GRP75_HUMAN
ID GRP75_HUMAN Reviewed; 679 AA.
AC P38646; B2RCM1; P30036; P31932; Q1HB43; Q53H23; Q6GU03; Q9BWB7; Q9UC56;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 229.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=B-cell;
RX PubMed=7684501; DOI=10.1128/mcb.13.6.3598-3610.1993;
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 is a
RT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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; 349-360;
RP 378-391; 395-405; 469-485; 499-513 AND 542-555, AND IDENTIFICATION BY 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 IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [14]
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 and
RT multiple mitochondrial chaperones.";
RL Hum. Mol. Genet. 16:929-941(2007).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-135; LYS-138; LYS-143; LYS-234;
RP LYS-288; LYS-300; LYS-567 AND LYS-646, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [16]
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 protein,
RT involved in iron-sulfur cluster biogenesis.";
RL Hum. Mol. Genet. 19:3816-3834(2010).
RN [17]
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., Buerckstuemmer T.,
RA 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 [18]
RP FUNCTION.
RX PubMed=21123823; DOI=10.1182/blood-2010-06-293167;
RA Chen T.H., Kambal A., Krysiak K., Walshauser M.A., Raju G., Tibbitts J.F.,
RA Walter M.J.;
RT "Knockdown of Hspa9, a del(5q31.2) gene, results in a decrease in
RT hematopoietic progenitors in mice.";
RL Blood 117:1530-1539(2011).
RN [19]
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., He W.,
RA Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J.,
RA 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 [20]
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 for
RT mitochondrial function and cristae organization.";
RL Mol. Biol. Cell 23:247-257(2012).
RN [21]
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 [22]
RP INTERACTION WITH TESPA.
RX PubMed=23501103; DOI=10.1016/j.bbrc.2013.02.099;
RA Matsuzaki H., Fujimoto T., Tanaka M., Shirasawa S.;
RT "Tespa1 is a novel component of mitochondria-associated endoplasmic
RT reticulum membranes and affects mitochondrial calcium flux.";
RL Biochem. Biophys. Res. Commun. 433:322-326(2013).
RN [23]
RP INTERACTION WITH PDPN.
RX PubMed=23541579; DOI=10.1016/j.bbrc.2013.03.057;
RA Tsuneki M., Maruyama S., Yamazaki M., Xu B., Essa A., Abe T., Babkair H.,
RA Cheng J., Yamamoto T., Saku T.;
RT "Extracellular heat shock protein A9 is a novel interaction partner of
RT podoplanin in oral squamous cell carcinoma cells.";
RL Biochem. Biophys. Res. Commun. 434:124-130(2013).
RN [24]
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 1: An
RT essential mortalin co-chaperone.";
RL Int. J. Biol. Macromol. 56:140-148(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-87 AND SER-408, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [27]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-513, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [28]
RP INVOLVEMENT IN SIDBA4, VARIANTS SIDBA4 PRO-212; SER-388; LYS-415 AND
RP 458-ILE-ASN-459 DEL, AND VARIANTS LEU-200; LYS-539; TRP-573 AND LYS-577.
RX PubMed=26491070; DOI=10.1182/blood-2015-09-659854;
RA Schmitz-Abe K., Ciesielski S.J., Schmidt P.J., Campagna D.R., Rahimov F.,
RA Schilke B.A., Cuijpers M., Rieneck K., Lausen B., Linenberger M.L.,
RA Sendamarai A.K., Guo C., Hofmann I., Newburger P.E., Matthews D.,
RA Shimamura A., Snijders P.J., Towne M.C., Niemeyer C.M., Watson H.G.,
RA Dziegiel M.H., Heeney M.M., May A., Bottomley S.S., Swinkels D.W.,
RA Markianos K., Craig E.A., Fleming M.D.;
RT "Congenital sideroblastic anemia due to mutations in the mitochondrial
RT HSP70 homologue HSPA9.";
RL Blood 126:2734-2738(2015).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [30]
RP INVOLVEMENT IN EVPLS, AND VARIANTS EVPLS TRP-126 AND CYS-128.
RX PubMed=26598328; DOI=10.1038/srep17154;
RA Royer-Bertrand B., Castillo-Taucher S., Moreno-Salinas R., Cho T.J.,
RA Chae J.H., Choi M., Kim O.H., Dikoglu E., Campos-Xavier B., Girardi E.,
RA Superti-Furga G., Bonafe L., Rivolta C., Unger S., Superti-Furga A.;
RT "Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS
RT syndrome of congenital malformations and skeletal dysplasia.";
RL Sci. Rep. 5:17154-17154(2015).
RN [31]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FXN; NFU1; NFS1 AND ISCU,
RP AND MUTAGENESIS OF GLY-489.
RX PubMed=26702583; DOI=10.1016/j.mito.2015.12.005;
RA Shan Y., Cortopassi G.;
RT "Mitochondrial Hspa9/Mortalin regulates erythroid differentiation via iron-
RT sulfur cluster assembly.";
RL Mitochondrion 26:94-103(2016).
CC -!- FUNCTION: Chaperone protein which plays an important role in
CC mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and
CC stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU
CC (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC
CC assembly (PubMed:21123823, PubMed:26702583). May play a role in the
CC control of cell proliferation and cellular aging (By similarity).
CC {ECO:0000250|UniProtKB:P38647, ECO:0000269|PubMed:21123823,
CC ECO:0000269|PubMed:26702583}.
CC -!- SUBUNIT: Interacts strongly with the intermediate form of FXN and
CC weakly with its mature form (PubMed:17331979, PubMed:26702583).
CC Interacts with HSCB (PubMed:20668094). Associates with the
CC mitochondrial contact site and cristae organizing system (MICOS)
CC complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19,
CC CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13.
CC This complex was also known under the names MINOS or MitOS complex. The
CC MICOS complex associates with mitochondrial outer membrane proteins
CC SAMM50, MTX1, MTX2 and DNAJC11, mitochondrial inner membrane protein
CC TMEM11 and with HSPA9 (PubMed:22114354). Interacts with DNLZ, the
CC interaction is required to prevent self-aggregation (PubMed:23462535).
CC Interacts with TESPA1 (PubMed:23501103). Interacts with PDPN
CC (PubMed:23541579). Interacts with NFU1, NFS1 and ISCU
CC (PubMed:26702583). {ECO:0000269|PubMed:17331979,
CC ECO:0000269|PubMed:20668094, ECO:0000269|PubMed:22114354,
CC ECO:0000269|PubMed:23462535, ECO:0000269|PubMed:23501103,
CC ECO:0000269|PubMed:23541579, ECO:0000269|PubMed:26702583}.
CC -!- INTERACTION:
CC P38646; P00533: EGFR; NbExp=5; IntAct=EBI-354932, EBI-297353;
CC P38646; Q9HAV7: GRPEL1; NbExp=2; IntAct=EBI-354932, EBI-1043499;
CC P38646; Q8IWL3: HSCB; NbExp=15; IntAct=EBI-354932, EBI-1805738;
CC P38646; Q8WX92: NELFB; NbExp=2; IntAct=EBI-354932, EBI-347721;
CC P38646; Q99650: OSMR; NbExp=4; IntAct=EBI-354932, EBI-2804080;
CC P38646; P04637: TP53; NbExp=6; IntAct=EBI-354932, EBI-366083;
CC P38646; O15350: TP73; NbExp=11; IntAct=EBI-354932, EBI-389606;
CC P38646; P13693: TPT1; NbExp=4; IntAct=EBI-354932, EBI-1783169;
CC P38646; A4D2J0: YKT6; NbExp=3; IntAct=EBI-354932, EBI-10173443;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:22002106,
CC ECO:0000269|PubMed:26702583}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:22002106}.
CC -!- DISEASE: Anemia, sideroblastic, 4 (SIDBA4) [MIM:182170]: A form of
CC sideroblastic anemia, a bone marrow disorder defined by the presence of
CC pathologic iron deposits in erythroblast mitochondria. Sideroblastic
CC anemia is characterized by anemia of varying severity, hypochromic
CC peripheral erythrocytes, systemic iron overload secondary to chronic
CC ineffective erythropoiesis, and the presence of bone marrow ringed
CC sideroblasts. Sideroblasts are characterized by iron-loaded
CC mitochondria clustered around the nucleus. SIDBA4 has been reported to
CC be inherited as an autosomal recessive disease, with a pseudodominant
CC pattern of inheritance in some families. {ECO:0000269|PubMed:26491070}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Even-plus syndrome (EVPLS) [MIM:616854]: An autosomal
CC recessive syndrome characterized by epiphyseal and vertebral dysplasia,
CC prenatal-onset short stature, a distinct craniofacial phenotype with
CC microtia, a flat facial profile with flat nose and triangular nares,
CC cardiac malformations, and additional findings such as anal atresia,
CC hypodontia, aplasia cutis, and others. {ECO:0000269|PubMed:26598328}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}.
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 CCDS; CCDS4208.1; -.
DR PIR; B48127; B48127.
DR RefSeq; NP_004125.3; NM_004134.6.
DR PDB; 3N8E; X-ray; 2.80 A; A/B=439-597.
DR PDB; 4KBO; X-ray; 2.80 A; A=52-431.
DR PDB; 6NHK; X-ray; 2.78 A; A/B=54-429.
DR PDB; 6P2U; X-ray; 2.00 A; A=52-431.
DR PDB; 6PMT; X-ray; 2.30 A; A=52-431.
DR PDBsum; 3N8E; -.
DR PDBsum; 4KBO; -.
DR PDBsum; 6NHK; -.
DR PDBsum; 6P2U; -.
DR PDBsum; 6PMT; -.
DR AlphaFoldDB; P38646; -.
DR SMR; P38646; -.
DR BioGRID; 109545; 556.
DR ComplexPortal; CPX-6129; TIM23 mitochondrial inner membrane pre-sequence translocase complex, TIM17A variant.
DR ComplexPortal; CPX-6130; TIM23 mitochondrial inner membrane pre-sequence translocase complex, TIM17B variant.
DR CORUM; P38646; -.
DR DIP; DIP-32936N; -.
DR IntAct; P38646; 185.
DR MINT; P38646; -.
DR STRING; 9606.ENSP00000297185; -.
DR BindingDB; P38646; -.
DR ChEMBL; CHEMBL4295757; -.
DR GlyGen; P38646; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P38646; -.
DR MetOSite; P38646; -.
DR PhosphoSitePlus; P38646; -.
DR SwissPalm; P38646; -.
DR BioMuta; HSPA9; -.
DR DMDM; 21264428; -.
DR DOSAC-COBS-2DPAGE; P38646; -.
DR OGP; P38646; -.
DR REPRODUCTION-2DPAGE; IPI00007765; -.
DR SWISS-2DPAGE; P38646; -.
DR UCD-2DPAGE; P38646; -.
DR EPD; P38646; -.
DR jPOST; P38646; -.
DR MassIVE; P38646; -.
DR MaxQB; P38646; -.
DR PaxDb; P38646; -.
DR PeptideAtlas; P38646; -.
DR PRIDE; P38646; -.
DR ProteomicsDB; 55304; -.
DR TopDownProteomics; P38646; -.
DR ABCD; P38646; 8 sequenced antibodies.
DR Antibodypedia; 646; 778 antibodies from 47 providers.
DR DNASU; 3313; -.
DR Ensembl; ENST00000297185.9; ENSP00000297185.3; ENSG00000113013.16.
DR GeneID; 3313; -.
DR KEGG; hsa:3313; -.
DR MANE-Select; ENST00000297185.9; ENSP00000297185.3; NM_004134.7; NP_004125.3.
DR UCSC; uc003ldf.4; human.
DR CTD; 3313; -.
DR DisGeNET; 3313; -.
DR GeneCards; HSPA9; -.
DR HGNC; HGNC:5244; HSPA9.
DR HPA; ENSG00000113013; Low tissue specificity.
DR MalaCards; HSPA9; -.
DR MIM; 182170; phenotype.
DR MIM; 600548; gene.
DR MIM; 616854; phenotype.
DR neXtProt; NX_P38646; -.
DR OpenTargets; ENSG00000113013; -.
DR Orphanet; 260305; Autosomal recessive sideroblastic anemia.
DR Orphanet; 496751; EVEN-plus syndrome.
DR PharmGKB; PA162391712; -.
DR VEuPathDB; HostDB:ENSG00000113013; -.
DR eggNOG; KOG0102; Eukaryota.
DR GeneTree; ENSGT00920000149123; -.
DR HOGENOM; CLU_005965_2_1_1; -.
DR InParanoid; P38646; -.
DR OMA; ISIKRHM; -.
DR OrthoDB; 288077at2759; -.
DR PhylomeDB; P38646; -.
DR TreeFam; TF105046; -.
DR BRENDA; 3.6.4.10; 2681.
DR PathwayCommons; P38646; -.
DR Reactome; R-HSA-1268020; Mitochondrial protein import.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-HSA-8949613; Cristae formation.
DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation.
DR SignaLink; P38646; -.
DR SIGNOR; P38646; -.
DR BioGRID-ORCS; 3313; 755 hits in 1059 CRISPR screens.
DR ChiTaRS; HSPA9; human.
DR EvolutionaryTrace; P38646; -.
DR GeneWiki; HSPA9; -.
DR GenomeRNAi; 3313; -.
DR Pharos; P38646; Tchem.
DR PRO; PR:P38646; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P38646; protein.
DR Bgee; ENSG00000113013; Expressed in adrenal tissue and 208 other tissues.
DR ExpressionAtlas; P38646; baseline and differential.
DR Genevisible; P38646; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0140275; C:MIB complex; HDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IC:ComplexPortal.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0001401; C:SAM complex; HDA:UniProtKB.
DR GO; GO:0005744; C:TIM23 mitochondrial import inner membrane translocase complex; IC:ComplexPortal.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0140662; F:ATP-dependent protein folding chaperone; IEA:InterPro.
DR GO; GO:0031072; F:heat shock protein binding; IBA:GO_Central.
DR GO; GO:0051787; F:misfolded protein binding; IBA:GO_Central.
DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0034620; P:cellular response to unfolded protein; IBA:GO_Central.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0007007; P:inner mitochondrial membrane organization; IC:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IC:ComplexPortal.
DR GO; GO:0016226; P:iron-sulfur cluster assembly; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0045647; P:negative regulation of erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:1902037; P:negative regulation of hematopoietic stem cell differentiation; IEA:Ensembl.
DR GO; GO:1903707; P:negative regulation of hemopoiesis; IEA:Ensembl.
DR GO; GO:0006611; P:protein export from nucleus; IEA:Ensembl.
DR GO; GO:0042026; P:protein refolding; IBA:GO_Central.
DR GO; GO:0045646; P:regulation of erythrocyte differentiation; IMP:UniProtKB.
DR Gene3D; 1.20.1270.10; -; 1.
DR Gene3D; 2.60.34.10; -; 1.
DR HAMAP; MF_00332; DnaK; 1.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR012725; Chaperone_DnaK.
DR InterPro; IPR018181; Heat_shock_70_CS.
DR InterPro; IPR029048; HSP70_C_sf.
DR InterPro; IPR029047; HSP70_peptide-bd_sf.
DR InterPro; IPR013126; Hsp_70_fam.
DR PANTHER; PTHR19375; PTHR19375; 1.
DR Pfam; PF00012; HSP70; 1.
DR SUPFAM; SSF100920; SSF100920; 1.
DR SUPFAM; SSF53067; SSF53067; 2.
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;
KW Direct protein sequencing; Disease variant; Dwarfism; Methylation;
KW Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..46
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1286669,
FT ECO:0000269|PubMed:7498169, ECO:0000269|PubMed:9150948"
FT CHAIN 47..679
FT /note="Stress-70 protein, mitochondrial"
FT /id="PRO_0000013563"
FT REGION 1..432
FT /note="Interaction with NFS1"
FT /evidence="ECO:0000269|PubMed:26702583"
FT REGION 432..679
FT /note="Interaction with FXN and ISCU"
FT /evidence="ECO:0000269|PubMed:26702583"
FT REGION 656..679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 665..679
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 76
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 87
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 135
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 135
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 138
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 138
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 143
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 206
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 206
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:21908771"
FT MOD_RES 206
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 234
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 288
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 300
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 300
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 368
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 394
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 513
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 567
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 567
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 600
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 600
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 610
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 612
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT MOD_RES 646
