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Protein

Stress-70 protein, mitochondrial

Gene

HSPA9

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU (PubMed:26702583). Regulates erythropoiesis via stabilization of ISC assembly (PubMed:21123823, PubMed:26702583). May play a role in the control of cell proliferation and cellular aging (By similarity).By similarity2 Publications

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • RNA binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: UniProtKB

GO - Biological processi

  • erythrocyte differentiation Source: UniProtKB
  • interleukin-12-mediated signaling pathway Source: Reactome
  • iron-sulfur cluster assembly Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of erythrocyte differentiation Source: UniProtKB
  • negative regulation of hematopoietic stem cell differentiation Source: Ensembl
  • protein export from nucleus Source: Ensembl
  • protein folding Source: InterPro
  • regulation of erythrocyte differentiation Source: UniProtKB

Keywordsi

Molecular functionChaperone
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-1268020 Mitochondrial protein import
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-8949613 Cristae formation
R-HSA-8950505 Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
SIGNORiP38646

Names & Taxonomyi

Protein namesi
Recommended name:
Stress-70 protein, mitochondrial
Alternative name(s):
75 kDa glucose-regulated protein
Short name:
GRP-75
Heat shock 70 kDa protein 9
Mortalin
Short name:
MOT
Peptide-binding protein 74
Short name:
PBP74
Gene namesi
Name:HSPA9
Synonyms:GRP75, HSPA9B, mt-HSP70
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113013.12
HGNCiHGNC:5244 HSPA9
MIMi600548 gene
neXtProtiNX_P38646

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Anemia, sideroblastic, 4 (SIDBA4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA4 has been reported to be inherited as an autosomal recessive disease, with a pseudodominant pattern of inheritance in some families.
See also OMIM:182170
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076665212S → P in SIDBA4; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs768283289Ensembl.1
Natural variantiVAR_076666388G → S in SIDBA4; unknown pathological significance. 1 Publication1
Natural variantiVAR_076667415E → K in SIDBA4; unknown pathological significance. 1 Publication1
Natural variantiVAR_076668458 – 459Missing in SIDBA4. 1 Publication2
Even-plus syndrome (EVPLS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive syndrome characterized by epiphyseal and vertebral dysplasia, prenatal-onset short stature, a distinct craniofacial phenotype with microtia, a flat facial profile with flat nose and triangular nares, cardiac malformations, and additional findings such as anal atresia, hypodontia, aplasia cutis, and others.
See also OMIM:616854
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076662126R → W in EVPLS. 1 PublicationCorresponds to variant dbSNP:rs751478142EnsemblClinVar.1
Natural variantiVAR_076663128Y → C in EVPLS. 1 PublicationCorresponds to variant dbSNP:rs765368797EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi489G → E: Significant loss of interaction with FXN and ISCU. Significant increase in interaction with NFS1. 1 Publication1

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi3313
MalaCardsiHSPA9
MIMi182170 phenotype
616854 phenotype
OpenTargetsiENSG00000113013
PharmGKBiPA162391712

Polymorphism and mutation databases

BioMutaiHSPA9
DMDMi21264428

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 46Mitochondrion3 PublicationsAdd BLAST46
ChainiPRO_000001356347 – 679Stress-70 protein, mitochondrialAdd BLAST633

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei76N6-acetyllysineBy similarity1
Modified residuei87PhosphothreonineCombined sources1
Modified residuei135N6-acetyllysine; alternateCombined sources1
Modified residuei135N6-succinyllysine; alternateBy similarity1
Modified residuei138N6-acetyllysine; alternateCombined sources1
Modified residuei138N6-succinyllysine; alternateBy similarity1
Modified residuei143N6-acetyllysineCombined sources1
Modified residuei206N6-acetyllysine; alternateBy similarity1
Modified residuei206N6-malonyllysine; alternate1 Publication1
Modified residuei206N6-succinyllysine; alternateBy similarity1
Modified residuei234N6-acetyllysineCombined sources1
Modified residuei288N6-acetyllysineCombined sources1
Modified residuei300N6-acetyllysine; alternateCombined sources1
Modified residuei300N6-succinyllysine; alternateBy similarity1
Modified residuei368N6-succinyllysineBy similarity1
Modified residuei394N6-succinyllysineBy similarity1
Modified residuei408PhosphoserineCombined sources1
Modified residuei513Omega-N-methylarginineCombined sources1
Modified residuei567N6-acetyllysine; alternateCombined sources1
Modified residuei567N6-succinyllysine; alternateBy similarity1
Modified residuei600N6-acetyllysine; alternateBy similarity1
Modified residuei600N6-succinyllysine; alternateBy similarity1
Modified residuei610N6-succinyllysineBy similarity1
Modified residuei612N6-acetyllysineBy similarity1
Modified residuei646N6-acetyllysine; alternateCombined sources1
Modified residuei646N6-succinyllysine; alternateBy similarity1

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

EPDiP38646
MaxQBiP38646
PaxDbiP38646
PeptideAtlasiP38646
PRIDEiP38646
ProteomicsDBi55304
TopDownProteomicsiP38646

