Heat shock protein HSP 90-alpha

Details

Name
Heat shock protein HSP 90-alpha
Kind
protein
Synonyms
  • 3.6.4.10
  • Heat shock 86 kDa
  • Heat shock protein family C member 1
  • HSP 86
  • HSP86
  • HSP90A
  • HSPC1
  • HSPCA
  • LAP-2
  • Lipopolysaccharide-associated protein 2
  • LPS-associated protein 2
  • Renal carcinoma antigen NY-REN-38
Gene Name
HSP90AA1
UniProtKB Entry
P07900Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0002228|Heat shock protein HSP 90-alpha
MPEETQTQDQPMEEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNSSDALDKIR
YESLTDPSKLDSGKELHINLIPNKQDRTLTIVDTGIGMTKADLINNLGTIAKSGTKAFME
ALQAGADISMIGQFGVGFYSAYLVAEKVTVITKHNDDEQYAWESSAGGSFTVRTDTGEPM
GRGTKVILHLKEDQTEYLEERRIKEIVKKHSQFIGYPITLFVEKERDKEVSDDEAEEKED
KEEEKEKEEKESEDKPEIEDVGSDEEEEKKDGDKKKKKKIKEKYIDQEELNKTKPIWTRN
PDDITNEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFVPRRAPFDLFENRKKKNN
IKLYVRRVFIMDNCEELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNLVKKC
LELFTELAEDKENYKKFYEQFSKNIKLGIHEDSQNRKKLSELLRYYTSASGDEMVSLKDY
CTRMKENQKHIYYITGETKDQVANSAFVERLRKHGLEVIYMIEPIDEYCVQQLKEFEGKT
LVSVTKEGLELPEDEEEKKKQEEKKTKFENLCKIMKDILEKKVEKVVVSNRLVTSPCCIV
TSTYGWTANMERIMKAQALRDNSTMGYMAAKKHLEINPDHSIIETLRQKAEADKNDKSVK
DLVILLYETALLSSGFSLEDPQTHANRIYRMIKLGLGIDEDDPTADDTSAAVTEEMPPLE
GDDDTSRMEEVD
Number of residues
732
Molecular Weight
84659.015
Theoretical pI
4.66
GO Classification
Functions
ATP hydrolysis activity / ATP-dependent protein folding chaperone / CTP binding / dATP binding / disordered domain specific binding / DNA polymerase binding / GTP binding / histone deacetylase binding / mRNA binding / protein phosphatase binding / protein tyrosine kinase binding / Rho GDP-dissociation inhibitor binding / RNA binding / scaffold protein binding / sulfonylurea receptor binding / tau protein binding / transmembrane transporter binding / ubiquitin protein ligase binding / unfolded protein binding / UTP binding
Processes
activation of innate immune response / cardiac muscle cell apoptotic process / cellular response to virus / neuron migration / positive regulation of cardiac muscle contraction / positive regulation of cell size / positive regulation of defense response to virus by host / positive regulation of interferon-beta production / positive regulation of lamellipodium assembly / positive regulation of protein catabolic process / positive regulation of protein import into nucleus / positive regulation of protein phosphorylation / positive regulation of protein polymerization / positive regulation of tau-protein kinase activity / protein folding / protein insertion into mitochondrial outer membrane / protein stabilization / regulation of apoptotic process / regulation of postsynaptic membrane neurotransmitter receptor levels / regulation of protein localization / regulation of protein ubiquitination / regulation of protein-containing complex assembly / response to cocaine / response to estrogen / response to salt stress / response to xenobiotic stimulus / skeletal muscle contraction / telomerase holoenzyme complex assembly / telomere maintenance via telomerase
