| Tchem | Heat shock protein 75 kDa, mitochondrial |
Chaperone that expresses an ATPase activity. Involved in maintaining mitochondrial function and polarization, most likely through stabilization of mitochondrial complex I. Is a negative regulator of mitochondrial respiration able to modulate the balance between oxidative phosphorylation and aerobic glycolysis. The impact of TRAP1 on mitochondrial respiration is probably mediated by modulation of mitochondrial SRC and inhibition of SDHA.
This gene encodes a mitochondrial chaperone protein that is member of the heat shock protein 90 (HSP90) family. The encoded protein has ATPase activity and interacts with tumor necrosis factor type I. This protein may function in regulating cellular stress responses. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]
This gene encodes a mitochondrial chaperone protein that is member of the heat shock protein 90 (HSP90) family. The encoded protein has ATPase activity and interacts with tumor necrosis factor type I. This protein may function in regulating cellular stress responses. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]
Comments
| Disease | Target Count |
|---|---|
| Degenerative polyarthritis | 93 |
| Disease Progression | 125 |
| Stomach Neoplasms | 282 |
| Disease | Target Count | P-value |
|---|---|---|
| non-small cell lung cancer | 2798 | 1.7e-18 |
| ovarian cancer | 8491 | 7.5e-05 |
| lung cancer | 4473 | 1.4e-04 |
| medulloblastoma, large-cell | 6234 | 6.1e-03 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| VACTERL association | 23 | 3.326 | 1.7 |
| Disease | log2 FC | p |
|---|---|---|
| medulloblastoma, large-cell | 1.100 | 6.1e-03 |
| non-small cell lung cancer | 1.138 | 1.7e-18 |
| lung cancer | 1.700 | 1.4e-04 |
| ovarian cancer | 1.100 | 7.5e-05 |
CHEMBL560895
pKi 6.10
CHEMBL278315
pIC50 6.18
CHEMBL252164
pIC50 6.27
CHEMBL3104859
pKi 6.49
CHEMBL1230584
pKi 6.59
CHEMBL200102
pIC50 6.69
CHEMBL467399
pIC50 7.05
CHEMBL2103879
pIC50 7.29
CHEMBL2419341
pKd 7.29
CHEMBL2419342
pKd 8.23
CHEMBL1910764
pKd 8.24
| PMID | Text | |
|---|---|---|
| 26929380 | A previously unobserved coiled-coil dimer conformation may precede dimer closure. TRAP1 exists in an autoinhibited state with the ATP lid bound to the ATP-binding pocket. ATP displaces this and signals the cis-bound ATP status to the next subunit. | |
| 26722505 | TRAP1 is highly expressed in kidney cancer and correlates with patients prognosis | |
| 26517089 | Overexpression of TRAP1 in breast cancer cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis in breast cancer. | |
| 26464709 | Our results indicate that GRP94 and TRAP1 might contribute more to the carcinogenesis or biology of SCLC than HSP90alpha and HSP90beta | |
| 26202366 | results of the present study show that TRAP1 provides cardioprotection against myocardial I/R by ameliorating mitochondrial dysfunction | |
| 26084290 | TRAP1 is a downstream effector of BRAF cytoprotective pathway in mitochondria and TRAP1 targeting may represent a novel strategy to improve the activity of proapoptotic agents in BRAF-driven CRC cells. | |
| 26071104 | a correlation between TRAP1 and AKT expression is found in vivo in human colorectal tumours. These results provide new insights into TRAP1 role in the regulation of cell migration in cancer cells, tumour progression and metastatic mechanisms. | |
| 26022780 | The combined presence of pain, fatigue and nausea is strongly associated with p.Ile253Val (OR 7.5, P = 0.0001) and with two other interacting variants (OR 18, P = 0.0005). | |
| 25564869 | Our findings demonstrate that SDH inhibition by TRAP1 is oncogenic not only by inducing pseudohypoxia, but also by protecting tumor cells from oxidative stress | |
| 25531069 | crystal structure of the mitochondrial Hsp90, TRAP1, revealed an extension of the N-terminal beta-strand previously shown to cross between protomers in the closed state | |
| 25493016 | Oxidative stress in ulcerative colitis could lead to the increase of cytoprotective protein TRAP1, which in turn could promote cancer progression by preventing or protecting the oxidative damaged epithelial cells from undergoing apoptosis. | |
| 25438697 | TRAP1 expression was associated with increased risk of lymph node metastasis, while high TRAP1 expression correlated with poor prognosis in esophageal squamous cell cancer. | |
| 25239454 | dual HSP90/TRAP1 inhibitor HSP990 showed activity against the TRAP1 network and high cytostatic potential in BRAF-mutated colorectal carcinoma cells | |
| 24990602 | The article summarizes the central regulatory function of TRAP1 with homeostatic roles at the crossroad between different kinds of cell functions/metabolism during the transformation process or, possibly, during normal development. [review] | |
| 24962791 | TRAP1-dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: relevance in human colorectal tumors | |
| 24754231 | study shows that TRAP1 was overexpressed in most patients with ESCC, and caused an increase in antiapoptosis potency | |
| 24567527 | TRAP1 controls NSCLC proliferation, apoptosis, and mitochondrial function, and its status has prognostic potential in NSCLC. | |
| 24297638 | High TRAP1 expression is associated with resistance to anthracyclins in breast carcinoma. | |
| 24152966 | Identify mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT. | |
| 24113185 | This study demonstrates for the first time that TRAP1 is associated with ribosomes and with several translation factors in colon carcinoma cells. | |
| 23842546 | Mitochondrial Hsp90 and TRAP-1 are global regulators of tumor metabolic reprogramming, including oxidative phosphorylation, and are required for disease maintenance. | |
| 23747254 | TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. | |
| 23525905 | Overexpression of TRAP1 is able to mitigate Pink1 but not parkin loss-of-function phenotypes. | |
| 23364796 | HIV-1 Tat upregulates the expression of TNF receptor-associated protein 1 (TRAP1; HSP90L; HSP75) in Jurkat cells | |
| 23284813 | TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression. | |
| 23273922 | Early mesangial nephritis initiates a cascade of inflammatory signals that lead to up-regulation of Trap1 and a consequent down-regulation of renal DNaseI by transcriptional interference. | |
| 23139614 | Mitochondria TRAP-1 affects the lymph node metastasis in colorectal cancer, and may be a potential biomarker for LNM and a prognostic factor in CRC. | |
| 22978347 | Immunohistochemical evaluation of TRAP1 together with ERalpha provides significant prognostic information. TRAP1 alone is significantly associated with chemotherapy response and overall survival. | |
| 22319455 | alpha-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1 | |
| 21979464 | The proposed TRAP1 network has an impact in vivo, as it is conserved in human colorectal cancers, is controlled by ER-localized TRAP1 interacting with TBP7 and provides a novel model of the ER-mitochondria crosstalk. | |
| 21878357 | TRAP-1-directed compartmentalized protein folding is broadly exploited in cancer. | |
| 21381076 | HSP75 likely reduces the hypertrophy and fibrosis induced by pressure overload through blocking TAK/P38, JNK, and AKT signaling pathways | |
| 21338643 | Mitochondria could be a potential regulator of the unfolded protein response in the endoplasmic reticulum via mitochondrial TRAP1. | |
| 20877624 | Observational study of gene-disease association. (HuGE Navigator) | |
| 20647321 | Depletion of TRAP1 by short hairpin RNA in colorectal carcinoma cells lowered Sorcin levels in mitochondria, whereas the depletion of Sorcin by small interfering RNA increased TRAP1 degradation. | |
