Full text data of LAMTOR1
LAMTOR1
(C11orf59, PDRO)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Ragulator complex protein LAMTOR1 (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)
Ragulator complex protein LAMTOR1 (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)
UniProt
Q6IAA8
ID LTOR1_HUMAN Reviewed; 161 AA.
AC Q6IAA8; Q8WZ09; Q9NWT0;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-FEB-2007, sequence version 2.
DT 22-JAN-2014, entry version 76.
DE RecName: Full=Ragulator complex protein LAMTOR1;
DE AltName: Full=Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1;
DE AltName: Full=Lipid raft adaptor protein p18;
DE AltName: Full=Protein associated with DRMs and endosomes;
DE AltName: Full=p27Kip1-releasing factor from RhoA;
DE Short=p27RF-Rho;
GN Name=LAMTOR1; Synonyms=C11orf59, PDRO; ORFNames=PP7157;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 48-60 AND 135-147, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MMP14 AND CDKN1B.
RX PubMed=19654316; DOI=10.1074/jbc.M109.041400;
RA Hoshino D., Tomari T., Nagano M., Koshikawa N., Seiki M.;
RT "A novel protein associated with membrane-type 1 matrix
RT metalloproteinase binds p27(kip1) and regulates RhoA activation, actin
RT remodeling, and matrigel invasion.";
RL J. Biol. Chem. 284:27315-27326(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP FUNCTION, IDENTIFICATION IN RAGULATOR COMPLEX, AND INTERACTION WITH
RP RRAGB AND RRAGD.
RX PubMed=20381137; DOI=10.1016/j.cell.2010.02.024;
RA Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S.,
RA Sabatini D.M.;
RT "Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is
RT necessary for its activation by amino acids.";
RL Cell 141:290-303(2010).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY CHOLESTEROL.
RX PubMed=20544018; DOI=10.1371/journal.pone.0010977;
RA Guillaumot P., Luquain C., Malek M., Huber A.L., Brugiere S.,
RA Garin J., Grunwald D., Regnier D., Petrilli V., Lefai E., Manie S.N.;
RT "Pdro, a protein associated with late endosomes and lysosomes and
RT implicated in cellular cholesterol homeostasis.";
RL PLoS ONE 5:E10977-E10977(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION IN MTORC1 SIGNALING, IDENTIFICATION IN RAGULATOR COMPLEX, AND
RP INTERACTION WITH MTORC1 COMPLEX AND RAG GTPASES.
RX PubMed=22980980; DOI=10.1016/j.cell.2012.07.032;
RA Bar-Peled L., Schweitzer L.D., Zoncu R., Sabatini D.M.;
RT "Ragulator is a GEF for the Rag GTPases that signal amino acid levels
RT to mTORC1.";
RL Cell 150:1196-1208(2012).
CC -!- FUNCTION: As part of the Ragulator complex it is involved in amino
CC acid sensing and activation of mTORC1, a signaling complex
CC promoting cell growth in response to growth factors, energy
CC levels, and amino acids. Activated by amino acids through a
CC mechanism involving the lysosomal V-ATPase, the Ragulator
CC functions as a guanine nucleotide exchange factor activating the
CC small GTPases Rag. Activated Ragulator and Rag GTPases function as
CC a scaffold recruiting mTORC1 to lysosomes where it is in turn
CC activated. LAMTOR1 is directly responsible for anchoring the
CC Ragulator complex to membranes. Also required for late
CC endosomes/lysosomes biogenesis it may regulate both the recycling
CC of receptors through endosomes and the MAPK signaling pathway
CC through recruitment of some of its components to late endosomes.
CC May be involved in cholesterol homeostasis regulating LDL uptake
CC and cholesterol release from late endosomes/lysosomes. May also
CC play a role in RHOA activation.
CC -!- SUBUNIT: Part of the Ragulator complex composed of LAMTOR1,
CC LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5. LAMTOR4 and LAMTOR5 form a
CC heterodimer that interacts, through LAMTOR1, with a LAMTOR2,
CC LAMTOR3 heterodimer. The Ragulator complex interacts with both the
CC mTORC1 complex and heterodimers constituted of the Rag GTPases
CC RRAGA, RRAGB, RRAGC and RRAGD; regulated by amino acid
CC availability. Interacts with LAMTOR2 and LAMTOR3; the interaction
CC is direct. Interacts with RRAGB and RRAGD; the interaction is
CC direct indicating that it probably constitutes the main RAG-
CC interacting subunit of the Ragulator complex. Interacts with
CC MMP14. Interacts with CDKN1B; prevents the interaction of CDKN1B
CC with RHOA leaving RHOA in a form accessible to activation by
CC ARHGEF2.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Lipid-anchor;
CC Cytoplasmic side. Lysosome membrane; Lipid-anchor; Cytoplasmic
CC side. Cell membrane.
CC -!- INDUCTION: Down-regulated by cholesterol (at protein level).
CC -!- SIMILARITY: Belongs to the LAMTOR1 family.
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DR EMBL; AF289583; AAL55767.1; -; mRNA.
DR EMBL; CR457247; CAG33528.1; -; mRNA.
DR EMBL; AK000632; BAA91297.1; -; mRNA.
DR EMBL; BC001706; AAH01706.1; -; mRNA.
DR RefSeq; NP_060377.1; NM_017907.2.
DR UniGene; Hs.731528; -.
DR ProteinModelPortal; Q6IAA8; -.
DR IntAct; Q6IAA8; 16.
DR MINT; MINT-1372069; -.
DR STRING; 9606.ENSP00000278671; -.
DR PhosphoSite; Q6IAA8; -.
DR DMDM; 125863645; -.
DR PaxDb; Q6IAA8; -.
DR PeptideAtlas; Q6IAA8; -.
DR PRIDE; Q6IAA8; -.
DR Ensembl; ENST00000278671; ENSP00000278671; ENSG00000149357.
DR GeneID; 55004; -.
DR KEGG; hsa:55004; -.
DR UCSC; uc001ort.3; human.
DR CTD; 55004; -.
DR GeneCards; GC11M071809; -.
DR H-InvDB; HIX0009905; -.
DR HGNC; HGNC:26068; LAMTOR1.
DR HPA; HPA002997; -.
DR MIM; 613510; gene.
DR neXtProt; NX_Q6IAA8; -.
DR PharmGKB; PA143485354; -.
DR eggNOG; NOG73401; -.
DR HOVERGEN; HBG081218; -.
DR InParanoid; Q6IAA8; -.
DR OMA; KIAAYAY; -.
DR PhylomeDB; Q6IAA8; -.
DR GenomeRNAi; 55004; -.
DR NextBio; 58336; -.
DR PRO; PR:Q6IAA8; -.
DR ArrayExpress; Q6IAA8; -.
DR Bgee; Q6IAA8; -.
DR CleanEx; HS_C11orf59; -.
DR Genevestigator; Q6IAA8; -.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0071986; C:Ragulator complex; IDA:UniProtKB.
DR GO; GO:0016049; P:cell growth; IMP:UniProtKB.
DR GO; GO:0034613; P:cellular protein localization; IMP:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IMP:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0032439; P:endosome localization; ISS:UniProtKB.
DR GO; GO:0007032; P:endosome organization; ISS:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; ISS:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling cascade; IMP:UniProtKB.
DR GO; GO:0010874; P:regulation of cholesterol efflux; IMP:UniProtKB.
DR GO; GO:0010872; P:regulation of cholesterol esterification; IMP:UniProtKB.
DR GO; GO:0060620; P:regulation of cholesterol import; IMP:UniProtKB.
DR GO; GO:0001919; P:regulation of receptor recycling; ISS:UniProtKB.
DR InterPro; IPR028209; LAMTOR1.
DR InterPro; IPR026310; LAMTOR1/MEH1.
DR PANTHER; PTHR13401; PTHR13401; 1.
DR Pfam; PF15454; LAMTOR; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Complete proteome; Direct protein sequencing; Endosome;
KW Lipoprotein; Lysosome; Membrane; Myristate; Phosphoprotein;
KW Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed (Potential).
FT CHAIN 2 161 Ragulator complex protein LAMTOR1.
FT /FTId=PRO_0000274292.
FT REGION 121 161 Interaction with LAMTOR2 and LAMTOR3 (By
FT similarity).
FT MOD_RES 27 27 Phosphoserine.
FT LIPID 2 2 N-myristoyl glycine (Potential).
FT VARIANT 73 73 S -> L (in dbSNP:rs1053443).
FT /FTId=VAR_030250.
FT CONFLICT 50 50 E -> V (in Ref. 2; CAG33528).
FT CONFLICT 60 60 K -> R (in Ref. 1; AAL55767).
FT CONFLICT 69 69 S -> P (in Ref. 2; CAG33528).
SQ SEQUENCE 161 AA; 17745 MW; 610CC6C548356051 CRC64;
MGCCYSSENE DSDQDREERK LLLDPSSPPT KALNGAEPNY HSLPSARTDE QALLSSILAK
TASNIIDVSA ADSQGMEQHE YMDRARQYST RLAVLSSSLT HWKKLPPLPS LTSQPHQVLA
SEPIPFSDLQ QVSRIAAYAY SALSQIRVDA KEELVVQFGI P
//
ID LTOR1_HUMAN Reviewed; 161 AA.
AC Q6IAA8; Q8WZ09; Q9NWT0;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-FEB-2007, sequence version 2.
DT 22-JAN-2014, entry version 76.
DE RecName: Full=Ragulator complex protein LAMTOR1;
DE AltName: Full=Late endosomal/lysosomal adaptor and MAPK and MTOR activator 1;
DE AltName: Full=Lipid raft adaptor protein p18;
DE AltName: Full=Protein associated with DRMs and endosomes;
DE AltName: Full=p27Kip1-releasing factor from RhoA;
DE Short=p27RF-Rho;
GN Name=LAMTOR1; Synonyms=C11orf59, PDRO; ORFNames=PP7157;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 48-60 AND 135-147, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MMP14 AND CDKN1B.
RX PubMed=19654316; DOI=10.1074/jbc.M109.041400;
RA Hoshino D., Tomari T., Nagano M., Koshikawa N., Seiki M.;
RT "A novel protein associated with membrane-type 1 matrix
RT metalloproteinase binds p27(kip1) and regulates RhoA activation, actin
RT remodeling, and matrigel invasion.";
RL J. Biol. Chem. 284:27315-27326(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP FUNCTION, IDENTIFICATION IN RAGULATOR COMPLEX, AND INTERACTION WITH
RP RRAGB AND RRAGD.
RX PubMed=20381137; DOI=10.1016/j.cell.2010.02.024;
RA Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S.,
RA Sabatini D.M.;
RT "Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is
RT necessary for its activation by amino acids.";
RL Cell 141:290-303(2010).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY CHOLESTEROL.
RX PubMed=20544018; DOI=10.1371/journal.pone.0010977;
RA Guillaumot P., Luquain C., Malek M., Huber A.L., Brugiere S.,
RA Garin J., Grunwald D., Regnier D., Petrilli V., Lefai E., Manie S.N.;
RT "Pdro, a protein associated with late endosomes and lysosomes and
RT implicated in cellular cholesterol homeostasis.";
RL PLoS ONE 5:E10977-E10977(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION IN MTORC1 SIGNALING, IDENTIFICATION IN RAGULATOR COMPLEX, AND
RP INTERACTION WITH MTORC1 COMPLEX AND RAG GTPASES.
RX PubMed=22980980; DOI=10.1016/j.cell.2012.07.032;
RA Bar-Peled L., Schweitzer L.D., Zoncu R., Sabatini D.M.;
RT "Ragulator is a GEF for the Rag GTPases that signal amino acid levels
RT to mTORC1.";
RL Cell 150:1196-1208(2012).
CC -!- FUNCTION: As part of the Ragulator complex it is involved in amino
CC acid sensing and activation of mTORC1, a signaling complex
CC promoting cell growth in response to growth factors, energy
CC levels, and amino acids. Activated by amino acids through a
CC mechanism involving the lysosomal V-ATPase, the Ragulator
CC functions as a guanine nucleotide exchange factor activating the
CC small GTPases Rag. Activated Ragulator and Rag GTPases function as
CC a scaffold recruiting mTORC1 to lysosomes where it is in turn
CC activated. LAMTOR1 is directly responsible for anchoring the
CC Ragulator complex to membranes. Also required for late
CC endosomes/lysosomes biogenesis it may regulate both the recycling
CC of receptors through endosomes and the MAPK signaling pathway
CC through recruitment of some of its components to late endosomes.
CC May be involved in cholesterol homeostasis regulating LDL uptake
CC and cholesterol release from late endosomes/lysosomes. May also
CC play a role in RHOA activation.
CC -!- SUBUNIT: Part of the Ragulator complex composed of LAMTOR1,
CC LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5. LAMTOR4 and LAMTOR5 form a
CC heterodimer that interacts, through LAMTOR1, with a LAMTOR2,
CC LAMTOR3 heterodimer. The Ragulator complex interacts with both the
CC mTORC1 complex and heterodimers constituted of the Rag GTPases
CC RRAGA, RRAGB, RRAGC and RRAGD; regulated by amino acid
CC availability. Interacts with LAMTOR2 and LAMTOR3; the interaction
CC is direct. Interacts with RRAGB and RRAGD; the interaction is
CC direct indicating that it probably constitutes the main RAG-
CC interacting subunit of the Ragulator complex. Interacts with
CC MMP14. Interacts with CDKN1B; prevents the interaction of CDKN1B
CC with RHOA leaving RHOA in a form accessible to activation by
CC ARHGEF2.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane; Lipid-anchor;
CC Cytoplasmic side. Lysosome membrane; Lipid-anchor; Cytoplasmic
CC side. Cell membrane.
CC -!- INDUCTION: Down-regulated by cholesterol (at protein level).
CC -!- SIMILARITY: Belongs to the LAMTOR1 family.
CC -----------------------------------------------------------------------
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DR EMBL; AF289583; AAL55767.1; -; mRNA.
DR EMBL; CR457247; CAG33528.1; -; mRNA.
DR EMBL; AK000632; BAA91297.1; -; mRNA.
DR EMBL; BC001706; AAH01706.1; -; mRNA.
DR RefSeq; NP_060377.1; NM_017907.2.
DR UniGene; Hs.731528; -.
DR ProteinModelPortal; Q6IAA8; -.
DR IntAct; Q6IAA8; 16.
DR MINT; MINT-1372069; -.
DR STRING; 9606.ENSP00000278671; -.
DR PhosphoSite; Q6IAA8; -.
DR DMDM; 125863645; -.
DR PaxDb; Q6IAA8; -.
DR PeptideAtlas; Q6IAA8; -.
DR PRIDE; Q6IAA8; -.
DR Ensembl; ENST00000278671; ENSP00000278671; ENSG00000149357.
DR GeneID; 55004; -.
DR KEGG; hsa:55004; -.
DR UCSC; uc001ort.3; human.
DR CTD; 55004; -.
DR GeneCards; GC11M071809; -.
DR H-InvDB; HIX0009905; -.
DR HGNC; HGNC:26068; LAMTOR1.
DR HPA; HPA002997; -.
DR MIM; 613510; gene.
DR neXtProt; NX_Q6IAA8; -.
DR PharmGKB; PA143485354; -.
DR eggNOG; NOG73401; -.
DR HOVERGEN; HBG081218; -.
DR InParanoid; Q6IAA8; -.
DR OMA; KIAAYAY; -.
DR PhylomeDB; Q6IAA8; -.
DR GenomeRNAi; 55004; -.
DR NextBio; 58336; -.
DR PRO; PR:Q6IAA8; -.
DR ArrayExpress; Q6IAA8; -.
DR Bgee; Q6IAA8; -.
DR CleanEx; HS_C11orf59; -.
DR Genevestigator; Q6IAA8; -.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0071986; C:Ragulator complex; IDA:UniProtKB.
DR GO; GO:0016049; P:cell growth; IMP:UniProtKB.
DR GO; GO:0034613; P:cellular protein localization; IMP:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IMP:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0032439; P:endosome localization; ISS:UniProtKB.
DR GO; GO:0007032; P:endosome organization; ISS:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; ISS:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling cascade; IMP:UniProtKB.
DR GO; GO:0010874; P:regulation of cholesterol efflux; IMP:UniProtKB.
DR GO; GO:0010872; P:regulation of cholesterol esterification; IMP:UniProtKB.
DR GO; GO:0060620; P:regulation of cholesterol import; IMP:UniProtKB.
DR GO; GO:0001919; P:regulation of receptor recycling; ISS:UniProtKB.
DR InterPro; IPR028209; LAMTOR1.
DR InterPro; IPR026310; LAMTOR1/MEH1.
DR PANTHER; PTHR13401; PTHR13401; 1.
DR Pfam; PF15454; LAMTOR; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Complete proteome; Direct protein sequencing; Endosome;
KW Lipoprotein; Lysosome; Membrane; Myristate; Phosphoprotein;
KW Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed (Potential).
FT CHAIN 2 161 Ragulator complex protein LAMTOR1.
FT /FTId=PRO_0000274292.
FT REGION 121 161 Interaction with LAMTOR2 and LAMTOR3 (By
FT similarity).
FT MOD_RES 27 27 Phosphoserine.
FT LIPID 2 2 N-myristoyl glycine (Potential).
FT VARIANT 73 73 S -> L (in dbSNP:rs1053443).
FT /FTId=VAR_030250.
FT CONFLICT 50 50 E -> V (in Ref. 2; CAG33528).
FT CONFLICT 60 60 K -> R (in Ref. 1; AAL55767).
FT CONFLICT 69 69 S -> P (in Ref. 2; CAG33528).
SQ SEQUENCE 161 AA; 17745 MW; 610CC6C548356051 CRC64;
MGCCYSSENE DSDQDREERK LLLDPSSPPT KALNGAEPNY HSLPSARTDE QALLSSILAK
TASNIIDVSA ADSQGMEQHE YMDRARQYST RLAVLSSSLT HWKKLPPLPS LTSQPHQVLA
SEPIPFSDLQ QVSRIAAYAY SALSQIRVDA KEELVVQFGI P
//
MIM
613510
*RECORD*
*FIELD* NO
613510
*FIELD* TI
*613510 CHROMOSOME 11 OPEN READING FRAME 59; C11ORF59
;;p27(Kip1)-RELEASING FACTOR FROM RHOA; p27RF-Rho;;
read morePROTEIN ASSOCIATED WITH DETERGENT-RESISTANT MEMBRANES AND ENDOSOMES;
PDRO
*FIELD* TX
CLONING
Hoshino et al. (2009) stated that C11ORF59, which they called p27RF-Rho,
was first identified as a protein that copurified with matrix
metalloproteinase-1 (MMP1; 120353) from a human melanoma cell line. The
161-amino acid protein contains 1 myristoylation and 2 palmitoylation
sites at its N terminus. Northern blot analysis detected variable
expression of p27RF-Rho mRNA in all human tissues examined. Orthologs of
p27RF-Rho were identified in a number of vertebrate species. p27RF-Rho
localized to a punctate distribution in a human fibrosarcoma cell line,
and Western blot analysis detected p27RF-Rho at an apparent molecular
mass of 17 kD.
Using mass spectrometry to identify proteins that purified with
detergent-resistant membranes from SHEP human neuroblastoma cells,
followed by RT-PCR, Guillaumot et al. (2010) cloned C11ORF59, which they
called PDRO. The deduced 161-amino acid protein contains a dileucine
motif near its N-terminal end in addition to the N-terminal
myristoylation and palmitoylation sites. Confocal microscopy showed that
fluorescence-tagged PDRO localized to ring-shaped structures that also
expressed markers of late endosomes and lysosomes.
GENE FUNCTION
RhoA (165390) is a small GTPase that has a pivotal role in regulating
the organization of the actin cytoskeleton. Using knockdown and
overexpression studies, Hoshino et al. (2009) found that p27RF-Rho
enhanced the activation of RhoA by releasing it from inhibition by
cytoplasmic p27(Kip1) (CDKN1B; 600778) in human cell lines. p27RF-Rho
bound and sequestered p27(Kip1), allowing RhoA to be activated by its
guanine nucleotide exchange factors (see ARHGEF1, 601855), initiating
cell motility and invasiveness.
Using mutation analysis, Guillaumot et al. (2010) showed that the
myristoylation and palmitoylation sites of PDRO were required to target
PDRO to detergent-resistant membranes in vitro and to perinuclear late
endosomes and lysosomes in intact SHEP cells. Expression of PDRO mRNA
and protein was upregulated by depletion of cellular cholesterol and
downregulated by cholesterol loading. Knockdown of PDRO via small
interfering RNA increased cellular free cholesterol content, which was
due, at least in part, to elevated uptake of low-density lipoprotein and
cholesterol egress from late endosomes and lysosomes. PDRO-knockdown
cells also displayed elevated cholesterol efflux. Conversely,
overexpression of PDRO reduced cellular free cholesterol content.
Guillaumot et al. (2010) concluded that PDRO is involved in cellular
cholesterol homeostasis, which may be linked to its role in regulating
the actin cytoskeleton.
GENE STRUCTURE
Guillaumot et al. (2010) identified 5 putative sterol response elements
in the upstream region of the C11ORF59 gene.
MAPPING
By genomic sequence analysis, Guillaumot et al. (2010) mapped the
C11ORF59 gene to chromosome 11q13.4.
*FIELD* RF
1. Guillaumot, P.; Luquain, C.; Malek, M.; Huber, A.-L.; Brugiere,
S.; Garin, J.; Grunwald, D.; Regnier, D.; Petrilli, V.; Lefai, E.;
Manie, S. N.: Pdro, a protein associated with late endosomes and
lysosomes and implicated in cellular cholesterol homeostasis. PLoS
One 5: e10977, 2010. Note: Electronic Article.
2. Hoshino, D.; Tomari, T.; Nagano, M.; Koshikawa, N.; Seiki, M.:
A novel protein associated with membrane-type 1 matrix metalloproteinase
binds p27(kip1) and regulates RhoA activation, actin remodeling, and
matrigel invasion. J. Biol. Chem. 284: 27315-27326, 2009.
*FIELD* CD
Patricia A. Hartz: 7/29/2010
*FIELD* ED
wwang: 07/29/2010
wwang: 7/29/2010
*RECORD*
*FIELD* NO
613510
*FIELD* TI
*613510 CHROMOSOME 11 OPEN READING FRAME 59; C11ORF59
;;p27(Kip1)-RELEASING FACTOR FROM RHOA; p27RF-Rho;;
read morePROTEIN ASSOCIATED WITH DETERGENT-RESISTANT MEMBRANES AND ENDOSOMES;
PDRO
*FIELD* TX
CLONING
Hoshino et al. (2009) stated that C11ORF59, which they called p27RF-Rho,
was first identified as a protein that copurified with matrix
metalloproteinase-1 (MMP1; 120353) from a human melanoma cell line. The
161-amino acid protein contains 1 myristoylation and 2 palmitoylation
sites at its N terminus. Northern blot analysis detected variable
expression of p27RF-Rho mRNA in all human tissues examined. Orthologs of
p27RF-Rho were identified in a number of vertebrate species. p27RF-Rho
localized to a punctate distribution in a human fibrosarcoma cell line,
and Western blot analysis detected p27RF-Rho at an apparent molecular
mass of 17 kD.
Using mass spectrometry to identify proteins that purified with
detergent-resistant membranes from SHEP human neuroblastoma cells,
followed by RT-PCR, Guillaumot et al. (2010) cloned C11ORF59, which they
called PDRO. The deduced 161-amino acid protein contains a dileucine
motif near its N-terminal end in addition to the N-terminal
myristoylation and palmitoylation sites. Confocal microscopy showed that
fluorescence-tagged PDRO localized to ring-shaped structures that also
expressed markers of late endosomes and lysosomes.
GENE FUNCTION
RhoA (165390) is a small GTPase that has a pivotal role in regulating
the organization of the actin cytoskeleton. Using knockdown and
overexpression studies, Hoshino et al. (2009) found that p27RF-Rho
enhanced the activation of RhoA by releasing it from inhibition by
cytoplasmic p27(Kip1) (CDKN1B; 600778) in human cell lines. p27RF-Rho
bound and sequestered p27(Kip1), allowing RhoA to be activated by its
guanine nucleotide exchange factors (see ARHGEF1, 601855), initiating
cell motility and invasiveness.
Using mutation analysis, Guillaumot et al. (2010) showed that the
myristoylation and palmitoylation sites of PDRO were required to target
PDRO to detergent-resistant membranes in vitro and to perinuclear late
endosomes and lysosomes in intact SHEP cells. Expression of PDRO mRNA
and protein was upregulated by depletion of cellular cholesterol and
downregulated by cholesterol loading. Knockdown of PDRO via small
interfering RNA increased cellular free cholesterol content, which was
due, at least in part, to elevated uptake of low-density lipoprotein and
cholesterol egress from late endosomes and lysosomes. PDRO-knockdown
cells also displayed elevated cholesterol efflux. Conversely,
overexpression of PDRO reduced cellular free cholesterol content.
Guillaumot et al. (2010) concluded that PDRO is involved in cellular
cholesterol homeostasis, which may be linked to its role in regulating
the actin cytoskeleton.
GENE STRUCTURE
Guillaumot et al. (2010) identified 5 putative sterol response elements
in the upstream region of the C11ORF59 gene.
MAPPING
By genomic sequence analysis, Guillaumot et al. (2010) mapped the
C11ORF59 gene to chromosome 11q13.4.
*FIELD* RF
1. Guillaumot, P.; Luquain, C.; Malek, M.; Huber, A.-L.; Brugiere,
S.; Garin, J.; Grunwald, D.; Regnier, D.; Petrilli, V.; Lefai, E.;
Manie, S. N.: Pdro, a protein associated with late endosomes and
lysosomes and implicated in cellular cholesterol homeostasis. PLoS
One 5: e10977, 2010. Note: Electronic Article.
2. Hoshino, D.; Tomari, T.; Nagano, M.; Koshikawa, N.; Seiki, M.:
A novel protein associated with membrane-type 1 matrix metalloproteinase
binds p27(kip1) and regulates RhoA activation, actin remodeling, and
matrigel invasion. J. Biol. Chem. 284: 27315-27326, 2009.
*FIELD* CD
Patricia A. Hartz: 7/29/2010
*FIELD* ED
wwang: 07/29/2010
wwang: 7/29/2010