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Protein

Hamartin

Gene

Tsc1

Organism
Mus musculus (Mouse)
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 (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 Publications

GO - Molecular functioni

  • chaperone binding Source: MGI
  • GTPase activating protein binding Source: Ensembl
  • 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
  • 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 cell proliferation Source: MGI
  • negative regulation of cell size Source: MGI
  • 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: 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: Ensembl
  • positive regulation of stress fiber assembly Source: Ensembl
  • potassium ion transport Source: MGI
  • protein heterooligomerization Source: Ensembl
  • protein stabilization Source: MGI
  • regulation of actin cytoskeleton organization Source: GO_Central
  • regulation of cell cycle Source: GO_Central
  • regulation of cell-matrix adhesion Source: MGI
  • regulation of GTPase activity Source: GO_Central
  • 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 functionChaperone

Enzyme and pathway databases

ReactomeiR-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:
Hamartin
Alternative name(s):
Tuberous sclerosis 1 protein homolog
Gene namesi
Name:Tsc1
Synonyms:Kiaa0243
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1929183 Tsc1

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

Disruption phenotypei

Conditional knockout in glia causes an increase in HSP90AA1 ATPase activity and a down-regulation of ULK1, ERBB2, ESR1 and NR3C1 protein levels in the brain.1 Publication

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003799221 – 1161HamartinAdd BLAST1161

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei484PhosphoserineBy similarity1
Modified residuei502PhosphoserineCombined sources1
Modified residuei508PhosphoserineBy similarity1
Modified residuei518PhosphoserineBy similarity1
Modified residuei592PhosphoserineCombined sources1
Modified residuei595PhosphoserineBy similarity1
Modified residuei1094PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-502 does not affect interaction with TSC2.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9EP53
PeptideAtlasiQ9EP53
PRIDEiQ9EP53

PTM databases

iPTMnetiQ9EP53
PhosphoSitePlusiQ9EP53

Expressioni

Gene expression databases

BgeeiENSMUSG00000026812
ExpressionAtlasiQ9EP53 baseline and differential
GenevisibleiQ9EP53 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).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
Tsc2Q610376EBI-1202690,EBI-7924402

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi211115, 123 interactors
IntActiQ9EP53, 120 interactors
MINTiQ9EP53
STRINGi10090.ENSMUSP00000028155

Structurei

3D structure databases

ProteinModelPortaliQ9EP53
SMRiQ9EP53
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili721 – 849Sequence analysisAdd BLAST129
Coiled coili879 – 917Sequence analysisAdd BLAST39
Coiled coili967 – 991Sequence analysisAdd BLAST25

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi312 – 315Poly-Ser4
Compositional biasi692 – 695Poly-Leu4
Compositional biasi1035 – 1040Poly-Ser6
Compositional biasi1106 – 1111Poly-Ser6

Domaini

The putative coiled-coil domain is necessary for interaction with TSC2.By similarity

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IG36 Eukaryota
ENOG411020J LUCA
GeneTreeiENSGT00390000014148
HOGENOMiHOG000232119
InParanoidiQ9EP53
KOiK07206
OMAiPYDHLFE
OrthoDBiEOG091G01O5
TreeFamiTF325466

Family and domain databases

InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR007483 Hamartin
PANTHERiPTHR15154 PTHR15154, 1 hit
PfamiView protein in Pfam
PF04388 Hamartin, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9EP53-1) [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
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
Length:1,161
Mass (Da):128,746
Last modified:March 1, 2001 - v1
Checksum:iF80ACF8492007801
GO
Isoform 2 (identifier: Q9EP53-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     381-381: Missing.

Show »
Length:1,160
Mass (Da):128,675
Checksum:i3D47312F1393101A
GO
Isoform 3 (identifier: Q9EP53-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     381-381: Missing.
     678-682: Missing.

Show »
Length:1,155
Mass (Da):128,249
Checksum:iED4C4AE278DFECED
GO
Isoform 4 (identifier: Q9EP53-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     381-381: Missing.
     1056-1067: Missing.

Show »
Length:1,148
Mass (Da):127,377
Checksum:i3E6EB98C8A3DC42E
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_037747381Missing in isoform 2, isoform 3 and isoform 4. 4 Publications1
Alternative sequenceiVSP_037748678 – 682Missing in isoform 3. 2 Publications5
Alternative sequenceiVSP_0377491056 – 1067Missing in isoform 4. 1 PublicationAdd BLAST12

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 Translation: CAM22294.1
AL731851 Genomic DNA Translation: CAM22295.1
AL731851 Genomic DNA Translation: CAM22296.2
CH466542 Genomic DNA Translation: EDL08392.1
BC052399 mRNA Translation: AAH52399.1
AK122229 mRNA Translation: BAC65511.1
CCDSiCCDS15844.1 [Q9EP53-2]
CCDS71013.1 [Q9EP53-3]
CCDS79762.1 [Q9EP53-1]
RefSeqiNP_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]
UniGeneiMm.224354

Genome annotation databases

EnsembliENSMUST00000028155; ENSMUSP00000028155; ENSMUSG00000026812 [Q9EP53-2]
ENSMUST00000113867; ENSMUSP00000109498; ENSMUSG00000026812 [Q9EP53-3]
ENSMUST00000113869; ENSMUSP00000109500; ENSMUSG00000026812 [Q9EP53-1]
ENSMUST00000113870; ENSMUSP00000109501; ENSMUSG00000026812 [Q9EP53-2]
GeneIDi64930
KEGGimmu:64930
UCSCiuc008iyw.2 mouse [Q9EP53-1]
uc008iyx.2 mouse [Q9EP53-3]
uc008iyz.2 mouse [Q9EP53-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiTSC1_MOUSE
AccessioniPrimary (citable) accession number: Q9EP53
Secondary accession number(s): A2AHW1
, Q3UHF2, Q7TS92, Q80U55, Q924U7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 28, 2009
Last sequence update: March 1, 2001
Last modified: April 25, 2018
This is version 114 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health