ARL3_MOUSE
ID ARL3_MOUSE Reviewed; 182 AA.
AC Q9WUL7;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=ADP-ribosylation factor-like protein 3 {ECO:0000305};
GN Name=Arl3 {ECO:0000312|MGI:MGI:1929699};
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], INTERACTION WITH PDE6D, AND MUTAGENESIS OF
RP THR-31 AND GLN-71.
RX PubMed=10518933; DOI=10.1016/s0014-5793(99)01117-5;
RA Linari M., Hanzal-Bayer M., Becker J.;
RT "The delta subunit of rod specific cyclic GMP phosphodiesterase, PDE delta,
RT interacts with the Arf-like protein Arl3 in a GTP specific manner.";
RL FEBS Lett. 458:55-59(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, INTERACTION WITH PDE6D, AND GTP/GDP-BINDING.
RX PubMed=15979089; DOI=10.1016/j.jmb.2005.05.036;
RA Hanzal-Bayer M., Linari M., Wittinghofer A.;
RT "Properties of the interaction of Arf-like protein 2 with PDEdelta.";
RL J. Mol. Biol. 350:1074-1082(2005).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=16565502; DOI=10.2353/ajpath.2006.050941;
RA Schrick J.J., Vogel P., Abuin A., Hampton B., Rice D.S.;
RT "ADP-ribosylation factor-like 3 is involved in kidney and photoreceptor
RT development.";
RL Am. J. Pathol. 168:1288-1298(2006).
RN [5]
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 [6]
RP FUNCTION, AND INTERACTION WITH GGA1.
RX PubMed=25405894; DOI=10.1038/ncomms6482;
RA Kim H., Xu H., Yao Q., Li W., Huang Q., Outeda P., Cebotaru V.,
RA Chiaravalli M., Boletta A., Piontek K., Germino G.G., Weinman E.J.,
RA Watnick T., Qian F.;
RT "Ciliary membrane proteins traffic through the Golgi via a
RT Rabep1/GGA1/Arl3-dependent mechanism.";
RL Nat. Commun. 5:5482-5482(2014).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH GDP AND MAGNESIUM
RP IONS.
RX PubMed=11188688; DOI=10.1016/s0969-2126(00)00531-1;
RA Hillig R.C., Hanzal-Bayer M., Linari M., Becker J., Wittinghofer A.,
RA Renault L.;
RT "Structural and biochemical properties show ARL3-GDP as a distinct GTP
RT binding protein.";
RL Structure 8:1239-1245(2000).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 17-177 IN COMPLEX WITH HUMAN RP2
RP AND GTP, FUNCTION, INTERACTION WITH HUMAN RP2, AND MUTAGENESIS OF GLN-49;
RP GLN-71; LYS-98; GLU-164 AND ASP-168.
RX PubMed=18376416; DOI=10.1038/nsmb.1396;
RA Veltel S., Gasper R., Eisenacher E., Wittinghofer A.;
RT "The retinitis pigmentosa 2 gene product is a GTPase-activating protein for
RT Arf-like 3.";
RL Nat. Struct. Mol. Biol. 15:373-380(2008).
CC -!- FUNCTION: Small GTP-binding protein which cycles between an inactive
CC GDP-bound and an active GTP-bound form, and the rate of cycling is
CC regulated by guanine nucleotide exchange factors (GEF) and GTPase-
CC activating proteins (GAP) (PubMed:18376416). Required for normal
CC cytokinesis and cilia signaling. Required for targeting proteins to the
CC cilium, including myristoylated NPHP3 and prenylated INPP5E. Targets
CC NPHP3 to the ciliary membrane by releasing myristoylated NPHP3 from
CC UNC119B cargo adapter into the cilium (By similarity). Requires
CC assistance from GTPase-activating proteins (GAPs) like RP2 and PDE6D,
CC in order to cycle between inactive GDP-bound and active GTP-bound forms
CC (PubMed:15979089). Required for PKD1:PKD2 complex targeting from the
CC trans-Golgi network to the cilium (PubMed:25405894).
CC {ECO:0000250|UniProtKB:P36405, ECO:0000269|PubMed:15979089,
CC ECO:0000269|PubMed:18376416, ECO:0000269|PubMed:25405894}.
