UniProtKB - Q9P0N9 (TBCD7_HUMAN)
Protein
TBC1 domain family member 7
Gene
TBC1D7
Organism
Homo sapiens (Human)
Status
Functioni
Component of the TSC-TBC complex, that contains TBC1D7 in addition to the TSC1-TSC2 complex and consists of the functional complex possessing GTPase-activating protein (GAP) activity toward RHEB in response to alterations in specific cellular growth conditions. The small GTPase RHEB is a direct activator of the protein kinase activity of mTORC1 and the TSC-TBC complex acts as a negative regulator of mTORC1 signaling cascade by acting as a GAP for RHEB. Participates in the proper sensing of growth factors and glucose, but not amino acids, by mTORC1. It is unclear whether TBC1D7 acts as a GTPase-activating protein and additional studies are required to answer this question.1 Publication
Caution
Was initially identified as a negative regulator of the TSC1-TSC2 complex (PubMed:17658474). However, it was later shown that TBC1D7 is part of the TSC-TBC complex and participates in GTPase-activating protein activity, leading to inhibition of the TOR signaling cascade (PubMed:22795129). The differences between 2 reports might be explained by experimental conditions in the initial report, in which they overexpressed the TBC1D7 subunit, possibly leading to disrupt the stoichiometric complex and its downstream functions.2 Publications
GO - Molecular functioni
- GTPase activator activity Source: UniProtKB
- small GTPase binding Source: UniProtKB
GO - Biological processi
- activation of GTPase activity Source: UniProtKB
- negative regulation of cilium assembly Source: UniProtKB
- negative regulation of TOR signaling Source: UniProtKB
- positive regulation of GTPase activity Source: UniProtKB
- positive regulation of protein ubiquitination Source: UniProtKB
- response to growth factor Source: UniProtKB
Keywordsi
Molecular function | GTPase activation |
Enzyme and pathway databases
PathwayCommonsi | Q9P0N9 |
Reactomei | R-HSA-8854214, TBC/RABGAPs |
Names & Taxonomyi
Protein namesi | Recommended name: TBC1 domain family member 7Alternative name(s): Cell migration-inducing protein 23 |
Gene namesi | Name:TBC1D7 Synonyms:TBC7 ORF Names:HSPC239 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:21066, TBC1D7 |
MIMi | 612655, gene |
neXtProti | NX_Q9P0N9 |
VEuPathDBi | HostDB:ENSG00000145979.17 |
Subcellular locationi
Other locations
- Cytoplasmic vesicle 1 Publication
Note: Localizes in the cytoplasmic vesicles of the endomembrane in association with TSC1-TSC2 complex.
Cytoskeleton
- ciliary basal body Source: UniProtKB
Cytosol
- cytosol Source: Reactome
Other locations
- cytoplasmic vesicle Source: UniProtKB
Keywords - Cellular componenti
Cytoplasmic vesiclePathology & Biotechi
Involvement in diseasei
Macrocephaly/megalencephaly syndrome, autosomal recessive (MGCPH)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA disorder characterized by abnormal enlargement of the cerebral hemispheres, mental retardation, large head, optic atrophy and underdeveloped skeletal musculature. Head enlargement may be evident at birth or the head may become abnormally large in the early years of life. Additional clinical features include behavioral abnormalities, psychosis, learning difficulties, prognathism, myopia and astigmatism.
Related information in OMIMOrganism-specific databases
DisGeNETi | 107080638 51256 |
MalaCardsi | TBC1D7 |
MIMi | 248000, phenotype |
OpenTargetsi | ENSG00000145979 |
Orphaneti | 268920, Isolated megalencephaly |
PharmGKBi | PA134929978 |
Miscellaneous databases
Pharosi | Q9P0N9, Tbio |
Genetic variation databases
BioMutai | TBC1D7 |
DMDMi | 37538019 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000208031 | 1 – 293 | TBC1 domain family member 7Add BLAST | 293 |
Proteomic databases
EPDi | Q9P0N9 |
jPOSTi | Q9P0N9 |
MassIVEi | Q9P0N9 |
MaxQBi | Q9P0N9 |
PaxDbi | Q9P0N9 |
PeptideAtlasi | Q9P0N9 |
PRIDEi | Q9P0N9 |
ProteomicsDBi | 61499 77329 83587 [Q9P0N9-1] 83588 [Q9P0N9-2] |
TopDownProteomicsi | Q9P0N9-1 [Q9P0N9-1] |
PTM databases
iPTMneti | Q9P0N9 |
PhosphoSitePlusi | Q9P0N9 |
Expressioni
Tissue specificityi
Highly expressed in heart, and slightly in kidney, liver and placenta.1 Publication
Gene expression databases
Bgeei | ENSG00000145979, Expressed in cortical plate and 200 other tissues |
ExpressionAtlasi | Q9P0N9, baseline and differential |
Genevisiblei | Q9P0N9, HS |
Organism-specific databases
HPAi | ENSG00000145979, Low tissue specificity |
Interactioni
Subunit structurei
Component of the TSC-TBC complex (also named Rhebulator complex), composed of the TSC1-TSC2 heterodimer and TBC1D7.
