Full text data of HSPA9
HSPA9
(GRP75, HSPA9B, mt-HSP70)
[Confidence: low (only semi-automatic identification from reviews)]
Stress-70 protein, mitochondrial (75 kDa glucose-regulated protein; GRP-75; Heat shock 70 kDa protein 9; Mortalin; MOT; Peptide-binding protein 74; PBP74; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Stress-70 protein, mitochondrial (75 kDa glucose-regulated protein; GRP-75; Heat shock 70 kDa protein 9; Mortalin; MOT; Peptide-binding protein 74; PBP74; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P38646
ID GRP75_HUMAN Reviewed; 679 AA.
AC P38646; B2RCM1; P30036; P31932; Q1HB43; Q53H23; Q6GU03; Q9BWB7;
read moreAC Q9UC56;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Stress-70 protein, mitochondrial;
DE AltName: Full=75 kDa glucose-regulated protein;
DE Short=GRP-75;
DE AltName: Full=Heat shock 70 kDa protein 9;
DE AltName: Full=Mortalin;
DE Short=MOT;
DE AltName: Full=Peptide-binding protein 74;
DE Short=PBP74;
DE Flags: Precursor;
GN Name=HSPA9; Synonyms=GRP75, HSPA9B, mt-HSP70;
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].
RC TISSUE=B-cell;
RX PubMed=7684501;
RA Domanico S.Z., Denagel D.C., Dahlseid J.N., Green J.M., Pierce S.K.;
RT "Cloning of the gene encoding peptide-binding protein 74 shows that it
RT is a new member of the heat shock protein 70 family.";
RL Mol. Cell. Biol. 13:3598-3610(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7829505; DOI=10.1074/jbc.270.4.1705;
RA Bhattacharyya T., Karnezis A.N., Murphy S.P., Hoang T., Freeman B.C.,
RA Phillips B., Morimoto R.I.;
RT "Cloning and subcellular localization of human mitochondrial hsp70.";
RL J. Biol. Chem. 270:1705-1710(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TYR-184.
RG NIEHS SNPs program;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-74.
RC TISSUE=Muscle;
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 [8]
RP PROTEIN SEQUENCE OF 47-68.
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 [9]
RP PROTEIN SEQUENCE OF 47-66.
RC TISSUE=Mammary gland;
RX PubMed=7498169; DOI=10.1002/elps.11501601202;
RA Giometti C.S., Tollaksen S.L., Chubb C., Williams C., Huberman E.;
RT "Analysis of proteins from human breast epithelial cells using two-
RT dimensional gel electrophoresis.";
RL Electrophoresis 16:1215-1224(1995).
RN [10]
RP PROTEIN SEQUENCE OF 47-56.
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 [11]
RP SEQUENCE REVISION.
RC TISSUE=Liver;
RX PubMed=8313870; DOI=10.1002/elps.11501401181;
RA Hughes G.J., Frutiger S., Paquet N., Pasquali C., Sanchez J.-C.,
RA Tissot J.-D., Bairoch A., Appel R.D., Hochstrasser D.F.;
RT "Human liver protein map: update 1993.";
RL Electrophoresis 14:1216-1222(1993).
RN [12]
RP PROTEIN SEQUENCE OF 86-99; 108-121; 160-173; 188-202; 207-234;
RP 349-360; 378-391; 395-405; 469-485; 499-513 AND 542-555, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
RP INTERACTION WITH FXN.
RX PubMed=17331979; DOI=10.1093/hmg/ddm038;
RA Shan Y., Napoli E., Cortopassi G.;
RT "Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex
RT and multiple mitochondrial chaperones.";
RL Hum. Mol. Genet. 16:929-941(2007).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-135; LYS-138; LYS-143;
RP LYS-234; LYS-288; LYS-300; LYS-567 AND LYS-646, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
RP INTERACTION WITH HSCB.
RX PubMed=20668094; DOI=10.1093/hmg/ddq301;
RA Uhrigshardt H., Singh A., Kovtunovych G., Ghosh M., Rouault T.A.;
RT "Characterization of the human HSC20, an unusual DnaJ type III
RT protein, involved in iron-sulfur cluster biogenesis.";
RL Hum. Mol. Genet. 19:3816-3834(2010).
RN [16]
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 [17]
RP MALONYLATION AT LYS-206.
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 [18]
RP IDENTIFICATION IN THE MINOS/MITOS COMPLEX.
RX PubMed=22114354; DOI=10.1091/mbc.E11-09-0774;
RA Alkhaja A.K., Jans D.C., Nikolov M., Vukotic M., Lytovchenko O.,
RA Ludewig F., Schliebs W., Riedel D., Urlaub H., Jakobs S., Deckers M.;
RT "MINOS1 is a conserved component of mitofilin complexes and required
RT for mitochondrial function and cristae organization.";
RL Mol. Biol. Cell 23:247-257(2012).
RN [19]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=22002106; DOI=10.1074/mcp.M111.013680;
RA Ahmad Y., Boisvert F.M., Lundberg E., Uhlen M., Lamond A.I.;
RT "Systematic analysis of protein pools, isoforms, and modifications
RT affecting turnover and subcellular localization.";
RL Mol. Cell. Proteomics 11:M111.013680.01-M111.013680.15(2012).
RN [20]
RP INTERACTION WITH DNLZ.
RX PubMed=23462535; DOI=10.1016/j.ijbiomac.2013.02.009;
RA Dores-Silva P.R., Minari K., Ramos C.H., Barbosa L.R., Borges J.C.;
RT "Structural and stability studies of the human mtHsp70-escort protein
RT 1: An essential mortalin co-chaperone.";
RL Int. J. Biol. Macromol. 56:140-148(2013).
CC -!- FUNCTION: Implicated in the control of cell proliferation and
CC cellular aging. May also act as a chaperone.
CC -!- SUBUNIT: Interacts with FXN. Interacts with HSCB. Component of the
CC MINOS/MitOS complex, that includes IMMT, HSPA9 and CHCHD3 and
CC associates with mitochondrial outer membrane proteins SAMM50, MTX1
CC and MTX2. Interacts with DNLZ, the interaction is required to
CC prevent self-aggregation.
CC -!- INTERACTION:
CC P00533:EGFR; NbExp=4; IntAct=EBI-354932, EBI-297353;
CC Q8WX92:NELFB; NbExp=2; IntAct=EBI-354932, EBI-347721;
CC P04637:TP53; NbExp=6; IntAct=EBI-354932, EBI-366083;
CC O15350:TP73; NbExp=11; IntAct=EBI-354932, EBI-389606;
CC -!- SUBCELLULAR LOCATION: Mitochondrion. Nucleus, nucleolus.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/hspa9b/";
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DR EMBL; L11066; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L15189; AAA67526.1; -; mRNA.
DR EMBL; AK315177; BAG37618.1; -; mRNA.
DR EMBL; AK222758; BAD96478.1; -; mRNA.
DR EMBL; DQ531046; ABF50973.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62129.1; -; Genomic_DNA.
DR EMBL; BC000478; AAH00478.1; -; mRNA.
DR EMBL; BC024034; AAH24034.1; -; mRNA.
DR PIR; B48127; B48127.
DR RefSeq; NP_004125.3; NM_004134.6.
DR UniGene; Hs.184233; -.
DR PDB; 3N8E; X-ray; 2.80 A; A/B=439-597.
DR PDBsum; 3N8E; -.
DR ProteinModelPortal; P38646; -.
DR SMR; P38646; 55-651.
DR IntAct; P38646; 41.
DR MINT; MINT-1143092; -.
DR PhosphoSite; P38646; -.
DR DMDM; 21264428; -.
DR DOSAC-COBS-2DPAGE; P38646; -.
DR OGP; P38646; -.
DR REPRODUCTION-2DPAGE; IPI00007765; -.
DR SWISS-2DPAGE; P38646; -.
DR UCD-2DPAGE; P38646; -.
DR PaxDb; P38646; -.
DR PRIDE; P38646; -.
DR DNASU; 3313; -.
DR Ensembl; ENST00000297185; ENSP00000297185; ENSG00000113013.
DR GeneID; 3313; -.
DR KEGG; hsa:3313; -.
DR UCSC; uc003ldf.3; human.
DR CTD; 3313; -.
DR GeneCards; GC05M137890; -.
DR HGNC; HGNC:5244; HSPA9.
DR HPA; CAB005219; -.
DR HPA; HPA000898; -.
DR MIM; 600548; gene.
DR neXtProt; NX_P38646; -.
DR PharmGKB; PA162391712; -.
DR eggNOG; COG0443; -.
DR HOVERGEN; HBG051845; -.
DR InParanoid; P38646; -.
DR KO; K04043; -.
DR OMA; MITKNTT; -.
DR OrthoDB; EOG715Q3K; -.
DR PhylomeDB; P38646; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; HSPA9; human.
DR EvolutionaryTrace; P38646; -.
DR GeneWiki; HSPA9; -.
DR GenomeRNAi; 3313; -.
DR NextBio; 13142; -.
DR PRO; PR:P38646; -.
DR ArrayExpress; P38646; -.
