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ARL8B_BOVIN
ID   ARL8B_BOVIN             Reviewed;         186 AA.
AC   Q2KI07;
DT   18-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT   07-MAR-2006, sequence version 1.
DT   03-AUG-2022, entry version 94.
DE   RecName: Full=ADP-ribosylation factor-like protein 8B {ECO:0000305};
DE            EC=3.6.5.2 {ECO:0000250|UniProtKB:Q9NVJ2};
GN   Name=ARL8B;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Rumen;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JAN-2006) 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}.
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DR   EMBL; BC112814; AAI12815.1; -; mRNA.
DR   RefSeq; NP_001039536.1; NM_001046071.2.
DR   AlphaFoldDB; Q2KI07; -.
DR   SMR; Q2KI07; -.
DR   STRING; 9913.ENSBTAP00000017150; -.
DR   PaxDb; Q2KI07; -.
DR   PRIDE; Q2KI07; -.
DR   GeneID; 511009; -.
DR   KEGG; bta:511009; -.
DR   CTD; 55207; -.
DR   eggNOG; KOG0075; Eukaryota.
DR   InParanoid; Q2KI07; -.
DR   OrthoDB; 1123043at2759; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR   GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
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; IBA:GO_Central.
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:0008089; P:anterograde axonal transport; IBA:GO_Central.
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_0000232920"
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;  21511 MW;  76E994890D4861EC CRC64;
     MLALISRLLD WFRSLFWKEE MELTLVGLQY SGKTTFVNVI ASGQFSEDMI PTVGFNMRKV
     TKGNVTIKIW DIGGQPRFQS MWERYCRGVN AIVYMIDAAD REKIEASRNE LHNLLDKPQL
     QGIPVLVLGN KRDLPNALDE KQLIEKMNLS AIQDREICCY SISCKEKDNI DITLQWLIQH
     SKSRRS
 
 
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