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Q6IAA8 (LTOR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 82. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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:
Ragulator complex protein LAMTOR1
Alternative name(s):
Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1
Lipid raft adaptor protein p18
Protein associated with DRMs and endosomes
p27Kip1-releasing factor from RhoA
Short name=p27RF-Rho
Gene names
Name:LAMTOR1
Synonyms:C11orf59, PDRO
ORF Names:PP7157
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length161 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to membranes. Also required for late endosomes/lysosomes biogenesis it may regulate both the recycling of receptors through endosomes and the MAPK signaling pathway through recruitment of some of its components to late endosomes. May be involved in cholesterol homeostasis regulating LDL uptake and cholesterol release from late endosomes/lysosomes. May also play a role in RHOA activation. Ref.9 Ref.11 Ref.12 Ref.15

Subunit structure

Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5. LAMTOR4 and LAMTOR5 form a heterodimer that interacts, through LAMTOR1, with a LAMTOR2, LAMTOR3 heterodimer. The Ragulator complex interacts with both the mTORC1 complex and heterodimers constituted of the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD; regulated by amino acid availability. Interacts with LAMTOR2 and LAMTOR3; the interaction is direct. Interacts with RRAGB and RRAGD; the interaction is direct indicating that it probably constitutes the main RAG-interacting subunit of the Ragulator complex. Interacts with MMP14. Interacts with CDKN1B; prevents the interaction of CDKN1B with RHOA leaving RHOA in a form accessible to activation by ARHGEF2. Ref.9 Ref.11 Ref.15

Subcellular location

Late endosome membrane; Lipid-anchor; Cytoplasmic side. Lysosome membrane; Lipid-anchor; Cytoplasmic side. Cell membrane Ref.9 Ref.12.

Induction

Down-regulated by cholesterol (at protein level). Ref.12

Sequence similarities

Belongs to the LAMTOR1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Endosome
Lysosome
Membrane
   Coding sequence diversityPolymorphism
   PTMLipoprotein
Myristate
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcell growth

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cellular protein localization

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cellular response to amino acid stimulus

Inferred from mutant phenotype Ref.11. Source: UniProtKB

cholesterol homeostasis

Inferred from mutant phenotype Ref.12. Source: UniProtKB

endosome localization

Inferred from sequence or structural similarity. Source: UniProtKB

endosome organization

Inferred from sequence or structural similarity. Source: UniProtKB

lysosome localization

Inferred from sequence or structural similarity. Source: UniProtKB

lysosome organization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of TOR signaling

Inferred from mutant phenotype Ref.11. Source: UniProtKB

regulation of GTPase activity

Inferred from direct assay Ref.15. Source: GOC

regulation of cholesterol efflux

Inferred from mutant phenotype Ref.12. Source: UniProtKB

regulation of cholesterol esterification

Inferred from mutant phenotype Ref.12. Source: UniProtKB

regulation of cholesterol import

Inferred from mutant phenotype Ref.12. Source: UniProtKB

regulation of receptor recycling

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from direct assay. Source: HPA

Ragulator complex

Inferred from direct assay Ref.11. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

late endosome membrane

Inferred from sequence or structural similarity. Source: UniProtKB

lysosomal membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosome

Inferred from direct assay Ref.12. Source: UniProtKB

membrane raft

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_functionprotein binding

Inferred from physical interaction Ref.11. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Potential
Chain2 – 161160Ragulator complex protein LAMTOR1
PRO_0000274292

Regions

Region121 – 16141Interaction with LAMTOR2 and LAMTOR3 By similarity

Amino acid modifications

Modified residue271Phosphoserine Ref.13
Lipidation21N-myristoyl glycine Potential

Natural variations

Natural variant731S → L.
Corresponds to variant rs1053443 [ dbSNP | Ensembl ].
VAR_030250

Experimental info

Sequence conflict501E → V in CAG33528. Ref.2
Sequence conflict601K → R in AAL55767. Ref.1
Sequence conflict691S → P in CAG33528. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q6IAA8 [UniParc].

Last modified February 6, 2007. Version 2.
Checksum: 610CC6C548356051

FASTA16117,745
        10         20         30         40         50         60 
MGCCYSSENE DSDQDREERK LLLDPSSPPT KALNGAEPNY HSLPSARTDE QALLSSILAK 

        70         80         90        100        110        120 
TASNIIDVSA ADSQGMEQHE YMDRARQYST RLAVLSSSLT HWKKLPPLPS LTSQPHQVLA 

       130        140        150        160 
SEPIPFSDLQ QVSRIAAYAY SALSQIRVDA KEELVVQFGI P 

« Hide

References

« Hide 'large scale' references
[1]"Large-scale cDNA transfection screening for genes related to cancer development and progression."
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. expand/collapse author list , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"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].
Tissue: Skin.
[5]Bienvenut W.V.
Submitted (JUN-2005) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 48-60 AND 135-147, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: B-cell lymphoma.
[6]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"A novel protein associated with membrane-type 1 matrix metalloproteinase binds p27(kip1) and regulates RhoA activation, actin remodeling, and matrigel invasion."
Hoshino D., Tomari T., Nagano M., Koshikawa N., Seiki M.
J. Biol. Chem. 284:27315-27326(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MMP14 AND CDKN1B.
[10]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[11]"Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids."
Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M.
Cell 141:290-303(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN RAGULATOR COMPLEX, INTERACTION WITH RRAGB AND RRAGD.
[12]"Pdro, a protein associated with late endosomes and lysosomes and implicated in cellular cholesterol homeostasis."
Guillaumot P., Luquain C., Malek M., Huber A.L., Brugiere S., Garin J., Grunwald D., Regnier D., Petrilli V., Lefai E., Manie S.N.
PLoS ONE 5:E10977-E10977(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY CHOLESTEROL.
[13]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Ragulator is a GEF for the Rag GTPases that signal amino acid levels to mTORC1."
Bar-Peled L., Schweitzer L.D., Zoncu R., Sabatini D.M.
Cell 150:1196-1208(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MTORC1 SIGNALING, IDENTIFICATION IN RAGULATOR COMPLEX, INTERACTION WITH MTORC1 COMPLEX AND RAG GTPASES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF289583 mRNA. Translation: AAL55767.1.
CR457247 mRNA. Translation: CAG33528.1.
AK000632 mRNA. Translation: BAA91297.1.
BC001706 mRNA. Translation: AAH01706.1.
CCDSCCDS8209.1.
RefSeqNP_060377.1. NM_017907.2.
UniGeneHs.731528.

3D structure databases

ProteinModelPortalQ6IAA8.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120336. 15 interactions.
IntActQ6IAA8. 16 interactions.
MINTMINT-1372069.
STRING9606.ENSP00000278671.

PTM databases

PhosphoSiteQ6IAA8.

Polymorphism databases

DMDM125863645.

Proteomic databases

MaxQBQ6IAA8.
PaxDbQ6IAA8.
PeptideAtlasQ6IAA8.
PRIDEQ6IAA8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000278671; ENSP00000278671; ENSG00000149357.
GeneID55004.
KEGGhsa:55004.
UCSCuc001ort.3. human.

Organism-specific databases

CTD55004.
GeneCardsGC11M071809.
H-InvDBHIX0009905.
HGNCHGNC:26068. LAMTOR1.
HPAHPA002997.
MIM613510. gene.
neXtProtNX_Q6IAA8.
PharmGKBPA143485354.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG73401.
HOVERGENHBG081218.
InParanoidQ6IAA8.
OMAPYSDVQQ.
PhylomeDBQ6IAA8.
TreeFamTF323788.

Gene expression databases

ArrayExpressQ6IAA8.
BgeeQ6IAA8.
CleanExHS_C11orf59.
GenevestigatorQ6IAA8.

Family and domain databases

InterProIPR026310. LAMTOR1-like.
IPR028209. LAMTOR1/MEH1.
[Graphical view]
PANTHERPTHR13401. PTHR13401. 1 hit.
PfamPF15454. LAMTOR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi55004.
NextBio58336.
PROQ6IAA8.
SOURCESearch...

Entry information

Entry nameLTOR1_HUMAN
AccessionPrimary (citable) accession number: Q6IAA8
Secondary accession number(s): Q8WZ09, Q9NWT0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 6, 2007
Last sequence update: February 6, 2007
Last modified: July 9, 2014
This is version 82 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Uncharacterized protein families (UPF)

List of uncharacterized protein family (UPF) entries

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM