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Q9DCJ1 (LST8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length326 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 326326Target of rapamycin complex subunit LST8
PRO_0000326500

Regions

Repeat1 – 3737WD 1
Repeat40 – 8041WD 2
Repeat83 – 12240WD 3
Repeat126 – 16540WD 4
Repeat168 – 20740WD 5
Repeat218 – 25740WD 6
Repeat268 – 30942WD 7

Amino acid modifications

Modified residue11N-acetylmethionine By similarity

Experimental info

Sequence conflict241V → G in BAC39006. Ref.2
Sequence conflict1271V → G in BAC39006. Ref.2
Sequence conflict1711S → F in AAF37719. Ref.1
Sequence conflict1951Y → F in AAF37719. Ref.1
Sequence conflict2061D → E in AAF37719. Ref.1
Sequence conflict2291S → G in BAC33243. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9DCJ1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 2F6E75383905667A

FASTA32635,851
        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 

« Hide

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.
CCDSCCDS28484.1.
RefSeqNP_001239392.1. NM_001252463.1.
NP_001239393.1. NM_001252464.1.
NP_001239394.1. NM_001252465.1.
NP_064372.2. NM_019988.5.
UniGeneMm.289516.

3D structure databases

ProteinModelPortalQ9DCJ1.
SMRQ9DCJ1. Positions 8-324.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid208141. 3 interactions.
DIPDIP-46976N.
IntActQ9DCJ1. 3 interactions.

PTM databases

PhosphoSiteQ9DCJ1.

Proteomic databases

PaxDbQ9DCJ1.
PRIDEQ9DCJ1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000070888; ENSMUSP00000065004; ENSMUSG00000024142.
ENSMUST00000179163; ENSMUSP00000136287; ENSMUSG00000024142.
GeneID56716.
KEGGmmu:56716.
UCSCuc008awg.3. mouse.

Organism-specific databases

CTD64223.
MGIMGI:1929514. Mlst8.

Phylogenomic databases

eggNOGCOG2319.
GeneTreeENSGT00390000014795.
HOGENOMHOG000208395.
HOVERGENHBG054763.
InParanoidQ9DCJ1.
KOK08266.
OMAAGHHTVK.
OrthoDBEOG7BCNBX.
PhylomeDBQ9DCJ1.
TreeFamTF318577.

Gene expression databases

BgeeQ9DCJ1.
GenevestigatorQ9DCJ1.

Family and domain databases

Gene3D2.130.10.10. 1 hit.
InterProIPR020472. G-protein_beta_WD-40_rep.
IPR011047. Quinonprotein_ADH-like_supfam.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamPF00400. WD40. 5 hits.
[Graphical view]
PRINTSPR00320. GPROTEINBRPT.
SMARTSM00320. WD40. 6 hits.
[Graphical view]
SUPFAMSSF50998. SSF50998. 1 hit.
PROSITEPS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 3 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio313187.
PROQ9DCJ1.
SOURCESearch...

Entry information

Entry nameLST8_MOUSE
AccessionPrimary (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: July 9, 2014
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot