UniProtKB - Q9EP53 (TSC1_MOUSE)
Hamartin
Tsc1
Functioni
In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling (By similarity).
Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling (PubMed:16707451).
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 (By similarity).
Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (By similarity).
By similarity2 PublicationsGO - Molecular functioni
- ATPase inhibitor activity Source: UniProtKB
- chaperone binding Source: MGI
- GTPase activating protein binding Source: MGI
- Hsp70 protein binding Source: MGI
- Hsp90 protein binding Source: MGI
- protein-containing complex binding Source: MGI
- protein N-terminus binding Source: UniProtKB
GO - Biological processi
- activation of GTPase activity Source: MGI
- adaptive immune response Source: MGI
- adult locomotory behavior Source: ParkinsonsUK-UCL
- associative learning Source: MGI
- cardiac muscle cell differentiation Source: MGI
- cell-matrix adhesion Source: MGI
- cell projection organization Source: MGI
- cellular response to oxygen-glucose deprivation Source: ParkinsonsUK-UCL
- cerebral cortex development Source: MGI
- glucose import Source: MGI
- hippocampus development Source: MGI
- kidney development Source: MGI
- memory T cell differentiation Source: MGI
- myelination Source: MGI
- negative regulation of ATP-dependent activity Source: UniProtKB
- negative regulation of cell population proliferation Source: MGI
- negative regulation of cell size Source: MGI
- negative regulation of GTPase activity Source: MGI
- negative regulation of macroautophagy Source: ParkinsonsUK-UCL
- negative regulation of neuron projection development Source: MGI
- negative regulation of oxidative stress-induced neuron death Source: MGI
- negative regulation of TOR signaling Source: ParkinsonsUK-UCL
- negative regulation of translation Source: MGI
- nervous system development Source: MGI
- neural tube closure Source: MGI
- positive regulation of focal adhesion assembly Source: MGI
- positive regulation of macroautophagy Source: MGI
- positive regulation of stress fiber assembly Source: MGI
- potassium ion transport Source: MGI
- protein stabilization Source: UniProtKB
- regulation of cell cycle Source: GO_Central
- regulation of cell-matrix adhesion Source: MGI
- regulation of focal adhesion assembly Source: MGI
- regulation of neuron death Source: ParkinsonsUK-UCL
- regulation of phosphoprotein phosphatase activity Source: MGI
- regulation of protein kinase activity Source: MGI
- regulation of stress fiber assembly Source: MGI
- regulation of translation Source: MGI
- response to insulin Source: MGI
- rRNA export from nucleus Source: MGI
- synapse organization Source: MGI
Keywordsi
Molecular function | Chaperone |
Enzyme and pathway databases
Reactomei | R-MMU-1632852, Macroautophagy R-MMU-165181, Inhibition of TSC complex formation by PKB R-MMU-380972, Energy dependent regulation of mTOR by LKB1-AMPK R-MMU-5628897, TP53 Regulates Metabolic Genes R-MMU-8854214, TBC/RABGAPs |
Names & Taxonomyi
Protein namesi | Recommended name: HamartinAlternative name(s): Tuberous sclerosis 1 protein homolog |
Gene namesi | Name:Tsc1 Synonyms:Kiaa0243 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1929183, Tsc1 |
VEuPathDBi | HostDB:ENSMUSG00000026812 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Other locations
- Membrane By similarity; Peripheral membrane protein By similarity
Note: At steady state found in association with membranes.By similarity
Cytoskeleton
- actin filament Source: Ensembl
- cytoskeleton Source: MGI
Cytosol
- cytosol Source: MGI
- TSC1-TSC2 complex Source: MGI
Nucleus
- nucleus Source: ParkinsonsUK-UCL
Other locations
- cell cortex Source: MGI
- cell projection Source: MGI
- chaperone complex Source: MGI
- cytoplasm Source: MGI
- growth cone Source: MGI
- intracellular membrane-bounded organelle Source: MGI
- lamellipodium Source: MGI
- lipid droplet Source: MGI
- membrane Source: MGI
- perinuclear region of cytoplasm Source: ParkinsonsUK-UCL
- postsynaptic density Source: SynGO
- protein-containing complex Source: MGI
Keywords - Cellular componenti
Cytoplasm, MembranePathology & Biotechi
Disruption phenotypei
Keywords - Diseasei
Tumor suppressorPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000379922 | 1 – 1161 | HamartinAdd BLAST | 1161 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 484 | PhosphoserineBy similarity | 1 | |
Modified residuei | 502 | PhosphoserineCombined sources | 1 | |
Modified residuei | 508 | PhosphoserineBy similarity | 1 | |
Modified residuei | 518 | PhosphoserineBy similarity | 1 | |
Modified residuei | 592 | PhosphoserineCombined sources | 1 | |
Modified residuei | 595 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1094 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9EP53 |
jPOSTi | Q9EP53 |
MaxQBi | Q9EP53 |
PaxDbi | Q9EP53 |
PeptideAtlasi | Q9EP53 |
PRIDEi | Q9EP53 |
ProteomicsDBi | 300032 [Q9EP53-1] 300033 [Q9EP53-2] 300034 [Q9EP53-3] 300035 [Q9EP53-4] |
PTM databases
iPTMneti | Q9EP53 |
PhosphoSitePlusi | Q9EP53 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000026812, Expressed in ventromedial nucleus of hypothalamus and 318 other tissues |
ExpressionAtlasi | Q9EP53, baseline and differential |
Genevisiblei | Q9EP53, MM |
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 (By similarity).
