TSC2
entrez
7249
canonical
uniprot
P49815
canonical
ensembl
ENSG00000103197
resolver
ensp
ENSP00000219476
resolver
ensp
ENSP00000344383
resolver
ensp
ENSP00000371978
resolver
ensp
ENSP00000384468
resolver
ensp
ENSP00000399232
resolver
ensp
ENSP00000406980
resolver
ensp
ENSP00000454487
resolver
ensp
ENSP00000493846
resolver
ensp
ENSP00000493990
resolver
ensp
ENSP00000494514
resolver
ensp
ENSP00000495099
resolver
ensp
ENSP00000495110
resolver
ensp
ENSP00000495146
resolver
ensp
ENSP00000495459
resolver
ensp
ENSP00000496262
resolver
ensp
ENSP00000590584
resolver
ensp
ENSP00000611825
resolver
ensp
ENSP00000611826
resolver
enst
ENST00000439117
resolver
enst
ENST00000568454
resolver
enst
ENST00000642365
resolver
enst
ENST00000642561
resolver
enst
ENST00000642797
resolver
enst
ENST00000941767
resolver
genesymbol
DKFZp686N1252
resolver
genesymbol
TSC2
resolver
genesymbol_syn
TSC4
resolver
hgnc
HGNC:12363
resolver
uniprot
A0A2R8Y6C9
resolver
uniprot
A0A2R8YCP8
resolver
uniprot
A0A2R8YDZ2
resolver
uniprot
A7E2E2
resolver
uniprot
B3KWH7
resolver
uniprot
B4DIL8
resolver
uniprot
B4DIQ7
resolver
uniprot
B4DRN2
resolver
uniprot
B7Z2B8
resolver
uniprot
C9J378
resolver
uniprot
F6VK09
resolver
uniprot
H3BMQ0
resolver
uniprot
O75275
resolver
uniprot
Q4LE71
resolver
uniprot
Q5HYF7
resolver
uniprot
Q8TAZ1
resolver
uniprot
X5D2U8
resolver
uniprot
X5D7Q2
resolver
uniprot_entry
A0A2R8Y6C9_HUMAN
resolver
uniprot_entry
A0A2R8YCP8_HUMAN
resolver
uniprot_entry
A0A2R8YDZ2_HUMAN
resolver
uniprot_entry
B3KWH7_HUMAN
resolver
uniprot_entry
F6VK09_HUMAN
resolver
uniprot_entry
H3BMQ0_HUMAN
resolver
uniprot_entry
Q5HYF7_HUMAN
resolver
uniprot_entry
TSC2_HUMAN
resolver
uniprot_entry
X5D2U8_HUMAN
resolver
uniprot_entry
X5D7Q2_HUMAN
resolver
uniprot_sec
A7E2E2
resolver
uniprot_sec
B4DIL8
resolver
uniprot_sec
B4DIQ7
resolver
uniprot_sec
B4DRN2
resolver
uniprot_sec
B7Z2B8
resolver
uniprot_sec
C9J378
resolver
uniprot_sec
O75275
resolver
uniprot_sec
Q4LE71
resolver
uniprot_sec
Q8TAZ1
resolver
amino_acid_sequence
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV
uniprot
proteins
disease_involvement
DISEASE: Tuberous sclerosis 2 (TSC2) [MIM:613254]: 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:10069705, ECO:0000269|PubMed:10205261, ECO:0000269|PubMed:10533067, ECO:0000269|PubMed:10570911, ECO:0000269|PubMed:10607950, ECO:0000269|PubMed:10732801, ECO:0000269|PubMed:10735580, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12820960, ECO:0000269|PubMed:15024740, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:15595939, ECO:0000269|PubMed:15963462, ECO:0000269|PubMed:8824881, ECO:0000269|PubMed:9302281, ECO:0000269|PubMed:9463313, ECO:0000269|PubMed:9829910}. 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:10823953, 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: 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:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:33436626, PubMed:35772404). Within the TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12172553, PubMed:12820960, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:33436626). 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:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:35772404). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity). {ECO:0000250|UniProtKB:P49816, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12820960, ECO:0000269|PubMed:12842888, ECO:0000269|PubMed:12906785, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:22819219, ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:28215400, ECO:0000269|PubMed:33436626, ECO:0000269|PubMed:35772404}.
