ARL6

Summary

Gene Symbol: ARL6
Description: ADP ribosylation factor like GTPase 6
Alias: BBS3, RP55, ADP-ribosylation factor-like protein 6, Bardet-Biedl syndrome 3 protein
Species: human
Products:     ARL6

Top Publications

  1. Pretorius P, Baye L, Nishimura D, Searby C, Bugge K, Yang B, et al. Identification and functional analysis of the vision-specific BBS3 (ARL6) long isoform. PLoS Genet. 2010;6:e1000884 pubmed publisher
    ..We have identified a novel transcript of a known BBS gene, BBS3 (ARL6), which includes an additional exon...
  2. Chiang A, Nishimura D, Searby C, Elbedour K, Carmi R, Ferguson A, et al. Comparative genomic analysis identifies an ADP-ribosylation factor-like gene as the cause of Bardet-Biedl syndrome (BBS3). Am J Hum Genet. 2004;75:475-84 pubmed
    ..One of these genes, ADP-ribosylation factor-like 6 (ARL6), contains a homozygous stop mutation that segregates completely with the disease in the Bedouin kindred originally ..
  3. Fan Y, Esmail M, Ansley S, Blacque O, Boroevich K, Ross A, et al. Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nat Genet. 2004;36:989-93 pubmed
    ..Using a bioinformatic screen for ciliary genes in combination with mutational analyses, we identified ARL6 as the gene underlying Bardet-Biedl syndrome type 3, a multisystemic disorder characterized by obesity, blindness, ..
  4. Wiens C, Tong Y, Esmail M, Oh E, Gerdes J, Wang J, et al. Bardet-Biedl syndrome-associated small GTPase ARL6 (BBS3) functions at or near the ciliary gate and modulates Wnt signaling. J Biol Chem. 2010;285:16218-30 pubmed publisher
    ..Here, we present the crystal structure of ARL6, mutations in which cause Bardet-Biedl syndrome (BBS3), and reveal its unique ring-like localization at the distal ..
  5. Ingley E, Williams J, Walker C, Tsai S, Colley S, Sayer M, et al. A novel ADP-ribosylation like factor (ARL-6), interacts with the protein-conducting channel SEC61beta subunit. FEBS Lett. 1999;459:69-74 pubmed
    ..These results demonstrate that ARL-6, a novel member of the ADP-ribosylation factor-like family, interacts with the SEC61beta subunit. ..
  6. Pasqualato S, Renault L, Cherfils J. Arf, Arl, Arp and Sar proteins: a family of GTP-binding proteins with a structural device for 'front-back' communication. EMBO Rep. 2002;3:1035-41 pubmed
    ..that propagate information across the protein and identify them in all of the Arf family proteins other than Arl6 and Arl4/Arl7...
  7. Kahn R, Volpicelli Daley L, Bowzard B, Shrivastava Ranjan P, Li Y, Zhou C, et al. Arf family GTPases: roles in membrane traffic and microtubule dynamics. Biochem Soc Trans. 2005;33:1269-72 pubmed
    ..At least six Arf family members were found in very early eukaryotes, including orthologues of Arf, Sar, Arl2, Arl3, Arl6 and Arl8. While roles for Arfs in membrane traffic are well known, those for most of the Arls remain unknown...
  8. Kobayashi T, Hori Y, Ueda N, Kajiho H, Muraoka S, Shima F, et al. Biochemical characterization of missense mutations in the Arf/Arl-family small GTPase Arl6 causing Bardet-Biedl syndrome. Biochem Biophys Res Commun. 2009;381:439-42 pubmed publisher
    ..Mutations in the Arf/Arl-family GTPase Arl6 have been recently shown to be responsible for BBS type 3...
  9. Pereiro I, Valverde D, Piñeiro Gallego T, Baiget M, Borrego S, Ayuso C, et al. New mutations in BBS genes in small consanguineous families with Bardet-Biedl syndrome: detection of candidate regions by homozygosity mapping. Mol Vis. 2010;16:137-43 pubmed
    ..the disease-causing mutation in six of the families studied, five of which had novel sequence variants in BBS3, BBS6, and BBS12. This is the first null mutation reported in BBS3...

More Information

Publications36

  1. Huang H, Dai E, Liu J, Tu C, Yang T, Tsai H. The embryonic expression patterns and the knockdown phenotypes of zebrafish ADP-ribosylation factor-like 6 interacting protein gene. Dev Dyn. 2009;238:232-40 pubmed publisher
    ADP-ribosylation factor-like 6 (Arl6) mutation is linked to human disease and Arl6 interacts with Arl6 interacting protein (Arl6ip). However, the expression pattern and function of Arl6ip during embryogenesis are unknown...
  2. Chamling X, Seo S, Searby C, Kim G, Slusarski D, Sheffield V. The centriolar satellite protein AZI1 interacts with BBS4 and regulates ciliary trafficking of the BBSome. PLoS Genet. 2014;10:e1004083 pubmed publisher
    ..Under conditions in which the BBSome does not normally enter cilia, such as in BBS3 or BBS5 depleted cells, knock down of AZI1 with siRNA restores BBSome trafficking to cilia...
  3. Chandrasekar S, Namboothiri S, Sen P, Sarangapani S. Screening for mutation hotspots in Bardet-Biedl syndrome patients from India. Indian J Med Res. 2018;147:177-182 pubmed publisher
    ..In the 64 BBS patients (44 males, 20 females) were studied, mutations were predominant in BBS10 and ARL6 genes; the c.272T>C; p.(I91T) mutation in ARL6 gene was a recurrent mutation. One novel non-sense mutation c...
  4. Ye F, Nager A, Nachury M. BBSome trains remove activated GPCRs from cilia by enabling passage through the transition zone. J Cell Biol. 2018;217:1847-1868 pubmed publisher
    ..The BBSome and the small guanosine triphosphatase Arl6, which triggers BBSome coat polymerization, are required for the exit of activated signaling receptors from cilia, ..
  5. Leitch C, Lodh S, Prieto Echagüe V, Badano J, Zaghloul N. Basal body proteins regulate Notch signaling through endosomal trafficking. J Cell Sci. 2014;127:2407-19 pubmed publisher
    ..We observe similar defects with disruption of BBS3. Loss of another basal body protein, ALMS1, also enhances Notch activation and the accumulation of receptor in late ..
  6. Lindstrand A, Frangakis S, Carvalho C, Richardson E, McFadden K, Willer J, et al. Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome. Am J Hum Genet. 2016;99:318-36 pubmed publisher
    ..5%), including 13 different deletions in eight BBS genes (BBS1, BBS2, ARL6/BBS3, BBS4, BBS5, BBS7, BBS9, and NPHP1) and a deletion and a duplication in other ciliopathy-associated genes (..
  7. Nozaki S, Katoh Y, Kobayashi T, Nakayama K. BBS1 is involved in retrograde trafficking of ciliary GPCRs in the context of the BBSome complex. PLoS ONE. 2018;13:e0195005 pubmed publisher
    ..of the BBSome to promote cargo trafficking has been proposed to be regulated by the Arf-like small GTPase ARL6/BBS3, through its interaction with the BBS1 subunit of the BBSome...
  8. Ece Solmaz A, Onay H, AtIk T, Aykut A, Cerrah Gunes M, Ozalp Yuregir O, et al. Targeted multi-gene panel testing for the diagnosis of Bardet Biedl syndrome: Identification of nine novel mutations across BBS1, BBS2, BBS4, BBS7, BBS9, BBS10 genes. Eur J Med Genet. 2015;58:689-94 pubmed publisher
    ..were investigated using a next generation sequencing panel which included 17 known BBS causing genes (BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12, MKS1, NPHP6, WDPCP, SDCCAG8, NPHP1)...
  9. Kawasaki M, Izu Y, Hayata T, Ideno H, Nifuji A, Sheffield V, et al. Bardet-Biedl syndrome 3 regulates the development of cranial base midline structures. Bone. 2017;101:179-190 pubmed publisher
    ..The patients manifest a characteristic craniofacial dysmorphology but the effects of Bbs3 deficiency in the developmental process during the craniofacial pathogenesis are still incompletely understood...
  10. Nachury M. The molecular machines that traffic signaling receptors into and out of cilia. Curr Opin Cell Biol. 2018;51:124-131 pubmed publisher
    ..complex promotes the entry of signaling receptors into cilia while the BBSome and its membrane recruitment factor Arl6GTP ferry activated signaling receptors out of cilia...
  11. Aston K, Carrell D. Genome-wide study of single-nucleotide polymorphisms associated with azoospermia and severe oligozoospermia. J Androl. 2009;30:711-25 pubmed publisher
  12. Jin H, White S, Shida T, Schulz S, Aguiar M, Gygi S, et al. The conserved Bardet-Biedl syndrome proteins assemble a coat that traffics membrane proteins to cilia. Cell. 2010;141:1208-19 pubmed publisher
    ..The BBSome is the major effector of the Arf-like GTPase Arl6/BBS3, and the BBSome and GTP-bound Arl6 colocalize at ciliary punctae in an interdependent manner...
  13. Biswas P, Duncan J, Maranhao B, Kozak I, Branham K, Gabriel L, et al. Genetic analysis of 10 pedigrees with inherited retinal degeneration by exome sequencing and phenotype-genotype association. Physiol Genomics. 2017;49:216-229 pubmed publisher
    ..Met323Val fsX20), RPE65 (p.Phe252Ser, Thr454Leu fsX31), ARL6 (p.Arg121His), USH2A (p.Gly3142Ter, p.Cys3294Trp), PDE6B (p.Gln652Ter), and DHDDS (p...
  14. Liew G, Ye F, Nager A, Murphy J, Lee J, Aguiar M, et al. The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3. Dev Cell. 2014;31:265-78 pubmed publisher
    ..GTP loading onto the Arf-like GTPase ARL6/BBS3 drives assembly of a membrane-apposed BBSome coat that promotes cargo entry into cilia, yet how and where ARL6 is ..
  15. Su X, Driscoll K, Yao G, Raed A, Wu M, Beales P, et al. Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of polycystic kidney disease 1 protein. Hum Mol Genet. 2014;23:5441-51 pubmed publisher
    ..Expression of a pathogenic BBS3/Arl6 mutant (T31R) that locks Arl6 in the GDP form leads to stunted cilia and inhibition of PC1 on primary cilia...
  16. Mourão A, Nager A, Nachury M, Lorentzen E. Structural basis for membrane targeting of the BBSome by ARL6. Nat Struct Mol Biol. 2014;21:1035-41 pubmed publisher
    ..critical step in BBSome-mediated sorting is recruitment of the BBSome to membranes by the GTP-bound Arf-like GTPase ARL6. We have determined crystal structures of Chlamydomonas reinhardtii ARL6-GDP, ARL6-GTP and the ARL6-GTP-BBS1 ..
  17. Li C, He J, Chen J, Zhao J, Gu D, Hixson J, et al. Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study. Hypertension. 2016;68:348-55 pubmed publisher
    ..75×10(-10)) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium. ..
  18. Zhang Q, Hu J, Ling K. Molecular views of Arf-like small GTPases in cilia and ciliopathies. Exp Cell Res. 2013;319:2316-22 pubmed publisher
    ..However, how these small GTPases affect cilia formation and function remains poorly understood. Here we review and discuss the ciliary role of three Arf-like small GTPases (Arls), Arl3, Arl6, and Arl13b.
  19. Khan S, Ullah I, Irfanullah -, Touseef M, Basit S, Khan M, et al. Novel homozygous mutations in the genes ARL6 and BBS10 underlying Bardet-Biedl syndrome. Gene. 2013;515:84-8 pubmed publisher
    ..Linkage in the family A was established to ARL6 on chromosome 3q11.2, while family B showed linkage to BBS10 on chromosome 12q21.2...
  20. Zhang Q, Nishimura D, Seo S, Vogel T, Morgan D, Searby C, et al. Bardet-Biedl syndrome 3 (Bbs3) knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes. Proc Natl Acad Sci U S A. 2011;108:20678-83 pubmed publisher
    ..BBS3 (ARL6), an ADP ribosylation factor-like small GTPase, is not part of the BBSome complex...
  21. Jacobs S, Schilf C, Fliegert F, Koling S, Weber Y, Schurmann A, et al. ADP-ribosylation factor (ARF)-like 4, 6, and 7 represent a subgroup of the ARF family characterization by rapid nucleotide exchange and a nuclear localization signal. FEBS Lett. 1999;456:384-8 pubmed
    The novel ARF-like GTPase ARL7 is a close relative of ARL4 and ARL6 (71% and 59%) identical amino acids)...
  22. Liangpunsakul S, Lai X, Ross R, Yu Z, Modlik E, Westerhold C, et al. Novel serum biomarkers for detection of excessive alcohol use. Alcohol Clin Exp Res. 2015;39:556-65 pubmed publisher
    ..acyltransferase (LCAT), hepatocyte growth factor-like protein (MST1), and ADP-ribosylation factor 6 (ARL6)...
  23. Sheffield V, Carmi R, Kwitek Black A, Rokhlina T, Nishimura D, Duyk G, et al. Identification of a Bardet-Biedl syndrome locus on chromosome 3 and evaluation of an efficient approach to homozygosity mapping. Hum Mol Genet. 1994;3:1331-5 pubmed
    ..In addition, we demonstrate the feasibility of using pooled DNA samples from members of large kindreds as an efficient approach to homozygosity mapping. ..
  24. Gencer S, Oleinik N, Kim J, Panneer Selvam S, De Palma R, Dany M, et al. TGF-β receptor I/II trafficking and signaling at primary cilia are inhibited by ceramide to attenuate cell migration and tumor metastasis. Sci Signal. 2017;10: pubmed publisher
    ..the formation of the Smad7-TβRI inhibitory complex and increased the association between TβRI and the transporter Arl6 through a previously unknown cilia-targeting signal (Ala31Thr32Ala33Leu34
  25. Klink B, Zent E, Juneja P, Kuhlee A, Raunser S, Wittinghofer A. A recombinant BBSome core complex and how it interacts with ciliary cargo. elife. 2017;6: pubmed publisher
    ..involves the BBSome, an eight-membered protein complex that is recruited to ciliary membranes by the G-protein Arl6. BBSome malfunction leads to Bardet-Biedl syndrome, a ciliopathy with severe consequences...
  26. Pretorius P, Aldahmesh M, Alkuraya F, Sheffield V, Slusarski D. Functional analysis of BBS3 A89V that results in non-syndromic retinal degeneration. Hum Mol Genet. 2011;20:1625-32 pubmed publisher
    ..mapping with a consanguineous family with isolated retinitis pigmentosa identified a missense mutation in BBS3, a known BBS gene. The mutation in BBS3 encodes a single amino acid change at position 89 from alanine to valine...