Q9Z136 (TSC1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hamartin

Alternative name(s):
Tuberous sclerosis 1 protein homolog

Gene names

Name:

Tsc1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1163 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity.
Subunit structure	Interacts with DOCK7 By similarity. Interacts with TSC2, leading to stabilize TSC2. In the absence of TSC2, TSC1 self-aggregates. Interacts with FBXW5 and TBC1D7 By similarity. Ref.2
Subcellular location	Cytoplasm By similarity. Membrane; Peripheral membrane protein By similarity. Note: At steady state found in association with membranes By similarity. Ref.2
Tissue specificity	Highly expressed in brain, spleen and kidney, followed by liver and heart.
Domain	The putative coiled-coil domain is necessary for interaction with TSC2 By similarity.
Post-translational modification	Phosphorylation at Ser-505 does not affect interaction with TSC2.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Disease	Tumor suppressor
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of Rho GTPase activity Inferred from electronic annotation. Source: Compara cardiac muscle cell differentiation Inferred from electronic annotation. Source: Compara cell projection organization Inferred from electronic annotation. Source: Compara cell-matrix adhesion Inferred from electronic annotation. Source: Compara cerebral cortex development Inferred from electronic annotation. Source: Compara hippocampus development Inferred from electronic annotation. Source: Compara kidney development Inferred from electronic annotation. Source: Compara myelination Inferred from electronic annotation. Source: Compara negative regulation of TOR signaling cascade Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of cell size Inferred from electronic annotation. Source: Compara negative regulation of translation Inferred from electronic annotation. Source: Compara neural tube closure Inferred from electronic annotation. Source: Compara positive regulation of focal adhesion assembly Inferred from electronic annotation. Source: Compara potassium ion transport Inferred from electronic annotation. Source: Compara protein heterooligomerization Inferred from direct assay PubMed 17379185. Source: RGD protein stabilization Inferred from electronic annotation. Source: Compara rRNA export from nucleus Inferred from electronic annotation. Source: Compara regulation of focal adhesion assembly Inferred from mutant phenotype PubMed 15611338. Source: RGD regulation of phosphoprotein phosphatase activity Inferred from electronic annotation. Source: Compara regulation of protein kinase activity Inferred from electronic annotation. Source: Compara regulation of stress fiber assembly Inferred from mutant phenotype PubMed 15611338. Source: RGD response to insulin stimulus Inferred from electronic annotation. Source: Compara synapse organization Inferred from electronic annotation. Source: Compara
Cellular_component	TSC1-TSC2 complex Inferred from electronic annotation. Source: Compara actin filament Inferred from electronic annotation. Source: Compara cell cortex Inferred from electronic annotation. Source: Compara cytoskeletal part Inferred from direct assay PubMed 12147258. Source: RGD cytosol Inferred from direct assay PubMed 12147258. Source: RGD growth cone Inferred from direct assay PubMed 12226091. Source: RGD intracellular membrane-bounded organelle Inferred from direct assay PubMed 12147258. Source: RGD lamellipodium Inferred from electronic annotation. Source: Compara membrane Inferred from electronic annotation. Source: UniProtKB-SubCell protein complex Inferred from direct assay PubMed 17379185. Source: RGD
Molecular_function	GTPase regulator activity Inferred from mutant phenotype PubMed 15611338. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1163	1163	Hamartin		PRO_0000065652
Regions
	Coiled coil	721 – 919	199	Potential
	Coiled coil	970 – 994	25	Potential
	Compositional bias	1038 – 1043	6	Poly-Ser
Amino acid modifications
	Modified residue	394	1	Phosphoserine By similarity
	Modified residue	505	1	Phosphoserine By similarity
	Modified residue	511	1	Phosphoserine By similarity
	Modified residue	598	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	287	1	H → Q in chemically induced renal carcinogenesis. Ref.1
	Mutagenesis	674	1	V → L in chemically induced renal carcinogenesis. Ref.1
	Mutagenesis	1027	1	R → W in chemically induced renal carcinogenesis. Ref.1
	Mutagenesis	1106	1	M → V in chemically induced renal carcinogenesis. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9Z136 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: CB5AE6A12AE3B0A1	FASTA	1,163	129,022
	10 20 30 40 50 60 MAQLANIGEL LSMLDSSTLG VRDDVTTIFK ESLNSERGPM LVNTLVDYYL ETNSQPVLHI 70 80 90 100 110 120 LTTLQEPHDK HLLDKMNEYV GKAATRLSIL SLLGHVVRLQ PSWKHKLSQA PLLPSLLKCL 130 140 150 160 170 180 KMDTDVVVLT TGVLVLITML PMIPQSGKQH LLDFFDIFGR LSSWCLKKPG HVTEVYLVHL 190 200 210 220 230 240 HASVYALFHR LYGMYPCNFV SFLRSHYSMK ENVETFEEVV KPMMEHVRIH PELVTGSKDH 250 260 270 280 290 300 ELDPRRWKTL ETHDVVIECA KISLDPTEAS YEDGDAVSHQ LSACFPHRSA DVTTSSYVDT 310 320 330 340 350 360 QNSYGGATST PSSTSRLMLF STPGQLPQSL SSLSTRPLPE PLQASLWSPS AVCGMTTPPT 370 380 390 400 410 420 SPGNVPADLS HPYSKAFGTT TGGKGTPSGT PATSPPPAPP CPQDDCAHGP ASQASATPPR 430 440 450 460 470 480 KEERADSSRP YLPRQQDVPS DRGLEDLPGS KGSVTLRNLP DFLGDLASEE DSIEKDKEEA 490 500 510 520 530 540 AISKELSEIT TAEADPVAPR GGFDSPFYRD SLSGSQRKTH SAASGTQGFS VNPEPLHSSL 550 560 570 580 590 600 DKHGPDTPKQ AFTPIDPPSG SADASPAGDR DRQTSLETSI LTPSPCKIPP QRGVSFGSGQ 610 620 630 640 650 660 LPPYDHLFEV ALPKTACHFV SKKTEELLKK AKGNPEEDCV PSTSPMEVLD RLLEQGAGAH 670 680 690 700 710 720 SKELSRLSLP SKSVDWTHFG GSPPSDEIRT LRDQLLLLHN QLLYERFKRQ QHALRNRRLL 730 740 750 760 770 780 RKVIRAAALE EHNAAMKDQL KLQEKDIQMW KVSLQKEQAR YSQLQQQRDT MVTQLHSQIR 790 800 810 820 830 840 QLQHDREEFY NQSQELQTKL EDCRSMIAEL RVELKKANSK VCHTELLLSQ VSQKLSNSES 850 860 870 880 890 900 VQQQMEFLNR QLLVLGEVNE LYLEQLQSKH PDTTKEVEMM KTAYRKELEK NRSHLLQQNQ 910 920 930 940 950 960 RLDASQRRVL ELESLLAKKD HLLLEQKKYL EDVKSQASGQ LLAAESRYEA QRKITRVLEL 970 980 990 1000 1010 1020 EILDLYGRLE KDGRLQKLEE DRAEAAEAAE ERLDCCTDGC SDSLLGHNEE AAGHNGETRT 1030 1040 1050 1060 1070 1080 SRPGGTRASC GGRVTGGSSS SSSELSTPEK PPNQRFSSRW EPTMGEPSSS IPTTVGSLPS 1090 1100 1110 1120 1130 1140 SKSFLGMKTR ELFRNKSESQ CDEDGMTMSS FSETLKTELG KDSAGMENKT PPSLDAPHPS 1150 1160 SPSSDSMGQL HIMDYNETHH EHS

References

[1]	"Isolation and characterization of a rat homologue of the human tuberous sclerosis 1 gene (Tsc1) and analysis of its mutations in rat renal carcinomas." Satake N., Kobayashi T., Kobayashi E., Izumi K., Hino O. Cancer Res. 59:849-855(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF HIS-287; VAL-674; ARG-1027 AND MET-1106. Strain: Long Evans. Tissue: Kidney.
[2]	"Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles." Plank T.L., Yeung R.S., Henske E.P. Cancer Res. 58:4766-4770(1998) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH TSC2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB011821 mRNA. Translation: BAA75254.1.
IPI	IPI00208147.
RefSeq	NP_068626.1. NM_021854.1.
UniGene	Rn.205837. Rn.230448.
3D structure databases
ProteinModelPortal	Q9Z136.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Z136. 1 interaction.
STRING	10116.ENSRNOP00000016904.
PTM databases
PhosphoSite	Q9Z136.
Proteomic databases
PaxDb	Q9Z136.
PRIDE	Q9Z136.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000016904; ENSRNOP00000016904; ENSRNOG00000011470.
GeneID	60445.
KEGG	rno:60445.
UCSC	RGD:620124. rat.
Organism-specific databases
CTD	7248.
RGD	620124. Tsc1.
Phylogenomic databases
eggNOG	NOG68098.
GeneTree	ENSGT00390000014148.
HOGENOM	HOG000232119.
HOVERGEN	HBG012559.
InParanoid	Q9Z136.
KO	K07206.
OMA	EHNAAMK.
OrthoDB	EOG4S4PFD.
Gene expression databases
Genevestigator	Q9Z136.
GermOnline	ENSRNOG00000011470. Rattus norvegicus.
Family and domain databases
InterPro	IPR007483. Hamartin. [Graphical view]
PANTHER	PTHR15154. PTHR15154. 1 hit.
Pfam	PF04388. Hamartin. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	612184.

Entry information

Entry name

TSC1_RAT

Accession

Primary (citable) accession number: Q9Z136

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 1999
Last modified:	April 3, 2013
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program