RAB5A_MACFA
ID RAB5A_MACFA Reviewed; 215 AA.
AC P61271;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Ras-related protein Rab-5A;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P20339};
GN Name=RAB5A; ORFNames=QmoA-10711;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Medulla oblongata;
RA Osada N., Hida M., Kusuda J., Tanuma R., Iseki K., Hirai M., Terao K.,
RA Suzuki Y., Sugano S., Hashimoto K.;
RT "Isolation of full-length cDNA clones from macaque brain cDNA libraries.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
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 RAB5A is required for the fusion of plasma membranes and early
CC endosomes. Contributes to the regulation of filopodia
CC extension.Required for the exosomal release of SDCBP, CD63, PDCD6IP and
CC syndecan. Regulates maturation of apoptotic cell-containing phagosomes,
CC probably downstream of DYN2 and PIK3C3. {ECO:0000250|UniProtKB:P18066,
CC ECO:0000250|UniProtKB:P20339, ECO:0000250|UniProtKB:Q9CQD1}.
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 (By
CC similarity). Interacts with PIK3CB. Interacts with EEA1. Interacts with
CC RIN1 and GAPVD1, which regulate its pathway, probably by acting as a
CC GEF. Interacts with RINL. Interacts with ALS2CL, SUN2, ZFYVE20 and
CC RUFY1. Interacts with RABEP1; one RABEP1 homodimer binds two RAB5A
CC chains, but at opposite sides of the dimer. Interacts with OCRL and
CC INPP5F. May be a component of a complex composed of RAB5A, DYN2 and
CC PIK3C3. Does not interact with the BLOC-3 complex (heterodimer of HPS1
CC and HPS4). Interacts with CLN5. Interacts with APPL2 (By similarity).
CC Interacts with F8A1/F8A2/F8A3 (By similarity). Found in a complex with
CC F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A
CC onto early endosomes (By similarity). {ECO:0000250|UniProtKB:P18066,
CC ECO:0000250|UniProtKB:P20339, ECO:0000250|UniProtKB:Q0IIG7,
CC ECO:0000250|UniProtKB:Q9CQD1}.
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; AB062987; BAB60752.1; -; mRNA.
DR RefSeq; NP_001270902.1; NM_001283973.1.
DR RefSeq; XP_005545726.1; XM_005545669.2.
DR AlphaFoldDB; P61271; -.
DR SMR; P61271; -.
DR STRING; 9541.XP_005545726.1; -.
DR Ensembl; ENSMFAT00000024008; ENSMFAP00000005334; ENSMFAG00000002326.
DR GeneID; 102144117; -.
DR CTD; 5868; -.
DR VEuPathDB; HostDB:ENSMFAG00000002326; -.
DR eggNOG; KOG0092; Eukaryota.
DR GeneTree; ENSGT00940000154337; -.
DR OMA; DGIDCAE; -.
DR OrthoDB; 1340129at2759; -.
DR Proteomes; UP000233100; Chromosome 2.
DR Bgee; ENSMFAG00000002326; Expressed in temporal lobe and 13 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
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:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
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 2: Evidence at transcript 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_0000121105"
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 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 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"
SQ SEQUENCE 215 AA; 23659 MW; DDDE3FD8B37C2606 CRC64;
MANRGATRPN GPNTGNKICQ FKLVLLGESA VGKSSLVLRF VKGQFHEFQE STIGAAFLTQ
TVCLDDTTVK FEIWDTAGQE RYHSLAPMYY RGAQAAIVVY DITNEESFAR AKNWVKELQR
QASPNIVIAL SGNKADLANK RAVDFQEAQS YADDNSLLFM ETSAKTSMNV NEIFMAIAKK
LPKNEPQNPG ANSARGRGVD LTEPTQPTRS QCCSN
