ARL6_MOUSE
ID ARL6_MOUSE Reviewed; 186 AA.
AC O88848; Q3TY77;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=ADP-ribosylation factor-like protein 6;
GN Name=Arl6; Synonyms=Bbs3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10508919; DOI=10.1016/s0014-5793(99)01188-6;
RA Ingley E., Williams J.H., Walker C.E., Tsai S., Colley S., Sayer M.S.,
RA Tilbrook P.A., Sarna M., Beaumont J.G., Klinken S.P.;
RT "A novel ADP-ribosylation like factor (ARL-6), interacts with the protein-
RT conducting channel SEC61beta subunit.";
RL FEBS Lett. 459:69-74(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Visual cortex;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=20333246; DOI=10.1371/journal.pgen.1000884;
RA Pretorius P.R., Baye L.M., Nishimura D.Y., Searby C.C., Bugge K., Yang B.,
RA Mullins R.F., Stone E.M., Sheffield V.C., Slusarski D.C.;
RT "Identification and functional analysis of the vision-specific BBS3 (ARL6)
RT long isoform.";
RL PLoS Genet. 6:E1000884-E1000884(2010).
RN [5]
RP FUNCTION.
RX PubMed=24939912; DOI=10.1093/hmg/ddu267;
RA Su X., Driscoll K., Yao G., Raed A., Wu M., Beales P.L., Zhou J.;
RT "Bardet-Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of
RT polycystic kidney disease 1 protein.";
RL Hum. Mol. Genet. 23:5441-5451(2014).
CC -!- FUNCTION: Involved in membrane protein trafficking at the base of the
CC ciliary organelle (By similarity). Mediates recruitment onto plasma
CC membrane of the BBSome complex which would constitute a coat complex
CC required for sorting of specific membrane proteins to the primary cilia
CC (By similarity). Together with BBS1, is necessary for correct
CC trafficking of PKD1 to primary cilia (PubMed:24939912). Together with
CC the BBSome complex and LTZL1, controls SMO ciliary trafficking and
CC contributes to the sonic hedgehog (SHH) pathway regulation (By
CC similarity). May regulate cilia assembly and disassembly and subsequent
CC ciliary signaling events such as the Wnt signaling cascade (By
CC similarity). Isoform 2 may be required for proper retinal function and
CC organization (PubMed:20333246). {ECO:0000250|UniProtKB:Q9H0F7,
CC ECO:0000269|PubMed:20333246, ECO:0000269|PubMed:24939912}.
CC -!- SUBUNIT: Interacts with SEC61B, ARL6IP1, ARL6IP2, ARL6IP3, ARL6IP4
CC ARL6IP5 and ARL6IP6. Interacts (GTP-bound form) with the BBSome a
CC complex that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and
CC BBIP10. Interacts (GTP-free form) with IFT27.
CC {ECO:0000250|UniProtKB:Q9H0F7}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}; Cytoplasmic side
CC {ECO:0000250}. Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000250}.
CC Cytoplasm, cytoskeleton, cilium basal body {ECO:0000250}. Note=Appears
CC in a pattern of punctae flanking the microtubule axoneme that likely
CC correspond to small membrane-associated patches. Localizes to the so-
CC called ciliary gate where vesicles carrying ciliary cargo fuse with the
CC membrane (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Bbs3;
CC IsoId=O88848-1; Sequence=Displayed;
CC Name=2; Synonyms=Bbs3l;
CC IsoId=O88848-2; Sequence=VSP_040512;
CC -!- TISSUE SPECIFICITY: Most abundant in brain and kidney. Expressed in
CC heart and eye. Isoform 2 is expressed only in the retina.
CC {ECO:0000269|PubMed:20333246}.
CC -!- DISRUPTION PHENOTYPE: Isoform 2 deficient mice present a disruption of
CC the normal photoreceptor architecture. {ECO:0000269|PubMed:20333246}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
CC {ECO:0000305}.
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DR EMBL; AF031903; AAC62194.1; -; mRNA.
DR EMBL; AK158832; BAE34686.1; -; mRNA.
DR EMBL; AK003778; BAB22990.1; -; mRNA.
DR CCDS; CCDS28259.1; -. [O88848-1]
DR CCDS; CCDS84248.1; -. [O88848-2]
DR RefSeq; NP_001334173.1; NM_001347244.1. [O88848-2]
DR RefSeq; NP_062639.3; NM_019665.3. [O88848-1]
DR AlphaFoldDB; O88848; -.
DR SMR; O88848; -.
DR BioGRID; 207885; 1.
DR CORUM; O88848; -.
DR IntAct; O88848; 10.
DR STRING; 10090.ENSMUSP00000023405; -.
DR PhosphoSitePlus; O88848; -.
DR EPD; O88848; -.
DR MaxQB; O88848; -.
DR PaxDb; O88848; -.
DR PeptideAtlas; O88848; -.
DR PRIDE; O88848; -.
DR ProteomicsDB; 283173; -. [O88848-1]
DR ProteomicsDB; 283174; -. [O88848-2]
DR ABCD; O88848; 1 sequenced antibody.
DR Antibodypedia; 15743; 140 antibodies from 30 providers.
DR DNASU; 56297; -.
DR Ensembl; ENSMUST00000023405; ENSMUSP00000023405; ENSMUSG00000022722. [O88848-1]
DR Ensembl; ENSMUST00000099646; ENSMUSP00000097238; ENSMUSG00000022722. [O88848-2]
DR Ensembl; ENSMUST00000118438; ENSMUSP00000113127; ENSMUSG00000022722. [O88848-2]
DR GeneID; 56297; -.
DR KEGG; mmu:56297; -.
DR UCSC; uc007zpl.2; mouse. [O88848-1]
DR UCSC; uc007zpm.2; mouse. [O88848-2]
DR CTD; 84100; -.
DR MGI; MGI:1927136; Arl6.
DR VEuPathDB; HostDB:ENSMUSG00000022722; -.
DR eggNOG; KOG0070; Eukaryota.
DR GeneTree; ENSGT00940000156459; -.
DR InParanoid; O88848; -.
DR OMA; WQIVPSN; -.
DR OrthoDB; 1271528at2759; -.
DR PhylomeDB; O88848; -.
DR TreeFam; TF105466; -.
DR Reactome; R-MMU-5620922; BBSome-mediated cargo-targeting to cilium.
DR BioGRID-ORCS; 56297; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Arl6; mouse.
DR PRO; PR:O88848; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; O88848; protein.
DR Bgee; ENSMUSG00000022722; Expressed in olfactory epithelium and 258 other tissues.
DR ExpressionAtlas; O88848; baseline and differential.
DR Genevisible; O88848; MM.
DR GO; GO:0005879; C:axonemal microtubule; ISS:UniProtKB.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0030117; C:membrane coat; ISS:UniProtKB.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; ISS:MGI.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005543; F:phospholipid binding; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IEP:BHF-UCL.
DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central.
DR GO; GO:0006471; P:protein ADP-ribosylation; ISS:MGI.
DR GO; GO:0061512; P:protein localization to cilium; ISO:MGI.
DR GO; GO:0097499; P:protein localization to non-motile cilium; IDA:UniProtKB.
DR GO; GO:0051258; P:protein polymerization; ISS:UniProtKB.
DR GO; GO:0006612; P:protein targeting to membrane; ISS:UniProtKB.
DR GO; GO:1903445; P:protein transport from ciliary membrane to plasma membrane; IMP:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; ISS:MGI.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; IMP:MGI.
DR GO; GO:0010842; P:retina layer formation; IMP:MGI.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:MGI.
DR CDD; cd04157; Arl6; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR041839; Arl6.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR024156; Small_GTPase_ARF.
DR InterPro; IPR006689; Small_GTPase_ARF/SAR.
DR PANTHER; PTHR11711; PTHR11711; 1.
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 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection;
KW Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; GTP-binding;
KW Lipoprotein; Magnesium; Membrane; Metal-binding; Myristate;
KW Nucleotide-binding; Protein transport; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..186
FT /note="ADP-ribosylation factor-like protein 6"
FT /id="PRO_0000207473"
FT BINDING 24..31
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 50
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 50
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 69..73
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 130..133
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 179..186
FT /note="DQIQAVKT -> EKTVQSDPSCEDVKR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_040512"
SQ SEQUENCE 186 AA; 20959 MW; 4F26947318977386 CRC64;
MGLLDRLSGL LGLKKKEVHV LCLGLDNSGK TTIINKLKPS NAQSQDIVPT IGFSIEKFKS
SSLSFTVFDM SGQGRYRNLW EHYYKDGQAI IFVIDSSDKL RMVVAKEELD TLLNHPDIKH
RRIPILFFAN KMDLRDSVTS VKVSQLLCLE SIKDKPWHIC ASDAIKGEGL QEGVDWLQDQ
IQAVKT
