ARL8B
entrez
55207
canonical
uniprot
Q9NVJ2
canonical
ensembl
ENSG00000134108
resolver
ensp
ENSP00000256496
resolver
genesymbol
ARL8B
resolver
genesymbol_syn
ARL10C
resolver
genesymbol_syn
GIE1
resolver
hgnc
HGNC:25564
resolver
uniprot
B4DI85
resolver
uniprot_entry
ARL8B_HUMAN
resolver
uniprot_sec
B4DI85
resolver
amino_acid_sequence
MLALISRLLDWFRSLFWKEEMELTLVGLQYSGKTTFVNVIASGQFSEDMIPTVGFNMRKVTKGNVTIKIWDIGGQPRFRSMWERYCRGVNAIVYMIDAADREKIEASRNELHNLLDKPQLQGIPVLVLGNKRDLPNALDEKQLIEKMNLSAIQDREICCYSISCKEKDNIDITLQWLIQHSKSRRS
uniprot
proteins
ec_number
3.6.5.2
uniprot
proteins
function
FUNCTION: Small GTPase which cycles between active GTP-bound and inactive GDP-bound states (PubMed:15331635, PubMed:16537643). In its active state, binds to a variety of effector proteins playing a key role in the regulation of lysosomal positioning which is important for nutrient sensing, natural killer cell-mediated cytotoxicity and antigen presentation. Along with its effectors, orchestrates lysosomal transport and fusion (PubMed:16537643, PubMed:16650381, PubMed:25898167, PubMed:27808481, PubMed:28325809). Localizes specifically to lysosomal membranes and mediates anterograde lysosomal motility by recruiting PLEKHM2, which in turn recruits the motor protein kinesin-1 on lysosomes. Required for lysosomal and cytolytic granule exocytosis (PubMed:22172677, PubMed:24088571, PubMed:29592961). Critical factor involved in NK cell-mediated cytotoxicity. Drives the polarization of cytolytic granules and microtubule-organizing centers (MTOCs) toward the immune synapse between effector NK lymphocytes and target cells (PubMed:24088571). In neurons, mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles required for presynaptic biogenesis and synaptic function (By similarity). Also acts as a regulator of endosome to lysosome trafficking pathways of special significance for host defense (PubMed:21802320). Recruits RUFY1 onto early endosomes regulating endosomes to trans-Golgi network proteins retrieval (PubMed:36282215). Regulates cargo trafficking to lysosomes by binding to PLEKHM1 and recruiting the HOPS subunit VPS41, resulting in functional assembly of the HOPS complex on lysosomal membranes (PubMed:16537643, PubMed:25908847). Plays an important role in cargo delivery to lysosomes for antigen presentation and microbial killing. Directs the intersection of CD1d with lipid antigens in lysosomes, and plays a role in intersecting phagosomes with lysosomes to generate phagolysosomes that kill microbes (PubMed:21802320, PubMed:25908847). Involved in the process of MHC II presentation. Regulates the delivery of antigens to lysosomes and the formation of MHC II-peptide complexes through the recruitment of the HOPS complex to lysosomes allowing the fusion of late endosomes to lysosomes (By similarity). May play a role in chromosome segregation (PubMed:15331635). {ECO:0000250|UniProtKB:Q9CQW2, ECO:0000269|PubMed:15331635, ECO:0000269|PubMed:16537643, ECO:0000269|PubMed:16650381, ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:22172677, ECO:0000269|PubMed:24088571, ECO:0000269|PubMed:25898167, ECO:0000269|PubMed:25908847, ECO:0000269|PubMed:27808481, ECO:0000269|PubMed:28325809, ECO:0000269|PubMed:29592961, ECO:0000269|PubMed:36282215}.; FUNCTION: (Microbial infection) During Mycobacterium tuberculosis (Mtb) infection, is required for plasma membrane repair by controlling the exocytosis of lysosomes in macrophages. ARL8B secretion pathway is crucial to control the type of cell death of the M.tuberculosis-infected macrophages, distinguishing avirulent from virulent Mtb induced necrotic cell death. {ECO:0000269|PubMed:29592961}.; FUNCTION: (Microbial infection) During infection, coronaviruses such as SARS-CoV-2 and the chaperone HSPA5/GRP78 are probably co-released through ARL8B-dependent lysosomal exocytic pathway for unconventional egress. {ECO:0000269|PubMed:33157038}.
uniprot
proteins
mass_dalton
21539
uniprot
proteins
mutagenesis
MUTAGEN 2; /note="L->A: Diffuse cytoplasmic distribution and loss of localization to lysosomes. No effect on acetylation."; /evidence="ECO:0000269|PubMed:16537643"; MUTAGEN 2; /note="L->F: No effect on localization and acetylation."; /evidence="ECO:0000269|PubMed:16537643"; MUTAGEN 5..12; /note="ISRLLDWF->ASRALDWA: Diffuse cytoplasmic distribution and loss of localization to lysosomes. No effect on acetylation."; /evidence="ECO:0000269|PubMed:16537643"; MUTAGEN 34; /note="T->N: Binds GDP, hence is inactive. Alters chromosome segregation. Decreases interaction with VPS41. Loss of lysosomal location. Loss of interaction with PLEKHM1. Loss of interaction with RUFY3 and RUFY4."; /evidence="ECO:0000269|PubMed:15331635, ECO:0000269|PubMed:16650381, ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:35314674"; MUTAGEN 49..58; /note="Missing: Alters chromosome segregation."; /evidence="ECO:0000269|PubMed:15331635"; MUTAGEN 70; /note="W->R: Preferentially binds GTP."; /evidence="ECO:0000269|PubMed:15331635"; MUTAGEN 74..85; /note="Missing: Alters chromosome segregation."; /evidence="ECO:0000269|PubMed:15331635"; MUTAGEN 75; /note="Q->L: Prevents GTP hydrolysis, hence remains active. No effect on lysosomal location. Alters lysosomes cellular distribution and motility. Increases interaction with VPS41. No effect on interaction with PLEKHM1. Does not affect interaction with RUFY3 and RUFY4."; /evidence="ECO:0000269|PubMed:16537643, ECO:0000269|PubMed:16650381, ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:28325809, ECO:0000269|PubMed:35314674"; MUTAGEN 130; /note="N->I: Loss of GTP/GDP-binding. Affects chromosome segregation."; /evidence="ECO:0000269|PubMed:15331635"; MUTAGEN 141; /note="K->R: Abolished ubiquitination by RNF167."; /evidence="ECO:0000269|PubMed:27808481
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated at Lys-141 by RNF167, leading to its degradation. {ECO:0000269|PubMed:27808481}.
uniprot
proteins
protein_family
Arf family
uniprot
proteins
protein_family
Small GTPase superfamily
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15331635
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16537643
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
16650381
uniprot
proteins
pubmed
17897319
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21802320
uniprot
proteins
pubmed
22172677
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
24088571
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25898167
uniprot
proteins
pubmed
25908847
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27808481
uniprot
proteins
pubmed
28325809
uniprot
proteins
pubmed
29592961
uniprot
proteins
pubmed
33157038
uniprot
proteins
pubmed
35314674
uniprot
proteins
pubmed
36282215
uniprot
proteins
sequence_length
186
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Late endosome membrane {ECO:0000269|PubMed:16537643}. Lysosome membrane {ECO:0000269|PubMed:16650381, ECO:0000269|PubMed:21802320, ECO:0000269|PubMed:22172677, ECO:0000269|PubMed:25898167, ECO:0000269|PubMed:27808481, ECO:0000269|PubMed:28325809, ECO:0000269|PubMed:29592961}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:15331635}. Cell projection, axon {ECO:0000250|UniProtKB:Q9CQW2}. Synapse {ECO:0000250|UniProtKB:Q9CQW2}. Cytolytic granule membrane {ECO:0000269|PubMed:24088571}. Early endosome membrane {ECO:0000269|PubMed:36282215}. Note=GTP-bound form resides on lysosomal membranes, whereas GDP-bound form is likely associated with microtubular structures (PubMed:16650381). Localizes with microtubules at the spindle mid-zone during mitosis. In dendritic cells, localizes to MHC II+ compartments (By similarity). {ECO:0000250|UniProtKB:Q9CQW2, ECO:0000269|PubMed:15331635, ECO:0000269|PubMed:16650381}.
uniprot
proteins