Q9Y2Q5 (LTOR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ragulator complex protein LAMTOR2

Alternative name(s):
Endosomal adaptor protein p14
Late endosomal/lysosomal Mp1-interacting protein
Late endosomal/lysosomal adaptor and MAPK and MTOR activator 2
Mitogen-activated protein-binding protein-interacting protein
Roadblock domain-containing protein 3

Gene names

Name:	LAMTOR2
Synonyms:	MAPBPIP, ROBLD3
ORF Names:	HSPC003

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	125 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. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2. Ref.7 Ref.9
Subunit structure	Interacts with MAPK1 and MAP2K1 By similarity. 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 LAMTOR1 and LAMTOR3; the interaction is direct. Ref.7 Ref.9
Subcellular location	Late endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Lysosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity Ref.5.
Involvement in disease	Immunodeficiency due to defect in MAPBP-interacting protein (ID-MAPBPIP) [MIM:610798]: This form of primary immunodeficiency syndrome includes congenital neutropenia, partial albinism, short stature and B-cell and cytotoxic T-cell deficiency. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the GAMAD family.

Ontologies

Keywords
Cellular component	Endosome Lysosome Membrane
Coding sequence diversity	Alternative splicing
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of MAPKK activity Inferred from electronic annotation. Source: Compara cell growth Inferred from mutant phenotype Ref.7. Source: UniProtKB cellular protein localization Inferred from mutant phenotype Ref.7. Source: UniProtKB cellular response to amino acid stimulus Inferred from mutant phenotype Ref.7. Source: UniProtKB positive regulation of TOR signaling cascade Inferred from mutant phenotype Ref.7. Source: UniProtKB
Cellular_component	Ragulator complex Inferred from direct assay Ref.7. Source: UniProtKB lysosomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LAMTOR3	Q9UHA4	6	EBI-2643704,EBI-1038192

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y2Q5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y2Q5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     109-125: QALVQYLEEPLTQVAAS → VCGTDLCSPSAGPGFGAVPGGAPHPSGGILTALVEAGVRKEK

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9Y2Q5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     78-107: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 125	125	Ragulator complex protein LAMTOR2		PRO_0000220960
Regions
	Region	57 – 70	14	Required for location at endosomes By similarity
Natural variations
	Alternative sequence	78 – 107	30	Missing in isoform 3.		VSP_040980
	Alternative sequence	109 – 125	17	QALVQ…QVAAS → VCGTDLCSPSAGPGFGAVPG GAPHPSGGILTALVEAGVRK EK in isoform 2.		VSP_036543

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 69599211C2CBC03D	FASTA	125	13,508
	10 20 30 40 50 60 MLRPKALTQV LSQANTGGVQ STLLLNNEGS LLAYSGYGDT DARVTAAIAS NIWAAYDRNG 70 80 90 100 110 120 NQAFNEDNLK FILMDCMEGR VAITRVANLL LCMYAKETVG FGMLKAKAQA LVQYLEEPLT QVAAS
	Isoform 2 [UniParc]. Checksum: D45D4B887C721086	FASTA	150	15,609
	10 20 30 40 50 60 MLRPKALTQV LSQANTGGVQ STLLLNNEGS LLAYSGYGDT DARVTAAIAS NIWAAYDRNG 70 80 90 100 110 120 NQAFNEDNLK FILMDCMEGR VAITRVANLL LCMYAKETVG FGMLKAKAVC GTDLCSPSAG 130 140 150 PGFGAVPGGA PHPSGGILTA LVEAGVRKEK
	Isoform 3 [UniParc]. Checksum: 13ADB9F75E3E9E8C	FASTA	95	10,242
	10 20 30 40 50 60 MLRPKALTQV LSQANTGGVQ STLLLNNEGS LLAYSGYGDT DARVTAAIAS NIWAAYDRNG 70 80 90 NQAFNEDNLK FILMDCMAQA LVQYLEEPLT QVAAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Umbilical cord blood.
[2]	"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] (ISOFORM 3).
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORM 1). Tissue: Lung.
[5]	"Integral and associated lysosomal membrane proteins." Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H., Elsaesser H.-P., Mann M., Hasilik A. Traffic 8:1676-1686(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Placenta.
[6]	"A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14." Bohn G., Allroth A., Brandes G., Thiel J., Glocker E., Schaeffer A.A., Rathinam C., Taub N., Teis D., Zeidler C., Dewey R.A., Geffers R., Buer J., Huber L.A., Welte K., Grimbacher B., Klein C. Nat. Med. 13:38-45(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN IMMUNODEFICIENCY DUE TO DEFECT IN MAPBP-INTERACTING PROTEIN.
[7]	"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.
[8]	"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].
[9]	"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.

Web resources

MAPBPIPbase

ROBLD3 mutation db

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF070659 mRNA. Translation: AAD20965.1. AK307086 mRNA. No translation available. AL355388 Genomic DNA. Translation: CAH72635.1. AL355388 Genomic DNA. Translation: CAH72636.1. AL355388 Genomic DNA. Translation: CAH72637.1. BC024190 mRNA. Translation: AAH24190.1.
IPI	IPI00032409. IPI00477441. IPI00477454.
RefSeq	NP_001138736.1. NM_001145264.1. NP_054736.1. NM_014017.3.
UniGene	Hs.632483.
3D structure databases
ProteinModelPortal	Q9Y2Q5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y2Q5. 10 interactions.
STRING	9606.ENSP00000357288.
PTM databases
PhosphoSite	Q9Y2Q5.
Polymorphism databases
DMDM	12585246.
2D gel databases
OGP	Q9Y2Q5.
Proteomic databases
PaxDb	Q9Y2Q5.
PRIDE	Q9Y2Q5.
Protocols and materials databases
DNASU	28956.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368302; ENSP00000357285; ENSG00000116586. ENST00000368304; ENSP00000357287; ENSG00000116586. ENST00000368305; ENSP00000357288; ENSG00000116586.
GeneID	28956.
KEGG	hsa:28956.
UCSC	uc001fnb.3. human.
Organism-specific databases
CTD	28956.
GeneCards	GC01P156025.
HGNC	HGNC:29796. LAMTOR2.
HPA	HPA004126.
MIM	610389. gene. 610798. phenotype.
neXtProt	NX_Q9Y2Q5.
PharmGKB	PA164725527.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG237668.
HOVERGEN	HBG004518.
OMA	IASNIWS.
OrthoDB	EOG45DWQS.
PhylomeDB	Q9Y2Q5.
Gene expression databases
ArrayExpress	Q9Y2Q5.
Bgee	Q9Y2Q5.
Genevestigator	Q9Y2Q5.
GermOnline	ENSG00000116586. Homo sapiens.
Family and domain databases
InterPro	IPR004942. Dynein_light-rel. [Graphical view]
Pfam	PF03259. Robl_LC7. 1 hit. [Graphical view]
SMART	SM00960. Robl_LC7. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	28956.
NextBio	51776.
SOURCE	Search...

Entry information

Entry name

LTOR2_HUMAN

Accession

Primary (citable) accession number: Q9Y2Q5
Secondary accession number(s): Q5VY97, Q5VY98, Q5VY99

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 101 of the entry and version 1 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.