CPLM-014932

Genbank Nucleotide ID

Ragulator complex protein LAMTOR1

Protein Synonyms/Alias

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; p27RF-Rho

C11orf59; PDRO; PP7157

Homo sapiens (Human)

Position	Peptide	Type	References
20	DQDREERKLLLDPSS	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10]
31	DPSSPPTKALNGAEP	ubiquitination	[2, 3, 4, 7, 8, 9, 10]
60	LLSSILAKTASNIID	ubiquitination	[4, 8, 9]
103	SSSLTHWKKLPPLPS	ubiquitination	[9]
104	SSLTHWKKLPPLPSL	ubiquitination	[3, 8, 9]

[1] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
[2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[4] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
[5] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[6] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[7] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[8] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[10] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]

Functional Description

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.

REGION 121 161 Interaction with LAMTOR2 and LAMTOR3 (By
MOD_RES 27 27 Phosphoserine.
MOD_RES 63 63 Phosphoserine (By similarity).
LIPID 2 2 N-myristoyl glycine (Potential).

Cell membrane; Complete proteome; Direct protein sequencing; Endosome; Lipoprotein; Lysosome; Membrane; Myristate; Phosphoprotein; Polymorphism; Reference proteome.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005794; C:Golgi apparatus; IDA:HPA.
GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
GO:0005764; C:lysosome; IDA:UniProtKB.
GO:0005886; C:plasma membrane; IDA:HPA.
GO:0071986; C:Ragulator complex; IDA:UniProtKB.
GO:0016049; P:cell growth; IMP:UniProtKB.
GO:0034613; P:cellular protein localization; IMP:UniProtKB.
GO:0071230; P:cellular response to amino acid stimulus; IMP:UniProtKB.
GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
GO:0032439; P:endosome localization; ISS:UniProtKB.
GO:0007032; P:endosome organization; ISS:UniProtKB.
GO:0032418; P:lysosome localization; ISS:UniProtKB.
GO:0007040; P:lysosome organization; ISS:UniProtKB.
GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
GO:0032008; P:positive regulation of TOR signaling cascade; IMP:UniProtKB.
GO:0010874; P:regulation of cholesterol efflux; IMP:UniProtKB.
GO:0010872; P:regulation of cholesterol esterification; IMP:UniProtKB.
GO:0060620; P:regulation of cholesterol import; IMP:UniProtKB.
GO:0001919; P:regulation of receptor recycling; ISS:UniProtKB.