ID ARL8B_HUMAN Reviewed; 186 AA.
AC Q9NVJ2; B4DI85;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 24-JUL-2024, entry version 196.
DE RecName: Full=ADP-ribosylation factor-like protein 8B {ECO:0000305};
DE EC=3.6.5.2 {ECO:0000269|PubMed:15331635, ECO:0000269|PubMed:16537643};
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|HGNC:HGNC:25564}; Synonyms=ARL10C, GIE1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP MUTAGENESIS OF THR-34; 49-MET--ARG-58; TRP-70; 74-GLY--TYR-85 AND ASN-130,
RP SUBCELLULAR LOCATION, INTERACTION WITH TUBULIN, AND CATALYTIC ACTIVITY.
RC TISSUE=Brain;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Hippocampus, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Embryonic carcinoma, and Testis;
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 [7]
RP PROTEIN SEQUENCE OF 69-77; 147-155 AND 166-182, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF THR-34 AND GLN-75.
RX PubMed=16650381; DOI=10.1016/j.bbrc.2006.03.221;
RA Bagshaw R.D., Callahan J.W., Mahuran D.J.;
RT "The Arf-family protein, Arl8b, is involved in the spatial distribution of
RT lysosomes.";
RL Biochem. Biophys. Res. Commun. 344:1186-1191(2006).
RN [9]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION,
RP ACETYLATION AT MET-1, MUTAGENESIS OF LEU-2; 5-ILE--PHE-12 AND GLN-75, AND
RP CATALYTIC ACTIVITY.
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 [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION, INTERACTION WITH PLEKHM2, AND SUBCELLULAR LOCATION.
RX PubMed=22172677; DOI=10.1016/j.devcel.2011.10.007;
RA Rosa-Ferreira C., Munro S.;
RT "Arl8 and SKIP act together to link lysosomes to kinesin-1.";
RL Dev. Cell 21:1171-1178(2011).
RN [13]
RP FUNCTION, INTERACTION WITH VPS41, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP THR-34 AND GLN-75.
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 [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24088571; DOI=10.1091/mbc.e13-05-0259;
RA Tuli A., Thiery J., James A.M., Michelet X., Sharma M., Garg S.,
RA Sanborn K.B., Orange J.S., Lieberman J., Brenner M.B.;
RT "Arf-like GTPase Arl8b regulates lytic granule polarization and natural
RT killer cell-mediated cytotoxicity.";
RL Mol. Biol. Cell 24:3721-3735(2013).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP FUNCTION, INTERACTION WITH BORCS5, AND SUBCELLULAR LOCATION.
RX PubMed=25898167; DOI=10.1016/j.devcel.2015.02.011;
RA Pu J., Schindler C., Jia R., Jarnik M., Backlund P., Bonifacino J.S.;
RT "BORC, a multisubunit complex that regulates lysosome positioning.";
RL Dev. Cell 33:176-188(2015).
RN [19]
RP FUNCTION, AND INTERACTION WITH VPS41.
RX PubMed=25908847; DOI=10.1242/jcs.162651;
RA Khatter D., Raina V.B., Dwivedi D., Sindhwani A., Bahl S., Sharma M.;
RT "The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on
RT lysosomes.";
RL J. Cell Sci. 128:1746-1761(2015).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION AT LYS-141, AND MUTAGENESIS
RP OF LYS-141.
RX PubMed=27808481; DOI=10.1111/febs.13947;
RA Deshar R., Moon S., Yoo W., Cho E.B., Yoon S.K., Yoon J.B.;
RT "RNF167 targets Arl8B for degradation to regulate lysosome positioning and
RT endocytic trafficking.";
RL FEBS J. 283:4583-4599(2016).
RN [22]
RP FUNCTION, INTERACTION WITH PLEKHM1 AND PLEKHM2, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF THR-34 AND GLN-75.
RX PubMed=28325809; DOI=10.1083/jcb.201607085;
RA Marwaha R., Arya S.B., Jagga D., Kaur H., Tuli A., Sharma M.;
RT "The Rab7 effector PLEKHM1 binds Arl8b to promote cargo traffic to
RT lysosomes.";
RL J. Cell Biol. 216:1051-1070(2017).
RN [23]
RP FUNCTION (MICROBIAL INFECTION), FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=29592961; DOI=10.4049/jimmunol.1700829;
RA Michelet X., Tuli A., Gan H., Geadas C., Sharma M., Remold H.G.,
RA Brenner M.B.;
RT "Lysosome-Mediated Plasma Membrane Repair Is Dependent on the Small GTPase
RT Arl8b and Determines Cell Death Type in Mycobacterium tuberculosis
RT Infection.";
RL J. Immunol. 200:3160-3169(2018).
