ARL8B_MOUSE
ID ARL8B_MOUSE Reviewed; 186 AA.
AC Q9CQW2; Q3TXD7; Q3U769; Q3UBB1; Q3UJU2;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=ADP-ribosylation factor-like protein 8B {ECO:0000305};
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:Q9NVJ2};
DE AltName: Full=ADP-ribosylation factor-like protein 10C;
DE AltName: Full=Novel small G protein indispensable for equal chromosome segregation 1;
GN Name=Arl8b {ECO:0000312|MGI:MGI:1914416};
GN Synonyms=Arl10c, Gie1 {ECO:0000303|PubMed:15331635};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Embryo, Head, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J.,
RA Wiemann S., Schick M., Korn B.;
RT "Cloning of mouse full open reading frames in Gateway(R) system entry
RT vector (pDONR201).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21802320; DOI=10.1016/j.immuni.2011.06.009;
RA Garg S., Sharma M., Ung C., Tuli A., Barral D.C., Hava D.L., Veerapen N.,
RA Besra G.S., Hacohen N., Brenner M.B.;
RT "Lysosomal trafficking, antigen presentation, and microbial killing are
RT controlled by the Arf-like GTPase Arl8b.";
RL Immunity 35:182-193(2011).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25637027; DOI=10.4049/jimmunol.1401072;
RA Michelet X., Garg S., Wolf B.J., Tuli A., Ricciardi-Castagnoli P.,
RA Brenner M.B.;
RT "MHC class II presentation is controlled by the lysosomal small GTPase,
RT Arl8b.";
RL J. Immunol. 194:2079-2088(2015).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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, FUNCTION (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RX PubMed=33157038; DOI=10.1016/j.cell.2020.10.039;
RA Ghosh S., Dellibovi-Ragheb T.A., Kerviel A., Pak E., Qiu Q., Fisher M.,
RA Takvorian P.M., Bleck C., Hsu V.W., Fehr A.R., Perlman S., Achar S.R.,
RA Straus M.R., Whittaker G.R., de Haan C.A.M., Kehrl J., Altan-Bonnet G.,
RA Altan-Bonnet N.;
RT "beta-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic
RT Secretory Pathway.";
RL Cell 183:1520-1535(2020).
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 lysosomal
CC positioning which is important for nutrient sensing, natural killer
CC cell-mediated cytotoxicity and antigen presentation (PubMed:33157038,
CC PubMed:30174114). Along with its effectors, orchestrates lysosomal
CC transport and fusion. Localizes specifically to lysosomal membranes and
CC mediates anterograde lysosomal motility by recruiting PLEKHM2, which in
CC turn recruits the motor protein kinesin-1 on lysosomes. Required for
CC lysosomal and cytolytic granule exocytosis. Critical factor involved in
CC NK cell-mediated cytotoxicity. Drives the polarization of cytolytic
CC granules and microtubule-organizing centers (MTOCs) toward the immune
CC synapse between effector NK lymphocytes and target cells (By
CC similarity). In neurons, mediates the anterograde axonal long-range
CC transport of presynaptic lysosome-related vesicles required for
CC presynaptic biogenesis and synaptic function (PubMed:30174114). Also
CC acts as a regulator of endosome to lysosome trafficking pathways of
CC special significance for host defense. Regulates cargo trafficking to
CC lysosomes by binding to PLEKHM1 and recruiting the HOPS subunit VPS41,
CC resulting in functional assembly of the HOPS complex on lysosomal
CC membranes. Plays an important role in cargo delivery to lysosomes for
CC antigen presentation and microbial killing. Directs the intersection of
CC CD1d with lipid antigens in lysosomes, and plays a role in intersecting
CC phagosomes with lysosomes to generate phagolysosomes that kill microbes
CC (PubMed:21802320). Involved in the process of MHC II presentation.
CC Regulates the delivery of antigens to lysosomes and the formation of
CC MHC II-peptide complexes through the recruitment of the HOPS complex to
CC lysosomes allowing the fusion of late endosomes to lysosomes
CC (PubMed:25637027). May play a role in chromosome segregation (By
CC similarity). {ECO:0000250|UniProtKB:Q9NVJ2,
CC ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:25637027,
CC ECO:0000269|PubMed:30174114, ECO:0000269|PubMed:33157038}.
CC -!- FUNCTION: (Microbial infection) During infection, murine coronavirus
CC (MHV) and the chaperone HSPA5/GRP78 are co-released through ARL8B-
CC dependent lysosomal exocytic pathway for unconventional egress.
CC {ECO:0000269|PubMed:33157038}.
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:Q9NVJ2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:Q9NVJ2};
CC -!- SUBUNIT: Interacts with tubulin. Interacts with BORCS5; recruits ARL8B
CC to lysosomes. Interacts with VPS41; the interaction mediates the
CC recruitment of the HOPS complex to lysosomes. Interacts (GTP-bound
CC form) with PLEKHM2 (via RUN domain); the interaction is required to
CC recruit the motor protein kinesin-1 on lysosomes. Interacts (GTP-bound
CC form) with PLEKHM1 (via RUN domain); the interaction is required for
CC PLEKHM1 localization to lysosomes and for ARL8B function in delivery
CC and degradation of endocytic and autophagic cargo in lysosomes. PLEKHM1
CC and PLEKHM2 compete for interaction with ARL8B.
CC {ECO:0000250|UniProtKB:Q9NVJ2}.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000250|UniProtKB:Q9NVJ2}. Lysosome membrane
CC {ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:25637027,
CC ECO:0000269|PubMed:30174114, ECO:0000269|PubMed:33157038}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000250|UniProtKB:Q9NVJ2}. Cell projection,
CC axon {ECO:0000269|PubMed:30174114}. Synapse
CC {ECO:0000269|PubMed:30174114}. Cytolytic granule membrane
CC {ECO:0000250|UniProtKB:Q9NVJ2}. Note=GTP-bound form resides on
CC lysosomal membranes, whereas GDP-bound form is likely associated with
CC microtubular structures. Localizes with microtubules at the spindle
CC mid-zone during mitosis (By similarity). In dendritic cells, localizes
CC to MHC II+ compartments (PubMed:25637027).
CC {ECO:0000250|UniProtKB:Q9NVJ2, ECO:0000269|PubMed:25637027}.
CC -!- PTM: Ubiquitinated at Lys-141 by RNF167, leading to its degradation.
CC {ECO:0000250|UniProtKB:Q9NVJ2}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf 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; AB185206; BAD30090.1; -; mRNA.
DR EMBL; AK009279; BAB26190.1; -; mRNA.
DR EMBL; AK012024; BAB27980.1; -; mRNA.
DR EMBL; AK030689; BAC27079.1; -; mRNA.
DR EMBL; AK144177; BAE25749.1; -; mRNA.
DR EMBL; AK146307; BAE27063.1; -; mRNA.
DR EMBL; AK149822; BAE29104.1; -; mRNA.
DR EMBL; AK151036; BAE30053.1; -; mRNA.
DR EMBL; AK152798; BAE31503.1; -; mRNA.
DR EMBL; AK159311; BAE34979.1; -; mRNA.
DR EMBL; AK159348; BAE35010.1; -; mRNA.
DR EMBL; AK169929; BAE41467.1; -; mRNA.
DR EMBL; AK170645; BAE41932.1; -; mRNA.
DR EMBL; CT010337; CAJ18545.1; -; mRNA.
DR EMBL; BC013719; AAH13719.1; -; mRNA.
DR CCDS; CCDS39586.1; -.
DR RefSeq; NP_080287.1; NM_026011.3.
DR AlphaFoldDB; Q9CQW2; -.
DR SMR; Q9CQW2; -.
DR BioGRID; 211990; 11.
DR IntAct; Q9CQW2; 1.
DR MINT; Q9CQW2; -.
DR STRING; 10090.ENSMUSP00000032196; -.
DR iPTMnet; Q9CQW2; -.
DR PhosphoSitePlus; Q9CQW2; -.
DR SwissPalm; Q9CQW2; -.
DR EPD; Q9CQW2; -.
DR jPOST; Q9CQW2; -.
DR MaxQB; Q9CQW2; -.
DR PaxDb; Q9CQW2; -.
DR PeptideAtlas; Q9CQW2; -.
DR PRIDE; Q9CQW2; -.
DR ProteomicsDB; 274971; -.
DR TopDownProteomics; Q9CQW2; -.
DR Antibodypedia; 25235; 164 antibodies from 24 providers.