Interacts with TSC1 (via C-terminal half of the coiled-coil domain).
2 PublicationsBinary interactionsi
Hide detailsQ9P0N9
GO - Molecular functioni
- small GTPase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 119412, 54 interactors |
ComplexPortali | CPX-6142, TSC1-TSC2 complex |
CORUMi | Q9P0N9 |
IntActi | Q9P0N9, 33 interactors |
MINTi | Q9P0N9 |
STRINGi | 9606.ENSP00000475727 |
Miscellaneous databases
RNActi | Q9P0N9, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9P0N9 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 50 – 231 | Rab-GAP TBCPROSITE-ProRule annotationAdd BLAST | 182 |
Phylogenomic databases
eggNOGi | ENOG502QPZD, Eukaryota |
GeneTreei | ENSGT00390000009122 |
HOGENOMi | CLU_082520_0_0_1 |
InParanoidi | Q9P0N9 |
OMAi | KIWDKVC |
PhylomeDBi | Q9P0N9 |
TreeFami | TF323655 |
Family and domain databases
Gene3Di | 1.10.8.680, 1 hit |
InterProi | View protein in InterPro IPR000195, Rab-GTPase-TBC_dom IPR035969, Rab-GTPase_TBC_sf IPR039842, TBC1D7 IPR043039, TBC1D7_dom2 |
PANTHERi | PTHR13530, PTHR13530, 1 hit |
Pfami | View protein in Pfam PF00566, RabGAP-TBC, 1 hit |
SUPFAMi | SSF47923, SSF47923, 2 hits |
PROSITEi | View protein in PROSITE PS50086, TBC_RABGAP, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 13 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9P0N9-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MTEDSQRNFR SVYYEKVGFR GVEEKKSLEI LLKDDRLDTE KLCTFSQRFP
60 70 80 90 100
LPSMYRALVW KVLLGILPPH HESHAKVMMY RKEQYLDVLH ALKVVRFVSD
110 120 130 140 150
ATPQAEVYLR MYQLESGKLP RSPSFPLEPD DEVFLAIAKA MEEMVEDSVD
160 170 180 190 200
CYWITRRFVN QLNTKYRDSL PQLPKAFEQY LNLEDGRLLT HLRMCSAAPK
210 220 230 240 250
LPYDLWFKRC FAGCLPESSL QRVWDKVVSG SCKILVFVAV EILLTFKIKV
260 270 280 290
MALNSAEKIT KFLENIPQDS SDAIVSKAID LWHKHCGTPV HSS
Computationally mapped potential isoform sequencesi
There are 13 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ5SZL4 | Q5SZL4_HUMAN | TBC1 domain family member 7 | TBC1D7 | 249 | Annotation score: | ||
Q5SZL6 | Q5SZL6_HUMAN | TBC1 domain family member 7 | TBC1D7 | 238 | Annotation score: | ||
U3KPY5 | U3KPY5_HUMAN | TBC1 domain family member 7 | TBC1D7 | 164 | Annotation score: | ||
Q5SZL5 | Q5SZL5_HUMAN | TBC1 domain family member 7 | TBC1D7 | 207 | Annotation score: | ||
Q5SZL3 | Q5SZL3_HUMAN | TBC1 domain family member 7 | TBC1D7 | 194 | Annotation score: | ||
Q5SZL8 | Q5SZL8_HUMAN | TBC1 domain family member 7 | TBC1D7 | 130 | Annotation score: | ||
Q5SZM1 | Q5SZM1_HUMAN | TBC1 domain family member 7 | TBC1D7 | 156 | Annotation score: | ||
Q5SZM2 | Q5SZM2_HUMAN | TBC1 domain family member 7 | TBC1D7 | 136 | Annotation score: | ||
U3KQD8 | U3KQD8_HUMAN | TBC1 domain family member 7 | TBC1D7 | 152 | Annotation score: | ||
B4DK47 | B4DK47_HUMAN | TBC1 domain family member 7 | TBC1D7 | 179 | Annotation score: | ||
There are more potential isoformsShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 59 | V → I in BAD97165 (Ref. 6) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_052537 | 67 | L → W. Corresponds to variant dbSNP:rs543580EnsemblClinVar. | 1 | |
Natural variantiVAR_052538 | 136 | A → T. Corresponds to variant dbSNP:rs9381921EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044186 | 1 – 73 | MTEDS…PHHES → MEGASRNLASTPRV in isoform 3. 1 PublicationAdd BLAST | 73 | |
Alternative sequenceiVSP_041480 | 38 – 64 | Missing in isoform 2. 1 PublicationAdd BLAST | 27 | |
Alternative sequenceiVSP_044892 | 127 – 172 | Missing in isoform 4. 1 PublicationAdd BLAST | 46 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB449888 mRNA Translation: BAH16631.1 AY826820 mRNA Translation: AAX18640.1 AK057228 mRNA Translation: BAB71389.1 AF151073 mRNA Translation: AAF36159.1 AY542308 mRNA Translation: AAT08177.1 AK223445 mRNA Translation: BAD97165.1 AL008729 Genomic DNA No translation available. AL589984 Genomic DNA No translation available. CH471087 Genomic DNA Translation: EAW55325.1 CH471087 Genomic DNA Translation: EAW55323.1 BC050465 mRNA Translation: AAH50465.1 BC007054 mRNA Translation: AAH07054.1 |
CCDSi | CCDS4523.1 [Q9P0N9-1] CCDS47376.1 [Q9P0N9-2] CCDS58995.1 [Q9P0N9-4] |
RefSeqi | NP_001137436.1, NM_001143964.3 [Q9P0N9-1] NP_001137437.1, NM_001143965.3 [Q9P0N9-1] NP_001137438.1, NM_001143966.3 [Q9P0N9-2] NP_001245386.1, NM_001258457.2 [Q9P0N9-4] NP_001305734.1, NM_001318805.1 [Q9P0N9-1] NP_001305738.1, NM_001318809.1 [Q9P0N9-1] NP_057579.1, NM_016495.5 [Q9P0N9-1] |
Genome annotation databases
Ensembli | ENST00000343141; ENSP00000343100; ENSG00000145979 [Q9P0N9-4] ENST00000356436; ENSP00000348813; ENSG00000145979 [Q9P0N9-1] ENST00000379300; ENSP00000368602; ENSG00000145979 [Q9P0N9-1] ENST00000379307; ENSP00000368609; ENSG00000145979 [Q9P0N9-2] ENST00000606214; ENSP00000475727; ENSG00000145979 [Q9P0N9-1] |
GeneIDi | 107080638 51256 |
KEGGi | hsa:107080638 hsa:51256 |
UCSCi | uc003nal.5, human [Q9P0N9-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB449888 mRNA Translation: BAH16631.1 AY826820 mRNA Translation: AAX18640.1 AK057228 mRNA Translation: BAB71389.1 AF151073 mRNA Translation: AAF36159.1 AY542308 mRNA Translation: AAT08177.1 AK223445 mRNA Translation: BAD97165.1 AL008729 Genomic DNA No translation available. AL589984 Genomic DNA No translation available. CH471087 Genomic DNA Translation: EAW55325.1 CH471087 Genomic DNA Translation: EAW55323.1 BC050465 mRNA Translation: AAH50465.1 BC007054 mRNA Translation: AAH07054.1 |
CCDSi | CCDS4523.1 [Q9P0N9-1] CCDS47376.1 [Q9P0N9-2] CCDS58995.1 [Q9P0N9-4] |
RefSeqi | NP_001137436.1, NM_001143964.3 [Q9P0N9-1] NP_001137437.1, NM_001143965.3 [Q9P0N9-1] NP_001137438.1, NM_001143966.3 [Q9P0N9-2] NP_001245386.1, NM_001258457.2 [Q9P0N9-4] NP_001305734.1, NM_001318805.1 [Q9P0N9-1] NP_001305738.1, NM_001318809.1 [Q9P0N9-1] NP_057579.1, NM_016495.5 [Q9P0N9-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3QWL | X-ray | 1.90 | A | 1-293 | [»] | |
4Z6Y | X-ray | 2.81 | A/B/E/G | 21-293 | [»] | |
5EJC | X-ray | 3.10 | A/B | 18-293 | [»] | |
5ULO | X-ray | 2.14 | C/D | 115-126 | [»] | |
7DL2 | electron microscopy | 4.40 | E | 21-287 | [»] | |
SMRi | Q9P0N9 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 119412, 54 interactors |
ComplexPortali | CPX-6142, TSC1-TSC2 complex |
CORUMi | Q9P0N9 |
IntActi | Q9P0N9, 33 interactors |
MINTi | Q9P0N9 |
STRINGi | 9606.ENSP00000475727 |
PTM databases
iPTMneti | Q9P0N9 |
PhosphoSitePlusi | Q9P0N9 |
Genetic variation databases
BioMutai | TBC1D7 |
DMDMi | 37538019 |
Proteomic databases
EPDi | Q9P0N9 |
jPOSTi | Q9P0N9 |
MassIVEi | Q9P0N9 |
MaxQBi | Q9P0N9 |
PaxDbi | Q9P0N9 |
PeptideAtlasi | Q9P0N9 |
PRIDEi | Q9P0N9 |
ProteomicsDBi | 61499 77329 83587 [Q9P0N9-1] 83588 [Q9P0N9-2] |
TopDownProteomicsi | Q9P0N9-1 [Q9P0N9-1] |
Protocols and materials databases
Antibodypediai | 24944, 98 antibodies |
DNASUi | 51256 |
Genome annotation databases
Ensembli | ENST00000343141; ENSP00000343100; ENSG00000145979 [Q9P0N9-4] ENST00000356436; ENSP00000348813; ENSG00000145979 [Q9P0N9-1] ENST00000379300; ENSP00000368602; ENSG00000145979 [Q9P0N9-1] ENST00000379307; ENSP00000368609; ENSG00000145979 [Q9P0N9-2] ENST00000606214; ENSP00000475727; ENSG00000145979 [Q9P0N9-1] |
GeneIDi | 107080638 51256 |
KEGGi | hsa:107080638 hsa:51256 |
UCSCi | uc003nal.5, human [Q9P0N9-1] |
Organism-specific databases
CTDi | 107080638 51256 |
DisGeNETi | 107080638 51256 |
GeneCardsi | TBC1D7 TBC1D7-LOC100130357 |
HGNCi | HGNC:21066, TBC1D7 |
HPAi | ENSG00000145979, Low tissue specificity |
MalaCardsi | TBC1D7 |
MIMi | 248000, phenotype 612655, gene |
neXtProti | NX_Q9P0N9 |
OpenTargetsi | ENSG00000145979 |
Orphaneti | 268920, Isolated megalencephaly |
PharmGKBi | PA134929978 |
VEuPathDBi | HostDB:ENSG00000145979.17 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QPZD, Eukaryota |
GeneTreei | ENSGT00390000009122 |
HOGENOMi | CLU_082520_0_0_1 |
InParanoidi | Q9P0N9 |
OMAi | KIWDKVC |
PhylomeDBi | Q9P0N9 |
TreeFami | TF323655 |
Enzyme and pathway databases
PathwayCommonsi | Q9P0N9 |
Reactomei | R-HSA-8854214, TBC/RABGAPs |
Miscellaneous databases
BioGRID-ORCSi | 107080638, 0 hits in 3 CRISPR screens 51256, 10 hits in 1004 CRISPR screens |
Pharosi | Q9P0N9, Tbio |
PROi | PR:Q9P0N9 |
RNActi | Q9P0N9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000145979, Expressed in cortical plate and 200 other tissues |
ExpressionAtlasi | Q9P0N9, baseline and differential |
Genevisiblei | Q9P0N9, HS |
Family and domain databases
Gene3Di | 1.10.8.680, 1 hit |
InterProi | View protein in InterPro IPR000195, Rab-GTPase-TBC_dom IPR035969, Rab-GTPase_TBC_sf IPR039842, TBC1D7 IPR043039, TBC1D7_dom2 |
PANTHERi | PTHR13530, PTHR13530, 1 hit |
Pfami | View protein in Pfam PF00566, RabGAP-TBC, 1 hit |
SUPFAMi | SSF47923, SSF47923, 2 hits |
PROSITEi | View protein in PROSITE PS50086, TBC_RABGAP, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TBCD7_HUMAN | |
Accessioni | Q9P0N9Primary (citable) accession number: Q9P0N9 Secondary accession number(s): E7EV96 Q96MB8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 3, 2003 |
Last sequence update: | October 1, 2000 | |
Last modified: | April 7, 2021 | |
This is version 162 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references