ARL8B_MACFA
ID ARL8B_MACFA Reviewed; 186 AA.
AC Q4R4S4;
DT 18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=ADP-ribosylation factor-like protein 8B {ECO:0000305};
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:Q9NVJ2};
GN Name=ARL8B; ORFNames=QflA-10573;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Frontal cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
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. Along with its
CC effectors, orchestrates lysosomal transport and fusion. 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. Critical factor involved in NK cell-mediated
CC cytotoxicity. Drives the polarization of cytolytic granules and
CC microtubule-organizing centers (MTOCs) toward the immune synapse
CC between effector NK lymphocytes and target cells (By similarity). In
CC neurons, mediates the anterograde axonal long-range transport of
CC presynaptic lysosome-related vesicles required for presynaptic
CC biogenesis and synaptic function (By similarity). Also acts as a
CC regulator of endosome to lysosome trafficking pathways of special
CC significance for host defense. Regulates cargo trafficking to lysosomes
CC by binding to PLEKHM1 and recruiting the HOPS subunit VPS41, resulting
CC in functional assembly of the HOPS complex on lysosomal membranes.
CC Plays an important role in cargo delivery to lysosomes for antigen
CC presentation and microbial killing. Directs the intersection of CD1d
CC with lipid antigens in lysosomes, and plays a role in intersecting
CC phagosomes with lysosomes to generate phagolysosomes that kill microbes
CC (By similarity). 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 (By
CC similarity). May play a role in chromosome segregation (By similarity).
CC {ECO:0000250|UniProtKB:Q9CQW2, ECO:0000250|UniProtKB:Q9NVJ2}.
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:0000250|UniProtKB:Q9NVJ2}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250|UniProtKB:Q9NVJ2}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q9CQW2}. Synapse {ECO:0000250|UniProtKB:Q9CQW2}.
CC Cytolytic granule membrane {ECO:0000250|UniProtKB:Q9NVJ2}. Note=GTP-
CC bound form resides on lysosomal membranes, whereas GDP-bound form is
CC likely associated with microtubular structures. Localizes with
CC microtubules at the spindle mid-zone during mitosis (By similarity). In
CC dendritic cells, localizes to MHC II+ compartments (By similarity).
CC {ECO:0000250|UniProtKB:Q9CQW2, ECO:0000250|UniProtKB:Q9NVJ2}.
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; AB169820; BAE01901.1; -; mRNA.
DR AlphaFoldDB; Q4R4S4; -.
DR SMR; Q4R4S4; -.
DR STRING; 9541.XP_005596017.1; -.
DR eggNOG; KOG0075; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0061909; P:autophagosome-lysosome fusion; ISS:UniProtKB.
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; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0032418; P:lysosome localization; ISS:UniProtKB.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; ISS:UniProtKB.
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 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 2: Evidence at transcript 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_0000232922"
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"
SQ SEQUENCE 186 AA; 21581 MW; BD867C6B344502BB CRC64;
MLALISRLLD WFRSLFWKEE MELTLVGLQY SGKTTFVNVI ASGQFSEDMI PTVGFNMRKV
TKGNVTIKIW DIGGQPRYRS MWERYCRGVN AIVYMIDAAD REKIEASRNE LHNLLDKPQL
QGIPVLVLGN KRDLPNALDE KQLIEKMNLS AIQDREICCY SISCKEKDNI DITLQWLIQY
SKSRRS