DR Bgee; P38646; -.
DR Genevestigator; P38646; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051082; F:unfolded protein binding; TAS:UniProtKB.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0006626; P:protein targeting to mitochondrion; TAS:Reactome.
DR InterPro; IPR012725; Chaperone_DnaK.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR013126; Hsp_70_fam.
DR Pfam; PF00012; HSP70; 1.
DR PRINTS; PR00301; HEATSHOCK70.
DR TIGRFAMs; TIGR02350; prok_dnaK; 1.
DR PROSITE; PS00297; HSP70_1; 1.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Chaperone; Complete proteome;
KW Direct protein sequencing; Mitochondrion; Nucleotide-binding; Nucleus;
KW Polymorphism; Reference proteome; Transit peptide.
FT TRANSIT 1 46 Mitochondrion.
FT CHAIN 47 679 Stress-70 protein, mitochondrial.
FT /FTId=PRO_0000013563.
FT MOD_RES 76 76 N6-acetyllysine (By similarity).
FT MOD_RES 135 135 N6-acetyllysine.
FT MOD_RES 138 138 N6-acetyllysine.
FT MOD_RES 143 143 N6-acetyllysine.
FT MOD_RES 206 206 N6-acetyllysine; alternate (By
FT similarity).
FT MOD_RES 206 206 N6-malonyllysine; alternate.
FT MOD_RES 234 234 N6-acetyllysine.
FT MOD_RES 288 288 N6-acetyllysine.
FT MOD_RES 300 300 N6-acetyllysine.
FT MOD_RES 567 567 N6-acetyllysine.
FT MOD_RES 600 600 N6-acetyllysine (By similarity).
FT MOD_RES 612 612 N6-acetyllysine (By similarity).
FT MOD_RES 646 646 N6-acetyllysine.
FT VARIANT 74 74 Q -> R (in dbSNP:rs17856004).
FT /FTId=VAR_046482.
FT VARIANT 127 127 R -> G (in dbSNP:rs35091799).
FT /FTId=VAR_049622.
FT VARIANT 184 184 H -> Y.
FT /FTId=VAR_046483.
FT VARIANT 225 225 A -> G (in dbSNP:rs34558740).
FT /FTId=VAR_049623.
FT CONFLICT 48 48 S -> P (in Ref. 9; AA sequence).
FT CONFLICT 66 66 C -> S (in Ref. 9; AA sequence).
FT CONFLICT 176 176 E -> V (in Ref. 3; BAG37618).
FT CONFLICT 184 184 H -> R (in Ref. 7; AAH00478/AAH24034).
FT CONFLICT 249 249 T -> A (in Ref. 4; BAD96478).
FT CONFLICT 385 385 L -> P (in Ref. 4; BAD96478).
FT CONFLICT 540 540 G -> R (in Ref. 2; AAA67526).
FT STRAND 445 448
FT STRAND 452 458
FT STRAND 463 472
FT STRAND 482 490
FT HELIX 494 496
FT STRAND 497 505
FT STRAND 518 524
FT STRAND 530 536
FT TURN 537 539
FT STRAND 542 548
FT HELIX 555 567
FT HELIX 569 590
SQ SEQUENCE 679 AA; 73680 MW; 90969A8D06757753 CRC64;
MISASRAAAA RLVGAAASRG PTAARHQDSW NGLSHEAFRL VSRRDYASEA IKGAVVGIDL
GTTNSCVAVM EGKQAKVLEN AEGARTTPSV VAFTADGERL VGMPAKRQAV TNPNNTFYAT
KRLIGRRYDD PEVQKDIKNV PFKIVRASNG DAWVEAHGKL YSPSQIGAFV LMKMKETAEN
YLGHTAKNAV ITVPAYFNDS QRQATKDAGQ ISGLNVLRVI NEPTAAALAY GLDKSEDKVI
AVYDLGGGTF DISILEIQKG VFEVKSTNGD TFLGGEDFDQ ALLRHIVKEF KRETGVDLTK
DNMALQRVRE AAEKAKCELS SSVQTDINLP YLTMDSSGPK HLNMKLTRAQ FEGIVTDLIR
RTIAPCQKAM QDAEVSKSDI GEVILVGGMT RMPKVQQTVQ DLFGRAPSKA VNPDEAVAIG
AAIQGGVLAG DVTDVLLLDV TPLSLGIETL GGVFTKLINR NTTIPTKKSQ VFSTAADGQT
QVEIKVCQGE REMAGDNKLL GQFTLIGIPP APRGVPQIEV TFDIDANGIV HVSAKDKGTG
REQQIVIQSS GGLSKDDIEN MVKNAEKYAE EDRRKKERVE AVNMAEGIIH DTETKMEEFK
DQLPADECNK LKEEISKMRE LLARKDSETG ENIRQAASSL QQASLKLFEM AYKKMASERE
GSGSSGTGEQ KEDQKEEKQ
//
ID GRP75_HUMAN Reviewed; 679 AA.
