Tbio TSC1 Hamartin

Protein Summary

Description

In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (PubMed:12271141, PubMed:28215400). Seems not to be required for TSC2 GAP activity towards RHEB (PubMed:15340059). Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling (By similarity). Acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (PubMed:16464865, PubMed:29127155). This gene is a tumor suppressor gene that encodes the growth inhibitory protein hamartin. The encoded protein interacts with and stabilizes the GTPase activating protein tuberin. This hamartin-tuberin complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signalling which is a major regulator of anabolic cell growth. This protein also functions as a co-chaperone for Hsp90 that inhibits its ATPase activity. This protein functions as a facilitator of Hsp90-mediated folding of kinase and non-kinase clients, including Tsc2 and thereby preventing their ubiquitination and proteasomal degradation. Mutations in this gene have been associated with tuberous sclerosis. [provided by RefSeq, Apr 2018]

Uniprot Accession IDs

• Q92574
• B7Z897
• Q5VVN5

Gene Name

• TSC1

Ensembl ID

• ENST00000298552
• ENSP00000298552
• ENSG00000165699
• ENST00000440111
• ENSP00000394524
• ENST00000545250
• ENSP00000444017
• ENST00000643072
• ENSP00000496691
• ENST00000643875
• ENSP00000495158
• ENST00000646625
• ENSP00000496263

Symbol

• KIAA0243
• TSC
• LAM
• TSC

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.97
disease perturbation	0.93
hub protein	0.92
histone modification site profile	0.85
kinase perturbation	0.84

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 260.41   (req: < 5)

Gene RIFs: 156   (req: <= 3)

Antibodies: 1764   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 260.41   (req: >= 5)

Gene RIFs: 156   (req: > 3)

Antibodies: 1764   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 46

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (163)

Explore Interacting Targets

1 – 10 of 163

• See Interactions on String-DB

TBC1D7

Tbio

Novelty:  0.06502242

p_int:  1

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

AKTIP

Tbio

Novelty:  0.00315951

p_int:  0.999867388

p_ni:  0.000132588

p_wrong:  2.4e-8

Score:  0.336

Data Source:  BioPlex,STRINGDB

TSC2

Tbio

Novelty:  0.00067416

Score:  0.999

Data Source:  Reactome,STRINGDB

RHEB

Tbio

Family:  Enzyme

Novelty:  0.00313935

Score:  0.998

Data Source:  STRINGDB

AKT1

Tchem

Family:  Kinase

Novelty:  0.00003185

Score:  0.988

Data Source:  STRINGDB

RPTOR

Tbio

Novelty:  0.00119147

Score:  0.987

Data Source:  STRINGDB

MTOR

Tclin

Family:  Kinase

Novelty:  0.00012333

Score:  0.984

Data Source:  STRINGDB

RICTOR

Tbio

Novelty:  0.00250734

Score:  0.98

Data Source:  STRINGDB

RRAGA

Tbio

Novelty:  0.02022668

Score:  0.975

Data Source:  STRINGDB

RPS6KA1

Tchem

Family:  Kinase

Novelty:  0.00178073

Score:  0.975

Data Source:  STRINGDB

Nearest Tclin Targets (1)

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Upstream (1)

1 – 1 of 1

TNF

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  4

1: mTOR signaling pathway

2: Human papillomavirus infection

3: Human cytomegalovirus infection

4: Herpes simplex virus 1 infection

Pathways (52)

Reactome (16)

KEGG (13)

PathwayCommons (5)

WikiPathways (18)

Autophagy (R-HSA-9612973)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Autophagy	109 targets	R-HSA-9612973
Reactome	Cellular responses to external stimuli	487 targets	R-HSA-8953897
Reactome	Energy dependent regulation of mTOR by LKB1-AMPK	28 targets	R-HSA-380972
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436

Name	Explore in Pharos	Explore in Source
Autophagy	109 targets	R-HSA-9612973
Cellular responses to external stimuli	487 targets	R-HSA-8953897
Energy dependent regulation of mTOR by LKB1-AMPK	28 targets	R-HSA-380972
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (61)

Functions (6)

Components (15)

Processes (40)

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1 – 6 of 6

GO Term	Evidence	Assigned by
ATPase inhibitor activity	Inferred from Direct Assay (IDA)	UniProtKB
Hsp70 protein binding	Inferred from Direct Assay (IDA)	UniProtKB
chaperone binding	Inferred from Physical Interaction (IPI)	UniProtKB
Hsp90 protein binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein N-terminus binding	Inferred from Physical Interaction (IPI)	UniProtKB
GTPase activating protein binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations (null)

No disease associations found

GWAS Traits (33)

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5

1 – 5 of 33

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
eosinophil count	EFO_0004842	3	9	13		98.4
mean platelet volume	EFO_0004584	4	4	6		98.4
platelet count	EFO_0004309	3	4	5		98.1
eosinophil percentage of leukocytes	EFO_0007991	2	7	10		97.4
red blood cell distribution width	EFO_0005192	3	4	6		97.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
eosinophil count	EFO_0004842	13		98.4
mean platelet volume	EFO_0004584	6		98.4
platelet count	EFO_0004309	5		98.1
eosinophil percentage of leukocytes	EFO_0007991	10		97.4
red blood cell distribution width	EFO_0005192	6		97.2

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Chaperone
Coiled coil
Complete proteome
Cytoplasm
Disease mutation
Epilepsy
Membrane
Phosphoprotein

GWAS Trait Find Similar Targets

No Header	No Header
basophil count
basophil percentage of granulocytes
basophil percentage of leukocytes
eosinophil count
eosinophil percentage of granulocytes
eosinophil percentage of leukocytes
granulocyte count
HbA1c measurement
hematological measurement
leukocyte count

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
integument phenotype
liver/biliary system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (14)

1 – 5 of 14

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	TSC complex subunit 1	VGNC:48987	464818
Macaque	TSC complex subunit 1		714645
Mouse	tuberous sclerosis 1	MGI:1929183	64930
Rat	TSC complex subunit 1	RGD:620124	60445
Dog	TSC complex subunit 1	VGNC:47890	480688

Species	Name	OMA	EggNOG	Inparanoid
Chimp	TSC complex subunit 1
Macaque	TSC complex subunit 1
Mouse	tuberous sclerosis 1
Rat	TSC complex subunit 1
Dog	TSC complex subunit 1

Publication Statistics

PubMed Score 260.41

PubMed score by year

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PubTator Score 929.17

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Related Publications

Text Mined References (202)

GeneRif Annotations (156)

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PMID	Year	Title