RAB7A_RAT
ID RAB7A_RAT Reviewed; 207 AA.
AC P09527; Q4AEF6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Ras-related protein Rab-7a;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P51149};
DE AltName: Full=Ras-related protein BRL-RAS;
DE AltName: Full=Ras-related protein p23;
GN Name=Rab7a; Synonyms=Rab7;
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=Buffalo; TISSUE=Liver;
RX PubMed=3057452; DOI=10.1093/nar/16.21.9979;
RA Bucci C., Franzio R., Chiariotti L., Brown A.L., Rechler M.M., Bruni C.B.;
RT "A new member of the ras gene superfamily identified in a rat liver cell
RT line.";
RL Nucleic Acids Res. 16:9979-9994(1988).
RN [2]
RP SEQUENCE REVISION TO N-TERMINUS.
RA Bruni C.B.;
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Bone;
RA Zhao H., Gao L., Vaananen K.H.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer 344/DuCrj, and LEC/Crj;
RX PubMed=15978772; DOI=10.1016/j.ygeno.2005.05.007;
RA Tsuji A.B., Sugyo A., Ogiu T., Sagara M., Kimura T., Ishikawa A., Sudo H.,
RA Ohtsuki M., Aburatani H., Imai T., Harada Y.N.;
RT "Fine mapping of radiation susceptibility and gene expression analysis of
RT LEC congenic rat lines.";
RL Genomics 86:271-279(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH
RP RAC1.
RX PubMed=16040606; DOI=10.1074/jbc.m414213200;
RA Sun Y., Bueki K.G., Ettala O., Vaeaeraeniemi J.P., Vaeaenaenen H.K.;
RT "Possible role of direct Rac1-Rab7 interaction in ruffled border formation
RT of osteoclasts.";
RL J. Biol. Chem. 280:32356-32361(2005).
RN [7]
RP FUNCTION, INTERACTION WITH NTRK1/TRKA, AND TISSUE SPECIFICITY.
RX PubMed=16306406; DOI=10.1523/jneurosci.2029-05.2005;
RA Saxena S., Bucci C., Weis J., Kruttgen A.;
RT "The small GTPase Rab7 controls the endosomal trafficking and neuritogenic
RT signaling of the nerve growth factor receptor TrkA.";
RL J. Neurosci. 25:10930-10940(2005).
RN [8]
RP SUBUNIT, AND INTERACTION WITH CHM.
RX PubMed=18756270; DOI=10.1038/emboj.2008.164;
RA Guo Z., Wu Y.W., Das D., Delon C., Cramer J., Yu S., Thuns S., Lupilova N.,
RA Waldmann H., Brunsveld L., Goody R.S., Alexandrov K., Blankenfeldt W.;
RT "Structures of RabGGTase-substrate/product complexes provide insights into
RT the evolution of protein prenylation.";
RL EMBO J. 27:2444-2456(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1-185 IN COMPLEX WITH GTP ANALOG
RP AND CHM.
RX PubMed=15186776; DOI=10.1016/j.cell.2004.05.017;
RA Rak A., Pylypenko O., Niculae A., Pyatkov K., Goody R.S., Alexandrov K.;
RT "Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab
RT prenylation and choroideremia disease.";
RL Cell 117:749-760(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 playing a key role in the regulation of endo-
CC lysosomal trafficking. Governs early-to-late endosomal maturation,
CC microtubule minus-end as well as plus-end directed endosomal migration
CC and positioning, and endosome-lysosome transport through different
CC protein-protein interaction cascades (By similarity). Plays a central
CC role, not only in endosomal traffic, but also in many other cellular
CC and physiological events, such as growth-factor-mediated cell
CC signaling, nutrient-transporter-mediated nutrient uptake, neurotrophin
CC transport in the axons of neurons and lipid metabolism (By similarity).