| 20628086 | Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) | |
| 20499060 | up-regulated in prostate cancer tissue | |
| 20471161 | In many tumors TRAP1 may activate proliferation whilst inhibiting metastatic spread. | |
| 19948822 | These data identify TRAP-1 as a novel mitochondrial survival factor differentially expressed in localized and metastatic prostate cancer compared with normal prostate. | |
| 19913121 | Observational study of gene-disease association. (HuGE Navigator) | |
| 19490362 | TRAP1 works synergistically with tumor necrosis factor receptor 1 (TNFR1) to modulate expression of the cell adhesion molecule N-cadherin, and alters inter-cellular adhesion of neuronal cells. | |
| 19217207 | TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells. | |
| 18815895 | Data show that mtDNA variability is able to influence the cellular response to heat stress by modulating both the transcription of HSP60 and 75 and their intra-mitochondrial protein levels. | |
| 18790094 | mitochondrial ribosomal protein S12 3'-UTR interacts specifically with TRAP1 (tumor necrosis factor receptor-associated protein1), hnRNPM4 (heterogeneous nuclear ribonucleoprotein M4), Hsp70 and Hsp60 (heat shock proteins 70 and 60), and alpha-tubulin | |
| 18287101 | analysis of the ATPase cycle of the mitochondrial Hsp90 analog Trap1 | |
| 18091755 | Hsp75 can provide protection against ischemia-like in vitro injury | |
| 17853063 | TRAP-1 protects cells from oxidative stress and apoptosis | |
| 17579517 | PINK1 protects against oxidative-stress-induced cell death by suppressing cytochrome c release from mitochondria, and this protective action of PINK1 depends on its kinase activity to phosphorylate TRAP1. | |
| 16927372 | TRAP1 might play a role in protecting mitochondria against damaging stimuli via decrease of reactive oxygen species generation | |
| 15292218 | suppression of the expression of TRAP1 in mitochondria might play an important role in the induction of apoptosis caused via formation of ROS |
MARELRALLLWGRRLRPLLRAPALAAVPGGKPILCPRRTTAQLGPRRNPAWSLQAGRLFSTQTAEDKEEP 1 - 70 LHSIISSTESVQGSTSKHEFQAETKKLLDIVARSLYSEKEVFIRELISNASDALEKLRHKLVSDGQALPE 71 - 140 MEIHLQTNAEKGTITIQDTGIGMTQEELVSNLGTIARSGSKAFLDALQNQAEASSKIIGQFGVGFYSAFM 141 - 210 VADRVEVYSRSAAPGSLGYQWLSDGSGVFEIAEASGVRTGTKIIIHLKSDCKEFSSEARVRDVVTKYSNF 211 - 280 VSFPLYLNGRRMNTLQAIWMMDPKDVREWQHEEFYRYVAQAHDKPRYTLHYKTDAPLNIRSIFYVPDMKP 281 - 350 SMFDVSRELGSSVALYSRKVLIQTKATDILPKWLRFIRGVVDSEDIPLNLSRELLQESALIRKLRDVLQQ 351 - 420 RLIKFFIDQSKKDAEKYAKFFEDYGLFMREGIVTATEQEVKEDIAKLLRYESSALPSGQLTSLSEYASRM 421 - 490 RAGTRNIYYLCAPNRHLAEHSPYYEAMKKKDTEVLFCFEQFDELTLLHLREFDKKKLISVETDIVVDHYK 491 - 560 EEKFEDRSPAAECLSEKETEELMAWMRNVLGSRVTNVKVTLRLDTHPAMVTVLEMGAARHFLRMQQLAKT 561 - 630 QEERAQLLQPTLEINPRHALIKKLNQLRASEPGLAQLLVDQIYENAMIAAGLVDDPRAMVGRLNELLVKA 631 - 700 LERH 701 - 704 //
| PMID | Year | Title | |
|---|---|---|---|
| 26929380 | 2016 | Mitochondrial Hsp90 is a ligand-activated molecular chaperone coupling ATP binding to dimer closure through a coiled-coil intermediate. | |
| 26722505 | 2015 | Expression of tumor necrosis factor receptor-associated protein 1 and its clinical significance in kidney cancer. | |
| 26517089 | 2015 | Aberrantly upregulated TRAP1 is required for tumorigenesis of breast cancer. | |
| 26464709 | 2015 | Differential expression of heat shock protein 90 isoforms in small cell lung cancer. | |
| 26202366 | 2015 | TRAP1 Provides Protection Against Myocardial Ischemia-Reperfusion Injury by Ameliorating Mitochondrial Dysfunction. | |
| 26084290 | 2015 | Targeting TRAP1 as a downstream effector of BRAF cytoprotective pathway: a novel strategy for human BRAF-driven colorectal carcinoma. | |
| 26071104 | 2015 | TRAP1 controls cell migration of cancer cells in metabolic stress conditions: Correlations with AKT/p70S6K pathways. | |
| 26022780 | 2015 | Hurt, tired and queasy: Specific variants in the ATPase domain of the TRAP1 mitochondrial chaperone are associated with common, chronic "functional" symptomatology including pain, fatigue and gastrointestinal dysmotility. | |
| 25944712 | 2015 | N-terminome analysis of the human mitochondrial proteome. | |
| 25564869 | 2014 | Inhibition of succinate dehydrogenase by the mitochondrial chaperone TRAP1 has anti-oxidant and anti-apoptotic effects on tumor cells. | |
| 25531069 | 2014 | A novel N-terminal extension in mitochondrial TRAP1 serves as a thermal regulator of chaperone activity. | |
| 25493016 | 2014 | Up-regulation of mitochondrial chaperone TRAP1 in ulcerative colitis associated colorectal cancer. | |
| 25438697 | 2014 | TRAP1 shows clinical significance and promotes cellular migration and invasion through STAT3/MMP2 pathway in human esophageal squamous cell cancer. | |
| 25239454 | 2014 | TRAP1 is involved in BRAF regulation and downstream attenuation of ERK phosphorylation and cell-cycle progression: a novel target for BRAF-mutated colorectal tumors. | |
| 24990602 | 2014 | TRAP1 revisited: novel localizations and functions of a 'next-generation' biomarker (review). | |
| 24962791 | 2014 | TRAP1-dependent regulation of p70S6K is involved in the attenuation of protein synthesis and cell migration: relevance in human colorectal tumors. | |
| 24754231 | 2014 | Suppression of tumor necrosis factor receptor-associated protein 1 expression induces inhibition of cell proliferation and tumor growth in human esophageal cancer cells. | |
| 24567527 | 2014 | TRAP1 regulates proliferation, mitochondrial function, and has prognostic significance in NSCLC. | |
| 24522549 | 2014 | Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease. | |
| 24297638 | 2014 | TRAP1 role in endoplasmic reticulum stress protection favors resistance to anthracyclins in breast carcinoma cells. | |
| 24275569 | 2014 | An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. | |
| 24152966 | 2014 | Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association. | |
| 24113185 | 2013 | Translational control in the stress adaptive response of cancer cells: a novel role for the heat shock protein TRAP1. | |
| 23842546 | 2013 | Landscape of the mitochondrial Hsp90 metabolome in tumours. | |
| 23747254 | 2013 | The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase. | |
| 23564345 | 2013 | Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis. | |
| 23525905 | 2013 | TRAP1 rescues PINK1 loss-of-function phenotypes. | |
| 23376485 | 2013 | Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. | |
| 23319000 | 2014 | Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid. | |
| 23284813 | 2012 | TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression. | |
| 23273922 | 2013 | Impact of the tumor necrosis factor receptor-associated protein 1 (Trap1) on renal DNaseI shutdown and on progression of murine and human lupus nephritis. | |
| 23186163 | 2013 | Toward a comprehensive characterization of a human cancer cell phosphoproteome. | |
| 23139614 | 2012 | Correlation between mitochondrial TRAP-1 expression and lymph node metastasis in colorectal cancer. | |
| 22978347 | 2012 | Role of TRAP1 and estrogen receptor alpha in patients with ovarian cancer -a study of the OVCAD consortium. | |
| 22658674 | 2012 | Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. | |
| 22319455 | 2012 | The mitochondrial chaperone protein TRAP1 mitigates ?-Synuclein toxicity. | |
| 21979464 | 2012 | TRAP1 and the proteasome regulatory particle TBP7/Rpt3 interact in the endoplasmic reticulum and control cellular ubiquitination of specific mitochondrial proteins. | |
| 21878357 | 2012 | TRAP-1, the mitochondrial Hsp90. | |
| 21381076 | 2011 | HSP75 protects against cardiac hypertrophy and fibrosis. | |
| 21338643 | 2011 | Mitochondrial TRAP1 regulates the unfolded protein response in the endoplasmic reticulum. | |
