HSP90AB1

HSP90AB1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1QZ2, 1UYM, 2L6J, 3FWV, 3NMQ, 3PRY, 3UQ3, 5FWL, 5FWM, 5FWK
Identifiers
Aliases	HSP90AB1, D6S182, HSP84, HSP90B, HSPC2, HSPCB, heat shock protein 90kDa alpha family class B member 1, heat shock protein 90 alpha family class B member 1
External IDs	OMIM: 140572; MGI: 96247; HomoloGene: 74306; GeneCards: HSP90AB1; OMA:HSP90AB1 - orthologs
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p21.1 Start 44,246,166 bp[1] End 44,253,888 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 B3|17 22.59 cM Start 45,878,701 bp[2] End 45,884,197 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in frontal pole Brodmann area 10 paraflocculus of cerebellum lateral nuclear group of thalamus middle frontal gyrus pars compacta pons tibialis anterior muscle pars reticulata spinal ganglia Top expressed in mandibular prominence Gonadal ridge maxillary prominence epiblast tail of embryo primitive streak gastrula subiculum hand habenula More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding transmembrane transporter binding unfolded protein binding GTP binding histone deacetylase binding UTP binding nitric-oxide synthase regulator activity kinase binding MHC class II protein complex binding protein kinase regulator activity CTP binding dATP binding double-stranded RNA binding TPR domain binding sulfonylurea receptor binding protein kinase binding RNA binding ATP binding heat shock protein binding peptide binding protein homodimerization activity ATP-dependent protein binding cadherin binding protein dimerization activity DNA polymerase binding disordered domain specific binding histone methyltransferase binding protein binding identical protein binding ubiquitin protein ligase binding tau protein binding Cellular component cytoplasm melanosome intracellular anatomical structure nucleoplasm cell surface brush border membrane basolateral plasma membrane apical plasma membrane mitochondrion inclusion body COP9 signalosome extracellular exosome ooplasm sperm head plasma membrane lysosomal membrane extracellular region nucleus cytosol plasma membrane membrane aryl hydrocarbon receptor complex secretory granule lumen ficolin-1-rich granule lumen protein-containing complex soma dendritic growth cone axonal growth cone perinuclear region of cytoplasm HSP90-CDC37 chaperone complex Biological process negative regulation of neuron apoptotic process cellular response to interleukin-4 response to salt stress Fc-gamma receptor signaling pathway involved in phagocytosis placenta development positive regulation of nitric oxide biosynthetic process regulation of protein ubiquitination cellular response to organic cyclic compound response to stress negative regulation of apoptotic process response to organic substance supramolecular fiber organization positive regulation of protein serine/threonine kinase activity response to unfolded protein regulation of type I interferon-mediated signaling pathway regulation of interferon-gamma-mediated signaling pathway protein folding positive regulation of cell size regulation of cellular response to heat positive regulation of protein binding virion attachment to host cell protein stabilization positive regulation of phosphoprotein phosphatase activity response to cocaine negative regulation of complement-dependent cytotoxicity xenobiotic metabolic process telomere maintenance via telomerase positive regulation of transforming growth factor beta receptor signaling pathway negative regulation of proteasomal ubiquitin-dependent protein catabolic process neutrophil degranulation positive regulation of cell differentiation chaperone-mediated protein complex assembly positive regulation of telomerase activity negative regulation of transforming growth factor beta activation telomerase holoenzyme complex assembly positive regulation of protein localization to cell surface central nervous system neuron axonogenesis establishment of cell polarity positive regulation of peptidyl-serine phosphorylation axon extension negative regulation of protein metabolic process positive regulation of protein kinase B signaling negative regulation of proteasomal protein catabolic process positive regulation of tau-protein kinase activity positive regulation of cyclin-dependent protein kinase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3326 15516 Ensembl ENSG00000096384 ENSMUSG00000023944 UniProt P08238 Q6PK50 P11499 RefSeq (mRNA) NM_001271969 NM_001271970 NM_001271971 NM_001271972 NM_007355 NM_001371238 NM_008302 RefSeq (protein) NP_001258898 NP_001258899 NP_001258900 NP_001258901 NP_031381 NP_001358167 NP_001258901.1 NP_032328 Location (UCSC) Chr 6: 44.25 – 44.25 Mb Chr 17: 45.88 – 45.88 Mb PubMed search [3] [4]
Wikidata
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Heat shock protein HSP 90-beta also called HSP90beta is a protein that in humans is encoded by the HSP90AB1 gene.^[5][6][7]

HSP90AB1 is a molecular chaperone. Chaperones are proteins that bind to other proteins, thereby stabilizing them^{[8][9][10][11][12][13][14]} in an ATP-dependent manner.^[15] Chaperones stabilize new proteins during translation, mature proteins which are partially unstable but also proteins that have become partially denatured due to various kinds of cellular stress. In case proper folding or refolding is impossible, HSPs mediate protein degradation. They also have specialized functions, such as intracellular transport into organelles.

