Full text data of HSPD1
HSPD1
(HSP60)
[Confidence: high (present in two of the MS resources)]
60 kDa heat shock protein, mitochondrial (60 kDa chaperonin; Chaperonin 60; CPN60; Heat shock protein 60; HSP-60; Hsp60; HuCHA60; Mitochondrial matrix protein P1; P60 lymphocyte protein; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
60 kDa heat shock protein, mitochondrial (60 kDa chaperonin; Chaperonin 60; CPN60; Heat shock protein 60; HSP-60; Hsp60; HuCHA60; Mitochondrial matrix protein P1; P60 lymphocyte protein; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P10809
ID CH60_HUMAN Reviewed; 573 AA.
AC P10809; B2R5M6; Q38L19; Q9UCR6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1990, sequence version 2.
DT 22-JAN-2014, entry version 173.
DE RecName: Full=60 kDa heat shock protein, mitochondrial;
DE AltName: Full=60 kDa chaperonin;
DE AltName: Full=Chaperonin 60;
DE Short=CPN60;
DE AltName: Full=Heat shock protein 60;
DE Short=HSP-60;
DE Short=Hsp60;
DE AltName: Full=HuCHA60;
DE AltName: Full=Mitochondrial matrix protein P1;
DE AltName: Full=P60 lymphocyte protein;
DE Flags: Precursor;
GN Name=HSPD1; Synonyms=HSP60;
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].
RX PubMed=2568584;
RA Jindal S., Dudani A.K., Singh B., Harley C.B., Gupta R.S.;
RT "Primary structure of a human mitochondrial protein homologous to the
RT bacterial and plant chaperonins and to the 65-kilodalton mycobacterial
RT antigen.";
RL Mol. Cell. Biol. 9:2279-2283(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1980192; DOI=10.1089/dna.1990.9.545;
RA Venner T.J., Singh B., Gupta R.S.;
RT "Nucleotide sequences and novel structural features of human and
RT Chinese hamster hsp60 (chaperonin) gene families.";
RL DNA Cell Biol. 9:545-552(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12483302; DOI=10.1007/s00439-002-0837-9;
RA Hansen J.J., Bross P., Westergaard M., Nielsen M.N., Eiberg H.,
RA Boerglum A.D., Mogensen J., Kristiansen K., Bolund L., Gregersen N.;
RT "Genomic structure of the human mitochondrial chaperonin genes: HSP60
RT and HSP10 are localised head to head on chromosome 2 separated by a
RT bidirectional promoter.";
RL Hum. Genet. 112:71-77(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Tan J., Ong R., Hibberd M.L., Seielstad M.;
RT "Genetic variation in immune response genes.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, Skin, and Uterus;
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 [7]
RP PROTEIN SEQUENCE OF 27-573.
RX PubMed=2907406;
RA Waldinger D., Eckerskorn C., Lottspeich F., Cleve H.;
RT "Amino-acid sequence homology of a polymorphic cellular protein from
RT human lymphocytes and the chaperonins from Escherichia coli (groEL)
RT and chloroplasts (Rubisco-binding protein).";
RL Biol. Chem. Hoppe-Seyler 369:1185-1189(1988).
RN [8]
RP PROTEIN SEQUENCE OF 27-55.
RC TISSUE=Colon carcinoma;
RX PubMed=2079031; DOI=10.1002/elps.1150111019;
RA Ward L.D., Hong J., Whitehead R.H., Simpson R.J.;
RT "Development of a database of amino acid sequences for human colon
RT carcinoma proteins separated by two-dimensional polyacrylamide gel
RT electrophoresis.";
RL Electrophoresis 11:883-891(1990).
RN [9]
RP PROTEIN SEQUENCE OF 27-55, AND INTERACTION WITH HTLV-1 P40TAX.
RX PubMed=1731090;
RA Nagata K., Ide Y., Takagi T., Ohtani K., Aoshima M., Tozawa H.,
RA Nakamura M., Sugamura K.;
RT "Complex formation of human T-cell leukemia virus type I p40tax
RT transactivator with cellular polypeptides.";
RL J. Virol. 66:1040-1049(1992).
RN [10]
RP PROTEIN SEQUENCE OF 27-50.
RC TISSUE=Mammary carcinoma;
RX PubMed=9150946; DOI=10.1002/elps.1150180342;
RA Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E.,
RA Simpson R.J., Dorow D.S.;
RT "Two-dimensional electrophoretic analysis of human breast carcinoma
RT proteins: mapping of proteins that bind to the SH3 domain of mixed
RT lineage kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [11]
RP PROTEIN SEQUENCE OF 27-46.
RC TISSUE=Heart;
RX PubMed=7895732; DOI=10.1002/elps.11501501209;
RA Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J.;
RT "The human myocardial two-dimensional gel protein database: update
RT 1994.";
RL Electrophoresis 15:1459-1465(1994).
RN [12]
RP PROTEIN SEQUENCE OF 27-37.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [13]
RP PROTEIN SEQUENCE OF 27-35.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [14]
RP PROTEIN SEQUENCE OF 61-72, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [15]
RP PROTEIN SEQUENCE OF 61-72; 206-218; 237-249; 251-290; 430-446 AND
RP 463-469, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [16]
RP PROTEIN SEQUENCE OF 97-121; 251-268 AND 430-446.
RC TISSUE=Adipocyte;
RX PubMed=15242332; DOI=10.1042/BJ20040647;
RA Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.;
RT "Vectorial proteomics reveal targeting, phosphorylation and specific
RT fragmentation of polymerase I and transcript release factor (PTRF) at
RT the surface of caveolae in human adipocytes.";
RL Biochem. J. 383:237-248(2004).
RN [17]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [18]
RP MITOCHONDRIAL IMPORT.
RX PubMed=1972619; DOI=10.1016/0006-291X(90)90344-M;
RA Singh B., Patel H.V., Ridley R.G., Freeman K.B., Gupta R.S.;
RT "Mitochondrial import of the human chaperonin (HSP60) protein.";
RL Biochem. Biophys. Res. Commun. 169:391-396(1990).
RN [19]
RP INTERACTION WITH HBV PROTEIN X.
RX PubMed=15120623; DOI=10.1016/j.bbrc.2004.04.046;
RA Tanaka Y., Kanai F., Kawakami T., Tateishi K., Ijichi H., Kawabe T.,
RA Arakawa Y., Kawakami T., Nishimura T., Shirakata Y., Koike K.,
RA Omata M.;
RT "Interaction of the hepatitis B virus X protein (HBx) with heat shock
RT protein 60 enhances HBx-mediated apoptosis.";
RL Biochem. Biophys. Res. Commun. 318:461-469(2004).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, 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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-82; LYS-125; LYS-130;
RP LYS-202; LYS-218; LYS-269; LYS-352; LYS-359; LYS-396 AND LYS-469, AND
RP 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
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 [27]
RP MALONYLATION AT LYS-133.
RX PubMed=21908771; DOI=10.1074/mcp.M111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP INTERACTION WITH ATAD3A.
RX PubMed=22664726; DOI=10.1016/j.mito.2012.05.005;
RA Merle N., Feraud O., Gilquin B., Hubstenberger A.,
RA Kieffer-Jacquinot S., Assard N., Bennaceur-Griscelli A., Honnorat J.,
RA Baudier J.;
RT "ATAD3B is a human embryonic stem cell specific mitochondrial protein,
RT re-expressed in cancer cells, that functions as dominant negative for
RT the ubiquitous ATAD3A.";
RL Mitochondrion 12:441-448(2012).
RN [30]
RP INTERACTION WITH METTL20 AND METTL21B.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine
RT methyltransferases preferentially interact with molecular chaperones
RT to regulate their activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
RN [31]
RP VARIANT SPG13 ILE-98.
RX PubMed=11898127; DOI=10.1086/339935;
RA Hansen J.J., Durr A., Cournu-Rebeix I., Georgopoulos C., Ang D.,
RA Nielsen M.N., Davoine C.-S., Brice A., Fontaine B., Gregersen N.,
RA Bross P.;
RT "Hereditary spastic paraplegia SPG13 is associated with a mutation in
RT the gene encoding the mitochondrial chaperonin Hsp60.";
RL Am. J. Hum. Genet. 70:1328-1332(2002).
RN [32]
RP VARIANT HLD4 GLY-29, AND CHARACTERIZATION OF VARIANT HLD4 GLY-29.
RX PubMed=18571143; DOI=10.1016/j.ajhg.2008.05.016;
RA Magen D., Georgopoulos C., Bross P., Ang D., Segev Y., Goldsher D.,
RA Nemirovski A., Shahar E., Ravid S., Luder A., Heno B.,
RA Gershoni-Baruch R., Skorecki K., Mandel H.;
RT "Mitochondrial Hsp60 chaperonopathy causes an autosomal-recessive
RT neurodegenerative disorder linked to brain hypomyelination and
RT leukodystrophy.";
RL Am. J. Hum. Genet. 83:30-42(2008).
CC -!- FUNCTION: Implicated in mitochondrial protein import and
CC macromolecular assembly. May facilitate the correct folding of
CC imported proteins. May also prevent misfolding and promote the
CC refolding and proper assembly of unfolded polypeptides generated
CC under stress conditions in the mitochondrial matrix.
CC -!- SUBUNIT: Interacts with HRAS (By similarity). Interacts with HBV
CC protein X and HTLV-1 protein p40tax. Interacts with ATAD3A.
CC Interacts with METTL20 and METTL21B.
CC -!- INTERACTION:
CC P38398:BRCA1; NbExp=2; IntAct=EBI-352528, EBI-349905;
CC P49789:FHIT; NbExp=5; IntAct=EBI-352528, EBI-741760;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- DISEASE: Spastic paraplegia 13, autosomal dominant (SPG13)
CC [MIM:605280]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness
CC and spasticity of the lower limbs. Rate of progression and the
CC severity of symptoms are quite variable. Initial symptoms may
CC include difficulty with balance, weakness and stiffness in the
CC legs, muscle spasms, and dragging the toes when walking. In some
CC forms of the disorder, bladder symptoms (such as incontinence) may
CC appear, or the weakness and stiffness may spread to other parts of
CC the body. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- DISEASE: Leukodystrophy, hypomyelinating, 4 (HLD4) [MIM:612233]: A
CC severe autosomal recessive hypomyelinating leukodystrophy.
CC Clinically characterized by infantile-onset rotary nystagmus,
CC progressive spastic paraplegia, neurologic regression, motor
CC impairment, profound mental retardation. Death usually occurs
CC within the first two decades of life. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the chaperonin (HSP60) family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HSPD1";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HSPD1ID40888ch2q33.html";
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DR EMBL; M22382; AAA60127.1; -; mRNA.
DR EMBL; M34664; AAA36022.1; -; mRNA.
DR EMBL; AJ250915; CAB75426.1; -; Genomic_DNA.
DR EMBL; DQ217936; ABB01006.1; -; Genomic_DNA.
DR EMBL; AK312240; BAG35173.1; -; mRNA.