AC P38646; B2RCM1; P30036; P31932; Q1HB43; Q53H23; Q6GU03; Q9BWB7;
read moreAC Q9UC56;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 2.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Stress-70 protein, mitochondrial;
DE AltName: Full=75 kDa glucose-regulated protein;
DE Short=GRP-75;
DE AltName: Full=Heat shock 70 kDa protein 9;
DE AltName: Full=Mortalin;
DE Short=MOT;
DE AltName: Full=Peptide-binding protein 74;
DE Short=PBP74;
DE Flags: Precursor;
GN Name=HSPA9; Synonyms=GRP75, HSPA9B, mt-HSP70;
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].
RC TISSUE=B-cell;
RX PubMed=7684501;
RA Domanico S.Z., Denagel D.C., Dahlseid J.N., Green J.M., Pierce S.K.;
RT "Cloning of the gene encoding peptide-binding protein 74 shows that it
RT is a new member of the heat shock protein 70 family.";
RL Mol. Cell. Biol. 13:3598-3610(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7829505; DOI=10.1074/jbc.270.4.1705;
RA Bhattacharyya T., Karnezis A.N., Murphy S.P., Hoang T., Freeman B.C.,
RA Phillips B., Morimoto R.I.;
RT "Cloning and subcellular localization of human mitochondrial hsp70.";
RL J. Biol. Chem. 270:1705-1710(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TYR-184.
RG NIEHS SNPs program;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-74.
RC TISSUE=Muscle;
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 [8]
RP PROTEIN SEQUENCE OF 47-68.
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 [9]
RP PROTEIN SEQUENCE OF 47-66.
RC TISSUE=Mammary gland;
RX PubMed=7498169; DOI=10.1002/elps.11501601202;
RA Giometti C.S., Tollaksen S.L., Chubb C., Williams C., Huberman E.;
RT "Analysis of proteins from human breast epithelial cells using two-
RT dimensional gel electrophoresis.";
RL Electrophoresis 16:1215-1224(1995).
RN [10]
RP PROTEIN SEQUENCE OF 47-56.
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 [11]
RP SEQUENCE REVISION.
RC TISSUE=Liver;
RX PubMed=8313870; DOI=10.1002/elps.11501401181;
RA Hughes G.J., Frutiger S., Paquet N., Pasquali C., Sanchez J.-C.,
RA Tissot J.-D., Bairoch A., Appel R.D., Hochstrasser D.F.;
RT "Human liver protein map: update 1993.";
RL Electrophoresis 14:1216-1222(1993).
RN [12]
RP PROTEIN SEQUENCE OF 86-99; 108-121; 160-173; 188-202; 207-234;
RP 349-360; 378-391; 395-405; 469-485; 499-513 AND 542-555, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [13]
RP INTERACTION WITH FXN.
RX PubMed=17331979; DOI=10.1093/hmg/ddm038;
RA Shan Y., Napoli E., Cortopassi G.;
RT "Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex
RT and multiple mitochondrial chaperones.";
RL Hum. Mol. Genet. 16:929-941(2007).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-135; LYS-138; LYS-143;
RP LYS-234; LYS-288; LYS-300; LYS-567 AND LYS-646, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
RP INTERACTION WITH HSCB.
RX PubMed=20668094; DOI=10.1093/hmg/ddq301;
RA Uhrigshardt H., Singh A., Kovtunovych G., Ghosh M., Rouault T.A.;
RT "Characterization of the human HSC20, an unusual DnaJ type III
RT protein, involved in iron-sulfur cluster biogenesis.";
RL Hum. Mol. Genet. 19:3816-3834(2010).
RN [16]
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 [17]
RP MALONYLATION AT LYS-206.
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 [18]
RP IDENTIFICATION IN THE MINOS/MITOS COMPLEX.
RX PubMed=22114354; DOI=10.1091/mbc.E11-09-0774;
RA Alkhaja A.K., Jans D.C., Nikolov M., Vukotic M., Lytovchenko O.,
RA Ludewig F., Schliebs W., Riedel D., Urlaub H., Jakobs S., Deckers M.;
RT "MINOS1 is a conserved component of mitofilin complexes and required
RT for mitochondrial function and cristae organization.";
RL Mol. Biol. Cell 23:247-257(2012).
