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Protein

Hamartin

Gene

TSC1

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

Functioni

In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (PubMed:12271141, PubMed:28215400). Seems not to be required for TSC2 GAP activity towards RHEB (PubMed:15340059). Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling (By similarity). 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).By similarity5 Publications

GO - Molecular functioni

  • ATPase inhibitor activity Source: UniProtKB
  • chaperone binding Source: UniProtKB
  • GTPase activating protein binding Source: Ensembl
  • Hsp70 protein binding Source: UniProtKB
  • Hsp90 protein binding Source: UniProtKB
  • protein N-terminus binding Source: UniProtKB

GO - Biological processi

  • activation of GTPase activity Source: UniProtKB
  • adaptive immune response Source: Ensembl
  • adult locomotory behavior Source: ParkinsonsUK-UCL
  • cardiac muscle cell differentiation Source: Ensembl
  • cell-matrix adhesion Source: UniProtKB
  • cell projection organization Source: Ensembl
  • cellular response to oxygen-glucose deprivation Source: ParkinsonsUK-UCL
  • cerebral cortex development Source: Ensembl
  • glucose import Source: Ensembl
  • hippocampus development Source: Ensembl
  • kidney development Source: Ensembl
  • memory T cell differentiation Source: Ensembl
  • myelination Source: Ensembl
  • negative regulation of ATPase activity Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of cell size Source: Ensembl
  • negative regulation of GTPase activity Source: Ensembl
  • negative regulation of insulin receptor signaling pathway Source: GO_Central
  • negative regulation of macroautophagy Source: ParkinsonsUK-UCL
  • negative regulation of neuron projection development Source: Ensembl
  • negative regulation of oxidative stress-induced neuron death Source: Ensembl
  • negative regulation of TOR signaling Source: UniProtKB
  • negative regulation of translation Source: UniProtKB
  • neural tube closure Source: Ensembl
  • positive regulation of focal adhesion assembly Source: UniProtKB
  • positive regulation of macroautophagy Source: Ensembl
  • positive regulation of stress fiber assembly Source: Ensembl
  • potassium ion transport Source: Ensembl
  • protein heterooligomerization Source: Ensembl
  • protein stabilization Source: UniProtKB
  • regulation of cell cycle Source: GO_Central
  • regulation of cell-matrix adhesion Source: UniProtKB
  • regulation of neuron death Source: ParkinsonsUK-UCL
  • regulation of phosphoprotein phosphatase activity Source: UniProtKB
  • regulation of protein kinase activity Source: Ensembl
  • regulation of stress fiber assembly Source: UniProtKB
  • regulation of translation Source: UniProtKB
  • response to insulin Source: UniProtKB
  • rRNA export from nucleus Source: UniProtKB
  • synapse organization Source: Ensembl

Keywordsi

Molecular functionChaperone

Enzyme and pathway databases

ReactomeiR-HSA-1632852 Macroautophagy
R-HSA-165181 Inhibition of TSC complex formation by PKB
R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-8854214 TBC/RABGAPs
SABIO-RKiQ92574
SignaLinkiQ92574
SIGNORiQ92574

Names & Taxonomyi

Protein namesi
Recommended name:
Hamartin
Alternative name(s):
Tuberous sclerosis 1 protein
Gene namesi
Name:TSC1
Synonyms:KIAA0243, TSC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000165699.13
HGNCiHGNC:12362 TSC1
MIMi605284 gene
neXtProtiNX_Q92574

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 1 (TSC1)8 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:191100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00939751E → D in TSC1; unknown pathological significance. Corresponds to variant dbSNP:rs118203342EnsemblClinVar.1
Natural variantiVAR_07063661L → R in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203345EnsemblClinVar.1
Natural variantiVAR_05438772L → P in TSC1. 1 PublicationCorresponds to variant dbSNP:rs118203354EnsemblClinVar.1
Natural variantiVAR_070637117L → P in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling. 3 PublicationsCorresponds to variant dbSNP:rs118203368EnsemblClinVar.1
Natural variantiVAR_070638126V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514843EnsemblClinVar.1
Natural variantiVAR_070639128Missing in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 Publication1
Natural variantiVAR_070640132G → D in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514784EnsemblClinVar.1
Natural variantiVAR_070641133V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203381EnsemblClinVar.1
Natural variantiVAR_078845165 – 1164Missing in TSC1. 1 PublicationAdd BLAST1000
Natural variantiVAR_070643180L → P in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203396EnsemblClinVar.1
Natural variantiVAR_009399191L → H in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203403EnsemblClinVar.1
Natural variantiVAR_009400198 – 199NF → I in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling. 1 Publication2
Natural variantiVAR_009401224M → R in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203426EnsemblClinVar.1
Natural variantiVAR_070645246R → K in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203436EnsemblClinVar.1
Natural variantiVAR_070646305G → R in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203468EnsemblClinVar.1
Natural variantiVAR_070647305G → W in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203468EnsemblClinVar.1
Natural variantiVAR_070648336R → Q in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514808EnsemblClinVar.1
Natural variantiVAR_070649362P → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514864EnsemblClinVar.1
Natural variantiVAR_070650411L → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514840EnsemblClinVar.1
Natural variantiVAR_009403417T → I in TSC1; unknown pathological significance; does not affect interaction with TSC2. 3 PublicationsCorresponds to variant dbSNP:rs77464996EnsemblClinVar.1
Natural variantiVAR_054391500R → Q in TSC1. 1 PublicationCorresponds to variant dbSNP:rs118203538EnsemblClinVar.1
Natural variantiVAR_070653523A → P in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203548EnsemblClinVar.1
Natural variantiVAR_009405586 – 589CKIP → S in TSC1. 4
Natural variantiVAR_009407654Q → E in TSC1. 1 PublicationCorresponds to variant dbSNP:rs75820036EnsemblClinVar.1
Natural variantiVAR_070655693D → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514800EnsemblClinVar.1
Natural variantiVAR_070656698L → R in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514802EnsemblClinVar.1
Natural variantiVAR_070657701Q → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203639EnsemblClinVar.1
Natural variantiVAR_009408726A → E in TSC1. 1 PublicationCorresponds to variant dbSNP:rs118203655EnsemblClinVar.1
Natural variantiVAR_070658762N → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203670EnsemblClinVar.1
Natural variantiVAR_070659811R → G in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514814EnsemblClinVar.1
Natural variantiVAR_070660883A → T in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203721EnsemblClinVar.1
Natural variantiVAR_009412899T → S in TSC1. 1 PublicationCorresponds to variant dbSNP:rs76801599EnsemblClinVar.1
Natural variantiVAR_070661978L → V in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514859EnsemblClinVar.1
Natural variantiVAR_0706621043Missing in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 Publication1
Natural variantiVAR_0706641146D → Y in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514806EnsemblClinVar.1
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
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_07884422R → W in FCORD2; somatic mutation; decreased interaction with TSC2; decreased function in negative regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs749030456EnsemblClinVar.1
Natural variantiVAR_078846204R → C in FCORD2; somatic mutation; decreased interaction with TSC2; decreased function in negative regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs1060505021Ensembl.1

Keywords - Diseasei

Disease mutation, Epilepsy, Tumor suppressor

Organism-specific databases

DisGeNETi7248
GeneReviewsiTSC1
MalaCardsiTSC1
MIMi191100 phenotype
606690 phenotype
607341 phenotype
OpenTargetsiENSG00000165699
Orphaneti269008 Isolated focal cortical dysplasia type IIb
538 Lymphangioleiomyomatosis
805 Tuberous sclerosis
PharmGKBiPA37034

Polymorphism and mutation databases

BioMutaiTSC1
DMDMi9297077

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000656511 – 1164HamartinAdd BLAST1164

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei487PhosphoserineCombined sources1
Modified residuei505PhosphoserineCombined sources1 Publication1
Modified residuei511PhosphoserineCombined sources1
Modified residuei521PhosphoserineCombined sources1
Modified residuei598PhosphoserineCombined sources1
Modified residuei1100PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Ser-505 does not affect interaction with TSC2.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ92574
PaxDbiQ92574
PeptideAtlasiQ92574
PRIDEiQ92574
ProteomicsDBi75334
75335 [Q92574-2]

PTM databases

CarbonylDBiQ92574
iPTMnetiQ92574
PhosphoSitePlusiQ92574

Expressioni

Tissue specificityi

Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney. Also expressed in embryonic kidney cells.

Gene expression databases

BgeeiENSG00000165699
CleanExiHS_TSC1
ExpressionAtlasiQ92574 baseline and differential
GenevisibleiQ92574 HS

Organism-specific databases

HPAiCAB011568
CAB012481
HPA074132

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). 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 (PubMed:29127155). Interacts (via C-terminus) with the closed form of HSP90AA1 (via the middle domain and TPR repeat-binding motif) (PubMed:29127155). Interacts with TSC2; the interaction stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:15963462, PubMed:16464865, PubMed:9580671, PubMed:9809973, PubMed:29127155, PubMed:28215400). Interacts with DOCK7 (PubMed:15963462). Interacts with FBXW5 (PubMed:18381890). Interacts with TBC1D7 (PubMed:17658474).9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • chaperone binding Source: UniProtKB
  • GTPase activating protein binding Source: Ensembl
  • Hsp70 protein binding Source: UniProtKB
  • Hsp90 protein binding Source: UniProtKB
  • protein N-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113099, 60 interactors
CORUMiQ92574
IntActiQ92574, 44 interactors
MINTiQ92574
STRINGi9606.ENSP00000298552

Structurei

Secondary structure

11164
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi941 – 971Combined sources31
Helixi975 – 991Combined sources17

3D structure databases

ProteinModelPortaliQ92574
SMRiQ92574
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili721 – 997Sequence analysisAdd BLAST277

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1034 – 1037Poly-Gly4
Compositional biasi1038 – 1043Poly-Ser6

Domaini

The C-terminal putative coiled-coil domain is necessary for interaction with TSC2.1 Publication

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IG36 Eukaryota
ENOG411020J LUCA
GeneTreeiENSGT00390000014148
HOGENOMiHOG000232119
HOVERGENiHBG012559
InParanoidiQ92574
KOiK07206
OMAiPYDHLFE
OrthoDBiEOG091G01O5
PhylomeDBiQ92574
TreeFamiTF325466

Family and domain databases

InterProiView protein in InterPro
IPR007483 Hamartin
PANTHERiPTHR15154 PTHR15154, 1 hit
PfamiView protein in Pfam
PF04388 Hamartin, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q92574-1) [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
MAQQANVGEL LAMLDSPMLG VRDDVTAVFK ENLNSDRGPM LVNTLVDYYL
60 70 80 90 100
ETSSQPALHI LTTLQEPHDK HLLDRINEYV GKAATRLSIL SLLGHVIRLQ
110 120 130 140 150
PSWKHKLSQA PLLPSLLKCL KMDTDVVVLT TGVLVLITML PMIPQSGKQH
160 170 180 190 200
LLDFFDIFGR LSSWCLKKPG HVAEVYLVHL HASVYALFHR LYGMYPCNFV
210 220 230 240 250
SFLRSHYSMK ENLETFEEVV KPMMEHVRIH PELVTGSKDH ELDPRRWKRL
260 270 280 290 300
ETHDVVIECA KISLDPTEAS YEDGYSVSHQ ISARFPHRSA DVTTSPYADT
310 320 330 340 350
QNSYGCATST PYSTSRLMLL NMPGQLPQTL SSPSTRLITE PPQATLWSPS
360 370 380 390 400
MVCGMTTPPT SPGNVPPDLS HPYSKVFGTT AGGKGTPLGT PATSPPPAPL
410 420 430 440 450
CHSDDYVHIS LPQATVTPPR KEERMDSARP CLHRQHHLLN DRGSEEPPGS
460 470 480 490 500
KGSVTLSDLP GFLGDLASEE DSIEKDKEEA AISRELSEIT TAEAEPVVPR
510 520 530 540 550
GGFDSPFYRD SLPGSQRKTH SAASSSQGAS VNPEPLHSSL DKLGPDTPKQ
560 570 580 590 600
AFTPIDLPCG SADESPAGDR ECQTSLETSI FTPSPCKIPP PTRVGFGSGQ
610 620 630 640 650
PPPYDHLFEV ALPKTAHHFV IRKTEELLKK AKGNTEEDGV PSTSPMEVLD
660 670 680 690 700
RLIQQGADAH SKELNKLPLP SKSVDWTHFG GSPPSDEIRT LRDQLLLLHN
710 720 730 740 750
QLLYERFKRQ QHALRNRRLL RKVIKAAALE EHNAAMKDQL KLQEKDIQMW
760 770 780 790 800
KVSLQKEQAR YNQLQEQRDT MVTKLHSQIR QLQHDREEFY NQSQELQTKL
810 820 830 840 850
EDCRNMIAEL RIELKKANNK VCHTELLLSQ VSQKLSNSES VQQQMEFLNR
860 870 880 890 900
QLLVLGEVNE LYLEQLQNKH SDTTKEVEMM KAAYRKELEK NRSHVLQQTQ
910 920 930 940 950
RLDTSQKRIL ELESHLAKKD HLLLEQKKYL EDVKLQARGQ LQAAESRYEA
960 970 980 990 1000
QKRITQVFEL EILDLYGRLE KDGLLKKLEE EKAEAAEAAE ERLDCCNDGC
1010 1020 1030 1040 1050
SDSMVGHNEE ASGHNGETKT PRPSSARGSS GSRGGGGSSS SSSELSTPEK
1060 1070 1080 1090 1100
PPHQRAGPFS SRWETTMGEA SASIPTTVGS LPSSKSFLGM KARELFRNKS
1110 1120 1130 1140 1150
ESQCDEDGMT SSLSESLKTE LGKDLGVEAK IPLNLDGPHP SPPTPDSVGQ
1160
LHIMDYNETH HEHS
Length:1,164
Mass (Da):129,767
Last modified:November 1, 1998 - v2
Checksum:iEF15509385C7AACC
GO
Isoform 2 (identifier: Q92574-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     70-120: Missing.

Note: No experimental confirmation available.
Show »
Length:1,113
Mass (Da):124,015
Checksum:i6EA012443870A73C
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07884422R → W in FCORD2; somatic mutation; decreased interaction with TSC2; decreased function in negative regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs749030456EnsemblClinVar.1
Natural variantiVAR_00939751E → D in TSC1; unknown pathological significance. Corresponds to variant dbSNP:rs118203342EnsemblClinVar.1
Natural variantiVAR_07063661L → R in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203345EnsemblClinVar.1
Natural variantiVAR_05438668H → R in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. 1 PublicationCorresponds to variant dbSNP:rs118203347EnsemblClinVar.1
Natural variantiVAR_05438772L → P in TSC1. 1 PublicationCorresponds to variant dbSNP:rs118203354EnsemblClinVar.1
Natural variantiVAR_070637117L → P in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling. 3 PublicationsCorresponds to variant dbSNP:rs118203368EnsemblClinVar.1
Natural variantiVAR_070638126V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514843EnsemblClinVar.1
Natural variantiVAR_070639128Missing in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 Publication1
Natural variantiVAR_070640132G → D in TSC1; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514784EnsemblClinVar.1
Natural variantiVAR_070641133V → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203381EnsemblClinVar.1
Natural variantiVAR_054388158F → C in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. 1 PublicationCorresponds to variant dbSNP:rs118203385EnsemblClinVar.1
Natural variantiVAR_070642158F → S Found in a patient suspected of having tuberous sclerosis; unknown pathological significance; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203385EnsemblClinVar.1
Natural variantiVAR_078845165 – 1164Missing in TSC1. 1 PublicationAdd BLAST1000
Natural variantiVAR_070643180L → P in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203396EnsemblClinVar.1
Natural variantiVAR_009398190R → S. 1
Natural variantiVAR_009399191L → H in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203403EnsemblClinVar.1
Natural variantiVAR_009400198 – 199NF → I in TSC1; reduced expression; altered subcellular localization; reduced interaction with TSC2; reduced inhibition of TORC1 signaling. 1 Publication2
Natural variantiVAR_078846204R → C in FCORD2; somatic mutation; decreased interaction with TSC2; decreased function in negative regulation of TOR signaling. 1 PublicationCorresponds to variant dbSNP:rs1060505021Ensembl.1
Natural variantiVAR_070644204R → P Found in a patient suspected of having tuberous sclerosis; reduced expression; altered subcellular localization; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514834EnsemblClinVar.1
Natural variantiVAR_054389206H → D in a bladder tumor; somatic mutation; reduced stability; does not affect interaction with TSC2. 1 Publication1
Natural variantiVAR_054390216F → L in a bladder tumor; diffuse punctate cytoplasmic distribution in aminoacid-starved conditions; does not affect interaction with TSC2. 1 Publication1
Natural variantiVAR_009401224M → R in TSC1; reduced expression; reduced inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203426EnsemblClinVar.1
Natural variantiVAR_070645246R → K in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203436EnsemblClinVar.1
Natural variantiVAR_070646305G → R in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203468EnsemblClinVar.1
Natural variantiVAR_070647305G → W in TSC1; unknown pathological significance; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203468EnsemblClinVar.1
Natural variantiVAR_009402322M → T5 PublicationsCorresponds to variant dbSNP:rs1073123EnsemblClinVar.1
Natural variantiVAR_070648336R → Q in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514808EnsemblClinVar.1
Natural variantiVAR_070649362P → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514864EnsemblClinVar.1
Natural variantiVAR_070650411L → I in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514840EnsemblClinVar.1
Natural variantiVAR_009403417T → I in TSC1; unknown pathological significance; does not affect interaction with TSC2. 3 PublicationsCorresponds to variant dbSNP:rs77464996EnsemblClinVar.1
Natural variantiVAR_070651448P → S Rare polymorphism; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203518EnsemblClinVar.1
Natural variantiVAR_054391500R → Q in TSC1. 1 PublicationCorresponds to variant dbSNP:rs118203538EnsemblClinVar.1
Natural variantiVAR_070652509R → Q Rare polymorphism; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203543EnsemblClinVar.1
Natural variantiVAR_070653523A → P in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203548EnsemblClinVar.1
Natural variantiVAR_070654567A → V Rare polymorphism; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514880EnsemblClinVar.1
Natural variantiVAR_009404577E → D1 PublicationCorresponds to variant dbSNP:rs118203571EnsemblClinVar.1
Natural variantiVAR_009405586 – 589CKIP → S in TSC1. 4
Natural variantiVAR_009406587K → R2 PublicationsCorresponds to variant dbSNP:rs118203576EnsemblClinVar.1
Natural variantiVAR_009407654Q → E in TSC1. 1 PublicationCorresponds to variant dbSNP:rs75820036EnsemblClinVar.1
Natural variantiVAR_070655693D → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514800EnsemblClinVar.1
Natural variantiVAR_070656698L → R in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514802EnsemblClinVar.1
Natural variantiVAR_070657701Q → H in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203639EnsemblClinVar.1
Natural variantiVAR_009408726A → E in TSC1. 1 PublicationCorresponds to variant dbSNP:rs118203655EnsemblClinVar.1
Natural variantiVAR_009409732H → Y Rare polymorphism; might be associated with susceptibility to focal cortical dysplasia of the Taylor balloon cell type. 4 PublicationsCorresponds to variant dbSNP:rs118203657EnsemblClinVar.1
Natural variantiVAR_070658762N → S in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203670EnsemblClinVar.1
Natural variantiVAR_009410809E → Q1 PublicationCorresponds to variant dbSNP:rs118203692EnsemblClinVar.1
Natural variantiVAR_070659811R → G in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514814EnsemblClinVar.1
Natural variantiVAR_009411829S → R1 PublicationCorresponds to variant dbSNP:rs118203699EnsemblClinVar.1
Natural variantiVAR_070660883A → T in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203721EnsemblClinVar.1
Natural variantiVAR_009412899T → S in TSC1. 1 PublicationCorresponds to variant dbSNP:rs76801599EnsemblClinVar.1
Natural variantiVAR_070661978L → V in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514859EnsemblClinVar.1
Natural variantiVAR_0094131035G → S Rare polymorphism; no effect on expression; no effect on inhibition of TORC1 signaling. 3 PublicationsCorresponds to variant dbSNP:rs118203742EnsemblClinVar.1
Natural variantiVAR_0706621043Missing in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 Publication1
Natural variantiVAR_0706631097R → H Rare polymorphism; no effect on expression; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs118203750EnsemblClinVar.1
Natural variantiVAR_0094141108G → S1 PublicationCorresponds to variant dbSNP:rs118203753EnsemblClinVar.1
Natural variantiVAR_0706641146D → Y in TSC1; unknown pathological significance; no effect on expression; no effect on subcellular localization; no effect on inhibition of TORC1 signaling. 1 PublicationCorresponds to variant dbSNP:rs397514806EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04289070 – 120Missing in isoform 2. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013168 mRNA Translation: AAC51674.1
AK303030 mRNA Translation: BAH13883.1
AL445645 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW88021.1
AC002096 Genomic DNA No translation available.
D87683 mRNA Translation: BAA13436.1
AF234185 Genomic DNA Translation: AAF61948.1
CCDSiCCDS55350.1 [Q92574-2]
CCDS6956.1 [Q92574-1]
PIRiT03814
RefSeqiNP_000359.1, NM_000368.4 [Q92574-1]
NP_001155898.1, NM_001162426.1
NP_001155899.1, NM_001162427.1 [Q92574-2]
XP_005272268.1, XM_005272211.1 [Q92574-1]
XP_006717334.1, XM_006717271.1 [Q92574-1]
XP_011517281.1, XM_011518979.2 [Q92574-1]
XP_016870585.1, XM_017015096.1 [Q92574-1]
XP_016870586.1, XM_017015097.1 [Q92574-1]
UniGeneiHs.370854

Genome annotation databases

EnsembliENST00000298552; ENSP00000298552; ENSG00000165699 [Q92574-1]
ENST00000440111; ENSP00000394524; ENSG00000165699 [Q92574-1]
ENST00000545250; ENSP00000444017; ENSG00000165699 [Q92574-2]
ENST00000643072; ENSP00000496691; ENSG00000165699 [Q92574-2]
ENST00000643875; ENSP00000495158; ENSG00000165699 [Q92574-1]
ENST00000646625; ENSP00000496263; ENSG00000165699 [Q92574-1]
GeneIDi7248
KEGGihsa:7248
UCSCiuc064wss.1 human [Q92574-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTSC1_HUMAN
AccessioniPrimary (citable) accession number: Q92574
Secondary accession number(s): B7Z897, Q5VVN5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1998
Last modified: July 18, 2018
This is version 181 of the entry and version 2 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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