| 21269460 | 2011 | Initial characterization of the human central proteome. | |
| 20877624 | 2010 | Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. | |
| 20647321 | 2010 | Mitochondrial chaperone Trap1 and the calcium binding protein Sorcin interact and protect cells against apoptosis induced by antiblastic agents. | |
| 20628086 | 2010 | Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. | |
| 20499060 | 2010 | Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy. | |
| 20471161 | 2010 | Tumor necrosis factor receptor-associated protein 1(TRAP1) regulates genes involved in cell cycle and metastases. | |
| 19948822 | 2010 | Cytoprotective mitochondrial chaperone TRAP-1 as a novel molecular target in localized and metastatic prostate cancer. | |
| 19946888 | 2010 | Defining the membrane proteome of NK cells. | |
| 19913121 | 2009 | Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. | |
| 19608861 | 2009 | Lysine acetylation targets protein complexes and co-regulates major cellular functions. | |
| 19490362 | 2009 | Tumor necrosis factor receptor-associated protein 1 regulates cell adhesion and synaptic morphology via modulation of N-cadherin expression. | |
| 19217207 | 2009 | TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells. | |
| 18815895 | 2009 | Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines. | |
| 18790094 | 2008 | cis-acting sequences and trans-acting factors in the localization of mRNA for mitochondrial ribosomal proteins. | |
| 18669648 | 2008 | A quantitative atlas of mitotic phosphorylation. | |
| 18287101 | 2008 | The ATPase cycle of the mitochondrial Hsp90 analog Trap1. | |
| 18221368 | 2008 | Biochemical aspects of the neuroprotective mechanism of PTEN-induced kinase-1 (PINK1). | |
| 18091755 | 2008 | Overexpression of mitochondrial Hsp70/Hsp75 protects astrocytes against ischemic injury in vitro. | |
| 17853063 | 2007 | Tumor necrosis factor-associated protein 1 (TRAP-1) protects cells from oxidative stress and apoptosis. | |
| 17579517 | 2007 | PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. | |
| 16927372 | 2007 | Iron chelation study in a normal human hepatocyte cell line suggests that tumor necrosis factor receptor-associated protein 1 (TRAP1) regulates production of reactive oxygen species. | |
| 16551573 | 2006 | AROS-29 is involved in adaptive response to oxidative stress. | |
| 16482509 | 2006 | Binding specificity of Toll-like receptor cytoplasmic domains. | |
| 16269234 | 2005 | The HSP90 family of genes in the human genome: insights into their divergence and evolution. | |
| 15616553 | 2004 | The sequence and analysis of duplication-rich human chromosome 16. | |
| 15489334 | 2004 | The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | |
| 15292218 | 2004 | Involvement of tumor necrosis factor receptor-associated protein 1 (TRAP1) in apoptosis induced by beta-hydroxyisovalerylshikonin. | |
| 14702039 | 2004 | Complete sequencing and characterization of 21,243 full-length human cDNAs. | |
| 12477932 | 2002 | Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. | |
| 11278302 | 2001 | Transforming growth factor-beta receptor-associated protein 1 is a Smad4 chaperone. | |
| 10652318 | 2000 | The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties. | |
| 10545594 | 1999 | A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses. | |
| 9545258 | 1998 | A novel protein distinguishes between quiescent and activated forms of the type I transforming growth factor beta receptor. | |
| 8756626 | 1996 | A new member of the hsp90 family of molecular chaperones interacts with the retinoblastoma protein during mitosis and after heat shock. | |
| 8125298 | 1994 | Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. | |
| 7876093 | 1995 | Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor. |
