RAB10_RAT
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 03-AUG-2022, entry version 145.
DE RecName: Full=Ras-related protein Rab-10;
DE EC=3.6.5.2;
GN Name=Rab10;
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).
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 (By similarity). 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 (By similarity).
CC That Rab is mainly involved in the biosynthetic transport of proteins
CC from the Golgi to the plasma membrane (By similarity). Regulates, for
CC instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery
CC to the plasma membrane (By similarity). In parallel, it 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, it is involved in
CC axonogenesis through regulation of vesicular membrane trafficking
CC toward the axonal plasma membrane (PubMed:21856246). In epithelial
CC cells, it regulates transport from the Golgi to the basolateral
CC membrane (By similarity). May play a role in the basolateral recycling
CC pathway and in phagosome maturation (By similarity). May play a role in
CC endoplasmic reticulum dynamics and morphology controlling tubulation
CC along microtubules and tubules fusion (By similarity). Together with
CC LRRK2, RAB8A, and RILPL1, it regulates ciliogenesis (By similarity).
CC When phosphorylated by LRRK2 on Thr-73, it binds RILPL1 and inhibits
CC ciliogenesis (By similarity). {ECO:0000250|UniProtKB:P24409,
CC ECO:0000250|UniProtKB:P61026, ECO:0000250|UniProtKB:P61027,
CC ECO:0000269|PubMed:21856246}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; 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 -!- ACTIVITY REGULATION: Rab activation is generally mediated by a guanine
CC exchange factor (GEF), while inactivation through hydrolysis of bound
CC GTP is catalyzed by a GTPase activating protein (GAP) (By similarity).
CC That Rab is activated by the DENND4C guanine exchange factor (GEF)
CC (Probable). That Rab is activated by the DENND4C and RABIF guanine
CC exchange factors (GEF) (By similarity). {ECO:0000250|UniProtKB:P61026,
CC ECO:0000305}.
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 {ECO:0000250|UniProtKB:P24409, ECO:0000250|UniProtKB:P61026,
CC ECO:0000250|UniProtKB:P61027, ECO:0000269|PubMed:21856246}.
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}. 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). {ECO:0000250|UniProtKB:P24409,
CC ECO:0000250|UniProtKB:P61026, ECO:0000269|PubMed:20576682}.
CC -!- TISSUE SPECIFICITY: Highest levels in neural and muscle tissues.
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.
CC {ECO:0000250|UniProtKB:P61026}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; M83677; AAA41991.1; -; mRNA.
DR PIR; B42148; B42148.
DR AlphaFoldDB; P35281; -.
DR SMR; P35281; -.
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; P35281; -.
DR PRIDE; P35281; -.
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:0098993; C:anchored component of synaptic vesicle membrane; IDA:SynGO.
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:0070382; C:exocytic vesicle; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0032593; C:insulin-responsive compartment; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:RGD.
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; IBA:GO_Central.
DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central.
DR GO; GO:0005802; C:trans-Golgi network; IDA:RGD.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
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; IBA:GO_Central.
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: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: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: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:0009306; P:protein secretion; IBA:GO_Central.
DR GO; GO:0045055; P:regulated exocytosis; ISO:RGD.
DR GO; GO:0017157; P:regulation of exocytosis; IBA:GO_Central.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IBA:GO_Central.
DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 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; Membrane; Nucleotide-binding; Phosphoprotein;
KW Prenylation; Protein transport; Reference proteome; Transport;
KW Ubl conjugation.
FT CHAIN 1..200
FT /note="Ras-related protein Rab-10"
FT /id="PRO_0000121148"
FT MOTIF 38..46
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 16..23
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 18..24
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61026"
FT BINDING 35..41
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61026"
FT BINDING 64..68
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61026,
FT ECO:0000250|UniProtKB:Q9H0U4"
FT BINDING 122..125
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61026"
FT BINDING 152..154
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61026,
FT ECO:0000250|UniProtKB:Q9H0U4"
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