RN [19]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=22002106; DOI=10.1074/mcp.M111.013680;
RA Ahmad Y., Boisvert F.M., Lundberg E., Uhlen M., Lamond A.I.;
RT "Systematic analysis of protein pools, isoforms, and modifications
RT affecting turnover and subcellular localization.";
RL Mol. Cell. Proteomics 11:M111.013680.01-M111.013680.15(2012).
RN [20]
RP INTERACTION WITH DNLZ.
RX PubMed=23462535; DOI=10.1016/j.ijbiomac.2013.02.009;
RA Dores-Silva P.R., Minari K., Ramos C.H., Barbosa L.R., Borges J.C.;
RT "Structural and stability studies of the human mtHsp70-escort protein
RT 1: An essential mortalin co-chaperone.";
RL Int. J. Biol. Macromol. 56:140-148(2013).
CC -!- FUNCTION: Implicated in the control of cell proliferation and
CC cellular aging. May also act as a chaperone.
CC -!- SUBUNIT: Interacts with FXN. Interacts with HSCB. Component of the
CC MINOS/MitOS complex, that includes IMMT, HSPA9 and CHCHD3 and
CC associates with mitochondrial outer membrane proteins SAMM50, MTX1
CC and MTX2. Interacts with DNLZ, the interaction is required to
CC prevent self-aggregation.
CC -!- INTERACTION:
CC P00533:EGFR; NbExp=4; IntAct=EBI-354932, EBI-297353;
CC Q8WX92:NELFB; NbExp=2; IntAct=EBI-354932, EBI-347721;
CC P04637:TP53; NbExp=6; IntAct=EBI-354932, EBI-366083;
CC O15350:TP73; NbExp=11; IntAct=EBI-354932, EBI-389606;
CC -!- SUBCELLULAR LOCATION: Mitochondrion. Nucleus, nucleolus.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/hspa9b/";
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; L11066; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; L15189; AAA67526.1; -; mRNA.
DR EMBL; AK315177; BAG37618.1; -; mRNA.
DR EMBL; AK222758; BAD96478.1; -; mRNA.
DR EMBL; DQ531046; ABF50973.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62129.1; -; Genomic_DNA.
DR EMBL; BC000478; AAH00478.1; -; mRNA.
DR EMBL; BC024034; AAH24034.1; -; mRNA.
DR PIR; B48127; B48127.
DR RefSeq; NP_004125.3; NM_004134.6.
DR UniGene; Hs.184233; -.
DR PDB; 3N8E; X-ray; 2.80 A; A/B=439-597.
DR PDBsum; 3N8E; -.
DR ProteinModelPortal; P38646; -.
DR SMR; P38646; 55-651.
DR IntAct; P38646; 41.
DR MINT; MINT-1143092; -.
DR PhosphoSite; P38646; -.
DR DMDM; 21264428; -.
DR DOSAC-COBS-2DPAGE; P38646; -.
DR OGP; P38646; -.
DR REPRODUCTION-2DPAGE; IPI00007765; -.
DR SWISS-2DPAGE; P38646; -.
DR UCD-2DPAGE; P38646; -.
DR PaxDb; P38646; -.
DR PRIDE; P38646; -.
DR DNASU; 3313; -.
DR Ensembl; ENST00000297185; ENSP00000297185; ENSG00000113013.
DR GeneID; 3313; -.
DR KEGG; hsa:3313; -.
DR UCSC; uc003ldf.3; human.
DR CTD; 3313; -.
DR GeneCards; GC05M137890; -.
DR HGNC; HGNC:5244; HSPA9.
DR HPA; CAB005219; -.
DR HPA; HPA000898; -.
DR MIM; 600548; gene.
DR neXtProt; NX_P38646; -.
DR PharmGKB; PA162391712; -.
DR eggNOG; COG0443; -.
DR HOVERGEN; HBG051845; -.
DR InParanoid; P38646; -.
DR KO; K04043; -.
DR OMA; MITKNTT; -.
DR OrthoDB; EOG715Q3K; -.
DR PhylomeDB; P38646; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; HSPA9; human.
DR EvolutionaryTrace; P38646; -.
DR GeneWiki; HSPA9; -.
DR GenomeRNAi; 3313; -.
DR NextBio; 13142; -.
DR PRO; PR:P38646; -.
DR ArrayExpress; P38646; -.
DR Bgee; P38646; -.
DR Genevestigator; P38646; -.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051082; F:unfolded protein binding; TAS:UniProtKB.
DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0006626; P:protein targeting to mitochondrion; TAS:Reactome.
