Full text data of TRAP1
TRAP1
(HSP75)
[Confidence: low (only semi-automatic identification from reviews)]
Heat shock protein 75 kDa, mitochondrial; HSP 75 (TNFR-associated protein 1; Tumor necrosis factor type 1 receptor-associated protein; TRAP-1; Flags: Precursor)
Heat shock protein 75 kDa, mitochondrial; HSP 75 (TNFR-associated protein 1; Tumor necrosis factor type 1 receptor-associated protein; TRAP-1; Flags: Precursor)
UniProt
Q12931
ID TRAP1_HUMAN Reviewed; 704 AA.
AC Q12931; D3DUC8; O43642; O75235; Q9UHL5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-JUN-2005, sequence version 3.
DT 22-JAN-2014, entry version 141.
DE RecName: Full=Heat shock protein 75 kDa, mitochondrial;
DE Short=HSP 75;
DE AltName: Full=TNFR-associated protein 1;
DE AltName: Full=Tumor necrosis factor type 1 receptor-associated protein;
DE Short=TRAP-1;
DE Flags: Precursor;
GN Name=TRAP1; Synonyms=HSP75;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-307.
RX PubMed=10545594; DOI=10.1093/hmg/8.12.2155;
RA Simmons A.D., Musy M.M., Lopes C.S., Hwang L.-Y., Yang Y.-P.,
RA Lovett M.;
RT "A direct interaction between EXT proteins and glycosyltransferases is
RT defective in hereditary multiple exostoses.";
RL Hum. Mol. Genet. 8:2155-2164(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-704, AND VARIANT GLY-307.
RX PubMed=7876093; DOI=10.1074/jbc.270.28.16630;
RA Song H.Y., Dunbar J.D., Zhang Y.X., Guo D., Donner D.B.;
RT "Identification of a protein with homology to hsp90 that binds the
RT type 1 tumor necrosis factor receptor.";
RL J. Biol. Chem. 270:3574-3581(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 53-704, AND VARIANT GLU-395.
RX PubMed=8756626;
RA Chen C.-F., Chen Y., Dai K., Chen P.-L., Riley D.J., Lee W.-H.;
RT "A new member of the hsp90 family of molecular chaperones interacts
RT with the retinoblastoma protein during mitosis and after heat shock.";
RL Mol. Cell. Biol. 16:4691-4699(1996).
RN [7]
RP CHARACTERIZATION.
RX PubMed=10652318; DOI=10.1074/jbc.275.5.3305;
RA Felts S.J., Owen B.A.L., Nguyen P., Trepel J., Donner D.B., Toft D.O.;
RT "The hsp90-related protein TRAP1 is a mitochondrial protein with
RT distinct functional properties.";
RL J. Biol. Chem. 275:3305-3312(2000).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-494, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-332; LYS-424 AND LYS-466,
RP AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION AS NEGATIVE REGULATOR OF MITOCHONDRIAL RESPIRATION, AND
RP INTERACTION WITH SDHA.
RX PubMed=23747254; DOI=10.1016/j.cmet.2013.04.019;
RA Sciacovelli M., Guzzo G., Morello V., Frezza C., Zheng L., Nannini N.,
RA Calabrese F., Laudiero G., Esposito F., Landriscina M., Defilippi P.,
RA Bernardi P., Rasola A.;
RT "The mitochondrial chaperone TRAP1 promotes neoplastic growth by
RT inhibiting succinate dehydrogenase.";
RL Cell Metab. 17:988-999(2013).
RN [13]
RP FUNCTION.
RX PubMed=23525905; DOI=10.1093/hmg/ddt132;
RA Zhang L., Karsten P., Hamm S., Pogson J.H., Muller-Rischart A.K.,
RA Exner N., Haass C., Whitworth A.J., Winklhofer K.F., Schulz J.B.,
RA Voigt A.;
RT "TRAP1 rescues PINK1 loss-of-function phenotypes.";
RL Hum. Mol. Genet. 22:2829-2841(2013).
RN [14]
RP FUNCTION AS NEGATIVE REGULATOR OF MITOCHONDRIAL RESPIRATION,
RP INTERACTION WITH SRC, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=23564345; DOI=10.1073/pnas.1220659110;
RA Yoshida S., Tsutsumi S., Muhlebach G., Sourbier C., Lee M.J., Lee S.,
RA Vartholomaiou E., Tatokoro M., Beebe K., Miyajima N., Mohney R.P.,
RA Chen Y., Hasumi H., Xu W., Fukushima H., Nakamura K., Koga F.,
RA Kihara K., Trepel J., Picard D., Neckers L.;
RT "Molecular chaperone TRAP1 regulates a metabolic switch between
RT mitochondrial respiration and aerobic glycolysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E1604-E1612(2013).
CC -!- FUNCTION: Chaperone that expresses an ATPase activity. Involved in
CC maintaining mitochondrial function and polarization, most likely
CC through stabilization of mitochondrial complex I. Is a negative
CC regulator of mitochondrial respiration able to modulate the
CC balance between oxidative phosphorylation and aerobic glycolysis.
