UniProt functional annotation for Q15286



	UniProt functional annotation for Q15286

UniProt code: Q15286.

Organism: Homo sapiens (Human).

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

Function: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth. Together with TBC1D13 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes. {ECO:0000250|UniProtKB:Q6PHN9, ECO:0000269|PubMed:16950109, ECO:0000269|PubMed:21951725}.

Activity regulation: Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (PubMed:20154091). That Rab is activated by the guanine exchange factors DENND1A, DENND1B and DENND1C (PubMed:20154091). {ECO:0000269|PubMed:20154091}.

Subunit: Interacts with DENND1A and DENND1B; in a nucleotide-dependent manner (PubMed:20154091, PubMed:22065758). Interacts with DENND1C; weak interaction which is nucleotide-independent (PubMed:20154091). Interacts (GTP-bound form) with ACAP2 and MICALL1; the interaction is direct and probably recruits ACAP2 and MICALL1 to membranes (PubMed:21951725). Interacts with EHD1; the interaction is indirect through MICALL1 and probably recruits EHD1 to membranes (By similarity). Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-72 disrupts these interactions (PubMed:29125462). {ECO:0000250|UniProtKB:Q6PHN9, ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:21951725, ECO:0000269|PubMed:22065758, ECO:0000269|PubMed:29125462}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:16950109, ECO:0000269|PubMed:21951725}; Lipid-anchor {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:16950109}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000269|PubMed:16950109}. Endosome {ECO:0000269|PubMed:16950109, ECO:0000269|PubMed:21951725}. Melanosome {ECO:0000269|PubMed:17081065}. Note=Present on sorting endosomes and recycling endosome tubules (PubMed:16950109). Tends to be enriched in PIP2-positive cell membrane domains (PubMed:16950109). During mitosis, associated with the plasma membrane and present at the ingressing furrow during early cytokinesis as well as at the intercellular bridge later during cytokinesis (PubMed:16950109). Identified in stage I to stage IV melanosomes (PubMed:17081065). {ECO:0000269|PubMed:16950109, ECO:0000269|PubMed:17081065}.

Ptm: AMPylation at Tyr-77 by L.pneumophila DrrA occurs in the switch 2 region and leads to moderate inactivation of the GTPase activity. It appears to prolong the lifetime of the GTP state of RAB1B by restricting access of GTPase effectors to switch 2 and blocking effector-stimulated GTP hydrolysis, thereby rendering RAB35 constitutively active. {ECO:0000269|PubMed:21822290, ECO:0000269|PubMed:22307087}.

Ptm: Phosphocholinated by L.pneumophila AnkX. Both GDP-bound and GTP- bound forms can be phosphocholinated. Phosphocholination inhibits the GEF activity of DENND1A.

Similarity: Belongs to the small GTPase superfamily. Rab family. {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:		The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is involved in the process of endocytosis and is an essential rate-limiting regulator of the fast recycling pathway back to the plasma membrane. During cytokinesis, required for the postfurrowing terminal steps, namely for intercellular bridge stability and abscission, possibly by controlling phosphatidylinositol 4,5-bis phosphate (PIP2) and SEPT2 localization at the intercellular bridge. May indirectly regulate neurite outgrowth. Together with TBC1D13 may be involved in regulation of insulin-induced glucose transporter SLC2A4/GLUT4 translocation to the plasma membrane in adipocytes. {ECO:0000250\|UniProtKB:Q6PHN9, ECO:0000269\|PubMed:16950109, ECO:0000269\|PubMed:21951725}.


Activity regulation:		Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP) (PubMed:20154091). That Rab is activated by the guanine exchange factors DENND1A, DENND1B and DENND1C (PubMed:20154091). {ECO:0000269\|PubMed:20154091}.
Subunit:		Interacts with DENND1A and DENND1B; in a nucleotide-dependent manner (PubMed:20154091, PubMed:22065758). Interacts with DENND1C; weak interaction which is nucleotide-independent (PubMed:20154091). Interacts (GTP-bound form) with ACAP2 and MICALL1; the interaction is direct and probably recruits ACAP2 and MICALL1 to membranes (PubMed:21951725). Interacts with EHD1; the interaction is indirect through MICALL1 and probably recruits EHD1 to membranes (By similarity). Interacts with GDI1, GDI2, CHM and CHML; phosphorylation at Thr-72 disrupts these interactions (PubMed:29125462). {ECO:0000250\|UniProtKB:Q6PHN9, ECO:0000269\|PubMed:20154091, ECO:0000269\|PubMed:21951725, ECO:0000269\|PubMed:22065758, ECO:0000269\|PubMed:29125462}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:16950109, ECO:0000269\|PubMed:21951725}; Lipid-anchor {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Membrane, clathrin-coated pit {ECO:0000269\|PubMed:16950109}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000269\|PubMed:16950109}. Endosome {ECO:0000269\|PubMed:16950109, ECO:0000269\|PubMed:21951725}. Melanosome {ECO:0000269\|PubMed:17081065}. Note=Present on sorting endosomes and recycling endosome tubules (PubMed:16950109). Tends to be enriched in PIP2-positive cell membrane domains (PubMed:16950109). During mitosis, associated with the plasma membrane and present at the ingressing furrow during early cytokinesis as well as at the intercellular bridge later during cytokinesis (PubMed:16950109). Identified in stage I to stage IV melanosomes (PubMed:17081065). {ECO:0000269\|PubMed:16950109, ECO:0000269\|PubMed:17081065}.
Ptm:		AMPylation at Tyr-77 by L.pneumophila DrrA occurs in the switch 2 region and leads to moderate inactivation of the GTPase activity. It appears to prolong the lifetime of the GTP state of RAB1B by restricting access of GTPase effectors to switch 2 and blocking effector-stimulated GTP hydrolysis, thereby rendering RAB35 constitutively active. {ECO:0000269\|PubMed:21822290, ECO:0000269\|PubMed:22307087}.
Ptm:		Phosphocholinated by L.pneumophila AnkX. Both GDP-bound and GTP- bound forms can be phosphocholinated. Phosphocholination inhibits the GEF activity of DENND1A.
Similarity:		Belongs to the small GTPase superfamily. Rab family. {ECO:0000305}.