DR DNASU; 67166; -.
DR Ensembl; ENSMUST00000032196; ENSMUSP00000032196; ENSMUSG00000030105.
DR GeneID; 67166; -.
DR KEGG; mmu:67166; -.
DR UCSC; uc009ddo.1; mouse.
DR CTD; 55207; -.
DR MGI; MGI:1914416; Arl8b.
DR VEuPathDB; HostDB:ENSMUSG00000030105; -.
DR eggNOG; KOG0075; Eukaryota.
DR GeneTree; ENSGT00940000154861; -.
DR HOGENOM; CLU_040729_10_0_1; -.
DR InParanoid; Q9CQW2; -.
DR OMA; SASWLWQ; -.
DR OrthoDB; 1123043at2759; -.
DR PhylomeDB; Q9CQW2; -.
DR TreeFam; TF105470; -.
DR BioGRID-ORCS; 67166; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Arl8b; mouse.
DR PRO; PR:Q9CQW2; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9CQW2; protein.
DR Bgee; ENSMUSG00000030105; Expressed in dentate gyrus of hippocampal formation granule cell and 278 other tissues.
DR ExpressionAtlas; Q9CQW2; baseline and differential.
DR Genevisible; Q9CQW2; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0101004; C:cytolytic granule membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; ISO:MGI.
DR GO; GO:0051233; C:spindle midzone; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0043014; F:alpha-tubulin binding; ISO:MGI.
DR GO; GO:0048487; F:beta-tubulin binding; ISO:MGI.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0008089; P:anterograde axonal transport; IDA:UniProtKB.
DR GO; GO:0002747; P:antigen processing and presentation following phagocytosis; ISS:UniProtKB.
DR GO; GO:0002505; P:antigen processing and presentation of polysaccharide antigen via MHC class II; IDA:UniProtKB.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; ISO:MGI.
DR GO; GO:1990927; P:calcium ion regulated lysosome exocytosis; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; ISO:MGI.
DR GO; GO:0016197; P:endosomal transport; IMP:MGI.
DR GO; GO:0090117; P:endosome to lysosome transport of low-density lipoprotein particle; ISS:UniProtKB.
DR GO; GO:1902774; P:late endosome to lysosome transport; IDA:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; ISS:UniProtKB.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISO:MGI.
DR GO; GO:0090385; P:phagosome-lysosome fusion; ISS:UniProtKB.
DR GO; GO:0001778; P:plasma membrane repair; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0046754; P:viral exocytosis; IMP:UniProtKB.
DR CDD; cd04159; Arl10_like; 1.
DR Gene3D; 3.40.50.300; -; 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 Pfam; PF00025; Arf; 1.
DR PRINTS; PR00328; SAR1GTPBP.
DR SMART; SM00178; SAR; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51417; ARF; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cell projection; Chromosome partition;
KW Cytoplasm; Cytoskeleton; Endosome; GTP-binding; Hydrolase; Isopeptide bond;
KW Lysosome; Membrane; Mitosis; Nucleotide-binding; Protein transport;
KW Reference proteome; Synapse; Transport; Ubl conjugation.
FT CHAIN 1..186
FT /note="ADP-ribosylation factor-like protein 8B"
FT /id="PRO_0000232923"
FT INTRAMEM 1..19
FT /note="Note=Mediates targeting to membranes"
FT /evidence="ECO:0000250|UniProtKB:Q9NVJ2"
FT BINDING 29..35
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NVJ2"
FT BINDING 71..75
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P62330"
FT BINDING 130..133
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9NVJ2"
FT CROSSLNK 141
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9NVJ2"
FT CONFLICT 47
FT /note="E -> G (in Ref. 2; BAE30053)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="E -> G (in Ref. 2; BAE31503)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="C -> Y (in Ref. 2; BAE27063)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 186 AA; 21539 MW; 5030B01AFD749223 CRC64;
MLALISRLLD WFRSLFWKEE MELTLVGLQY SGKTTFVNVI ASGQFSEDMI PTVGFNMRKV
TKGNVTIKIW DIGGQPRFRS MWERYCRGVN AIVYMIDAAD REKIEASRNE LHNLLDKPQL
QGIPVLVLGN KRDLPNALDE KQLIEKMNLS AIQDREICCY SISCKEKDNI DITLQWLIQH
SKSRRS