CC Also involved in regulation of some specialized endosomal membrane
CC trafficking, such as maturation of melanosomes, pathogen-induced
CC phagosomes (or vacuoles) and autophagosomes (By similarity). Plays a
CC role in the maturation and acidification of phagosomes that engulf
CC pathogens, such as S.aureus and Mycobacteria (By similarity). Plays a
CC role in the fusion of phagosomes with lysosomes (By similarity). Plays
CC important roles in microbial pathogen infection and survival, as well
CC as in participating in the life cycle of viruses (By similarity).
CC Microbial pathogens possess survival strategies governed by RAB7A,
CC sometimes by employing RAB7A function (e.g. Salmonella) and sometimes
CC by excluding RAB7A function (e.g. Mycobacterium) (By similarity). In
CC concert with RAC1, plays a role in regulating the formation of RBs
CC (ruffled borders) in osteoclasts (PubMed:16040606). Controls the
CC endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA
CC (PubMed:16306406). Regulates the endocytic trafficking of the EGF-EGFR
CC complex by regulating its lysosomal degradation (By similarity).
CC Involved in the ADRB2-stimulated lipolysis through lipophagy, a
CC cytosolic lipase-independent autophagic pathway. Required for the
CC exosomal release of SDCBP, CD63 and syndecan (By similarity). Required
CC for vesicular trafficking and cell surface expression of ACE2 (By
CC similarity). May play a role in PRPH neuronal intermediate filament
CC assembly (By similarity). {ECO:0000250|UniProtKB:P51149,
CC ECO:0000250|UniProtKB:P51150, ECO:0000269|PubMed:16040606,
CC ECO:0000269|PubMed:16306406}.
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:P51149};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P51149};
CC -!- SUBUNIT: Interacts with NTRK1/TRKA (PubMed:16306406). Interacts with
CC RILP (By similarity). Interacts with PSMA7 (By similarity). Interacts
CC with RNF115 (By similarity). Interacts with and FYCO1 (By similarity).
CC Interacts with the PIK3C3/VPS34-PIK3R4 complex (By similarity). The
CC GTP-bound form interacts with OSBPL1A (By similarity). The GTP-bound
CC form interacts with RAC1 (PubMed:16040606). Interacts with CLN3 (By
CC similarity). Interacts with CHM, the substrate-binding subunit of the
CC Rab geranylgeranyltransferase complex (PubMed:18756270,
CC PubMed:15186776). Interacts with C9orf72 (By similarity). Does not
CC interact with HPS4 and the BLOC-3 complex (heterodimer of HPS1 and
CC HPS4). Interacts with CLN5 (By similarity). Interacts with PLEKHM1 (via
CC N- and C-terminus) (By similarity). Interacts with PRPH; the
CC interaction is direct (By similarity). Interacts with VPS13A (By
CC similarity). The GDP-bound form interacts with RIMOC1 (By similarity).
CC Interacts with the MON1A-CCZ1B complex and this interaction is enhanced
CC in the presence of RIMOC1 (By similarity).
CC {ECO:0000250|UniProtKB:P51149, ECO:0000250|UniProtKB:P51150,
CC ECO:0000269|PubMed:15186776, ECO:0000269|PubMed:16040606,
CC ECO:0000269|PubMed:16306406, ECO:0000269|PubMed:18756270}.
CC -!- INTERACTION:
CC P09527; P37727: Chm; NbExp=2; IntAct=EBI-916225, EBI-1039231;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000250|UniProtKB:P51149}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Late endosome membrane
CC {ECO:0000269|PubMed:16040606}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Lysosome membrane
CC {ECO:0000269|PubMed:16040606}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Melanosome membrane
CC {ECO:0000250|UniProtKB:P51149}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cytoplasmic vesicle,
CC autophagosome membrane {ECO:0000250|UniProtKB:P51149}; Peripheral
CC membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Lipid
CC droplet {ECO:0000250|UniProtKB:P51150}. Endosome membrane
CC {ECO:0000250|UniProtKB:P51149}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:P51150}. Mitochondrion membrane
CC {ECO:0000250|UniProtKB:P51149}; Peripheral membrane protein
CC {ECO:0000305}. Note=Colocalizes with OSBPL1A at the late endosome.
CC Found in the ruffled border (a late endosomal-like compartment in the
CC plasma membrane) of bone-resorbing osteoclasts. Recruited to phagosomes
CC containing S.aureus or Mycobacterium. Lipid droplet localization is
CC increased upon ADRB2 stimulation. Recruited to damaged mitochondria
CC during mitophagy in a RIMOC1-dependent manner.
CC {ECO:0000250|UniProtKB:P51149, ECO:0000250|UniProtKB:P51150}.
CC -!- TISSUE SPECIFICITY: Expressed in osteoclasts and in neurons.
CC {ECO:0000269|PubMed:16040606, ECO:0000269|PubMed:16306406}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; X12535; CAA31053.1; -; mRNA.
DR EMBL; AF286535; AAG00543.1; -; mRNA.
DR EMBL; AB158427; BAE16999.1; -; mRNA.
DR EMBL; AB158428; BAE17000.1; -; mRNA.
DR EMBL; BC072470; AAH72470.1; -; mRNA.
DR PIR; S01934; S01934.
DR RefSeq; NP_076440.1; NM_023950.3.
DR RefSeq; XP_006236911.1; XM_006236849.3.
DR PDB; 1VG0; X-ray; 2.20 A; B=1-207.
DR PDB; 1VG1; X-ray; 1.90 A; A=1-185.
DR PDB; 1VG8; X-ray; 1.70 A; A/B/C/D=1-207.
DR PDB; 1VG9; X-ray; 2.50 A; B/D/F/H=1-185.
DR PDBsum; 1VG0; -.
DR PDBsum; 1VG1; -.
DR PDBsum; 1VG8; -.
DR PDBsum; 1VG9; -.
DR AlphaFoldDB; P09527; -.
DR SMR; P09527; -.
DR BioGRID; 248093; 5.
DR IntAct; P09527; 10.
DR MINT; P09527; -.
DR STRING; 10116.ENSRNOP00000016432; -.
DR iPTMnet; P09527; -.
DR PhosphoSitePlus; P09527; -.
DR SwissPalm; P09527; -.
DR jPOST; P09527; -.
DR PaxDb; P09527; -.
DR PRIDE; P09527; -.
DR Ensembl; ENSRNOT00000016432; ENSRNOP00000016432; ENSRNOG00000012247.
DR GeneID; 29448; -.
DR KEGG; rno:29448; -.
DR UCSC; RGD:61908; rat.
DR CTD; 7879; -.
DR RGD; 61908; Rab7a.
DR eggNOG; KOG0394; Eukaryota.
DR GeneTree; ENSGT00940000155864; -.
DR InParanoid; P09527; -.
DR OMA; IQACPRD; -.
DR OrthoDB; 1172019at2759; -.
DR PhylomeDB; P09527; -.
DR TreeFam; TF105605; -.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-8854214; TBC/RABGAPs.
DR Reactome; R-RNO-8873719; RAB geranylgeranylation.
DR Reactome; R-RNO-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR Reactome; R-RNO-9013405; RHOD GTPase cycle.
DR Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR Reactome; R-RNO-9013407; RHOH GTPase cycle.
DR Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR Reactome; R-RNO-9035034; RHOF GTPase cycle.
DR EvolutionaryTrace; P09527; -.
DR PRO; PR:P09527; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000012247; Expressed in lung and 19 other tissues.
DR ExpressionAtlas; P09527; baseline and differential.
DR Genevisible; P09527; RN.
DR GO; GO:0097208; C:alveolar lamellar body; IDA:RGD.
DR GO; GO:0098993; C:anchored component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; ISO:RGD.
DR GO; GO:0032419; C:extrinsic component of lysosome membrane; ISS:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005770; C:late endosome; IDA:RGD.
DR GO; GO:0031902; C:late endosome membrane; ISS:GO_Central.
DR GO; GO:0005811; C:lipid droplet; ISS:GO_Central.
