Mutations in this gene lead to tuberous sclerosis complex. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. The protein associates with hamartin in a cytosolic complex, possibly acting as a chaperone for hamartin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 200... See more...

Aliases for TSC2 Gene

Aliases for TSC2 Gene

  • TSC Complex Subunit 2 2 3 5
  • Protein Phosphatase 1, Regulatory Subunit 160 2 3
  • Tuberous Sclerosis 2 Protein 3 4
  • Tuberin 3 4
  • TSC4 3 4
  • Tuberous Sclerosis 2 2
  • PPP1R160 3
  • LAM 3

External Ids for TSC2 Gene

Previous HGNC Symbols for TSC2 Gene

  • TSC4

Previous GeneCards Identifiers for TSC2 Gene

  • GC16P002115
  • GC16P002038
  • GC16P002037
  • GC16P002097
  • GC16P002070
  • GC16P002072
  • GC16P002288
  • GC16P002323
  • GC16P002345
  • GC16P002080
  • GC16P002087
  • GC16P002105
  • GC16P002135
  • GC16P002176
  • GC16P002192
  • GC16P002209
  • GC16P002248

Summaries for TSC2 Gene

Entrez Gene Summary for TSC2 Gene

  • Mutations in this gene lead to tuberous sclerosis complex. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. The protein associates with hamartin in a cytosolic complex, possibly acting as a chaperone for hamartin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

CIViC Summary for TSC2 Gene

GeneCards Summary for TSC2 Gene

TSC2 (TSC Complex Subunit 2) is a Protein Coding gene. Diseases associated with TSC2 include Focal Cortical Dysplasia, Type Ii and Lymphangioleiomyomatosis. Among its related pathways are mTOR signalling and Direct p53 effectors. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and binding. An important paralog of this gene is RALGAPA2.

UniProtKB/Swiss-Prot Summary for TSC2 Gene

  • In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (PubMed:12271141, PubMed:28215400). Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:15340059). May also play a role in microtubule-mediated protein transport (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity).

Gene Wiki entry for TSC2 Gene

Additional gene information for TSC2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TSC2 Gene

Genomics for TSC2 Gene

GeneHancer (GH) Regulatory Elements for TSC2 Gene

Promoters and enhancers for TSC2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TSC2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TSC2

Top Transcription factor binding sites by QIAGEN in the TSC2 gene promoter:
  • NF-1
  • STAT3

Genomic Locations for TSC2 Gene

Genomic Locations for TSC2 Gene
chr16:2,047,936-2,089,491
(GRCh38/hg38)
Size:
41,556 bases
Orientation:
Plus strand
chr16:2,097,466-2,138,716
(GRCh37/hg19)
Size:
41,251 bases
Orientation:
Plus strand

Genomic View for TSC2 Gene

Genes around TSC2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TSC2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TSC2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TSC2 Gene

Proteins for TSC2 Gene

  • Protein details for TSC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49815-TSC2_HUMAN
    Recommended name:
    Tuberin
    Protein Accession:
    P49815
    Secondary Accessions:
    • A7E2E2
    • B4DIL8
    • B4DIQ7
    • B4DRN2
    • B7Z2B8
    • C9J378
    • O75275
    • Q4LE71
    • Q8TAZ1

    Protein attributes for TSC2 Gene

    Size:
    1807 amino acids
    Molecular mass:
    200608 Da
    Quaternary structure:
    • Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2 (PubMed:29127155). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (PubMed:29127155). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex thereby stabilizing TSC2 (PubMed:29127155). Interacts with TSC1 and HERC1; the interaction with TSC1 stabilizes TSC2 and prevents the interaction with HERC1 (PubMed:9580671, PubMed:10585443, PubMed:15963462, PubMed:16464865). May also interact with the adapter molecule RABEP1 (PubMed:9045618). The final complex may contain TSC2 and RABEP1 linked to RAB5 (PubMed:9045618). Interacts with HSPA1 and HSPA8 (PubMed:15963462). Interacts with DAPK1 (PubMed:18974095). Interacts with FBXW5 (PubMed:18381890). Interacts with NAA10 (via C-terminal domain) (PubMed:20145209). Interacts with RRAGA (polyubiquitinated) (PubMed:25936802). Interacts with WDR45B (PubMed:28561066). Interacts with RPAP3 and URI1 (PubMed:28561026).
    • (Microbial infection) Interacts with human cytomegalovirus protein UL38; this interaction inhibits cellular stress response mediated by mTORC1.
    Miscellaneous:
    • [Isoform 8]: May be due to an intron retention.
    SequenceCaution:
    • Sequence=BAE06082.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for TSC2 Gene

neXtProt entry for TSC2 Gene

Post-translational modifications for TSC2 Gene

  • Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1. Phosphorylation at Ser-939 and Thr-1462 by PKB/AKT1 is induced by growth factor stimulation. Phosphorylation by AMPK activates it and leads to negatively regulates the mTORC1 complex. Phosphorylated at Ser-1798 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling. Phosphorylated by DAPK1.
  • Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase complex, leading to its subsequent degradation. Ubiquitinated by MYCBP2 independently of its phosphorylation status leading to subsequent degradation; association with TSC1 protects from ubiquitination.
  • Ubiquitination at Lys72, Lys34, Lys438, Lys634, Lys658, Lys914, Lys930, Lys1251, Lys1701, and Lys1739
  • Modification sites at PhosphoSitePlus