CC -!- SUBUNIT: Found in a complex with ARL3, RP2 and UNC119 (or UNC119B); RP2
CC induces hydrolysis of GTP ARL3 in the complex, leading to the release
CC of UNC119 (or UNC119B). Interacts with RP2; interaction is direct and
CC stimulated with the activated GTP-bound form of ARL3. Interacts with
CC SYS1. Interacts with ARL2BP; the GTP-bound form interacts with ARL2BP.
CC Microtubule-associated protein. Does not interact with TBCC (By
CC similarity). Interacts with RP2 (PubMed:18376416). Interacts with
CC PDE6D; the interaction occurs specifically with the GTP-bound form of
CC ARL3 (PubMed:10518933, PubMed:15979089). Interacts with GGA1; the
CC interaction recruits PKD1:PKD2 complex to trans-Golgi network and is
CC required for ciliary targeting of PKD1:PKD2 complex (PubMed:25405894).
CC Interacts with DNAAF9 (By similarity). {ECO:0000250|UniProtKB:P36405,
CC ECO:0000269|PubMed:10518933, ECO:0000269|PubMed:15979089,
CC ECO:0000269|PubMed:18376416, ECO:0000269|PubMed:25405894}.
CC -!- INTERACTION:
CC Q9WUL7; Q8C6E0: Cfap36; NbExp=5; IntAct=EBI-6860857, EBI-16180842;
CC Q9WUL7; Q96G28: CFAP36; Xeno; NbExp=2; IntAct=EBI-6860857, EBI-2654750;
CC Q9WUL7; O43924: PDE6D; Xeno; NbExp=4; IntAct=EBI-6860857, EBI-712685;
CC Q9WUL7; O75695: RP2; Xeno; NbExp=5; IntAct=EBI-6860857, EBI-7996807;
CC Q9WUL7; Q13432: UNC119; Xeno; NbExp=3; IntAct=EBI-6860857, EBI-711260;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Peripheral membrane
CC protein; Cytoplasmic side. Cytoplasm, cytoskeleton, spindle. Nucleus.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250}. Cytoplasm {ECO:0000250}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:P36405}. Note=Detected predominantly in the
CC photoreceptor connecting cilium. Centrosome-associated throughout the
CC cell cycle. Not detected to interphase microtubules (By similarity).
CC Present on the mitotic spindle. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Lethality by 3 weeks of age. Mice exhibit
CC abnormal development of renal, hepatic, and pancreatic epithelial
CC tubule structures. Mice show abnormal epithelial cell proliferation and
CC cyst formation. Moreover, they exhibit photoreceptor degeneration as
CC early as postnatal day 14. {ECO:0000269|PubMed:16565502}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
CC {ECO:0000305}.
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DR EMBL; AF143241; AAD33067.1; -; mRNA.
DR EMBL; BC042941; AAH42941.1; -; mRNA.
DR CCDS; CCDS38010.1; -.
DR RefSeq; NP_062692.1; NM_019718.2.
DR PDB; 1FZQ; X-ray; 1.70 A; A=2-182.
DR PDB; 3BH6; X-ray; 2.60 A; A=17-177.
DR PDB; 3BH7; X-ray; 1.90 A; A=17-177.
DR PDB; 4GOJ; X-ray; 2.10 A; A/B=1-182.
DR PDB; 4ZI2; X-ray; 2.20 A; A/B=1-182.
DR PDB; 4ZI3; X-ray; 2.00 A; A/B=1-182.
DR PDB; 7OK7; X-ray; 3.15 A; A/B/C/D/E/F=3-182.
DR PDBsum; 1FZQ; -.
DR PDBsum; 3BH6; -.
DR PDBsum; 3BH7; -.
DR PDBsum; 4GOJ; -.
DR PDBsum; 4ZI2; -.
DR PDBsum; 4ZI3; -.
DR PDBsum; 7OK7; -.
DR AlphaFoldDB; Q9WUL7; -.
DR SMR; Q9WUL7; -.
DR BioGRID; 207916; 3.
DR CORUM; Q9WUL7; -.
DR DIP; DIP-29025N; -.
DR IntAct; Q9WUL7; 8.
DR MINT; Q9WUL7; -.
DR STRING; 10090.ENSMUSP00000026009; -.