Components
apical plasma membrane / axonal growth cone / basolateral plasma membrane / brush border membrane / cell surface / collagen-containing extracellular matrix / dendritic growth cone / ficolin-1-rich granule lumen / mitochondrion / neuronal cell body / perinuclear region of cytoplasm / protein-containing complex / secretory granule lumen / sperm mitochondrial sheath / sperm plasma membrane
General Function
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 (PubMed:11274138, PubMed:12526792, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155). 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 (PubMed: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 (PubMed:26991466, PubMed:27295069). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed: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 (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues (PubMed: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 (PubMed:25973397). Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression (PubMed:25973397). Binds bacterial lipopolysaccharide (LPS) and mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205). Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation (PubMed:24613385). Mediates the association of TOMM70 with IRF3 or TBK1 in mitochondrial outer membrane which promotes host antiviral response (PubMed:20628368, PubMed:25609812)
Specific Function
Atp binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0010783|Heat shock protein HSP 90-alpha (HSP90AA1)
ATGCCCCCGTGTTCGGGCGGGGACGGCTCCACCCCTCCTGGGCCCTCCCTTCGGGACAGG
GACTGTCCCGCCCAGAGTGCTGAATACCCGCGCGACCGTCTGGATCCCCGCCCAGGAAGC
CCCTCTGAAGCCTCCTCGCCGCCGTTTCTGAGAAGCAGGGCACCTGTTAACTGGTACCAA
GAAAAGGCCCAAGTGTTTCTCTGGCATCTGATGGTGTCTGGATCCACCACTCTACTCTGT
CTCTGGAAACAGCCCTTCCACGTCTCTGCATTCCCTGTCACCGCGTCACTGGCCTTCAGA
CAGAGCCAAGGTGCAGGGCAACACCTCTACAAGGATCTGCAGCCATTTATATTGCTTAGG
CTACTGATGCCTGAGGAAACCCAGACCCAAGACCAACCGATGGAGGAGGAGGAGGTTGAG
ACGTTCGCCTTTCAGGCAGAAATTGCCCAGTTGATGTCATTGATCATCAATACTTTCTAC
TCGAACAAAGAGATCTTTCTGAGAGAGCTCATTTCAAATTCATCAGATGCATTGGACAAA
ATCCGGTATGAAAGCTTGACAGATCCCAGTAAATTAGACTCTGGGAAAGAGCTGCATATT
AACCTTATACCGAACAAACAAGATCGAACTCTCACTATTGTGGATACTGGAATTGGAATG
ACCAAGGCTGACTTGATCAATAACCTTGGTACTATCGCCAAGTCTGGGACCAAAGCGTTC
ATGGAAGCTTTGCAGGCTGGTGCAGATATCTCTATGATTGGCCAGTTCGGTGTTGGTTTT
TATTCTGCTTATTTGGTTGCTGAGAAAGTAACTGTGATCACCAAACATAACGATGATGAG
CAGTACGCTTGGGAGTCCTCAGCAGGGGGATCATTCACAGTGAGGACAGACACAGGTGAA
CCTATGGGTCGTGGAACAAAAGTTATCCTACACCTGAAAGAAGACCAAACTGAGTACTTG
GAGGAACGAAGAATAAAGGAGATTGTGAAGAAACATTCTCAGTTTATTGGATATCCCATT
ACTCTTTTTGTGGAGAAGGAACGTGATAAAGAAGTAAGCGATGATGAGGCTGAAGAAAAG
GAAGACAAAGAAGAAGAAAAAGAAAAAGAAGAGAAAGAGTCGGAAGACAAACCTGAAATT
GAAGATGTTGGTTCTGATGAGGAAGAAGAAAAGAAGGATGGTGACAAGAAGAAGAAGAAG
AAGATTAAGGAAAAGTACATCGATCAAGAAGAGCTCAACAAAACAAAGCCCATCTGGACC
AGAAATCCCGACGATATTACTAATGAGGAGTACGGAGAATTCTATAAGAGCTTGACCAAT
GACTGGGAAGATCACTTGGCAGTGAAGCATTTTTCAGTTGAAGGACAGTTGGAATTCAGA
GCCCTTCTATTTGTCCCACGACGTGCTCCTTTTGATCTGTTTGAAAACAGAAAGAAAAAG
AACAACATCAAATTGTATGTACGCAGAGTTTTCATCATGGATAACTGTGAGGAGCTAATC
CCTGAATATCTGAACTTCATTAGAGGGGTGGTAGACTCGGAGGATCTCCCTCTAAACATA
TCCCGTGAGATGTTGCAACAAAGCAAAATTTTGAAAGTTATCAGGAAGAATTTGGTCAAA
AAATGCTTAGAACTCTTTACTGAACTGGCGGAAGATAAAGAGAACTACAAGAAATTCTAT
GAGCAGTTCTCTAAAAACATAAAGCTTGGAATACACGAAGACTCTCAAAATCGGAAGAAG
CTTTCAGAGCTGTTAAGGTACTACACATCTGCCTCTGGTGATGAGATGGTTTCTCTCAAG
GACTACTGCACCAGAATGAAGGAGAACCAGAAACATATCTATTATATCACAGGTGAGACC
AAGGACCAGGTAGCTAACTCAGCCTTTGTGGAACGTCTTCGGAAACATGGCTTAGAAGTG
ATCTATATGATTGAGCCCATTGATGAGTACTGTGTCCAACAGCTGAAGGAATTTGAGGGG
AAGACTTTAGTGTCAGTCACCAAAGAAGGCCTGGAACTTCCAGAGGATGAAGAAGAGAAA
AAGAAGCAGGAAGAGAAAAAAACAAAGTTTGAGAACCTCTGCAAAATCATGAAAGACATA
TTGGAGAAAAAAGTTGAAAAGGTGGTTGTGTCAAACCGATTGGTGACATCTCCATGCTGT
ATTGTCACAAGCACATATGGCTGGACAGCAAACATGGAGAGAATCATGAAAGCTCAAGCC
CTAAGAGACAACTCAACAATGGGTTACATGGCAGCAAAGAAACACCTGGAGATAAACCCT
GACCATTCCATTATTGAGACCTTAAGGCAAAAGGCAGAGGCTGATAAGAACGACAAGTCT
GTGAAGGATCTGGTCATCTTGCTTTATGAAACTGCGCTCCTGTCTTCTGGCTTCAGTCTG
GAAGATCCCCAGACACATGCTAACAGGATCTACAGGATGATCAAACTTGGTCTGGGTATT
GATGAAGATGACCCTACTGCTGATGATACCAGTGCTGCTGTAACTGAAGAAATGCCACCC
CTTGAAGGAGATGACGACACATCACGCATGGAAGAAGTAGACTAA
Chromosome Location
14
Locus
14q32.31
External Identifiers
ResourceLink
UniProtKB IDP07900
UniProtKB Entry NameHS90A_HUMAN
GenBank Protein ID32488
GenBank Gene IDX15183
GeneCard IDHSP90AA1
GenAtlas IDHSP90AA1
HGNC IDHGNC:5253
PDB ID(s)1BYQ, 1OSF, 1UY6, 1UY7, 1UY8, 1UY9, 1UYC, 1UYD, 1UYE, 1UYF, 1UYG, 1UYH, 1UYI, 1UYK, 1UYL, 1YC1, 1YC3, 1YC4, 1YER, 1YES, 1YET, 2BSM, 2BT0, 2BUG, 2BYH, 2BYI, 2BZ5, 2C2L, 2CCS, 2CCT, 2CCU, 2FWY, 2FWZ, 2H55, 2JJC, 2K5B, 2QF6, 2QFO, 2QG0, 2QG2, 2UWD, 2VCI, 2VCJ, 2WI1, 2WI2, 2WI3, 2WI4, 2WI5, 2WI6, 2WI7, 2XAB, 2XDK, 2XDL, 2XDS, 2XDU, 2XDX, 2XHR, 2XHT, 2XHX, 2XJG, 2XJJ, 2XJX, 2XK2, 2YE2, 2YE3, 2YE4, 2YE5, 2YE6, 2YE7, 2YE8, 2YE9, 2YEA, 2YEB, 2YEC, 2YED, 2YEE, 2YEF, 2YEG, 2YEH, 2YEI, 2YEJ, 2YI0, 2YI5, 2YI6, 2YI7, 2YJW, 2YJX, 2YK2, 2YK9, 2YKB, 2YKC, 2YKE, 2YKI, 2YKJ, 3B24, 3B25, 3B26, 3B27, 3B28, 3BM9, 3BMY, 3D0B, 3EKO, 3EKR, 3FT5, 3FT8, 3HEK, 3HHU, 3HYY, 3HYZ, 3HZ1, 3HZ5, 3INW, 3INX, 3K97, 3K98, 3K99, 3MNR, 3O0I, 3OW6, 3OWB, 3OWD, 3Q6M, 3Q6N, 3QDD, 3QTF, 3R4M, 3R4N, 3R4O, 3R4P, 3R91, 3R92, 3RKZ, 3RLP, 3RLQ, 3RLR, 3T0H, 3T0Z, 3T10, 3T1K, 3T2S, 3TUH, 3VHA, 3VHC, 3VHD, 3WHA, 3WQ9, 4AIF, 4AWO, 4AWP, 4AWQ, 4B7P, 4BQG, 4BQJ, 4CGQ, 4CGU, 4CGV, 4CGW, 4CWF, 4CWN, 4CWO, 4CWP, 4CWQ, 4CWR, 4CWS, 4CWT, 4EEH, 4EFT, 4EFU, 4EGH, 4EGI, 4EGK, 4FCP, 4FCQ, 4FCR, 4HY6, 4JQL, 4L8Z, 4L90, 4L91, 4L93, 4L94, 4LWE, 4LWF, 4LWG, 4LWH, 4LWI, 4NH7, 4NH8, 4O04, 4O05, 4O07, 4O09, 4O0B, 4R3M, 4U93, 4W7T, 4XIP, 4XIQ, 4XIR, 4XIT, 4YKQ, 4YKR, 4YKT, 4YKU, 4YKW, 4YKX, 4YKY, 4YKZ, 5CF0, 5FNC, 5FND, 5FNF, 5GGZ, 5J20, 5J27, 5J2V, 5J2X, 5J64, 5J6L, 5J6M, 5J6N, 5J80, 5J82, 5J86, 5J8M, 5J8U, 5J9X, 5LNY, 5LNZ, 5LO0, 5LO1, 5LO5, 5LO6, 5LQ9, 5LR1, 5LR7, 