Antibody Products

No data available for DME Specific Peptides for TSC2 Gene

Domains & Families for TSC2 Gene

Gene Families for TSC2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for TSC2 Gene

Blocks:
  • Rap/ran-GAP
  • Tuberin signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TSC2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ59538, highly similar to Tuberin (B4DIL8_HUMAN)
  • Tuberous sclerosis 2 protein (TSC2_HUMAN)
genes like me logo Genes that share domains with TSC2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for TSC2 Gene

Function for TSC2 Gene

Molecular function for TSC2 Gene

UniProtKB/Swiss-Prot Function:
In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (PubMed:12271141, PubMed:28215400). Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:15340059). May also play a role in microtubule-mediated protein transport (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity).

Phenotypes From GWAS Catalog for TSC2 Gene

Gene Ontology (GO) - Molecular Function for TSC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005096 GTPase activator activity IEA,IDA 9045618
GO:0005515 protein binding IPI 9580671
GO:0019902 phosphatase binding IDA 19389623
GO:0031267 small GTPase binding IPI 25936802
GO:0042803 protein homodimerization activity IPI 10585443
genes like me logo Genes that share ontologies with TSC2: view
genes like me logo Genes that share phenotypes with TSC2: view

Human Phenotype Ontology for TSC2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TSC2 Gene

MGI Knock Outs for TSC2:

Animal Model Products

CRISPR Products

miRNA for TSC2 Gene

miRTarBase miRNAs that target TSC2

Clone Products

  • Addgene plasmids for TSC2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TSC2 Gene

Localization for TSC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TSC2 Gene

Cytoplasm. Membrane; Peripheral membrane protein. Note=At steady state found in association with membranes.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TSC2 gene
Compartment Confidence
nucleus 5
cytosol 5
lysosome 5
golgi apparatus 5
plasma membrane 4
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 2
endoplasmic reticulum 2
endosome 2

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TSC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 NOT nucleus IEA,IDA 16636147
GO:0005737 colocalizes_with cytoplasm IBA,IDA 17114346
GO:0005764 lysosome IDA 25936802
GO:0005794 NOT Golgi apparatus IDA 10585443
GO:0005829 cytosol IDA,TAS --
genes like me logo Genes that share ontologies with TSC2: view

Pathways & Interactions for TSC2 Gene

PathCards logo

SuperPathways for TSC2 Gene

SuperPathway Contained pathways
1 RET signaling
2 Regulation of lipid metabolism Insulin signaling-generic cascades
.59
.59
.51
.44
.43
.34
3 mTOR signalling
4 GAB1 signalosome
5 AMP-activated Protein Kinase (AMPK) Signaling
genes like me logo Genes that share pathways with TSC2: view

Pathways by source for TSC2 Gene

15 GeneGo (Thomson Reuters) pathways for TSC2 Gene
  • Development CNTF receptor signaling
  • Development Endothelin-1/EDNRA transactivation of EGFR
  • Development Growth hormone signaling via PI3K/AKT and MAPK cascades
  • Development IGF-1 receptor signaling
  • Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis
6 Qiagen pathways for TSC2 Gene
  • 14-3-3 Induced Intracellular Signaling
  • Akt Signaling
  • AMPK Enzyme Complex Pathway
  • Glioblastoma Multiforme
  • Molecular Mechanisms of Cancer
3 Cell Signaling Technology pathways for TSC2 Gene
1 GeneTex pathway for TSC2 Gene

SIGNOR curated interactions for TSC2 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for TSC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001843 neural tube closure ISS --
GO:0006469 negative regulation of protein kinase activity ISS --
GO:0006606 protein import into nucleus ISS --
GO:0006897 endocytosis TAS 9045618
GO:0007507 heart development ISS --
genes like me logo Genes that share ontologies with TSC2: view

Drugs & Compounds for TSC2 Gene

(24) Drugs for TSC2 Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Everolimus Approved Pharma mTOR inhibitor, mTOR Inhibitors, Kinase Inhibitors, Mammalian target of rapamycin (mTOR) inhibitors 1952
Miconazole Approved, Investigational, Vet_approved Pharma Antagonist, Pore Blocker, Channel blocker 4175
Sirolimus Approved, Investigational Pharma Kinase Inhibitors, Mammalian target of rapamycin (mTOR) inhibitors 2191
Anti-Bacterial Agents Pharma 13688
Antibiotics, Antitubercular Pharma 8696

(10) Additional Compounds for TSC2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TSC2: view

Transcripts for TSC2 Gene

mRNA/cDNA for TSC2 Gene

12 REFSEQ mRNAs :
49 NCBI additional mRNA sequence :
69 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products