UniProt functional annotation for P55258



	UniProt functional annotation for P55258

UniProt code: P55258.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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 polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (By similarity). Together with MYO5B and RAB11A participates in epithelial cell polarization (By similarity). May be involved in ciliogenesis (By similarity). Together with MICALL2, may also regulate adherens junction assembly (PubMed:18094055). May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis (By similarity). Involved in autophagy (By similarity). {ECO:0000250|UniProtKB:P35280, ECO:0000250|UniProtKB:P61006, ECO:0000269|PubMed:18094055}.

Activity regulation: Activated in response to insulin. {ECO:0000250}.

Subunit: Interacts (GTP-bound form) with MICALL1; regulates RAB8A association with recycling endosomes (PubMed:18094055). Interacts with MICALL2; competes with RAB13 and is involved in E-cadherin endocytic recycling (PubMed:18094055). Interacts (GTP-bound form) with MICAL1, MICALCL, MICAL3 and EHBP1L1; two molecules of RAB8A can bind to one molecule of the effector protein; ternary complexes of RAB8A, RAB13 and either MICAL1 or EHBP1L1 are possible (By similarity). Interacts (GTP- bound form) with EHBP1 (By similarity). Interacts with EHD1 (By similarity). Interacts with MAP4K2 and SYTL4 (PubMed:8643544, PubMed:12590134). Interacts with SGSM1 and SGSM3 (PubMed:17509819). Interacts with RABIF, RIMS2, RPH3A and RPH3A (PubMed:12578829, PubMed:16541104). Interacts with OPTN (By similarity). Interacts with RAB3IP (PubMed:19625297). Interacts with MYO5B (By similarity). Interacts with PIFO (PubMed:20643351). Interacts with BIRC6/bruce (By similarity). Interacts with OCRL (By similarity). Interacts with AHI1 (PubMed:19625297). Interacts with DCDC1 (By similarity). Interacts with LRRK2; interaction facilitates phosphorylation of Thr-72 (By similarity). Interacts with RAB31P, GDI1, GDI2, CHM, CHML, RABGGTA, RABGGTB, TBC1D15 and INPP5B; these interactions are dependent on Thr-72 not being phosphorylated (By similarity). Interacts with RILPL1 and RILPL2; these interactions are dependent on the phosphorylation of Thr- 72 by LRRK2 (PubMed:29125462). {ECO:0000250|UniProtKB:P61006, ECO:0000269|PubMed:12578829, ECO:0000269|PubMed:12590134, ECO:0000269|PubMed:16541104, ECO:0000269|PubMed:17509819, ECO:0000269|PubMed:18094055, ECO:0000269|PubMed:19625297, ECO:0000269|PubMed:20643351, ECO:0000269|PubMed:29125462, ECO:0000269|PubMed:8643544}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:18094055}; Lipid-anchor {ECO:0000269|PubMed:18094055}; Cytoplasmic side {ECO:0000269|PubMed:18094055}. Golgi apparatus {ECO:0000250|UniProtKB:P61006}. Recycling endosome membrane {ECO:0000269|PubMed:18094055}. Cell projection, cilium {ECO:0000250|UniProtKB:P61006}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:P61006}; Lipid-anchor {ECO:0000250|UniProtKB:P61006}; Cytoplasmic side {ECO:0000250|UniProtKB:P61006}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole {ECO:0000269|PubMed:23807208}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269|PubMed:19625297, ECO:0000269|PubMed:23807208}. Midbody {ECO:0000250|UniProtKB:P61006}. Cytoplasm {ECO:0000250|UniProtKB:P61006}. Note=Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane. In the GDP-bound form, present in the perinuclear region. Shows a polarized distribution to distal regions of cell protrusions in the GTP-bound form. Colocalizes with PARD3, PRKCI, EXOC5, OCLN, PODXL and RAB11A in apical membrane initiation sites (AMIS) during the generation of apical surface and lumenogenesis. Localizes to tubular recycling endosome. Recruited to phagosomes containing S.aureus or Mycobacterium (By similarity). Non-phosphorylated RAB8A predominantly localizes to the cytoplasm whereas phosphorylated RAB8A localizes to the membrane (By similarity). {ECO:0000250|UniProtKB:P61006}.

Ptm: Phosphorylation of Thr-72 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2. {ECO:0000250|UniProtKB:P61006}.

Similarity: Belongs to the small GTPase superfamily. Rab family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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 polarized vesicular trafficking and neurotransmitter release. Together with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (By similarity). Together with MYO5B and RAB11A participates in epithelial cell polarization (By similarity). May be involved in ciliogenesis (By similarity). Together with MICALL2, may also regulate adherens junction assembly (PubMed:18094055). May play a role in insulin-induced transport to the plasma membrane of the glucose transporter GLUT4 and therefore play a role in glucose homeostasis (By similarity). Involved in autophagy (By similarity). {ECO:0000250\|UniProtKB:P35280, ECO:0000250\|UniProtKB:P61006, ECO:0000269\|PubMed:18094055}.


Activity regulation:		Activated in response to insulin. {ECO:0000250}.
Subunit:		Interacts (GTP-bound form) with MICALL1; regulates RAB8A association with recycling endosomes (PubMed:18094055). Interacts with MICALL2; competes with RAB13 and is involved in E-cadherin endocytic recycling (PubMed:18094055). Interacts (GTP-bound form) with MICAL1, MICALCL, MICAL3 and EHBP1L1; two molecules of RAB8A can bind to one molecule of the effector protein; ternary complexes of RAB8A, RAB13 and either MICAL1 or EHBP1L1 are possible (By similarity). Interacts (GTP- bound form) with EHBP1 (By similarity). Interacts with EHD1 (By similarity). Interacts with MAP4K2 and SYTL4 (PubMed:8643544, PubMed:12590134). Interacts with SGSM1 and SGSM3 (PubMed:17509819). Interacts with RABIF, RIMS2, RPH3A and RPH3A (PubMed:12578829, PubMed:16541104). Interacts with OPTN (By similarity). Interacts with RAB3IP (PubMed:19625297). Interacts with MYO5B (By similarity). Interacts with PIFO (PubMed:20643351). Interacts with BIRC6/bruce (By similarity). Interacts with OCRL (By similarity). Interacts with AHI1 (PubMed:19625297). Interacts with DCDC1 (By similarity). Interacts with LRRK2; interaction facilitates phosphorylation of Thr-72 (By similarity). Interacts with RAB31P, GDI1, GDI2, CHM, CHML, RABGGTA, RABGGTB, TBC1D15 and INPP5B; these interactions are dependent on Thr-72 not being phosphorylated (By similarity). Interacts with RILPL1 and RILPL2; these interactions are dependent on the phosphorylation of Thr- 72 by LRRK2 (PubMed:29125462). {ECO:0000250\|UniProtKB:P61006, ECO:0000269\|PubMed:12578829, ECO:0000269\|PubMed:12590134, ECO:0000269\|PubMed:16541104, ECO:0000269\|PubMed:17509819, ECO:0000269\|PubMed:18094055, ECO:0000269\|PubMed:19625297, ECO:0000269\|PubMed:20643351, ECO:0000269\|PubMed:29125462, ECO:0000269\|PubMed:8643544}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:18094055}; Lipid-anchor {ECO:0000269\|PubMed:18094055}; Cytoplasmic side {ECO:0000269\|PubMed:18094055}. Golgi apparatus {ECO:0000250\|UniProtKB:P61006}. Recycling endosome membrane {ECO:0000269\|PubMed:18094055}. Cell projection, cilium {ECO:0000250\|UniProtKB:P61006}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250\|UniProtKB:P61006}; Lipid-anchor {ECO:0000250\|UniProtKB:P61006}; Cytoplasmic side {ECO:0000250\|UniProtKB:P61006}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole {ECO:0000269\|PubMed:23807208}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269\|PubMed:19625297, ECO:0000269\|PubMed:23807208}. Midbody {ECO:0000250\|UniProtKB:P61006}. Cytoplasm {ECO:0000250\|UniProtKB:P61006}. Note=Colocalizes with OPTN at the Golgi complex and in vesicular structures close to the plasma membrane. In the GDP-bound form, present in the perinuclear region. Shows a polarized distribution to distal regions of cell protrusions in the GTP-bound form. Colocalizes with PARD3, PRKCI, EXOC5, OCLN, PODXL and RAB11A in apical membrane initiation sites (AMIS) during the generation of apical surface and lumenogenesis. Localizes to tubular recycling endosome. Recruited to phagosomes containing S.aureus or Mycobacterium (By similarity). Non-phosphorylated RAB8A predominantly localizes to the cytoplasm whereas phosphorylated RAB8A localizes to the membrane (By similarity). {ECO:0000250\|UniProtKB:P61006}.
Ptm:		Phosphorylation of Thr-72 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2. {ECO:0000250\|UniProtKB:P61006}.
Similarity:		Belongs to the small GTPase superfamily. Rab family. {ECO:0000305}.