5LRL, 5LRZ, 5LS1, 5M4E, 5M4H, 5NYH, 5NYI, 5OCI, 5OD7, 5ODX, 5T21, 5VYY, 5XQD, 5XQE, 5XR5, 5XR9, 5XRB, 5XRD, 5XRE, 5ZR3, 6B99, 6B9A, 6CEO, 6CYG, 6CYH, 6EI5, 6EL5, 6ELN, 6ELO, 6ELP, 6EY8, 6EY9, 6EYA, 6EYB, 6F1N, 6FCJ, 6FDP, 6GP4, 6GP8, 6GPF, 6GPH, 6GPO, 6GPP, 6GPR, 6GPT, 6GPW, 6GPY, 6GQ6, 6GQR, 6GQS, 6GQU, 6GR1, 6GR3, 6GR4, 6GR5, 6HHR, 6KSQ, 6LR9, 6LSZ, 6LT8, 6LTI, 6LTK, 6N8X, 6OLX, 6TN4, 6TN5, 6U98, 6U99, 6U9A, 6U9B, 7DMC, 7KRJ, 7KW7, 7L7I, 7L7J, 7LSZ, 7LT0, 7RXZ, 7RY0, 7RY1, 7S8Y, 7S8Z, 7S90, 7S95, 7S98, 7S99, 7S9F, 7S9G, 7S9H, 7S9I, 7UR3, 8AGI, 8AGJ, 8AGL, 8B7I, 8B7J, 8FFV, 8FFW, 8KI4, 8W4V, 8W8K, 8X2R
KEGG IDhsa:3320
IUPHAR/Guide To Pharmacology ID2905
NCBI Gene ID3320
General References
  1. Yamazaki M, Akaogi K, Miwa T, Imai T, Soeda E, Yokoyama K: Nucleotide sequence of a full-length cDNA for 90 kDa heat-shock protein from human peripheral blood lymphocytes. Nucleic Acids Res. 1989 Sep 12;17(17):7108. [Article]
  2. Yamazaki M, Tashiro H, Yokoyama K, Soeda E: Molecular cloning of cDNA encoding a human heat-shock protein whose expression is induced by adenovirus type 12 E1A in HeLa cells. Agric Biol Chem. 1990 Dec;54(12):3163-70. [Article]
  3. Hickey E, Brandon SE, Smale G, Lloyd D, Weber LA: Sequence and regulation of a gene encoding a human 89-kilodalton heat shock protein. Mol Cell Biol. 1989 Jun;9(6):2615-26. [Article]
  4. Chen B, Piel WH, Gui L, Bruford E, Monteiro A: The HSP90 family of genes in the human genome: insights into their divergence and evolution. Genomics. 2005 Dec;86(6):627-37. Epub 2005 Nov 2. [Article]
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  6. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. Epub 2003 Jan 1. [Article]
  7. Hoffmann T, Hovemann B: Heat-shock proteins, Hsp84 and Hsp86, of mice and men: two related genes encode formerly identified tumour-specific transplantation antigens. Gene. 1988 Dec 30;74(2):491-501. [Article]
  8. Walter T, Drabent B, Krebs H, Tomalak M, Heiss S, Benecke BJ: Cloning and analysis of a human 86-kDa heat-shock-protein-encoding gene. Gene. 1989 Nov 15;83(1):105-15. [Article]
  9. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  10. Lees-Miller SP, Anderson CW: Two human 90-kDa heat shock proteins are phosphorylated in vivo at conserved serines that are phosphorylated in vitro by casein kinase II. J Biol Chem. 1989 Feb 15;264(5):2431-7. [Article]
  11. Stewart S, Sundaram M, Zhang Y, Lee J, Han M, Guan KL: Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization. Mol Cell Biol. 1999 Aug;19(8):5523-34. [Article]
  12. Martinez-Ruiz A, Villanueva L, Gonzalez de Orduna C, Lopez-Ferrer D, Higueras MA, Tarin C, Rodriguez-Crespo I, Vazquez J, Lamas S: S-nitrosylation of Hsp90 promotes the inhibition of its ATPase and endothelial nitric oxide synthase regulatory activities. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8525-30. Epub 2005 Jun 3. [Article]
  13. Lees-Miller SP, Anderson CW: The human double-stranded DNA-activated protein kinase phosphorylates the 90-kDa heat-shock protein, hsp90 alpha at two NH2-terminal threonine residues. J Biol Chem. 1989 Oct 15;264(29):17275-80. [Article]
  14. Minami Y, Kimura Y, Kawasaki H, Suzuki K, Yahara I: The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo. Mol Cell Biol. 1994 Feb;14(2):1459-64. [Article]
  15. Nemoto T, Ohara-Nemoto Y, Ota M, Takagi T, Yokoyama K: Mechanism of dimer formation of the 90-kDa heat-shock protein. Eur J Biochem. 1995 Oct 1;233(1):1-8. [Article]
  16. Silverstein AM, Galigniana MD, Chen MS, Owens-Grillo JK, Chinkers M, Pratt WB: Protein phosphatase 5 is a major component of glucocorticoid receptor.hsp90 complexes with properties of an FK506-binding immunophilin. J Biol Chem. 1997 Jun 27;272(26):16224-30. [Article]
  17. Young JC, Obermann WM, Hartl FU: Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa domain of hsp90. J Biol Chem. 1998 Jul 17;273(29):18007-10. [Article]
  18. Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jager D, Jager E, Knuth A, Chen YT, Old LJ: Antigens recognized by autologous antibody in patients with renal-cell carcinoma. Int J Cancer. 1999 Nov 12;83(4):456-64. [Article]
  19. Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE: Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. J Biol Chem. 2001 May 11;276(19):15571-4. Epub 2001 Mar 23. [Article]
  20. Guo Y, Guettouche T, Fenna M, Boellmann F, Pratt WB, Toft DO, Smith DF, Voellmy R: Evidence for a mechanism of repression of heat shock factor 1 transcriptional activity by a multichaperone complex. J Biol Chem. 2001 Dec 7;276(49):45791-9. Epub 2001 Oct 2. [Article]
  21. Triantafilou K, Triantafilou M, Dedrick RL: A CD14-independent LPS receptor cluster. Nat Immunol. 2001 Apr;2(4):338-45. [Article]
  22. Brychzy A, Rein T, Winklhofer KF, Hartl FU, Young JC, Obermann WM: Cofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone system. EMBO J. 2003 Jul 15;22(14):3613-23. [Article]
  23. Lotz GP, Lin H, Harst A, Obermann WM: Aha1 binds to the middle domain of Hsp90, contributes to client protein activation, and stimulates the ATPase activity of the molecular chaperone. J Biol Chem. 2003 May 9;278(19):17228-35. Epub 2003 Feb 24. [Article]
  24. Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y: SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 2004 Aug;6(8):731-40. Epub 2004 Jul 4. [Article]
  25. Zeke T, Morrice N, Vazquez-Martin C, Cohen PT: Human protein phosphatase 5 dissociates from heat-shock proteins and is proteolytically activated in response to arachidonic acid and the microtubule-depolymerizing drug nocodazole. Biochem J. 2005 Jan 1;385(Pt 1):45-56. [Article]
  26. Yang J, Roe SM, Cliff MJ, Williams MA, Ladbury JE, Cohen PT, Barford D: Molecular basis for TPR domain-mediated regulation of protein phosphatase 5. EMBO J. 2005 Jan 12;24(1):1-10. Epub 2004 Dec 2. [Article]
  27. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [Article]
  28. Beranova-Giorgianni S, Zhao Y, Desiderio DM, Giorgianni F: Phosphoproteomic analysis of the human pituitary. Pituitary. 2006;9(2):109-20. [Article]
  29. Cliff MJ, Harris R, Barford D, Ladbury JE, Williams MA: Conformational diversity in the TPR domain-mediated interaction of protein phosphatase 5 with Hsp90. Structure. 2006 Mar;14(3):415-26. [Article]
  30. Carrascal M, Ovelleiro D, Casas V, Gay M, Abian J: Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment. J Proteome Res. 2008 Dec;7(12):5167-76. [Article]
  31. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [Article]
  32. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  33. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  34. Han G, Ye M, Zhou H, Jiang X, Feng S, Jiang X, Tian R, Wan D, Zou H, Gu J: Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography. Proteomics. 2008 Apr;8(7):1346-61. doi: 10.1002/pmic.200700884. [Article]
  35. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  36. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  37. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  38. Gano JJ, Simon JA: A proteomic investigation of ligand-dependent HSP90 complexes reveals CHORDC1 as a novel ADP-dependent HSP90-interacting protein. Mol Cell Proteomics. 2010 Feb;9(2):255-70. doi: 10.1074/mcp.M900261-MCP200. Epub 2009 Oct 28. [Article]
  39. Giannakopoulos NV, Luo JK, Papov V, Zou W, Lenschow DJ, Jacobs BS, Borden EC, Li J, Virgin HW, Zhang DE: Proteomic identification of proteins conjugated to ISG15 in mouse and human cells. Biochem Biophys Res Commun. 2005 Oct 21;336(2):496-506. [Article]
  40. Chi A, Valencia JC, Hu ZZ, Watabe H, Yamaguchi H, Mangini NJ, Huang H, Canfield VA, Cheng KC, Yang F, Abe R, Yamagishi S, Shabanowitz J, Hearing VJ, Wu C, Appella E, Hunt DF: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J Proteome Res. 2006 Nov;5(11):3135-44. [Article]
  41. Baba M, Hong SB, Sharma N, Warren MB, Nickerson ML, Iwamatsu A, Esposito D, Gillette WK, Hopkins RF 3rd, Hartley JL, Furihata M, Oishi S, Zhen W, Burke TR Jr, Linehan WM, Schmidt LS, Zbar B: Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15552-7. Epub 2006 Oct 6. [Article]
  42. Hawkins TA, Haramis AP, Etard C, Prodromou C, Vaughan CK, Ashworth R, Ray S, Behra M, Holder N, Talbot WS, Pearl LH, Strahle U, Wilson SW: The ATPase-dependent chaperoning activity of Hsp90a regulates thick filament formation and integration during skeletal muscle myofibrillogenesis. Development. 2008 Mar;135(6):1147-56. doi: 10.1242/dev.018150. Epub 2008 Feb 6. [Article]
  43. Retzlaff M, Stahl M, Eberl HC, Lagleder S, Beck J, Kessler H, Buchner J: Hsp90 is regulated by a switch point in the C-terminal domain. EMBO Rep. 2009 Oct;10(10):1147-53. doi: 10.1038/embor.2009.153. Epub 2009 Aug 21. [Article]