CC The impact of TRAP1 on mitochondrial respiration is probably
CC mediated by modulation of mitochondrial SRC and inhibition of
CC SDHA.
CC -!- SUBUNIT: Binds to the intracellular domain of tumor necrosis
CC factor type 1 receptor. Binds to RB1. Interacts with SRC.
CC Interacts with SDHA.
CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane.
CC Mitochondrion matrix.
CC -!- TISSUE SPECIFICITY: Found in skeletal muscle, liver, heart, brain,
CC kidney, pancreas, lung, placenta and bladder. Expression is higly
CC reduced in bladder cancer and renal cell carcinoma specimens
CC compared to healthy tissues, but it is increased in other type of
CC tumors.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA87704.1; Type=Frameshift; Positions=656;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TRAP1ID42692ch16p13.html";
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DR EMBL; AF154108; AAF15314.1; -; mRNA.
DR EMBL; AC005203; AAC24722.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85338.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85340.1; -; Genomic_DNA.
DR EMBL; BC018950; AAH18950.1; -; mRNA.
DR EMBL; BC023585; AAH23585.1; -; mRNA.
DR EMBL; U12595; AAA87704.1; ALT_FRAME; mRNA.
DR EMBL; AF043254; AAC02679.1; -; mRNA.
DR RefSeq; NP_057376.2; NM_016292.2.
DR UniGene; Hs.30345; -.
DR ProteinModelPortal; Q12931; -.
DR SMR; Q12931; 84-697.
DR DIP; DIP-6250N; -.
DR IntAct; Q12931; 26.
DR MINT; MINT-1510364; -.
DR STRING; 9606.ENSP00000246957; -.
DR BindingDB; Q12931; -.
DR ChEMBL; CHEMBL1075132; -.
DR PhosphoSite; Q12931; -.
DR DMDM; 67477458; -.
DR REPRODUCTION-2DPAGE; IPI00030275; -.
DR PaxDb; Q12931; -.
DR PeptideAtlas; Q12931; -.
DR PRIDE; Q12931; -.
DR Ensembl; ENST00000246957; ENSP00000246957; ENSG00000126602.
DR GeneID; 10131; -.
DR KEGG; hsa:10131; -.
DR UCSC; uc002cvs.3; human.
DR CTD; 10131; -.
DR GeneCards; GC16M003710; -.
DR H-InvDB; HIX0012776; -.
DR HGNC; HGNC:16264; TRAP1.
DR HPA; HPA041082; -.
DR HPA; HPA044227; -.
DR MIM; 606219; gene.
DR neXtProt; NX_Q12931; -.
DR PharmGKB; PA36781; -.
DR eggNOG; COG0326; -.
DR HOGENOM; HOG000031987; -.
DR HOVERGEN; HBG103147; -.
DR InParanoid; Q12931; -.
DR KO; K09488; -.
DR OMA; AHDKPRY; -.
DR OrthoDB; EOG7C8GGM; -.
DR PhylomeDB; Q12931; -.
DR ChiTaRS; TRAP1; human.
DR GeneWiki; TRAP1; -.
DR GenomeRNAi; 10131; -.
DR NextBio; 38323; -.
DR PRO; PR:Q12931; -.
DR ArrayExpress; Q12931; -.
DR Bgee; Q12931; -.
DR CleanEx; HS_TRAP1; -.
DR Genevestigator; Q12931; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; NAS:UniProtKB.
DR GO; GO:1901856; P:negative regulation of cellular respiration; IMP:UniProtKB.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0006950; P:response to stress; IEA:InterPro.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR003594; HATPase_ATP-bd.
DR InterPro; IPR001404; Hsp90_fam.
DR InterPro; IPR020575; Hsp90_N.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR PANTHER; PTHR11528; PTHR11528; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF00183; HSP90; 1.
DR PIRSF; PIRSF002583; Hsp90; 1.
DR PRINTS; PR00775; HEATSHOCK90.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS00298; HSP90; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Chaperone; Complete proteome; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome; Transit peptide.
FT TRANSIT 1 59 Mitochondrion (By similarity).
FT CHAIN 60 704 Heat shock protein 75 kDa, mitochondrial.
FT /FTId=PRO_0000013604.
FT BINDING 119 119 ATP (By similarity).
FT BINDING 158 158 ATP (By similarity).
FT BINDING 171 171 ATP (By similarity).
FT BINDING 205 205 ATP; via amide nitrogen (By similarity).
FT BINDING 402 402 ATP (By similarity).
FT MOD_RES 170 170 Phosphoserine (By similarity).
FT MOD_RES 174 174 Phosphothreonine (By similarity).
FT MOD_RES 262 262 N6-acetyllysine (By similarity).
FT MOD_RES 324 324 N6-acetyllysine (By similarity).
FT MOD_RES 332 332 N6-acetyllysine.
