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Protein

Tuberin

Gene

TSC2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity3 Publications

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB
  • Hsp90 protein binding Source: UniProtKB
  • phosphatase binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • small GTPase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionGTPase activation
Biological processHost-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-1632852 Macroautophagy
R-HSA-165181 Inhibition of TSC complex formation by PKB
R-HSA-198323 AKT phosphorylates targets in the cytosol
R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-8854214 TBC/RABGAPs
SABIO-RKiP49815
SignaLinkiP49815
SIGNORiP49815

Names & Taxonomyi

Protein namesi
Recommended name:
Tuberin
Alternative name(s):
Tuberous sclerosis 2 protein
Gene namesi
Name:TSC2
Synonyms:TSC4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000103197.16
HGNCiHGNC:12363 TSC2
MIMi191092 gene
neXtProtiNX_P49815

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Tuberous sclerosis 2 (TSC2)16 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:613254
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_009415137H → R in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45517107EnsemblClinVar.1
Natural variantiVAR_008020227C → Y in TSC2. Corresponds to variant dbSNP:rs45517122EnsemblClinVar.1
Natural variantiVAR_009417258K → N in TSC2. Corresponds to variant dbSNP:rs137854875EnsemblClinVar.1
Natural variantiVAR_009418261R → P in TSC2. Corresponds to variant dbSNP:rs45502703EnsemblClinVar.1
Natural variantiVAR_005646292L → P in TSC2. Corresponds to variant dbSNP:rs45517138EnsemblClinVar.1
Natural variantiVAR_009422294G → E in TSC2. Corresponds to variant dbSNP:rs45487497EnsemblClinVar.1
Natural variantiVAR_009423304W → WGMALW in TSC2. 1
Natural variantiVAR_008021331N → K in TSC2. Corresponds to variant dbSNP:rs45517153EnsemblClinVar.1
Natural variantiVAR_009426361L → P in TSC2. Corresponds to variant dbSNP:rs45517147EnsemblClinVar.1
Natural variantiVAR_009427365Missing in TSC2. 1
Natural variantiVAR_005647407Y → D in TSC2. Corresponds to variant dbSNP:rs45517156EnsemblClinVar.1
Natural variantiVAR_005648449M → I in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45443091EnsemblClinVar.1
Natural variantiVAR_008022486N → I in TSC2. Corresponds to variant dbSNP:rs45486599EnsemblClinVar.1
Natural variantiVAR_009432525N → S in TSC2. Corresponds to variant dbSNP:rs45457694EnsemblClinVar.1
Natural variantiVAR_009435599K → M in TSC2; impairs repression of EIF4EBP1 phosphorylation. 1 PublicationCorresponds to variant dbSNP:rs45517202EnsemblClinVar.1
Natural variantiVAR_005651611R → W in TSC2; impairs phosphorylation at S-1387, S-1418 and S-1420. 4 PublicationsCorresponds to variant dbSNP:rs45469298EnsemblClinVar.1
Natural variantiVAR_009436614A → D in TSC2. Corresponds to variant dbSNP:rs45454398EnsemblClinVar.1
Natural variantiVAR_009437647D → N in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45509392EnsemblClinVar.1
Natural variantiVAR_009438694Missing in TSC2. 1
Natural variantiVAR_009439696C → Y in TSC2. Corresponds to variant dbSNP:rs45486196EnsemblClinVar.1
Natural variantiVAR_009440717L → R in TSC2. 2 PublicationsCorresponds to variant dbSNP:rs45517214EnsemblClinVar.1
Natural variantiVAR_009441769V → E in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45499191EnsemblClinVar.1
Natural variantiVAR_008026816P → L in TSC2. Corresponds to variant dbSNP:rs45517236EnsemblClinVar.1
Natural variantiVAR_005652826L → M in TSC2. Corresponds to variant dbSNP:rs45517238EnsemblClinVar.1
Natural variantiVAR_009442895M → V in TSC2. Corresponds to variant dbSNP:rs45470695EnsemblClinVar.1
Natural variantiVAR_005653905R → Q in TSC2. Corresponds to variant dbSNP:rs45517259EnsemblClinVar.1
Natural variantiVAR_005654905R → W in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45517258EnsemblClinVar.1
Natural variantiVAR_009443963V → M in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45517275EnsemblClinVar.1
Natural variantiVAR_0229191027L → P in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45438192EnsemblClinVar.1
Natural variantiVAR_0056551084D → E in TSC2. Corresponds to variant dbSNP:rs45517286EnsemblClinVar.1
Natural variantiVAR_0080271144V → M in TSC2. Corresponds to variant dbSNP:rs45517294EnsemblClinVar.1
Natural variantiVAR_0056561200R → W in TSC2. Corresponds to variant dbSNP:rs45438205EnsemblClinVar.1
Natural variantiVAR_0056571227P → L in TSC2. 1 Publication1
Natural variantiVAR_0056581240R → W in TSC2. 1 Publication1
Natural variantiVAR_0056591295D → V in TSC2. 1
Natural variantiVAR_0080281315P → S in TSC2. Corresponds to variant dbSNP:rs397514916EnsemblClinVar.1
Natural variantiVAR_0094451497P → R in TSC2. Corresponds to variant dbSNP:rs45497997EnsemblClinVar.1
Natural variantiVAR_0094461498S → N in TSC2. Corresponds to variant dbSNP:rs137854879EnsemblClinVar.1
Natural variantiVAR_0056601509Missing in TSC2; unknown pathological significance. 2 Publications1
Natural variantiVAR_0056611549Y → C in TSC2. Corresponds to variant dbSNP:rs45517355EnsemblClinVar.1
Natural variantiVAR_0094471594L → M in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45511204EnsemblClinVar.1
Natural variantiVAR_0056621614Missing in TSC2. 1
Natural variantiVAR_0094481620H → Y in TSC2. Corresponds to variant dbSNP:rs45446901EnsemblClinVar.1
Natural variantiVAR_0056631643N → I in TSC2. Corresponds to variant dbSNP:rs45517380EnsemblClinVar.1
Natural variantiVAR_0094491643N → K in TSC2; Abolishes GAP activity. 2 PublicationsCorresponds to variant dbSNP:rs45517381EnsemblClinVar.1
Natural variantiVAR_0056641650Y → C in TSC2. Corresponds to variant dbSNP:rs45501091EnsemblClinVar.1
Natural variantiVAR_0094501651N → S in TSC2; greatly reduces the ability to enhance the RHEB GTPase activity. 4 PublicationsCorresponds to variant dbSNP:rs45517382EnsemblClinVar.1
Natural variantiVAR_0186031653S → F in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45517383EnsemblClinVar.1
Natural variantiVAR_0094511675P → L in TSC2. 3 PublicationsCorresponds to variant dbSNP:rs45483392EnsemblClinVar.1
Natural variantiVAR_0094521681N → K in TSC2; Abolishes GAP activity. 2 PublicationsCorresponds to variant dbSNP:rs45476793EnsemblClinVar.1
Natural variantiVAR_0056651690D → Y in TSC2. Corresponds to variant dbSNP:rs137854882EnsemblClinVar.1
Natural variantiVAR_0094531704S → T in TSC2. Corresponds to variant dbSNP:rs45474691EnsemblClinVar.1
Natural variantiVAR_0080301709P → L in TSC2. Corresponds to variant dbSNP:rs45517393EnsemblClinVar.1
Natural variantiVAR_0056661712A → E in TSC2. 1 Publication1
Natural variantiVAR_0094541743R → P in TSC2; Abolishes GAP activity. 1 PublicationCorresponds to variant dbSNP:rs45507199EnsemblClinVar.1
Natural variantiVAR_0080311743R → Q in TSC2. Corresponds to variant dbSNP:rs45507199EnsemblClinVar.1
Natural variantiVAR_0094551744L → P in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45517413EnsemblClinVar.1
Natural variantiVAR_0094561746 – 1751Missing in TSC2. 2 Publications6
Natural variantiVAR_0056671750L → F in TSC2. Corresponds to variant dbSNP:rs45459299EnsemblClinVar.1
Natural variantiVAR_0080321773H → P in TSC2. Corresponds to variant dbSNP:rs45517418EnsemblClinVar.1
Natural variantiVAR_0080331783E → Q in TSC2. 1
Lymphangioleiomyomatosis (LAM)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionProgressive 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.
See also OMIM:606690
Focal cortical dysplasia 2 (FCORD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:607341
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0788471547V → I in FCORD2; somatic mutation; decreased function in negative regulation of TOR signaling; does not affect interaction with TSC1. 1 PublicationCorresponds to variant dbSNP:rs745895675EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi939S → A: Inhibits insulin-stimulated phosphorylation and activation of S6K1; when associated with A-1462. 1
Mutagenesisi1330T → A: Abolishes AMPK-mediated phosphorylation; when associated with A-1448. 1 Publication1
Mutagenesisi1448S → A: Abolishes AMPK-mediated phosphorylation; when associated with A-1330. 1 Publication1
Mutagenesisi1462T → A: Inhibits insulin-stimulated phosphorylation and activation of S6K1; when associated with A-939. 1
Mutagenesisi1637 – 1639KKR → QQQ: Abolishes GAP activity. 1 Publication3
Mutagenesisi1745R → Q: Abolishes GAP activity. 1 Publication1
Mutagenesisi1749 – 1751RLR → QLQ: No effect. 1 Publication3

