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    TOMM70 translocase of outer mitochondrial membrane 70 [ Homo sapiens (human) ]

    Gene ID: 9868, updated on 28-Oct-2024

    Summary

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    Official Symbol
    TOMM70provided by HGNC
    Official Full Name
    translocase of outer mitochondrial membrane 70provided by HGNC
    Primary source
    HGNC:HGNC:11985
    See related
    Ensembl:ENSG00000154174 MIM:606081; AllianceGenome:HGNC:11985
    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
    Tom70; TOMM70A
    Summary
    This gene encodes an import receptor of the outer mitochondrial membrane that is part of the translocase of the outer membrane complex. This protein is involved in the import of mitochondrial precursor proteins. The protein interacts with the SARS-CoV and SARS-Cov-2 ORF9b proteins. [provided by RefSeq, Dec 2021]
    Annotation information
    Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
    Expression
    Ubiquitous expression in brain (RPKM 23.1), thyroid (RPKM 20.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TOMM70 in Genome Data Viewer
    Location:
    3q12.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (100363431..100401089, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (103068774..103106448, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (100082275..100119933, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene hESC enhancers GRCh37_chr3:99979240-99979908 and GRCh37_chr3:99979909-99980577 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:99981915-99982583 Neighboring gene TBC1 domain family member 23 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20153 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:100047046-100047276 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:100053369-100053937 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20154 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20155 Neighboring gene Sharpr-MPRA regulatory region 4023 Neighboring gene nitrilase family member 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:100118351-100119270 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20157 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14571 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20158 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20159 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14572 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:100126809-100127334 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:100127335-100127860 Neighboring gene leukemia NUP98 fusion partner 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:100170016-100170553 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:100184868-100185368 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr3:100195719-100196404 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14573 Neighboring gene transmembrane protein 45A Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:100280470-100281334

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Characterization of a human import component of the mitochondrial outer membrane, TOMM70A. Edmonson AM, et al. Cell Commun Adhes, 2002 Jan-Feb. PMID 12200962
    2. Human mitochondrial import receptor Tom70 functions as a monomer. Fan AC, et al. Biochem J, 2010 Aug 1. PMID 20504278, Free PMC Article
    3. Mutations in TOMM70 lead to multi-OXPHOS deficiencies and cause severe anemia, lactic acidosis, and developmental delay. Wei X, et al. J Hum Genet, 2020 Mar. PMID 31907385
    4. SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms. O'Donoghue SI, et al. Mol Syst Biol, 2021 Sep. PMID 34519429, Free PMC Article
    5. Evolution of enhanced innate immune evasion by SARS-CoV-2. Thorne LG, et al. Nature, 2022 Feb. PMID 34942634, Free PMC Article

    See all (124) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis.
      Title: The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis.
    2. Mitochondria shed their outer membrane in response to infection-induced stress.
      Title: Mitochondria shed their outer membrane in response to infection-induced stress.
    3. Relation between ORF8a and the mitochondrial protein TOM70 in SARS-CoV-2 infection.
      Title: Relation between ORF8a and the mitochondrial protein TOM70 in SARS-CoV-2 infection.
    4. Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting to Two Binding Sites in TOM70 and Recruitment of Hsp90.
      Title: Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting to Two Binding Sites in TOM70 and Recruitment of Hsp90.
    5. De novo mutations in TOMM70, a receptor of the mitochondrial import translocase, cause neurological impairment.
      Title: De novo mutations in TOMM70, a receptor of the mitochondrial import translocase, cause neurological impairment.
    6. Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions.
      Title: Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions.
    7. Mutations in TOMM70 lead to multi-OXPHOS deficiencies and cause severe anemia, lactic acidosis, and developmental delay.
      Title: Mutations in TOMM70 lead to multi-OXPHOS deficiencies and cause severe anemia, lactic acidosis, and developmental delay.
    8. SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70.
      Title: SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70.
    9. TOM70, but not TOM20, clusters in distinct OMM foci, frequently overlapping with sites in which the endoplasmic reticulum (ER) contacts mitochondria. Functionally, TOM70 depletion specifically impairs inositol trisphosphates (IP3)-linked ER to mitochondria Ca(2+) transfer. This phenomenon is dependent on the capacity of TOM70 to interact with IP3-receptors and favor their functional recruitment close to mitochondria.
      Title: TOM70 Sustains Cell Bioenergetics by Promoting IP3R3-Mediated ER to Mitochondria Ca(2+) Transfer.
    10. Collectively, this study characterizes a novel protein complex, Tom70/Hsp90/IRF3/Bax, that is important for Sendai virus-induced apoptosis.
      Title: Tom70 mediates Sendai virus-induced apoptosis on mitochondria.
    Submit: New GeneRIF Correction See all GeneRIFs (25)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of translocase of outer mitochondrial membrane 70 homolog A (TOMM70A) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ90470

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables mitochondrion targeting sequence binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables mitochondrion targeting sequence binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables molecular adaptor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    contributes_to protein transmembrane transporter activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    contributes_to protein transmembrane transporter activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein transmembrane transporter activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in activation of innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular response to virus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of cell growth involved in cardiac muscle cell development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of defense response to virus by host IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of interferon-beta production IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein targeting to mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein import into mitochondrial matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein import into mitochondrial matrix ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein insertion into mitochondrial inner membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein insertion into mitochondrial inner membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein insertion into mitochondrial outer membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in protein targeting to mitochondrion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in protein targeting to mitochondrion TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in response to thyroxine IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of TOM complex NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in extracellular exosome HDA PubMed 
    located_in membrane HDA PubMed 
    is_active_in mitochondrial membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in mitochondrial outer membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial outer membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrial outer membrane TAS
    Traceable Author Statement
    more info
    		  
    part_of mitochondrial outer membrane translocase complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    part_of mitochondrial outer membrane translocase complex TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    mitochondrial import receptor subunit TOM70
    Names
    mitochondrial precursor proteins import receptor
    translocase of outer membrane 70 kDa subunit
    translocase of outer mitochondrial membrane 70 homolog A
    translocase of outer mitochondrial membrane protein 70

    NCBI Reference Sequences (RefSeq)

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    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.

    mRNA and Protein(s)

    1. NM_014820.5 → NP_055635.3  mitochondrial import receptor subunit TOM70

      See identical proteins and their annotated locations for NP_055635.3

      Status: REVIEWED

      Source sequence(s)
      AB018262, AC093003, AW044465, BC065555
      Consensus CDS
      CCDS33807.1
      UniProtKB/Swiss-Prot
      D3DN48, O94826
      UniProtKB/TrEMBL
      B4DZ87
      Related
      ENSP00000284320.5, ENST00000284320.6
      Conserved Domains (2) summary
      TIGR00990
      Location:41 → 601
      3a0801s09; mitochondrial precursor proteins import receptor (72 kDa mitochondrial outermembrane protein) (mitochondrial import receptor for the ADP/ATP carrier) (translocase of outermembrane tom70)
      sd00006
      Location:114 → 142
      TPR; TPR repeat [structural motif]

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      100363431..100401089 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      103068774..103106448 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O94826.1 GenPept UniProtKB/Swiss-Prot:O94826

    Gene LinkOut

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

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