TSC1
entrez
7248
canonical
uniprot
Q92574
canonical
ensembl
ENSG00000165699
resolver
ensp
ENSP00000298552
resolver
ensp
ENSP00000386093
resolver
ensp
ENSP00000493639
resolver
ensp
ENSP00000493773
resolver
ensp
ENSP00000494682
resolver
ensp
ENSP00000494685
resolver
ensp
ENSP00000494916
resolver
ensp
ENSP00000495158
resolver
ensp
ENSP00000495428
resolver
ensp
ENSP00000495533
resolver
ensp
ENSP00000495830
resolver
ensp
ENSP00000496126
resolver
ensp
ENSP00000496263
resolver
ensp
ENSP00000496691
resolver
ensp
ENSP00000496772
resolver
ensp
ENSP00000519726
resolver
ensp
ENSP00000581284
resolver
ensp
ENSP00000581285
resolver
ensp
ENSP00000605932
resolver
enst
ENST00000403810
resolver
enst
ENST00000475903
resolver
enst
ENST00000642617
resolver
enst
ENST00000642627
resolver
enst
ENST00000643583
resolver
enst
ENST00000643691
resolver
enst
ENST00000644097
resolver
enst
ENST00000644184
resolver
enst
ENST00000645129
resolver
enst
ENST00000714465
resolver
enst
ENST00000911225
resolver
enst
ENST00000911226
resolver
enst
ENST00000935873
resolver
genesymbol
TSC1
resolver
genesymbol_syn
KIAA0243
resolver
genesymbol_syn
TSC
resolver
hgnc
HGNC:12362
resolver
uniprot
A0A2R8Y5M3
resolver
uniprot
A0A2R8Y5N2
resolver
uniprot
A0A2R8Y5S3
resolver
uniprot
A0A2R8Y6S1
resolver
uniprot
A0A2R8YD74
resolver
uniprot
A0A2R8YFV7
resolver
uniprot
A0A2R8YGL0
resolver
uniprot
A0AAQ5BI41
resolver
uniprot
B7Z897
resolver
uniprot
Q32NF0
resolver
uniprot
Q5VVN5
resolver
uniprot
Q86WV8
resolver
uniprot
X5D9D2
resolver
uniprot_entry
A0A2R8Y5M3_HUMAN
resolver
uniprot_entry
A0A2R8Y5N2_HUMAN
resolver
uniprot_entry
A0A2R8Y5S3_HUMAN
resolver
uniprot_entry
A0A2R8Y6S1_HUMAN
resolver
uniprot_entry
A0A2R8YD74_HUMAN
resolver
uniprot_entry
A0A2R8YFV7_HUMAN
resolver
uniprot_entry
A0AAQ5BI41_HUMAN
resolver
uniprot_entry
Q32NF0_HUMAN
resolver
uniprot_entry
Q86WV8_HUMAN
resolver
uniprot_entry
TSC1_HUMAN
resolver
uniprot_entry
X5D9D2_HUMAN
resolver
uniprot_sec
A0A2R8YGL0
resolver
uniprot_sec
B7Z897
resolver
uniprot_sec
Q5VVN5
resolver
amino_acid_sequence
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHS
uniprot
proteins
disease_involvement
DISEASE: Tuberous sclerosis 1 (TSC1) [MIM:191100]: An autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of disease-associated causes. {ECO:0000269|PubMed:10227394, ECO:0000269|PubMed:10533069, ECO:0000269|PubMed:10570911, ECO:0000269|PubMed:10874311, ECO:0000269|PubMed:11829138, ECO:0000269|PubMed:18830229, ECO:0000269|PubMed:22161988, ECO:0000269|PubMed:9328481}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Lymphangioleiomyomatosis (LAM) [MIM:606690]: Progressive and often fatal lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. It affects almost exclusively young women and can occur as an isolated disorder or in association with tuberous sclerosis complex. {ECO:0000269|PubMed:11829138}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Focal cortical dysplasia 2 (FCORD2) [MIM:607341]: A form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults. FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities. It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells. {ECO:0000269|PubMed:28215400}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12906785, PubMed:15340059, PubMed:24529379, PubMed:28215400). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12906785, PubMed:15340059, PubMed:24529379). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12271141, PubMed:24529379, PubMed:28215400, PubMed:33215753). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Within the TSC-TBC complex, TSC1 stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:28215400). Acts as a tumor suppressor (PubMed:9242607). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also 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). {ECO:0000250|UniProtKB:Q9Z136, ECO:0000269|PubMed:10585443, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:16464865, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:29127155, ECO:0000269|PubMed:33215753, ECO:0000269|PubMed:9242607}.
uniprot
proteins
mass_dalton
129767
uniprot
proteins
mutagenesis
MUTAGEN 30; /note="K->R: Severe reduction of PELI1-induced ubiquitination."; /evidence="ECO:0000269|PubMed:33215753"; MUTAGEN 632; /note="K->R: Moderate reduction of PELI1-induced ubiquitination."; /evidence="ECO:0000269|PubMed:33215753"; MUTAGEN 941; /note="L->A: Abolished interaction with TBC1D7; when associated with 965-A--A-969."; /evidence="ECO:0000269|PubMed:26893383"; MUTAGEN 954..962; /note="ITQVFELEI->ATQVAELEA: Reduced interaction with TBC1D7 without affecting interaction with TSC2."; /evidence="ECO:0000269|PubMed:26893383"; MUTAGEN 954; /note="I->A: Abolished interaction with TBC1D7."; /evidence="ECO:0000269|PubMed:26893383"; MUTAGEN 958; /note="F->A: Abolished interaction with TBC1D7."; /evidence="ECO:0000269|PubMed:26893383"; MUTAGEN 962; /note="I->A: Abolished interaction with TBC1D7."; /evidence="ECO:0000269|PubMed:26893383"; MUTAGEN 965..969; /note="LYGRL->AAGRA: Slightly reduced interaction with TBC1D7 without affecting interaction with TSC2."; /evidence="ECO:0000269|PubMed:26893383
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-505 does not affect interaction with TSC2. {ECO:0000269|PubMed:15963462}.; PTM: 'Lys-63'-linked ubiquitinated at Lys-30 by PELI1; the ubiquitination promotes TSC1/TSC2 complex stability. {ECO:0000269|PubMed:15963462}.
uniprot
proteins
pubmed
10227394
uniprot
proteins
pubmed
10533067
uniprot
proteins
pubmed
10533069
uniprot
proteins
pubmed
10570911
uniprot
proteins
pubmed
10585443
uniprot
proteins
pubmed
10607950
uniprot
proteins
pubmed
10874311
uniprot
proteins
pubmed
11829138
uniprot
proteins
pubmed
12112044
uniprot
proteins
pubmed
12172553
uniprot
proteins
pubmed
12271141
uniprot
proteins
pubmed
12906785
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15164053
uniprot
proteins
pubmed
15340059
uniprot
proteins
pubmed
15963462
uniprot
proteins
pubmed
16464865
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17658474
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18381890
uniprot
proteins
pubmed
18397877
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18830229
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22161988
uniprot
proteins
pubmed
22795129
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24529379
uniprot
proteins
pubmed
26893383
uniprot
proteins
pubmed
28215400
uniprot
proteins
pubmed
28561026
uniprot
proteins
pubmed
28561066
uniprot
proteins
pubmed
29127155
uniprot
proteins
pubmed
33215753
uniprot
proteins
pubmed
33436626
uniprot
proteins
pubmed
9039502
uniprot
proteins
pubmed
9242607
uniprot
proteins
pubmed
9328481
uniprot
proteins
pubmed
9580671
uniprot
proteins
pubmed
9809973
uniprot
proteins
pubmed
9924605
uniprot
proteins
sequence_length
1164
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:24529379}; Peripheral membrane protein {ECO:0000269|PubMed:9809973}. Cytoplasm, cytosol {ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:9809973}. Note=Recruited to lysosomal membranes in a RHEB-dependent process in absence of nutrients (PubMed:24529379). In response to nutrients, the complex dissociates from lysosomal membranes and relocalizes to the cytosol (PubMed:24529379). {ECO:0000269|PubMed:24529379}.
uniprot
proteins