RAB5A_RAT
ID RAB5A_RAT Reviewed; 215 AA.
AC M0RC99; O88565;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Ras-related protein Rab-5A;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P20339};
DE AltName: Full=Small GTP-binding protein rab5 {ECO:0000303|Ref.1};
GN Name=Rab5a {ECO:0000312|RGD:620936};
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=Wistar;
RA Looman A.C., Hofsommer S., Stevens P.A.;
RT "Small GTP-binding protein rab5 from rat type II pneumocytes.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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 extension.
CC Required for the exosomal release of SDCBP, CD63, PDCD6IP and syndecan.
CC Regulates maturation of apoptotic cell-containing phagosomes, probably
CC 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 EEA1. Interacts with
CC RIN1 and GAPVD1, which regulate its pathway, probably by acting as a
CC GEF. Interacts with ALS2CL, SUN2, ZFYVE20 and RUFY1. Interacts with
CC RABEP1; one RABEP1 homodimer binds two RAB5A chains, but at opposite
CC sides of the dimer. Interacts with SGSM1, SGSM3 and PIK3CB. Interacts
CC with RINL. 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}.
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; AF072935; AAC26004.1; -; mRNA.
DR EMBL; AABR06079878; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474184; EDL82849.1; -; Genomic_DNA.
DR EMBL; BC161848; AAI61848.1; -; mRNA.
DR RefSeq; NP_073183.1; NM_022692.1.
DR RefSeq; XP_003751425.1; XM_003751377.4.
DR RefSeq; XP_003752788.1; XM_003752740.4.
DR AlphaFoldDB; M0RC99; -.
DR SMR; M0RC99; -.
DR BioGRID; 249171; 2.
DR IntAct; M0RC99; 4.
DR MINT; M0RC99; -.
DR STRING; 10116.ENSRNOP00000067210; -.
DR PhosphoSitePlus; M0RC99; -.
DR jPOST; M0RC99; -.
DR PaxDb; M0RC99; -.
DR PRIDE; M0RC99; -.
DR Ensembl; ENSRNOT00000100183; ENSRNOP00000096260; ENSRNOG00000062595.
DR GeneID; 100361891; -.
DR GeneID; 64633; -.
DR KEGG; rno:100361891; -.
DR KEGG; rno:64633; -.
DR CTD; 100361891; -.
DR CTD; 5868; -.
DR RGD; 620936; Rab5a.
DR eggNOG; KOG0092; Eukaryota.
DR GeneTree; ENSGT00940000154337; -.
DR InParanoid; M0RC99; -.
DR OrthoDB; 1340129at2759; -.
DR TreeFam; TF300199; -.
DR Reactome; R-RNO-1660499; Synthesis of PIPs at the plasma membrane.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-RNO-8873719; RAB geranylgeranylation.
DR Reactome; R-RNO-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-RNO-983231; Factors involved in megakaryocyte development and platelet production.
DR PRO; PR:M0RC99; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Proteomes; UP000234681; Unassembled WGS sequence.
DR GO; GO:0015629; C:actin cytoskeleton; ISO:RGD.
DR GO; GO:0098993; C:anchored component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0030424; C:axon; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043679; C:axon terminus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0098559; C:cytoplasmic side of early endosome membrane; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; ISO:RGD.
DR GO; GO:0005768; C:endosome; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010008; C:endosome membrane; ISO:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045121; C:membrane raft; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:ParkinsonsUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0098842; C:postsynaptic early endosome; IDA:SynGO.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0055037; C:recycling endosome; IDA:RGD.
DR GO; GO:0001726; C:ruffle; ISO:RGD.
DR GO; GO:0036477; C:somatodendritic compartment; IDA:ParkinsonsUK-UCL.
DR GO; GO:0008021; C:synaptic vesicle; IDA:SynGO.
DR GO; GO:0043195; C:terminal bouton; HDA:ParkinsonsUK-UCL.
DR GO; GO:0042589; C:zymogen granule membrane; IDA:RGD.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; ISO:RGD.
DR GO; GO:0051021; F:GDP-dissociation inhibitor binding; IDA:RGD.
DR GO; GO:0005525; F:GTP binding; ISO:RGD.
DR GO; GO:0003924; F:GTPase activity; ISO:RGD.
DR GO; GO:0019001; F:guanyl nucleotide binding; ISO:RGD.
DR GO; GO:0150093; P:amyloid-beta clearance by transcytosis; ISO:RGD.
DR GO; GO:0045022; P:early endosome to late endosome transport; ISO:RGD.
DR GO; GO:0006897; P:endocytosis; IMP:RGD.
DR GO; GO:0007032; P:endosome organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR GO; GO:0045921; P:positive regulation of exocytosis; ISO:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:2000286; P:receptor internalization involved in canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0030100; P:regulation of endocytosis; IBA:GO_Central.
DR GO; GO:0051036; P:regulation of endosome size; ISO:RGD.
DR GO; GO:0051489; P:regulation of filopodium assembly; ISO:RGD.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IMP:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISS:ParkinsonsUK-UCL.
DR GO; GO:0036465; P:synaptic vesicle recycling; ISO:RGD.
DR GO; GO:0016192; P:vesicle-mediated transport; NAS:RGD.
DR GO; GO:0039694; P:viral RNA genome replication; ISO:RGD.
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_0000430501"
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"
FT CONFLICT 167
FT /note="P -> S (in Ref. 1; AAC26004, 3; EDL82849 and 4;
FT AAI61848)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 215 AA; 23625 MW; 716AB5CC4ECAFD77 CRC64;
MANRGATRPN GPNTGNKICQ FKLVLLGESA VGKSSLVLRF VKGQFHEFQE STIGAAFLTQ
TVCLDDTTVK FEIWDTAGQE RYHSLAPMYY RGAQAAIVVY DITNEESFSR AKNWVKELQR
QASPNIVIAL SGNKADLANK RAVDFQEAQS YADDNSLLFM ETSAKTPMNV NEIFMAIAKK
LPKNEPQNPG ANSARGRGVD LTEPAQPARS QCCSN
