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    Tbc1d1 TBC1 domain family, member 1 [ Mus musculus (house mouse) ]

    Gene ID: 57915, updated on 27-Nov-2024

    Summary

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    Official Symbol
    Tbc1d1provided by MGI
    Official Full Name
    TBC1 domain family, member 1provided by MGI
    Primary source
    MGI:MGI:1889508
    See related
    Ensembl:ENSMUSG00000029174 AllianceGenome:MGI:1889508
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Nob1; Tbc1; Nobq1; mKIAA1108; 1110062G02Rik
    Summary
    Predicted to enable GTPase activator activity. Predicted to be involved in negative regulation of insulin secretion involved in cellular response to glucose stimulus. Predicted to be located in cytosol. Predicted to be active in Golgi apparatus. Is expressed in several structures, including adrenal medulla; brain; genitourinary system; gut gland; and retina. Orthologous to human TBC1D1 (TBC1 domain family member 1). [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in testis adult (RPKM 11.3), bladder adult (RPKM 9.9) and 27 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Tbc1d1 in Genome Data Viewer
    Location:
    5 C3.1; 5 32.8 cM
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 5 NC_000071.7 (64313648..64508829)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 5 NC_000071.6 (64156305..64351486)

    Chromosome 5 - NC_000071.7Genomic Context describing neighboring genes Neighboring gene STARR-positive B cell enhancer ABC_E9641 Neighboring gene STARR-positive B cell enhancer ABC_E6330 Neighboring gene STARR-seq mESC enhancer starr_13198 Neighboring gene phosphoglucomutase 2 Neighboring gene STARR-positive B cell enhancer mm9_chr5:64540539-64540839 Neighboring gene STARR-positive B cell enhancer ABC_E2744 Neighboring gene predicted gene, 22559 Neighboring gene STARR-seq mESC enhancer starr_13200 Neighboring gene predicted gene 15824 Neighboring gene STARR-positive B cell enhancer ABC_E8056 Neighboring gene predicted gene, 38634 Neighboring gene peptidylprolyl isomerase A pseudogene 22 Neighboring gene STARR-positive B cell enhancer ABC_E6331 Neighboring gene STARR-seq mESC enhancer starr_13205 Neighboring gene CapStarr-seq enhancer MGSCv37_chr5:64773751-64773860 Neighboring gene STARR-seq mESC enhancer starr_13208 Neighboring gene STARR-seq mESC enhancer starr_13209 Neighboring gene predicted gene 43837 Neighboring gene RIKEN cDNA 1700027F09 gene Neighboring gene predicted gene, 31363

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism. Szekeres F, et al. Am J Physiol Endocrinol Metab, 2012 Aug 15. PMID 22693207
    2. Rab2A regulates the progression of nonalcoholic fatty liver disease downstream of AMPK-TBC1D1 axis by stabilizing PPARγ. Chen ZY, et al. PLoS Biol, 2022 Jan. PMID 35061665, Free PMC Article
    3. Conventional knockout of Tbc1d1 in mice impairs insulin- and AICAR-stimulated glucose uptake in skeletal muscle. Dokas J, et al. Endocrinology, 2013 Oct. PMID 23892475
    4. The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle. Stöckli J, et al. Diabetes, 2015 Jun. PMID 25576050
    5. TBC1D1 regulates insulin- and contraction-induced glucose transport in mouse skeletal muscle. An D, et al. Diabetes, 2010 Jun. PMID 20299473, Free PMC Article

    See all (71) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. TBC1Domain Family Member 25 deficiency aggravates cerebral ischemia-reperfusion injury via TAK1-JNK/p38 pathway.
      Title: TBC1Domain Family Member 25 deficiency aggravates cerebral ischemia-reperfusion injury via TAK1-JNK/p38 pathway.
    2. The RabGAPs TBC1D1 and TBC1D4 Control Uptake of Long-Chain Fatty Acids Into Skeletal Muscle via Fatty Acid Transporter SLC27A4/FATP4.
      Title: The RabGAPs TBC1D1 and TBC1D4 Control Uptake of Long-Chain Fatty Acids Into Skeletal Muscle via Fatty Acid Transporter SLC27A4/FATP4.
    3. With increased glucose uptake and utilization involving AMPK-TBC1D1 signaling.
      Title: Improved exercise capacity in cyclophilin-D knockout mice associated with enhanced oxygen utilization efficiency and augmented glucose uptake via AMPK-TBC1D1 signaling nexus.
    4. The interaction enhances the efficiency by which AMPK phosphorylates TBC1D1 on its key regulatory site, Ser(237) Furthermore, the interaction is reduced by a naturally occurring R125W mutation in the PTB1 domain of TBC1D1, previously found to be associated with severe familial obesity in females, with a concomitant reduction in Ser(237) phosphorylation.
      Title: Isoform-specific AMPK association with TBC1D1 is reduced by a mutation associated with severe obesity.
    5. Isolated pancreatic islets from D1KO mice exhibited substantially increased glucose-stimulated insulin secretion compared with controls.TBC1D1 exerts its function via a signaling pathway at the level of membrane depolarization. In line, ultrastructural analysis of isolated pancreatic islets revealed both higher insulin-granule density and number of docked granules in beta-cells from D1KO mice compared with WT controls.
      Title: Deletion of the RabGAP TBC1D1 Leads to Enhanced Insulin Secretion and Fatty Acid Oxidation in Islets From Male Mice.
    6. in obese leptin-deficient mice, lack of TBC1D1 has no impact on feeding behavior or energy intake but results in increased energy expenditure, altered energy substrate preference with increased fatty acid oxidation and suppression of obesity; TBC1D1 may have an evolutionary conserved role in regulating energy homeostasis in vertebrates
      Title: Tbc1d1 deletion suppresses obesity in leptin-deficient mice.
    7. These findings demonstrate that the AMPK-TBC1D1 signaling nexus interacts with the PKB-mTOR pathway via IGF1 secretion, which consequently controls expression of lipogenic genes in the adipose tissue
      Title: Disruption of the AMPK-TBC1D1 nexus increases lipogenic gene expression and causes obesity in mice via promoting IGF1 secretion.
    8. Rab28 is a substrate for the GAP domains of both TBC1D1 and TBC1D4 in vitro.
      Title: Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking.
    9. Tbc1d1 knockout mice have GLUT4 expression and glucose uptake defects in skeletal muscle and adipose tissue. These defects combine in AS160 KO/Tbc1d1 KO mice, supporting nonredundant functions for AS160 and Tbc1d1.
      Title: Rab GAPs AS160 and Tbc1d1 play nonredundant roles in the regulation of glucose and energy homeostasis in mice.
    10. Data (including data from mice with Tbc1d1 gene deletion) suggest Tbc1d1 controls basal intracellular GLUT4 retention in large skeletal muscles; in small muscles (extensor digitorum longus) Tbc1d1 does not regulate basal GLUT4 cell surface exposure.
      Title: Deletion of the Rab GAP Tbc1d1 modifies glucose, lipid, and energy homeostasis in mice.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    Phenotypes

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    Associated conditions

    Description Tests
    New Zealand obese QTL 1
    GeneReviews: Not available

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)

    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

    • MGC106104, MGC144097

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables GTPase activator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables GTPase activator activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of insulin secretion involved in cellular response to glucose stimulus IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of insulin secretion involved in cellular response to glucose stimulus ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in regulation of protein localization ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    is_active_in Golgi apparatus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    TBC1 domain family member 1
    Names
    tre-2/USP6, BUB2, cdc16) domain family, member 1

    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_001289514.1 → NP_001276443.1  TBC1 domain family member 1 isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC131679
      Consensus CDS
      CCDS71593.1
      UniProtKB/TrEMBL
      E9Q6L4
      Related
      ENSMUSP00000113643.2, ENSMUST00000119756.6
      Conserved Domains (3) summary
      smart00164
      Location:662 → 879
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      cd01269
      Location:35 → 236
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:560 → 610
      DUF3350; Domain of unknown function (DUF3350)

    2. NM_001310611.1 → NP_001297540.1  TBC1 domain family member 1 isoform 3

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) contains two alternate in-frame exons compared to variant 1. The encoded isoform (3) is longer than isoform 1.
      Source sequence(s)
      AC131679, AC132271
      Consensus CDS
      CCDS80287.1
      UniProtKB/Swiss-Prot
      E9QLW9, Q60949, Q80TJ9, Q923F8
      Related
      ENSMUSP00000044577.7, ENSMUST00000043893.13
      Conserved Domains (5) summary
      smart00164
      Location:884 → 1101
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG1196
      Location:1102 → 1236
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd01269
      Location:164 → 365
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:782 → 832
      DUF3350; Domain of unknown function (DUF3350)
      cl17171
      Location:16 → 164
      PH-like; Pleckstrin homology-like domain

    3. NM_019636.3 → NP_062610.2  TBC1 domain family member 1 isoform 1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) encodes isoform 1.
      Source sequence(s)
      AC131679, AC132271
      Consensus CDS
      CCDS39094.1
      UniProtKB/TrEMBL
      Q3U3T9
      Related
      ENSMUSP00000098756.3, ENSMUST00000101195.9
      Conserved Domains (5) summary
      smart00164
      Location:791 → 1008
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG1196
      Location:1009 → 1143
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd01269
      Location:164 → 365
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:689 → 739
      DUF3350; Domain of unknown function (DUF3350)
      cl17171
      Location:16 → 164
      PH-like; Pleckstrin homology-like domain

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000071.7 Reference GRCm39 C57BL/6J

      Range
      64313648..64508829
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011240758.3 → XP_011239060.1  TBC1 domain family member 1 isoform X1

      UniProtKB/Swiss-Prot
      E9QLW9, Q60949, Q80TJ9, Q923F8
      Conserved Domains (5) summary
      smart00164
      Location:884 → 1101
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG1196
      Location:1102 → 1236
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd01269
      Location:164 → 365
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:782 → 832
      DUF3350; Domain of unknown function (DUF3350)
      cl17171
      Location:16 → 164
      PH-like; Pleckstrin homology-like domain

    2. XM_006504036.4 → XP_006504099.1  TBC1 domain family member 1 isoform X2

      Conserved Domains (5) summary
      smart00164
      Location:847 → 1064
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG1196
      Location:1065 → 1199
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd01269
      Location:164 → 365
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:745 → 795
      DUF3350; Domain of unknown function (DUF3350)
      cl17171
      Location:16 → 164
      PH-like; Pleckstrin homology-like domain

    3. XM_036165386.1 → XP_036021279.1  TBC1 domain family member 1 isoform X5

      Conserved Domains (5) summary
      smart00164
      Location:754 → 971
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG1196
      Location:972 → 1106
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd00934
      Location:21 → 150
      PTB; Phosphotyrosine-binding (PTB) PH-like fold
      cd01269
      Location:164 → 365
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:647 → 702
      DUF3350; Domain of unknown function (DUF3350)

    4. XM_011240757.4 → XP_011239059.1  TBC1 domain family member 1 isoform X1

      UniProtKB/Swiss-Prot
      E9QLW9, Q60949, Q80TJ9, Q923F8
      Conserved Domains (5) summary
      smart00164
      Location:884 → 1101
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG1196
      Location:1102 → 1236
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd01269
      Location:164 → 365
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:782 → 832
      DUF3350; Domain of unknown function (DUF3350)
      cl17171
      Location:16 → 164
      PH-like; Pleckstrin homology-like domain

    5. XM_006504037.5 → XP_006504100.1  TBC1 domain family member 1 isoform X3

      UniProtKB/TrEMBL
      Q3U3T9
      Related
      ENSMUSP00000112493.2, ENSMUST00000121370.8
      Conserved Domains (5) summary
      smart00164
      Location:791 → 1008
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG1196
      Location:1009 → 1143
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd01269
      Location:164 → 365
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:689 → 739
      DUF3350; Domain of unknown function (DUF3350)
      cl17171
      Location:16 → 164
      PH-like; Pleckstrin homology-like domain

    6. XM_006504038.5 → XP_006504101.1  TBC1 domain family member 1 isoform X4

      Conserved Domains (4) summary
      smart00164
      Location:755 → 972
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG1196
      Location:973 → 1107
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd01269
      Location:35 → 236
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:653 → 703
      DUF3350; Domain of unknown function (DUF3350)

    7. XM_030254740.2 → XP_030110600.1  TBC1 domain family member 1 isoform X6

      Conserved Domains (4) summary
      smart00164
      Location:659 → 876
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG1196
      Location:877 → 1011
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd01269
      Location:43 → 140
      PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
      pfam11830
      Location:557 → 607
      DUF3350; Domain of unknown function (DUF3350)

    8. XM_011240759.3 → XP_011239061.1  TBC1 domain family member 1 isoform X7

      UniProtKB/TrEMBL
      Q3TGE9
      Conserved Domains (3) summary
      smart00164
      Location:116 → 333
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG4372
      Location:352 → 468
      COG4372; Uncharacterized conserved protein, contains DUF3084 domain [Function unknown]
      pfam11830
      Location:14 → 64
      DUF3350; Domain of unknown function (DUF3350)

    9. XM_036165387.1 → XP_036021280.1  TBC1 domain family member 1 isoform X8

      UniProtKB/TrEMBL
      Q3TGE9
      Related
      ENSMUST00000140960.3
      Conserved Domains (3) summary
      smart00164
      Location:115 → 332
      TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
      COG4372
      Location:351 → 467
      COG4372; Uncharacterized conserved protein, contains DUF3084 domain [Function unknown]
      pfam11830
      Location:8 → 63
      DUF3350; Domain of unknown function (DUF3350)
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q60949.3 GenPept UniProtKB/Swiss-Prot:Q60949

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