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Q12931 (TRAP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Heat shock protein 75 kDa, mitochondrial

Short name=HSP 75
Alternative name(s):
TNFR-associated protein 1
Tumor necrosis factor type 1 receptor-associated protein
Short name=TRAP-1
Gene names
Name:TRAP1
Synonyms:HSP75
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length704 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.11 Ref.12 Ref.13

Subunit structure

Binds to the intracellular domain of tumor necrosis factor type 1 receptor. Binds to RB1. Interacts with SRC. Interacts with SDHA. Ref.11 Ref.13

Subcellular location

Mitochondrion. Mitochondrion inner membrane. Mitochondrion matrix Ref.13.

Tissue specificity

Found in skeletal muscle, liver, heart, brain, kidney, pancreas, lung, placenta and bladder. Expression is higly reduced in bladder cancer and renal cell carcinoma specimens compared to healthy tissues, but it is increased in other type of tumors. Ref.13

Sequence similarities

Belongs to the heat shock protein 90 family.

Sequence caution

The sequence AAA87704.1 differs from that shown. Reason: Frameshift at position 656.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5959Mitochondrion By similarity
Chain60 – 704645Heat shock protein 75 kDa, mitochondrial HAMAP-Rule MF_00505
PRO_0000013604

Sites

Binding site1191ATP By similarity
Binding site1581ATP By similarity
Binding site1711ATP By similarity
Binding site2051ATP; via amide nitrogen By similarity
Binding site4021ATP By similarity

Amino acid modifications

Modified residue1701Phosphoserine By similarity
Modified residue1741Phosphothreonine By similarity
Modified residue2621N6-acetyllysine By similarity
Modified residue3241N6-acetyllysine By similarity
Modified residue3321N6-acetyllysine Ref.9
Modified residue4241N6-acetyllysine Ref.9
Modified residue4311N6-acetyllysine By similarity
Modified residue4661N6-acetyllysine Ref.9
Modified residue4941Phosphothreonine Ref.8

Natural variations

Natural variant3071R → G. Ref.1 Ref.5
Corresponds to variant rs13926 [ dbSNP | Ensembl ].
VAR_016108
Natural variant3951D → E. Ref.6
Corresponds to variant rs1136948 [ dbSNP | Ensembl ].
VAR_049625
Natural variant5721E → K.
Corresponds to variant rs55766649 [ dbSNP | Ensembl ].
VAR_061272
Natural variant6921R → H.
Corresponds to variant rs2791 [ dbSNP | Ensembl ].
VAR_049626

Experimental info

Sequence conflict17 – 193PLL → ALR in AAA87704. Ref.5
Sequence conflict531L → M in AAC02679. Ref.6
Sequence conflict475 – 4762Missing in AAC02679. Ref.6
Sequence conflict488 – 4914SRMR → AHW in AAC02679. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Q12931 [UniParc].

Last modified June 7, 2005. Version 3.
Checksum: 4B16DE3D2B9E0285

FASTA70480,110
        10         20         30         40         50         60 
MARELRALLL WGRRLRPLLR APALAAVPGG KPILCPRRTT AQLGPRRNPA WSLQAGRLFS 

        70         80         90        100        110        120 
TQTAEDKEEP LHSIISSTES VQGSTSKHEF QAETKKLLDI VARSLYSEKE VFIRELISNA 

       130        140        150        160        170        180 
SDALEKLRHK LVSDGQALPE MEIHLQTNAE KGTITIQDTG IGMTQEELVS NLGTIARSGS 

       190        200        210        220        230        240 
KAFLDALQNQ AEASSKIIGQ FGVGFYSAFM VADRVEVYSR SAAPGSLGYQ WLSDGSGVFE 

       250        260        270        280        290        300 
IAEASGVRTG TKIIIHLKSD CKEFSSEARV RDVVTKYSNF VSFPLYLNGR RMNTLQAIWM 

       310        320        330        340        350        360 
MDPKDVREWQ HEEFYRYVAQ AHDKPRYTLH YKTDAPLNIR SIFYVPDMKP SMFDVSRELG 

       370        380        390        400        410        420 
SSVALYSRKV LIQTKATDIL PKWLRFIRGV VDSEDIPLNL SRELLQESAL IRKLRDVLQQ 

       430        440        450        460        470        480 
RLIKFFIDQS KKDAEKYAKF FEDYGLFMRE GIVTATEQEV KEDIAKLLRY ESSALPSGQL 

       490        500        510        520        530        540 
TSLSEYASRM RAGTRNIYYL CAPNRHLAEH SPYYEAMKKK DTEVLFCFEQ FDELTLLHLR 

       550        560        570        580        590        600 
EFDKKKLISV ETDIVVDHYK EEKFEDRSPA AECLSEKETE ELMAWMRNVL GSRVTNVKVT 

       610        620        630        640        650        660 
LRLDTHPAMV TVLEMGAARH FLRMQQLAKT QEERAQLLQP TLEINPRHAL IKKLNQLRAS 

       670        680        690        700 
EPGLAQLLVD QIYENAMIAA GLVDDPRAMV GRLNELLVKA LERH 

« Hide

References

« Hide 'large scale' references
[1]"A direct interaction between EXT proteins and glycosyltransferases is defective in hereditary multiple exostoses."
Simmons A.D., Musy M.M., Lopes C.S., Hwang L.-Y., Yang Y.-P., Lovett M.
Hum. Mol. Genet. 8:2155-2164(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLY-307.
[2]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain and Eye.
[5]"Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor."
Song H.Y., Dunbar J.D., Zhang Y.X., Guo D., Donner D.B.
J. Biol. Chem. 270:3574-3581(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 16-704, VARIANT GLY-307.
[6]"A new member of the hsp90 family of molecular chaperones interacts with the retinoblastoma protein during mitosis and after heat shock."
Chen C.-F., Chen Y., Dai K., Chen P.-L., Riley D.J., Lee W.-H.
Mol. Cell. Biol. 16:4691-4699(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 53-704, VARIANT GLU-395.
[7]"The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties."
Felts S.J., Owen B.A.L., Nguyen P., Trepel J., Donner D.B., Toft D.O.
J. Biol. Chem. 275:3305-3312(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-494, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-332; LYS-424 AND LYS-466, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase."
Sciacovelli M., Guzzo G., Morello V., Frezza C., Zheng L., Nannini N., Calabrese F., Laudiero G., Esposito F., Landriscina M., Defilippi P., Bernardi P., Rasola A.
Cell Metab. 17:988-999(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS NEGATIVE REGULATOR OF MITOCHONDRIAL RESPIRATION, INTERACTION WITH SDHA.
[12]"TRAP1 rescues PINK1 loss-of-function phenotypes."
Zhang L., Karsten P., Hamm S., Pogson J.H., Muller-Rischart A.K., Exner N., Haass C., Whitworth A.J., Winklhofer K.F., Schulz J.B., Voigt A.
Hum. Mol. Genet. 22:2829-2841(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis."
Yoshida S., Tsutsumi S., Muhlebach G., Sourbier C., Lee M.J., Lee S., Vartholomaiou E., Tatokoro M., Beebe K., Miyajima N., Mohney R.P., Chen Y., Hasumi H., Xu W., Fukushima H., Nakamura K., Koga F., Kihara K. expand/collapse author list , Trepel J., Picard D., Neckers L.
Proc. Natl. Acad. Sci. U.S.A. 110:E1604-E1612(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS NEGATIVE REGULATOR OF MITOCHONDRIAL RESPIRATION, INTERACTION WITH SRC, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF154108 mRNA. Translation: AAF15314.1.
AC005203 Genomic DNA. Translation: AAC24722.1.
CH471112 Genomic DNA. Translation: EAW85338.1.
CH471112 Genomic DNA. Translation: EAW85340.1.
BC018950 mRNA. Translation: AAH18950.1.
BC023585 mRNA. Translation: AAH23585.1.
U12595 mRNA. Translation: AAA87704.1. Frameshift.
AF043254 mRNA. Translation: AAC02679.1.
RefSeqNP_057376.2. NM_016292.2.
UniGeneHs.30345.

3D structure databases

ProteinModelPortalQ12931.
SMRQ12931. Positions 84-697.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115435. 46 interactions.
DIPDIP-6250N.
IntActQ12931. 26 interactions.
MINTMINT-1510364.
STRING9606.ENSP00000246957.

Chemistry

BindingDBQ12931.
ChEMBLCHEMBL1075132.

PTM databases

PhosphoSiteQ12931.

Polymorphism databases

DMDM67477458.

2D gel databases

REPRODUCTION-2DPAGEIPI00030275.

Proteomic databases

PaxDbQ12931.
PeptideAtlasQ12931.
PRIDEQ12931.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000246957; ENSP00000246957; ENSG00000126602.
GeneID10131.
KEGGhsa:10131.
UCSCuc002cvs.3. human.

Organism-specific databases

CTD10131.
GeneCardsGC16M003710.
H-InvDBHIX0012776.
HGNCHGNC:16264. TRAP1.
HPAHPA041082.
HPA044227.
MIM606219. gene.
neXtProtNX_Q12931.
PharmGKBPA36781.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0326.
HOGENOMHOG000031987.
HOVERGENHBG103147.
InParanoidQ12931.
KOK09488.
OMAAHDKPRY.
OrthoDBEOG7C8GGM.
PhylomeDBQ12931.
TreeFamTF315234.

Gene expression databases

ArrayExpressQ12931.
BgeeQ12931.
CleanExHS_TRAP1.
GenevestigatorQ12931.

Family and domain databases

Gene3D3.30.565.10. 1 hit.
HAMAPMF_00505. HSP90.
InterProIPR003594. HATPase_ATP-bd.
IPR001404. Hsp90_fam.
IPR020575. Hsp90_N.
IPR020568. Ribosomal_S5_D2-typ_fold.
[Graphical view]
PANTHERPTHR11528. PTHR11528. 1 hit.
PfamPF02518. HATPase_c. 1 hit.
PF00183. HSP90. 1 hit.
[Graphical view]
PIRSFPIRSF002583. Hsp90. 1 hit.
PRINTSPR00775. HEATSHOCK90.
SMARTSM00387. HATPase_c. 1 hit.
[Graphical view]
SUPFAMSSF54211. SSF54211. 1 hit.
SSF55874. SSF55874. 1 hit.
ProtoNetSearch...

Other

ChiTaRSTRAP1. human.
GeneWikiTRAP1.
GenomeRNAi10131.
NextBio38323.
PROQ12931.
SOURCESearch...

Entry information

Entry nameTRAP1_HUMAN
AccessionPrimary (citable) accession number: Q12931
Secondary accession number(s): D3DUC8 expand/collapse secondary AC list , O43642, O75235, Q9UHL5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 7, 2005
Last modified: April 16, 2014
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM