UniProt functional annotation for P20339



	UniProt functional annotation for P20339

UniProt code: P20339.

Organism: Homo sapiens (Human).

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

Function: Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Active GTP-bound form is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB5A is required for the fusion of plasma membranes and early endosomes (PubMed:10818110, PubMed:14617813, PubMed:16410077, PubMed:15378032). Contributes to the regulation of filopodia extension (PubMed:14978216). Required for the exosomal release of SDCBP, CD63, PDCD6IP and syndecan (PubMed:22660413). Regulates maturation of apoptotic cell-containing phagosomes, probably downstream of DYN2 and PIK3C3 (By similarity). {ECO:0000250|UniProtKB:Q9CQD1, ECO:0000269|PubMed:10818110, ECO:0000269|PubMed:14617813, ECO:0000269|PubMed:14978216, ECO:0000269|PubMed:15378032, ECO:0000269|PubMed:16410077, ECO:0000269|PubMed:22660413}.

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; EC=3.6.5.2; Evidence={ECO:0000269|PubMed:15378032}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000305|PubMed:15378032};

Activity regulation: Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. {ECO:0000250|UniProtKB:P18066}.

Subunit: Interacts with SGSM1 and SGSM3 (By similarity). Interacts with PIK3CB (By similarity). Interacts with GDI1; this promotes dissociation from membranes; phosphorylation at Ser-84 disrupts this interaction (PubMed:23815289, PubMed:29125462). Interacts with GDI2; phosphorylation at Ser-84 disrupts the interaction (PubMed:29125462). Interacts with EEA1 (PubMed:10491193, PubMed:20534488). Interacts with RIN1 and GAPVD1, which regulate its pathway, probably by acting as a GEF (PubMed:11703925, PubMed:16410077). Interacts with RINL. Interacts with ALS2CL, SUN2, ZFYVE20 and RUFY1 (PubMed:10818110, PubMed:11062261, PubMed:15388334, PubMed:14617813, PubMed:16034420). Interacts with RABEP1; one RABEP1 homodimer binds two RAB5A chains, but at opposite sides of the dimer (PubMed:15378032). Interacts with OCRL (PubMed:25869668). Interacts with INPP5F. May be a component of a complex composed of RAB5A, DYN2 and PIK3C3 (By similarity). Does not interact with BLOC-3 complex (heterodimer of HPS1 and HPS4) (By similarity). Interacts with CLN5 (PubMed:22431521). Interacts with APPL2 (By similarity). Interacts with F8A1/F8A2/F8A3 (By similarity). Found in a complex with F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A onto early endosomes (By similarity). {ECO:0000250|UniProtKB:P18066, ECO:0000250|UniProtKB:Q0IIG7, ECO:0000250|UniProtKB:Q9CQD1, ECO:0000269|PubMed:10491193, ECO:0000269|PubMed:10818110, ECO:0000269|PubMed:11062261, ECO:0000269|PubMed:11703925, ECO:0000269|PubMed:14617813, ECO:0000269|PubMed:14684892, ECO:0000269|PubMed:15378032, ECO:0000269|PubMed:15388334, ECO:0000269|PubMed:16034420, ECO:0000269|PubMed:16410077, ECO:0000269|PubMed:20534488, ECO:0000269|PubMed:22431521, ECO:0000269|PubMed:23815289, ECO:0000269|PubMed:25869668, ECO:0000269|PubMed:29125462}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:23815289}; Lipid-anchor {ECO:0000305|PubMed:7991565}; Cytoplasmic side {ECO:0000269|PubMed:23382462}. Early endosome membrane {ECO:0000269|PubMed:23815289, ECO:0000269|PubMed:25869668}; Lipid- anchor {ECO:0000305|PubMed:7991565}. Melanosome {ECO:0000269|PubMed:17081065}. Cytoplasmic vesicle {ECO:0000269|PubMed:10818110}. Cell projection, ruffle {ECO:0000250|UniProtKB:P18066}. Membrane {ECO:0000269|PubMed:23815289}. Cytoplasm, cytosol {ECO:0000269|PubMed:23382462}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:Q9CQD1}. Endosome membrane {ECO:0000269|PubMed:22431521, ECO:0000269|PubMed:23382462}. Note=Enriched in stage I melanosomes (PubMed:17081065). Alternates between membrane-bound and cytosolic forms (Probable). {ECO:0000269|PubMed:17081065, ECO:0000305}.

Ptm: Phosphorylation of Ser-84 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including RAB GDP dissociation inhibitors GDI1 and GDI2. {ECO:0000269|PubMed:29125462}.

Ptm: (Microbial infection) Glycosylated on arginine residues by S.typhimurium protein Ssek3. {ECO:0000269|PubMed:32974215}.

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:		Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Active GTP-bound form is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB5A is required for the fusion of plasma membranes and early endosomes (PubMed:10818110, PubMed:14617813, PubMed:16410077, PubMed:15378032). Contributes to the regulation of filopodia extension (PubMed:14978216). Required for the exosomal release of SDCBP, CD63, PDCD6IP and syndecan (PubMed:22660413). Regulates maturation of apoptotic cell-containing phagosomes, probably downstream of DYN2 and PIK3C3 (By similarity). {ECO:0000250\|UniProtKB:Q9CQD1, ECO:0000269\|PubMed:10818110, ECO:0000269\|PubMed:14617813, ECO:0000269\|PubMed:14978216, ECO:0000269\|PubMed:15378032, ECO:0000269\|PubMed:16410077, ECO:0000269\|PubMed:22660413}.


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; EC=3.6.5.2; Evidence={ECO:0000269\|PubMed:15378032}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; Evidence={ECO:0000305\|PubMed:15378032};
Activity regulation:		Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP. {ECO:0000250\|UniProtKB:P18066}.
Subunit:		Interacts with SGSM1 and SGSM3 (By similarity). Interacts with PIK3CB (By similarity). Interacts with GDI1; this promotes dissociation from membranes; phosphorylation at Ser-84 disrupts this interaction (PubMed:23815289, PubMed:29125462). Interacts with GDI2; phosphorylation at Ser-84 disrupts the interaction (PubMed:29125462). Interacts with EEA1 (PubMed:10491193, PubMed:20534488). Interacts with RIN1 and GAPVD1, which regulate its pathway, probably by acting as a GEF (PubMed:11703925, PubMed:16410077). Interacts with RINL. Interacts with ALS2CL, SUN2, ZFYVE20 and RUFY1 (PubMed:10818110, PubMed:11062261, PubMed:15388334, PubMed:14617813, PubMed:16034420). Interacts with RABEP1; one RABEP1 homodimer binds two RAB5A chains, but at opposite sides of the dimer (PubMed:15378032). Interacts with OCRL (PubMed:25869668). Interacts with INPP5F. May be a component of a complex composed of RAB5A, DYN2 and PIK3C3 (By similarity). Does not interact with BLOC-3 complex (heterodimer of HPS1 and HPS4) (By similarity). Interacts with CLN5 (PubMed:22431521). Interacts with APPL2 (By similarity). Interacts with F8A1/F8A2/F8A3 (By similarity). Found in a complex with F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A onto early endosomes (By similarity). {ECO:0000250\|UniProtKB:P18066, ECO:0000250\|UniProtKB:Q0IIG7, ECO:0000250\|UniProtKB:Q9CQD1, ECO:0000269\|PubMed:10491193, ECO:0000269\|PubMed:10818110, ECO:0000269\|PubMed:11062261, ECO:0000269\|PubMed:11703925, ECO:0000269\|PubMed:14617813, ECO:0000269\|PubMed:14684892, ECO:0000269\|PubMed:15378032, ECO:0000269\|PubMed:15388334, ECO:0000269\|PubMed:16034420, ECO:0000269\|PubMed:16410077, ECO:0000269\|PubMed:20534488, ECO:0000269\|PubMed:22431521, ECO:0000269\|PubMed:23815289, ECO:0000269\|PubMed:25869668, ECO:0000269\|PubMed:29125462}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:23815289}; Lipid-anchor {ECO:0000305\|PubMed:7991565}; Cytoplasmic side {ECO:0000269\|PubMed:23382462}. Early endosome membrane {ECO:0000269\|PubMed:23815289, ECO:0000269\|PubMed:25869668}; Lipid- anchor {ECO:0000305\|PubMed:7991565}. Melanosome {ECO:0000269\|PubMed:17081065}. Cytoplasmic vesicle {ECO:0000269\|PubMed:10818110}. Cell projection, ruffle {ECO:0000250\|UniProtKB:P18066}. Membrane {ECO:0000269\|PubMed:23815289}. Cytoplasm, cytosol {ECO:0000269\|PubMed:23382462}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250\|UniProtKB:Q9CQD1}. Endosome membrane {ECO:0000269\|PubMed:22431521, ECO:0000269\|PubMed:23382462}. Note=Enriched in stage I melanosomes (PubMed:17081065). Alternates between membrane-bound and cytosolic forms (Probable). {ECO:0000269\|PubMed:17081065, ECO:0000305}.
Ptm:		Phosphorylation of Ser-84 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including RAB GDP dissociation inhibitors GDI1 and GDI2. {ECO:0000269\|PubMed:29125462}.
Ptm:		(Microbial infection) Glycosylated on arginine residues by S.typhimurium protein Ssek3. {ECO:0000269\|PubMed:32974215}.
Similarity:		Belongs to the small GTPase superfamily. Rab family. {ECO:0000305}.