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 646
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P38647"
FT VARIANT 74
FT /note="Q -> R (in dbSNP:rs17856004)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_046482"
FT VARIANT 126
FT /note="R -> W (in EVPLS; dbSNP:rs751478142)"
FT /evidence="ECO:0000269|PubMed:26598328"
FT /id="VAR_076662"
FT VARIANT 127
FT /note="R -> G (in dbSNP:rs35091799)"
FT /id="VAR_049622"
FT VARIANT 128
FT /note="Y -> C (in EVPLS; dbSNP:rs765368797)"
FT /evidence="ECO:0000269|PubMed:26598328"
FT /id="VAR_076663"
FT VARIANT 184
FT /note="H -> Y"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_046483"
FT VARIANT 200
FT /note="S -> L (in dbSNP:rs199715716)"
FT /evidence="ECO:0000269|PubMed:26491070"
FT /id="VAR_076664"
FT VARIANT 212
FT /note="S -> P (in SIDBA4; unknown pathological
FT significance; dbSNP:rs768283289)"
FT /evidence="ECO:0000269|PubMed:26491070"
FT /id="VAR_076665"
FT VARIANT 225
FT /note="A -> G (in dbSNP:rs34558740)"
FT /id="VAR_049623"
FT VARIANT 388
FT /note="G -> S (in SIDBA4; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26491070"
FT /id="VAR_076666"
FT VARIANT 415
FT /note="E -> K (in SIDBA4; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26491070"
FT /id="VAR_076667"
FT VARIANT 458..459
FT /note="Missing (in SIDBA4)"
FT /evidence="ECO:0000269|PubMed:26491070"
FT /id="VAR_076668"
FT VARIANT 539
FT /note="T -> K"
FT /evidence="ECO:0000269|PubMed:26491070"
FT /id="VAR_076669"
FT VARIANT 573
FT /note="R -> W (in dbSNP:rs147723579)"
FT /evidence="ECO:0000269|PubMed:26491070"
FT /id="VAR_076670"
FT VARIANT 577
FT /note="E -> K (in dbSNP:rs905439101)"
FT /evidence="ECO:0000269|PubMed:26491070"
FT /id="VAR_076671"
FT MUTAGEN 489
FT /note="G->E: Significant loss of interaction with FXN and
FT ISCU. Significant increase in interaction with NFS1."
FT /evidence="ECO:0000269|PubMed:26702583"
FT CONFLICT 48
FT /note="S -> P (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 66
FT /note="C -> S (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="E -> V (in Ref. 3; BAG37618)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="H -> R (in Ref. 7; AAH00478/AAH24034)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="T -> A (in Ref. 4; BAD96478)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="L -> P (in Ref. 4; BAD96478)"
FT /evidence="ECO:0000305"
FT CONFLICT 540
FT /note="G -> R (in Ref. 2; AAA67526)"
FT /evidence="ECO:0000305"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 62..71
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:6NHK"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:6P2U"
FT TURN 107..111
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:6P2U"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 131..139
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 142..146
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 163..182
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 199..211
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 222..229
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 236..245
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 250..258
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 261..270
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 275..293
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:6PMT"
FT HELIX 302..318
FT /evidence="ECO:0007829|PDB:6P2U"
FT TURN 319..321
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 323..334
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 339..347
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 348..354
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 356..360
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 363..372
FT /evidence="ECO:0007829|PDB:6P2U"
FT TURN 377..379
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 382..387
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 388..391
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 393..403
FT /evidence="ECO:0007829|PDB:6P2U"
FT TURN 413..415
FT /evidence="ECO:0007829|PDB:6P2U"
FT HELIX 416..428
FT /evidence="ECO:0007829|PDB:6P2U"
FT STRAND 445..448
FT /evidence="ECO:0007829|PDB:3N8E"
FT STRAND 452..458
FT /evidence="ECO:0007829|PDB:3N8E"
FT STRAND 463..472
FT /evidence="ECO:0007829|PDB:3N8E"
FT STRAND 482..490
FT /evidence="ECO:0007829|PDB:3N8E"
FT HELIX 494..496
FT /evidence="ECO:0007829|PDB:3N8E"
FT STRAND 497..505
FT /evidence="ECO:0007829|PDB:3N8E"
FT STRAND 518..524
FT /evidence="ECO:0007829|PDB:3N8E"
FT STRAND 530..536
FT /evidence="ECO:0007829|PDB:3N8E"
FT TURN 537..539
FT /evidence="ECO:0007829|PDB:3N8E"
FT STRAND 542..548
FT /evidence="ECO:0007829|PDB:3N8E"
FT HELIX 555..567
FT /evidence="ECO:0007829|PDB:3N8E"
FT HELIX 569..590
FT /evidence="ECO:0007829|PDB:3N8E"
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
