P49816 (TSC2_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 113.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Tuberin Alternative name(s): Tuberous sclerosis 2 protein homolog | ||
| Gene names |
| ||
| Organism | Rattus norvegicus (Rat) [Reference proteome] | ||
| Taxonomic identifier | 10116 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus![]() |
Protein attributes
| Sequence length | 1809 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | In complex with TSC1, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 By similarity. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling By similarity. Specifically stimulates the intrinsic GTPase activity of the Ras-related protein RAP1A and RAB5. Suggesting a possible mechanism for its role in regulating cellular growth. |
| Subunit structure | Interacts with TSC1 and HERC1; the interaction with TSC1 stabilizes TSC2 and prevents the interaction with HERC1. May also interact with the adapter molecule RABEP1. The final complex contains TSC2 and RABEP1 linked to RAB5. Interacts with HSPA1 and HSPA8 By similarity. Interacts with DAPK1 By similarity. Ref.3 |
| Tissue specificity | CNS, uterus, heart, skeletal muscle, kidney and spleen. |
| Post-translational modification | Phosphorylation at Ser-1388, Ser-1420 or Ser-1422 does not affect interaction with TSC1. Phosphorylation at Ser-939 and Thr-1466 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-1800 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling By similarity. Phosphorylated by DAPK1 By similarity. Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase complex, leading to its subsequent degradation By similarity. |
| Involvement in disease | A germline insertion in Tsc2 is the cause of the Eker rat model of inherited cancer susceptibility. Gives rise to a spectrum of epithelial and nonepithelial neoplasms. |
| Sequence similarities | Contains 1 Rap-GAP domain. |
Ontologies
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] Note: Additional isoforms seem to exist. | ||||||
| Isoform 1 (identifier: P49816-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P49816-2) The sequence of this isoform differs from the canonical sequence as follows: 947-989: Missing. | ||||||
| Isoform 3 (identifier: P49816-3) The sequence of this isoform differs from the canonical sequence as follows: 1272-1294: Missing. | ||||||
| Isoform 4 (identifier: P49816-4) The sequence of this isoform differs from the canonical sequence as follows: 947-989: Missing. 1272-1294: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1809 | 1809 | Tuberin | PRO_0000065656 | |||||
Regions | |||||||||
| Domain | 1533 – 1760 | 228 | Rap-GAP | ||||||
Amino acid modifications | |||||||||
| Modified residue | 927 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 939 | 1 | Phosphoserine; by PKB/AKT1 By similarity | ||||||
| Modified residue | 981 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1132 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1155 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1340 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1341 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1349 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1366 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1389 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1413 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1420 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1422 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1452 | 1 | Phosphoserine; by AMPK By similarity | ||||||
| Modified residue | 1456 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 1466 | 1 | Phosphothreonine; by PKB/AKT1 By similarity | ||||||
| Modified residue | 1800 | 1 | Phosphoserine; by RPS6KA1 By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 947 – 989 | 43 | Missing in isoform 2 and isoform 4. | VSP_004481 | |||||
| Alternative sequence | 1272 – 1294 | 23 | Missing in isoform 3 and isoform 4. | VSP_004482 | |||||
Experimental info | |||||||||
| Mutagenesis | 314 | 1 | N → S in chemically induced renal carcinoma. Ref.4 | ||||||
| Mutagenesis | 713 | 1 | L → R in chemically induced renal carcinoma. Ref.4 | ||||||
| Sequence conflict | 932 | 1 | K → S in BAA08914. Ref.2 | ||||||
| Sequence conflict | 1514 | 1 | C → F in BAA08914. Ref.2 | ||||||
| Sequence conflict | 1730 | 1 | R → S in BAA08914. Ref.2 | ||||||
Sequences
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References
| [1] | "Identification of tuberous sclerosis 2 messenger RNA splice variants that are conserved and differentially expressed in rat and human tissues." Xiao G.-H., Jin F., Yeung R.S. Cell Growth Differ. 6:1185-1191(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4). Strain: Wistar. Tissue: Kidney. |
| [2] | "cDNA structure, alternative splicing and exon-intron organization of the predisposing tuberous sclerosis (Tsc2) gene of the Eker rat model." Kobayashi T., Nishizawa M., Hirayama Y., Kobayashi E., Hino O. Nucleic Acids Res. 23:2608-2613(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: Long Evans. Tissue: Brain and Kidney. |
| [3] | "The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis." Xiao G.-H., Shoarinejad F., Jin F., Golemis E.A., Yeung R.S. J. Biol. Chem. 272:6097-6100(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAB5. |
| [4] | "Isolation and characterization of a rat homologue of the human tuberous sclerosis 1 gene (Tsc1) and analysis of its mutations in rat renal carcinomas." Satake N., Kobayashi T., Kobayashi E., Izumi K., Hino O. Cancer Res. 59:849-855(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASN-314 AND LEU-713. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U24150 mRNA. Translation: AAC52289.1. D50413 mRNA. Translation: BAA08914.1. |
| IPI | IPI00230778. IPI00230779. IPI00230780. IPI00323980. |
| PIR | S57329. |
| RefSeq | NP_036812.2. NM_012680.3. |
| UniGene | Rn.5875. |
3D structure databases | |
| ProteinModelPortal | P49816. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P49816. 2 interactions. |
| MINT | MINT-4783802. |
| STRING | 10116.ENSRNOP00000016221. |
PTM databases | |
| PhosphoSite | P49816. |
Proteomic databases | |
| PaxDb | P49816. |
| PRIDE | P49816. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENSRNOT00000016221; ENSRNOP00000016221; ENSRNOG00000011375. |
| GeneID | 24855. |
| KEGG | rno:24855. |
| UCSC | RGD:3908. rat. |
Organism-specific databases | |
| CTD | 7249. |
| RGD | 3908. Tsc2. |
Phylogenomic databases | |
| eggNOG | NOG290929. |
| GeneTree | ENSGT00390000017866. |
| HOGENOM | HOG000045987. |
| HOVERGEN | HBG018005. |
| InParanoid | P49816. |
| KO | K07207. |
| OrthoDB | EOG4N8R3W. |
Gene expression databases | |
| ArrayExpress | P49816. |
| Genevestigator | P49816. |
| GermOnline | ENSRNOG00000011375. Rattus norvegicus. |
Family and domain databases | |
| Gene3D | 1.25.10.10. 3 hits. |
| InterPro | IPR011989. ARM-like. IPR016024. ARM-type_fold. IPR000331. Rap_GAP_dom. IPR003913. Tuberin. IPR018515. Tuberin-type_domain. IPR027107. Tuberin/Ral-act_asu. IPR024584. Tuberin_N. [Graphical view] |
| PANTHER | PTHR10063. PTHR10063. 1 hit. |
| Pfam | PF11864. DUF3384. 1 hit. PF02145. Rap_GAP. 1 hit. PF03542. Tuberin. 1 hit. [Graphical view] |
| PRINTS | PR01431. TUBERIN. |
| SUPFAM | SSF48371. ARM-type_fold. 1 hit. |
| PROSITE | PS50085. RAPGAP. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 604654. |
Entry information
| Entry name | TSC2_RAT | ||||||||
| Accession | Primary (citable) accession number: P49816 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| SIMILARITY comments Index of protein domains and families |

Clusters with
