/or functional form(s) to bind to monoubiquitinated PCNA
  • BRCA1 and HSP90AA1 cooperate in homologous and non-homologous DNA double-strand-break repair and G2/M checkpoint activation
  • HSP90AA1 and HSP90B1 play key roles in controlling KCNQ4 homeostasis via the HSP40-HSP70-HOP-HSP90 chaperone pathway and the ubiquitin-proteasome pathway
  • HSP90AA1 was co-localized with AHR after the nuclear translocation
  • forms a stable complex at the cilium neck for the interaction of signalling molecules in IGF1 receptor signalling
  • stress inducible isoform of the molecular chaperone HSP90
  • HSP90AA1 and HSPA5 interact with PRDM14 and participate in cancer regulation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text an essential component of the protective heat shock response
    PATHWAY
    metabolism
    signaling
    a component
  • can form tetra-, hexa- or dodecamers that exhibit a chaperone activity
  • chaperone complex comprising HSP90AA1 and TTC1 that is recruited to the membrane protein VAPA, and regulates intracellular vesicle transport
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • dsDNA-activated protein kinase
  • pp60c-src and 50-kDa phosphoprotein
  • myogenic differentiation 1, MYOD1
  • androgen receptor, AR
  • casein kinase II, CKII
  • calmodulin
  • 51 kDa FKBP, FKBP51
  • Ah receptor-interacting protein AIP
  • 52 kDa FK506-binding protein, FKBP52
  • homeodomain-only protein, HOP
  • FKBP51/54
  • cell division cycle 37 homolog (S. cerevisiae), CDC37
  • proto-oncogene MTG8 (ETO/CDR)
  • phosphoprotein phosphatase 5, PP5
  • tetratricopeptide repeat protein 1, TPR1
  • glucocorticosteroid receptor, GR
  • death-associated protein 3, DAP3
  • glutamyl-prolyl-tRNA synthetase, EPRS
  • Serine/threonine kinase Akt/PKB
  • HBV X-associated protein 2, XAP2
  • carboxyl terminus of Hsc70-interacting protein, CHIP )
  • protooncogene Pim-1
  • apolipoprotein B48, apoB48
  • protein kinase RNA-activated, PKR
  • G alpha(12)
  • extracellular signal-regulated kinase 1, ERK1 and extracellular signal-regulated kinase 1, ERK2
  • phosphatidylinositide-3-OH kinase (PI3K) and 3-phosphoinositide-dependent protein kinase-1, PDK1
  • FKBP59, small acidic protein p23, Hsp-interacting and Hsp40
  • IKKalpha, IKKbeta and NEMO
  • estrogen receptor, ER
  • endothelial nitric oxide synthase, eNOS
  • Cyclophilin 40 (CyP40)
  • asialoglycoprotein, ASGPR
  • TP53
  • IRE1alpha and PERK
  • EGFRvIII
  • peroxisome proliferator-activated receptor alpha, PPARalpha
  • serine/threonine-protein kinase LKB1
  • activator of Hsp90 ATPase, Aha1
  • Tom70
  • signal transducer and activator of transcription 3, STAT3
  • telomerase reverse transcriptase, TERT
  • activator of Hsp90 ATPase, Aha1 and high copy Hsp90 suppressor, Hch1
  • C. jejuni surface lipoprotein JlpA
  • Heat shock factor 1, HSF1
  • Connexin 43, Cx43
  • matrix metalloproteinase 2, MMP2
  • ubiquitin fusion degradation protein 2, UFD2a and CHIP
  • CDK11p46
  • protein phosphatase 5, Ppp5
  • v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), ERBB2
  • VEGF receptor 2 VEGFR2
  • interleukin-1 receptor-associated kinase 1, IRAK1
  • WAF-1/CIP1 stabilizing protein 39, WISp39 and cyclin-dependent kinase inhibitor 1A (p21, Cip1), p21
  • Neural Wiskott-Aldrich syndrome protein, N-WASP
  • Hsp90-associating relative of Cdc37, HARC
  • small serine/threonine kinase, SSTK
  • Shepherdin
  • histone deacetylase 6, HDAC6
  • Sp1 transcription factor, SP1
  • ribosomal protein S3, rpS3
  • Checkpoint kinase 1, Chk1
  • hypoxia-responsive pro-apoptotic protein, HGTD-P
  • Ron(M1254T)
  • GC-receptor, GCR
  • Breast cancer metastasis suppressor 1, BRMS1
  • receptor-interacting protein 1, RIP1 and triad domain-containing protein 3, Triad3A
  • orphan nuclear receptor small heterodimer partner, SHP
  • N-myc downstream regulated 1, NDRG1
  • Death-associated protein kinase, DAPK
  • vascular endothelial growth factor receptor 3, VEGFR3
  • TTC4 is a nucleoplasmic protein which interacts with HSP90AA1 and HSPA4, and also with the replication protein CDC6
  • RAF1, HSF1, CDC37, and MAP2K1 interacted with both HSP90AA1 and HSP90AB1, and the relative patterns of these interactions were not affected by heat shock 4)
  • TPR (tetratricopeptide repeat)-containing protein associated with Hsp (heat-shock protein) 90], Tah1
  • TbetaRI and TbetaRII
