Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Hamartin

Gene

Tsc1

Organism
Rattus norvegicus (Rat)
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 (By similarity). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (By similarity). 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 similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChaperone

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Hamartin
Alternative name(s):
Tuberous sclerosis 1 protein homolog
Gene namesi
Name:Tsc1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi620124 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi287H → Q in chemically induced renal carcinogenesis. 1 Publication1
Mutagenesisi674V → L in chemically induced renal carcinogenesis. 1 Publication1
Mutagenesisi1027R → W in chemically induced renal carcinogenesis. 1 Publication1
Mutagenesisi1106M → V in chemically induced renal carcinogenesis. 1 Publication1

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000656521 – 1163HamartinAdd BLAST1163

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei487PhosphoserineBy similarity1
Modified residuei505PhosphoserineBy similarity1
Modified residuei511PhosphoserineBy similarity1
Modified residuei521PhosphoserineBy similarity1
Modified residuei595PhosphoserineBy similarity1
Modified residuei598PhosphoserineBy similarity1
Modified residuei1097PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-505 does not affect interaction with TSC2.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9Z136
PRIDEiQ9Z136

PTM databases

iPTMnetiQ9Z136
PhosphoSitePlusiQ9Z136

Expressioni

Tissue specificityi

Highly expressed in brain, spleen and kidney, followed by liver and heart.

Gene expression databases

BgeeiENSRNOG00000011470 Expressed in 9 organ(s), highest expression level in skeletal muscle tissue
GenevisibleiQ9Z136 RN

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). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (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) (By similarity). Interacts with TSC2; the interaction stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:16707451). Interacts with DOCK7 (By similarity). Interacts with FBXW5 (By similarity). Interacts with TBC1D7 (By similarity).By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi248838, 6 interactors
CORUMiQ9Z136
IntActiQ9Z136, 1 interactor
STRINGi10116.ENSRNOP00000016904

Structurei

3D structure databases

ProteinModelPortaliQ9Z136
SMRiQ9Z136
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili721 – 919Sequence analysisAdd BLAST199
Coiled coili970 – 994Sequence analysisAdd BLAST25

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1038 – 1043Poly-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
HOVERGENiHBG012559
InParanoidiQ9Z136
KOiK07206
OMAiPYDHLFE
OrthoDBiEOG091G01O5
PhylomeDBiQ9Z136
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

Sequencei

Sequence statusi: Complete.

Q9Z136-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAQLANIGEL LSMLDSSTLG VRDDVTTIFK ESLNSERGPM LVNTLVDYYL
60 70 80 90 100
ETNSQPVLHI LTTLQEPHDK HLLDKMNEYV 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 YEDGDAVSHQ LSACFPHRSA DVTTSSYVDT
310 320 330 340 350
QNSYGGATST PSSTSRLMLF STPGQLPQSL SSLSTRPLPE PLQASLWSPS
360 370 380 390 400
AVCGMTTPPT SPGNVPADLS HPYSKAFGTT TGGKGTPSGT PATSPPPAPP
410 420 430 440 450
CPQDDCAHGP ASQASATPPR KEERADSSRP YLPRQQDVPS DRGLEDLPGS
460 470 480 490 500
KGSVTLRNLP DFLGDLASEE DSIEKDKEEA AISKELSEIT TAEADPVAPR
510 520 530 540 550
GGFDSPFYRD SLSGSQRKTH SAASGTQGFS VNPEPLHSSL DKHGPDTPKQ
560 570 580 590 600
AFTPIDPPSG SADASPAGDR DRQTSLETSI LTPSPCKIPP QRGVSFGSGQ
610 620 630 640 650
LPPYDHLFEV ALPKTACHFV SKKTEELLKK AKGNPEEDCV PSTSPMEVLD
660 670 680 690 700
RLLEQGAGAH SKELSRLSLP SKSVDWTHFG GSPPSDEIRT LRDQLLLLHN
710 720 730 740 750
QLLYERFKRQ QHALRNRRLL RKVIRAAALE EHNAAMKDQL KLQEKDIQMW
760 770 780 790 800
KVSLQKEQAR YSQLQQQRDT MVTQLHSQIR QLQHDREEFY NQSQELQTKL
810 820 830 840 850
EDCRSMIAEL RVELKKANSK VCHTELLLSQ VSQKLSNSES VQQQMEFLNR
860 870 880 890 900
QLLVLGEVNE LYLEQLQSKH PDTTKEVEMM KTAYRKELEK NRSHLLQQNQ
910 920 930 940 950
RLDASQRRVL ELESLLAKKD HLLLEQKKYL EDVKSQASGQ LLAAESRYEA
960 970 980 990 1000
QRKITRVLEL EILDLYGRLE KDGRLQKLEE DRAEAAEAAE ERLDCCTDGC
1010 1020 1030 1040 1050
SDSLLGHNEE AAGHNGETRT SRPGGTRASC GGRVTGGSSS SSSELSTPEK
1060 1070 1080 1090 1100
PPNQRFSSRW EPTMGEPSSS IPTTVGSLPS SKSFLGMKTR ELFRNKSESQ
1110 1120 1130 1140 1150
CDEDGMTMSS FSETLKTELG KDSAGMENKT PPSLDAPHPS SPSSDSMGQL
1160
HIMDYNETHH EHS
Length:1,163
Mass (Da):129,022
Last modified:May 1, 1999 - v1
Checksum:iCB5AE6A12AE3B0A1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB011821 mRNA Translation: BAA75254.1
RefSeqiNP_068626.1, NM_021854.1
XP_006233905.1, XM_006233843.2
XP_006233906.1, XM_006233844.2
XP_006233907.1, XM_006233845.2
XP_006233908.1, XM_006233846.2
XP_006233909.1, XM_006233847.3
UniGeneiRn.205837
Rn.230448

Genome annotation databases

EnsembliENSRNOT00000016904; ENSRNOP00000016904; ENSRNOG00000011470
GeneIDi60445
KEGGirno:60445
UCSCiRGD:620124 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB011821 mRNA Translation: BAA75254.1
RefSeqiNP_068626.1, NM_021854.1
XP_006233905.1, XM_006233843.2
XP_006233906.1, XM_006233844.2
XP_006233907.1, XM_006233845.2
XP_006233908.1, XM_006233846.2
XP_006233909.1, XM_006233847.3
UniGeneiRn.205837
Rn.230448

3D structure databases

ProteinModelPortaliQ9Z136
SMRiQ9Z136
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248838, 6 interactors
CORUMiQ9Z136
IntActiQ9Z136, 1 interactor
STRINGi10116.ENSRNOP00000016904

PTM databases

iPTMnetiQ9Z136
PhosphoSitePlusiQ9Z136

Proteomic databases

PaxDbiQ9Z136
PRIDEiQ9Z136

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000016904; ENSRNOP00000016904; ENSRNOG00000011470
GeneIDi60445
KEGGirno:60445
UCSCiRGD:620124 rat

Organism-specific databases

CTDi7248
RGDi620124 Tsc1

Phylogenomic databases

eggNOGiENOG410IG36 Eukaryota
ENOG411020J LUCA
GeneTreeiENSGT00390000014148
HOGENOMiHOG000232119
HOVERGENiHBG012559
InParanoidiQ9Z136
KOiK07206
OMAiPYDHLFE
OrthoDBiEOG091G01O5
PhylomeDBiQ9Z136
TreeFamiTF325466

Enzyme and pathway databases

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

Miscellaneous databases

PROiPR:Q9Z136

Gene expression databases

BgeeiENSRNOG00000011470 Expressed in 9 organ(s), highest expression level in skeletal muscle tissue
GenevisibleiQ9Z136 RN

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
ProtoNetiSearch...

Entry informationi

Entry nameiTSC1_RAT
AccessioniPrimary (citable) accession number: Q9Z136
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1999
Last modified: September 12, 2018
This is version 128 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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again