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Protein

Tuberin

Gene

TSC2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. May also play a role in microtubule-mediated protein transport. Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5.3 Publications

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

Keywords - Biological processi

Host-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.
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

HGNCiHGNC:12363. TSC2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • lysosome Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • TSC1-TSC2 complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Tuberous sclerosis 2 (TSC2)13 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti137 – 1371H → R in TSC2; unknown pathological significance. 1 Publication
Corresponds to variant rs45517107 [ dbSNP | Ensembl ].
VAR_009415
Natural varianti227 – 2271C → Y in TSC2.
Corresponds to variant rs45517122 [ dbSNP | Ensembl ].
VAR_008020
Natural varianti258 – 2581K → N in TSC2.
VAR_009417
Natural varianti261 – 2611R → P in TSC2.
Corresponds to variant rs45502703 [ dbSNP | Ensembl ].
VAR_009418
Natural varianti292 – 2921L → P in TSC2.
Corresponds to variant rs45517138 [ dbSNP | Ensembl ].
VAR_005646
Natural varianti294 – 2941G → E in TSC2.
Corresponds to variant rs45487497 [ dbSNP | Ensembl ].
VAR_009422
Natural varianti304 – 3041W → WGMALW in TSC2.
VAR_009423
Natural varianti320 – 3201L → F Could be associated with TSC2. 3 Publications
Corresponds to variant rs1131825 [ dbSNP | Ensembl ].
VAR_009425
Natural varianti331 – 3311N → K in TSC2.
Corresponds to variant rs45517153 [ dbSNP | Ensembl ].
VAR_008021
Natural varianti361 – 3611L → P in TSC2.
Corresponds to variant rs45517147 [ dbSNP | Ensembl ].
VAR_009426
Natural varianti365 – 3651Missing in TSC2.
VAR_009427
Natural varianti407 – 4071Y → D in TSC2.
VAR_005647
Natural varianti449 – 4491M → I in TSC2. 1 Publication
VAR_005648
Natural varianti486 – 4861N → I in TSC2.
VAR_008022
Natural varianti525 – 5251N → S in TSC2.
VAR_009432
Natural varianti599 – 5991K → M in TSC2; impairs repression of EIF4EBP1 phosphorylation. 1 Publication
VAR_009435
Natural varianti611 – 6111R → Q in TSC2 and LAM; impairs phosphorylation at S-1387, S-1418 and S-1420; enhances ubiquitination by MYCBP2. 5 Publications
VAR_005650
Natural varianti611 – 6111R → W in TSC2; impairs phosphorylation at S-1387, S-1418 and S-1420. 4 Publications
VAR_005651
Natural varianti614 – 6141A → D in TSC2.
VAR_009436
Natural varianti647 – 6471D → N in TSC2; unknown pathological significance. 1 Publication
VAR_009437
Natural varianti694 – 6941Missing in TSC2.
VAR_009438
Natural varianti696 – 6961C → Y in TSC2.
VAR_009439
Natural varianti717 – 7171L → R in TSC2. 2 Publications
VAR_009440
Natural varianti769 – 7691V → E in TSC2; unknown pathological significance. 1 Publication
VAR_009441
Natural varianti816 – 8161P → L in TSC2.
VAR_008026
Natural varianti826 – 8261L → M in TSC2.
VAR_005652
Natural varianti895 – 8951M → V in TSC2.
VAR_009442
Natural varianti905 – 9051R → Q in TSC2.
VAR_005653
Natural varianti905 – 9051R → W in TSC2. 1 Publication
VAR_005654
Natural varianti963 – 9631V → M in TSC2; unknown pathological significance. 1 Publication
VAR_009443
Natural varianti1027 – 10271L → P in TSC2. 1 Publication
VAR_022919
Natural varianti1084 – 10841D → E in TSC2.
VAR_005655
Natural varianti1144 – 11441V → M in TSC2.
VAR_008027
Natural varianti1200 – 12001R → W in TSC2.
VAR_005656
Natural varianti1227 – 12271P → L in TSC2. 1 Publication
VAR_005657
Natural varianti1240 – 12401R → W in TSC2. 1 Publication
VAR_005658
Natural varianti1295 – 12951D → V in TSC2.
VAR_005659
Natural varianti1315 – 13151P → S in TSC2.
VAR_008028
Natural varianti1329 – 13291R → H in TSC2.
Corresponds to variant rs45517323 [ dbSNP | Ensembl ].
VAR_008029
Natural varianti1497 – 14971P → R in TSC2.
VAR_009445
Natural varianti1498 – 14981S → N in TSC2.
VAR_009446
Natural varianti1509 – 15091Missing in TSC2; unknown pathological significance. 2 Publications
VAR_005660
Natural varianti1549 – 15491Y → C in TSC2.
VAR_005661
Natural varianti1594 – 15941L → M in TSC2; unknown pathological significance. 1 Publication
VAR_009447
Natural varianti1614 – 16141Missing in TSC2.
VAR_005662
Natural varianti1620 – 16201H → Y in TSC2.
VAR_009448
Natural varianti1643 – 16431N → I in TSC2.
VAR_005663
Natural varianti1643 – 16431N → K in TSC2; Abolishes GAP activity. 2 Publications
VAR_009449
Natural varianti1650 – 16501Y → C in TSC2.
VAR_005664
Natural varianti1651 – 16511N → S in TSC2; greatly reduces the ability to enhance the RHEB GTPase activity. 4 Publications
VAR_009450
Natural varianti1653 – 16531S → F in TSC2. 1 Publication
VAR_018603
Natural varianti1675 – 16751P → L in TSC2. 3 Publications
VAR_009451
Natural varianti1681 – 16811N → K in TSC2; Abolishes GAP activity. 2 Publications
VAR_009452
Natural varianti1690 – 16901D → Y in TSC2.
VAR_005665
Natural varianti1704 – 17041S → T in TSC2.
VAR_009453
Natural varianti1709 – 17091P → L in TSC2.
VAR_008030
Natural varianti1712 – 17121A → E in TSC2. 1 Publication
VAR_005666
Natural varianti1743 – 17431R → P in TSC2; Abolishes GAP activity. 1 Publication
VAR_009454
Natural varianti1743 – 17431R → Q in TSC2.
VAR_008031
Natural varianti1744 – 17441L → P in TSC2. 1 Publication
VAR_009455
Natural varianti1746 – 17516Missing in TSC2. 2 Publications
VAR_009456
Natural varianti1750 – 17501L → F in TSC2.
VAR_005667
Natural varianti1773 – 17731H → P in TSC2.
VAR_008032
Natural varianti1783 – 17831E → Q in TSC2.
VAR_008033
Lymphangioleiomyomatosis (LAM)1 Publication
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
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti611 – 6111R → Q in TSC2 and LAM; impairs phosphorylation at S-1387, S-1418 and S-1420; enhances ubiquitination by MYCBP2. 5 Publications
VAR_005650

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi939 – 9391S → A: Inhibits insulin-stimulated phosphorylation and activation of S6K1; when associated with A-1462.
Mutagenesisi1330 – 13301T → A: Abolishes AMPK-mediated phosphorylation; when associated with A-1448. 1 Publication
Mutagenesisi1448 – 14481S → A: Abolishes AMPK-mediated phosphorylation; when associated with A-1330. 1 Publication
Mutagenesisi1462 – 14621T → A: Inhibits insulin-stimulated phosphorylation and activation of S6K1; when associated with A-939.
Mutagenesisi1637 – 16393KKR → QQQ: Abolishes GAP activity. 1 Publication
Mutagenesisi1745 – 17451R → Q: Abolishes GAP activity. 1 Publication
Mutagenesisi1749 – 17513RLR → QLQ: No effect. 1 Publication

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

MalaCardsiTSC2.
MIMi606690. phenotype.
613254. phenotype.
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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 18071807TuberinPRO_0000065654Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei540 – 5401Phosphoserine1 Publication
Modified residuei664 – 6641Phosphoserine1 Publication
Modified residuei927 – 9271PhosphothreonineCombined sources
Modified residuei939 – 9391Phosphoserine; by PKB/AKT12 Publications
Modified residuei981 – 9811PhosphoserineCombined sources
Modified residuei1132 – 11321PhosphoserineCombined sources
Modified residuei1155 – 11551PhosphoserineCombined sources
Modified residuei1330 – 13301Phosphothreonine; by AMPK1 Publication
Modified residuei1337 – 13371PhosphoserineCombined sources
Modified residuei1338 – 13381PhosphoserineCombined sources
Modified residuei1346 – 13461PhosphoserineCombined sources
Modified residuei1364 – 13641PhosphoserineCombined sources
Modified residuei1387 – 13871PhosphoserineCombined sources1 Publication
Modified residuei1411 – 14111PhosphoserineCombined sources
Modified residuei1418 – 14181Phosphoserine1 Publication
Modified residuei1420 – 14201PhosphoserineCombined sources1 Publication
Modified residuei1448 – 14481Phosphoserine; by AMPK1 Publication
Modified residuei1452 – 14521PhosphoserineCombined sources
Modified residuei1462 – 14621Phosphothreonine; by PKB/AKT1Combined sources2 Publications
Modified residuei1764 – 17641PhosphoserineBy similarity
Modified residuei1798 – 17981Phosphoserine; by RPS6KA1Combined sources2 Publications
Modified residuei1799 – 17991PhosphoserineCombined sources

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.

PTM databases

iPTMnetiP49815.
PhosphoSiteiP49815.
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

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 contains TSC2 and RABEP1 linked to RAB5 (Probable). 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 human cytomegalovirus protein UL38; this interaction inhibits cellular stress response mediated by mTORC1 (PubMed:18407068).Curated10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PPP1CAP621362EBI-396587,EBI-357253
SIRT1Q96EB62EBI-396587,EBI-1802965
TSC1Q9257410EBI-396587,EBI-1047085
YWHABP319464EBI-396587,EBI-359815
YWHAZP631047EBI-396587,EBI-347088

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi113100. 64 interactions.
IntActiP49815. 15 interactions.
MINTiMINT-250244.
STRINGi9606.ENSP00000219476.

Structurei

3D structure databases

ProteinModelPortaliP49815.
SMRiP49815. Positions 1517-1691.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1531 – 1758228Rap-GAPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 400400Required for interaction with TSC1Add
BLAST

Sequence similaritiesi

Contains 1 Rap-GAP domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

Gene3Di1.25.10.10. 3 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000331. Rap_GAP_dom.
IPR003913. Tuberin.
IPR018515. Tuberin-type_domain.
IPR024584. Tuberin_N.
[Graphical view]
PANTHERiPTHR10063:SF1. PTHR10063:SF1. 4 hits.
PfamiPF11864. DUF3384. 1 hit.
PF02145. Rap_GAP. 1 hit.
PF03542. Tuberin. 1 hit.
[Graphical view]
PRINTSiPR01431. TUBERIN.
SUPFAMiSSF111347. SSF111347. 1 hit.
SSF48371. SSF48371. 1 hit.
PROSITEiPS50085. RAPGAP. 1 hit.
[Graphical view]

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.

Show »
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti187 – 1871N → S in BAG61344 (Ref. 7) Curated
Sequence conflicti210 – 2101A → V in AAI50301 (PubMed:15489334).Curated
Sequence conflicti335 – 3351S → P in BAG61344 (Ref. 7) Curated
Sequence conflicti392 – 3921E → V in BAG58569 (Ref. 7) Curated
Sequence conflicti422 – 4221S → P in BAG58569 (Ref. 7) Curated
Sequence conflicti660 – 6601S → N in BAG61344 (Ref. 7) Curated
Sequence conflicti704 – 7041K → E in AAI50301 (PubMed:15489334).Curated
Sequence conflicti706 – 7061L → P in BAG58569 (Ref. 7) Curated
Sequence conflicti1015 – 10151L → M in AAI50301 (PubMed:15489334).Curated
Sequence conflicti1239 – 12391E → V in BAG61344 (Ref. 7) Curated
Sequence conflicti1398 – 13981L → V in BAG61344 (Ref. 7) Curated
Sequence conflicti1672 – 16721I → M in AAI50301 (PubMed:15489334).Curated
Sequence conflicti1807 – 18071V → A in BAG61344 (Ref. 7) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti94 – 941P → T.1 Publication
Corresponds to variant rs1051616 [ dbSNP | Ensembl ].
VAR_008019
Natural varianti137 – 1371H → R in TSC2; unknown pathological significance. 1 Publication
Corresponds to variant rs45517107 [ dbSNP | Ensembl ].
VAR_009415
Natural varianti160 – 1601L → V.
Corresponds to variant rs45517109 [ dbSNP | Ensembl ].
VAR_009416
Natural varianti227 – 2271C → Y in TSC2.
Corresponds to variant rs45517122 [ dbSNP | Ensembl ].
VAR_008020
Natural varianti258 – 2581K → N in TSC2.
VAR_009417
Natural varianti261 – 2611R → P in TSC2.
Corresponds to variant rs45502703 [ dbSNP | Ensembl ].
VAR_009418
Natural varianti261 – 2611R → W.
Corresponds to variant rs45517130 [ dbSNP | Ensembl ].
VAR_009419
Natural varianti286 – 2861M → T.
Corresponds to variant rs45517136 [ dbSNP | Ensembl ].
VAR_009420
Natural varianti286 – 2861M → V.
Corresponds to variant rs1800748 [ dbSNP | Ensembl ].
VAR_009421
Natural varianti292 – 2921L → P in TSC2.
Corresponds to variant rs45517138 [ dbSNP | Ensembl ].
VAR_005646
Natural varianti294 – 2941G → E in TSC2.
Corresponds to variant rs45487497 [ dbSNP | Ensembl ].
VAR_009422
Natural varianti304 – 3041W → WGMALW in TSC2.
VAR_009423
Natural varianti309 – 3091L → Q.
VAR_009424
Natural varianti320 – 3201L → F Could be associated with TSC2. 3 Publications
Corresponds to variant rs1131825 [ dbSNP | Ensembl ].
VAR_009425
Natural varianti331 – 3311N → K in TSC2.
Corresponds to variant rs45517153 [ dbSNP | Ensembl ].
VAR_008021
Natural varianti361 – 3611L → P in TSC2.
Corresponds to variant rs45517147 [ dbSNP | Ensembl ].
VAR_009426
Natural varianti365 – 3651Missing in TSC2.
VAR_009427
Natural varianti367 – 3671R → Q.1 Publication
Corresponds to variant rs1800725 [ dbSNP | Ensembl ].
VAR_009428
Natural varianti378 – 3781P → L.
Corresponds to variant rs45517154 [ dbSNP | Ensembl ].
VAR_009429
Natural varianti407 – 4071Y → D in TSC2.
VAR_005647
Natural varianti440 – 4401G → S.
Corresponds to variant rs45484298 [ dbSNP | Ensembl ].
VAR_009430
Natural varianti449 – 4491M → I in TSC2. 1 Publication
VAR_005648
Natural varianti463 – 4631I → V.
VAR_009431
Natural varianti486 – 4861N → I in TSC2.
VAR_008022
Natural varianti490 – 4901I → V.
VAR_008023
Natural varianti525 – 5251N → S in TSC2.
VAR_009432
Natural varianti536 – 5361A → V.
VAR_008024
Natural varianti583 – 5831A → T.
Corresponds to variant rs1800729 [ dbSNP | Ensembl ].
VAR_009433
Natural varianti593 – 5931H → R.
VAR_009434
Natural varianti599 – 5991K → M in TSC2; impairs repression of EIF4EBP1 phosphorylation. 1 Publication
VAR_009435
Natural varianti607 – 6071A → T.1 Publication
VAR_005649
Natural varianti611 – 6111R → Q in TSC2 and LAM; impairs phosphorylation at S-1387, S-1418 and S-1420; enhances ubiquitination by MYCBP2. 5 Publications
VAR_005650
Natural varianti611 – 6111R → W in TSC2; impairs phosphorylation at S-1387, S-1418 and S-1420. 4 Publications
VAR_005651
Natural varianti614 – 6141A → D in TSC2.
VAR_009436
Natural varianti615 – 6151F → S.
VAR_008025
Natural varianti619 – 6191L → F.1 Publication