FT MOD_RES 401 401 Phosphoserine.
FT MOD_RES 424 424 N6-acetyllysine.
FT MOD_RES 431 431 N6-acetyllysine (By similarity).
FT MOD_RES 466 466 N6-acetyllysine.
FT MOD_RES 494 494 Phosphothreonine.
FT VARIANT 307 307 R -> G (in dbSNP:rs13926).
FT /FTId=VAR_016108.
FT VARIANT 395 395 D -> E (in dbSNP:rs1136948).
FT /FTId=VAR_049625.
FT VARIANT 572 572 E -> K (in dbSNP:rs55766649).
FT /FTId=VAR_061272.
FT VARIANT 692 692 R -> H (in dbSNP:rs2791).
FT /FTId=VAR_049626.
FT CONFLICT 17 19 PLL -> ALR (in Ref. 5; AAA87704).
FT CONFLICT 53 53 L -> M (in Ref. 6; AAC02679).
FT CONFLICT 475 476 Missing (in Ref. 6; AAC02679).
FT CONFLICT 488 491 SRMR -> AHW (in Ref. 6; AAC02679).
SQ SEQUENCE 704 AA; 80110 MW; 4B16DE3D2B9E0285 CRC64;
MARELRALLL WGRRLRPLLR APALAAVPGG KPILCPRRTT AQLGPRRNPA WSLQAGRLFS
TQTAEDKEEP LHSIISSTES VQGSTSKHEF QAETKKLLDI VARSLYSEKE VFIRELISNA
SDALEKLRHK LVSDGQALPE MEIHLQTNAE KGTITIQDTG IGMTQEELVS NLGTIARSGS
KAFLDALQNQ AEASSKIIGQ FGVGFYSAFM VADRVEVYSR SAAPGSLGYQ WLSDGSGVFE
IAEASGVRTG TKIIIHLKSD CKEFSSEARV RDVVTKYSNF VSFPLYLNGR RMNTLQAIWM
MDPKDVREWQ HEEFYRYVAQ AHDKPRYTLH YKTDAPLNIR SIFYVPDMKP SMFDVSRELG
SSVALYSRKV LIQTKATDIL PKWLRFIRGV VDSEDIPLNL SRELLQESAL IRKLRDVLQQ
RLIKFFIDQS KKDAEKYAKF FEDYGLFMRE GIVTATEQEV KEDIAKLLRY ESSALPSGQL
TSLSEYASRM RAGTRNIYYL CAPNRHLAEH SPYYEAMKKK DTEVLFCFEQ FDELTLLHLR
EFDKKKLISV ETDIVVDHYK EEKFEDRSPA AECLSEKETE ELMAWMRNVL GSRVTNVKVT
LRLDTHPAMV TVLEMGAARH FLRMQQLAKT QEERAQLLQP TLEINPRHAL IKKLNQLRAS
EPGLAQLLVD QIYENAMIAA GLVDDPRAMV GRLNELLVKA LERH
//
ID TRAP1_HUMAN Reviewed; 704 AA.
AC Q12931; D3DUC8; O43642; O75235; Q9UHL5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
read moreDT 07-JUN-2005, sequence version 3.
DT 22-JAN-2014, entry version 141.
DE RecName: Full=Heat shock protein 75 kDa, mitochondrial;
DE Short=HSP 75;
DE AltName: Full=TNFR-associated protein 1;
DE AltName: Full=Tumor necrosis factor type 1 receptor-associated protein;
DE Short=TRAP-1;
DE Flags: Precursor;
GN Name=TRAP1; Synonyms=HSP75;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-307.
RX PubMed=10545594; DOI=10.1093/hmg/8.12.2155;
RA Simmons A.D., Musy M.M., Lopes C.S., Hwang L.-Y., Yang Y.-P.,
RA Lovett M.;
RT "A direct interaction between EXT proteins and glycosyltransferases is
RT defective in hereditary multiple exostoses.";
RL Hum. Mol. Genet. 8:2155-2164(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 16-704, AND VARIANT GLY-307.
RX PubMed=7876093; DOI=10.1074/jbc.270.28.16630;
RA Song H.Y., Dunbar J.D., Zhang Y.X., Guo D., Donner D.B.;
RT "Identification of a protein with homology to hsp90 that binds the
RT type 1 tumor necrosis factor receptor.";
RL J. Biol. Chem. 270:3574-3581(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 53-704, AND VARIANT GLU-395.
RX PubMed=8756626;
RA Chen C.-F., Chen Y., Dai K., Chen P.-L., Riley D.J., Lee W.-H.;
RT "A new member of the hsp90 family of molecular chaperones interacts
RT with the retinoblastoma protein during mitosis and after heat shock.";
RL Mol. Cell. Biol. 16:4691-4699(1996).
RN [7]
RP CHARACTERIZATION.
RX PubMed=10652318; DOI=10.1074/jbc.275.5.3305;
RA Felts S.J., Owen B.A.L., Nguyen P., Trepel J., Donner D.B., Toft D.O.;
RT "The hsp90-related protein TRAP1 is a mitochondrial protein with
RT distinct functional properties.";
RL J. Biol. Chem. 275:3305-3312(2000).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-494, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-332; LYS-424 AND LYS-466,
RP AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION AS NEGATIVE REGULATOR OF MITOCHONDRIAL RESPIRATION, AND
RP INTERACTION WITH SDHA.
RX PubMed=23747254; DOI=10.1016/j.cmet.2013.04.019;
RA Sciacovelli M., Guzzo G., Morello V., Frezza C., Zheng L., Nannini N.,
RA Calabrese F., Laudiero G., Esposito F., Landriscina M., Defilippi P.,
RA Bernardi P., Rasola A.;
RT "The mitochondrial chaperone TRAP1 promotes neoplastic growth by
RT inhibiting succinate dehydrogenase.";
RL Cell Metab. 17:988-999(2013).
RN [13]
RP FUNCTION.
RX PubMed=23525905; DOI=10.1093/hmg/ddt132;
RA Zhang L., Karsten P., Hamm S., Pogson J.H., Muller-Rischart A.K.,
RA Exner N., Haass C., Whitworth A.J., Winklhofer K.F., Schulz J.B.,
RA Voigt A.;
RT "TRAP1 rescues PINK1 loss-of-function phenotypes.";
RL Hum. Mol. Genet. 22:2829-2841(2013).
RN [14]
RP FUNCTION AS NEGATIVE REGULATOR OF MITOCHONDRIAL RESPIRATION,
RP INTERACTION WITH SRC, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=23564345; DOI=10.1073/pnas.1220659110;
RA Yoshida S., Tsutsumi S., Muhlebach G., Sourbier C., Lee M.J., Lee S.,
RA Vartholomaiou E., Tatokoro M., Beebe K., Miyajima N., Mohney R.P.,
RA Chen Y., Hasumi H., Xu W., Fukushima H., Nakamura K., Koga F.,
RA Kihara K., Trepel J., Picard D., Neckers L.;
RT "Molecular chaperone TRAP1 regulates a metabolic switch between
RT mitochondrial respiration and aerobic glycolysis.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E1604-E1612(2013).
CC -!- FUNCTION: Chaperone that expresses an ATPase activity. Involved in
CC maintaining mitochondrial function and polarization, most likely
CC through stabilization of mitochondrial complex I. Is a negative
CC regulator of mitochondrial respiration able to modulate the
CC balance between oxidative phosphorylation and aerobic glycolysis.
CC The impact of TRAP1 on mitochondrial respiration is probably
CC mediated by modulation of mitochondrial SRC and inhibition of
CC SDHA.
CC -!- SUBUNIT: Binds to the intracellular domain of tumor necrosis
CC factor type 1 receptor. Binds to RB1. Interacts with SRC.
CC Interacts with SDHA.
CC -!- SUBCELLULAR LOCATION: Mitochondrion. Mitochondrion inner membrane.
CC Mitochondrion matrix.
CC -!- TISSUE SPECIFICITY: Found in skeletal muscle, liver, heart, brain,
CC kidney, pancreas, lung, placenta and bladder. Expression is higly
CC reduced in bladder cancer and renal cell carcinoma specimens
CC compared to healthy tissues, but it is increased in other type of
CC tumors.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA87704.1; Type=Frameshift; Positions=656;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TRAP1ID42692ch16p13.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF154108; AAF15314.1; -; mRNA.
DR EMBL; AC005203; AAC24722.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85338.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85340.1; -; Genomic_DNA.
DR EMBL; BC018950; AAH18950.1; -; mRNA.
DR EMBL; BC023585; AAH23585.1; -; mRNA.
DR EMBL; U12595; AAA87704.1; ALT_FRAME; mRNA.
DR EMBL; AF043254; AAC02679.1; -; mRNA.
DR RefSeq; NP_057376.2; NM_016292.2.
DR UniGene; Hs.30345; -.
DR ProteinModelPortal; Q12931; -.
DR SMR; Q12931; 84-697.
DR DIP; DIP-6250N; -.
DR IntAct; Q12931; 26.
DR MINT; MINT-1510364; -.
DR STRING; 9606.ENSP00000246957; -.
DR BindingDB; Q12931; -.
DR ChEMBL; CHEMBL1075132; -.
DR PhosphoSite; Q12931; -.
DR DMDM; 67477458; -.
DR REPRODUCTION-2DPAGE; IPI00030275; -.
DR PaxDb; Q12931; -.
DR PeptideAtlas; Q12931; -.
DR PRIDE; Q12931; -.
DR Ensembl; ENST00000246957; ENSP00000246957; ENSG00000126602.
DR GeneID; 10131; -.
DR KEGG; hsa:10131; -.
DR UCSC; uc002cvs.3; human.
DR CTD; 10131; -.
DR GeneCards; GC16M003710; -.
DR H-InvDB; HIX0012776; -.
DR HGNC; HGNC:16264; TRAP1.
DR HPA; HPA041082; -.
DR HPA; HPA044227; -.
DR MIM; 606219; gene.
DR neXtProt; NX_Q12931; -.
DR PharmGKB; PA36781; -.
DR eggNOG; COG0326; -.
DR HOGENOM; HOG000031987; -.
DR HOVERGEN; HBG103147; -.
DR InParanoid; Q12931; -.
DR KO; K09488; -.
DR OMA; AHDKPRY; -.
DR OrthoDB; EOG7C8GGM; -.
DR PhylomeDB; Q12931; -.
DR ChiTaRS; TRAP1; human.
DR GeneWiki; TRAP1; -.
DR GenomeRNAi; 10131; -.
DR NextBio; 38323; -.
DR PRO; PR:Q12931; -.
DR ArrayExpress; Q12931; -.
DR Bgee; Q12931; -.
DR CleanEx; HS_TRAP1; -.
DR Genevestigator; Q12931; -.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; NAS:UniProtKB.
DR GO; GO:1901856; P:negative regulation of cellular respiration; IMP:UniProtKB.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0006950; P:response to stress; IEA:InterPro.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR003594; HATPase_ATP-bd.
DR InterPro; IPR001404; Hsp90_fam.
DR InterPro; IPR020575; Hsp90_N.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR PANTHER; PTHR11528; PTHR11528; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF00183; HSP90; 1.
DR PIRSF; PIRSF002583; Hsp90; 1.
DR PRINTS; PR00775; HEATSHOCK90.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS00298; HSP90; FALSE_NEG.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Chaperone; Complete proteome; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome; Transit peptide.
FT TRANSIT 1 59 Mitochondrion (By similarity).
FT CHAIN 60 704 Heat shock protein 75 kDa, mitochondrial.
FT /FTId=PRO_0000013604.
FT BINDING 119 119 ATP (By similarity).
FT BINDING 158 158 ATP (By similarity).
FT BINDING 171 171 ATP (By similarity).
FT BINDING 205 205 ATP; via amide nitrogen (By similarity).
FT BINDING 402 402 ATP (By similarity).
FT MOD_RES 170 170 Phosphoserine (By similarity).
FT MOD_RES 174 174 Phosphothreonine (By similarity).
FT MOD_RES 262 262 N6-acetyllysine (By similarity).
FT MOD_RES 324 324 N6-acetyllysine (By similarity).
FT MOD_RES 332 332 N6-acetyllysine.
FT MOD_RES 401 401 Phosphoserine.
FT MOD_RES 424 424 N6-acetyllysine.
FT MOD_RES 431 431 N6-acetyllysine (By similarity).
FT MOD_RES 466 466 N6-acetyllysine.
FT MOD_RES 494 494 Phosphothreonine.
FT VARIANT 307 307 R -> G (in dbSNP:rs13926).
FT /FTId=VAR_016108.
FT VARIANT 395 395 D -> E (in dbSNP:rs1136948).
FT /FTId=VAR_049625.
FT VARIANT 572 572 E -> K (in dbSNP:rs55766649).
FT /FTId=VAR_061272.
FT VARIANT 692 692 R -> H (in dbSNP:rs2791).
FT /FTId=VAR_049626.
FT CONFLICT 17 19 PLL -> ALR (in Ref. 5; AAA87704).
FT CONFLICT 53 53 L -> M (in Ref. 6; AAC02679).
FT CONFLICT 475 476 Missing (in Ref. 6; AAC02679).
FT CONFLICT 488 491 SRMR -> AHW (in Ref. 6; AAC02679).
SQ SEQUENCE 704 AA; 80110 MW; 4B16DE3D2B9E0285 CRC64;
MARELRALLL WGRRLRPLLR APALAAVPGG KPILCPRRTT AQLGPRRNPA WSLQAGRLFS
TQTAEDKEEP LHSIISSTES VQGSTSKHEF QAETKKLLDI VARSLYSEKE VFIRELISNA
SDALEKLRHK LVSDGQALPE MEIHLQTNAE KGTITIQDTG IGMTQEELVS NLGTIARSGS
KAFLDALQNQ AEASSKIIGQ FGVGFYSAFM VADRVEVYSR SAAPGSLGYQ WLSDGSGVFE
IAEASGVRTG TKIIIHLKSD CKEFSSEARV RDVVTKYSNF VSFPLYLNGR RMNTLQAIWM
MDPKDVREWQ HEEFYRYVAQ AHDKPRYTLH YKTDAPLNIR SIFYVPDMKP SMFDVSRELG
SSVALYSRKV LIQTKATDIL PKWLRFIRGV VDSEDIPLNL SRELLQESAL IRKLRDVLQQ
RLIKFFIDQS KKDAEKYAKF FEDYGLFMRE GIVTATEQEV KEDIAKLLRY ESSALPSGQL
TSLSEYASRM RAGTRNIYYL CAPNRHLAEH SPYYEAMKKK DTEVLFCFEQ FDELTLLHLR
EFDKKKLISV ETDIVVDHYK EEKFEDRSPA AECLSEKETE ELMAWMRNVL GSRVTNVKVT
LRLDTHPAMV TVLEMGAARH FLRMQQLAKT QEERAQLLQP TLEINPRHAL IKKLNQLRAS
EPGLAQLLVD QIYENAMIAA GLVDDPRAMV GRLNELLVKA LERH
//
MIM
606219
*RECORD*
*FIELD* NO
606219
*FIELD* TI
*606219 TUMOR NECROSIS FACTOR RECEPTOR-ASSOCIATED PROTEIN 1; TRAP1
;;TNFR-ASSOCIATED PROTEIN 1 HEAT-SHOCK PROTEIN, 75-KD; HSP75;;
read moreHSP90-LIKE PROTEIN; HSP90L
*FIELD* TX
DESCRIPTION
HSP90 proteins are highly conserved molecular chaperones that have key
roles in signal transduction, protein folding, protein degradation, and
morphologic evolution. HSP90 proteins normally associate with other
cochaperones and play important roles in folding newly synthesized
proteins or stabilizing and refolding denatured proteins after stress.
TRAP1 is a mitochondrial HSP90 protein. Other HSP90 proteins are found
in cytosol (see HSP90AA1; 140571) and endoplasmic reticulum (HSP90B1;
191175) (Chen et al., 2005).
CLONING
Using a yeast 2-hybrid screen of a Gal4/HeLa cDNA library with the
intracellular domain of TNFR1 (191190) as bait, followed by 5-prime
RACE, Song et al. (1995) isolated a partial cDNA encoding TRAP1. The
deduced 661-amino acid protein is 60% similar to HSP90 family members,
although it lacks the highly charged domain found in HSP90 proteins.
Northern blot analysis revealed variable but ubiquitous expression of a
2.7-kb TRAP1 transcript.
By yeast 2-hybrid screening of several cDNA libraries with an
N-terminally truncated retinoblastoma protein (RB1; 614041) as bait,
Chen et al. (1996) obtained a nearly complete cDNA encoding TRAP1, which
they termed HSP75. HSP75 has 698 amino acids. Immunoprecipitation,
immunoblot analysis, and immunofluorescence microscopy demonstrated
expression of a 75-kD cytoplasmic protein that colocalized with RB1
during mitosis but not during other phases. During heat shock, HSP75
migrated to the nucleus.
In a yeast 2-hybrid screen with exostosin-2 (EXT2; 608210) as bait,
Simmons et al. (1999) isolated TRAP1. They reported that the full-length
cDNA sequence encodes a 704-amino acid protein (GenBank GENBANK
AF154108).
Using immunofluorescence microscopy, Felts et al. (2000) demonstrated a
mitochondrial localization for TRAP1. TRAP1 possesses a mitochondrial
localization sequence, STQTAED, beginning after cleavage at position 59.
Sequence analysis predicted that TRAP1 is 54% identical to a Drosophila
homolog.
By database analysis, Chen et al. (2005) identified several TRAP1
variants. Like other HSP90 proteins, the 704-amino acid TRAP1 protein
has a highly conserved N-terminal domain, a middle domain involved in
ATPase activity, a charged domain, and a C-terminal domain, but it lacks
the charged domain found immediately after the N-terminal domain in
other HSP90 proteins. It also has a signal peptide and gln-rich region.
GENE FUNCTION
Using yeast 2-hybrid and GST pull-down analyses, Song et al. (1995)
found that TRAP1 interacted with the N-terminal half of TNFR1.
Binding analysis by Chen et al. (1996) showed that HSP75 used an LxCxE
motif to bind to the T antigen-binding domains of RB1. Western blot
analysis indicated that HSP75 could refold denatured RB1, suggesting
that HSP75 acts as a chaperone for RB1.
Binding analysis by Simmons et al. (1999) showed that TRAP1 interacted
with the C-terminal ends of the proteins encoded by both multiple
exostoses-causing genes, EXT1 (608177) and EXT2, but not with EXTL1
(601738) or EXTL3 (605744). The interaction required the presence of a
his residue in the EXT proteins, the loss of which had been identified
in a single family with type I multiple exostoses (133700) by Raskind et
al. (1998).
Felts et al. (2000) reported that TRAP1 lacked the chaperone activities
of HSP90 and also failed to interact with cochaperones of HSP90.
However, TRAP1 did bind ATP and expressed an ATPase activity that could
be blocked by the HSP90 inhibitor geldanamycin.
GENE STRUCTURE
Chen et al. (2005) determined that the TRAP1 gene contains 19 exons.
MAPPING
Simmons et al. (1999) stated that the TRAP1 gene maps to chromosome 16.
By genomic sequence analysis, Chen et al. (2005) mapped the TRAP1 gene
to chromosome 16p13.3.
NOMENCLATURE
Chen et al. (2005) provided a revised nomenclature system for the HSP90
gene family. Under this system, the root HSP90A indicates cytosolic
HSP90, HSP90B indicates endoplasmic reticulum HSP90, and TRAP indicates
mitochondrial HSP90. HSP90A was divided into 2 classes, with HSP90AA
representing conventional HSP90-alpha, and HSP90AB representing
HSP90-beta. The number following the root/class represents the gene in
that class, and a 'P' at the end indicates a putative pseudogene. Chen
et al. (2005) also proposed the alias HSP90L for TRAP1.
*FIELD* RF
1. Chen, B.; Piel, W. H.; Gui, L.; Bruford, E.; Monteiro, A.: The
HSP90 family of genes in the human genome: insights into their divergence
and evolution. Genomics 86: 627-637, 2005.
2. Chen, C.-F.; Chen, Y.; Dai, K.; Chen, P.-L.; Riley, D. J.; Lee,
W.-H.: A new member of the hsp90 family of molecular chaperones interacts
with the retinoblastoma protein during mitosis and after heat shock. Molec.
Cell. Biol. 16: 4691-4699, 1996.
3. Felts, S. J.; Owen, B. A. L.; Nguyen, P.; Trepel, J.; Donner, D.
B.; Toft, D. O.: The hsp90-related protein TRAP1 is a mitochondrial
protein with distinct functional properties. J. Biol. Chem. 275:
3305-3312, 2000.
4. Raskind, W. H.; Conrad, E. U., III; Matsushita, M.; Wijsman, E.
M.; Wells, D. E.; Chapman, N.; Sandell, L. J.; Wagner, M.; Houck,
J.: Evaluation of locus heterogeneity and EXT1 mutations in 34 families
with hereditary multiple exostoses. Hum. Mutat. 11: 231-239, 1998.
5. Simmons, A. D.; Musy, M. M.; Lopes, C. S.; Hwang, L.-Y.; Yang,
Y.-P.; Lovett, M.: A direct interaction between EXT proteins and
glycosyltransferases is defective in hereditary multiple exostoses. Hum.
Molec. Genet. 8: 2155-2164, 1999.
6. Song, H. Y.; Dunbar, J. D.; Zhang, Y. X.; Guo, D.; Donner, D. B.
: Identification of a protein with homology to hsp90 that binds the
type 1 tumor necrosis factor receptor. J. Biol. Chem. 270: 3574-3581,
1995.
*FIELD* CN
Matthew B. Gross - updated: 8/12/2008
*FIELD* CD
Paul J. Converse: 8/22/2001
*FIELD* ED
alopez: 06/17/2011
carol: 11/5/2009
mgross: 8/12/2008
ckniffin: 10/30/2003
mgross: 8/22/2001
*RECORD*
*FIELD* NO
606219
*FIELD* TI
*606219 TUMOR NECROSIS FACTOR RECEPTOR-ASSOCIATED PROTEIN 1; TRAP1
;;TNFR-ASSOCIATED PROTEIN 1 HEAT-SHOCK PROTEIN, 75-KD; HSP75;;
read moreHSP90-LIKE PROTEIN; HSP90L
*FIELD* TX
DESCRIPTION
HSP90 proteins are highly conserved molecular chaperones that have key
roles in signal transduction, protein folding, protein degradation, and
morphologic evolution. HSP90 proteins normally associate with other
cochaperones and play important roles in folding newly synthesized
proteins or stabilizing and refolding denatured proteins after stress.
TRAP1 is a mitochondrial HSP90 protein. Other HSP90 proteins are found
in cytosol (see HSP90AA1; 140571) and endoplasmic reticulum (HSP90B1;
191175) (Chen et al., 2005).
CLONING
Using a yeast 2-hybrid screen of a Gal4/HeLa cDNA library with the
intracellular domain of TNFR1 (191190) as bait, followed by 5-prime
RACE, Song et al. (1995) isolated a partial cDNA encoding TRAP1. The
deduced 661-amino acid protein is 60% similar to HSP90 family members,
although it lacks the highly charged domain found in HSP90 proteins.
Northern blot analysis revealed variable but ubiquitous expression of a
2.7-kb TRAP1 transcript.
By yeast 2-hybrid screening of several cDNA libraries with an
N-terminally truncated retinoblastoma protein (RB1; 614041) as bait,
Chen et al. (1996) obtained a nearly complete cDNA encoding TRAP1, which
they termed HSP75. HSP75 has 698 amino acids. Immunoprecipitation,
immunoblot analysis, and immunofluorescence microscopy demonstrated
expression of a 75-kD cytoplasmic protein that colocalized with RB1
during mitosis but not during other phases. During heat shock, HSP75
migrated to the nucleus.
In a yeast 2-hybrid screen with exostosin-2 (EXT2; 608210) as bait,
Simmons et al. (1999) isolated TRAP1. They reported that the full-length
cDNA sequence encodes a 704-amino acid protein (GenBank GENBANK
AF154108).
Using immunofluorescence microscopy, Felts et al. (2000) demonstrated a
mitochondrial localization for TRAP1. TRAP1 possesses a mitochondrial
localization sequence, STQTAED, beginning after cleavage at position 59.
Sequence analysis predicted that TRAP1 is 54% identical to a Drosophila
homolog.
By database analysis, Chen et al. (2005) identified several TRAP1
variants. Like other HSP90 proteins, the 704-amino acid TRAP1 protein
has a highly conserved N-terminal domain, a middle domain involved in
ATPase activity, a charged domain, and a C-terminal domain, but it lacks
the charged domain found immediately after the N-terminal domain in
other HSP90 proteins. It also has a signal peptide and gln-rich region.
GENE FUNCTION
Using yeast 2-hybrid and GST pull-down analyses, Song et al. (1995)
found that TRAP1 interacted with the N-terminal half of TNFR1.
Binding analysis by Chen et al. (1996) showed that HSP75 used an LxCxE
motif to bind to the T antigen-binding domains of RB1. Western blot
analysis indicated that HSP75 could refold denatured RB1, suggesting
that HSP75 acts as a chaperone for RB1.
Binding analysis by Simmons et al. (1999) showed that TRAP1 interacted
with the C-terminal ends of the proteins encoded by both multiple
exostoses-causing genes, EXT1 (608177) and EXT2, but not with EXTL1
(601738) or EXTL3 (605744). The interaction required the presence of a
his residue in the EXT proteins, the loss of which had been identified
in a single family with type I multiple exostoses (133700) by Raskind et
al. (1998).
Felts et al. (2000) reported that TRAP1 lacked the chaperone activities
of HSP90 and also failed to interact with cochaperones of HSP90.
However, TRAP1 did bind ATP and expressed an ATPase activity that could
be blocked by the HSP90 inhibitor geldanamycin.
GENE STRUCTURE
Chen et al. (2005) determined that the TRAP1 gene contains 19 exons.
MAPPING
Simmons et al. (1999) stated that the TRAP1 gene maps to chromosome 16.
By genomic sequence analysis, Chen et al. (2005) mapped the TRAP1 gene
to chromosome 16p13.3.
NOMENCLATURE
Chen et al. (2005) provided a revised nomenclature system for the HSP90
gene family. Under this system, the root HSP90A indicates cytosolic
HSP90, HSP90B indicates endoplasmic reticulum HSP90, and TRAP indicates
mitochondrial HSP90. HSP90A was divided into 2 classes, with HSP90AA
representing conventional HSP90-alpha, and HSP90AB representing
HSP90-beta. The number following the root/class represents the gene in
that class, and a 'P' at the end indicates a putative pseudogene. Chen
et al. (2005) also proposed the alias HSP90L for TRAP1.
*FIELD* RF
1. Chen, B.; Piel, W. H.; Gui, L.; Bruford, E.; Monteiro, A.: The
HSP90 family of genes in the human genome: insights into their divergence
and evolution. Genomics 86: 627-637, 2005.
2. Chen, C.-F.; Chen, Y.; Dai, K.; Chen, P.-L.; Riley, D. J.; Lee,
W.-H.: A new member of the hsp90 family of molecular chaperones interacts
with the retinoblastoma protein during mitosis and after heat shock. Molec.
Cell. Biol. 16: 4691-4699, 1996.
3. Felts, S. J.; Owen, B. A. L.; Nguyen, P.; Trepel, J.; Donner, D.
B.; Toft, D. O.: The hsp90-related protein TRAP1 is a mitochondrial
protein with distinct functional properties. J. Biol. Chem. 275:
3305-3312, 2000.
4. Raskind, W. H.; Conrad, E. U., III; Matsushita, M.; Wijsman, E.
M.; Wells, D. E.; Chapman, N.; Sandell, L. J.; Wagner, M.; Houck,
J.: Evaluation of locus heterogeneity and EXT1 mutations in 34 families
with hereditary multiple exostoses. Hum. Mutat. 11: 231-239, 1998.
5. Simmons, A. D.; Musy, M. M.; Lopes, C. S.; Hwang, L.-Y.; Yang,
Y.-P.; Lovett, M.: A direct interaction between EXT proteins and
glycosyltransferases is defective in hereditary multiple exostoses. Hum.
Molec. Genet. 8: 2155-2164, 1999.
6. Song, H. Y.; Dunbar, J. D.; Zhang, Y. X.; Guo, D.; Donner, D. B.
: Identification of a protein with homology to hsp90 that binds the
type 1 tumor necrosis factor receptor. J. Biol. Chem. 270: 3574-3581,
1995.
*FIELD* CN
Matthew B. Gross - updated: 8/12/2008
*FIELD* CD
Paul J. Converse: 8/22/2001
*FIELD* ED
alopez: 06/17/2011
carol: 11/5/2009
mgross: 8/12/2008
ckniffin: 10/30/2003
mgross: 8/22/2001