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 (By similarity).
Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (By similarity).
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 (By similarity).
Interacts with DOCK7 (By similarity).
Interacts with FBXW5 (By similarity).
Interacts with TBC1D7 (By similarity).
Interacts with WDR45B (By similarity).
Interacts with RPAP3 and URI1 (By similarity).
By similarity1 PublicationBinary interactionsi
GO - Molecular functioni
- chaperone binding Source: MGI
- GTPase activating protein binding Source: MGI
- Hsp70 protein binding Source: MGI
- Hsp90 protein binding Source: MGI
- protein N-terminus binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 211115, 132 interactors |
IntActi | Q9EP53, 122 interactors |
MINTi | Q9EP53 |
STRINGi | 10090.ENSMUSP00000109500 |
Miscellaneous databases
RNActi | Q9EP53, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 296 – 336 | DisorderedSequence analysisAdd BLAST | 41 | |
Regioni | 353 – 591 | DisorderedSequence analysisAdd BLAST | 239 | |
Regioni | 403 – 784 | Mediates interaction with WDR45BBy similarityAdd BLAST | 382 | |
Regioni | 1003 – 1077 | DisorderedSequence analysisAdd BLAST | 75 | |
Regioni | 1092 – 1161 | DisorderedSequence analysisAdd BLAST | 70 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 721 – 849 | Sequence analysisAdd BLAST | 129 | |
Coiled coili | 879 – 917 | Sequence analysisAdd BLAST | 39 | |
Coiled coili | 967 – 991 | Sequence analysisAdd BLAST | 25 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 419 – 441 | Basic and acidic residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 465 – 481 | Basic and acidic residuesSequence analysisAdd BLAST | 17 | |
Compositional biasi | 506 – 533 | Polar residuesSequence analysisAdd BLAST | 28 | |
Compositional biasi | 568 – 582 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 1029 – 1051 | Polar residuesSequence analysisAdd BLAST | 23 | |
Compositional biasi | 1060 – 1077 | Polar residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 1099 – 1149 | Polar residuesSequence analysisAdd BLAST | 51 |
Domaini
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | ENOG502QQPT, Eukaryota |
GeneTreei | ENSGT00390000014148 |
HOGENOMi | CLU_011546_0_0_1 |
InParanoidi | Q9EP53 |
OMAi | NRMASYS |
OrthoDBi | 131264at2759 |
PhylomeDBi | Q9EP53 |
TreeFami | TF325466 |
Family and domain databases
InterProi | View protein in InterPro IPR016024, ARM-type_fold IPR007483, Hamartin |
PANTHERi | PTHR15154, PTHR15154, 1 hit |
Pfami | View protein in Pfam PF04388, Hamartin, 1 hit |
SUPFAMi | SSF48371, SSF48371, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAQLANIGEL LSMLDSSTLG VRDDVTAIFK ESLNSERGPM LVNTLVDYYL
60 70 80 90 100
ETNSQPVLHI LTTLQEPHDK HLLDKINEYV GKAATRLSIL SLLGHVVRLQ
110 120 130 140 150
PSWKHKLSQA PLLPSLLKCL KMDTDVVVLT TGVLVLITML PMIPQSGKQH
160 170 180 190 200
LLDFFDIFGR LSSWCLKKPG HVTEVYLVHL HASVYALFHR LYGMYPCNFV
210 220 230 240 250
SFLRSHYSMK ENVETFEEVV KPMMEHVRIH PELVTGSKDH ELDPRRWKTL
260 270 280 290 300
ETHDVVIECA KISLDPTEAS YEDGYSVSHQ LSACFPYRSA DVTTSPYVDT
310 320 330 340 350