Corresponds to variant rs1131826 [ dbSNP | Ensembl ].
VAR_060584
Natural varianti647 – 6471D → N in TSC2; unknown pathological significance. 1 Publication
VAR_009437
Natural varianti694 – 6941Missing in TSC2.
VAR_009438
Natural varianti696 – 6961C → Y in TSC2.
VAR_009439
Natural varianti717 – 7171L → R in TSC2. 2 Publications
VAR_009440
Natural varianti769 – 7691V → E in TSC2; unknown pathological significance. 1 Publication
VAR_009441
Natural varianti802 – 8021S → R.2 Publications
Corresponds to variant rs1051621 [ dbSNP | Ensembl ].
VAR_060585
Natural varianti816 – 8161P → L in TSC2.
VAR_008026
Natural varianti826 – 8261L → M in TSC2.
VAR_005652
Natural varianti862 – 8621A → V.1 Publication
VAR_018600
Natural varianti895 – 8951M → V in TSC2.
VAR_009442
Natural varianti905 – 9051R → Q in TSC2.
VAR_005653
Natural varianti905 – 9051R → W in TSC2. 1 Publication
VAR_005654
Natural varianti963 – 9631V → M in TSC2; unknown pathological significance. 1 Publication
VAR_009443
Natural varianti1027 – 10271L → P in TSC2. 1 Publication
VAR_022919
Natural varianti1084 – 10841D → E in TSC2.
VAR_005655
Natural varianti1141 – 11411A → V.
Corresponds to variant rs34870424 [ dbSNP | Ensembl ].
VAR_057014
Natural varianti1144 – 11441V → M in TSC2.
VAR_008027
Natural varianti1200 – 12001R → W in TSC2.
VAR_005656
Natural varianti1227 – 12271P → L in TSC2. 1 Publication
VAR_005657
Natural varianti1240 – 12401R → W in TSC2. 1 Publication
VAR_005658
Natural varianti1282 – 12821S → G.
VAR_009444
Natural varianti1295 – 12951D → V in TSC2.
VAR_005659
Natural varianti1315 – 13151P → S in TSC2.
VAR_008028
Natural varianti1329 – 13291R → H in TSC2.
Corresponds to variant rs45517323 [ dbSNP | Ensembl ].
VAR_008029
Natural varianti1341 – 13411S → R.1 Publication
VAR_022920
Natural varianti1429 – 14291A → S.1 Publication
Corresponds to variant rs45474795 [ dbSNP | Ensembl ].
VAR_018601
Natural varianti1450 – 14501P → R.1 Publication
VAR_018602
Natural varianti1497 – 14971P → R in TSC2.
VAR_009445
Natural varianti1498 – 14981S → N in TSC2.
VAR_009446
Natural varianti1509 – 15091Missing in TSC2; unknown pathological significance. 2 Publications
VAR_005660
Natural varianti1549 – 15491Y → C in TSC2.
VAR_005661
Natural varianti1594 – 15941L → M in TSC2; unknown pathological significance. 1 Publication
VAR_009447
Natural varianti1614 – 16141Missing in TSC2.
VAR_005662
Natural varianti1620 – 16201H → Y in TSC2.
VAR_009448
Natural varianti1636 – 16361D → N.1 Publication
VAR_022921
Natural varianti1643 – 16431N → I in TSC2.
VAR_005663
Natural varianti1643 – 16431N → K in TSC2; Abolishes GAP activity. 2 Publications
VAR_009449
Natural varianti1650 – 16501Y → C in TSC2.
VAR_005664
Natural varianti1651 – 16511N → S in TSC2; greatly reduces the ability to enhance the RHEB GTPase activity. 4 Publications
VAR_009450
Natural varianti1653 – 16531S → F in TSC2. 1 Publication
VAR_018603
Natural varianti1673 – 16731V → L.1 Publication
VAR_022922
Natural varianti1675 – 16751P → L in TSC2. 3 Publications
VAR_009451
Natural varianti1681 – 16811N → K in TSC2; Abolishes GAP activity. 2 Publications
VAR_009452
Natural varianti1690 – 16901D → Y in TSC2.
VAR_005665
Natural varianti1704 – 17041S → T in TSC2.
VAR_009453
Natural varianti1709 – 17091P → L in TSC2.
VAR_008030
Natural varianti1712 – 17121A → E in TSC2. 1 Publication
VAR_005666
Natural varianti1743 – 17431R → P in TSC2; Abolishes GAP activity. 1 Publication
VAR_009454
Natural varianti1743 – 17431R → Q in TSC2.
VAR_008031
Natural varianti1744 – 17441L → P in TSC2. 1 Publication
VAR_009455
Natural varianti1746 – 17516Missing in TSC2. 2 Publications
VAR_009456
Natural varianti1750 – 17501L → F in TSC2.
VAR_005667
Natural varianti1773 – 17731H → P in TSC2.
VAR_008032
Natural varianti1774 – 17741S → T.
Corresponds to variant rs9209 [ dbSNP | Ensembl ].
VAR_057015
Natural varianti1783 – 17831E → Q in TSC2.
VAR_008033
Natural varianti1787 – 17871G → S.
Corresponds to variant rs45517419 [ dbSNP | Ensembl ].
VAR_009457
Natural varianti1791 – 17911G → S.
VAR_009458

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4949Missing in isoform 7. 1 PublicationVSP_054163Add
BLAST
Alternative sequencei76 – 11237Missing in isoform 6. 1 PublicationVSP_038355Add
BLAST
Alternative sequencei113 – 239127GERLG…SLPLF → VRPRATLGWVTSGCPLTVLS LLGRVWTPASVSCWAQGLGA DGLWSWMACGVSWCHEVCVT VGTASSPVNRWSLHLPLMGC SGDHMRQFSQSAEIVPGSWC GATVLFCPCTLSGPLPCSLH SICAGLG in isoform 8. 2 PublicationsVSP_055896Add
BLAST
Alternative sequencei240 – 18071568Missing in isoform 8. 2 PublicationsVSP_055897Add
BLAST
Alternative sequencei946 – 98944Missing in isoform 3 and isoform 5. 2 PublicationsVSP_004471Add
BLAST
Alternative sequencei946 – 98843Missing in isoform 2, isoform 6 and isoform 7. 1 PublicationVSP_004470Add
BLAST
Alternative sequencei1272 – 129423Missing in isoform 4, isoform 5, isoform 6 and isoform 7. 3 PublicationsVSP_004472Add
BLAST

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]
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]
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]
GeneIDi7249.
KEGGihsa:7249.
UCSCiuc002con.4. human. [P49815-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Tuberous sclerosis database Tuberous sclerosis 2 (TSC2)

Leiden Open Variation Database (LOVD)

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]
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]
UniGeneiHs.90303.

3D structure databases

ProteinModelPortaliP49815.
SMRiP49815. Positions 1517-1691.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113100. 64 interactions.
IntActiP49815. 15 interactions.
MINTiMINT-250244.
STRINGi9606.ENSP00000219476.

PTM databases

iPTMnetiP49815.
PhosphoSiteiP49815.
SwissPalmiP49815.

Polymorphism and mutation databases

BioMutaiTSC2.
DMDMi269849475.

Proteomic databases

EPDiP49815.
MaxQBiP49815.
PaxDbiP49815.
PeptideAtlasiP49815.
PRIDEiP49815.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]
GeneIDi7249.
KEGGihsa:7249.
UCSCiuc002con.4. human. [P49815-1]

Organism-specific databases

CTDi7249.
GeneCardsiTSC2.
GeneReviewsiTSC2.
HGNCiHGNC:12363. TSC2.
HPAiCAB002225.
HPA030409.
HPA049679.
MalaCardsiTSC2.
MIMi191092. gene.
606690. phenotype.
613254. phenotype.
neXtProtiNX_P49815.
Orphaneti88924. Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis.
538. Lymphangioleiomyomatosis.
805. Tuberous sclerosis.
PharmGKBiPA37035.
GenAtlasiSearch...

Phylogenomic databases

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

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.
SignaLinkiP49815.
SIGNORiP49815.

Miscellaneous databases

GeneWikiiTSC2.
GenomeRNAii7249.
PROiP49815.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000103197.
CleanExiHS_TSC2.
ExpressionAtlasiP49815. baseline and differential.
GenevisibleiP49815. HS.

Family and domain databases

Gene3Di1.25.10.10. 3 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000331. Rap_GAP_dom.
IPR003913. Tuberin.
IPR018515. Tuberin-type_domain.
IPR024584. Tuberin_N.
[Graphical view]
PANTHERiPTHR10063:SF1. PTHR10063:SF1. 4 hits.
PfamiPF11864. DUF3384. 1 hit.
PF02145. Rap_GAP. 1 hit.
PF03542. Tuberin. 1 hit.
[Graphical view]
PRINTSiPR01431. TUBERIN.
SUPFAMiSSF111347. SSF111347. 1 hit.
SSF48371. SSF48371. 1 hit.
PROSITEiPS50085. RAPGAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTSC2_HUMAN
AccessioniPrimary (citable) accession number: P49815
Secondary accession number(s): A7E2E2
, B4DIL8, B4DIQ7, B4DRN2, B7Z2B8, C9J378, O75275, Q4LE71, Q8TAZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: November 24, 2009
Last modified: September 7, 2016
This is version 185 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.