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

Summary

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 activation of GTPase activity; intracellular protein transport; and regulation of protein localization. Predicted to be located in cytosol. 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, Apr 2022]
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

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_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Spontaneous (1) 1 citation
Gene trapped (3)
Targeted (4) 1 citation
QTL (1) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:488717

AI385682 (e-PCR)
- UniSTS:159379

AU022322 (e-PCR)
- UniSTS:207789

NoName (e-PCR)
- UniSTS:235182

AW555803 (e-PCR)
- UniSTS:179167

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables GTPase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in activation of GTPase activity	IBA Inferred from Biological aspect of Ancestor 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
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)

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

See identical proteins and their annotated locations for NP_001297540.1

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

See identical proteins and their annotated locations for NP_062610.2

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

NC_000071.7 Reference GRCm39 C57BL/6J

Range

64313648..64508829

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

See identical proteins and their annotated locations for XP_011239060.1

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

See identical proteins and their annotated locations for XP_011239059.1

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

See identical proteins and their annotated locations for XP_006504100.1

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
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)
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)
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)
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)