HSP90AA1Heat shock protein HSP 90-alpha

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11274138"
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11276205"
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          "source": "PubMed",
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        {
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "25609812"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "27353360"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "29127155"
        },
        {
          "evidenceCode": "ECO:0000303",
          "source": "PubMed",
          "id": "25973397"
        },
        {
          "evidenceCode": "ECO:0000303",
          "source": "PubMed",
          "id": "26991466"
        },
        {
          "evidenceCode": "ECO:0000303",
          "source": "PubMed",
          "id": "27295069"
        }
      ],
      "value": "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)"
    }
  ],
  "commentType": "FUNCTION"
}

{
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    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000305",
          "source": "PubMed",
          "id": "22066472"
        }
      ],
      "value": "(Microbial infection) 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"
    }
  ],
  "commentType": "FUNCTION"
}

{
  "commentType": "BIOPHYSICOCHEMICAL PROPERTIES",
  "kineticParameters": {
    "michaelisConstants": [
      {
        "constant": 300.0,
        "unit": "uM",
        "substrate": "ATP",
        "evidences": [
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "18400751"
          }
        ]
      }
    ]
  }
}

{
  "commentType": "CATALYTIC ACTIVITY",
  "reaction": {
    "name": "ATP + H2O = ADP + phosphate + H(+)",
    "reactionCrossReferences": [
      {
        "database": "Rhea",
        "id": "RHEA:13065"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:15377"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:15378"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:30616"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:43474"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:456216"
      }
    ],
    "ecNumber": "3.6.4.10",
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "12526792"
      }
    ]
  }
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18400751"
        },
        {
          "evidenceCode": "ECO:0000269",
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      ],
      "value": "In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation (PubMed:18400751). Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation (PubMed:18400751). After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state (PubMed:18400751). Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by geldanamycin, Ganetespib (STA-9090) and SNX-2112 (PubMed:12526792, PubMed:29127155)"
    }
  ],
  "commentType": "ACTIVITY REGULATION"
}

Eukaryota → Metazoa → Chordata → Craniata → Vertebrata → Euteleostomi → Mammalia → Eutheria → Euarchontoglires → Primates → Haplorrhini → Catarrhini → Hominidae → Homo

{
  "names": {
    "recommendedName": {
      "fullName": {
        "evidences": [
          {
            "evidenceCode": "ECO:0000305"
          }
        ],
        "value": "Heat shock protein HSP 90-alpha"
      },
      "ecNumbers": [
        {
          "evidences": [
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "12526792"
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          ],
          "value": "3.6.4.10"
        }
      ]
    },
    "alternativeNames": [
      {
        "fullName": {
          "value": "Heat shock 86 kDa"
        },
        "shortNames": [
          {
            "value": "HSP 86"
          },
          {
            "value": "HSP86"
          }
        ]
      },
      {
        "fullName": {
          "value": "Heat shock protein family C member 1"
        }
      },
      {
        "fullName": {
          "value": "Lipopolysaccharide-associated protein 2"
        },
        "shortNames": [
          {
            "value": "LAP-2"
          },
          {
            "value": "LPS-associated protein 2"
          }
        ]
      },
      {
        "fullName": {
          "value": "Renal carcinoma antigen NY-REN-38"
        }
      }
    ]
  },
  "genes": [
    {
      "geneName": {
        "evidences": [
          {
            "evidenceCode": "ECO:0000312",
            "source": "HGNC",
            "id": "HGNC:5253"
          }
        ],
        "value": "HSP90AA1"
      },
      "synonyms": [
        {
          "value": "HSP90A"
        },
        {
          "value": "HSPC1"
        },
        {
          "value": "HSPCA"
        }
      ]
    }
  ]
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "16139798"
        }
      ],
      "value": "ISGylated"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15937123"
        }
      ],
      "value": "S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P07901"
        }
      ],
      "value": "Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. Ubiquitination promotes translocation into the cytoplasm away from the membrane and secretory pathways"
    }
  ],
  "commentType": "PTM"
}

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          "source": "PubMed",
          "id": "30559449"
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          "source": "PubMed",
          "id": "41742417"
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          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "7588731"
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8289821"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9195923"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9660753"
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      ],
      "value": "Homodimer (PubMed:18400751, PubMed:29127155, PubMed:7588731, PubMed:8289821). Identified in NR3C1/GCR steroid receptor-chaperone complexes formed at least by NR3C1, HSP90AA1 and a variety of proteins containing TPR repeats such as FKBP4, FKBP5, PPID, PPP5C or STIP1 (PubMed:15383005, PubMed:9195923). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (PubMed:29127155). The closed form interacts (via the middle domain and TPR repeat-binding motif) with co-chaperone TSC1 (via C-terminus) (PubMed:29127155). Interacts with TOM34 (PubMed:9660753). Interacts with TERT; the interaction, together with PTGES3, is required for correct assembly and stabilization of the TERT holoenzyme complex (PubMed:11274138, PubMed:9817749). Interacts with CHORDC1 and DNAJC7 (PubMed:12853476, PubMed:19875381). Interacts with STUB1 and UBE2N; may couple the chaperone and ubiquitination systems (PubMed:16307917, PubMed:27353360). Interacts (via TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction is direct and activates PPP5C phosphatase activity (PubMed:15383005, PubMed:15577939, PubMed:16531226, PubMed:27353360). Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8 (PubMed:11276205). Interacts with KSR1 (PubMed:10409742). Interacts with co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1 ATPase activity (PubMed:23569206, PubMed:27353360). May interact with NWD1 (PubMed:24681825). Interacts with FNIP1 and FNIP2; the interaction inhibits HSP90AA1 ATPase activity (PubMed:17028174, PubMed:27353360). Interacts with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the interaction activates HSP90AA1 ATPase activity and results in the dissociation of TSC1 from HSP90AA1 (PubMed:12604615, PubMed:27353360, PubMed:29127155). Interacts with FLCN in the presence of FNIP1 (PubMed:27353360). Interacts with HSP70, STIP1 and PTGES3 (PubMed:27353360). Interacts with SMYD3; this interaction enhances SMYD3 histone-lysine N-methyltransferase (PubMed:15235609, PubMed:25738358). Interacts with SGTA (via TPR repeats) (PubMed:15708368). Interacts with TTC1 (via TPR repeats) (PubMed:15708368). Interacts with HSF1 in an ATP-dependent manner (PubMed:11583998, PubMed:26517842). Interacts with MET; the interaction suppresses MET kinase activity (PubMed:26517842). Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (PubMed:26517842). Interacts with HIF1A, KEAP1 and RHOBTB2 (PubMed:26517842). Interacts with HSF1; this interaction is decreased in a IER5-dependent manner, promoting HSF1 accumulation in the nucleus, homotrimerization and DNA-binding activities (PubMed:26754925). Interacts with STUB1 and SMAD3 (PubMed:24613385). Interacts with HSP90AB1; interaction is constitutive (PubMed:20353823). Interacts with HECTD1 (via N-terminus) (By similarity). Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD) (By similarity). Interacts with NLPR12 (PubMed:17947705, PubMed:30559449). Interacts with PDCL3 (By similarity). Interacts with TOMM70; the interaction is required for preprotein mitochondrial import (PubMed:12526792). Interacts with TOMM70, IRF3 and TBK1; the interactions are direct and mediate the association of TOMM70 with IRF3 and TBK1 (PubMed:20628368). Forms a complex with ASL, ASS1 and NOS2; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway. Interacts with RNASEK; the interaction is increased by arsenite and heat stress (PubMed:41742417)"
    }
  ],
  "commentType": "SUBUNIT"
}

{
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          "source": "PubMed",
          "id": "29743370"
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      ],
      "value": "(Microbial infection) Interacts with herpes simplex virus 1 protein US11; this interaction inhibits TBK1-induced interferon production"
    }
  ],
  "commentType": "SUBUNIT"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "22066472"
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      ],
      "value": "(Microbial infection) Interacts with N.meningitidis serogroup B adhesin A (nadA). Interaction is stabilized by ADP and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin) and inhibited by ATP. Decreasing HSP90 levels increases adhesion and entry of bacterial into human Chang cells; increasing its levels leads to decreased adhseion and invasion"
    }
  ],
  "commentType": "SUBUNIT"
}