Human HSPs are classified into 5 major groups according to the HGNC:^[16][17]

• HSP70
• DnaJ (HSP40)
• HSPB (small heat shock proteins)
• HSPC (HSP90)
• chaperonins

Chaperonins are characterized by their barrel-shaped structure with binding sites for client proteins inside the barrels.

The human HSP90 group consists of 5 members according to the HGNC:^[17][18]

• HSP90AA1 (heat shock protein 90 kDa alpha, class A, member 1)
• HSP90AA3P (heat shock protein 90 alpha family class A member 3, pseudogene)
• HSP90AB1 (heat shock protein 90 kDa alpha, class B, member 1) (this protein)
• HSP90B1 (heat shock protein 90 kDA beta, member 1)
• TRAP1 (TNF receptor associated protein 1)

Whereas HSP90AA1 and HSP90AB1 are located primarily in the cytoplasm of the cells, HSP90B1 can be found in the endoplasmic reticulum and Trap1 in mitochondria.

Co-chaperones bind to HSPs and influence their activity, substrate (client) specificity and interaction with other HSPs.^[14] For example, the co-chaperone CDC37 (cell division cycle 37) stabilizes the cell cycle regulatory proteins CDK4 (cyclin dependent kinase 4) and Cdk6.^[19] Hop (HSP organizing protein) mediates the interaction between different HSPs, forming HSP70–HSP90 complexes.^[20][21] TOM70 (translocase of the outer mitochondrial membrane of ~70 kDa) mediates translocation of client proteins through the import pore into the mitochondrial matrix.^[21][22]

Human HPS90AB1 shares 60% overall homology to its closest relative HSP90AA1.^[23] Murine HSP90AB1 was cloned in 1987 based on homology of the corresponding Drosophila melanogaster gene.^[24][25]

HSP90AB1 is active as homodimer, forming a V-shaped structure.^{[21][26][27][28][29][30]} It consists of three major domains:

• N-terminal domain (NTD) containing the ATP binding site
• middle domain, primarily responsible for substrate binding
• C-terminal domain (CTD) which is the dimerization domain (base of the V).

Between these domains, there are short charged domains. Co-chaperones primarily bind to the NTD and CTD. The latter Co-chaperones usually contain a tetratricopeptide repeat (TPR) domain which binds to a MEEVD motif at the C-terminus of the HSP.^[21][31] Inhibition of HSP90 activity by geldanamycin derivatives is based on their binding to the ATP binding site.^[15]

Client proteins are steroid hormone receptors, kinases, ubiquitin ligases, transcription factors and proteins from many more families.^[14][32][33] Examples of HSP90AB1 client proteins are p38MAPK/MAPK14 (mitogen activated protein kinase 14),^[34] ERK5 (extracellular regulated kinase 5),^[35] or the checkpoint kinase Wee1.^[36]

Cystic fibrosis (CF, mucoviscidosis) is a genetic disease with increased viscosity of various secretions leading to organ failure of lung, pancreas and other organs. It is caused in nearly all cases by a deletion of phenylalanine 508 of CFTR (cystic fibrosis transmembrane conductance regulator). This mutation causes a maturation defect of this ion channel protein with increased degradation, mediated by HSPs. Deletion of the co-chaperone AHA1 (activator of heat shock 90kDa protein ATPase homolog 1) leads to stabilization of CFTR and opens up a perspective for a new therapy.^[37]

HSP90AB1 and its co-chaperones are frequently overexpressed in cancer cells.^[38] They are able to stabilize mutant proteins thereby allowing survival and increased proliferation of cancer cells. This renders HSPs potential targets for cancer treatment.^[39][40][41] In salivary gland tumors, expression of HSP90AA1 and HSP90AB1 correlates with malignancy, proliferation and metastasis.^[42] The same is basically true for lung cancers where a correlation with survival was found.^[43]

The 2015 version of this article was updated by an external expert under a dual publication model. The corresponding academic peer reviewed article was published in Gene and can be cited as: Michael Haase, Guido Fitze (7 September 2015). "HSP90AB1: Helping the good and the bad". Gene. Gene Wiki Review Series. 575 (2 Pt 1): 171–186. doi:10.1016/J.GENE.2015.08.063. ISSN 0378-1119. PMC 5675009. PMID 26358502. Wikidata Q38584468.