  • USP50 may act through a HSP90AA1-dependent mechanism to counteract CDC25B mitotic inducing activity and prevent WEE1 degradation
  • TELO2-TTI1-TTI2 complex is a PIKK-specific cochaperone for HSP90AA1
  • LATS1 and LATS2 are novel HSP90AA1 clients and HSP90AA1 inhibitors can disrupt the LATS tumor suppressor pathway in cancer cells
  • HSP90AA1 interacts predominantly with the cytosolic, inactive pool of PI4KB, shielding it from proteolytic degradation but also sequestering it to the cytosol until an extracellular stimulus triggers its translocation to the Golgi or plasma membrane and subsequent activation
  • interacts and protects GABARAPL1 from its degradation by the proteasome
  • HSP90AA1 plays a critical role in the regulation of HCV RNA polymerase phosphorylation via the PDK1-PKN2 signaling pathway
  • HECTD1 is a substrates of HSP90AA1
  • involved in the regulation of OGT and O-GlcNAc modification and HSP90AA1 inhibitors might be used to modulate O-GlcNAc modification
  • SUGT1, a cochaperone for HSP90AA1, 1s a novel PLK1 substrate during mitosis
  • FKBP6 is a cochaperone that interacts with HSP90AA1
  • TCF12 expression is required for secreted HSP90AA1 to enhance colorectal cancer cell spreading
  • HSP90AA1 interacts and stabilizes KDM4B protein
  • similar to other atypical Rho GTPases, RHOBTB2 was found to have retained the capacity to bind GTP, modulated by the HSP90AA1 ATPase cycle
  • HSP90AA1 and HSP90AB1, and not HSP90B1-GRP94 or TRAP1, are responsible for maintaining proper cellular levels of ARNTL protein (r
  • importance of CUL5 in multiple aspects of the cellular response to HSP90AA1 inhibition
  • supports tumor growth and angiogenesis through PRKD2 protein stabilization
  • in response to cellular proliferation and DNA damage, proteasome and HSP90AA1-mediated regulation of POLB and XRCC1 alters the DNA repair complex architecture
  • interactions of AICDA with EEF1A1 and heat-shock protein 90 kD (HSP90AA1) are inversely correlated
  • HSP90AA1 and CDC37 cochaperone complex-mediated protein folding is thus an important part of the RIPK3 activation process during necroptosis.
  • FLCN is an HSP90AA1 client protein and its binding partners FNIP1/FNIP2 function as co-chaperones
  • FKBP8 binding to HSP90AA1 did not substantially influence its ATPase activity
  • SUGT1-HSP90AA1 complex contributes to the E3 ligase activity of the CUL4A complex that is necessary for CENPA ubiquitylation and CENPA deposition at the centromere
  • UNC45B is a unique chaperone in which the TPR domain recruits HSP90AA1
  • because methylation represses ESR1 activity, the observed complex formation between SMYD2 and HSP90AA1/PTGES3 may contribute to ESR1 regulation
  • STIP1 is a co-chaperone of HSPA4 and HSP90AA1 that regulates a number of cell biology processes via interactions with cellular proteins
  • HSP90AA1 interacted with HMGCR, the rate&
    • 8209;limiting enzyme of mevalonate pathway, and regulated its protein expression level by inhibiting protein degradation
    cell & other
    REGULATION
    activated by stress-regulated cochaperone aha1
    activator of 90 kDa heat shock protein ATPase homolog 1, AHA1
    cpr6
    inhibited by geldanamycin and radicicol
    Cdc37 can inhibit the ATPase activity of Hsp90
    HOP homeobox, HOP
    inhibition of its ATPase by its cochaperone PTGES3
    Other methylated by SMYD2 in various cell types (HSP90AA1 methylation in muscle, contributing to the formation of a protein complex containing SMYD22, HSP90AA1, and the sarcomeric protein titin)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer
    tumoral   translocation    
    with BCL6 in primary diffuse large B-cell lymphomas of the central nervous system
    constitutional       loss of function
    loss of HSP90AA1 function abolishes BRCA1-dependent DSB repair
    tumoral     --over  
    highly expressed in leukemia cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • FNIP1/FNIP2 expression can potentially serve as a predictive indicator of tumour response to HSPAA1 inhibitors
    • Therapy target Hsp90 protein is an attractive pharmaceutical anti-cancer target
    SystemTypeDisorderPubmed
    cancer  
    modification of proteins is involved in many important cellular processes
    diabete  
    HSP90AA1 inhibitors might be used to modulate O-GlcNAc modification and reverse its adverse effects in diabetes and its complications and cardiovascular and neurodegenerative diseases
    ANIMAL & CELL MODELS