ADP-ribosylation factor-like protein 8B (ARL8B)
The protein contains 186 amino acids for an estimated molecular weight of 21539 Da.
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:16650381, PubMed:16537643, PubMed:28325809, PubMed:25898167). 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:29592961, PubMed:24088571). 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). 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 me (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Anterograde axonal transport
Antigen processing and presentation following phagocytosis
Antigen processing and presentation of polysaccharide antigen via MHC class II
Autophagosome-lysosome fusion
Calcium ion regulated lysosome exocytosis
Cell cycle
Cell division
Chromosome segregation
Endosomal transport
Endosome to lysosome transport of low-density lipoprotein particle
Late endosome to lysosome transport
Lysosome localization
Metabolic process
Natural killer cell mediated cytotoxicity
Phagosome-lysosome fusion
Plasma membrane repair
Protein transport
Small GTPase mediated signal transduction
Viral exocytosis
Cellular Component
Axon cytoplasm
Cell junction
Cytolytic granule membrane
Cytoplasm
Cytosol
Extracellular exosome
Late endosome membrane
Lysosomal membrane
Lysosome
Membrane
Midbody
Spindle midzone
Synapse
Vacuolar membrane
Molecular Function
Alpha-tubulin binding
Beta-tubulin binding
GDP binding
GTP binding
GTPase activity
The reference OMIM entry for this protein is 616596
Adp-ribosylation factor-like 8b; arl8b
Small g protein indispensable for equal chromosome segregation 1; gie1
DESCRIPTION
Small GTPases function as molecular switches and work in conjunction with a range of cellular targets to elicit or regulate biologic function. ARL8A (616597) and ARL8B form a distinct subfamily of small GTPases (Okai et al., 2004).CLONING
By database analysis to identify novel small GTPases, followed by PCR of a human brain cDNA library, Okai et al. (2004) cloned ARL8B, which they called GIE1. The deduced 186-amino acid GIE1 protein has 5 motifs conserved in small GTPases, including GTP-binding domains and a putative effector domain, but it lacks a putative lipid modification motif found in other small GTPases. GIE1 shares 91% identity with GIE2 (ARL8A), and the GIE proteins share about 30% identity with other small GTPases. Northern blot analysis of 12 human tissues detected ubiquitous expression of a major 3.5-kb GIE1 transcript and a minor 2.0-kb transcript. An antibody that did not differentiate between GIE1 and GIE2 detected an apparent 22-kD polypeptide in rat PC12 cells. Immunohistochemical analysis revealed that GIE localized to the cytoplasm along with microtubules during interphase, then redistributed to spindle midzone in anaphase and to the midbody in late telophase. Database analysis revealed 2 GIE genes in mammals, a single GIE ortholog in Drosophila and C. elegans, and no ortholog in yeast. Bagshaw et al. (2006) found that epitope-tagged ARL8B localized to lysosomes in transfected HeLa and Vero green monkey kidney cells.GENE FUNCTION
Using thin-layer chromatography, Okai et al. (2004) found both GTP- and GDP-bound forms of epitope-tagged GIE1 following expression in HeLa cells, suggesting that GIE1 cycles between both nucleotide-bound forms. Overexpression of a dominant-negative GIE1 mutant or a mutant lacking the effector domain induced abnormal chromosomes and appearance of micronuclei. Knockdown of Drosophila Gie resulted in formation of chromatin bridges at anaphase, with occasional lagging chromosomes and missegregation. Epitope-tagged GIE1 immunoprecipitated with beta-tubulin (TUBB; 191130) from HeLa cells. GIE1 also interacted with alpha-tubulin (see 191110), but not with gamma-tubulin (see 191135). GIE1 cosedimented with stabilized microtubules, but not with free tubulin. Mutation analysis revealed that the effector domain, but not the nucleotide-binding domains, was required for interaction of GIE1 with beta-tubulin. Using human ARL8B mutants that exclusively bound GTP or GDP, Bagshaw et al. (2006) found that GTP-ARL8B localized to lysosomal membranes, whereas GDP-ARL8B distributed in a diffuse, perinuclear pattern in transfected HeLa cells. GDP-ARL8B likely associated with microtubular structures. Overexpression of GTP-ARL8B caused dispersal of lysosomes to the cell periphery and into membrane projections. Pu et al. (2015) identified a protein complex in HeLa cells that they called BLOC1 (see 601444)-related complex, or BORC. BORC recruited ARL8B to lysosomes and mediated kinesin-dependent movement of lysosomes toward the cell periphery along the plus ends of microtubules. Knockdown of BORC subunits, but not BLOC subunits, caused dissociation of ARL8B from lysosomes and collapse of lysosomes into the pericentriolar region. In turn, loss of BORC reduced cell spreading and cell migration. Knockdown of ARL8B also reduced cell spreading and migration and caused clustering of lysosomes in the juxtanuclear region. Pu et al. (2015) concluded that BORC acts at an early stag ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 7, 2018: Protein entry updated
Automatic update: OMIM entry 616596 was added.
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed