Q9DCJ1 (LST8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Target of rapamycin complex subunit LST8
Short name=TORC subunit LST8

Alternative name(s):
G protein beta subunit-like
Short name=Protein GbetaL
Mammalian lethal with SEC13 protein 8
Short name=mLST8

Gene names

Name:	Mlst8
Synonyms:	Gbl, Lst8

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	326 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Ref.5
Subunit structure	Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR By similarity. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR By similarity. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Interacts directly with MTOR and RPTOR. Interacts with RHEB By similarity. Interacts with MTOR. Ref.4 Ref.6
Subcellular location	Cytoplasm By similarity.
Disruption phenotype	Death around E10.5 due to multiple defects in vascular system development. In addition, they exhibit a delayed development of their cephalic region. Ref.5
Sequence similarities	Belongs to the WD repeat LST8 family. Contains 7 WD repeats.

Ontologies

Keywords
Cellular component	Cytoplasm
Domain	Repeat WD repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	positive regulation of actin filament polymerization Inferred from mutant phenotype. Source: MGI positive regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype. Source: MGI regulation of Rac GTPase activity Inferred from mutant phenotype. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 326	326	Target of rapamycin complex subunit LST8		PRO_0000326500
Regions
	Repeat	1 – 37	37	WD 1
	Repeat	40 – 80	41	WD 2
	Repeat	83 – 122	40	WD 3
	Repeat	126 – 165	40	WD 4
	Repeat	168 – 207	40	WD 5
	Repeat	218 – 257	40	WD 6
	Repeat	268 – 309	42	WD 7
Amino acid modifications
	Modified residue	3	1	Phosphothreonine By similarity
	Modified residue	7	1	Phosphothreonine By similarity
Experimental info
	Sequence conflict	24	1	V → G in BAC39006. Ref.2
	Sequence conflict	127	1	V → G in BAC39006. Ref.2
	Sequence conflict	171	1	S → F in AAF37719. Ref.1
	Sequence conflict	195	1	Y → F in AAF37719. Ref.1
	Sequence conflict	206	1	D → E in AAF37719. Ref.1
	Sequence conflict	229	1	S → G in BAC33243. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9DCJ1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 2F6E75383905667A	FASTA	326	35,851
	10 20 30 40 50 60 MNTTPGTVGS DPVILATAGY DHTVRFWQAH SGICTRTVQH QDSQVNALEI TPDRSMIAAA 70 80 90 100 110 120 GYQHIRMYDL NSNNPNPIIS YDGVSKNIAS VGFHEDGRWM YTGGEDCTAR IWDLRSRNLQ 130 140 150 160 170 180 CQRIFQVNAP INCVCLHPNQ AELIVGDQSG AIHIWDLKTD HNEQLIPEPE SSITSAHIDP 190 200 210 220 230 240 DASYMAAVNS AGNCYVWNLT GGIGDDVTQL IPKTKIPAHT RYALQCRFSP DSTLLATCSA 250 260 270 280 290 300 DQTCKIWRTS NFSLMTELSI KSSNPGESSR GWMWGCAFSG DSQYIVTASS DNLARLWCVE 310 320 TGEIKREYGG HQKAVVCLAF NDSVLG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Insulin regulation of a novel WD-40 repeat protein in adipocytes." Rodgers B.D., Levine M.A., Bernier M., Montrose-Rafizadeh C. J. Endocrinol. 168:325-332(2001) [PubMed: 11182770] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Head, Hypothalamus, Kidney and Thymus.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Kidney.
[4]	"GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR." Kim D.-H., Sarbassov D.D., Ali S.M., Latek R.R., Guntur K.V.P., Erdjument-Bromage H., Tempst P., Sabatini D.M. Mol. Cell 11:895-904(2003) [PubMed: 12718876] [Abstract] Cited for: INTERACTION WITH MTOR.
[5]	"Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1." Guertin D.A., Stevens D.M., Thoreen C.C., Burds A.A., Kalaany N.Y., Moffat J., Brown M., Fitzgerald K.J., Sabatini D.M. Dev. Cell 11:859-871(2006) [PubMed: 17141160] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]	"Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes." Takai H., Xie Y., de Lange T., Pavletich N.P. Genes Dev. 24:2019-2030(2010) [PubMed: 20801936] [Abstract] Cited for: INTERACTION WITH MTOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF237676 mRNA. Translation: AAF37719.1. AK002751 mRNA. Translation: BAB22328.1. AK038515 mRNA. Translation: BAC30024.1. AK040100 mRNA. Translation: BAC30510.1. AK048102 mRNA. Translation: BAC33243.1. AK077680 mRNA. Translation: BAC36952.1. AK083731 mRNA. Translation: BAC39006.1. BC015279 mRNA. Translation: AAH15279.1.
IPI	IPI00458055.
RefSeq	NP_001239392.1. NM_001252463.1. NP_001239393.1. NM_001252464.1. NP_064372.2. NM_019988.5.
UniGene	Mm.289516.
3D structure databases
ProteinModelPortal	Q9DCJ1.
SMR	Q9DCJ1. Positions 6-324.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9DCJ1. 3 interactions.
STRING	Q9DCJ1.
PTM databases
PhosphoSite	Q9DCJ1.
Proteomic databases
PRIDE	Q9DCJ1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000070888; ENSMUSP00000065004; ENSMUSG00000024142.
GeneID	56716.
KEGG	mmu:56716.
UCSC	uc008awg.2. mouse.
Organism-specific databases
CTD	64223.
MGI	MGI:1929514. Mlst8.
Phylogenomic databases
eggNOG	roNOG14158.
GeneTree	ENSGT00390000014795.
HOGENOM	HBG317546.
HOVERGEN	HBG054763.
InParanoid	Q9DCJ1.
OMA	NNKGNCY.
OrthoDB	EOG4TXBS3.
PhylomeDB	Q9DCJ1.
Gene expression databases
ArrayExpress	Q9DCJ1.
Bgee	Q9DCJ1.
Genevestigator	Q9DCJ1.
Family and domain databases
InterPro	IPR020472. G-protein_beta_WD-40_rep. IPR015943. WD40/YVTN_repeat-like_dom. IPR001680. WD40_repeat. IPR011046. WD40_repeat-like_dom. IPR019775. WD40_repeat_CS. IPR017986. WD40_repeat_dom. [Graphical view]
Gene3D	G3DSA:2.130.10.10. WD40/YVTN_repeat-like. 1 hit.
KO	K08266.
Pfam	PF00400. WD40. 7 hits. [Graphical view]
PRINTS	PR00320. GPROTEINBRPT.
SMART	SM00320. WD40. 6 hits. [Graphical view]
SUPFAM	SSF50978. WD40_like. 1 hit.
PROSITE	PS00678. WD_REPEATS_1. 1 hit. PS50082. WD_REPEATS_2. 3 hits. PS50294. WD_REPEATS_REGION. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	313187.
SOURCE	Search...

Entry information

Entry name

LST8_MOUSE

Accession

Primary (citable) accession number: Q9DCJ1
Secondary accession number(s): Q8BNG8, Q8C882, Q9JKK6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 8, 2008
Last sequence update:	June 1, 2001
Last modified:	January 25, 2012
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program