DR InterPro; IPR012725; Chaperone_DnaK.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR013126; Hsp_70_fam.
DR Pfam; PF00012; HSP70; 1.
DR PRINTS; PR00301; HEATSHOCK70.
DR TIGRFAMs; TIGR02350; prok_dnaK; 1.
DR PROSITE; PS00297; HSP70_1; 1.
DR PROSITE; PS00329; HSP70_2; 1.
DR PROSITE; PS01036; HSP70_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Chaperone; Complete proteome;
KW Direct protein sequencing; Mitochondrion; Nucleotide-binding; Nucleus;
KW Polymorphism; Reference proteome; Transit peptide.
FT TRANSIT 1 46 Mitochondrion.
FT CHAIN 47 679 Stress-70 protein, mitochondrial.
FT /FTId=PRO_0000013563.
FT MOD_RES 76 76 N6-acetyllysine (By similarity).
FT MOD_RES 135 135 N6-acetyllysine.
FT MOD_RES 138 138 N6-acetyllysine.
FT MOD_RES 143 143 N6-acetyllysine.
FT MOD_RES 206 206 N6-acetyllysine; alternate (By
FT similarity).
FT MOD_RES 206 206 N6-malonyllysine; alternate.
FT MOD_RES 234 234 N6-acetyllysine.
FT MOD_RES 288 288 N6-acetyllysine.
FT MOD_RES 300 300 N6-acetyllysine.
FT MOD_RES 567 567 N6-acetyllysine.
FT MOD_RES 600 600 N6-acetyllysine (By similarity).
FT MOD_RES 612 612 N6-acetyllysine (By similarity).
FT MOD_RES 646 646 N6-acetyllysine.
FT VARIANT 74 74 Q -> R (in dbSNP:rs17856004).
FT /FTId=VAR_046482.
FT VARIANT 127 127 R -> G (in dbSNP:rs35091799).
FT /FTId=VAR_049622.
FT VARIANT 184 184 H -> Y.
FT /FTId=VAR_046483.
FT VARIANT 225 225 A -> G (in dbSNP:rs34558740).
FT /FTId=VAR_049623.
FT CONFLICT 48 48 S -> P (in Ref. 9; AA sequence).
FT CONFLICT 66 66 C -> S (in Ref. 9; AA sequence).
FT CONFLICT 176 176 E -> V (in Ref. 3; BAG37618).
FT CONFLICT 184 184 H -> R (in Ref. 7; AAH00478/AAH24034).
FT CONFLICT 249 249 T -> A (in Ref. 4; BAD96478).
FT CONFLICT 385 385 L -> P (in Ref. 4; BAD96478).
FT CONFLICT 540 540 G -> R (in Ref. 2; AAA67526).
FT STRAND 445 448
FT STRAND 452 458
FT STRAND 463 472
FT STRAND 482 490
FT HELIX 494 496
FT STRAND 497 505
FT STRAND 518 524
FT STRAND 530 536
FT TURN 537 539
FT STRAND 542 548
FT HELIX 555 567
FT HELIX 569 590
SQ SEQUENCE 679 AA; 73680 MW; 90969A8D06757753 CRC64;
MISASRAAAA RLVGAAASRG PTAARHQDSW NGLSHEAFRL VSRRDYASEA IKGAVVGIDL
GTTNSCVAVM EGKQAKVLEN AEGARTTPSV VAFTADGERL VGMPAKRQAV TNPNNTFYAT
KRLIGRRYDD PEVQKDIKNV PFKIVRASNG DAWVEAHGKL YSPSQIGAFV LMKMKETAEN
YLGHTAKNAV ITVPAYFNDS QRQATKDAGQ ISGLNVLRVI NEPTAAALAY GLDKSEDKVI
AVYDLGGGTF DISILEIQKG VFEVKSTNGD TFLGGEDFDQ ALLRHIVKEF KRETGVDLTK
DNMALQRVRE AAEKAKCELS SSVQTDINLP YLTMDSSGPK HLNMKLTRAQ FEGIVTDLIR
RTIAPCQKAM QDAEVSKSDI GEVILVGGMT RMPKVQQTVQ DLFGRAPSKA VNPDEAVAIG
AAIQGGVLAG DVTDVLLLDV TPLSLGIETL GGVFTKLINR NTTIPTKKSQ VFSTAADGQT
QVEIKVCQGE REMAGDNKLL GQFTLIGIPP APRGVPQIEV TFDIDANGIV HVSAKDKGTG
REQQIVIQSS GGLSKDDIEN MVKNAEKYAE EDRRKKERVE AVNMAEGIIH DTETKMEEFK
DQLPADECNK LKEEISKMRE LLARKDSETG ENIRQAASSL QQASLKLFEM AYKKMASERE
GSGSSGTGEQ KEDQKEEKQ
//
MIM
600548
*RECORD*
*FIELD* NO
600548
*FIELD* TI
*600548 HEAT-SHOCK 70-KD PROTEIN 9; HSPA9
;;HSPA9B;;
MORTALIN;;
MORTALIN 2; MOT2;;
read moreMORTALIN, PERINUCLEAR;;
GLUCOSE-REGULATED PROTEIN, 75-KD; GRP75
*FIELD* TX
DESCRIPTION
HSPA9 is a highly conserved member of the HSP70 family of proteins (see
140550). It functions as a chaperone in the mitochondria, cytoplasm, and
centrosome (summary by Chen et al., 2011).
CLONING
Mortalin has been shown to exhibit differential distributions in cells
with mortal and immortal phenotypes. All immortal human and mouse cells
that have been tested are devoid of the uniformly distributed cytosolic
form of the protein that is characteristic of normal cells. Kaul et al.
(1995) cloned mortalin cDNA from an immortal cell line, RS-4,
established from mouse fibroblasts. The cDNA exhibited the structure of
the perinuclear form, Mot2.
GENE FUNCTION
By immunoprecipitation analysis of mitochondria from human lymphoblasts
and transfected COS-7 cells, Shan et al. (2007) showed that frataxin
(FXN; 606829), which is encoded by the gene mutated in Friedreich ataxia
(229300), interacted directly with several mitochondrial proteins,
including the mitochondrial chaperone HSPA9. Reciprocal
immunoprecipitation analysis confirmed the interaction of FXN and HSPA9
in transfected HEK293 cells.
Heterozygous deletions spanning chromosome 5q31.2 occur frequently in
myelodysplastic syndromes (153550). Chen et al. (2011) purified human
cord blood hematopoietic progenitor cells and grew them under culture
conditions that supported erythroid, myeloid, or megakaryocytic cell
growth. They found that short hairpin RNA-mediated knockdown of HSPA9 in
these progenitors reduced growth predominantly in erythroid progenitors.
Knockdown of HSPA9 in erythroid cultures was associated with an
increased number of cells in the G0/G1 phase of the cell cycle and
accelerated apoptosis. Knockdown of Hspa9 in mouse bone marrow cells,
followed by transplantation into wildtype recipients, also resulted in
loss of erythroid cell number. Chen et al. (2011) concluded that
haploinsufficiency for HSPA9 may contribute to abnormal hematopoiesis in
myelodysplastic syndromes with deletions spanning chromosome 5q31.2.
MAPPING
Using FISH, Kaul et al. (1995) mapped the human mortalin gene to
chromosome 5q31.1. Gross (2011) mapped the HSPA9 gene to chromosome
5q31.2 based on an alignment of the HSPA9 sequence (GenBank GENBANK
AK222758) with the genomic sequence.
In mouse, Kaul et al. (1995) mapped mortalin-related genes to
chromosomes 18 and X.
*FIELD* RF
1. Chen, T. H.-P.; Kambal, A.; Krysiak, K.; Walshauser, M. A.; Raju,
G.; Tibbitts, J. F.; Walter, M. J.: Knockdown of Hspa9, a del(5q31.2)
gene, results in a decrease in hematopoietic progenitors in mice. Blood 117:
1530-1539, 2011.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 9/12/2011.
3. Kaul, S. C.; Wadhwa, R.; Matsuda, Y.; Hensler, P. J.; Pereira-Smith,
O. M.; Komatsu, Y.; Mitsui, Y.: Mouse and human chromosomal assignments
of mortalin, a novel member of the murine hsp70 family of proteins. FEBS
Lett. 361: 269-272, 1995.
4. Shan, Y.; Napoli, E.; Cortopassi, G.: Mitochondrial frataxin interacts
with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Hum.
Molec. Genet. 16: 929-941, 2007.