Keywords - Diseasei

Disease mutation, Epilepsy, Tumor suppressor

Organism-specific databases

DisGeNETi7249
GeneReviewsiTSC2
MalaCardsiTSC2
MIMi606690 phenotype
607341 phenotype
613254 phenotype
OpenTargetsiENSG00000103197
Orphaneti88924 Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
538 Lymphangioleiomyomatosis
805 Tuberous sclerosis
PharmGKBiPA37035

Polymorphism and mutation databases

BioMutaiTSC2
DMDMi269849475

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000656541 – 1807TuberinAdd BLAST1807

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei540Phosphoserine1 Publication1
Modified residuei664Phosphoserine1 Publication1
Modified residuei927PhosphothreonineCombined sources1
Modified residuei939Phosphoserine; by PKB/AKT12 Publications1
Modified residuei981PhosphoserineCombined sources1
Modified residuei1132PhosphoserineCombined sources1
Modified residuei1155PhosphoserineCombined sources1
Modified residuei1330Phosphothreonine; by AMPK1 Publication1
Modified residuei1337PhosphoserineCombined sources1
Modified residuei1338PhosphoserineCombined sources1
Modified residuei1346PhosphoserineCombined sources1
Modified residuei1364PhosphoserineCombined sources1
Modified residuei1387PhosphoserineCombined sources1 Publication1
Modified residuei1411PhosphoserineCombined sources1
Modified residuei1418Phosphoserine1 Publication1
Modified residuei1420PhosphoserineCombined sources1 Publication1
Modified residuei1448Phosphoserine; by AMPK1 Publication1
Modified residuei1452PhosphoserineCombined sources1
Modified residuei1462Phosphothreonine; by PKB/AKT1Combined sources2 Publications1
Modified residuei1764PhosphoserineBy similarity1
Modified residuei1798Phosphoserine; by RPS6KA1Combined sources2 Publications1
Modified residuei1799PhosphoserineCombined sources1

Post-translational modificationi

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 DAPK1.4 Publications
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.2 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP49815
MaxQBiP49815
PaxDbiP49815
PeptideAtlasiP49815
PRIDEiP49815
ProteomicsDBi56142
56143 [P49815-2]
56144 [P49815-3]
56145 [P49815-4]
56146 [P49815-5]
56147 [P49815-6]

PTM databases

iPTMnetiP49815
PhosphoSitePlusiP49815
SwissPalmiP49815

Expressioni

Tissue specificityi

Liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle, kidney, lung and placenta.

Gene expression databases

BgeeiENSG00000103197
CleanExiHS_TSC2
ExpressionAtlasiP49815 baseline and differential
GenevisibleiP49815 HS

Organism-specific databases

HPAiCAB002225
HPA030409
HPA049679

Interactioni

Subunit structurei

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).11 Publications
(Microbial infection) Interacts with human cytomegalovirus protein UL38; this interaction inhibits cellular stress response mediated by mTORC1.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • Hsp90 protein binding Source: UniProtKB
  • phosphatase binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • small GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113100, 79 interactors
CORUMiP49815
IntActiP49815, 20 interactors
MINTiP49815
STRINGi9606.ENSP00000219476

Structurei

3D structure databases

ProteinModelPortaliP49815
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1531 – 1758Rap-GAPPROSITE-ProRule annotationAdd BLAST228

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 400Required for interaction with TSC1Add BLAST400

Phylogenomic databases

eggNOGiKOG3687 Eukaryota
ENOG410XPFJ LUCA
GeneTreeiENSGT00760000119182
HOGENOMiHOG000045987
HOVERGENiHBG018005
InParanoidiP49815
KOiK07207
OMAiCADQRPE
OrthoDBiEOG091G00O2
PhylomeDBiP49815
TreeFamiTF324484

Family and domain databases

Gene3Di3.40.50.11210, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR035974 Rap/Ran-GAP_sf
IPR000331 Rap_GAP_dom
IPR003913 Tuberin
IPR018515 Tuberin-type_domain
IPR027107 Tuberin/Ral-act_asu
IPR024584 Tuberin_N
PANTHERiPTHR10063 PTHR10063, 1 hit
PfamiView protein in Pfam
PF11864 DUF3384, 1 hit
PF02145 Rap_GAP, 1 hit
PF03542 Tuberin, 1 hit
PRINTSiPR01431 TUBERIN
SUPFAMiSSF111347 SSF111347, 1 hit
SSF48371 SSF48371, 1 hit
PROSITEiView protein in PROSITE
PS50085 RAPGAP, 1 hit

