ID GRP75_RAT Reviewed; 679 AA. AC P48721; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 02-OCT-2024, entry version 170. DE RecName: Full=Stress-70 protein, mitochondrial {ECO:0000305}; 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 AltName: Full=Peptide-binding protein 74; DE Short=PBP74; DE AltName: Full=mtHSP70; DE Flags: Precursor; GN Name=Hspa9 {ECO:0000312|RGD:1311806}; Synonyms=Grp75, Hspa9a; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION. RX PubMed=7811387; DOI=10.1089/dna.1994.13.1213; RA Webster T.J., Naylor D.J., Hartman D.J., Hoej P.B., Hoogenraad N.J.; RT "cDNA cloning and efficient mitochondrial import of pre-mtHSP70 from rat RT liver."; RL DNA Cell Biol. 13:1213-1220(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7629893; DOI=10.1002/jnr.490400612; RA Massa S.M., Longo F.M., Zuo J., Wang S., Chen J., Sharp F.R.; RT "Cloning of rat grp75, an hsp70-family member, and its expression in normal RT and ischemic brain."; RL J. Neurosci. Res. 40:807-819(1995). RN [3] RP PROTEIN SEQUENCE OF 80-98 AND 484-503. RX PubMed=2372296; DOI=10.1016/0006-291x(90)91281-v; RA Akamizu T., Saji M., Kohn L.D.; RT "A microsequencing approach to identify proteins which appear to interact RT with thyrotropin in rat FRTL-5 thyroid cells."; RL Biochem. Biophys. Res. Commun. 170:351-358(1990). RN [4] RP PROTEIN SEQUENCE OF 188-202; 266-284; 499-513 AND 577-595, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord; RA Lubec G., Vishwanath V., Afjehi-Sadat L.; RL Submitted (NOV-2006) to UniProtKB. RN [5] RP INTERACTION WITH ITPR1 AND VDAC1, AND SUBCELLULAR LOCATION. RX PubMed=17178908; DOI=10.1083/jcb.200608073; RA Szabadkai G., Bianchi K., Varnai P., De Stefani D., Wieckowski M.R., RA Cavagna D., Nagy A.I., Balla T., Rizzuto R.; RT "Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial RT Ca2+ channels."; RL J. Cell Biol. 175:901-911(2006). 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 Regulates erythropoiesis via stabilization of ISC assembly. May play a CC role in cell cycle regulation via its interaction with and promotion of CC degradation of TP53 (By similarity). May play a role in the control of CC cell proliferation and cellular aging (By similarity). Molecular CC adapter that regulates mitochondrial calcium-dependent apoptosis by CC coupling two calcium channels, ITPR1 and VDAC1, at the mitochondria- CC associated endoplasmic reticulum (ER) membrane to facilitate calcium CC transport from the ER lumen to the mitochondria intermembrane space, CC thus providing calcium for the downstream calcium channel MCU that CC directly releases it into mitochondria matrix (By similarity). CC {ECO:0000250|UniProtKB:P38646, ECO:0000250|UniProtKB:P38647}. CC -!- SUBUNIT: Interacts strongly with the intermediate form of FXN and CC weakly with its mature form. Interacts with HSCB. 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. Interacts with DNLZ, the interaction is required CC to prevent self-aggregation. Interacts with TESPA1. Interacts with CC PDPN. Interacts with NFU1, NFS1 and ISCU. Interacts with TP53; the CC interaction promotes TP53 degradation (By similarity). Interacts (via CC SBD domain) with UBXN2A; the interaction with UBXN2A inhibits CC HSPA9/MOT-2 interaction with and degradation of TP53, thereby promotes CC TP53 translocation to the nucleus (By similarity). Interacts with ITPR1 CC AND VDAC1; this interaction couples ITPR1 to VDAC1 (PubMed:17178908). CC {ECO:0000250|UniProtKB:P38646, ECO:0000269|PubMed:17178908}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:7811387}. CC Nucleus, nucleolus {ECO:0000250|UniProtKB:P38646}. Cytoplasm CC {ECO:0000269|PubMed:17178908}. Mitochondrion matrix CC {ECO:0000269|PubMed:17178908}. Note=Found in a complex with HSPA9 and CC VDAC1 at the endoplasmic reticulum-mitochondria contact sites. CC {ECO:0000269|PubMed:17178908}. CC -!- SIMILARITY: Belongs to the heat shock protein 70 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; S75280; AAB33049.1; -; mRNA. DR EMBL; S78556; AAB34982.1; -; mRNA. DR PIR; I56581; I56581. DR AlphaFoldDB; P48721; -. DR SMR; P48721; -. DR IntAct; P48721; 5. DR MINT; P48721; -. DR STRING; 10116.ENSRNOP00000026696; -. DR CarbonylDB; P48721; -. DR GlyGen; P48721; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P48721; -. DR PhosphoSitePlus; P48721; -. DR SwissPalm; P48721; -. DR jPOST; P48721; -. DR PaxDb; 10116-ENSRNOP00000026696; -. DR ABCD; P48721; 1 sequenced antibody. DR UCSC; RGD:1311806; rat. DR AGR; RGD:1311806; -. DR RGD; 1311806; Hspa9. DR eggNOG; KOG0102; Eukaryota. DR InParanoid; P48721; -. DR PhylomeDB; P48721; -. DR Reactome; R-RNO-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-RNO-6799198; Complex I biogenesis. DR Reactome; R-RNO-9837999; Mitochondrial protein degradation. DR Reactome; R-RNO-9865881; Complex III assembly. DR PRO; PR:P48721; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB. DR GO; GO:0042645; C:mitochondrial nucleoid; ISO:RGD. DR GO; GO:0005739; C:mitochondrion; ISO:RGD. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. 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:0019899; F:enzyme binding; ISO:RGD. DR GO; GO:0017134; F:fibroblast growth factor binding; IPI:RGD. DR GO; GO:0031072; F:heat shock protein binding; IPI:RGD. DR GO; GO:0044183; F:protein folding chaperone; IBA:GO_Central. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:RGD. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD. DR GO; GO:0051082; F:unfolded protein binding; IEA:InterPro. DR GO; GO:0036444; P:calcium import into the mitochondrion; IMP:UniProtKB. DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD. DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IBA:GO_Central. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0016226; P:iron-sulfur cluster assembly; ISS:UniProtKB. DR GO; GO:0045647; P:negative regulation of erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:1902037; P:negative regulation of hematopoietic stem cell differentiation; ISS:UniProtKB. DR GO; GO:1903707; P:negative regulation of hemopoiesis; ISS:UniProtKB. DR GO; GO:0006611; P:protein export from nucleus; ISO:RGD. DR GO; GO:0042026; P:protein refolding; IBA:GO_Central. DR GO; GO:0045646; P:regulation of erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0051593; P:response to folic acid; IEP:RGD. DR GO; GO:0097068; P:response to thyroxine; IEP:RGD. DR GO; GO:0009636; P:response to toxic substance; IEP:RGD. DR CDD; cd11733; HSPA9-like_NBD; 1. DR Gene3D; 1.20.1270.10; -; 1. DR Gene3D; 3.30.30.30; -; 1. DR Gene3D; 3.30.420.40; -; 2. 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 NCBIfam; TIGR02350; prok_dnaK; 1. DR PANTHER; PTHR19375; HEAT SHOCK PROTEIN 70KDA; 1. DR PANTHER; PTHR19375:SF184; STRESS-70 PROTEIN, MITOCHONDRIAL; 1. DR Pfam; PF00012; HSP70; 1. DR PRINTS; PR00301; HEATSHOCK70. DR SUPFAM; SSF53067; Actin-like ATPase domain; 2. DR SUPFAM; SSF100920; Heat shock protein 70kD (HSP70), peptide-binding domain; 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 Acetylation; ATP-binding; Chaperone; Cytoplasm; Direct protein sequencing; KW Methylation; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Transit peptide. FT TRANSIT 1..46 FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:P38646" FT CHAIN 47..679 FT /note="Stress-70 protein, mitochondrial" FT /id="PRO_0000013565" FT REGION 1..432 FT /note="Interaction with NFS1" FT /evidence="ECO:0000250|UniProtKB:P38646" FT REGION 432..679 FT /note="Interaction with FXN and ISCU" FT /evidence="ECO:0000250|UniProtKB:P38646" FT REGION 655..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:0000250|UniProtKB:P38646" FT MOD_RES 135 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P38646" 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:0000250|UniProtKB:P38646" 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:0000250|UniProtKB:P38646" 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:0000250" 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:0000250|UniProtKB:P38646" FT MOD_RES 288 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P38646" FT MOD_RES 300 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P38646" FT MOD_RES 300 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P38647" FT MOD_RES 360 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P38647" FT MOD_RES 360 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:0000250|UniProtKB:P38646" FT MOD_RES 513 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P38646" FT MOD_RES 567 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P38646" 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:0000250|UniProtKB:P38646" FT MOD_RES 646 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P38647" FT CONFLICT 37 FT /note="V -> A (in Ref. 2; AAB34982)" FT /evidence="ECO:0000305" FT CONFLICT 81 FT /note="A -> S (in Ref. 1; AAB33049)" FT /evidence="ECO:0000305" FT CONFLICT 373 FT /note="R -> A (in Ref. 2; AAB34982)" FT /evidence="ECO:0000305" FT CONFLICT 487 FT /note="C -> T (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 493 FT /note="M -> Q (in Ref. 3; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 589 FT /note="I -> V (in Ref. 1; AAB33049)" FT /evidence="ECO:0000305" SQ SEQUENCE 679 AA; 73858 MW; 4616EDE5307691A4 CRC64; MISASRAAAA RLVGTTASRS PAAARHQDGW NGLSHEVFRF VSRRDYASEA IKGAVVGIDL GTTNSCVAVM EGKQAKVLEN AEGARTTPSV VAFTPDGERL VGMPAKRQAV TNPNNTFYAT KRLIGRRYDD PEVQKDTKNV PFKIVRASNG DAWVEAHGKL YSPSQIGAFV LMKMKETAEN YLGHTAKNAV ITVPAYFNDS QRQATKDAGQ ISGLNVLRVI NEPTAAALAY GLDKSEDKVI AVYDLGGGTF DISILEIQKG VFEVKSTNGD TFLGGEDFDQ ALLRHIVKEF KRETGVDLTK DNMALQRVRE AAEKAKCELS SSVQTDINLP YLTMDASGPK HLNMKLTRAQ FEGIVTDLIK RTIAPCQKAM QDREVSKSDI 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 GSGSSSTGEQ KEDQKEEKQ //