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    HSPA9 heat shock 70kDa protein 9 (mortalin) [ Homo sapiens ]

    Gene ID: 3313, updated on 19-May-2012
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    Summary

    Official Symbol
    HSPA9provided by HGNC
    Official Full Name
    heat shock 70kDa protein 9 (mortalin)provided by HGNC
    Primary source
    HGNC:5244
    See related
    Ensembl:ENSG00000113013; HPRD:02770; MIM:600548; Vega:OTTHUMG00000129206
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CSA; MOT; MOT2; GRP75; PBP74; GRP-75; HSPA9B; MTHSP75; MGC4500
    Summary
    This gene encodes a member of the heat shock protein 70 gene family. The encoded protein is primarily localized to the mitochondria but is also found in the endoplasmic reticulum, plasma membrane and cytoplasmic vesicles. This protein is a heat-shock cognate protein. This protein plays a role in cell proliferation, stress response and maintenance of the mitochondria. A pseudogene of this gene is found on chromosome 2.[provided by RefSeq, May 2010]
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    Genomic context

    Location :
    5q31.1
    Sequence :
    Chromosome: 5; NC_000005.9 (137890571..137911318, complement)
    See HSPA9 in Epigenomics, MapViewer

    Chromosome 5 - NC_000005.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100652898 Neighboring gene ribosomal protein L7 pseudogene 19 Neighboring gene eukaryotic translation termination factor 1 Neighboring gene small nucleolar RNA, C/D box 63 Neighboring gene ribosomal protein L10a pseudogene 10 Neighboring gene catenin (cadherin-associated protein), alpha 1, 102kDa Neighboring gene leucine rich repeat transmembrane neuronal 2

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Integrative analysis of the ubiquitin proteome isolated using Tandem Ubiquitin Binding Entities (TUBEs). Lopitz-Otsoa F, et al. J Proteomics, 2012 Jun 6. PMID 22178446.
    2. The DNLZ/HEP zinc-binding subdomain is critical for regulation of the mitochondrial chaperone HSPA9. Vu MT, et al. Protein Sci, 2012 Feb. PMID 22162012.
    3. MINOS1 is a conserved component of mitofilin complexes and required for mitochondrial function and cristae organization. Alkhaja AK, et al. Mol Biol Cell, 2012 Jan. PMID 22114354.
    4. Proteomic analysis of the 20S proteasome (PSMA3)-interacting proteins reveals a functional link between the proteasome and mRNA metabolism. Fedorova OA, et al. Biochem Biophys Res Commun, 2011 Dec 16. PMID 22079093.
    5. Nuclear GRP75 binds retinoic acid receptors to promote neuronal differentiation of neuroblastoma. Shih YY, et al. PLoS One, 2011. PMID 22022577.

    See all (104) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Cytoprotective efficacy of mortalin under Abeta-induced stress in SH-SY5Y cells is mediated, at least in part, by inhibition of mPTP opening.
      Title: Inhibition of mitochondrial permeability transition pore opening is involved in the protective effects of mortalin overexpression against beta-amyloid-induced apoptosis in SH-SY5Y cells.
    2. Nef's interaction with cellular mortalin is required for Nef secretion.
      Title: Secretion modification region-derived peptide disrupts HIV-1 Nef's interaction with mortalin and blocks virus and Nef exosome release.
    3. The present study further demonstrated that GRP75 translocates into the nucleus and physically interacts with retinoid receptors (RARalpha and RXRalpha) to augment retinoic acid-elicited neuronal differentiation.
      Title: Nuclear GRP75 binds retinoic acid receptors to promote neuronal differentiation of neuroblastoma.
    4. HSP70 as a critical regulator of ARF-mediated autophagy, and reinforce the importance of mitochondrial trafficking of ARF for its autophagy function
      Title: Interaction of the ARF tumor suppressor with cytosolic HSP70 contributes to its autophagy function.
    5. Mortalin is up-regulated in liver tumors.
      Title: Expression of mortalin detected in human liver cancer by tissue microarrays.
    6. Cisplatin resistance of lung cancer cells is associated with overexpression of GRP75 gene
      Title: [RNA Interference targeting GRP75 decreases cisplatin resistance in human lung adenocarcinoma cell].
    7. the relatively decreased mortalin expression level and its impaired interaction with Parkin could affect its roles in mitochondrial function.
      Title: Mitochondrial dysfunction induced by knockdown of mortalin is rescued by Parkin.
    8. Targeting mortalin-p53 interaction with either mortalin small hairpin RNA or a chemical or peptide inhibitor could induce p53-mediated tumor cell-specific apoptosis in hepatocellular carcinoma; p53-null hepatoma or normal hepatocytes remain unaffected.
      Title: Mortalin-p53 interaction in cancer cells is stress dependent and constitutes a selective target for cancer therapy.
    9. These findings implicate a conserved histidine as critical for DNLZ regulation of mitochondrial HSPA9 catalytic activity.
      Title: A conserved histidine in human DNLZ/HEP is required for stimulation of HSPA9 ATPase activity.
    10. Data show that mortalin can afford protection against Abeta(1-42)-induced neurotoxicity in SH-SY5Y cells.
      Title: Mortalin overexpression attenuates beta-amyloid-induced neurotoxicity in SH-SY5Y cells.
    Submit: New GeneRIF Correction See all (39)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Over expression of hsp70 with a herpes viral amplicon vector protects cultured hippocampal rat neurons from gp120 neurotoxicity PubMed
    env The exposure of permissive CD4+ cells to HIV-1 gp120 increases the synthesis and nuclear translocation of 70kDa heat shock protein PubMed
    Pr55(Gag) gag Hsp70 co-sediments with HIV-1 capsid protein in sucrose density gradients, providing evidence that it is specifically incorporated into HIV-1 virions through an interaction with HIV-1 Gag proteins PubMed
    gag Hsp70 is incorporated into HIV-1 virions through an interaction with HIV-1 Gag PubMed
    Tat tat Hsp70 and Hsp90 and Cdc37 regulate the stabilization and folding of CDK9 as well as the assembly of an active CDK9/cyclin T1 complex responsible for P-TEFb-mediated HIV-1 Tat transactivation PubMed
    Vpr vpr HIV-1 Vpr competes with Hsp70 for binding to karyopherin alpha PubMed
    matrix gag Hsp70 facilitates nuclear import of HIV-1 preintegration complexes by stimulating the binding of HIV-1 Matrix to karyopherin alpha PubMed

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_004125.3 NP_003365.1 VDAC1    BIND  PubMed PBP74 interacts with hVDAC1. 
    P38646 P05230 FGF1    HPRD  PubMed  
    P38646 P14625 HSP90B1    HPRD  PubMed  
    P38646 P53602 MVD    HPRD  PubMed  
    P38646 Q6EEV6 SUMO4    HPRD  PubMed  
    P38646 P04637 TP53    HPRD  PubMed  
    P38646 P61981 YWHAG    HPRD  PubMed  
    BioGRID:109545 BioGRID:113911 BAP1    BioGRID  PubMed Co-purification 
    BioGRID:109545 BioGRID:107463 CDKN2A    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:126272 DNAJC19    BioGRID  PubMed Biochemical Activity 
    BioGRID:109545 BioGRID:608915 DNLZ    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109545 BioGRID:128177 EIF2C3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:108537 FGF1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:109545 BioGRID:116452 GPN1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:109212 GTF2A1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:109268 H2AFX    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:115719 HAX1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:115331 HDAC5    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:109318 HDGF    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:109420 HNRNPA1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:109622 ICT1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:136699 MINOS1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:109545 BioGRID:110682 MVD    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:109545 BioGRID:111657 PSMA3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:123598 RNF146    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:116983 SIRT1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:116982 SIRT3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:116734 SPG20    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:109545 BioGRID:113188 SUMO1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:112497 SUMO2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:132223 SUMO4    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:114896 TBPL1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:113010 TP53    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:109545 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109545 BioGRID:113364 YWHAG    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    • Homologs of the HSPA9 gene: The HSPA9 gene is conserved in chimpanzee, , dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, , S.pombe, , N.crassa, A.thaliana, rice, and P.falciparum.
    • Map Viewer (Mouse, Rat)

    Pathways from BioSystems

    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • Mitochondrial Protein Import, organism-specific biosystem (from REACTOME)
      Mitochondrial Protein Import, organism-specific biosystemA human mitochondrion contains about 1500 proteins, more than 99% of which are encoded in the nucleus, synthesized in the cytosol and imported into the mitochondrion. Proteins are targeted to four lo...
    • RNA degradation, organism-specific biosystem (from KEGG)
      RNA degradation, organism-specific biosystemThe correct processing, quality control and turnover of cellular RNA molecules are critical to many aspects in the expression of genetic information. In eukaryotes, two major pathways of mRNA decay e...
    • RNA degradation, conserved biosystem (from KEGG)
      RNA degradation, conserved biosystemThe correct processing, quality control and turnover of cellular RNA molecules are critical to many aspects in the expression of genetic information. In eukaryotes, two major pathways of mRNA decay e...
    • Tuberculosis, organism-specific biosystem (from KEGG)
      Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
    • Tuberculosis, conserved biosystem (from KEGG)
      Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enzyme binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		  
    unfolded protein binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    anti-apoptosis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    protein export from nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein folding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    mitochondrial nucleoid IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    mitochondrion TAS
    Traceable Author Statement
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    stress-70 protein, mitochondrial
    Names
    stress-70 protein, mitochondrial
    mortalin-2
    p66-mortalin
    mortalin, perinuclear
    heat shock 70kD protein 9B
    peptide-binding protein 74
    75 kDa glucose-regulated protein
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029469.1 RefSeqGene

      Range
      5001..25748
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_004134.6 → NP_004125.3  stress-70 protein, mitochondrial precursor

      Status: REVIEWED

      Source sequence(s)
      AC011385, AC113340, AK225488, AK315177, DC356852
      Consensus CDS
      CCDS4208.1
      UniProtKB/Swiss-Prot
      P38646
      Related
      ENSP00000297185, OTTHUMP00000159494, ENST00000297185, OTTHUMT00000251285
      Conserved Domains (1) summary
      PRK00290
      Location:52 – 656
      Blast Score: 2716
      dnaK; molecular chaperone DnaK; Provisional

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000005.9 Reference GRCh37.p5 Primary Assembly

      Range
      137890571..137911318, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000137.1 Alternate HuRef

      Range
      133080998..133101775, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC011385.6 (79100..93627) None
    genomic AC113340.2 (77982..84038) None
    genomic CH471062.2 EAW62128.1
      EAW62129.1
    genomic DQ531046.1 ABF50973.1
    mRNA AK023317.1 None
    mRNA AK222758.1 BAD96478.1
    mRNA AK225488.1 None
    mRNA AK293990.1 BAH11643.1
    mRNA AK297795.1 BAH12669.1
    mRNA AK297897.1 BAH12688.1
    mRNA AK315177.1 BAG37618.1
    mRNA AU130219.1 None
    mRNA BC000478.2 AAH00478.1
    mRNA BC024034.2 AAH24034.1
    mRNA BC030634.1 AAH30634.1
    mRNA BX426279.2 None
    mRNA DC356852.1 None
    mRNA DQ185038.1 ABD14419.1
    mRNA DQ480334.1 ABF19573.1
    mRNA L11066.1 None
    mRNA L15189.1 AAA67526.1
    other-genetic EU446981.1 ABZ92510.1
    other-genetic JF432370.1 ADZ15587.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P38646.2 GenPept UniProtKB/Swiss-Prot:P38646
    Q2F839 GenPept UniProtKB/TrEMBL:Q2F839
    Q8N1C8 GenPept UniProtKB/TrEMBL:Q8N1C8
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

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