UniProt functional annotation for Q9NQL2



	UniProt functional annotation for Q9NQL2

UniProt code: Q9NQL2.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279). Forms heterodimeric Rag complexes with RRAGA or RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form (PubMed:24095279). In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279). This is a crucial step in the activation of the TOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279). {ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:24095279}.

Catalytic activity: Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000305|PubMed:24095279}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000305|PubMed:24095279};

Activity regulation: In high-amino acid conditions, activated by GTPase activating protein (GAP) FLCN that stimulates RRAGD GTPase activity to turn it into its active GDP-bound form. {ECO:0000269|PubMed:24095279}.

Subunit: Forms a heterodimer with RRAGA in a sequence-independent manner and RRAGB (PubMed:11073942, PubMed:14660641). Heterodimerization stabilizes RRAG proteins (PubMed:11073942, PubMed:14660641, PubMed:25561175, PubMed:25567906). In complex with RRAGB, interacts with RPTOR; this interaction is particularly efficient with GTP-loaded RRAGB and GDP-loaded RRAGC (PubMed:18497260). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound, and Ragulator (By similarity). Interacts with NOL8 (PubMed:14660641). Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGD and is negatively regulated by amino acids (PubMed:22575674). The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor (PubMed:25561175, PubMed:25567906). Interacts with SESN1, SESN2 and SESN3 (PubMed:25259925). {ECO:0000250|UniProtKB:Q9HB90, ECO:0000269|PubMed:11073942, ECO:0000269|PubMed:14660641, ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:22575674, ECO:0000269|PubMed:25259925, ECO:0000269|PubMed:25561175, ECO:0000269|PubMed:25567906}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:11073942}. Nucleus {ECO:0000269|PubMed:11073942}. Lysosome {ECO:0000269|PubMed:20381137}. Note=Predominantly cytoplasmic. May shuttle between the cytoplasm and nucleus, depending on the bound nucleotide state of associated RRAGA (PubMed:11073942). {ECO:0000269|PubMed:11073942}.

Similarity: Belongs to the GTR/RAG GTP-binding protein family. {ECO:0000305}.

Sequence caution: Sequence=AAH03088.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279). Forms heterodimeric Rag complexes with RRAGA or RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form (PubMed:24095279). In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279). This is a crucial step in the activation of the TOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279). {ECO:0000269\|PubMed:20381137, ECO:0000269\|PubMed:24095279}.


Catalytic activity:		Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; Evidence={ECO:0000305\|PubMed:24095279}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000305\|PubMed:24095279};
Activity regulation:		In high-amino acid conditions, activated by GTPase activating protein (GAP) FLCN that stimulates RRAGD GTPase activity to turn it into its active GDP-bound form. {ECO:0000269\|PubMed:24095279}.
Subunit:		Forms a heterodimer with RRAGA in a sequence-independent manner and RRAGB (PubMed:11073942, PubMed:14660641). Heterodimerization stabilizes RRAG proteins (PubMed:11073942, PubMed:14660641, PubMed:25561175, PubMed:25567906). In complex with RRAGB, interacts with RPTOR; this interaction is particularly efficient with GTP-loaded RRAGB and GDP-loaded RRAGC (PubMed:18497260). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RRAGA/RagA or RRAGB/RagB GDP-bound, RRAGC/RagC or RRAGD/RagD GTP-bound, and Ragulator (By similarity). Interacts with NOL8 (PubMed:14660641). Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGD and is negatively regulated by amino acids (PubMed:22575674). The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor (PubMed:25561175, PubMed:25567906). Interacts with SESN1, SESN2 and SESN3 (PubMed:25259925). {ECO:0000250\|UniProtKB:Q9HB90, ECO:0000269\|PubMed:11073942, ECO:0000269\|PubMed:14660641, ECO:0000269\|PubMed:18497260, ECO:0000269\|PubMed:22575674, ECO:0000269\|PubMed:25259925, ECO:0000269\|PubMed:25561175, ECO:0000269\|PubMed:25567906}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:11073942}. Nucleus {ECO:0000269\|PubMed:11073942}. Lysosome {ECO:0000269\|PubMed:20381137}. Note=Predominantly cytoplasmic. May shuttle between the cytoplasm and nucleus, depending on the bound nucleotide state of associated RRAGA (PubMed:11073942). {ECO:0000269\|PubMed:11073942}.
Similarity:		Belongs to the GTR/RAG GTP-binding protein family. {ECO:0000305}.
Sequence caution:		Sequence=AAH03088.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};