*FIELD* CN
Matthew B. Gross - updated: 09/12/2011
Patricia A. Hartz - updated: 8/4/2011
Patricia A. Hartz - updated: 3/18/2010
Alan F. Scott - updated: 3/10/1996
*FIELD* CD
Victor A. McKusick: 5/22/1995
*FIELD* ED
mgross: 09/12/2011
terry: 8/4/2011
mgross: 3/18/2010
terry: 3/18/2010
alopez: 9/5/2000
alopez: 9/4/1998
terry: 7/24/1998
carol: 7/24/1998
dkim: 7/24/1998
alopez: 9/12/1997
alopez: 9/5/1997
terry: 4/17/1996
mark: 3/10/1996
mark: 6/5/1995
mark: 5/22/1995
*RECORD*
*FIELD* NO
600548
*FIELD* TI
*600548 HEAT-SHOCK 70-KD PROTEIN 9; HSPA9
;;HSPA9B;;
MORTALIN;;
MORTALIN 2; MOT2;;
read moreMORTALIN, PERINUCLEAR;;
GLUCOSE-REGULATED PROTEIN, 75-KD; GRP75
*FIELD* TX
DESCRIPTION
HSPA9 is a highly conserved member of the HSP70 family of proteins (see
140550). It functions as a chaperone in the mitochondria, cytoplasm, and
centrosome (summary by Chen et al., 2011).
CLONING
Mortalin has been shown to exhibit differential distributions in cells
with mortal and immortal phenotypes. All immortal human and mouse cells
that have been tested are devoid of the uniformly distributed cytosolic
form of the protein that is characteristic of normal cells. Kaul et al.
(1995) cloned mortalin cDNA from an immortal cell line, RS-4,
established from mouse fibroblasts. The cDNA exhibited the structure of
the perinuclear form, Mot2.
GENE FUNCTION
By immunoprecipitation analysis of mitochondria from human lymphoblasts
and transfected COS-7 cells, Shan et al. (2007) showed that frataxin
(FXN; 606829), which is encoded by the gene mutated in Friedreich ataxia
(229300), interacted directly with several mitochondrial proteins,
including the mitochondrial chaperone HSPA9. Reciprocal
immunoprecipitation analysis confirmed the interaction of FXN and HSPA9
in transfected HEK293 cells.
Heterozygous deletions spanning chromosome 5q31.2 occur frequently in
myelodysplastic syndromes (153550). Chen et al. (2011) purified human
cord blood hematopoietic progenitor cells and grew them under culture
conditions that supported erythroid, myeloid, or megakaryocytic cell
growth. They found that short hairpin RNA-mediated knockdown of HSPA9 in
these progenitors reduced growth predominantly in erythroid progenitors.
Knockdown of HSPA9 in erythroid cultures was associated with an
increased number of cells in the G0/G1 phase of the cell cycle and
accelerated apoptosis. Knockdown of Hspa9 in mouse bone marrow cells,
followed by transplantation into wildtype recipients, also resulted in
loss of erythroid cell number. Chen et al. (2011) concluded that
haploinsufficiency for HSPA9 may contribute to abnormal hematopoiesis in
myelodysplastic syndromes with deletions spanning chromosome 5q31.2.
MAPPING
Using FISH, Kaul et al. (1995) mapped the human mortalin gene to
chromosome 5q31.1. Gross (2011) mapped the HSPA9 gene to chromosome
5q31.2 based on an alignment of the HSPA9 sequence (GenBank GENBANK
AK222758) with the genomic sequence.
In mouse, Kaul et al. (1995) mapped mortalin-related genes to
chromosomes 18 and X.
*FIELD* RF
1. Chen, T. H.-P.; Kambal, A.; Krysiak, K.; Walshauser, M. A.; Raju,
G.; Tibbitts, J. F.; Walter, M. J.: Knockdown of Hspa9, a del(5q31.2)
gene, results in a decrease in hematopoietic progenitors in mice. Blood 117:
1530-1539, 2011.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 9/12/2011.
3. Kaul, S. C.; Wadhwa, R.; Matsuda, Y.; Hensler, P. J.; Pereira-Smith,
O. M.; Komatsu, Y.; Mitsui, Y.: Mouse and human chromosomal assignments
of mortalin, a novel member of the murine hsp70 family of proteins. FEBS
Lett. 361: 269-272, 1995.
4. Shan, Y.; Napoli, E.; Cortopassi, G.: Mitochondrial frataxin interacts
with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Hum.
Molec. Genet. 16: 929-941, 2007.
*FIELD* CN
Matthew B. Gross - updated: 09/12/2011
Patricia A. Hartz - updated: 8/4/2011
Patricia A. Hartz - updated: 3/18/2010
Alan F. Scott - updated: 3/10/1996
*FIELD* CD
Victor A. McKusick: 5/22/1995
*FIELD* ED
mgross: 09/12/2011
terry: 8/4/2011
mgross: 3/18/2010
terry: 3/18/2010
alopez: 9/5/2000
alopez: 9/4/1998
terry: 7/24/1998
carol: 7/24/1998
dkim: 7/24/1998
alopez: 9/12/1997
alopez: 9/5/1997
terry: 4/17/1996
mark: 3/10/1996
mark: 6/5/1995
mark: 5/22/1995