DR EMBL; BC002676; AAH02676.1; -; mRNA.
DR EMBL; BC003030; AAH03030.1; -; mRNA.
DR EMBL; BC067082; AAH67082.1; -; mRNA.
DR EMBL; BC073746; AAH73746.1; -; mRNA.
DR PIR; A32800; A32800.
DR RefSeq; NP_002147.2; NM_002156.4.
DR RefSeq; NP_955472.1; NM_199440.1.
DR RefSeq; XP_005246575.1; XM_005246518.1.
DR UniGene; Hs.595053; -.
DR UniGene; Hs.727543; -.
DR ProteinModelPortal; P10809; -.
DR SMR; P10809; 27-550.
DR DIP; DIP-58N; -.
DR IntAct; P10809; 60.
DR MINT; MINT-1162735; -.
DR STRING; 9606.ENSP00000340019; -.
DR ChEMBL; CHEMBL4721; -.
DR PhosphoSite; P10809; -.
DR DMDM; 129379; -.
DR DOSAC-COBS-2DPAGE; P10809; -.
DR OGP; P10809; -.
DR REPRODUCTION-2DPAGE; IPI00784154; -.
DR REPRODUCTION-2DPAGE; P10809; -.
DR SWISS-2DPAGE; P10809; -.
DR UCD-2DPAGE; P10809; -.
DR PaxDb; P10809; -.
DR PRIDE; P10809; -.
DR DNASU; 3329; -.
DR Ensembl; ENST00000345042; ENSP00000340019; ENSG00000144381.
DR Ensembl; ENST00000388968; ENSP00000373620; ENSG00000144381.
DR GeneID; 3329; -.
DR KEGG; hsa:3329; -.
DR UCSC; uc002uui.3; human.
DR CTD; 3329; -.
DR GeneCards; GC02M198315; -.
DR HGNC; HGNC:5261; HSPD1.
DR HPA; CAB002775; -.
DR HPA; HPA001523; -.
DR MIM; 118190; gene.
DR MIM; 605280; phenotype.
DR MIM; 612233; phenotype.
DR neXtProt; NX_P10809; -.
DR Orphanet; 100994; Autosomal dominant spastic paraplegia type 13.
DR Orphanet; 280288; Pelizaeus-Merzbacher-like due to HSPD1 mutation.
DR PharmGKB; PA29527; -.
DR eggNOG; COG0459; -.
DR HOGENOM; HOG000076290; -.
DR HOVERGEN; HBG001982; -.
DR InParanoid; P10809; -.
DR KO; K04077; -.
DR OMA; NMKELLP; -.
DR OrthoDB; EOG7HTHGJ; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; HSPD1; human.
DR GeneWiki; GroEL; -.
DR GenomeRNAi; 3329; -.
DR NextBio; 13188; -.
DR PRO; PR:P10809; -.
DR ArrayExpress; P10809; -.
DR Bgee; P10809; -.
DR CleanEx; HS_HSPD1; -.
DR Genevestigator; P10809; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005905; C:coated pit; IDA:BHF-UCL.
DR GO; GO:0030135; C:coated vesicle; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0046696; C:lipopolysaccharide receptor complex; IDA:BHF-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:BHF-UCL.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0030141; C:secretory granule; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATPase activity; ISS:BHF-UCL.
DR GO; GO:0003688; F:DNA replication origin binding; ISS:BHF-UCL.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:BHF-UCL.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:BHF-UCL.
DR GO; GO:0051082; F:unfolded protein binding; IC:UniProtKB.
DR GO; GO:0006458; P:'de novo' protein folding; ISS:BHF-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:BHF-UCL.
DR GO; GO:0002368; P:B cell cytokine production; IDA:BHF-UCL.
DR GO; GO:0042100; P:B cell proliferation; IDA:BHF-UCL.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; ISS:BHF-UCL.
DR GO; GO:0048291; P:isotype switching to IgG isotypes; IDA:BHF-UCL.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:BHF-UCL.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:BHF-UCL.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:BHF-UCL.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:BHF-UCL.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IDA:BHF-UCL.
DR GO; GO:0050870; P:positive regulation of T cell activation; IDA:BHF-UCL.
DR GO; GO:0002842; P:positive regulation of T cell mediated immune response to tumor cell; IDA:BHF-UCL.
DR GO; GO:0051604; P:protein maturation; ISS:BHF-UCL.
DR GO; GO:0042026; P:protein refolding; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; IDA:BHF-UCL.
DR GO; GO:0042110; P:T cell activation; IDA:MGI.
DR Gene3D; 1.10.560.10; -; 2.
DR Gene3D; 3.50.7.10; -; 1.
DR InterPro; IPR018370; Chaperonin_Cpn60_CS.
DR InterPro; IPR001844; Chaprnin_Cpn60.
DR InterPro; IPR002423; Cpn60/TCP-1.
DR InterPro; IPR027409; GroEL-like_apical_dom.
DR InterPro; IPR027413; GROEL-like_equatorial.
DR PANTHER; PTHR11353; PTHR11353; 1.
DR Pfam; PF00118; Cpn60_TCP1; 1.
DR PRINTS; PR00298; CHAPERONIN60.
DR SUPFAM; SSF48592; SSF48592; 2.
DR SUPFAM; SSF52029; SSF52029; 1.
DR TIGRFAMs; TIGR02348; GroEL; 1.
DR PROSITE; PS00296; CHAPERONINS_CPN60; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Chaperone; Complete proteome;
KW Direct protein sequencing; Disease mutation;
KW Hereditary spastic paraplegia; Host-virus interaction; Leukodystrophy;
KW Mitochondrion; Neurodegeneration; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1 26 Mitochondrion.
FT CHAIN 27 573 60 kDa heat shock protein, mitochondrial.
FT /FTId=PRO_0000005026.
FT MOD_RES 70 70 Phosphoserine.
FT MOD_RES 75 75 N6-acetyllysine (By similarity).
FT MOD_RES 82 82 N6-acetyllysine.
FT MOD_RES 87 87 N6-acetyllysine (By similarity).
FT MOD_RES 91 91 N6-acetyllysine (By similarity).
FT MOD_RES 125 125 N6-acetyllysine.
FT MOD_RES 130 130 N6-acetyllysine.
FT MOD_RES 133 133 N6-acetyllysine; alternate (By
FT similarity).
FT MOD_RES 133 133 N6-malonyllysine; alternate.
FT MOD_RES 156 156 N6-acetyllysine (By similarity).
FT MOD_RES 191 191 N6-acetyllysine (By similarity).
FT MOD_RES 202 202 N6-acetyllysine.
FT MOD_RES 205 205 N6-acetyllysine (By similarity).
FT MOD_RES 218 218 N6-acetyllysine.
FT MOD_RES 236 236 N6-acetyllysine (By similarity).
FT MOD_RES 249 249 N6-acetyllysine (By similarity).
FT MOD_RES 250 250 N6-acetyllysine (By similarity).
FT MOD_RES 269 269 N6-acetyllysine.
FT MOD_RES 292 292 N6-acetyllysine (By similarity).
FT MOD_RES 314 314 N6-acetyllysine (By similarity).
FT MOD_RES 352 352 N6-acetyllysine.
FT MOD_RES 359 359 N6-acetyllysine.
FT MOD_RES 389 389 N6-acetyllysine (By similarity).
FT MOD_RES 396 396 N6-acetyllysine.
FT MOD_RES 410 410 Phosphoserine (By similarity).
FT MOD_RES 469 469 N6-acetyllysine.
FT MOD_RES 481 481 N6-acetyllysine (By similarity).
FT VARIANT 29 29 D -> G (in HLD4; transfection with the
FT mutant protein impairs cell growth that
FT worsens with increasing temperature).
FT /FTId=VAR_054785.
FT VARIANT 98 98 V -> I (in SPG13).
FT /FTId=VAR_026748.
FT CONFLICT 67 67 S -> G (in Ref. 2; AAA36022).
FT CONFLICT 111 111 D -> N (in Ref. 5; BAG35173).
FT CONFLICT 177 177 N -> S (in Ref. 5; BAG35173).
FT CONFLICT 202 202 K -> KAS (in Ref. 4; ABB01006).
FT CONFLICT 260 260 A -> T (in Ref. 5; BAG35173).
SQ SEQUENCE 573 AA; 61055 MW; E51E1BAD9615899C CRC64;
MLRLPTVFRQ MRPVSRVLAP HLTRAYAKDV KFGADARALM LQGVDLLADA VAVTMGPKGR
TVIIEQSWGS PKVTKDGVTV AKSIDLKDKY KNIGAKLVQD VANNTNEEAG DGTTTATVLA
RSIAKEGFEK ISKGANPVEI RRGVMLAVDA VIAELKKQSK PVTTPEEIAQ VATISANGDK
EIGNIISDAM KKVGRKGVIT VKDGKTLNDE LEIIEGMKFD RGYISPYFIN TSKGQKCEFQ
DAYVLLSEKK ISSIQSIVPA LEIANAHRKP LVIIAEDVDG EALSTLVLNR LKVGLQVVAV
KAPGFGDNRK NQLKDMAIAT GGAVFGEEGL TLNLEDVQPH DLGKVGEVIV TKDDAMLLKG
KGDKAQIEKR IQEIIEQLDV TTSEYEKEKL NERLAKLSDG VAVLKVGGTS DVEVNEKKDR
VTDALNATRA AVEEGIVLGG GCALLRCIPA LDSLTPANED QKIGIEIIKR TLKIPAMTIA
KNAGVEGSLI VEKIMQSSSE VGYDAMAGDF VNMVEKGIID PTKVVRTALL DAAGVASLLT
TAEVVVTEIP KEEKDPGMGA MGGMGGGMGG GMF
//
ID CH60_HUMAN Reviewed; 573 AA.
AC P10809; B2R5M6; Q38L19; Q9UCR6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-AUG-1990, sequence version 2.
DT 22-JAN-2014, entry version 173.
DE RecName: Full=60 kDa heat shock protein, mitochondrial;
DE AltName: Full=60 kDa chaperonin;
DE AltName: Full=Chaperonin 60;
DE Short=CPN60;
DE AltName: Full=Heat shock protein 60;
DE Short=HSP-60;
DE Short=Hsp60;
DE AltName: Full=HuCHA60;
DE AltName: Full=Mitochondrial matrix protein P1;
DE AltName: Full=P60 lymphocyte protein;
DE Flags: Precursor;
GN Name=HSPD1; Synonyms=HSP60;
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].
RX PubMed=2568584;
RA Jindal S., Dudani A.K., Singh B., Harley C.B., Gupta R.S.;
RT "Primary structure of a human mitochondrial protein homologous to the
RT bacterial and plant chaperonins and to the 65-kilodalton mycobacterial
RT antigen.";
RL Mol. Cell. Biol. 9:2279-2283(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1980192; DOI=10.1089/dna.1990.9.545;
RA Venner T.J., Singh B., Gupta R.S.;
RT "Nucleotide sequences and novel structural features of human and
RT Chinese hamster hsp60 (chaperonin) gene families.";
RL DNA Cell Biol. 9:545-552(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12483302; DOI=10.1007/s00439-002-0837-9;
RA Hansen J.J., Bross P., Westergaard M., Nielsen M.N., Eiberg H.,
RA Boerglum A.D., Mogensen J., Kristiansen K., Bolund L., Gregersen N.;
RT "Genomic structure of the human mitochondrial chaperonin genes: HSP60
RT and HSP10 are localised head to head on chromosome 2 separated by a
RT bidirectional promoter.";
RL Hum. Genet. 112:71-77(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Tan J., Ong R., Hibberd M.L., Seielstad M.;
RT "Genetic variation in immune response genes.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, Skin, and Uterus;
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 [7]
RP PROTEIN SEQUENCE OF 27-573.
RX PubMed=2907406;
RA Waldinger D., Eckerskorn C., Lottspeich F., Cleve H.;
RT "Amino-acid sequence homology of a polymorphic cellular protein from
RT human lymphocytes and the chaperonins from Escherichia coli (groEL)
RT and chloroplasts (Rubisco-binding protein).";
RL Biol. Chem. Hoppe-Seyler 369:1185-1189(1988).
RN [8]
RP PROTEIN SEQUENCE OF 27-55.
RC TISSUE=Colon carcinoma;
RX PubMed=2079031; DOI=10.1002/elps.1150111019;
RA Ward L.D., Hong J., Whitehead R.H., Simpson R.J.;
RT "Development of a database of amino acid sequences for human colon
RT carcinoma proteins separated by two-dimensional polyacrylamide gel
RT electrophoresis.";
RL Electrophoresis 11:883-891(1990).
RN [9]
RP PROTEIN SEQUENCE OF 27-55, AND INTERACTION WITH HTLV-1 P40TAX.
RX PubMed=1731090;
RA Nagata K., Ide Y., Takagi T., Ohtani K., Aoshima M., Tozawa H.,
RA Nakamura M., Sugamura K.;
RT "Complex formation of human T-cell leukemia virus type I p40tax
RT transactivator with cellular polypeptides.";
RL J. Virol. 66:1040-1049(1992).
RN [10]
RP PROTEIN SEQUENCE OF 27-50.
RC TISSUE=Mammary carcinoma;
RX PubMed=9150946; DOI=10.1002/elps.1150180342;
RA Rasmussen R.K., Ji H., Eddes J.S., Moritz R.L., Reid G.E.,
RA Simpson R.J., Dorow D.S.;
RT "Two-dimensional electrophoretic analysis of human breast carcinoma
RT proteins: mapping of proteins that bind to the SH3 domain of mixed
RT lineage kinase MLK2.";
RL Electrophoresis 18:588-598(1997).
RN [11]
RP PROTEIN SEQUENCE OF 27-46.
RC TISSUE=Heart;
RX PubMed=7895732; DOI=10.1002/elps.11501501209;
RA Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J.;
RT "The human myocardial two-dimensional gel protein database: update
RT 1994.";
RL Electrophoresis 15:1459-1465(1994).
RN [12]
RP PROTEIN SEQUENCE OF 27-37.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [13]
RP PROTEIN SEQUENCE OF 27-35.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [14]
RP PROTEIN SEQUENCE OF 61-72, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (OCT-2004) to UniProtKB.
RN [15]
RP PROTEIN SEQUENCE OF 61-72; 206-218; 237-249; 251-290; 430-446 AND
RP 463-469, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [16]
RP PROTEIN SEQUENCE OF 97-121; 251-268 AND 430-446.
RC TISSUE=Adipocyte;
RX PubMed=15242332; DOI=10.1042/BJ20040647;
RA Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.;
RT "Vectorial proteomics reveal targeting, phosphorylation and specific
RT fragmentation of polymerase I and transcript release factor (PTRF) at
RT the surface of caveolae in human adipocytes.";
RL Biochem. J. 383:237-248(2004).
RN [17]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Colon carcinoma;
RX PubMed=9150948; DOI=10.1002/elps.1150180344;
RA Ji H., Reid G.E., Moritz R.L., Eddes J.S., Burgess A.W., Simpson R.J.;
RT "A two-dimensional gel database of human colon carcinoma proteins.";
RL Electrophoresis 18:605-613(1997).
RN [18]
RP MITOCHONDRIAL IMPORT.
RX PubMed=1972619; DOI=10.1016/0006-291X(90)90344-M;
RA Singh B., Patel H.V., Ridley R.G., Freeman K.B., Gupta R.S.;
RT "Mitochondrial import of the human chaperonin (HSP60) protein.";
RL Biochem. Biophys. Res. Commun. 169:391-396(1990).
RN [19]
RP INTERACTION WITH HBV PROTEIN X.
RX PubMed=15120623; DOI=10.1016/j.bbrc.2004.04.046;
RA Tanaka Y., Kanai F., Kawakami T., Tateishi K., Ijichi H., Kawabe T.,
RA Arakawa Y., Kawakami T., Nishimura T., Shirakata Y., Koike K.,
RA Omata M.;
RT "Interaction of the hepatitis B virus X protein (HBx) with heat shock
RT protein 60 enhances HBx-mediated apoptosis.";
RL Biochem. Biophys. Res. Commun. 318:461-469(2004).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, 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 [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-82; LYS-125; LYS-130;
RP LYS-202; LYS-218; LYS-269; LYS-352; LYS-359; LYS-396 AND LYS-469, AND
RP 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [26]
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 [27]
RP MALONYLATION AT LYS-133.
RX PubMed=21908771; DOI=10.1074/mcp.M111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP INTERACTION WITH ATAD3A.
RX PubMed=22664726; DOI=10.1016/j.mito.2012.05.005;
RA Merle N., Feraud O., Gilquin B., Hubstenberger A.,
RA Kieffer-Jacquinot S., Assard N., Bennaceur-Griscelli A., Honnorat J.,
RA Baudier J.;
RT "ATAD3B is a human embryonic stem cell specific mitochondrial protein,
RT re-expressed in cancer cells, that functions as dominant negative for
RT the ubiquitous ATAD3A.";
RL Mitochondrion 12:441-448(2012).
RN [30]
RP INTERACTION WITH METTL20 AND METTL21B.
RX PubMed=23349634; DOI=10.1371/journal.pgen.1003210;
RA Cloutier P., Lavallee-Adam M., Faubert D., Blanchette M., Coulombe B.;
RT "A newly uncovered group of distantly related lysine
RT methyltransferases preferentially interact with molecular chaperones
RT to regulate their activity.";
RL PLoS Genet. 9:E1003210-E1003210(2013).
RN [31]
RP VARIANT SPG13 ILE-98.
RX PubMed=11898127; DOI=10.1086/339935;
RA Hansen J.J., Durr A., Cournu-Rebeix I., Georgopoulos C., Ang D.,
RA Nielsen M.N., Davoine C.-S., Brice A., Fontaine B., Gregersen N.,
RA Bross P.;
RT "Hereditary spastic paraplegia SPG13 is associated with a mutation in
RT the gene encoding the mitochondrial chaperonin Hsp60.";
RL Am. J. Hum. Genet. 70:1328-1332(2002).
RN [32]
RP VARIANT HLD4 GLY-29, AND CHARACTERIZATION OF VARIANT HLD4 GLY-29.
RX PubMed=18571143; DOI=10.1016/j.ajhg.2008.05.016;
RA Magen D., Georgopoulos C., Bross P., Ang D., Segev Y., Goldsher D.,
RA Nemirovski A., Shahar E., Ravid S., Luder A., Heno B.,
RA Gershoni-Baruch R., Skorecki K., Mandel H.;
RT "Mitochondrial Hsp60 chaperonopathy causes an autosomal-recessive
RT neurodegenerative disorder linked to brain hypomyelination and
RT leukodystrophy.";
RL Am. J. Hum. Genet. 83:30-42(2008).
CC -!- FUNCTION: Implicated in mitochondrial protein import and
CC macromolecular assembly. May facilitate the correct folding of
CC imported proteins. May also prevent misfolding and promote the
CC refolding and proper assembly of unfolded polypeptides generated
CC under stress conditions in the mitochondrial matrix.
CC -!- SUBUNIT: Interacts with HRAS (By similarity). Interacts with HBV
CC protein X and HTLV-1 protein p40tax. Interacts with ATAD3A.
CC Interacts with METTL20 and METTL21B.
CC -!- INTERACTION:
CC P38398:BRCA1; NbExp=2; IntAct=EBI-352528, EBI-349905;
CC P49789:FHIT; NbExp=5; IntAct=EBI-352528, EBI-741760;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC -!- DISEASE: Spastic paraplegia 13, autosomal dominant (SPG13)
CC [MIM:605280]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness
CC and spasticity of the lower limbs. Rate of progression and the
CC severity of symptoms are quite variable. Initial symptoms may
CC include difficulty with balance, weakness and stiffness in the
CC legs, muscle spasms, and dragging the toes when walking. In some
CC forms of the disorder, bladder symptoms (such as incontinence) may
CC appear, or the weakness and stiffness may spread to other parts of
CC the body. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- DISEASE: Leukodystrophy, hypomyelinating, 4 (HLD4) [MIM:612233]: A
CC severe autosomal recessive hypomyelinating leukodystrophy.
CC Clinically characterized by infantile-onset rotary nystagmus,
CC progressive spastic paraplegia, neurologic regression, motor
CC impairment, profound mental retardation. Death usually occurs
CC within the first two decades of life. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the chaperonin (HSP60) family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HSPD1";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/HSPD1ID40888ch2q33.html";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; M22382; AAA60127.1; -; mRNA.
DR EMBL; M34664; AAA36022.1; -; mRNA.
DR EMBL; AJ250915; CAB75426.1; -; Genomic_DNA.
DR EMBL; DQ217936; ABB01006.1; -; Genomic_DNA.
DR EMBL; AK312240; BAG35173.1; -; mRNA.
DR EMBL; BC002676; AAH02676.1; -; mRNA.
DR EMBL; BC003030; AAH03030.1; -; mRNA.
DR EMBL; BC067082; AAH67082.1; -; mRNA.
DR EMBL; BC073746; AAH73746.1; -; mRNA.
DR PIR; A32800; A32800.
DR RefSeq; NP_002147.2; NM_002156.4.
DR RefSeq; NP_955472.1; NM_199440.1.
DR RefSeq; XP_005246575.1; XM_005246518.1.
DR UniGene; Hs.595053; -.
DR UniGene; Hs.727543; -.
DR ProteinModelPortal; P10809; -.
DR SMR; P10809; 27-550.
DR DIP; DIP-58N; -.
DR IntAct; P10809; 60.
DR MINT; MINT-1162735; -.
DR STRING; 9606.ENSP00000340019; -.
DR ChEMBL; CHEMBL4721; -.
DR PhosphoSite; P10809; -.
DR DMDM; 129379; -.
DR DOSAC-COBS-2DPAGE; P10809; -.
DR OGP; P10809; -.
DR REPRODUCTION-2DPAGE; IPI00784154; -.
DR REPRODUCTION-2DPAGE; P10809; -.
DR SWISS-2DPAGE; P10809; -.
DR UCD-2DPAGE; P10809; -.
DR PaxDb; P10809; -.
DR PRIDE; P10809; -.
DR DNASU; 3329; -.
DR Ensembl; ENST00000345042; ENSP00000340019; ENSG00000144381.
DR Ensembl; ENST00000388968; ENSP00000373620; ENSG00000144381.
DR GeneID; 3329; -.
DR KEGG; hsa:3329; -.
DR UCSC; uc002uui.3; human.
DR CTD; 3329; -.
DR GeneCards; GC02M198315; -.
DR HGNC; HGNC:5261; HSPD1.
DR HPA; CAB002775; -.
DR HPA; HPA001523; -.
DR MIM; 118190; gene.
DR MIM; 605280; phenotype.
DR MIM; 612233; phenotype.
DR neXtProt; NX_P10809; -.
DR Orphanet; 100994; Autosomal dominant spastic paraplegia type 13.
DR Orphanet; 280288; Pelizaeus-Merzbacher-like due to HSPD1 mutation.
DR PharmGKB; PA29527; -.
DR eggNOG; COG0459; -.
DR HOGENOM; HOG000076290; -.
DR HOVERGEN; HBG001982; -.
DR InParanoid; P10809; -.
DR KO; K04077; -.
DR OMA; NMKELLP; -.
DR OrthoDB; EOG7HTHGJ; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; HSPD1; human.
DR GeneWiki; GroEL; -.
DR GenomeRNAi; 3329; -.
DR NextBio; 13188; -.
DR PRO; PR:P10809; -.
DR ArrayExpress; P10809; -.
DR Bgee; P10809; -.
DR CleanEx; HS_HSPD1; -.
DR Genevestigator; P10809; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005905; C:coated pit; IDA:BHF-UCL.
DR GO; GO:0030135; C:coated vesicle; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0046696; C:lipopolysaccharide receptor complex; IDA:BHF-UCL.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:BHF-UCL.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0030141; C:secretory granule; ISS:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATPase activity; ISS:BHF-UCL.
DR GO; GO:0003688; F:DNA replication origin binding; ISS:BHF-UCL.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:BHF-UCL.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:BHF-UCL.
DR GO; GO:0051082; F:unfolded protein binding; IC:UniProtKB.
DR GO; GO:0006458; P:'de novo' protein folding; ISS:BHF-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:BHF-UCL.
DR GO; GO:0002368; P:B cell cytokine production; IDA:BHF-UCL.
DR GO; GO:0042100; P:B cell proliferation; IDA:BHF-UCL.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; ISS:BHF-UCL.
DR GO; GO:0048291; P:isotype switching to IgG isotypes; IDA:BHF-UCL.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:BHF-UCL.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:BHF-UCL.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:BHF-UCL.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:BHF-UCL.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IDA:BHF-UCL.
DR GO; GO:0050870; P:positive regulation of T cell activation; IDA:BHF-UCL.
DR GO; GO:0002842; P:positive regulation of T cell mediated immune response to tumor cell; IDA:BHF-UCL.
DR GO; GO:0051604; P:protein maturation; ISS:BHF-UCL.
DR GO; GO:0042026; P:protein refolding; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; IDA:BHF-UCL.
DR GO; GO:0042110; P:T cell activation; IDA:MGI.
DR Gene3D; 1.10.560.10; -; 2.
DR Gene3D; 3.50.7.10; -; 1.
DR InterPro; IPR018370; Chaperonin_Cpn60_CS.
DR InterPro; IPR001844; Chaprnin_Cpn60.
DR InterPro; IPR002423; Cpn60/TCP-1.
DR InterPro; IPR027409; GroEL-like_apical_dom.
DR InterPro; IPR027413; GROEL-like_equatorial.
DR PANTHER; PTHR11353; PTHR11353; 1.
DR Pfam; PF00118; Cpn60_TCP1; 1.
DR PRINTS; PR00298; CHAPERONIN60.
DR SUPFAM; SSF48592; SSF48592; 2.
DR SUPFAM; SSF52029; SSF52029; 1.
DR TIGRFAMs; TIGR02348; GroEL; 1.
DR PROSITE; PS00296; CHAPERONINS_CPN60; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Chaperone; Complete proteome;
KW Direct protein sequencing; Disease mutation;
KW Hereditary spastic paraplegia; Host-virus interaction; Leukodystrophy;
KW Mitochondrion; Neurodegeneration; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1 26 Mitochondrion.
FT CHAIN 27 573 60 kDa heat shock protein, mitochondrial.
FT /FTId=PRO_0000005026.
FT MOD_RES 70 70 Phosphoserine.
FT MOD_RES 75 75 N6-acetyllysine (By similarity).
FT MOD_RES 82 82 N6-acetyllysine.
FT MOD_RES 87 87 N6-acetyllysine (By similarity).
FT MOD_RES 91 91 N6-acetyllysine (By similarity).
FT MOD_RES 125 125 N6-acetyllysine.
FT MOD_RES 130 130 N6-acetyllysine.
FT MOD_RES 133 133 N6-acetyllysine; alternate (By
FT similarity).
FT MOD_RES 133 133 N6-malonyllysine; alternate.
FT MOD_RES 156 156 N6-acetyllysine (By similarity).
FT MOD_RES 191 191 N6-acetyllysine (By similarity).
FT MOD_RES 202 202 N6-acetyllysine.
FT MOD_RES 205 205 N6-acetyllysine (By similarity).
FT MOD_RES 218 218 N6-acetyllysine.
FT MOD_RES 236 236 N6-acetyllysine (By similarity).
FT MOD_RES 249 249 N6-acetyllysine (By similarity).
FT MOD_RES 250 250 N6-acetyllysine (By similarity).
FT MOD_RES 269 269 N6-acetyllysine.
FT MOD_RES 292 292 N6-acetyllysine (By similarity).
FT MOD_RES 314 314 N6-acetyllysine (By similarity).
FT MOD_RES 352 352 N6-acetyllysine.
FT MOD_RES 359 359 N6-acetyllysine.
FT MOD_RES 389 389 N6-acetyllysine (By similarity).
FT MOD_RES 396 396 N6-acetyllysine.
FT MOD_RES 410 410 Phosphoserine (By similarity).
FT MOD_RES 469 469 N6-acetyllysine.
FT MOD_RES 481 481 N6-acetyllysine (By similarity).
FT VARIANT 29 29 D -> G (in HLD4; transfection with the
FT mutant protein impairs cell growth that
FT worsens with increasing temperature).
FT /FTId=VAR_054785.
FT VARIANT 98 98 V -> I (in SPG13).
FT /FTId=VAR_026748.
FT CONFLICT 67 67 S -> G (in Ref. 2; AAA36022).
FT CONFLICT 111 111 D -> N (in Ref. 5; BAG35173).
FT CONFLICT 177 177 N -> S (in Ref. 5; BAG35173).
FT CONFLICT 202 202 K -> KAS (in Ref. 4; ABB01006).
FT CONFLICT 260 260 A -> T (in Ref. 5; BAG35173).
SQ SEQUENCE 573 AA; 61055 MW; E51E1BAD9615899C CRC64;
MLRLPTVFRQ MRPVSRVLAP HLTRAYAKDV KFGADARALM LQGVDLLADA VAVTMGPKGR
TVIIEQSWGS PKVTKDGVTV AKSIDLKDKY KNIGAKLVQD VANNTNEEAG DGTTTATVLA
RSIAKEGFEK ISKGANPVEI RRGVMLAVDA VIAELKKQSK PVTTPEEIAQ VATISANGDK
EIGNIISDAM KKVGRKGVIT VKDGKTLNDE LEIIEGMKFD RGYISPYFIN TSKGQKCEFQ
DAYVLLSEKK ISSIQSIVPA LEIANAHRKP LVIIAEDVDG EALSTLVLNR LKVGLQVVAV
KAPGFGDNRK NQLKDMAIAT GGAVFGEEGL TLNLEDVQPH DLGKVGEVIV TKDDAMLLKG
KGDKAQIEKR IQEIIEQLDV TTSEYEKEKL NERLAKLSDG VAVLKVGGTS DVEVNEKKDR
VTDALNATRA AVEEGIVLGG GCALLRCIPA LDSLTPANED QKIGIEIIKR TLKIPAMTIA
KNAGVEGSLI VEKIMQSSSE VGYDAMAGDF VNMVEKGIID PTKVVRTALL DAAGVASLLT
TAEVVVTEIP KEEKDPGMGA MGGMGGGMGG GMF
//
MIM
118190
*RECORD*
*FIELD* NO
118190
*FIELD* TI
*118190 HEAT-SHOCK 60-KD PROTEIN 1; HSPD1
;;HSP60;;
CHAPERONIN, 60-KD; CPN60;;
GroEL, E. COLI, HOMOLOG OF
read more*FIELD* TX
DESCRIPTION
It had long been assumed that all information necessary for proper
folding of proteins and their assembly into oligomeric complexes was
contained within the primary sequence of the polypeptides and that no
catalyst or other accessory proteins were involved in this process.
However, this basic tenet of biochemistry was challenged by the
discovery of chaperonins, which are involved in the folding and assembly
of a number of different proteins (Cheng et al., 1989; Ellis, 1990;
Rothman, 1989). Members of the chaperonin family include the GroEL
protein of E. coli and HSP60, a protein present in eukaryotic cell
mitochondria. In both prokaryotic and eukaryotic systems, synthesis of
these proteins is induced in response to stresses, such as heat shock
(Venner et al., 1990).
CLONING
Venner et al. (1990) presented evidence of the existence of multiple
copies of the HSP60 gene in the human. All except one of these genes are
nonfunctional pseudogenes containing numerous changes such as base
substitutions, insertions, and deletions.
BIOCHEMICAL FEATURES
Azem et al. (1994) performed chemical crosslinking and electron
microscopy studies on bacterial chaperonins GroEL and GroES (HSPE1;
600141) to determine how they interact with unfolded proteins. GroEL is
an oligomer of 14 identical 57.3-kD subunits, with a structure of 2
stacked heptameric rings arranged around a 2-fold axis of symmetry
(Saibil et al., 1991). It appears as a hollow cylinder. In the presence
of ATP, 2 GroES rings (each made of 7 identical 10.4-kD subunits) can
successively bind a single GroEL core to make a functional symmetric
heterodimer. Although the central core of GroEL is obstructed by the 2
GroES rings at each end, this heterodimer can stably bind and assist the
refolding of the RuBisCo enzyme. While binding was thought to occur in
the central cavity, these data indicate that unfolded proteins may bind
and fold on the external envelope of some chaperonins (Azem et al.,
1994). Schmidt et al. (1994) suggested that the symmetric chaperonin
complex is functionally significant because complete folding of a
nonnative substrate protein in the presence of GroEL and GroES occurs
only in the presence of ATP, and not with ADP. Chaperonin-assisted
folding occurs by a catalytic cycle in which one ATP is hydrolyzed by
one ring of GroEL in a quantized manner with each turnover. Todd et al.
(1994) proposed a unifying model for chaperonin-facilitated protein
folding based on successive rounds of binding and release, and
partitioning between committed and kinetically trapped intermediates.
GENE FUNCTION
Zal et al. (2004) examined the antigen recognition of CD4
(186940)-positive/CD28 (186760)-null T lymphocytes from 21 patients with
acute coronary syndrome (ACS), 12 with chronic stable angina, and 9
healthy controls. CD4-positive/CD28-null cells from 12 of 21 patients
with ACS reacted with HSPD1; no response was detected to human
cytomegalovirus, Chlamydia pneumoniae, or oxidized LDL.
CD4-positive/CD28-null cells from patients with chronic stable angina
and controls did not react to any of the antigens. Zal et al. (2004)
concluded that HSPD1 is an antigen recognized by CD4-positive/CD28-null
T cells of patients with acute coronary syndrome and suggested that
HSPD1-specific CD4-positive/CD28-null cells may contribute to vascular
damage in these patients.
Zanin-Zhorov et al. (2006) reported that HSP60, as well as a synthetic
peptide derived from HSP60 (p227), acted as a costimulator of human
regulatory CD4-positive/CD25 (IL2RA; 147730)-positive T cells (Tregs),
which inhibit lymphoproliferation and IFNG (147570) and TNF (191160)
secretion by CD4-positive and CD8-positive T cells. HSP60 enhanced Treg
activity via TLR2 (603028), leading to activation of an intracellular
signaling cascade that included p38 (MAPK14; 600289), as well as
inhibition of ERK (see MAPK1; 176948) phosphorylation. Suppression of
target T cells was mediated by both cell-to-cell contact and by
secretion of TGFB (190180) and IL10 (124092), and it led to
downregulation of ERK, NFKB (see 164011), and TBET (TBX21; 604895)
expression. Zanin-Zhorov et al. (2006) concluded that the self-molecule
HSP60 can downregulate adaptive immune responses by upregulating Tregs
through TLR2 signaling.
Using a luciferase-reporter assay, Hansen et al. (2003) demonstrated
that the region between the HSP60 and HSP10 (600141) genes functions as
a bidirectional promoter.
Tokuriki and Tawfik (2009) examined the ability of the E. coli
GroEL/GroES (HSP10) chaperonins to buffer destabilizing and adaptive
mutations. Mutational drifts performed in vitro with 4 different enzymes
indicated the GroEL/GroES overexpression doubled the number of
accumulating mutations, and promoted the folding of enzyme variants
carrying mutations in the protein core and/or mutations with higher
destabilizing effects. The divergence of modified enzymatic specificity
occurred much faster under GroEL/GroES overexpression, in terms of the
number of adapted variants (greater than or equal to 2-fold) and their
improved specificity and activity (greater than or equal to 10-fold).
Tokuriki and Tawfik (2009) concluded that protein stability is a major
constraint in protein evolution, and that buffering mechanisms such as
chaperonins are key in alleviating this constraint.
GENE STRUCTURE
Venner et al. (1990) claimed that HSP60 is intronless. Hansen et al.
(2003) presented the full sequence of the HSP60 and HSP10 genes. They
found that both genes are linked head to head, comprising approximately
17 kb and consisting of 12 and 4 exons, respectively. The first exon of
HSP60 is noncoding, and the first exon of HSP10 ends with the start
codon.
MAPPING
By radiation hybrid analysis, Hansen et al. (2003) mapped the HSP60 gene
between markers AFMA121YH1 and WI-10756 on chromosome 2. This
localization and the position of 2 homologous fragments in the human
genome assembly were consistent with the cytogenetic location 2q33.1.
MOLECULAR GENETICS
Hereditary spastic paraplegia (HSP) represents a clinically and
genetically heterogeneous group of neurodegenerative disorders that are
characterized by progressive spasticity and weakness of the lower limbs.
Seventeen different loci had been mapped, and the corresponding genes
for 5 of these had been cloned and identified. Two of the 5 gene
products--paraplegin (SPG7; 602783) and spastin (SPG4; 182601)--feature
AAA+ domains and are predicted to possess chaperone activity. Paraplegin
is the human homolog of a yeast protease/chaperone that is involved in
mitochondrial protein quality control. The HSP60 gene maps to the same
region, namely 2q33.1, as does spastic paraplegia-13 (SPG13; 605280), as
determined by Fontaine et al. (2000). Speculating that the mitochondrial
chaperonin HSP60 or its co-chaperonin HSP10, which maps to the same
region, might be the site of mutation(s) causing SPG13, Hansen et al.
(2002) sequenced HSP60 in 2 affected members of the family with SPG13.
They found that both were heterozygous for a G-to-A variation at
position 292 of the HSP60 cDNA, resulting in the substitution of a
valine at position 72 in the mature HSP60 by isoleucine (V72I). Studies
in E. coli indicated that the V72I mutant protein is functionally
incapacitated. The authors suggested that SPG4, SPG7, and SPG13 can be
referred to as chaperonopathies.
By linkage studies, followed by candidate gene analysis, of a large
Israeli Bedouin family with autosomal recessive hypomyelinating
leukodystrophy (HLD4; 612233), Magen et al. (2008) identified a
homozygous mutation in the HSPD1 gene (118190.0002). The authors
suggested the designation 'MitCHAP60 disease.'
*FIELD* AV
.0001
SPASTIC PARAPLEGIA 13
HSPD1, VAL72ILE
In a French family with autosomal dominant spastic paraplegia mapping to
2q33.1 (605280), Hansen et al. (2002) found a G-to-A transition at
nucleotide 292 of the HSP60 cDNA, resulting in the substitution of a
valine residue at position 72 in the mature HSP60 with isoleucine (val72
to ile; V72I).
.0002
LEUKODYSTROPHY, HYPOMYELINATING, 4
HSPD1, ASP29GLY
In 10 affected members of a consanguineous Israeli Bedouin family with
autosomal recessive hypomelinating leukodystrophy (612233), Magen et al.
(2008) identified homozygosity for a genomic 1512A-G transition in exon
2 of the HSPD1 gene, resulting in an asp29-to-gly (D29G) substitution in
a highly conserved residue adjacent to the first 26 N-terminal residues
composing the mitochondrial matrix targeting sequence. In vitro
functional expression studies showed that transfection with the mutant
protein impaired cell growth that worsened with increasing temperature.
Common clinical features included infantile-onset rotary nystagmus,
progressive spastic paraplegia, neurologic regression, motor impairment,
profound mental retardation, and hypomyelinating leukodystrophy. Death
usually occurred within the first 2 decades of life. Heterozygous
carriers were unaffected.
*FIELD* RF
1. Azem, A.; Kessel, M.; Goloubinoff, P.: Characterization of a functional
GroEL-14(GroES-7)-2 chaperonin hetero-oligomer. Science 265: 653-656,
1994.
2. Cheng, M. Y.; Hartl, F.-U.; Martin, J.; Pollock, R. A.; Kalousek,
F.; Neupert, W.; Hallberg, E. M.; Hallberg, R. L.; Horwich, A. L.
: Mitochondrial heat-shock protein hsp60 is essential for assembly
of proteins imported into yeast mitochondria. Nature 337: 620-625,
1989.
3. Ellis, R. J.: The molecular chaperone concept. Semin. Cell Biol. 1:
1-9, 1990.
4. Fontaine, B.; Davoine, C.-S.; Durr, A.; Paternotte, C.; Feki, I.;
Weissenbach, J.; Hazan, J.; Brice, A.: A new locus for autosomal
dominant pure spastic paraplegia, on chromosome 2q24-q34. Am. J.
Hum. Genet. 66: 702-707, 2000.
5. Hansen, J. J.; Bross, P.; Westergaard, M.; Nielsen, M. N.; Eiberg,
H.; Borglum, A. D.; Mogensen, J.; Kristiansen, K.; Bolund, L.; Gregersen,
N.: Genomic structure of the human mitochondrial chaperonin genes:
HSP60 and HSP10 are localised head to head on chromosome 2 separated
by a bidirectional promoter. Hum. Genet. 112: 71-77, 2003. Note:
Erratum: Hum. Genet. 112: 436 only, 2003.
6. Hansen, J. J.; Durr, A.; Cournu-Rebeix, I.; Georgopoulos, C.; Ang,
D.; Nielsen, M. N.; Davoine, C.-S.; Brice, A.; Fontaine, B.; Gregersen,
N.; Bross, P.: Hereditary spastic paraplegia SPG13 is associated
with a mutation in the gene encoding the mitochondrial chaperonin
Hsp60. Am. J. Hum. Genet. 70: 1328-1332, 2002.
7. Magen, D.; Georgopoulos, C.; Bross, P.; Ang, D.; Segev, Y.; Goldsher,
D.; Nemirovski, A.; Shahar, E.; Ravid, S.; Luder, A.; Heno, B.; Gershoni-Baruch,
R.; Skorecki, K.; Mandel, H.: Mitochondrial Hsp60 chaperonopathy
causes an autosomal-recessive neurodegenerative disorder linked to
brain hypomyelination and leukodystrophy. Am. J. Hum. Genet. 83:
30-42, 2008.
8. Rothman, J. E.: Polypeptide chain binding proteins: catalysts
of protein folding and related processes in cells. Cell 59: 591-601,
1989.
9. Saibil, H.; Dong, Z.; Wood, S.; auf der Mauer, A.: Binding of
chaperonins. Nature 353: 25-26, 1991.
10. Schmidt, M.; Rutkat, K.; Rachel, R.; Pfeifer, G.; Jaenicke, R.;
Viitanen, P.; Lorimer, G.; Buchner, J.: Symmetric complexes of GroE
chaperonins as part of the functional cycle. Science 265: 656-659,
1994.
11. Todd, M. J.; Viitanen, P. V.; Lorimer, G. H.: Dynamics of the
chaperonin ATPase cycle: implications for facilitated protein folding. Science 265:
659-666, 1994.
12. Tokuriki, N.; Tawfik, D. S.: Chaperonin overexpression promotes
genetic variation and enzyme evolution. Nature 450: 668-673, 2009.
13. Venner, T. J.; Singh, B.; Gupta, R. S.: Nucleotide sequences
and novel structural features of human and Chinese hamster hsp60 (chaperonin)
gene families. DNA Cell Biol. 9: 545-552, 1990.
14. Zal, B.; Kaski, J. C.; Arno, G.; Akiyu, J. P.; Xu, Q.; Cole, D.;
Whelan, M.; Russell, N.; Madrigal, J. A.; Dodi, I. A.; Baboonian,
C.: Heat-shock protein 60-reactive CD4+CD28-null T cells in patients
with acute coronary syndromes. Circulation 109: 1230-1235, 2004.
15. Zanin-Zhorov, A.; Cahalon, L.; Tal, G.; Margalit, R.; Lider, O.;
Cohen, I. R.: Heat shock protein 60 enhances CD4+CD25+ regulatory
T cell function via innate TLR2 signaling. J. Clin. Invest. 116:
2022-2032, 2006.
*FIELD* CN
Ada Hamosh - updated: 6/16/2009
Cassandra L. Kniffin - updated: 8/11/2008
Paul J. Converse - updated: 11/16/2006
Marla J. F. O'Neill - updated: 1/31/2006
Victor A. McKusick - updated: 12/30/2002
Victor A. McKusick - updated: 5/17/2002
*FIELD* CD
Victor A. McKusick: 1/2/1991
*FIELD* ED
alopez: 06/17/2009
terry: 6/16/2009
ckniffin: 11/26/2008
wwang: 8/20/2008
ckniffin: 8/11/2008
mgross: 12/5/2006
mgross: 12/1/2006
terry: 11/16/2006
wwang: 2/3/2006
terry: 1/31/2006
terry: 3/16/2005
carol: 1/8/2003
tkritzer: 1/3/2003
terry: 12/30/2002
alopez: 5/24/2002
terry: 5/17/2002
terry: 7/24/1998
dkim: 7/21/1998
mark: 4/1/1996
carol: 10/11/1994
carol: 4/10/1992
supermim: 3/16/1992
carol: 2/1/1991
carol: 1/9/1991
carol: 1/2/1991
*RECORD*
*FIELD* NO
118190
*FIELD* TI
*118190 HEAT-SHOCK 60-KD PROTEIN 1; HSPD1
;;HSP60;;
CHAPERONIN, 60-KD; CPN60;;
GroEL, E. COLI, HOMOLOG OF
read more*FIELD* TX
DESCRIPTION
It had long been assumed that all information necessary for proper
folding of proteins and their assembly into oligomeric complexes was
contained within the primary sequence of the polypeptides and that no
catalyst or other accessory proteins were involved in this process.
However, this basic tenet of biochemistry was challenged by the
discovery of chaperonins, which are involved in the folding and assembly
of a number of different proteins (Cheng et al., 1989; Ellis, 1990;
Rothman, 1989). Members of the chaperonin family include the GroEL
protein of E. coli and HSP60, a protein present in eukaryotic cell
mitochondria. In both prokaryotic and eukaryotic systems, synthesis of
these proteins is induced in response to stresses, such as heat shock
(Venner et al., 1990).
CLONING
Venner et al. (1990) presented evidence of the existence of multiple
copies of the HSP60 gene in the human. All except one of these genes are
nonfunctional pseudogenes containing numerous changes such as base
substitutions, insertions, and deletions.
BIOCHEMICAL FEATURES
Azem et al. (1994) performed chemical crosslinking and electron
microscopy studies on bacterial chaperonins GroEL and GroES (HSPE1;
600141) to determine how they interact with unfolded proteins. GroEL is
an oligomer of 14 identical 57.3-kD subunits, with a structure of 2
stacked heptameric rings arranged around a 2-fold axis of symmetry
(Saibil et al., 1991). It appears as a hollow cylinder. In the presence
of ATP, 2 GroES rings (each made of 7 identical 10.4-kD subunits) can
successively bind a single GroEL core to make a functional symmetric
heterodimer. Although the central core of GroEL is obstructed by the 2
GroES rings at each end, this heterodimer can stably bind and assist the
refolding of the RuBisCo enzyme. While binding was thought to occur in
the central cavity, these data indicate that unfolded proteins may bind
and fold on the external envelope of some chaperonins (Azem et al.,
1994). Schmidt et al. (1994) suggested that the symmetric chaperonin
complex is functionally significant because complete folding of a
nonnative substrate protein in the presence of GroEL and GroES occurs
only in the presence of ATP, and not with ADP. Chaperonin-assisted
folding occurs by a catalytic cycle in which one ATP is hydrolyzed by
one ring of GroEL in a quantized manner with each turnover. Todd et al.
(1994) proposed a unifying model for chaperonin-facilitated protein
folding based on successive rounds of binding and release, and
partitioning between committed and kinetically trapped intermediates.
GENE FUNCTION
Zal et al. (2004) examined the antigen recognition of CD4
(186940)-positive/CD28 (186760)-null T lymphocytes from 21 patients with
acute coronary syndrome (ACS), 12 with chronic stable angina, and 9
healthy controls. CD4-positive/CD28-null cells from 12 of 21 patients
with ACS reacted with HSPD1; no response was detected to human
cytomegalovirus, Chlamydia pneumoniae, or oxidized LDL.
CD4-positive/CD28-null cells from patients with chronic stable angina
and controls did not react to any of the antigens. Zal et al. (2004)
concluded that HSPD1 is an antigen recognized by CD4-positive/CD28-null
T cells of patients with acute coronary syndrome and suggested that
HSPD1-specific CD4-positive/CD28-null cells may contribute to vascular
damage in these patients.
Zanin-Zhorov et al. (2006) reported that HSP60, as well as a synthetic
peptide derived from HSP60 (p227), acted as a costimulator of human
regulatory CD4-positive/CD25 (IL2RA; 147730)-positive T cells (Tregs),
which inhibit lymphoproliferation and IFNG (147570) and TNF (191160)
secretion by CD4-positive and CD8-positive T cells. HSP60 enhanced Treg
activity via TLR2 (603028), leading to activation of an intracellular
signaling cascade that included p38 (MAPK14; 600289), as well as
inhibition of ERK (see MAPK1; 176948) phosphorylation. Suppression of
target T cells was mediated by both cell-to-cell contact and by
secretion of TGFB (190180) and IL10 (124092), and it led to
downregulation of ERK, NFKB (see 164011), and TBET (TBX21; 604895)
expression. Zanin-Zhorov et al. (2006) concluded that the self-molecule
HSP60 can downregulate adaptive immune responses by upregulating Tregs
through TLR2 signaling.
Using a luciferase-reporter assay, Hansen et al. (2003) demonstrated
that the region between the HSP60 and HSP10 (600141) genes functions as
a bidirectional promoter.
Tokuriki and Tawfik (2009) examined the ability of the E. coli
GroEL/GroES (HSP10) chaperonins to buffer destabilizing and adaptive
mutations. Mutational drifts performed in vitro with 4 different enzymes
indicated the GroEL/GroES overexpression doubled the number of
accumulating mutations, and promoted the folding of enzyme variants
carrying mutations in the protein core and/or mutations with higher
destabilizing effects. The divergence of modified enzymatic specificity
occurred much faster under GroEL/GroES overexpression, in terms of the
number of adapted variants (greater than or equal to 2-fold) and their
improved specificity and activity (greater than or equal to 10-fold).
Tokuriki and Tawfik (2009) concluded that protein stability is a major
constraint in protein evolution, and that buffering mechanisms such as
chaperonins are key in alleviating this constraint.
GENE STRUCTURE
Venner et al. (1990) claimed that HSP60 is intronless. Hansen et al.
(2003) presented the full sequence of the HSP60 and HSP10 genes. They
found that both genes are linked head to head, comprising approximately
17 kb and consisting of 12 and 4 exons, respectively. The first exon of
HSP60 is noncoding, and the first exon of HSP10 ends with the start
codon.
MAPPING
By radiation hybrid analysis, Hansen et al. (2003) mapped the HSP60 gene
between markers AFMA121YH1 and WI-10756 on chromosome 2. This
localization and the position of 2 homologous fragments in the human
genome assembly were consistent with the cytogenetic location 2q33.1.
MOLECULAR GENETICS
Hereditary spastic paraplegia (HSP) represents a clinically and
genetically heterogeneous group of neurodegenerative disorders that are
characterized by progressive spasticity and weakness of the lower limbs.
Seventeen different loci had been mapped, and the corresponding genes
for 5 of these had been cloned and identified. Two of the 5 gene
products--paraplegin (SPG7; 602783) and spastin (SPG4; 182601)--feature
AAA+ domains and are predicted to possess chaperone activity. Paraplegin
is the human homolog of a yeast protease/chaperone that is involved in
mitochondrial protein quality control. The HSP60 gene maps to the same
region, namely 2q33.1, as does spastic paraplegia-13 (SPG13; 605280), as
determined by Fontaine et al. (2000). Speculating that the mitochondrial
chaperonin HSP60 or its co-chaperonin HSP10, which maps to the same
region, might be the site of mutation(s) causing SPG13, Hansen et al.
(2002) sequenced HSP60 in 2 affected members of the family with SPG13.
They found that both were heterozygous for a G-to-A variation at
position 292 of the HSP60 cDNA, resulting in the substitution of a
valine at position 72 in the mature HSP60 by isoleucine (V72I). Studies
in E. coli indicated that the V72I mutant protein is functionally
incapacitated. The authors suggested that SPG4, SPG7, and SPG13 can be
referred to as chaperonopathies.
By linkage studies, followed by candidate gene analysis, of a large
Israeli Bedouin family with autosomal recessive hypomyelinating
leukodystrophy (HLD4; 612233), Magen et al. (2008) identified a
homozygous mutation in the HSPD1 gene (118190.0002). The authors
suggested the designation 'MitCHAP60 disease.'
*FIELD* AV
.0001
SPASTIC PARAPLEGIA 13
HSPD1, VAL72ILE
In a French family with autosomal dominant spastic paraplegia mapping to
2q33.1 (605280), Hansen et al. (2002) found a G-to-A transition at
nucleotide 292 of the HSP60 cDNA, resulting in the substitution of a
valine residue at position 72 in the mature HSP60 with isoleucine (val72
to ile; V72I).
.0002
LEUKODYSTROPHY, HYPOMYELINATING, 4
HSPD1, ASP29GLY
In 10 affected members of a consanguineous Israeli Bedouin family with
autosomal recessive hypomelinating leukodystrophy (612233), Magen et al.
(2008) identified homozygosity for a genomic 1512A-G transition in exon
2 of the HSPD1 gene, resulting in an asp29-to-gly (D29G) substitution in
a highly conserved residue adjacent to the first 26 N-terminal residues
composing the mitochondrial matrix targeting sequence. In vitro
functional expression studies showed that transfection with the mutant
protein impaired cell growth that worsened with increasing temperature.
Common clinical features included infantile-onset rotary nystagmus,
progressive spastic paraplegia, neurologic regression, motor impairment,
profound mental retardation, and hypomyelinating leukodystrophy. Death
usually occurred within the first 2 decades of life. Heterozygous
carriers were unaffected.
*FIELD* RF
1. Azem, A.; Kessel, M.; Goloubinoff, P.: Characterization of a functional
GroEL-14(GroES-7)-2 chaperonin hetero-oligomer. Science 265: 653-656,
1994.
2. Cheng, M. Y.; Hartl, F.-U.; Martin, J.; Pollock, R. A.; Kalousek,
F.; Neupert, W.; Hallberg, E. M.; Hallberg, R. L.; Horwich, A. L.
: Mitochondrial heat-shock protein hsp60 is essential for assembly
of proteins imported into yeast mitochondria. Nature 337: 620-625,
1989.
3. Ellis, R. J.: The molecular chaperone concept. Semin. Cell Biol. 1:
1-9, 1990.
4. Fontaine, B.; Davoine, C.-S.; Durr, A.; Paternotte, C.; Feki, I.;
Weissenbach, J.; Hazan, J.; Brice, A.: A new locus for autosomal
dominant pure spastic paraplegia, on chromosome 2q24-q34. Am. J.
Hum. Genet. 66: 702-707, 2000.
5. Hansen, J. J.; Bross, P.; Westergaard, M.; Nielsen, M. N.; Eiberg,
H.; Borglum, A. D.; Mogensen, J.; Kristiansen, K.; Bolund, L.; Gregersen,
N.: Genomic structure of the human mitochondrial chaperonin genes:
HSP60 and HSP10 are localised head to head on chromosome 2 separated
by a bidirectional promoter. Hum. Genet. 112: 71-77, 2003. Note:
Erratum: Hum. Genet. 112: 436 only, 2003.
6. Hansen, J. J.; Durr, A.; Cournu-Rebeix, I.; Georgopoulos, C.; Ang,
D.; Nielsen, M. N.; Davoine, C.-S.; Brice, A.; Fontaine, B.; Gregersen,
N.; Bross, P.: Hereditary spastic paraplegia SPG13 is associated
with a mutation in the gene encoding the mitochondrial chaperonin
Hsp60. Am. J. Hum. Genet. 70: 1328-1332, 2002.
7. Magen, D.; Georgopoulos, C.; Bross, P.; Ang, D.; Segev, Y.; Goldsher,
D.; Nemirovski, A.; Shahar, E.; Ravid, S.; Luder, A.; Heno, B.; Gershoni-Baruch,
R.; Skorecki, K.; Mandel, H.: Mitochondrial Hsp60 chaperonopathy
causes an autosomal-recessive neurodegenerative disorder linked to
brain hypomyelination and leukodystrophy. Am. J. Hum. Genet. 83:
30-42, 2008.
8. Rothman, J. E.: Polypeptide chain binding proteins: catalysts
of protein folding and related processes in cells. Cell 59: 591-601,
1989.
9. Saibil, H.; Dong, Z.; Wood, S.; auf der Mauer, A.: Binding of
chaperonins. Nature 353: 25-26, 1991.
10. Schmidt, M.; Rutkat, K.; Rachel, R.; Pfeifer, G.; Jaenicke, R.;
Viitanen, P.; Lorimer, G.; Buchner, J.: Symmetric complexes of GroE
chaperonins as part of the functional cycle. Science 265: 656-659,
1994.
11. Todd, M. J.; Viitanen, P. V.; Lorimer, G. H.: Dynamics of the
chaperonin ATPase cycle: implications for facilitated protein folding. Science 265:
659-666, 1994.
12. Tokuriki, N.; Tawfik, D. S.: Chaperonin overexpression promotes
genetic variation and enzyme evolution. Nature 450: 668-673, 2009.
13. Venner, T. J.; Singh, B.; Gupta, R. S.: Nucleotide sequences
and novel structural features of human and Chinese hamster hsp60 (chaperonin)
gene families. DNA Cell Biol. 9: 545-552, 1990.
14. Zal, B.; Kaski, J. C.; Arno, G.; Akiyu, J. P.; Xu, Q.; Cole, D.;
Whelan, M.; Russell, N.; Madrigal, J. A.; Dodi, I. A.; Baboonian,
C.: Heat-shock protein 60-reactive CD4+CD28-null T cells in patients
with acute coronary syndromes. Circulation 109: 1230-1235, 2004.
15. Zanin-Zhorov, A.; Cahalon, L.; Tal, G.; Margalit, R.; Lider, O.;
Cohen, I. R.: Heat shock protein 60 enhances CD4+CD25+ regulatory
T cell function via innate TLR2 signaling. J. Clin. Invest. 116:
2022-2032, 2006.
*FIELD* CN
Ada Hamosh - updated: 6/16/2009
Cassandra L. Kniffin - updated: 8/11/2008
Paul J. Converse - updated: 11/16/2006
Marla J. F. O'Neill - updated: 1/31/2006
Victor A. McKusick - updated: 12/30/2002
Victor A. McKusick - updated: 5/17/2002
*FIELD* CD
Victor A. McKusick: 1/2/1991
*FIELD* ED
alopez: 06/17/2009
terry: 6/16/2009
ckniffin: 11/26/2008
wwang: 8/20/2008
ckniffin: 8/11/2008
mgross: 12/5/2006
mgross: 12/1/2006
terry: 11/16/2006
wwang: 2/3/2006
terry: 1/31/2006
terry: 3/16/2005
carol: 1/8/2003
tkritzer: 1/3/2003
terry: 12/30/2002
alopez: 5/24/2002
terry: 5/17/2002
terry: 7/24/1998
dkim: 7/21/1998
mark: 4/1/1996
carol: 10/11/1994
carol: 4/10/1992
supermim: 3/16/1992
carol: 2/1/1991
carol: 1/9/1991
carol: 1/2/1991
MIM
605280
*RECORD*
*FIELD* NO
605280
*FIELD* TI
#605280 SPASTIC PARAPLEGIA 13, AUTOSOMAL DOMINANT; SPG13
*FIELD* TX
A number sign (#) is used with this entry because spastic paraplegia-13
read morecan be caused by mutation in the mitochondrial chaperonin HSP60 (SSPD1;
118190).
For a general phenotypic description and a discussion of genetic
heterogeneity of autosomal dominant spastic paraplegia, see SPG3A
(182600).
MAPPING
Fontaine et al. (2000) reported a large family of French descent with
autosomal dominant pure spastic paraplegia. They excluded genetic
linkage to known loci for this general phenotype and performed a
genomewide search. They found evidence for linkage of the disorder
(SPG13) to polymorphic markers on 2q24-q34, with a maximum lod score of
3.0 with marker D2S2318.
Fontaine et al. (2000) compared the clinical features of the French
family showing linkage to 2q24 with those of 12 families showing linkage
to 2p (SPG4; 182601). The SPG13 family had significantly more patients
without Babinski signs, with increased reflexes in the upper limbs, and
with severe functional handicaps. Fontaine et al. (2000) noted that the
gene for autosomal recessive symmetric spastic cerebral palsy (603513)
had been mapped to 2q24-q25. Although this disease differs from SPG13 in
clinical presentation and in mode of inheritance, the authors could not
exclude the possibility that the disorders represent allelic mutations
of the same gene. The 2 mapping regions overlap and both disorders
affect the pyramidal tracts.
MOLECULAR GENETICS
Hansen et al. (2002) found a mutation in the gene encoding mitochondrial
chaperonin HSP60 (SSPD1) in affected members of the family with SPG13
reported by Fontaine et al. (2000).
*FIELD* RF
1. Fontaine, B.; Davoine, C.-S.; Durr, A.; Paternotte, C.; Feki, I.;
Weissenbach, J.; Hazan, J.; Brice, A.: A new locus for autosomal
dominant pure spastic paraplegia, on chromosome 2q24-q34. Am. J.
Hum. Genet. 66: 702-707, 2000.
2. Hansen, J. J.; Durr, A.; Cournu-Rebeix, I.; Georgopoulos, C.; Ang,
D.; Nielsen, M. N.; Davoine, C.-S.; Brice, A.; Fontaine, B.; Gregersen,
N.; Bross, P.: Hereditary spastic paraplegia SPG13 is associated
with a mutation in the gene encoding the mitochondrial chaperonin
Hsp60. Am. J. Hum. Genet. 70: 1328-1332, 2002.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GENITOURINARY:
[Bladder];
Urinary urgency;
Urinary incontinence;
Sphincter disturbances
NEUROLOGIC:
[Central nervous system];
Lower limb spasticity;
Lower limb weakness;
Spastic gait;
Hyperreflexia;
Extensor plantar responses;
Pyramidal signs;
Decreased vibratory sense in the lower limbs
MISCELLANEOUS:
Age of onset 17 to 68 years (mean 39);
Progressive disorder;
Severe phenotype;
Genetic heterogeneity, see SPG3A (182600)
*FIELD* CD
Cassandra L. Kniffin: 9/17/2002
*FIELD* ED
joanna: 10/23/2002
ckniffin: 10/23/2002
ckniffin: 9/30/2002
ckniffin: 9/27/2002
*FIELD* CN
Victor A. McKusick - updated: 5/17/2002
*FIELD* CD
Victor A. McKusick: 9/20/2000
*FIELD* ED
wwang: 11/11/2008
alopez: 5/24/2002
terry: 5/17/2002
carol: 9/20/2000
*RECORD*
*FIELD* NO
605280
*FIELD* TI
#605280 SPASTIC PARAPLEGIA 13, AUTOSOMAL DOMINANT; SPG13
*FIELD* TX
A number sign (#) is used with this entry because spastic paraplegia-13
read morecan be caused by mutation in the mitochondrial chaperonin HSP60 (SSPD1;
118190).
For a general phenotypic description and a discussion of genetic
heterogeneity of autosomal dominant spastic paraplegia, see SPG3A
(182600).
MAPPING
Fontaine et al. (2000) reported a large family of French descent with
autosomal dominant pure spastic paraplegia. They excluded genetic
linkage to known loci for this general phenotype and performed a
genomewide search. They found evidence for linkage of the disorder
(SPG13) to polymorphic markers on 2q24-q34, with a maximum lod score of
3.0 with marker D2S2318.
Fontaine et al. (2000) compared the clinical features of the French
family showing linkage to 2q24 with those of 12 families showing linkage
to 2p (SPG4; 182601). The SPG13 family had significantly more patients
without Babinski signs, with increased reflexes in the upper limbs, and
with severe functional handicaps. Fontaine et al. (2000) noted that the
gene for autosomal recessive symmetric spastic cerebral palsy (603513)
had been mapped to 2q24-q25. Although this disease differs from SPG13 in
clinical presentation and in mode of inheritance, the authors could not
exclude the possibility that the disorders represent allelic mutations
of the same gene. The 2 mapping regions overlap and both disorders
affect the pyramidal tracts.
MOLECULAR GENETICS
Hansen et al. (2002) found a mutation in the gene encoding mitochondrial
chaperonin HSP60 (SSPD1) in affected members of the family with SPG13
reported by Fontaine et al. (2000).
*FIELD* RF
1. Fontaine, B.; Davoine, C.-S.; Durr, A.; Paternotte, C.; Feki, I.;
Weissenbach, J.; Hazan, J.; Brice, A.: A new locus for autosomal
dominant pure spastic paraplegia, on chromosome 2q24-q34. Am. J.
Hum. Genet. 66: 702-707, 2000.
2. Hansen, J. J.; Durr, A.; Cournu-Rebeix, I.; Georgopoulos, C.; Ang,
D.; Nielsen, M. N.; Davoine, C.-S.; Brice, A.; Fontaine, B.; Gregersen,
N.; Bross, P.: Hereditary spastic paraplegia SPG13 is associated
with a mutation in the gene encoding the mitochondrial chaperonin
Hsp60. Am. J. Hum. Genet. 70: 1328-1332, 2002.
*FIELD* CS
INHERITANCE:
Autosomal dominant
GENITOURINARY:
[Bladder];
Urinary urgency;
Urinary incontinence;
Sphincter disturbances
NEUROLOGIC:
[Central nervous system];
Lower limb spasticity;
Lower limb weakness;
Spastic gait;
Hyperreflexia;
Extensor plantar responses;
Pyramidal signs;
Decreased vibratory sense in the lower limbs
MISCELLANEOUS:
Age of onset 17 to 68 years (mean 39);
Progressive disorder;
Severe phenotype;
Genetic heterogeneity, see SPG3A (182600)
*FIELD* CD
Cassandra L. Kniffin: 9/17/2002
*FIELD* ED
joanna: 10/23/2002
ckniffin: 10/23/2002
ckniffin: 9/30/2002
ckniffin: 9/27/2002
*FIELD* CN
Victor A. McKusick - updated: 5/17/2002
*FIELD* CD
Victor A. McKusick: 9/20/2000
*FIELD* ED
wwang: 11/11/2008
alopez: 5/24/2002
terry: 5/17/2002
carol: 9/20/2000
MIM
612233
*RECORD*
*FIELD* NO
612233
*FIELD* TI
#612233 LEUKODYSTROPHY, HYPOMYELINATING, 4; HLD4
;;MITOCHONDRIAL HSP60 CHAPERONOPATHY;;
read moreMITCHAP60 DISEASE
*FIELD* TX
A number sign (#) is used with this entry because this form of autosomal
recessive hypomyelinating leukodystrophy (HLD4), also known as
mitochondrial Hsp60 chaperonopathy, is caused by mutation in the HSPD1
gene (118190).
Autosomal dominant hereditary spastic paraplegia-13 (SPG13; 605280) is
an allelic disorder.
For a general phenotypic description and a discussion of genetic
heterogeneity of HLD, see 312080.
CLINICAL FEATURES
Magen et al. (2008) reported a large consanguineous Israeli Bedouin
family with an autosomal recessive form of severe hypomyelinating
leukoencephalopathy. Ten patients were examined in detail. All had onset
between birth and age 3 months of hypotonia, nystagmus, and psychomotor
developmental delay, followed by appearance of prominent spasticity,
developmental arrest, and regression. Head circumference, which was
normal at birth, showed decreased growth rate. Seizures were reported in
6 patients. Feeding problems commonly led to malnutrition and growth
failure. Death usually occurred within the first 2 decades of life from
aspiration pneumonia or sudden death of unknown cause. One patient
presented with hydrops fetalis and died at age 2 years. Patients with
the more severe course died before the age of 2 years, with some
patients never gaining social eye contact or any other developmental
milestone. These severely affected patients suffered from recurrent
episodes of shallow breathing and lethal apneic spells during acute
febrile illnesses. Patients who survived beyond the age of 2 years
developed progressive limb spasticity and contractures. Plasma lactate
levels were generally normal, although sometimes increased during
encephalopathic episodes, and there was no evidence of ragged red fibers
on muscle biopsies. MRI showed no evidence of normal myelination,
regardless of the age of the patient. All patients exhibited a thin
corpus callosum and various degrees of ventricular enlargement.
Enlargement of sulci and subarachnoid spaces, mainly in the frontal and
parietal areas, were observed in 6 of 8 patients, and the brainstem was
thin in all patients. The degree of widening of cerebral sulci was in
concordance with the severity of the clinical symptoms. There was a
range of intrafamilial and interfamilial phenotypic heterogeneity in
psychomotor impairment and in neurologic or developmental deterioration.
MOLECULAR GENETICS
By linkage studies, followed by candidate gene analysis, of a large
Israeli Bedouin family with autosomal recessive hypomyelinating
leukodystrophy, Magen et al. (2008) identified a homozygous mutation in
the HSPD1 gene (118190.0002). The authors suggested the designation
'MitCHAP60 disease.'
*FIELD* RF
1. Magen, D.; Georgopoulos, C.; Bross, P.; Ang, D.; Segev, Y.; Goldsher,
D.; Nemirovski, A.; Shahar, E.; Ravid, S.; Luder, A.; Heno, B.; Gershoni-Baruch,
R.; Skorecki, K.; Mandel, H.: Mitochondrial Hsp60 chaperonopathy
causes an autosomal-recessive neurodegenerative disorder linked to
brain hypomyelination and leukodystrophy. Am. J. Hum. Genet. 83:
30-42, 2008.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Head];
Microcephaly, acquired;
[Eyes];
Nystagmus;
Strabismus
RESPIRATORY:
Apneic episodes;
Shallow breathing
ABDOMEN:
[Gastrointestinal];
Feeding difficulties
SKELETAL:
Joint contractures
NEUROLOGIC:
[Central nervous system];
Hypotonia;
Psychomotor delay;
Mental retardation, profound;
No head control;
Seizures;
Spasticity, progressive;
Hyperreflexia;
Extensor plantar responses;
Choreoathetosis;
MRI shows no normal myelination;
Leukodystrophy, hypomyelinating
LABORATORY ABNORMALITIES:
Intermittent increase of urinary ethylmalonic acid;
Serum lactate may be increased during encephalopathic exacerbations
MISCELLANEOUS:
Onset between birth and 3 months of age;
Usually fatal in first 2 decades;
Exacerbation during febrile episodes;
Allelic disorder to autosomal dominant SPG13 (605280)
MOLECULAR BASIS:
Caused by mutation in the heat-shock 60-Kd protein 1 gene (HSPD1,
118190.0002)
*FIELD* CD
Cassandra L. Kniffin: 8/11/2008
*FIELD* ED
ckniffin: 11/25/2008
ckniffin: 8/11/2008
*FIELD* CD
Cassandra L. Kniffin: 8/11/2008
*FIELD* ED
terry: 02/16/2011
carol: 2/16/2011
ckniffin: 11/26/2008
wwang: 8/20/2008
ckniffin: 8/11/2008
*RECORD*
*FIELD* NO
612233
*FIELD* TI
#612233 LEUKODYSTROPHY, HYPOMYELINATING, 4; HLD4
;;MITOCHONDRIAL HSP60 CHAPERONOPATHY;;
read moreMITCHAP60 DISEASE
*FIELD* TX
A number sign (#) is used with this entry because this form of autosomal
recessive hypomyelinating leukodystrophy (HLD4), also known as
mitochondrial Hsp60 chaperonopathy, is caused by mutation in the HSPD1
gene (118190).
Autosomal dominant hereditary spastic paraplegia-13 (SPG13; 605280) is
an allelic disorder.
For a general phenotypic description and a discussion of genetic
heterogeneity of HLD, see 312080.
CLINICAL FEATURES
Magen et al. (2008) reported a large consanguineous Israeli Bedouin
family with an autosomal recessive form of severe hypomyelinating
leukoencephalopathy. Ten patients were examined in detail. All had onset
between birth and age 3 months of hypotonia, nystagmus, and psychomotor
developmental delay, followed by appearance of prominent spasticity,
developmental arrest, and regression. Head circumference, which was
normal at birth, showed decreased growth rate. Seizures were reported in
6 patients. Feeding problems commonly led to malnutrition and growth
failure. Death usually occurred within the first 2 decades of life from
aspiration pneumonia or sudden death of unknown cause. One patient
presented with hydrops fetalis and died at age 2 years. Patients with
the more severe course died before the age of 2 years, with some
patients never gaining social eye contact or any other developmental
milestone. These severely affected patients suffered from recurrent
episodes of shallow breathing and lethal apneic spells during acute
febrile illnesses. Patients who survived beyond the age of 2 years
developed progressive limb spasticity and contractures. Plasma lactate
levels were generally normal, although sometimes increased during
encephalopathic episodes, and there was no evidence of ragged red fibers
on muscle biopsies. MRI showed no evidence of normal myelination,
regardless of the age of the patient. All patients exhibited a thin
corpus callosum and various degrees of ventricular enlargement.
Enlargement of sulci and subarachnoid spaces, mainly in the frontal and
parietal areas, were observed in 6 of 8 patients, and the brainstem was
thin in all patients. The degree of widening of cerebral sulci was in
concordance with the severity of the clinical symptoms. There was a
range of intrafamilial and interfamilial phenotypic heterogeneity in
psychomotor impairment and in neurologic or developmental deterioration.
MOLECULAR GENETICS
By linkage studies, followed by candidate gene analysis, of a large
Israeli Bedouin family with autosomal recessive hypomyelinating
leukodystrophy, Magen et al. (2008) identified a homozygous mutation in
the HSPD1 gene (118190.0002). The authors suggested the designation
'MitCHAP60 disease.'
*FIELD* RF
1. Magen, D.; Georgopoulos, C.; Bross, P.; Ang, D.; Segev, Y.; Goldsher,
D.; Nemirovski, A.; Shahar, E.; Ravid, S.; Luder, A.; Heno, B.; Gershoni-Baruch,
R.; Skorecki, K.; Mandel, H.: Mitochondrial Hsp60 chaperonopathy
causes an autosomal-recessive neurodegenerative disorder linked to
brain hypomyelination and leukodystrophy. Am. J. Hum. Genet. 83:
30-42, 2008.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Head];
Microcephaly, acquired;
[Eyes];
Nystagmus;
Strabismus
RESPIRATORY:
Apneic episodes;
Shallow breathing
ABDOMEN:
[Gastrointestinal];
Feeding difficulties
SKELETAL:
Joint contractures
NEUROLOGIC:
[Central nervous system];
Hypotonia;
Psychomotor delay;
Mental retardation, profound;
No head control;
Seizures;
Spasticity, progressive;
Hyperreflexia;
Extensor plantar responses;
Choreoathetosis;
MRI shows no normal myelination;
Leukodystrophy, hypomyelinating
LABORATORY ABNORMALITIES:
Intermittent increase of urinary ethylmalonic acid;
Serum lactate may be increased during encephalopathic exacerbations
MISCELLANEOUS:
Onset between birth and 3 months of age;
Usually fatal in first 2 decades;
Exacerbation during febrile episodes;
Allelic disorder to autosomal dominant SPG13 (605280)
MOLECULAR BASIS:
Caused by mutation in the heat-shock 60-Kd protein 1 gene (HSPD1,
118190.0002)
*FIELD* CD
Cassandra L. Kniffin: 8/11/2008
*FIELD* ED
ckniffin: 11/25/2008
ckniffin: 8/11/2008
*FIELD* CD
Cassandra L. Kniffin: 8/11/2008
*FIELD* ED
terry: 02/16/2011
carol: 2/16/2011
ckniffin: 11/26/2008
wwang: 8/20/2008
ckniffin: 8/11/2008