ADP-ribosylation factor-like protein 3 (ARL3)
The protein contains 182 amino acids for an estimated molecular weight of 20456 Da.
Small GTP-binding protein which cycles between an inactive GDP-bound and an active GTP-bound form, and the rate of cycling is regulated by guanine nucleotide exchange factors (GEF) and GTPase-activating proteins (GAP) (PubMed:16525022, PubMed:18588884). Required for normal cytokinesis and cilia signaling (PubMed:22085962). Requires assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D, in order to cycle between inactive GDP-bound and active GTP-bound forms. Required for targeting proteins to the cilium, including myristoylated NPHP3 and prenylated INPP5E (PubMed:30269812). Targets NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from UNC119B cargo adapter into the cilium (PubMed:22085962). Required for PKD1:PKD2 complex targeting from the trans-Golgi network to the cilium (By similarity). (updated: Jan. 16, 2019)
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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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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| Variant | Description |
|---|---|
| dbSNP:rs1141895 | |
| JBTS35 | |
| JBTS35 | |
| RP83 |
Biological Process
Cilium assembly
Cytokinesis
Golgi to plasma membrane transport
Intraciliary transport
Kidney development
Mitotic cytokinesis
Organelle organization
Photoreceptor cell development
Positive regulation of microtubule polymerization
Post-Golgi vesicle-mediated transport
Protein localization to ciliary membrane
Protein localization to cilium
Protein transport
Small GTPase mediated signal transduction
Smoothened signaling pathway
The reference OMIM entry for this protein is 604695
Adp-ribosylation factor-like 3; arl3
Arfl3
CLONING
ADP-ribosylation factors (ARFs) are low molecular weight GTP-binding proteins belonging to the RAS superfamily; see ARF1 (103180). By sequence analysis of clones randomly isolated from a fetal brain cDNA library, Cavenagh et al. (1994) obtained an EST encoding ARL3. The predicted 182-amino acid ARL3 protein shares 97% amino acid identity with rat Arl3 and 43% identity with human ARF1. Like the ARFs, ARL3 has a glycine at position 2, the site of N myristoylation, and lacks cysteine residues near the C terminus, which are found in other members of the RAS family. Northern blot analysis detected a 1-kb ARL3 transcript in all tissues tested, with highest expression in heart and lung, and lower expression in brain, liver, kidney, ovary, and testis. A 5.5-kb transcript was also detected in most tissues, with highest expression in brain. Immunoblot analysis detected ARL3 in human tumor cell lines but not in normal rodent cells. Although ARL3 binds GTP, it is devoid of activity in the cholera toxin-dependent ADP-ribosylation of Gs (see 139320), and is therefore classified as an ARF-like protein. By immunohistochemical analysis of several mammalian cell lines, including human, Zhou et al. (2006) found that both ARL2 (601175) and ARL3 were expressed at centrosomes, in cytoplasmic punctae, and in the nucleus. ARL3 was also expressed at Golgi membranes and at the mitotic spindle, particularly in metaphase and anaphase. Both ARL2 and ARL3 localized to centrosomes throughout the cell cycle, and their expression in other structures was cell type specific.MAPPING
By somatic cell hybrid and radiation hybrid analyses, Kim (1998) mapped the ARL3 gene to chromosome 10q23.3.GENE FUNCTION
Mutations in the retinitis pigmentosa-2 gene (RP2; 300757) cause a severe form of X-linked retinal degeneration (see 312600). RP2 is a plasma membrane-associated protein which shares homology with tubulin-specific chaperone cofactor C (TBCC; 602971). The RP2 protein, like cofactor C, stimulates the GTPase activity of tubulin in combination with cofactor D. RP2 has also been shown to interact with ARL3 in a nucleotide- and myristoylation-dependent manner. Grayson et al. (2002) examined the relationship between RP2, cofactor C, and ARL3 in patient-derived cell lines and in the retina. In human retina, RP2 was localized to the plasma membrane in both rod and cone photoreceptors, extending from the outer segment through the inner segment to the synaptic terminals. In contrast, cofactor C and ARL3 localized predominantly to the photoreceptor-connecting cilium in rod and cone photoreceptors. Cofactor C was cytoplasmic in distribution, whereas ARL3 localized to other microtubule structures within all cells. Grayson et al. (2002) suggested that RP2 may function in concert with ARL3 to link the cell membrane with the cytoskeleton in photoreceptors as part of the cell signaling or vesicular transport machinery. Veltel et al. (2008) found that recombinant human RP2 formed a complex with murine Arl3 and with human HRG4 (UNC119; 604011), the retinal homolog of PDE-delta (PDE6D; 602676). RP2 induced hydrolysis of Arl3-GTP in the Arl3-HRG4 complex, leading to the release of HRG4, which bound only weakly to Arl3-GDP. Zhou et al. (2006) stated that ARL2 and ARL3 arose from a common ancestor early in eukaryotic evolution and that they remain highly related. However, Zhou et al. (2006) found that the 2 GTPases had distinct effects on microtubule func ... More on the omim web site
Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Dec. 9, 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.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604695 was added.