  44. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  45. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  46. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  47. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  48. Correa RG, Krajewska M, Ware CF, Gerlic M, Reed JC: The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling. Oncotarget. 2014 Mar 30;5(6):1666-82. [Article]
  49. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  50. Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP: Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell. 1997 Apr 18;89(2):239-50. [Article]
  51. Obermann WM, Sondermann H, Russo AA, Pavletich NP, Hartl FU: In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis. J Cell Biol. 1998 Nov 16;143(4):901-10. [Article]
  52. Zhang M, Windheim M, Roe SM, Peggie M, Cohen P, Prodromou C, Pearl LH: Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex. Mol Cell. 2005 Nov 23;20(4):525-38. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Rifabutinapproved, investigationalnotargetother/unknownDetails
Geldanamycinexperimental, investigationalyestargetinhibitorDetails
4-(1,3-Benzodioxol-5-Yl)-5-(5-Ethyl-2,4-Dihydroxyphenyl)-2h-Pyrazole-3-Carboxylic AcidexperimentalunknowntargetDetails
AlvespimycininvestigationalyestargetinhibitorDetails
4-(1h-Imidazol-4-Yl)-3-(5-Ethyl-2,4-Dihydroxy-Phenyl)-1h-PyrazoleexperimentalunknowntargetDetails
N-[4-(AMINOSULFONYL)BENZYL]-5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDEexperimentalunknowntargetDetails
TanespimycininvestigationalyestargetinhibitorDetails
SNX-5422investigationalyestargetinhibitorDetails
N-(4-ACETYLPHENYL)-5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDEexperimentalunknowntargetDetails
4-CHLORO-6-(4-{4-[4-(METHYLSULFONYL)BENZYL]PIPERAZIN-1-YL}-1H-PYRAZOL-5-YL)BENZENE-1,3-DIOLexperimentalunknowntargetDetails
5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-PIPERAZIN-1-YL-1H-PYRAZOLE-3-CARBOXAMIDEexperimentalunknowntargetDetails
5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-[4-(morpholin-4-ylmethyl)phenyl]isoxazole-3-carboxamideexperimentalunknowntargetDetails
5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-(4-METHOXYPHENYL)ISOXAZOLE-3-CARBOXAMIDEexperimentalunknowntargetDetails
2-amino-4-[2,4-dichloro-5-(2-pyrrolidin-1-ylethoxy)phenyl]-N-ethylthieno[2,3-d]pyrimidine-6-carboxamideexperimentalunknowntargetDetails
4-CHLORO-6-(4-PIPERAZIN-1-YL-1H-PYRAZOL-5-YL)BENZENE-1,3-DIOLexperimentalunknowntargetDetails
(3E)-3-[(phenylamino)methylidene]dihydrofuran-2(3H)-oneexperimentalunknowntargetDetails
6-(3-BROMO-2-NAPHTHYL)-1,3,5-TRIAZINE-2,4-DIAMINEexperimentalyestargetinhibitorDetails
3-({2-[(2-AMINO-6-METHYLPYRIMIDIN-4-YL)ETHYNYL]BENZYL}AMINO)-1,3-OXAZOL-2(3H)-ONEexperimentalunknowntargetDetails
N-[(2-AMINO-6-METHYLPYRIMIDIN-4-YL)METHYL]-3-{[(E)-(2-OXODIHYDROFURAN-3(2H)-YLIDENE)METHYL]AMINO}BENZENESULFONAMIDEexperimentalunknowntargetDetails
5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-(4-METHOXYPHENYL)-1H-PYRAZOLE-3-CARBOXAMIDEexperimentalunknowntargetDetails
4-bromo-6-(6-hydroxy-1,2-benzisoxazol-3-yl)benzene-1,3-diolexperimentalunknowntargetDetails
