ID RAB2A_CANLF Reviewed; 212 AA. AC P61105; P08886; DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 26-APR-2004, sequence version 1. DT 02-SEP-2026, entry version 135. DE RecName: Full=Ras-related protein Rab-2A; DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P53994}; GN Name=RAB2A; Synonyms=RAB2; OS Canis lupus familiaris (Dog) (Canis familiaris). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis. OX NCBI_TaxID=9615; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2115402; DOI=10.1016/0092-8674(90)90369-p; RA Chavrier P., Parton R.G., Hauri H.P., Simons K., Zerial M.; RT "Localization of low molecular weight GTP binding proteins to exocytic and RT endocytic compartments."; RL Cell 62:317-329(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Cocker spaniel; TISSUE=Kidney; RX PubMed=2123294; DOI=10.1128/mcb.10.12.6578-6585.1990; RA Chavrier P., Vingron M., Sander C., Simons K., Zerial M.; RT "Molecular cloning of YPT1/SEC4-related cDNAs from an epithelial cell RT line."; RL Mol. Cell. Biol. 10:6578-6585(1990). RN [3] RP ISOPRENYLATION AT CYS-211 AND CYS-212. RX PubMed=1648736; DOI=10.1073/pnas.88.14.6264; RA Khosravi-Far R., Lutz R.J., Cox A.D., Conroy L., Bourne J.R., Sinensky M., RA Balch W.E., Buss J.E., Der C.J.; RT "Isoprenoid modification of rab proteins terminating in CC or CXC motifs."; RL Proc. Natl. Acad. Sci. U.S.A. 88:6264-6268(1991). 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. Rabs cycle between active GTP-bound and inactive CC GDP-bound states. In their active state, drive transport of vesicular CC carriers from donor organelles to acceptor organelles to regulate the CC membrane traffic that maintains organelle identity and morphology. CC RAB2A regulates autophagy by promoting autophagosome-lysosome fusion CC via recruitment of the HOPS endosomal tethering complex; this process CC involves autophagosomal RAB2A and lysosomal RAB39A recruitment of HOPS CC subcomplexes VPS39-VPS11 and VPS41-VPS16-VPS18-VPS33A, respectively, CC which assemble into a functional complex to mediate membrane tethering CC and SNAREs-driven membrane fusion. Required for protein transport from CC the endoplasmic reticulum to the Golgi complex. Regulates the compacted CC morphology of the Golgi. Together with RAB2B, redundantly required for CC efficient autophagic flux. {ECO:0000250|UniProtKB:P61019}. 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:P53994}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670; CC Evidence={ECO:0000250|UniProtKB:P53994}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P61019}; CC -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors CC (GEFs) which promote the exchange of bound GDP for free GTP, GTPase CC activating proteins (GAPs) which increase the GTP hydrolysis activity, CC and GDP dissociation inhibitors (GDIs) which inhibit the dissociation CC of the nucleotide from the GTPase. {ECO:0000305}. CC -!- SUBUNIT: Interacts with PRKCI. Interacts with TRIP11 (By similarity). CC Interacts (in GTP-bound form) with GARIN1B (By similarity). Interacts CC (GTP-bound) with HOPS complex component VPS39; interaction contributes CC to obtaining a functional HOPS complex that promotes autophagosome- CC lysosome membrane fusion driven by STX17-SNAP29-VAMP8. May interact CC with VPS41 (By similarity). {ECO:0000250|UniProtKB:P53994, CC ECO:0000250|UniProtKB:P61019}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum-Golgi intermediate CC compartment membrane {ECO:0000250|UniProtKB:P61019}; Lipid-anchor CC {ECO:0000250|UniProtKB:P61019}; Cytoplasmic side {ECO:0000305}. CC Melanosome {ECO:0000250|UniProtKB:P61019}. Endoplasmic reticulum CC membrane {ECO:0000250|UniProtKB:P61019}; Lipid-anchor CC {ECO:0000250|UniProtKB:P61019}; Cytoplasmic side {ECO:0000305}. Golgi CC apparatus membrane {ECO:0000250|UniProtKB:P61019}; Lipid-anchor CC {ECO:0000250|UniProtKB:P61019}; Cytoplasmic side {ECO:0000305}. CC Cytoplasmic vesicle, secretory vesicle, acrosome CC {ECO:0000250|UniProtKB:P53994}. Cytoplasmic vesicle, autophagosome CC membrane {ECO:0000250|UniProtKB:P53994}; Lipid-anchor CC {ECO:0000250|UniProtKB:P61019}; Cytoplasmic side {ECO:0000305}. CC Note=Localized in the Golgi apparatus in the round spermatids and in CC the acrosome in the elongating spermatid (By similarity). Identified by CC mass spectrometry in melanosome fractions from stage I to stage IV (By CC similarity). {ECO:0000250|UniProtKB:P53994, CC ECO:0000250|UniProtKB:P61019}. 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:P61106}. CC -!- PTM: Prenylated. Prenylation is required for association with cellular CC membranes. {ECO:0000250|UniProtKB:P61019}. 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; M35521; AAA30888.1; -; mRNA. DR PIR; A39648; A39648. DR RefSeq; NP_001003318.1; NM_001003318.2. DR AlphaFoldDB; P61105; -. DR SMR; P61105; -. DR FunCoup; P61105; 2608. DR STRING; 9615.ENSCAFP00000010623; -. DR BindingDB; P61105; -. DR PaxDb; 9615-ENSCAFP00000010623; -. DR Ensembl; ENSCAFT00000011465; ENSCAFP00000010623; ENSCAFG00000007153. DR Ensembl; ENSCAFT00030030591; ENSCAFP00030026675; ENSCAFG00030016494. DR Ensembl; ENSCAFT00040031288; ENSCAFP00040027202; ENSCAFG00040016877. DR Ensembl; ENSCAFT00805022661; ENSCAFP00805017838; ENSCAFG00805012294. DR Ensembl; ENSCAFT00845050528.1; ENSCAFP00845039616.1; ENSCAFG00845028560.1. DR GeneID; 404009; -. DR KEGG; cfa:404009; -. DR CTD; 5862; -. DR VEuPathDB; HostDB:ENSCAFG00845028560; -. DR eggNOG; KOG0098; Eukaryota. DR GeneTree; ENSGT00940000153886; -. DR InParanoid; P61105; -. DR OrthoDB; 9989112at2759; -. DR PRO; PR:P61105; -. DR Proteomes; UP000805418; Chromosome 29. DR GO; GO:0001669; C:acrosomal vesicle; IEA:UniProtKB-SubCell. DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; ISS:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB. DR GO; GO:0042470; C:melanosome; ISS:UniProtKB. DR GO; GO:0003925; F:G protein activity; ISS:UniProtKB. DR GO; GO:0019003; F:GDP binding; ISS:UniProtKB. DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB. DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB. DR GO; GO:0061909; P:autophagosome-lysosome fusion; ISS:UniProtKB. DR GO; GO:0007030; P:Golgi organization; ISS:UniProtKB. DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB. DR CDD; cd01866; Rab2; 1. DR FunFam; 3.40.50.300:FF:000275; Putative ras-related protein Rab-2A; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR050209; Rab_GTPases_membrane_traffic. DR InterPro; IPR005225; Small_GTP-bd. DR InterPro; IPR001806; Small_GTPase. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR47979; DRAB11-RELATED; 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; Cytoplasmic vesicle; Endoplasmic reticulum; KW ER-Golgi transport; Golgi apparatus; GTP-binding; Hydrolase; Lipoprotein; KW Magnesium; Membrane; Metal-binding; Nucleotide-binding; Prenylation; KW Protein transport; Reference proteome; Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P61019" FT CHAIN 2..212 FT /note="Ras-related protein Rab-2A" FT /id="PRO_0000121065" FT REGION 2..19 FT /note="Required for interaction with PRKCI" FT /evidence="ECO:0000250" FT MOTIF 37..42 FT /note="Switch 1" FT /evidence="ECO:0000250|UniProtKB:P61106" FT MOTIF 63..72 FT /note="Switch 2" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 16 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 17 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 18 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 19 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 20 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 20 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P61019" FT BINDING 21 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 38 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 38 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 61 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P61019" FT BINDING 64 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 119 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 120 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 122 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 150 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT BINDING 151 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P61106" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:P61019" FT LIPID 211 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000269|PubMed:1648736" FT LIPID 212 FT /note="S-geranylgeranyl cysteine" FT /evidence="ECO:0000269|PubMed:1648736" SQ SEQUENCE 212 AA; 23546 MW; F8731E3F8FB399A3 CRC64; MAYAYLFKYI IIGDTGVGKS CLLLQFTDKR FQPVHDLTIG VEFGARMITI DGKQIKLQIW DTAGQESFRS ITRSYYRGAA GALLVYDITR RDTFNHLTTW LEDARQHSNS NMVIMLIGNK SDLESRREVK KEEGEAFARE HGLIFMETSA KTASNVEEAF INTAKEIYEK IQEGVFDINN EANGIKIGPQ HAATNATHAG NQGGQQAGGG CC //