ID RAB6B_CAEEL Reviewed; 205 AA.
AC Q22782;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 157.
DE RecName: Full=Ras-related protein rab-6.2;
GN Name=rab-6.2 {ECO:0000312|WormBase:T25G12.4};
GN ORFNames=T25G12.4 {ECO:0000312|WormBase:T25G12.4};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP INTERACTION WITH VPS-52, AND SUBCELLULAR LOCATION.
RX PubMed=21613545; DOI=10.1091/mbc.e10-06-0493;
RA Luo L., Hannemann M., Koenig S., Hegermann J., Ailion M., Cho M.K.,
RA Sasidharan N., Zweckstetter M., Rensing S.A., Eimer S.;
RT "The Caenorhabditis elegans GARP complex contains the conserved Vps51
RT subunit and is required to maintain lysosomal morphology.";
RL Mol. Biol. Cell 22:2564-2578(2011).
RN [3]
RP FUNCTION, INTERACTION WITH LIN-10, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF THR-24 AND GLN-69.
RX PubMed=22213799; DOI=10.1083/jcb.201104141;
RA Zhang D., Isack N.R., Glodowski D.R., Liu J., Chen C.C., Xu X.Z.,
RA Grant B.D., Rongo C.;
RT "RAB-6.2 and the retromer regulate glutamate receptor recycling through a
RT retrograde pathway.";
RL J. Cell Biol. 196:85-101(2012).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22992455; DOI=10.1242/jcs.116400;
RA Kimura K., Kimura A.;
RT "Rab6 is required for the exocytosis of cortical granules and the
RT recruitment of separase to the granules during the oocyte-to-embryo
RT transition in Caenorhabditis elegans.";
RL J. Cell Sci. 125:5897-5905(2012).
RN [5]
RP FUNCTION, INTERACTION WITH EAT-17, TISSUE SPECIFICITY, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF THR-24.
RX PubMed=23792950; DOI=10.1534/genetics.113.152538;
RA Straud S., Lee I., Song B., Avery L., You Y.J.;
RT "The jaw of the worm: GTPase-activating protein EAT-17 regulates grinder
RT formation in Caenorhabditis elegans.";
RL Genetics 195:115-125(2013).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=26891225; DOI=10.1371/journal.pone.0149314;
RA Zhang D., Dubey J., Koushika S.P., Rongo C.;
RT "RAB-6.1 and RAB-6.2 Promote Retrograde Transport in C. elegans.";
RL PLoS ONE 11:e0149314-e0149314(2016).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30665892; DOI=10.1242/jcs.223586;
RA Kim J.D., Chun A.Y., Mangan R.J., Brown G., Mourao Pacheco B., Doyle H.,
RA Leonard A., El Bejjani R.;
RT "A conserved retromer-independent function for RAB-6.2 in C. elegans
RT epidermis integrity.";
RL J. Cell Sci. 132:0-0(2019).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=33826611; DOI=10.1371/journal.pgen.1009511;
RA Michaud P., Shah V.N., Adjibade P., Houle F., Quevillon Huberdeau M.,
RA Rioux R., Lavoie-Ouellet C., Gu W., Mazroui R., Simard M.J.;
RT "The RabGAP TBC-11 controls Argonaute localization for proper microRNA
RT function in C. elegans.";
RL PLoS Genet. 17:e1009511-e1009511(2021).
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 (PubMed:22213799). Rabs cycle between an inactive
CC GDP-bound form and an active GTP-bound form that is able to recruit to
CC membranes different set of downstream effectors directly responsible
CC for vesicle formation, movement, tethering and fusion
CC (PubMed:22213799). In its active GTP-bound form, acts redundantly with
CC rab-6.1 (in its active GTP-bound form) to positively regulate the
CC retrograde trafficking of cargo molecules from endosomes to the Golgi
CC compartment (PubMed:22213799, PubMed:26891225). Required for the
CC retrograde trafficking of glr-1, a subunit of AMPA-type glutamate
CC receptors (AMPRs), out of early endosomes and into the Golgi
CC compartment in neurons (PubMed:22213799, PubMed:26891225). Its role in
CC glr-1 trafficking may partly be mediated by its interaction with lin-10
CC and association with components of the retromer complex such as rme-8
CC (PubMed:22213799). Together with rab-6.2, promotes the retrograde
CC trafficking of mig-14 from endosomes to Golgi structures in the
CC intestine (PubMed:26891225). Plays a role in the epidermis to promote
CC cuticle integrity and impermeability of the cuticle barrier to
CC exogenous molecules (PubMed:30665892). May have a role in the
CC glycosylation of the cuticular surface (PubMed:30665892). Required for
CC seam cell division and alae formation (PubMed:33826611). Required for
CC grinder formation, which is the feeding organ that breaks down food
CC (PubMed:23792950). In contrast to rab-6.1, may play a minor role in the
CC exocytosis of secretory vesicles (cortical granules) during the oocyte-
CC to-embryo transition (PubMed:22992455). {ECO:0000269|PubMed:22213799,
CC ECO:0000269|PubMed:22992455, ECO:0000269|PubMed:23792950,
CC ECO:0000269|PubMed:26891225, ECO:0000269|PubMed:30665892,
CC ECO:0000269|PubMed:33826611}.
CC -!- SUBUNIT: Interacts with GARP complex component vps-52
CC (PubMed:21613545). Interacts (in GTP-bound form) with lin-10
CC (PubMed:22213799). May interact (in GTP-bound form) with eat-17
CC (PubMed:23792950). {ECO:0000269|PubMed:21613545,
CC ECO:0000269|PubMed:22213799, ECO:0000269|PubMed:23792950}.
CC -!- SUBCELLULAR LOCATION: Perikaryon {ECO:0000269|PubMed:22213799,
CC ECO:0000269|PubMed:26891225}. Cell projection, dendrite
CC {ECO:0000269|PubMed:22213799, ECO:0000269|PubMed:26891225}. Golgi
CC apparatus {ECO:0000269|PubMed:21613545, ECO:0000269|PubMed:22213799,
CC ECO:0000269|PubMed:26891225}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:22992455}. Note=Co-localizes with glr-1 at or near
CC punctate structures in the neuron cell body and along the ventral cord
CC dendrites (PubMed:22213799). Co-localizes with lin-10 in neuronal cell
CC bodies (PubMed:22213799). Co-localizes with rme-8 in neuronal cell
CC bodies and dendrites (PubMed:22213799). Co-localizes with rab-6.1 in
CC neuronal cell bodies and dendrites and in Golgi structures in neurons
CC and the intestine (PubMed:26891225). Co-localizes with vps-52 at Golgi
CC structures (PubMed:21613545). Co-localizes with rab-6.1 at vesicular
CC structures throughout the oocyte cytoplasm (PubMed:22992455).
CC {ECO:0000269|PubMed:21613545, ECO:0000269|PubMed:22213799,
CC ECO:0000269|PubMed:22992455, ECO:0000269|PubMed:26891225}.
CC -!- TISSUE SPECIFICITY: Highly expressed in body wall muscles, pharyngeal
CC and vulval muscles, hypodermis, intestine, the gonad, coelomocytes, and
CC neurons, including command interneuron (at protein level)
CC (PubMed:22213799). Highly expressed in the terminal bulb muscles
CC (PubMed:23792950). {ECO:0000269|PubMed:22213799,
CC ECO:0000269|PubMed:23792950}.
CC -!- DISRUPTION PHENOTYPE: Grinder formation defects, whereby the grinder is
CC formed, but it is small (PubMed:23792950). Animals have a fragile
CC cuticle phenotype, which is prone to rupturing at random positions
CC along the body (PubMed:30665892). This phenotype is intensified in
CC response to hypotonic shock (PubMed:30665892). Due to a compromised
CC cuticle barrier, which increases permeability to exogenous chemicals,
CC all animals become paralyzed in response to acetylcholine agonist
CC tetramisole or the GABA agonist piperazine (PubMed:30665892). Resistant
CC to infection by the bacterium M. nematophilum and does not exhibit a
CC deformity at the anal region phenotype (also known as a dar phenotype),
CC which is possibly indicative of cuticle glycosylation defects
CC (PubMed:30665892). Reduces spontaneous reversal rate and
CC mechanosensitivity (PubMed:22213799). Disrupts the localization of glr-
CC 1, and there is a decreased number of glr-1-positive puncta along the
CC ventral cord dendrites (PubMed:22213799, PubMed:26891225). The reduced
CC number of glr-1-positive puncta along the ventral cord dendrites
CC phenotype is suppressed in an unc-11 e47 mutant background
CC (PubMed:22213799). The number of glr-1-positive puncta is further
CC reduced in a rab-6.1 RNAi-mediated knockdown in glr-1 expressing
CC neurons (PubMed:26891225). RNAi-mediated knockdown results in delayed
CC growth and grinder formation defects (PubMed:23792950). RNAi-mediated
CC knockdown disrupts seam cell division and alae formation
CC (PubMed:33826611). RNAi-mediated knockdown suppresses the seam cell
CC division and alae formation defects in the tbc-11 ok2576 mutant
CC (PubMed:33826611). {ECO:0000269|PubMed:22213799,
CC ECO:0000269|PubMed:23792950, ECO:0000269|PubMed:26891225,
CC ECO:0000269|PubMed:30665892, ECO:0000269|PubMed:33826611}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; BX284606; CCD74453.1; -; Genomic_DNA.
DR PIR; T34375; T34375.
DR RefSeq; NP_510790.1; NM_078389.3.
DR AlphaFoldDB; Q22782; -.
DR SMR; Q22782; -.
DR BioGRID; 46636; 7.
DR IntAct; Q22782; 3.
DR STRING; 6239.T25G12.4.1; -.
DR EPD; Q22782; -.
DR PaxDb; 6239-T25G12-4; -.
DR EnsemblMetazoa; T25G12.4.1; T25G12.4.1; WBGene00004270.
DR GeneID; 181759; -.
DR KEGG; cel:CELE_T25G12.4; -.
DR UCSC; T25G12.4; c. elegans.
DR AGR; WB:WBGene00004270; -.
DR WormBase; T25G12.4; CE07541; WBGene00004270; rab-6.2.
DR eggNOG; KOG0094; Eukaryota.
DR GeneTree; ENSGT00940000159656; -.
DR HOGENOM; CLU_041217_10_2_1; -.
DR InParanoid; Q22782; -.
DR OMA; TRFVYDH; -.
DR OrthoDB; 5483572at2759; -.
DR PhylomeDB; Q22782; -.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR Reactome; R-CEL-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR Reactome; R-CEL-6811438; Intra-Golgi traffic.
DR Reactome; R-CEL-6811440; Retrograde transport at the Trans-Golgi-Network.
DR Reactome; R-CEL-8854214; TBC/RABGAPs.
DR Reactome; R-CEL-8873719; RAB geranylgeranylation.
DR Reactome; R-CEL-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; Q22782; -.
DR PRO; PR:Q22782; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00004270; Expressed in pharyngeal muscle cell (C elegans) and 3 other cell types or tissues.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0031985; C:Golgi cisterna; IDA:WormBase.
DR GO; GO:0000138; C:Golgi trans cisterna; IDA:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IMP:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:UniProtKB.
DR GO; GO:0042335; P:cuticle development; IMP:UniProtKB.
DR GO; GO:0034498; P:early endosome to Golgi transport; IMP:UniProtKB.
DR GO; GO:0006891; P:intra-Golgi vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0007638; P:mechanosensory behavior; IMP:UniProtKB.
DR GO; GO:2000253; P:positive regulation of feeding behavior; IMP:UniProtKB.
DR GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR GO; GO:1903539; P:protein localization to postsynaptic membrane; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:2000311; P:regulation of AMPA receptor activity; IMP:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IBA:GO_Central.
DR GO; GO:0006890; P:retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum; IBA:GO_Central.
DR CDD; cd01861; Rab6; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR NCBIfam; TIGR00231; small_GTP; 1.
DR PANTHER; PTHR47977:SF37; RAB FAMILY GTPASE; 1.
DR PANTHER; PTHR47977; RAS-RELATED PROTEIN RAB; 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 Cell projection; Cytoplasmic vesicle; Golgi apparatus; GTP-binding;
KW Lipoprotein; Methylation; Nucleotide-binding; Prenylation;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..205
FT /note="Ras-related protein rab-6.2"
FT /id="PRO_0000121119"
FT BINDING 18..25
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 42
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 66..70
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 124..127
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 205
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 203
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 205
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 24
FT /note="T->N: Constitutively inactive (GDP-locked form). May
FT abolishes interaction with eat-17. Diffusely distributed in
FT the dendrites and cell body cytosol of neurons. Disrupts
FT the punctate localization of lin-10."
FT /evidence="ECO:0000269|PubMed:22213799,
FT ECO:0000269|PubMed:23792950"
FT MUTAGEN 69
FT /note="Q->L: Constitutively active (GTP-locked form).
FT Reduces spontaneous reversal rate and mechanosensitivity.
FT Punctate localization in the dendrites and cell body
FT cytosol of neurons as in wild-type. Promotes the punctate
FT localization of lin-10. Few glr-1-positive ventral cord
FT puncta accumulate, but several large glr-1-positive puncta
FT accumulate in neuron cell bodies. This is suppressed in a
FT unc-11 e47 mutant background."
FT /evidence="ECO:0000269|PubMed:22213799"
SQ SEQUENCE 205 AA; 23365 MW; CFD639343EB5B552 CRC64;
MSDFGNPLKK FKLVFLGEQS VGKTSLITRF MYDSFDNTYQ ATIGIDFLSK TMYLEDRTVR
LQLWDTAGQE RFRSLIPSYI RDSTVAVVVY DITNSNSFHQ TSKWIDDVRT ERGSDVIIML
VGNKTDLSDK RQVTTDEGER KAKELNVMFI ETSAKAGYNV KQLFRRIAGA LPGIIKDDPV
EPPNVVTMDP IRQRQIVTDE GSCWC
//