CCT-018159experimentalyestargetinhibitorDetails
4-chloro-6-{5-[(2-morpholin-4-ylethyl)amino]-1,2-benzisoxazol-3-yl}benzene-1,3-diolexperimentalunknowntargetDetails
8-(6-BROMO-BENZO[1,3]DIOXOL-5-YLSULFANYL)-9-(3-ISOPROPYLAMINO-PROPYL)-ADENINEexperimentalunknowntargetDetails
4-methyl-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-2-amineexperimentalunknowntargetDetails
(5E,7S)-2-amino-7-(4-fluoro-2-pyridin-3-ylphenyl)-4-methyl-7,8-dihydroquinazolin-5(6H)-one oximeexperimentalunknowntargetDetails
9-Butyl-8-(2,5-Dimethoxy-Benzyl)-2-Fluoro-9h-Purin-6-YlamineexperimentalunknowntargetDetails
8-(2-Chloro-3,4,5-Trimethoxy-Benzyl)-2-Fluoro-9-Pent-4-Ylnyl-9h-Purin-6-YlamineexperimentalunknowntargetDetails
8-(2,5-Dimethoxy-Benzyl)-2-Fluoro-9h-Purin-6-YlamineexperimentalunknowntargetDetails
9-Butyl-8-(3,4,5-Trimethoxybenzyl)-9h-Purin-6-AmineexperimentalyestargetinhibitorDetails
9-Butyl-8-(4-Methoxybenzyl)-9h-Purin-6-AmineexperimentalyestargetinhibitorDetails
9-Butyl-8-(3-Methoxybenzyl)-9h-Purin-6-AmineexperimentalyestargetinhibitorDetails
8-BENZO[1,3]DIOXOL-,5-YLMETHYL-9-BUTYL-9H-experimentalyestargetinhibitorDetails
9-Butyl-8-(2,5-Dimethoxy-Benzyl)-9h-Purin-6-YlamineexperimentalunknowntargetDetails
9-Butyl-8-(2-Chloro-3,4,5-Trimethoxy-Benzyl)-9h-Purin-6-YlamineexperimentalunknowntargetDetails
8-(2-Chloro-3,4,5-Trimethoxy-Benzyl)-9-Pent-4-Ylnyl-9h-Purin-6-YlamineexperimentalunknowntargetDetails
8-Benzo[1,3]Dioxol-,5-Ylmethyl-9-Butyl-2-Fluoro-9h-Purin-6-YlamineexperimentalunknowntargetDetails
8-(2,5-Dimethoxy-Benzyl)-2-Fluoro-9-Pent-9h-Purin-6-YlamineexperimentalunknowntargetDetails
4-{[(2R)-2-(2-methylphenyl)pyrrolidin-1-yl]carbonyl}benzene-1,3-diolexperimentalunknowntargetDetails
2-(1H-pyrrol-1-ylcarbonyl)benzene-1,3,5-triolexperimentalyestargetinhibitorDetails
2-[(2-methoxyethyl)amino]-4-(4-oxo-1,2,3,4-tetrahydro-9H-carbazol-9-yl)benzamideexperimentalunknowntargetDetails
4-(2-methoxyethoxy)-6-methylpyrimidin-2-amineexperimentalyestargetinhibitorDetails
4-(2,4-dichlorophenyl)-5-phenyldiazenyl-pyrimidin-2-amineexperimentalunknowntargetDetails
3,6-DIAMINO-5-CYANO-4-(4-ETHOXYPHENYL)THIENO[2,3-B]PYRIDINE-2-CARBOXAMIDEexperimentalunknowntargetDetails
2-AMINO-4-(2,4-DICHLOROPHENYL)-N-ETHYLTHIENO[2,3-D]PYRIMIDINE-6-CARBOXAMIDEexperimentalunknowntargetDetails
Nedocromilapproved, investigationalunknowntargetDetails
Copperapproved, investigationalunknowntargetDetails
Quercetinexperimental, investigationalunknowntargetDetails
PolaprezincexperimentalunknowntargetagonistDetails
Cromoglicic acidapprovedyestargetinhibitorDetails
RadicicolexperimentalyestargetinhibitorDetails
SNX-2112investigationalyestargetinhibitorDetails
RheinexperimentalyestargetinhibitorDetails
IPI-493investigationalyestargetinhibitorDetails
OnalespibinvestigationalyestargetinhibitorDetails
BIIB021investigationalyestargetinhibitorDetails
Amlexanoxapproved, investigational, withdrawnyestargetinhibitorDetails