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49815-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAKPTSKDSG LKEKFKILLG LGTPRPNPRS AEGKQTEFII TAEILRELSM
60 70 80 90 100
ECGLNNRIRM IGQICEVAKT KKFEEHAVEA LWKAVADLLQ PERPLEARHA
110 120 130 140 150
VLALLKAIVQ GQGERLGVLR ALFFKVIKDY PSNEDLHERL EVFKALTDNG
160 170 180 190 200
RHITYLEEEL ADFVLQWMDV GLSSEFLLVL VNLVKFNSCY LDEYIARMVQ
210 220 230 240 250
MICLLCVRTA SSVDIEVSLQ VLDAVVCYNC LPAESLPLFI VTLCRTINVK
260 270 280 290 300
ELCEPCWKLM RNLLGTHLGH SAIYNMCHLM EDRAYMEDAP LLRGAVFFVG
310 320 330 340 350
MALWGAHRLY SLRNSPTSVL PSFYQAMACP NEVVSYEIVL SITRLIKKYR
360 370 380 390 400
KELQVVAWDI LLNIIERLLQ QLQTLDSPEL RTIVHDLLTT VEELCDQNEF
410 420 430 440 450
HGSQERYFEL VERCADQRPE SSLLNLISYR AQSIHPAKDG WIQNLQALME
460 470 480 490 500
RFFRSESRGA VRIKVLDVLS FVLLINRQFY EEELINSVVI SQLSHIPEDK
510 520 530 540 550
DHQVRKLATQ LLVDLAEGCH THHFNSLLDI IEKVMARSLS PPPELEERDV
560 570 580 590 600
AAYSASLEDV KTAVLGLLVI LQTKLYTLPA SHATRVYEML VSHIQLHYKH
610 620 630 640 650
SYTLPIASSI RLQAFDFLLL LRADSLHRLG LPNKDGVVRF SPYCVCDYME
660 670 680 690 700
PERGSEKKTS GPLSPPTGPP GPAPAGPAVR LGSVPYSLLF RVLLQCLKQE
710 720 730 740 750
SDWKVLKLVL GRLPESLRYK VLIFTSPCSV DQLCSALCSM LSGPKTLERL
760 770 780 790 800
RGAPEGFSRT DLHLAVVPVL TALISYHNYL DKTKQREMVY CLEQGLIHRC
810 820 830 840 850
ASQCVVALSI CSVEMPDIII KALPVLVVKL THISATASMA VPLLEFLSTL
860 870 880 890 900
ARLPHLYRNF AAEQYASVFA ISLPYTNPSK FNQYIVCLAH HVIAMWFIRC
910 920 930 940 950
RLPFRKDFVP FITKGLRSNV LLSFDDTPEK DSFRARSTSL NERPKSLRIA
960 970 980 990 1000
RPPKQGLNNS PPVKEFKESS AAEAFRCRSI SVSEHVVRSR IQTSLTSASL
1010 1020 1030 1040 1050
GSADENSVAQ ADDSLKNLHL ELTETCLDMM ARYVFSNFTA VPKRSPVGEF
1060 1070 1080 1090 1100
LLAGGRTKTW LVGNKLVTVT TSVGTGTRSL LGLDSGELQS GPESSSSPGV
1110 1120 1130 1140 1150
HVRQTKEAPA KLESQAGQQV SRGARDRVRS MSGGHGLRVG ALDVPASQFL
1160 1170 1180 1190 1200
GSATSPGPRT APAAKPEKAS AGTRVPVQEK TNLAAYVPLL TQGWAEILVR
1210 1220 1230 1240 1250
RPTGNTSWLM SLENPLSPFS SDINNMPLQE LSNALMAAER FKEHRDTALY
1260 1270 1280 1290 1300
KSLSVPAAST AKPPPLPRSN TVASFSSLYQ SSCQGQLHRS VSWADSAVVM
1310 1320 1330 1340 1350
EEGSPGEVPV LVEPPGLEDV EAALGMDRRT DAYSRSSSVS SQEEKSLHAE
1360 1370 1380 1390 1400
ELVGRGIPIE RVVSSEGGRP SVDLSFQPSQ PLSKSSSSPE LQTLQDILGD
1410 1420 1430 1440 1450
PGDKADVGRL SPEVKARSQS GTLDGESAAW SASGEDSRGQ PEGPLPSSSP
1460 1470 1480 1490 1500
RSPSGLRPRG YTISDSAPSR RGKRVERDAL KSRATASNAE KVPGINPSFV
1510 1520 1530 1540 1550
FLQLYHSPFF GDESNKPILL PNESQSFERS VQLLDQIPSY DTHKIAVLYV
1560 1570 1580 1590 1600
GEGQSNSELA ILSNEHGSYR YTEFLTGLGR LIELKDCQPD KVYLGGLDVC
1610 1620 1630 1640 1650
GEDGQFTYCW HDDIMQAVFH IATLMPTKDV DKHRCDKKRH LGNDFVSIVY
1660 1670 1680 1690 1700
NDSGEDFKLG TIKGQFNFVH VIVTPLDYEC NLVSLQCRKD MEGLVDTSVA
1710 1720 1730 1740 1750
KIVSDRNLPF VARQMALHAN MASQVHHSRS NPTDIYPSKW IARLRHIKRL
1760 1770 1780 1790 1800
RQRICEEAAY SNPSLPLVHP PSHSKAPAQT PAEPTPGYEV GQRKRLISSV

EDFTEFV
Length:1,807
Mass (Da):200,608
Last modified:November 24, 2009 - v2
Checksum:i7B915C46970D7D31
GO
Isoform 2 (identifier: P49815-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     946-988: Missing.