QNSYGGSTST PSSSSRLMLF SPPGQLPQSL SSPSTRLLPE PLQASLWSPS
360 370 380 390 400
AVCGMTTPPT SPGNVPADLS HPYSKAFGTT AGGKGTPSGT PATSPPPAPP
410 420 430 440 450
CPQDDCVHGS AAQASATAPR KEERADSSRP YLHRQSNDRG LEDPPGSKGS
460 470 480 490 500
VTLRNLPDFL GDLASEEDSI EKDKEEAAIS KELSEITTAE ADPVVPRGGF
510 520 530 540 550
DSPFYRDSLS GSQRKTHSAA SGTQGSSVNP EPLHSSLDKH GPDTPKQAFT
560 570 580 590 600
PIDPPSGSAD VSPAGDRDRQ TSLETSILTP SPCKIPPQRG VSFGSGQLPP
610 620 630 640 650
YDHLFEVALP KTACHFVSKK TEELLKKVKG NPEEDCVPST SPMEVLDRLI
660 670 680 690 700
EQGAGAHSKE LSRLSLPSKS VDWTHFGGSP PSDELRTLRD QLLLLHNQLL
710 720 730 740 750
YERFKRQQHA LRNRRLLRKV IRAAALEEHN AAMKDQLKLQ EKDIQMWKVS
760 770 780 790 800
LQKEQARYSQ LQEQRDTMVT QLHSQIRQLQ HDREEFYNQS QELQTKLEDC
810 820 830 840 850
RNMIAELRVE LKKANNKVCH TELLLSQVSQ KLSNSESVQQ QMEFLNRQLL
860 870 880 890 900
VLGEVNELYL EQLQSKHPDT TKEVEMMKTA YRKELEKNRS HLLQQNQRLD
910 920 930 940 950
ASQRRVLELE SLLAKKDHLL LEQKKYLEDV KSQASGQLLA AESRYEAQRK
960 970 980 990 1000
ITRVLELEIL DLYGRLEKDG RLRKLEEDRA EAAEAAEERL DCCSDGCTDS
1010 1020 1030 1040 1050
LVGHNEEASG HNGETRTSRP GGTRASCGGR VTGGSSSSSS ELSTPEKPPS
1060 1070 1080 1090 1100
QRFSSRWEPA LGEPSSSIPT TVGSLPSSKS FLGMKARELF RNKSESQCDE
1110 1120 1130 1140 1150
DSVTMSSSSL SETLKTELGK DSGTENKTSL SLDAPHPSSP NSDNVGQLHI
1160
MDYNETHPEH S
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF2Z3X2 | F2Z3X2_MOUSE | Hamartin | Tsc1 | 459 | Annotation score: | ||
F2Z3W0 | F2Z3W0_MOUSE | Hamartin | Tsc1 | 368 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_037747 | 381 | Missing in isoform 2, isoform 3 and isoform 4. 4 Publications | 1 | |
Alternative sequenceiVSP_037748 | 678 – 682 | Missing in isoform 3. 2 Publications | 5 | |
Alternative sequenceiVSP_037749 | 1056 – 1067 | Missing in isoform 4. 1 PublicationAdd BLAST | 12 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ271911 Genomic DNA Translation: CAC20676.1 AJ271912 mRNA Translation: CAC20677.1 AK147428 mRNA Translation: BAE27905.1 AB047561 mRNA Translation: BAB60810.1 AL731851 Genomic DNA No translation available. CH466542 Genomic DNA Translation: EDL08392.1 BC052399 mRNA Translation: AAH52399.1 AK122229 mRNA Translation: BAC65511.1 |
CCDSi | CCDS15844.1 [Q9EP53-2] CCDS71013.1 [Q9EP53-3] CCDS79762.1 [Q9EP53-1] |
RefSeqi | NP_001276504.1, NM_001289575.1 [Q9EP53-1] NP_001276505.1, NM_001289576.1 [Q9EP53-3] NP_075025.2, NM_022887.4 [Q9EP53-2] XP_011237446.1, XM_011239144.1 [Q9EP53-2] |
Genome annotation databases
Ensembli | ENSMUST00000028155; ENSMUSP00000028155; ENSMUSG00000026812 [Q9EP53-2] ENSMUST00000113867; ENSMUSP00000109498; ENSMUSG00000026812 [Q9EP53-3] ENSMUST00000113869; ENSMUSP00000109500; ENSMUSG00000026812 [Q9EP53-1] ENSMUST00000113870; ENSMUSP00000109501; ENSMUSG00000026812 [Q9EP53-2] |
GeneIDi | 64930 |
KEGGi | mmu:64930 |
UCSCi | uc008iyw.2, mouse [Q9EP53-1] uc008iyx.2, mouse [Q9EP53-3] uc008iyz.2, mouse [Q9EP53-2] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ271911 Genomic DNA Translation: CAC20676.1 AJ271912 mRNA Translation: CAC20677.1 AK147428 mRNA Translation: BAE27905.1 AB047561 mRNA Translation: BAB60810.1 AL731851 Genomic DNA No translation available. CH466542 Genomic DNA Translation: EDL08392.1 BC052399 mRNA Translation: AAH52399.1 AK122229 mRNA Translation: BAC65511.1 |
CCDSi | CCDS15844.1 [Q9EP53-2] CCDS71013.1 [Q9EP53-3] CCDS79762.1 [Q9EP53-1] |
RefSeqi | NP_001276504.1, NM_001289575.1 [Q9EP53-1] NP_001276505.1, NM_001289576.1 [Q9EP53-3] NP_075025.2, NM_022887.4 [Q9EP53-2] XP_011237446.1, XM_011239144.1 [Q9EP53-2] |
3D structure databases
AlphaFoldDBi | Q9EP53 |
SMRi | Q9EP53 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 211115, 132 interactors |
IntActi | Q9EP53, 122 interactors |
MINTi | Q9EP53 |
STRINGi | 10090.ENSMUSP00000109500 |
PTM databases
iPTMneti | Q9EP53 |
PhosphoSitePlusi | Q9EP53 |
Proteomic databases
EPDi | Q9EP53 |
jPOSTi | Q9EP53 |
MaxQBi | Q9EP53 |
PaxDbi | Q9EP53 |
PeptideAtlasi | Q9EP53 |
PRIDEi | Q9EP53 |
ProteomicsDBi | 300032 [Q9EP53-1] 300033 [Q9EP53-2] 300034 [Q9EP53-3] 300035 [Q9EP53-4] |
Protocols and materials databases
Antibodypediai | 3164, 1864 antibodies from 46 providers |
DNASUi | 64930 |
Genome annotation databases
Ensembli | ENSMUST00000028155; ENSMUSP00000028155; ENSMUSG00000026812 [Q9EP53-2] ENSMUST00000113867; ENSMUSP00000109498; ENSMUSG00000026812 [Q9EP53-3] ENSMUST00000113869; ENSMUSP00000109500; ENSMUSG00000026812 [Q9EP53-1] ENSMUST00000113870; ENSMUSP00000109501; ENSMUSG00000026812 [Q9EP53-2] |
GeneIDi | 64930 |
KEGGi | mmu:64930 |
UCSCi | uc008iyw.2, mouse [Q9EP53-1] uc008iyx.2, mouse [Q9EP53-3] uc008iyz.2, mouse [Q9EP53-2] |
Organism-specific databases
CTDi | 7248 |
MGIi | MGI:1929183, Tsc1 |
VEuPathDBi | HostDB:ENSMUSG00000026812 |
Rougei | Search... |
Phylogenomic databases
eggNOGi | ENOG502QQPT, Eukaryota |
GeneTreei | ENSGT00390000014148 |
HOGENOMi | CLU_011546_0_0_1 |
InParanoidi | Q9EP53 |
OMAi | NRMASYS |
OrthoDBi | 131264at2759 |
PhylomeDBi | Q9EP53 |
TreeFami | TF325466 |
Enzyme and pathway databases
Reactomei | R-MMU-1632852, Macroautophagy R-MMU-165181, Inhibition of TSC complex formation by PKB R-MMU-380972, Energy dependent regulation of mTOR by LKB1-AMPK R-MMU-5628897, TP53 Regulates Metabolic Genes R-MMU-8854214, TBC/RABGAPs |
Miscellaneous databases
BioGRID-ORCSi | 64930, 20 hits in 82 CRISPR screens |
ChiTaRSi | Tsc1, mouse |
PROi | PR:Q9EP53 |
RNActi | Q9EP53, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000026812, Expressed in ventromedial nucleus of hypothalamus and 318 other tissues |
ExpressionAtlasi | Q9EP53, baseline and differential |
Genevisiblei | Q9EP53, MM |
Family and domain databases
InterProi | View protein in InterPro IPR016024, ARM-type_fold IPR007483, Hamartin |
PANTHERi | PTHR15154, PTHR15154, 1 hit |
Pfami | View protein in Pfam PF04388, Hamartin, 1 hit |
SUPFAMi | SSF48371, SSF48371, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TSC1_MOUSE | |
Accessioni | Q9EP53Primary (citable) accession number: Q9EP53 Secondary accession number(s): A2AHW1 Q924U7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 28, 2009 |
Last sequence update: | March 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 136 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot