ID ARL8_DROME Reviewed; 186 AA.
AC Q9VHV5;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 27-MAR-2024, entry version 164.
DE RecName: Full=ADP-ribosylation factor-like protein 8 {ECO:0000303|PubMed:29940804, ECO:0000312|FlyBase:FBgn0037551};
DE AltName: Full=Novel small G protein indispensable for equal chromosome segregation;
DE Short=dGie;
GN Name=Arl8 {ECO:0000303|PubMed:29940804, ECO:0000312|FlyBase:FBgn0037551};
GN Synonyms=Gie {ECO:0000303|PubMed:15331635,
GN ECO:0000312|FlyBase:FBgn0037551};
GN ORFNames=CG7891 {ECO:0000312|FlyBase:FBgn0037551};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH TUBULIN.
RX PubMed=15331635; DOI=10.1242/jcs.01347;
RA Okai T., Araki Y., Tada M., Tateno T., Kontani K., Katada T.;
RT "Novel small GTPase subfamily capable of associating with tubulin is
RT required for chromosome segregation.";
RL J. Cell Sci. 117:4705-4715(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=16537643; DOI=10.1242/jcs.02958;
RA Hofmann I., Munro S.;
RT "An N-terminally acetylated Arf-like GTPase is localised to lysosomes and
RT affects their motility.";
RL J. Cell Sci. 119:1494-1503(2006).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29940804; DOI=10.1080/15548627.2018.1458170;
RA Lund V.K., Madsen K.L., Kjaerulff O.;
RT "Drosophila Rab2 controls endosome-lysosome fusion and LAMP delivery to
RT late endosomes.";
RL Autophagy 14:1520-1542(2018).
RN [7]
RP FUNCTION, INTERACTION WITH RILPL, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF THR-34 AND GLN-75.
RX PubMed=30115618; DOI=10.1242/bio.035964;
RA Rosa-Ferreira C., Sweeney S.T., Munro S.;
RT "The small G protein Arl8 contributes to lysosomal function and long-range
RT axonal transport in Drosophila.";
RL Biol. Open 7:0-0(2018).
RN [8]
RP FUNCTION, INTERACTION WITH UNC-104, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=30174114; DOI=10.1016/j.neuron.2018.08.004;
RA Vukoja A., Rey U., Petzoldt A.G., Ott C., Vollweiter D., Quentin C.,
RA Puchkov D., Reynolds E., Lehmann M., Hohensee S., Rosa S., Lipowsky R.,
RA Sigrist S.J., Haucke V.;
RT "Presynaptic Biogenesis Requires Axonal Transport of Lysosome-Related
RT Vesicles.";
RL Neuron 99:1216-1232(2018).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=33822845; DOI=10.1083/jcb.202006040;
RA Goetz T.W.B., Puchkov D., Lysiuk V., Luetzkendorf J., Nikonenko A.G.,
RA Quentin C., Lehmann M., Sigrist S.J., Petzoldt A.G.;
RT "Rab2 regulates presynaptic precursor vesicle biogenesis at the trans-
RT Golgi.";
RL J. Cell Biol. 220:0-0(2021).
CC -!- FUNCTION: Required for normal functioning of the late endocytic pathway
CC including lysosome motility and late endosome-lysosome fusion
CC (PubMed:16537643, PubMed:29940804, PubMed:30115618). Not required for
CC the delivery of lysosomal membrane protein-containing vesicles to late
CC endosomes (PubMed:29940804). In larval motor neurons, mediates the
CC anterograde axonal long-range transport of presynaptic lysosome-related
CC vesicles required for presynaptic biogenesis and synaptic function
CC (PubMed:30174114, PubMed:30115618). Acts downstream of Rab2 during
CC presynaptic precursor vesicle biogenesis (PubMed:33822845). Essential
CC role in chromosome segregation (PubMed:15331635).
CC {ECO:0000269|PubMed:15331635, ECO:0000269|PubMed:16537643,
CC ECO:0000269|PubMed:29940804, ECO:0000269|PubMed:30115618,
CC ECO:0000269|PubMed:30174114, ECO:0000269|PubMed:33822845}.
CC -!- SUBUNIT: Interacts with tubulin (PubMed:15331635). Interacts (in GTP-
CC bound form) with Rilpl (PubMed:30115618). Interacts with unc-104
CC (PubMed:30174114). {ECO:0000269|PubMed:15331635,
CC ECO:0000269|PubMed:30115618, ECO:0000269|PubMed:30174114}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:16537643,
CC ECO:0000269|PubMed:30115618, ECO:0000269|PubMed:30174114}. Synapse
CC {ECO:0000269|PubMed:30115618, ECO:0000269|PubMed:30174114}. Cell
CC projection, axon {ECO:0000269|PubMed:30115618,
CC ECO:0000269|PubMed:30174114}. Perikaryon {ECO:0000269|PubMed:30115618,
CC ECO:0000269|PubMed:30174114}. Note=Localizes the perinuclear region
CC when associated with CG11448. {ECO:0000269|PubMed:30115618,
CC ECO:0000269|PubMed:30174114}.
CC -!- TISSUE SPECIFICITY: Expressed throughout development, from embryo to
CC adult stage, in different tissues such as larval motor neurons,
CC salivary glands, testis and ovaries (at protein level).
CC {ECO:0000269|PubMed:30115618}.
CC -!- DISRUPTION PHENOTYPE: Lethal from late larval stages (PubMed:29940804,
CC PubMed:30115618). In garland cells, results in defective late endosome-
CC lysosome fusion and inability to form a rapidly exchanging terminal
CC lysosomal network (PubMed:29940804). In motor neurons, results in
CC defective anterograde axonal long-range transport of lysosome-related
CC vesicles which leads to defective protein localization to presynaptic
CC active zone and synaptic vesicles (PubMed:30174114, PubMed:30115618,
CC PubMed:33822845). Fully mature presynaptic vesicles containing synaptic
CC vesicle proteins (e.g. VGlut) and presynaptic active zone proteins
CC (e.g. brp/Bruchpilot) accumulate in the soma of motor neurons
CC (PubMed:33822845). This results into a reduction of number of boutons
CC per synapses which limits neurotransmitter release and leads to
CC posterior paralysis (PubMed:30174114, PubMed:30115618). RNAi-mediated
CC knockdown in larval presynaptic motor neurons results in defective
CC presynaptic biogenesis (PubMed:30174114). {ECO:0000269|PubMed:29940804,
CC ECO:0000269|PubMed:30115618, ECO:0000269|PubMed:30174114,
CC ECO:0000269|PubMed:33822845}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
CC {ECO:0000305}.
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DR EMBL; AB185208; BAD30092.1; -; mRNA.
DR EMBL; AE014297; AAF54194.1; -; Genomic_DNA.
DR EMBL; AY094809; AAM11162.1; -; mRNA.
DR RefSeq; NP_001287225.1; NM_001300296.1.
DR RefSeq; NP_001287226.1; NM_001300297.1.
DR RefSeq; NP_649769.1; NM_141512.3.
DR AlphaFoldDB; Q9VHV5; -.
DR SMR; Q9VHV5; -.
DR BioGRID; 66144; 34.
DR IntAct; Q9VHV5; 5.
DR STRING; 7227.FBpp0308780; -.
DR PaxDb; 7227-FBpp0081290; -.
DR DNASU; 40961; -.
DR EnsemblMetazoa; FBtr0081794; FBpp0081290; FBgn0037551.
DR EnsemblMetazoa; FBtr0339723; FBpp0308779; FBgn0037551.
DR EnsemblMetazoa; FBtr0339724; FBpp0308780; FBgn0037551.
DR GeneID; 40961; -.
DR KEGG; dme:Dmel_CG7891; -.
DR UCSC; CG7891-RA; d. melanogaster.
DR AGR; FB:FBgn0037551; -.
DR CTD; 327551; -.
DR FlyBase; FBgn0037551; Arl8.
DR VEuPathDB; VectorBase:FBgn0037551; -.
DR eggNOG; KOG0075; Eukaryota.
DR GeneTree; ENSGT00940000165940; -.
DR HOGENOM; CLU_040729_10_0_1; -.
DR InParanoid; Q9VHV5; -.
DR OMA; FRNMWER; -.
DR OrthoDB; 607297at2759; -.
DR PhylomeDB; Q9VHV5; -.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 40961; 1 hit in 3 CRISPR screens.
DR ChiTaRS; Gie; fly.
DR GenomeRNAi; 40961; -.
DR PRO; PR:Q9VHV5; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037551; Expressed in saliva-secreting gland and 39 other cell types or tissues.
DR ExpressionAtlas; Q9VHV5; baseline and differential.
DR Genevisible; Q9VHV5; DM.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0098574; C:cytoplasmic side of lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:FlyBase.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:1990027; C:S bouton; IDA:UniProtKB.
DR GO; GO:0051233; C:spindle midzone; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0043014; F:alpha-tubulin binding; ISS:UniProtKB.
DR GO; GO:0048487; F:beta-tubulin binding; ISS:UniProtKB.
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; IEA:InterPro.
DR GO; GO:0008089; P:anterograde axonal transport; IMP:UniProtKB.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; IMP:FlyBase.
DR GO; GO:0098930; P:axonal transport; IMP:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:1902774; P:late endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; IMP:FlyBase.
DR GO; GO:0007269; P:neurotransmitter secretion; IMP:UniProtKB.
DR GO; GO:0099054; P:presynapse assembly; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0001666; P:response to hypoxia; IMP:FlyBase.
DR GO; GO:0000819; P:sister chromatid segregation; IMP:UniProtKB.
DR CDD; cd04159; Arl10_like; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR InterPro; IPR044154; Arl8a/8b.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR006689; Small_GTPase_ARF/SAR.
DR NCBIfam; TIGR00231; small_GTP; 1.
DR PANTHER; PTHR45732; ADP-RIBOSYLATION FACTOR-LIKE PROTEIN 8; 1.
DR PANTHER; PTHR45732:SF7; ADP-RIBOSYLATION FACTOR-LIKE PROTEIN 8; 1.
DR Pfam; PF00025; Arf; 1.
DR PRINTS; PR00328; SAR1GTPBP.
DR SMART; SM00177; ARF; 1.
DR SMART; SM00175; RAB; 1.
DR SMART; SM00178; SAR; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR PROSITE; PS51417; ARF; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cell projection; Chromosome partition;
KW GTP-binding; Lysosome; Membrane; Mitosis; Nucleotide-binding;
KW Protein transport; Reference proteome; Synapse; Transport.
FT CHAIN 1..186
FT /note="ADP-ribosylation factor-like protein 8"
FT /id="PRO_0000232927"
FT INTRAMEM 1..19
FT /note="Note=Mediates targeting to membranes"
FT /evidence="ECO:0000250"
FT BINDING 29..35
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 71..75
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 130..133
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MUTAGEN 34
FT /note="T->N: Probably constitutively inactive (GDP-locked
FT form). Abolishes interaction with CG11448."
FT /evidence="ECO:0000269|PubMed:30115618"
FT MUTAGEN 75
FT /note="Q->L: Probably constitutively active (GTP-locked
FT form). Does not affect interaction with CG11448."
FT /evidence="ECO:0000269|PubMed:30115618"
SQ SEQUENCE 186 AA; 21254 MW; B437D8EC4D001EE0 CRC64;
MLALINRILE WFKSIFWKEE MELTLVGLQF SGKTTFVNVI ASGQFAEDMI PTVGFNMRKI
TRGNVTIKVW DIGGQPRFRS MWERYCRGVN AIVYMVDAAD LDKLEASRNE LHSLLDKPQL
AGIPVLVLGN KRDLPGALDE TGLIERMNLS SIQDREICCY SISCKEKDNI DITLQWLIQH
SKSQSR
//