Note: No experimental confirmation available.
Show »
Length:1,764
Mass (Da):195,847
Checksum:iEECB8D3132AFFBA2
GO
Isoform 3 (identifier: P49815-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     946-989: Missing.

Note: No experimental confirmation available.
Show »
Length:1,763
Mass (Da):195,760
Checksum:i9EBB34789D67D71C
GO
Isoform 4 (identifier: P49815-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1272-1294: Missing.

Show »
Length:1,784
Mass (Da):198,097
Checksum:i36A09DD2BBCD369A
GO
Isoform 5 (identifier: P49815-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     946-989: Missing.
     1272-1294: Missing.

Show »
Length:1,740
Mass (Da):193,249
Checksum:iA0886EF0FBE7652E
GO
Isoform 6 (identifier: P49815-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     76-112: Missing.
     946-988: Missing.
     1272-1294: Missing.

Show »
Length:1,704
Mass (Da):189,298
Checksum:iAD89389C5CDB4B2C
GO
Isoform 7 (identifier: P49815-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: Missing.
     946-988: Missing.
     1272-1294: Missing.

Note: No experimental confirmation available.
Show »
Length:1,692
Mass (Da):187,956
Checksum:i2EBACFD19189839B
GO
Isoform 8 (identifier: P49815-8) [UniParc]FASTAAdd to basket
Also known as: H, I

The sequence of this isoform differs from the canonical sequence as follows:
     113-239: GERLGVLRAL...CLPAESLPLF → VRPRATLGWV...SLHSICAGLG
     240-1807: Missing.

Note: May be due to an intron retention.
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Length:239
Mass (Da):25,773
Checksum:i66E9726DB8FC2B57
GO

Sequence cautioni

The sequence BAE06082 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti187N → S in BAG61344 (Ref. 7) Curated1
Sequence conflicti210A → V in AAI50301 (PubMed:15489334).Curated1
Sequence conflicti335S → P in BAG61344 (Ref. 7) Curated1
Sequence conflicti392E → V in BAG58569 (Ref. 7) Curated1
Sequence conflicti422S → P in BAG58569 (Ref. 7) Curated1
Sequence conflicti660S → N in BAG61344 (Ref. 7) Curated1
Sequence conflicti704K → E in AAI50301 (PubMed:15489334).Curated1
Sequence conflicti706L → P in BAG58569 (Ref. 7) Curated1
Sequence conflicti1015L → M in AAI50301 (PubMed:15489334).Curated1
Sequence conflicti1239E → V in BAG61344 (Ref. 7) Curated1
Sequence conflicti1398L → V in BAG61344 (Ref. 7) Curated1
Sequence conflicti1672I → M in AAI50301 (PubMed:15489334).Curated1
Sequence conflicti1807V → A in BAG61344 (Ref. 7) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00801994P → T1 PublicationCorresponds to variant dbSNP:rs1051616EnsemblClinVar.1
Natural variantiVAR_009415137H → R in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45517107EnsemblClinVar.1
Natural variantiVAR_009416160L → V. Corresponds to variant dbSNP:rs45517109EnsemblClinVar.1
Natural variantiVAR_008020227C → Y in TSC2. Corresponds to variant dbSNP:rs45517122EnsemblClinVar.1
Natural variantiVAR_009417258K → N in TSC2. Corresponds to variant dbSNP:rs137854875EnsemblClinVar.1
Natural variantiVAR_009418261R → P in TSC2. Corresponds to variant dbSNP:rs45502703EnsemblClinVar.1
Natural variantiVAR_009419261R → W. Corresponds to variant dbSNP:rs45517130EnsemblClinVar.1
Natural variantiVAR_009420286M → T. Corresponds to variant dbSNP:rs45517136EnsemblClinVar.1
Natural variantiVAR_009421286M → V. Corresponds to variant dbSNP:rs1800748EnsemblClinVar.1
Natural variantiVAR_005646292L → P in TSC2. Corresponds to variant dbSNP:rs45517138EnsemblClinVar.1
Natural variantiVAR_009422294G → E in TSC2. Corresponds to variant dbSNP:rs45487497EnsemblClinVar.1
Natural variantiVAR_009423304W → WGMALW in TSC2. 1
Natural variantiVAR_009424309L → Q. Corresponds to variant dbSNP:rs137853986EnsemblClinVar.1
Natural variantiVAR_009425320L → F Could be associated with TSC2. 3 PublicationsCorresponds to variant dbSNP:rs1131825EnsemblClinVar.1
Natural variantiVAR_008021331N → K in TSC2. Corresponds to variant dbSNP:rs45517153EnsemblClinVar.1
Natural variantiVAR_009426361L → P in TSC2. Corresponds to variant dbSNP:rs45517147EnsemblClinVar.1
Natural variantiVAR_009427365Missing in TSC2. 1
Natural variantiVAR_009428367R → Q1 PublicationCorresponds to variant dbSNP:rs1800725EnsemblClinVar.1
Natural variantiVAR_009429378P → L. Corresponds to variant dbSNP:rs45517154EnsemblClinVar.1
Natural variantiVAR_005647407Y → D in TSC2. Corresponds to variant dbSNP:rs45517156EnsemblClinVar.1
Natural variantiVAR_009430440G → S. Corresponds to variant dbSNP:rs45484298EnsemblClinVar.1
Natural variantiVAR_005648449M → I in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45443091EnsemblClinVar.1
Natural variantiVAR_009431463I → V. Corresponds to variant dbSNP:rs45517171EnsemblClinVar.1
Natural variantiVAR_008022486N → I in TSC2. Corresponds to variant dbSNP:rs45486599EnsemblClinVar.1
Natural variantiVAR_008023490I → V. Corresponds to variant dbSNP:rs45517175EnsemblClinVar.1
Natural variantiVAR_009432525N → S in TSC2. Corresponds to variant dbSNP:rs45457694EnsemblClinVar.1
Natural variantiVAR_008024536A → V. Corresponds to variant dbSNP:rs45517187EnsemblClinVar.1
Natural variantiVAR_009433583A → T. Corresponds to variant dbSNP:rs1800729EnsemblClinVar.1
Natural variantiVAR_009434593H → R. Corresponds to variant dbSNP:rs45517198EnsemblClinVar.1
Natural variantiVAR_009435599K → M in TSC2; impairs repression of EIF4EBP1 phosphorylation. 1 PublicationCorresponds to variant dbSNP:rs45517202EnsemblClinVar.1
Natural variantiVAR_005649607A → T1 PublicationCorresponds to variant dbSNP:rs45517203EnsemblClinVar.1
Natural variantiVAR_005650611R → Q in TSC2 and LAM; impairs phosphorylation at S-1387, S-1418 and S-1420; enhances ubiquitination by MYCBP2. 5 PublicationsCorresponds to variant dbSNP:rs28934872EnsemblClinVar.1
Natural variantiVAR_005651611R → W in TSC2; impairs phosphorylation at S-1387, S-1418 and S-1420. 4 PublicationsCorresponds to variant dbSNP:rs45469298EnsemblClinVar.1
Natural variantiVAR_009436614A → D in TSC2. Corresponds to variant dbSNP:rs45454398EnsemblClinVar.1
Natural variantiVAR_008025615F → S. Corresponds to variant dbSNP:rs45481105EnsemblClinVar.1
Natural variantiVAR_060584619L → F1 PublicationCorresponds to variant dbSNP:rs1131826Ensembl.1
Natural variantiVAR_009437647D → N in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45509392EnsemblClinVar.1
Natural variantiVAR_009438694Missing in TSC2. 1
Natural variantiVAR_009439696C → Y in TSC2. Corresponds to variant dbSNP:rs45486196EnsemblClinVar.1
Natural variantiVAR_009440717L → R in TSC2. 2 PublicationsCorresponds to variant dbSNP:rs45517214EnsemblClinVar.1
Natural variantiVAR_009441769V → E in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45499191EnsemblClinVar.1
Natural variantiVAR_060585802S → R2 PublicationsCorresponds to variant dbSNP:rs1051621Ensembl.1
Natural variantiVAR_008026816P → L in TSC2. Corresponds to variant dbSNP:rs45517236EnsemblClinVar.1
Natural variantiVAR_005652826L → M in TSC2. Corresponds to variant dbSNP:rs45517238EnsemblClinVar.1
Natural variantiVAR_018600862A → V1 PublicationCorresponds to variant dbSNP:rs45517249EnsemblClinVar.1
Natural variantiVAR_009442895M → V in TSC2. Corresponds to variant dbSNP:rs45470695EnsemblClinVar.1
Natural variantiVAR_005653905R → Q in TSC2. Corresponds to variant dbSNP:rs45517259EnsemblClinVar.1
Natural variantiVAR_005654905R → W in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45517258EnsemblClinVar.1
Natural variantiVAR_009443963V → M in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45517275EnsemblClinVar.1
Natural variantiVAR_0229191027L → P in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45438192EnsemblClinVar.1
Natural variantiVAR_0056551084D → E in TSC2. Corresponds to variant dbSNP:rs45517286EnsemblClinVar.1
Natural variantiVAR_0570141141A → V. Corresponds to variant dbSNP:rs34870424EnsemblClinVar.1
Natural variantiVAR_0080271144V → M in TSC2. Corresponds to variant dbSNP:rs45517294EnsemblClinVar.1
Natural variantiVAR_0056561200R → W in TSC2. Corresponds to variant dbSNP:rs45438205EnsemblClinVar.1
Natural variantiVAR_0056571227P → L in TSC2. 1 Publication1
Natural variantiVAR_0056581240R → W in TSC2. 1 Publication1
Natural variantiVAR_0094441282S → G. Corresponds to variant dbSNP:rs45446700EnsemblClinVar.1
Natural variantiVAR_0056591295D → V in TSC2. 1
Natural variantiVAR_0080281315P → S in TSC2. Corresponds to variant dbSNP:rs397514916EnsemblClinVar.1
Natural variantiVAR_0080291329R → H. Corresponds to variant dbSNP:rs45517323EnsemblClinVar.1
Natural variantiVAR_0229201341S → R1 PublicationCorresponds to variant dbSNP:rs45462593EnsemblClinVar.1
Natural variantiVAR_0186011429A → S1 PublicationCorresponds to variant dbSNP:rs45474795EnsemblClinVar.1
Natural variantiVAR_0186021450P → R1 PublicationCorresponds to variant dbSNP:rs45517338EnsemblClinVar.1
Natural variantiVAR_0094451497P → R in TSC2. Corresponds to variant dbSNP:rs45497997EnsemblClinVar.1
Natural variantiVAR_0094461498S → N in TSC2. Corresponds to variant dbSNP:rs137854879EnsemblClinVar.1
Natural variantiVAR_0056601509Missing in TSC2; unknown pathological significance. 2 Publications1
Natural variantiVAR_0788471547V → I in FCORD2; somatic mutation; decreased function in negative regulation of TOR signaling; does not affect interaction with TSC1. 1 PublicationCorresponds to variant dbSNP:rs745895675EnsemblClinVar.1
Natural variantiVAR_0056611549Y → C in TSC2. Corresponds to variant dbSNP:rs45517355EnsemblClinVar.1
Natural variantiVAR_0094471594L → M in TSC2; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs45511204EnsemblClinVar.1
Natural variantiVAR_0056621614Missing in TSC2. 1
Natural variantiVAR_0094481620H → Y in TSC2. Corresponds to variant dbSNP:rs45446901EnsemblClinVar.1
Natural variantiVAR_0229211636D → N1 PublicationCorresponds to variant dbSNP:rs45482398EnsemblClinVar.1
Natural variantiVAR_0056631643N → I in TSC2. Corresponds to variant dbSNP:rs45517380EnsemblClinVar.1
Natural variantiVAR_0094491643N → K in TSC2; Abolishes GAP activity. 2 PublicationsCorresponds to variant dbSNP:rs45517381EnsemblClinVar.1
Natural variantiVAR_0056641650Y → C in TSC2. Corresponds to variant dbSNP:rs45501091EnsemblClinVar.1
Natural variantiVAR_0094501651N → S in TSC2; greatly reduces the ability to enhance the RHEB GTPase activity. 4 PublicationsCorresponds to variant dbSNP:rs45517382EnsemblClinVar.1
Natural variantiVAR_0186031653S → F in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45517383EnsemblClinVar.1
Natural variantiVAR_0229221673V → L1 PublicationCorresponds to variant dbSNP:rs45490993EnsemblClinVar.1
Natural variantiVAR_0094511675P → L in TSC2. 3 PublicationsCorresponds to variant dbSNP:rs45483392EnsemblClinVar.1
Natural variantiVAR_0094521681N → K in TSC2; Abolishes GAP activity. 2 PublicationsCorresponds to variant dbSNP:rs45476793EnsemblClinVar.1
Natural variantiVAR_0056651690D → Y in TSC2. Corresponds to variant dbSNP:rs137854882EnsemblClinVar.1
Natural variantiVAR_0094531704S → T in TSC2. Corresponds to variant dbSNP:rs45474691EnsemblClinVar.1
Natural variantiVAR_0080301709P → L in TSC2. Corresponds to variant dbSNP:rs45517393EnsemblClinVar.1
Natural variantiVAR_0056661712A → E in TSC2. 1 Publication1
Natural variantiVAR_0094541743R → P in TSC2; Abolishes GAP activity. 1 PublicationCorresponds to variant dbSNP:rs45507199EnsemblClinVar.1
Natural variantiVAR_0080311743R → Q in TSC2. Corresponds to variant dbSNP:rs45507199EnsemblClinVar.1
Natural variantiVAR_0094551744L → P in TSC2. 1 PublicationCorresponds to variant dbSNP:rs45517413EnsemblClinVar.1
Natural variantiVAR_0094561746 – 1751Missing in TSC2. 2 Publications6
Natural variantiVAR_0056671750L → F in TSC2. Corresponds to variant dbSNP:rs45459299EnsemblClinVar.1
Natural variantiVAR_0080321773H → P in TSC2. Corresponds to variant dbSNP:rs45517418EnsemblClinVar.1
Natural variantiVAR_0570151774S → T. Corresponds to variant dbSNP:rs9209EnsemblClinVar.1
Natural variantiVAR_0080331783E → Q in TSC2. 1
Natural variantiVAR_0094571787G → S. Corresponds to variant dbSNP:rs45517419EnsemblClinVar.1
Natural variantiVAR_0094581791G → S. Corresponds to variant dbSNP:rs45517421EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0541631 – 49Missing in isoform 7. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_03835576 – 112Missing in isoform 6. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_055896113 – 239GERLG…SLPLF → VRPRATLGWVTSGCPLTVLS LLGRVWTPASVSCWAQGLGA DGLWSWMACGVSWCHEVCVT VGTASSPVNRWSLHLPLMGC SGDHMRQFSQSAEIVPGSWC GATVLFCPCTLSGPLPCSLH SICAGLG in isoform 8. 2 PublicationsAdd BLAST127
Alternative sequenceiVSP_055897240 – 1807Missing in isoform 8. 2 PublicationsAdd BLAST1568
Alternative sequenceiVSP_004471946 – 989Missing in isoform 3 and isoform 5. 2 PublicationsAdd BLAST44
Alternative sequenceiVSP_004470946 – 988Missing in isoform 2, isoform 6 and isoform 7. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_0044721272 – 1294Missing in isoform 4, isoform 5, isoform 6 and isoform 7. 3 PublicationsAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X75621 mRNA Translation: CAA53287.1
L48546
, L48517, L48518, L48519, L48521, L48522, L48523, L48524, L48525, L48526, L48527, L48528, L48529, L48530, L48531, L48532, L48533, L48534, L48535, L48536, L48537, L48538, L48539, L48540, L48541, L48542, L48543, L48544, L48545 Genomic DNA Translation: AAB41564.1
KJ535038 mRNA Translation: AHW56677.1
KJ535051 mRNA Translation: AHW56690.1
AK294548 mRNA Translation: BAH11804.1
AK295672 mRNA Translation: BAG58530.1
AK295728 mRNA Translation: BAG58569.1
AK299343 mRNA Translation: BAG61344.1
AB210000 mRNA Translation: BAE06082.1 Different initiation.
AC005600 Genomic DNA Translation: AAC34210.1
AC093513 Genomic DNA No translation available.
CH471112 Genomic DNA Translation: EAW85556.1
BC150300 mRNA Translation: AAI50301.1
BC025364 mRNA Translation: AAH25364.1
BC046929 mRNA Translation: AAH46929.1
AB014460 Genomic DNA Translation: BAA32694.1
CCDSiCCDS10458.1 [P49815-1]
CCDS45384.1 [P49815-4]
CCDS58408.1 [P49815-5]
CCDS81933.1 [P49815-6]
CCDS81934.1 [P49815-7]
PIRiA49420
RefSeqiNP_000539.2, NM_000548.4 [P49815-1]
NP_001070651.1, NM_001077183.2 [P49815-5]
NP_001107854.1, NM_001114382.2 [P49815-4]
NP_001305756.1, NM_001318827.1 [P49815-6]
NP_001305758.1, NM_001318829.1 [P49815-7]
NP_001305760.1, NM_001318831.1
NP_001305761.1, NM_001318832.1
XP_005255586.2, XM_005255529.4 [P49815-2]
XP_016879105.1, XM_017023616.1 [P49815-3]
UniGeneiHs.90303

Genome annotation databases

EnsembliENST00000219476; ENSP00000219476; ENSG00000103197 [P49815-1]
ENST00000350773; ENSP00000344383; ENSG00000103197 [P49815-4]
ENST00000382538; ENSP00000371978; ENSG00000103197 [P49815-7]
ENST00000401874; ENSP00000384468; ENSG00000103197 [P49815-5]
ENST00000439673; ENSP00000399232; ENSG00000103197 [P49815-6]
ENST00000642936; ENSP00000494514; ENSG00000103197 [P49815-3]
ENST00000644043; ENSP00000496262; ENSG00000103197 [P49815-2]
GeneIDi7249
KEGGihsa:7249
UCSCiuc002con.4 human [P49815-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi