Q6IAA8 (LTOR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	161 AA.
Sequence status	Complete.
Protein existence	Evidence 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.8 Ref.10 Ref.11 Ref.14
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.8 Ref.10 Ref.14
Subcellular location	Late endosome membrane; Lipid-anchor; Cytoplasmic side. Lysosome membrane; Lipid-anchor; Cytoplasmic side. Cell membrane Ref.8 Ref.11.
Induction	Down-regulated by cholesterol (at protein level). Ref.11
Sequence similarities	Belongs to the LAMTOR1 family.

Ontologies

Keywords
Cellular component	Cell membrane Endosome Lysosome Membrane
Coding sequence diversity	Polymorphism
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell growth Inferred from mutant phenotype Ref.10. Source: UniProtKB cellular protein localization Inferred from mutant phenotype Ref.10. Source: UniProtKB cellular response to amino acid stimulus Inferred from mutant phenotype Ref.10. Source: UniProtKB cholesterol homeostasis Inferred from mutant phenotype Ref.11. 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 cascade Inferred from mutant phenotype Ref.10. Source: UniProtKB regulation of cholesterol efflux Inferred from mutant phenotype Ref.11. Source: UniProtKB regulation of cholesterol esterification Inferred from mutant phenotype Ref.11. Source: UniProtKB regulation of cholesterol import Inferred from mutant phenotype Ref.11. Source: UniProtKB regulation of receptor recycling Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from direct assay. Source: HPA Ragulator complex Inferred from direct assay Ref.10. Source: UniProtKB lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lysosome Inferred from direct assay Ref.11. Source: UniProtKB plasma membrane Inferred from direct assay. Source: HPA
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 161	161	Ragulator complex protein LAMTOR1		PRO_0000274292
Regions
	Region	121 – 161	41	Interaction with LAMTOR2 and LAMTOR3 By similarity
Amino acid modifications
	Modified residue	27	1	Phosphoserine Ref.12
	Modified residue	63	1	Phosphoserine By similarity
	Lipidation	2	1	N-myristoyl glycine Potential
Natural variations
	Natural variant	73	1	S → L. Corresponds to variant rs1053443 [ dbSNP | Ensembl ].		VAR_030250
Experimental info
	Sequence conflict	50	1	E → V in CAG33528. Ref.2
	Sequence conflict	60	1	K → R in AAL55767. Ref.1
	Sequence conflict	69	1	S → P in CAG33528. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q6IAA8 [UniParc]. Last modified February 6, 2007. Version 2. Checksum: 610CC6C548356051	FASTA	161	17,745
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, 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]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"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].
[14]	"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.
IPI	IPI00016670.
RefSeq	NP_060377.1. NM_017907.2.
UniGene	Hs.731528.
3D structure databases
ProteinModelPortal	Q6IAA8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6IAA8. 16 interactions.
MINT	MINT-1372069.
STRING	9606.ENSP00000278671.
PTM databases
PhosphoSite	Q6IAA8.
Polymorphism databases
DMDM	125863645.
Proteomic databases
PaxDb	Q6IAA8.
PeptideAtlas	Q6IAA8.
PRIDE	Q6IAA8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000278671; ENSP00000278671; ENSG00000149357.
GeneID	55004.
KEGG	hsa:55004.
UCSC	uc001ort.3. human.
Organism-specific databases
CTD	55004.
GeneCards	GC11M071809.
H-InvDB	HIX0009905.
HGNC	HGNC:26068. LAMTOR1.
HPA	HPA002997.
MIM	613510. gene.
neXtProt	NX_Q6IAA8.
PharmGKB	PA143485354.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG73401.
HOVERGEN	HBG081218.
InParanoid	Q6IAA8.
OMA	YAYSAIS.
OrthoDB	EOG4GQQ65.
PhylomeDB	Q6IAA8.
Gene expression databases
ArrayExpress	Q6IAA8.
Bgee	Q6IAA8.
CleanEx	HS_C11orf59.
Genevestigator	Q6IAA8.
Family and domain databases
InterPro	IPR026310. LAMTOR1. [Graphical view]
PANTHER	PTHR13401. PTHR13401. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	55004.
NextBio	58336.
SOURCE	Search...

Entry information

Entry name

LTOR1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 70 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.