ID RAB10_RAT Reviewed; 200 AA. AC P35281; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 02-SEP-2026, entry version 161. DE RecName: Full=Ras-related protein Rab-10; DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P61026}; GN Name=Rab10 {ECO:0000312|RGD:620879}; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; TISSUE=Brain; RX PubMed=1313420; DOI=10.1016/s0021-9258(18)42619-1; RA Elferink L.A., Anzai K., Scheller R.H.; RT "Rab15, a novel low molecular weight GTP-binding protein specifically RT expressed in rat brain."; RL J. Biol. Chem. 267:5768-5775(1992). RN [2] RP SUBCELLULAR LOCATION. RX PubMed=20576682; DOI=10.1152/ajprenal.00198.2010; RA Babbey C.M., Bacallao R.L., Dunn K.W.; RT "Rab10 associates with primary cilia and the exocyst complex in renal RT epithelial cells."; RL Am. J. Physiol. 299:F495-506(2010). RN [3] RP FUNCTION IN AXON DEVELOPMENT, AND INTERACTION WITH LLGL1 AND GDI1. RX PubMed=21856246; DOI=10.1016/j.devcel.2011.07.007; RA Wang T., Liu Y., Xu X.H., Deng C.Y., Wu K.Y., Zhu J., Fu X.Q., He M., RA Luo Z.G.; RT "Lgl1 activation of rab10 promotes axonal membrane trafficking underlying RT neuronal polarization."; RL Dev. Cell 21:431-444(2011). RN [4] RP FUNCTION, AND INTERACTION WITH MARCKS. RX PubMed=24662485; DOI=10.1038/cr.2014.33; RA Xu X.H., Deng C.Y., Liu Y., He M., Peng J., Wang T., Yuan L., Zheng Z.S., RA Blackshear P.J., Luo Z.G.; RT "MARCKS regulates membrane targeting of Rab10 vesicles to promote axon RT development."; RL Cell Res. 24:576-594(2014). CC -!- FUNCTION: The small GTPases Rab are key regulators of intracellular CC membrane trafficking, from the formation of transport vesicles to their CC fusion with membranes (PubMed:24662485). Rabs cycle between an inactive CC GDP-bound form and an active GTP-bound form that is able to recruit to CC membranes different set of downstream effectors directly responsible CC for vesicle formation, movement, tethering and fusion. RAB10 is mainly CC involved in the biosynthetic transport of proteins from the Golgi to CC the plasma membrane (By similarity). Regulates, for instance, CC SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the CC plasma membrane (By similarity). In parallel, RAB10 regulates the CC transport of TLR4, a toll-like receptor to the plasma membrane and CC therefore may be important for innate immune response (By similarity). CC Also plays a specific role in asymmetric protein transport to the CC plasma membrane (By similarity). In neurons, involved in axonogenesis CC through regulation of vesicular membrane trafficking toward the axonal CC plasma membrane (PubMed:21856246). In epithelial cells, regulates CC transport from the Golgi to the basolateral membrane (By similarity). CC May play a role in the basolateral recycling pathway and in phagosome CC maturation (By similarity). May play a role in endoplasmic reticulum CC dynamics and morphology controlling tubulation along microtubules and CC tubules fusion. Together with LRRK2, RAB8A, and RILPL1, regulates CC ciliogenesis. When phosphorylated by LRRK2 on Thr-73, binds RILPL1 and CC inhibits ciliogenesis. Participates in the export of a subset of CC neosynthesized proteins through a Rab8-Rab10-Rab11-dependent CC endososomal export route. Targeted to and stabilized on stressed CC lysosomes through LRRK2 phosphorylation where it promotes the CC extracellular release of lysosomal content through EHBP1 and EHNP1L1 CC effector proteins (By similarity). {ECO:0000250|UniProtKB:P24409, CC ECO:0000250|UniProtKB:P61026, ECO:0000250|UniProtKB:P61027, CC ECO:0000269|PubMed:21856246, ECO:0000269|PubMed:24662485}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + phosphate + H(+); Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2; CC Evidence={ECO:0000250|UniProtKB:P61026}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000250|UniProtKB:P61026}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P61026}; CC -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors CC (GEFs) DENND4C and RABIF which promote the exchange of bound GDP for CC free GTP. Regulated by GTPase activating proteins (GAPs) including CC TBC1D21 which increase the GTP hydrolysis activity. Inhibited by GDP CC dissociation inhibitors GDI1 and GDI2 which prevent Rab-GDP CC dissociation. {ECO:0000250|UniProtKB:P61026}. CC -!- SUBUNIT: Interacts with MYO5A; mediates the transport to the plasma CC membrane of SLC2A4/GLUT4 storage vesicles (By similarity). Interacts CC with GDI1 and with GDI2; negatively regulates RAB10 association with CC membranes and activation (By similarity). Interacts (GDP-bound form) CC with LLGL1; the interaction is direct and promotes RAB10 association CC with membranes and activation through competition with the Rab CC inhibitor GDI1 (PubMed:21856246). Interacts with EXOC4; probably CC associates with the exocyst (By similarity). Interacts (GTP-bound form) CC with MICALCL, MICAL1, MICAL3, EHBP1 and EHBP1L1; at least in case of CC MICAL1 two molecules of RAB10 can bind to one molecule of MICAL1 (By CC similarity). Interacts with TBC1D13 (By similarity). Interacts with CC SEC16A (By similarity). Interacts with CHM (By similarity). Interacts CC with LRRK2; interaction facilitates phosphorylation of Thr-73 (By CC similarity). Interacts with RILPL1 and RILPL2 when phosphorylated on CC Thr-73 (By similarity). Interacts with TBC1D21 (By similarity). CC Interacts with MARCKS (PubMed:24662485). {ECO:0000250|UniProtKB:P24409, CC ECO:0000250|UniProtKB:P61026, ECO:0000250|UniProtKB:P61027, CC ECO:0000269|PubMed:21856246, ECO:0000269|PubMed:24662485}. CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane {ECO:0000305}; CC Lipid-anchor {ECO:0000305|PubMed:20576682}; Cytoplasmic side CC {ECO:0000305|PubMed:20576682}. Golgi apparatus, trans-Golgi network CC membrane {ECO:0000250|UniProtKB:P24409}. Endosome membrane CC {ECO:0000250|UniProtKB:P61026}. Recycling endosome membrane CC {ECO:0000250|UniProtKB:P24409}. Cytoplasmic vesicle, phagosome membrane CC {ECO:0000250|UniProtKB:P24409}. Cell projection, cilium CC {ECO:0000269|PubMed:20576682}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P61027}. Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:P61027}. Lysosome CC {ECO:0000250|UniProtKB:P61027}. Note=Associates with SLC2A4/GLUT4 CC storage vesicles (By similarity). Localizes to the base of the cilium CC (PubMed:20576682). Transiently associates with phagosomes (By CC similarity). Localizes to the endoplasmic reticulum at domains of new CC tubule growth (By similarity). Localizes to enlarged lysosomes through CC LRRK2 phosphorylation (By similarity). {ECO:0000250|UniProtKB:P24409, CC ECO:0000250|UniProtKB:P61026, ECO:0000269|PubMed:20576682}. CC -!- TISSUE SPECIFICITY: Highest levels in neural and muscle tissues. CC -!- DOMAIN: Switch I, switch II and the interswitch regions are CC characteristic of Rab GTPases and mediate the interactions with Rab CC downstream effectors. The switch regions undergo conformational changes CC upon nucleotide binding which drives interaction with specific sets of CC effector proteins, with most effectors only binding to GTP-bound Rab. CC {ECO:0000250|UniProtKB:P62820}. CC -!- PTM: Phosphorylation of Thr-73 in the switch II region by LRRK2 CC prevents the association of RAB regulatory proteins, including CHM and CC RAB GDP dissociation inhibitors GDI1 and GDI2 (By similarity). CC Phosphorylation of Thr-73 by LRRK2 is stimulated by RAB29 and RAB32 (By CC similarity). Phosphorylation by LRRK2 is required for localization to CC stressed lysosomes (By similarity). {ECO:0000250|UniProtKB:P61026}. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M83677; AAA41991.1; -; mRNA. DR PIR; B42148; B42148. DR AlphaFoldDB; P35281; -. DR SMR; P35281; -. DR FunCoup; P35281; 2942. DR IntAct; P35281; 3. DR MINT; P35281; -. DR STRING; 10116.ENSRNOP00000065234; -. DR iPTMnet; P35281; -. DR PhosphoSitePlus; P35281; -. DR SwissPalm; P35281; -. DR jPOST; P35281; -. DR PaxDb; 10116-ENSRNOP00000065234; -. DR AGR; RGD:620879; -. DR RGD; 620879; Rab10. DR eggNOG; KOG0078; Eukaryota. DR InParanoid; P35281; -. DR PhylomeDB; P35281; -. DR Reactome; R-RNO-6798695; Neutrophil degranulation. DR Reactome; R-RNO-8873719; RAB geranylgeranylation. DR Reactome; R-RNO-8876198; RAB GEFs exchange GTP for GDP on RABs. DR PRO; PR:P35281; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005929; C:cilium; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0071782; C:endoplasmic reticulum tubular network; ISS:UniProtKB. DR GO; GO:0005768; C:endosome; ISS:UniProtKB. DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB. DR GO; GO:0000145; C:exocyst; ISO:RGD. DR GO; GO:0070382; C:exocytic vesicle; ISO:RGD. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; ISO:RGD. DR GO; GO:0032593; C:insulin-responsive compartment; ISS:UniProtKB. DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB. DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB. DR GO; GO:0099503; C:secretory vesicle; IBA:GO_Central. DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:SynGO. DR GO; GO:0005802; C:trans-Golgi network; IDA:RGD. DR GO; GO:0003925; F:G protein activity; ISS:UniProtKB. DR GO; GO:0019003; F:GDP binding; ISS:UniProtKB. DR GO; GO:0051021; F:GDP-dissociation inhibitor binding; IPI:RGD. DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB. DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB. DR GO; GO:0031489; F:myosin V binding; IPI:RGD. DR GO; GO:0019882; P:antigen processing and presentation; ISO:RGD. DR GO; GO:0007409; P:axonogenesis; IMP:UniProtKB. DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB. DR GO; GO:0032456; P:endocytic recycling; ISO:RGD. DR GO; GO:0071786; P:endoplasmic reticulum tubular network organization; ISS:UniProtKB. DR GO; GO:0016197; P:endosomal transport; ISS:UniProtKB. DR GO; GO:0045200; P:establishment of neuroblast polarity; IMP:UniProtKB. DR GO; GO:0097051; P:establishment of protein localization to endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0090150; P:establishment of protein localization to membrane; ISO:RGD. DR GO; GO:0006887; P:exocytosis; IBA:GO_Central. DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; ISS:UniProtKB. DR GO; GO:0006893; P:Golgi to plasma membrane transport; IMP:UniProtKB. DR GO; GO:1905504; P:negative regulation of motile cilium assembly; ISO:RGD. DR GO; GO:0030859; P:polarized epithelial cell differentiation; ISS:UniProtKB. DR GO; GO:1903361; P:protein localization to basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB. DR GO; GO:0045055; P:regulated exocytosis; ISO:RGD. DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB. DR CDD; cd01867; Rab8_Rab10_Rab13_like; 1. DR FunFam; 3.40.50.300:FF:000202; ras-related protein Rab-8A; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005225; Small_GTP-bd. DR InterPro; IPR001806; Small_GTPase. DR InterPro; IPR050305; Small_GTPase_Rab. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR47980; LD44762P; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00175; RAB; 1. DR SMART; SM00176; RAN; 1. DR SMART; SM00173; RAS; 1. DR SMART; SM00174; RHO; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51419; RAB; 1. PE 1: Evidence at protein level; KW Acetylation; Cell projection; Cytoplasm; Cytoplasmic vesicle; KW Endoplasmic reticulum; Endosome; Golgi apparatus; GTP-binding; Hydrolase; KW Isopeptide bond; Lipoprotein; Lysosome; Magnesium; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Prenylation; Protein transport; KW Reference proteome; Transport; Ubl conjugation. FT CHAIN 1..200 FT /note="Ras-related protein Rab-10" FT /id="PRO_0000121148" FT REGION 36..44 FT /note="Switch-I" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00753" FT REGION 67..83 FT /note="Switch-II" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00753" FT BINDING 18 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 19 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 20 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 21 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 22 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 23 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 23 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 24 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 35 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 36 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 40 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 41 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 41 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 64 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 67 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 122 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 123 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 125 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 126 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 152 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 153 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT BINDING 154 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61026" FT MOD_RES 73 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P61026" FT MOD_RES 102 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P61026" FT LIPID 199 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000250" FT LIPID 200 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000250" FT CROSSLNK 102 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P61026" FT CROSSLNK 136 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P61026" FT CROSSLNK 154 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P61026" SQ SEQUENCE 200 AA; 22858 MW; EFAF804FD4C3B6A3 CRC64; MAKKTYDLLF KLLLIGDSGV GKTCVLFRFS DDAFNTTFIS TIEIDFKIKT VELQGKKIKL QIWDTAGQER FHTITTSYYR GAMGIMLVYD ITNGKSFENI SKWLRNIDQH ANEDVERMLL RNKCDMDHKR VVPKGKGEQI AREHRIRFFE TSAKANINIE KAFLTLPEDI LRKTPVKEPN SENVDISSGG GVTGWKSKCC //