RN [24]
RP FUNCTION (MICROBIAL INFECTION).
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).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RUFY1.
RX PubMed=36282215; DOI=10.1083/jcb.202108001;
RA Rawat S., Chatterjee D., Marwaha R., Charak G., Kumar G., Shaw S.,
RA Khatter D., Sharma S., de Heus C., Liv N., Klumperman J., Tuli A.,
RA Sharma M.;
RT "RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo
RT sorting to lysosomes.";
RL J. Cell Biol. 222:0-0(2023).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 18-184 IN COMPLEX WITH GDP.
RG Structural genomics consortium (SGC);
RT "GTP-like conformation of GDP-bound ARL10C GTPase.";
RL Submitted (AUG-2005) to the PDB data bank.
CC -!- FUNCTION: Small GTPase which cycles between active GTP-bound and
CC inactive GDP-bound states (PubMed:15331635, PubMed:16537643). In its
CC active state, binds to a variety of effector proteins playing a key
CC role in the regulation of lysosomal positioning which is important for
CC nutrient sensing, natural killer cell-mediated cytotoxicity and antigen
CC presentation. Along with its effectors, orchestrates lysosomal
CC transport and fusion (PubMed:16537643, PubMed:16650381,
CC PubMed:25898167, PubMed:27808481, PubMed:28325809). Localizes
CC specifically to lysosomal membranes and mediates anterograde lysosomal
CC motility by recruiting PLEKHM2, which in turn recruits the motor
CC protein kinesin-1 on lysosomes. Required for lysosomal and cytolytic
CC granule exocytosis (PubMed:22172677, PubMed:24088571, PubMed:29592961).
CC Critical factor involved in NK cell-mediated cytotoxicity. Drives the
CC polarization of cytolytic granules and microtubule-organizing centers
CC (MTOCs) toward the immune synapse between effector NK lymphocytes and
CC target cells (PubMed:24088571). In neurons, mediates the anterograde
CC axonal long-range transport of presynaptic lysosome-related vesicles
CC required for presynaptic biogenesis and synaptic function (By
CC similarity). Also acts as a regulator of endosome to lysosome
CC trafficking pathways of special significance for host defense
CC (PubMed:21802320). Recruits RUFY1 onto early endosomes regulating
CC endosomes to trans-Golgi network proteins retrieval (PubMed:36282215).
CC Regulates cargo trafficking to lysosomes by binding to PLEKHM1 and
CC recruiting the HOPS subunit VPS41, resulting in functional assembly of
CC the HOPS complex on lysosomal membranes (PubMed:16537643,
CC PubMed:25908847). Plays an important role in cargo delivery to
CC lysosomes for antigen presentation and microbial killing. Directs the
CC intersection of CD1d with lipid antigens in lysosomes, and plays a role
CC in intersecting phagosomes with lysosomes to generate phagolysosomes
CC that kill microbes (PubMed:21802320, PubMed:25908847). Involved in the
CC process of MHC II presentation. Regulates the delivery of antigens to
CC lysosomes and the formation of MHC II-peptide complexes through the
CC recruitment of the HOPS complex to lysosomes allowing the fusion of
CC late endosomes to lysosomes (By similarity). May play a role in
CC chromosome segregation (PubMed:15331635).
CC {ECO:0000250|UniProtKB:Q9CQW2, ECO:0000269|PubMed:15331635,
CC ECO:0000269|PubMed:16537643, ECO:0000269|PubMed:16650381,
CC ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:22172677,
CC ECO:0000269|PubMed:24088571, ECO:0000269|PubMed:25898167,
CC ECO:0000269|PubMed:25908847, ECO:0000269|PubMed:27808481,
CC ECO:0000269|PubMed:28325809, ECO:0000269|PubMed:29592961,
CC ECO:0000269|PubMed:36282215}.
CC -!- FUNCTION: (Microbial infection) During Mycobacterium tuberculosis (Mtb)
CC infection, is required for plasma membrane repair by controlling the
CC exocytosis of lysosomes in macrophages. ARL8B secretion pathway is
CC crucial to control the type of cell death of the M. tuberculosis-
CC infected macrophages, distinguishing avirulent from virulent Mtb
CC induced necrotic cell death. {ECO:0000269|PubMed:29592961}.
CC -!- FUNCTION: (Microbial infection) During infection, coronaviruses such as
CC SARS-CoV-2 and the chaperone HSPA5/GRP78 are probably co-released
CC through ARL8B-dependent lysosomal exocytic pathway for unconventional
CC egress. {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:0000269|PubMed:15331635, ECO:0000269|PubMed:16537643};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000269|PubMed:15331635, ECO:0000269|PubMed:16537643};
CC -!- SUBUNIT: Interacts with tubulin (PubMed:15331635, Ref.26). Interacts
CC with BORCS5; recruits ARL8B to lysosomes (PubMed:25898167). Interacts
CC with VPS41; the interaction mediates the recruitment of the HOPS
CC complex to lysosomes (PubMed:21802320, PubMed:25908847). Interacts
CC (GTP-bound form) with PLEKHM2 (via RUN domain); the interaction is
CC required to recruit the motor protein kinesin-1 on lysosomes
CC (PubMed:22172677, PubMed:28325809). Interacts (GTP-bound form) with
CC PLEKHM1 (via RUN domain); the interaction is required for PLEKHM1
CC localization to lysosomes and for ARL8B function in delivery and
CC degradation of endocytic and autophagic cargo in lysosomes
CC (PubMed:28325809). PLEKHM1 and PLEKHM2 compete for interaction with
CC ARL8B (PubMed:28325809). Interacts (GTP-bound form) with RUFY1; the
CC interaction is required for RUFY1 endosomal location (PubMed:36282215).
CC {ECO:0000269|PubMed:15331635, ECO:0000269|PubMed:21802320,
CC ECO:0000269|PubMed:22172677, ECO:0000269|PubMed:25898167,
CC ECO:0000269|PubMed:25908847, ECO:0000269|PubMed:28325809,
CC ECO:0000269|PubMed:36282215, ECO:0000269|Ref.26}.
CC -!- INTERACTION:
CC Q9NVJ2; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-718376, EBI-7062247;
CC Q9NVJ2; Q9Y4G2: PLEKHM1; NbExp=20; IntAct=EBI-718376, EBI-473814;
CC Q9NVJ2; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-718376, EBI-10262251;
CC Q9NVJ2; Q13573: SNW1; NbExp=5; IntAct=EBI-718376, EBI-632715;
CC Q9NVJ2; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-718376, EBI-8638294;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:16537643}. Lysosome membrane
CC {ECO:0000269|PubMed:16650381, ECO:0000269|PubMed:21802320,
CC ECO:0000269|PubMed:22172677, ECO:0000269|PubMed:25898167,
CC ECO:0000269|PubMed:27808481, ECO:0000269|PubMed:28325809,
CC ECO:0000269|PubMed:29592961}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:15331635}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q9CQW2}. Synapse {ECO:0000250|UniProtKB:Q9CQW2}.
CC Cytolytic granule membrane {ECO:0000269|PubMed:24088571}. Early
CC endosome membrane {ECO:0000269|PubMed:36282215}. Note=GTP-bound form
CC resides on lysosomal membranes, whereas GDP-bound form is likely
CC associated with microtubular structures (PubMed:16650381). Localizes
CC with microtubules at the spindle mid-zone during mitosis. In dendritic
CC cells, localizes to MHC II+ compartments (By similarity).
CC {ECO:0000250|UniProtKB:Q9CQW2, ECO:0000269|PubMed:15331635,
CC ECO:0000269|PubMed:16650381}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NVJ2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NVJ2-2; Sequence=VSP_056238;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:15331635}.
CC -!- PTM: Ubiquitinated at Lys-141 by RNF167, leading to its degradation.
CC {ECO:0000269|PubMed:27808481}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
CC {ECO:0000305}.
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DR EMBL; AB118751; BAD23992.1; -; mRNA.
DR EMBL; AK001564; BAA91759.1; -; mRNA.
DR EMBL; AK295465; BAG58397.1; -; mRNA.
DR EMBL; CR457264; CAG33545.1; -; mRNA.
DR EMBL; AC021999; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026202; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW63919.1; -; Genomic_DNA.
DR EMBL; BC013131; AAH13131.1; -; mRNA.
DR EMBL; BC063125; AAH63125.1; -; mRNA.
DR CCDS; CCDS2566.1; -. [Q9NVJ2-1]
DR RefSeq; NP_060654.1; NM_018184.2. [Q9NVJ2-1]
DR PDB; 2AL7; X-ray; 1.85 A; A=18-184.
DR PDB; 8JC5; X-ray; 2.01 A; A/B=18-186.
DR PDB; 8JCA; X-ray; 1.65 A; A=18-186.
DR PDBsum; 2AL7; -.
DR PDBsum; 8JC5; -.
DR PDBsum; 8JCA; -.
DR AlphaFoldDB; Q9NVJ2; -.
DR SMR; Q9NVJ2; -.
DR BioGRID; 120503; 270.
DR IntAct; Q9NVJ2; 47.
DR MINT; Q9NVJ2; -.
DR STRING; 9606.ENSP00000479202; -.
DR ChEMBL; CHEMBL4295962; -.
DR GlyGen; Q9NVJ2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NVJ2; -.
DR PhosphoSitePlus; Q9NVJ2; -.
DR SwissPalm; Q9NVJ2; -.
DR BioMuta; ARL8B; -.
DR DMDM; 74752996; -.
DR jPOST; Q9NVJ2; -.
DR MassIVE; Q9NVJ2; -.
DR PaxDb; 9606-ENSP00000256496; -.
DR PeptideAtlas; Q9NVJ2; -.
DR ProteomicsDB; 4283; -.
DR ProteomicsDB; 82817; -. [Q9NVJ2-1]
DR Pumba; Q9NVJ2; -.
DR TopDownProteomics; Q9NVJ2-1; -. [Q9NVJ2-1]
DR Antibodypedia; 25235; 169 antibodies from 24 providers.
DR DNASU; 55207; -.
DR Ensembl; ENST00000256496.8; ENSP00000256496.3; ENSG00000134108.14. [Q9NVJ2-1]
DR Ensembl; ENST00000419534.2; ENSP00000402996.2; ENSG00000134108.14. [Q9NVJ2-2]
DR GeneID; 55207; -.
DR KEGG; hsa:55207; -.
DR MANE-Select; ENST00000256496.8; ENSP00000256496.3; NM_018184.3; NP_060654.1.
DR UCSC; uc003bqg.4; human. [Q9NVJ2-1]
DR AGR; HGNC:25564; -.
DR CTD; 55207; -.
DR DisGeNET; 55207; -.
DR GeneCards; ARL8B; -.
DR HGNC; HGNC:25564; ARL8B.
DR HPA; ENSG00000134108; Low tissue specificity.
DR MIM; 616596; gene.
DR neXtProt; NX_Q9NVJ2; -.
DR OpenTargets; ENSG00000134108; -.
DR PharmGKB; PA134959531; -.
DR VEuPathDB; HostDB:ENSG00000134108; -.
DR eggNOG; KOG0075; Eukaryota.
DR GeneTree; ENSGT00940000154861; -.
DR HOGENOM; CLU_040729_10_0_1; -.
DR InParanoid; Q9NVJ2; -.
DR OMA; CYSICKE; -.
DR OrthoDB; 607297at2759; -.
DR PhylomeDB; Q9NVJ2; -.
DR TreeFam; TF105470; -.
DR PathwayCommons; Q9NVJ2; -.
DR SignaLink; Q9NVJ2; -.
DR BioGRID-ORCS; 55207; 44 hits in 1157 CRISPR screens.
DR ChiTaRS; ARL8B; human.
DR EvolutionaryTrace; Q9NVJ2; -.
DR GeneWiki; ARL8B; -.
DR GenomeRNAi; 55207; -.
DR Pharos; Q9NVJ2; Tbio.
DR PRO; PR:Q9NVJ2; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NVJ2; Protein.
DR Bgee; ENSG00000134108; Expressed in middle temporal gyrus and 209 other cell types or tissues.
DR ExpressionAtlas; Q9NVJ2; baseline and differential.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0101004; C:cytolytic granule membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProt.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0051233; C:spindle midzone; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0003925; F:G protein activity; IDA:UniProt.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProt.
DR GO; GO:0008089; P:anterograde axonal transport; IBA:GO_Central.
DR GO; GO:0002747; P:antigen processing and presentation following phagocytosis; IMP:UniProtKB.
DR GO; GO:0002505; P:antigen processing and presentation of polysaccharide antigen via MHC class II; ISS:UniProtKB.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; IMP:UniProtKB.
DR GO; GO:1990927; P:calcium ion regulated lysosome exocytosis; IMP:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0034498; P:early endosome to Golgi transport; IDA:UniProt.
DR GO; GO:0090117; P:endosome to lysosome transport of low-density lipoprotein particle; IMP:UniProtKB.
DR GO; GO:1902774; P:late endosome to lysosome transport; IMP:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; IDA:UniProtKB.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IMP:UniProtKB.
DR GO; GO:0090385; P:phagosome-lysosome fusion; IMP:UniProtKB.
DR GO; GO:0001778; P:plasma membrane repair; IMP:UniProtKB.
DR GO; GO:1902946; P:protein localization to early endosome; IDA:UniProt.
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; 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:SF13; ADP-RIBOSYLATION FACTOR-LIKE PROTEIN 8B; 1.
DR Pfam; PF00025; Arf; 1.
DR PRINTS; PR00328; SAR1GTPBP.
DR SMART; SM00177; ARF; 1.
DR SMART; SM00175; RAB; 1.
DR SMART; SM00173; RAS; 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 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division;
KW Cell projection; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Endosome; GTP-binding; Hydrolase; Isopeptide bond; Lysosome; Membrane;
KW Nucleotide-binding; Protein transport; Reference proteome; Synapse;
KW Transport; Ubl conjugation.
FT CHAIN 1..186
FT /note="ADP-ribosylation factor-like protein 8B"
FT /id="PRO_0000232921"
FT INTRAMEM 1..19
FT /note="Note=Mediates targeting to membranes"
FT /evidence="ECO:0000269|PubMed:16537643"
FT BINDING 29..35
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|Ref.26"
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:0000269|Ref.26"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:16537643,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CROSSLNK 141
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:27808481"
FT VAR_SEQ 125..186
FT /note="VLVLGNKRDLPNALDEKQLIEKMNLSAIQDREICCYSISCKEKDNIDITLQW
FT LIQHSKSRRS -> ISHFSGLFSIQNLEEAEASPEVFQSFLAIILELLSVPLK (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056238"
FT MUTAGEN 2
FT /note="L->A: Diffuse cytoplasmic distribution and loss of
FT localization to lysosomes. No effect on acetylation."
FT /evidence="ECO:0000269|PubMed:16537643"
FT MUTAGEN 2
FT /note="L->F: No effect on localization and acetylation."
FT /evidence="ECO:0000269|PubMed:16537643"
FT MUTAGEN 5..12
FT /note="ISRLLDWF->ASRALDWA: Diffuse cytoplasmic distribution
FT and loss of localization to lysosomes. No effect on
FT acetylation."
FT /evidence="ECO:0000269|PubMed:16537643"
FT MUTAGEN 34
FT /note="T->N: Preferentially binds GDP. Alters chromosome
FT segregation. Decreases interaction with VPS41. Loss of
FT lysosomal location. Loss of interaction with PLEKHM1."
FT /evidence="ECO:0000269|PubMed:15331635,
FT ECO:0000269|PubMed:16650381, ECO:0000269|PubMed:21802320"
FT MUTAGEN 49..58
FT /note="Missing: Alters chromosome segregation."
FT /evidence="ECO:0000269|PubMed:15331635"
FT MUTAGEN 70
FT /note="W->R: Preferentially binds GTP."
FT /evidence="ECO:0000269|PubMed:15331635"
FT MUTAGEN 74..85
FT /note="Missing: Alters chromosome segregation."
FT /evidence="ECO:0000269|PubMed:15331635"
FT MUTAGEN 75
FT /note="Q->L: Prevents GTP hydrolysis. No effect on
FT lysosomal location. Alters lysosomes cellular distribution
FT and motility. Increases interaction with VPS41. No effect
FT on interaction with PLEKHM1."
FT /evidence="ECO:0000269|PubMed:16537643,
FT ECO:0000269|PubMed:16650381, ECO:0000269|PubMed:21802320,
FT ECO:0000269|PubMed:28325809"
FT MUTAGEN 130
FT /note="N->I: Loss of GTP/GDP-binding. Affects chromosome
FT segregation."
FT /evidence="ECO:0000269|PubMed:15331635"
FT MUTAGEN 141
FT /note="K->R: Abolished ubiquitination by RNF167."
FT /evidence="ECO:0000269|PubMed:27808481"
FT STRAND 19..26
FT /evidence="ECO:0007829|PDB:2AL7"
FT HELIX 33..40
FT /evidence="ECO:0007829|PDB:2AL7"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:2AL7"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:2AL7"
FT HELIX 76..81
FT /evidence="ECO:0007829|PDB:2AL7"
FT HELIX 82..86
FT /evidence="ECO:0007829|PDB:2AL7"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:2AL7"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:2AL7"
FT HELIX 104..115
FT /evidence="ECO:0007829|PDB:2AL7"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:2AL7"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:2AL7"
FT HELIX 140..146
FT /evidence="ECO:0007829|PDB:2AL7"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:2AL7"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:2AL7"
FT TURN 164..167
FT /evidence="ECO:0007829|PDB:2AL7"
FT HELIX 170..178
FT /evidence="ECO:0007829|PDB:2AL7"
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
//