RAB5A_BOVIN
ID RAB5A_BOVIN Reviewed; 215 AA.
AC Q0IIG7;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Ras-related protein Rab-5A;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P20339};
GN Name=RAB5A;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Brain cortex;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP MUTAGENESIS OF GLN-79, FUNCTION, INTERACTION WITH F8A1/F8A2/F8A3, AND FOUND
RP IN A COMPLEX WITH F8A1/F8A2/F8A3 AND HTT.
RX PubMed=16476778; DOI=10.1083/jcb.200509091;
RA Pal A., Severin F., Lommer B., Shevchenko A., Zerial M.;
RT "Huntingtin-HAP40 complex is a novel Rab5 effector that regulates early
RT endosome motility and is up-regulated in Huntington's disease.";
RL J. Cell Biol. 172:605-618(2006).
CC -!- FUNCTION: Small GTPase which cycles between active GTP-bound and
CC inactive GDP-bound states. In its active state, binds to a variety of
CC effector proteins to regulate cellular responses such as of
CC intracellular membrane trafficking, from the formation of transport
CC vesicles to their fusion with membranes. Active GTP-bound form is able
CC to recruit to membranes different sets of downstream effectors directly
CC responsible for vesicle formation, movement, tethering and fusion
CC (PubMed:16476778) (By similarity). RAB5A is required for the fusion of
CC plasma membranes and early endosomes. Contributes to the regulation of
CC filopodia extension.Required for the exosomal release of SDCBP, CD63,
CC PDCD6IP and syndecan. Regulates maturation of apoptotic cell-containing
CC phagosomes, probably downstream of DYN2 and PIK3C3.
CC {ECO:0000250|UniProtKB:P18066, ECO:0000250|UniProtKB:P20339,
CC ECO:0000250|UniProtKB:Q9CQD1, ECO:0000269|PubMed:16476778}.
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:P20339};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P20339};
CC -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors
CC (GEFs) which promote the exchange of bound GDP for free GTP.
CC {ECO:0000250|UniProtKB:P18066}.
CC -!- SUBUNIT: Interacts with GDI1; this promotes dissociation from
CC membranes; phosphorylation at Ser-84 disrupts this interaction (By
CC similarity). Interacts with GDI2; phosphorylation at Ser-84 disrupts
CC the interaction (By similarity). Interacts with SGSM1 and SGSM3.
CC Interacts with PIK3CB. Interacts with EEA1. Interacts with RIN1 and
CC GAPVD1, which regulate its pathway, probably by acting as a GEF.
CC Interacts with RINL. Interacts with ALS2CL, SUN2, ZFYVE20 and RUFY1.
CC Interacts with RABEP1; one RABEP1 homodimer binds two RAB5A chains, but
CC at opposite sides of the dimer. Interacts with OCRL and INPP5F. May be
CC a component of a complex composed of RAB5A, DYN2 and PIK3C3. Does not
CC interact with the BLOC-3 complex (heterodimer of HPS1 and HPS4).
CC Interacts with CLN5. Interacts with APPL2 (By similarity). Interacts
CC with F8A1/F8A2/F8A3 (PubMed:16476778). Found in a complex with
CC F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A
CC onto early endosome (PubMed:16476778). {ECO:0000250|UniProtKB:P18066,
CC ECO:0000250|UniProtKB:P20339, ECO:0000250|UniProtKB:Q9CQD1,
CC ECO:0000269|PubMed:16476778}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P20339};
CC Lipid-anchor {ECO:0000250|UniProtKB:P20339}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P18066}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P20339}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P20339}. Melanosome
CC {ECO:0000250|UniProtKB:P20339}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:P20339}. Cell projection, ruffle
CC {ECO:0000250|UniProtKB:P18066}. Membrane
CC {ECO:0000250|UniProtKB:P20339}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P20339}. Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000250|UniProtKB:Q9CQD1}. Endosome membrane
CC {ECO:0000250|UniProtKB:P20339}. Note=Enriched in stage I melanosomes.
CC Alternates between membrane-bound and cytosolic forms.
CC {ECO:0000250|UniProtKB:P20339}.
CC -!- PTM: Phosphorylation of Ser-84 in the switch II region by LRRK2
CC prevents the association of RAB regulatory proteins, including RAB GDP
CC dissociation inhibitors GDI1 and GDI2. {ECO:0000250|UniProtKB:P20339}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; BC122651; AAI22652.1; -; mRNA.
DR RefSeq; NP_001069654.1; NM_001076186.1.
DR AlphaFoldDB; Q0IIG7; -.
DR SMR; Q0IIG7; -.
DR STRING; 9913.ENSBTAP00000056220; -.
DR PaxDb; Q0IIG7; -.
DR PRIDE; Q0IIG7; -.
DR Ensembl; ENSBTAT00000064563; ENSBTAP00000056220; ENSBTAG00000046385.
DR GeneID; 539764; -.
DR KEGG; bta:539764; -.
DR CTD; 5868; -.
DR VEuPathDB; HostDB:ENSBTAG00000046385; -.
DR VGNC; VGNC:33658; RAB5A.
DR eggNOG; KOG0092; Eukaryota.
DR GeneTree; ENSGT00940000154337; -.
DR InParanoid; Q0IIG7; -.
DR OMA; DGIDCAE; -.
DR OrthoDB; 1340129at2759; -.
DR Proteomes; UP000009136; Chromosome 1.
DR Bgee; ENSBTAG00000046385; Expressed in occipital lobe and 104 other tissues.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0098993; C:anchored component of synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:AgBase.
DR GO; GO:0098559; C:cytoplasmic side of early endosome membrane; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098842; C:postsynaptic early endosome; IBA:GO_Central.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
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:0150093; P:amyloid-beta clearance by transcytosis; IEA:Ensembl.
DR GO; GO:0045022; P:early endosome to late endosome transport; IEA:Ensembl.
DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0044788; P:modulation by host of viral process; IEA:Ensembl.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR GO; GO:0045921; P:positive regulation of exocytosis; IEA:Ensembl.
DR GO; GO:2000286; P:receptor internalization involved in canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0030100; P:regulation of endocytosis; IBA:GO_Central.
DR GO; GO:0051036; P:regulation of endosome size; IEA:Ensembl.
DR GO; GO:0051489; P:regulation of filopodium assembly; IBA:GO_Central.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IBA:GO_Central.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0036465; P:synaptic vesicle recycling; IEA:Ensembl.
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 Cell membrane; Cell projection; Cytoplasm; Cytoplasmic vesicle;
KW Endocytosis; Endosome; GTP-binding; Hydrolase; Lipoprotein; Membrane;
KW Nucleotide-binding; Phagocytosis; Phosphoprotein; Prenylation;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..215
FT /note="Ras-related protein Rab-5A"
FT /id="PRO_0000283073"
FT REGION 181..215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 49..57
FT /note="Effector region"
FT /evidence="ECO:0000255"
FT COMPBIAS 186..215
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 27..35
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P20339"
FT BINDING 46..52
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P20339"
FT BINDING 75..79
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P20339,
FT ECO:0000305|PubMed:16476778"
FT BINDING 133..136
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P20339"
FT BINDING 163..165
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P20339"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20339"
FT LIPID 212
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P20339"
FT LIPID 213
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P20339"
FT MUTAGEN 79
FT /note="Q->L: Abnormal enlargement of early endosomes due to
FT endosomes fusion."
FT /evidence="ECO:0000269|PubMed:16476778"
SQ SEQUENCE 215 AA; 23689 MW; DDDE3FD8B36727B6 CRC64;
MANRGATRPN GPNTGNKICQ FKLVLLGESA VGKSSLVLRF VKGQFHEFQE STIGAAFLTQ
TVCLDDTTVK FEIWDTAGQE RYHSLAPMYY RGAQAAIVVY DITNEESFAR AKNWVKELQR
QASPNIVIAL SGNKADLANK RAVDFQEAQS YADDNSLLFM ETSAKTSMNV NEIFMAIAKK
LPKNEPQNPG ANSTRGRGVD LTEPTQPTRS QCCSN