DR GO; GO:0005764; C:lysosome; ISO:RGD.
DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0034045; C:phagophore assembly site membrane; ISO:RGD.
DR GO; GO:0030904; C:retromer complex; IEA:Ensembl.
DR GO; GO:0043195; C:terminal bouton; HDA:ParkinsonsUK-UCL.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; IDA:RGD.
DR GO; GO:0005525; F:GTP binding; IDA:RGD.
DR GO; GO:0003924; F:GTPase activity; ISO:RGD.
DR GO; GO:1905394; F:retromer complex binding; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; IPI:RGD.
DR GO; GO:0000045; P:autophagosome assembly; ISO:RGD.
DR GO; GO:0045453; P:bone resorption; IMP:RGD.
DR GO; GO:0045022; P:early endosome to late endosome transport; ISS:UniProtKB.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:RGD.
DR GO; GO:0099638; P:endosome to plasma membrane protein transport; ISS:UniProtKB.
DR GO; GO:0007174; P:epidermal growth factor catabolic process; ISO:RGD.
DR GO; GO:0051650; P:establishment of vesicle localization; ISO:RGD.
DR GO; GO:0046907; P:intracellular transport; ISO:RGD.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0061724; P:lipophagy; ISS:GO_Central.
DR GO; GO:1903542; P:negative regulation of exosomal secretion; ISO:RGD.
DR GO; GO:0090383; P:phagosome acidification; ISS:UniProtKB.
DR GO; GO:0090385; P:phagosome-lysosome fusion; ISS:UniProtKB.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; ISO:RGD.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0048524; P:positive regulation of viral process; ISO:RGD.
DR GO; GO:0006622; P:protein targeting to lysosome; ISO:RGD.
DR GO; GO:0022615; P:protein to membrane docking; ISO:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISO:RGD.
DR GO; GO:0019076; P:viral release from host cell; 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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Autophagy; Cytoplasmic vesicle; Endosome;
KW GTP-binding; Hydrolase; Lipid degradation; Lipid droplet; Lipid metabolism;
KW Lipoprotein; Lysosome; Membrane; Methylation; Mitochondrion;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Protein transport;
KW Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P51149"
FT CHAIN 2..207
FT /note="Ras-related protein Rab-7a"
FT /id="PRO_0000121124"
FT MOTIF 37..45
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 15..22
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 34..40
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 63..67
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 125..128
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT BINDING 156..157
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:P51149"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 207
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 205
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 207
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:1VG8"
FT HELIX 21..30
FT /evidence="ECO:0007829|PDB:1VG8"
FT STRAND 42..54
FT /evidence="ECO:0007829|PDB:1VG8"
FT STRAND 56..64
FT /evidence="ECO:0007829|PDB:1VG8"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:1VG8"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1VG8"
FT STRAND 82..89
FT /evidence="ECO:0007829|PDB:1VG8"
FT HELIX 93..97
FT /evidence="ECO:0007829|PDB:1VG8"
FT HELIX 99..110
FT /evidence="ECO:0007829|PDB:1VG8"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:1VG8"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:1VG8"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:1VG1"
FT HELIX 136..145
FT /evidence="ECO:0007829|PDB:1VG8"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:1VG8"
FT TURN 156..159
FT /evidence="ECO:0007829|PDB:1VG8"
FT HELIX 162..185
FT /evidence="ECO:0007829|PDB:1VG8"
SQ SEQUENCE 207 AA; 23504 MW; A2AF33B02F672971 CRC64;
MTSRKKVLLK VIILGDSGVG KTSLMNQYVN KKFSNQYKAT IGADFLTKEV MVDDRLVTMQ
IWDTAGQERF QSLGVAFYRG ADCCVLVFDV TAPNTFKTLD SWRDEFLIQA SPRDPENFPF
VVLGNKIDLE NRQVATKRAQ AWCYSKNNIP YFETSAKEAI NVEQAFQTIA RNALKQETEV
ELYNEFPEPI KLDKNERAKA SAESCSC