uniprot
proteins
mass_dalton
200608
uniprot
proteins
mutagenesis
MUTAGEN 939; /note="S->A: Inhibits insulin-stimulated phosphorylation and activation of RPS6KB1; when associated with A-1462."; /evidence="ECO:0000269|PubMed:12150915"; MUTAGEN 1271; /note="T->A: Abolishes AMPK-mediated phosphorylation; when associated with A-1387."; /evidence="ECO:0000269|PubMed:14651849"; MUTAGEN 1387; /note="S->A: Abolishes AMPK-mediated phosphorylation; when associated with A-1271."; /evidence="ECO:0000269|PubMed:14651849"; MUTAGEN 1462; /note="T->A: Inhibits insulin-stimulated phosphorylation and activation of RPS6KB1; when associated with A-939."; /evidence="ECO:0000269|PubMed:12150915"; MUTAGEN 1529; /note="R->A: Decreased GTPase-activating protein activity."; /evidence="ECO:0000269|PubMed:33436626"; MUTAGEN 1533; /note="L->A: Decreased GTPase-activating protein activity."; /evidence="ECO:0000269|PubMed:33436626"; MUTAGEN 1594; /note="L->A: Decreased GTPase-activating protein activity."; /evidence="ECO:0000269|PubMed:33436626"; MUTAGEN 1637..1639; /note="KKR->QQQ: Abolishes GAP activity."; /evidence="ECO:0000269|PubMed:15340059"; MUTAGEN 1638; /note="K->A: Decreased GTPase-activating protein activity."; /evidence="ECO:0000269|PubMed:33436626"; MUTAGEN 1639; /note="R->A: Decreased GTPase-activating protein activity."; /evidence="ECO:0000269|PubMed:33436626"; MUTAGEN 1666; /note="F->A: Decreased GTPase-activating protein activity."; /evidence="ECO:0000269|PubMed:33436626"; MUTAGEN 1745; /note="R->Q: Abolishes GAP activity."; /evidence="ECO:0000269|PubMed:15340059"; MUTAGEN 1749..1751; /note="RLR->QLQ: No effect."; /evidence="ECO:0000269|PubMed:15340059"; MUTAGEN 1749; /note="R->A: Decreased GTPase-activating protein activity."; /evidence="ECO:0000269|PubMed:33436626
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-939 and Thr-1462 by PKB/AKT1 in response to insulin signaling and growth factor stimulation inhibits the ability of the TSC-TBC complex to suppress mTORC1 signaling: phosphorylation promotes dissociation of the TSC-TBC complex from lysosomal membranes, leading to activation of mTORC1 by RHEB (PubMed:12150915, PubMed:12172553, PubMed:24529379). Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1 (PubMed:15963462). Phosphorylation by AMPK activates it and leads to negative regulation of the mTORC1 complex (PubMed:14651849). Phosphorylated at Ser-1798 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling (PubMed:15342917). Phosphorylated by DAPK1 (PubMed:18974095). {ECO:0000269|PubMed:12150915, ECO:0000269|PubMed:12172553, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15342917, ECO:0000269|PubMed:15963462, ECO:0000269|PubMed:18974095, ECO:0000269|PubMed:24529379}.; PTM: Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase complex, leading to its subsequent degradation (PubMed:18381890, PubMed:27278822). Ubiquitinated by MYCBP2 independently of its phosphorylation status leading to subsequent degradation; association with TSC1 protects from ubiquitination (PubMed:18308511). {ECO:0000269|PubMed:18308511, ECO:0000269|PubMed:18381890, ECO:0000269|PubMed:27278822}.
uniprot
proteins
pubmed
10069705
uniprot
proteins
pubmed
10205261
uniprot
proteins
pubmed
10533067
uniprot
proteins
pubmed
10570911
uniprot
proteins
pubmed
10585443
uniprot
proteins
pubmed
10607950
uniprot
proteins
pubmed
10732801
uniprot
proteins
pubmed
10735580
uniprot
proteins
pubmed
10823953
uniprot
proteins
pubmed
11829138
uniprot
proteins
pubmed
12150915
uniprot
proteins
pubmed
12172553
uniprot
proteins
pubmed
12271141
uniprot
proteins
pubmed
12820960
uniprot
proteins
pubmed
12842888
uniprot
proteins
pubmed
12906785
uniprot
proteins
pubmed
14651849
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15024740
uniprot
proteins
pubmed
15340059
uniprot
proteins
pubmed
15342917
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15595939
uniprot
proteins
pubmed
15616553
uniprot
proteins
pubmed
15963462
uniprot
proteins
pubmed
16464865
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18308511
uniprot
proteins
pubmed
18381890
uniprot
proteins
pubmed
18407068
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18974095
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20145209
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22795129
uniprot
proteins
pubmed
22819219
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24529379
uniprot
proteins
pubmed
24722188
uniprot
proteins
pubmed
25816988
uniprot
proteins
pubmed
25936802
uniprot
proteins
pubmed
27278822
uniprot
proteins
pubmed
28215400
uniprot
proteins
pubmed
28561026
uniprot
proteins
pubmed
28561066
uniprot
proteins
pubmed
29127155
uniprot
proteins
pubmed
33436626
uniprot
proteins
pubmed
33473107
uniprot
proteins
pubmed
35772404
uniprot
proteins
pubmed
7558029
uniprot
proteins
pubmed
8269512
uniprot
proteins
pubmed
8789450
uniprot
proteins
pubmed
8824881
uniprot
proteins
pubmed
9045618
uniprot
proteins
pubmed
9302281
uniprot
proteins
pubmed
9463313
uniprot
proteins
pubmed
9580671
uniprot
proteins
pubmed
9829910
uniprot
proteins
pubmed
9831664
uniprot
proteins
sequence_length
1807
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:24529379, ECO:0000269|PubMed:25816988}; Peripheral membrane protein {ECO:0000269|PubMed:24529379}. Cytoplasm, cytosol {ECO:0000269|PubMed:10585443, ECO:0000269|PubMed:24529379}. Note=Recruited to lysosomal membranes in a RHEB-dependent process in absence of nutrients (PubMed:24529379). In response to insulin signaling and phosphorylation by PKB/AKT1, the complex dissociates from lysosomal membranes and relocalizes to the cytosol (PubMed:24529379). {ECO:0000269|PubMed:24529379}.
uniprot
proteins