2D gel databases

DOSAC-COBS-2DPAGEiP38646
OGPiP38646
REPRODUCTION-2DPAGEiIPI00007765
SWISS-2DPAGEiP38646
UCD-2DPAGEiP38646

PTM databases

iPTMnetiP38646
PhosphoSitePlusiP38646
SwissPalmiP38646

Expressioni

Gene expression databases

BgeeiENSG00000113013
ExpressionAtlasiP38646 baseline and differential
GenevisibleiP38646 HS

Organism-specific databases

HPAiCAB005219
HPA000898

Interactioni

Subunit structurei

Interacts strongly with the intermediate form of FXN and weakly with its mature form (PubMed:17331979, PubMed:26702583). Interacts with HSCB (PubMed:20668094). Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MINOS1/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1, MTX2 and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9 (PubMed:22114354). Interacts with DNLZ, the interaction is required to prevent self-aggregation (PubMed:23462535). Interacts with TESPA1 (PubMed:23501103). Interacts with PDPN (PubMed:23541579). Interacts with NFU1, NFS1 and ISCU (PubMed:26702583).7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL
  • unfolded protein binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109545, 231 interactors
CORUMiP38646
DIPiDIP-32936N
IntActiP38646, 97 interactors
MINTiP38646
STRINGi9606.ENSP00000297185

Structurei

Secondary structure

1679
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi56 – 59Combined sources4
Beta strandi62 – 71Combined sources10
Beta strandi74 – 77Combined sources4
Beta strandi91 – 93Combined sources3
Beta strandi99 – 102Combined sources4
Helixi103 – 106Combined sources4
Turni107 – 111Combined sources5
Helixi113 – 115Combined sources3
Helixi120 – 122Combined sources3
Turni123 – 125Combined sources3
Helixi131 – 139Combined sources9
Beta strandi141 – 146Combined sources6
Beta strandi148 – 156Combined sources9
Beta strandi159 – 161Combined sources3
Helixi163 – 182Combined sources20
Beta strandi188 – 193Combined sources6
Helixi199 – 211Combined sources13
Beta strandi215 – 221Combined sources7
Helixi222 – 229Combined sources8
Helixi232 – 234Combined sources3
Beta strandi236 – 245Combined sources10
Beta strandi250 – 258Combined sources9
Beta strandi261 – 270Combined sources10
Helixi275 – 294Combined sources20
Helixi302 – 318Combined sources17
Turni319 – 321Combined sources3
Beta strandi323 – 333Combined sources11
Beta strandi340 – 347Combined sources8
Helixi348 – 354Combined sources7
Helixi356 – 360Combined sources5
Helixi363 – 372Combined sources10
Turni377 – 379Combined sources3
Beta strandi382 – 387Combined sources6
Helixi388 – 391Combined sources4
Helixi393 – 403Combined sources11
Turni413 – 415Combined sources3
Helixi416 – 428Combined sources13
Beta strandi445 – 448Combined sources4
Beta strandi452 – 458Combined sources7
Beta strandi463 – 472Combined sources10
Beta strandi482 – 490Combined sources9
Helixi494 – 496Combined sources3
Beta strandi497 – 505Combined sources9
Beta strandi518 – 524Combined sources7
Beta strandi530 – 536Combined sources7
Turni537 – 539Combined sources3
Beta strandi542 – 548Combined sources7
Helixi555 – 567Combined sources13
Helixi569 – 590Combined sources22

3D structure databases

ProteinModelPortaliP38646
SMRiP38646
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP38646

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 432Interaction with NFS11 PublicationAdd BLAST432
Regioni432 – 679Interaction with FXN and ISCU1 PublicationAdd BLAST248

Sequence similaritiesi

Belongs to the heat shock protein 70 family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0102 Eukaryota
COG0443 LUCA
GeneTreeiENSGT00920000149123
HOVERGENiHBG051845
InParanoidiP38646
KOiK04043
OMAiISIKRHM
OrthoDBiEOG091G0386
PhylomeDBiP38646
TreeFamiTF105046

Family and domain databases

Gene3Di1.20.1270.10, 1 hit
2.60.34.10, 1 hit
HAMAPiMF_00332 DnaK, 1 hit
InterProiView protein in InterPro
IPR012725 Chaperone_DnaK
IPR018181 Heat_shock_70_CS
IPR029048 HSP70_C_sf
IPR029047 HSP70_peptide-bd_sf
IPR013126 Hsp_70_fam
PANTHERiPTHR19375 PTHR19375, 1 hit
PfamiView protein in Pfam
PF00012 HSP70, 1 hit
PRINTSiPR00301 HEATSHOCK70
SUPFAMiSSF100920 SSF100920, 1 hit
TIGRFAMsiTIGR02350 prok_dnaK, 1 hit
PROSITEiView protein in PROSITE
PS00297 HSP70_1, 1 hit
PS00329 HSP70_2, 1 hit
PS01036 HSP70_3, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P38646-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MISASRAAAA RLVGAAASRG PTAARHQDSW NGLSHEAFRL VSRRDYASEA
60 70 80 90 100
IKGAVVGIDL GTTNSCVAVM EGKQAKVLEN AEGARTTPSV VAFTADGERL
110 120 130 140 150
VGMPAKRQAV TNPNNTFYAT KRLIGRRYDD PEVQKDIKNV PFKIVRASNG
160 170 180 190 200
DAWVEAHGKL YSPSQIGAFV LMKMKETAEN YLGHTAKNAV ITVPAYFNDS
210 220 230 240 250
QRQATKDAGQ ISGLNVLRVI NEPTAAALAY GLDKSEDKVI AVYDLGGGTF
260 270 280 290 300
DISILEIQKG VFEVKSTNGD TFLGGEDFDQ ALLRHIVKEF KRETGVDLTK
310 320 330 340 350
DNMALQRVRE AAEKAKCELS SSVQTDINLP YLTMDSSGPK HLNMKLTRAQ
360 370 380 390 400
FEGIVTDLIR RTIAPCQKAM QDAEVSKSDI GEVILVGGMT RMPKVQQTVQ
410 420 430 440 450
DLFGRAPSKA VNPDEAVAIG AAIQGGVLAG DVTDVLLLDV TPLSLGIETL
460 470 480 490 500
GGVFTKLINR NTTIPTKKSQ VFSTAADGQT QVEIKVCQGE REMAGDNKLL
510 520 530 540 550
GQFTLIGIPP APRGVPQIEV TFDIDANGIV HVSAKDKGTG REQQIVIQSS
560 570 580 590 600
GGLSKDDIEN MVKNAEKYAE EDRRKKERVE AVNMAEGIIH DTETKMEEFK
610 620 630 640 650
DQLPADECNK LKEEISKMRE LLARKDSETG ENIRQAASSL QQASLKLFEM
660 670
AYKKMASERE GSGSSGTGEQ KEDQKEEKQ
Length:679
Mass (Da):73,680
Last modified:May 27, 2002 - v2
Checksum:i90969A8D06757753
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti48S → P AA sequence (PubMed:7498169).Curated1
Sequence conflicti66C → S AA sequence (PubMed:7498169).Curated1
Sequence conflicti176E → V in BAG37618 (PubMed:14702039).Curated1
Sequence conflicti184H → R in AAH00478 (PubMed:15489334).Curated1
Sequence conflicti184H → R in AAH24034 (PubMed:15489334).Curated1
Sequence conflicti249T → A in BAD96478 (Ref. 4) Curated1
Sequence conflicti385L → P in BAD96478 (Ref. 4) Curated1
Sequence conflicti540G → R in AAA67526 (PubMed:7829505).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04648274Q → R1 PublicationCorresponds to variant dbSNP:rs17856004Ensembl.1
Natural variantiVAR_076662126R → W in EVPLS. 1 PublicationCorresponds to variant dbSNP:rs751478142EnsemblClinVar.1
Natural variantiVAR_049622127R → G. Corresponds to variant dbSNP:rs35091799Ensembl.1
Natural variantiVAR_076663128Y → C in EVPLS. 1 PublicationCorresponds to variant dbSNP:rs765368797EnsemblClinVar.1
Natural variantiVAR_046483184H → Y1 Publication1
Natural variantiVAR_076664200S → L1 PublicationCorresponds to variant dbSNP:rs199715716Ensembl.1
Natural variantiVAR_076665212S → P in SIDBA4; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs768283289Ensembl.1
Natural variantiVAR_049623225A → G. Corresponds to variant dbSNP:rs34558740Ensembl.1
Natural variantiVAR_076666388G → S in SIDBA4; unknown pathological significance. 1 Publication1
Natural variantiVAR_076667415E → K in SIDBA4; unknown pathological significance. 1 Publication1
Natural variantiVAR_076668458 – 459Missing in SIDBA4. 1 Publication2
Natural variantiVAR_076669539T → K1 Publication1
Natural variantiVAR_076670573R → W1 PublicationCorresponds to variant dbSNP:rs147723579Ensembl.1
Natural variantiVAR_076671577E → K1 PublicationCorresponds to variant dbSNP:rs905439101Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L11066 mRNA No translation available.
L15189 mRNA Translation: AAA67526.1
AK315177 mRNA Translation: BAG37618.1
AK222758 mRNA Translation: BAD96478.1
DQ531046 Genomic DNA Translation: ABF50973.1
CH471062 Genomic DNA Translation: EAW62129.1
BC000478 mRNA Translation: AAH00478.1
BC024034 mRNA Translation: AAH24034.1
CCDSiCCDS4208.1
PIRiB48127
RefSeqiNP_004125.3, NM_004134.6
UniGeneiHs.184233

Genome annotation databases

EnsembliENST00000297185; ENSP00000297185; ENSG00000113013
GeneIDi3313
KEGGihsa:3313
UCSCiuc003ldf.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGRP75_HUMAN
AccessioniPrimary (citable) accession number: P38646
Secondary accession number(s): B2RCM1
, P30036, P31932, Q1HB43, Q53H23, Q6GU03, Q9BWB7, Q9UC56
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: May 27, 2002
Last modified: July 18, 2018
This is version 201 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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