DR iPTMnet; Q9WUL7; -.
DR PhosphoSitePlus; Q9WUL7; -.
DR SwissPalm; Q9WUL7; -.
DR REPRODUCTION-2DPAGE; IPI00124787; -.
DR REPRODUCTION-2DPAGE; Q9WUL7; -.
DR EPD; Q9WUL7; -.
DR jPOST; Q9WUL7; -.
DR MaxQB; Q9WUL7; -.
DR PaxDb; Q9WUL7; -.
DR PRIDE; Q9WUL7; -.
DR ProteomicsDB; 274970; -.
DR Antibodypedia; 31479; 430 antibodies from 29 providers.
DR DNASU; 56350; -.
DR Ensembl; ENSMUST00000026009; ENSMUSP00000026009; ENSMUSG00000025035.
DR GeneID; 56350; -.
DR KEGG; mmu:56350; -.
DR UCSC; uc008htt.1; mouse.
DR CTD; 403; -.
DR MGI; MGI:1929699; Arl3.
DR VEuPathDB; HostDB:ENSMUSG00000025035; -.
DR eggNOG; KOG0074; Eukaryota.
DR GeneTree; ENSGT00940000155737; -.
DR HOGENOM; CLU_040729_12_0_1; -.
DR InParanoid; Q9WUL7; -.
DR OMA; ASEDITQ; -.
DR OrthoDB; 1271528at2759; -.
DR PhylomeDB; Q9WUL7; -.
DR TreeFam; TF105463; -.
DR Reactome; R-MMU-5624138; Trafficking of myristoylated proteins to the cilium.
DR BioGRID-ORCS; 56350; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Arl3; mouse.
DR EvolutionaryTrace; Q9WUL7; -.
DR PRO; PR:Q9WUL7; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9WUL7; protein.
DR Bgee; ENSMUSG00000025035; Expressed in retinal neural layer and 261 other tissues.
DR ExpressionAtlas; Q9WUL7; baseline and differential.
DR Genevisible; Q9WUL7; MM.
DR GO; GO:0005930; C:axoneme; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0035869; C:ciliary transition zone; IDA:UniProtKB.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005881; C:cytoplasmic microtubule; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0015630; C:microtubule cytoskeleton; IBA:GO_Central.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; ISS:UniProtKB.
DR GO; GO:0005876; C:spindle microtubule; ISS:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0032794; F:GTPase activating protein binding; IPI:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0006893; P:Golgi to plasma membrane transport; IMP:UniProtKB.
DR GO; GO:0042073; P:intraciliary transport; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IMP:UniProtKB.
DR GO; GO:0000281; P:mitotic cytokinesis; ISS:UniProtKB.
DR GO; GO:0042461; P:photoreceptor cell development; IMP:UniProtKB.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; ISO:MGI.
DR GO; GO:1903441; P:protein localization to ciliary membrane; IMP:UniProtKB.
DR GO; GO:0061512; P:protein localization to cilium; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; ISS:UniProtKB.
DR GO; GO:0007224; P:smoothened signaling pathway; IMP:MGI.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR044612; ARL2/3.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR006689; Small_GTPase_ARF/SAR.
DR PANTHER; PTHR45697; PTHR45697; 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 3D-structure; Cell cycle; Cell division; Cell projection; Cytoplasm;
KW Cytoskeleton; Golgi apparatus; GTP-binding; Lipoprotein; Magnesium;
KW Membrane; Metal-binding; Myristate; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..182
FT /note="ADP-ribosylation factor-like protein 3"
FT /id="PRO_0000207457"
FT BINDING 24..31
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:18376416"
FT BINDING 31
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 48
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:18376416"
FT BINDING 48
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 67..71
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 70
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:18376416"
FT BINDING 126..129
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:18376416"
FT BINDING 159..161
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:18376416"
FT MOD_RES 5
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P36405"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT MUTAGEN 31
FT /note="T->N: Inhibits interaction with PDE6D."
FT /evidence="ECO:0000269|PubMed:10518933"
FT MUTAGEN 49
FT /note="Q->L: Does not reduce the interaction with RP2."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 71
FT /note="Q->L: Does not inhibit interaction with PDE6D."
FT /evidence="ECO:0000269|PubMed:10518933,
FT ECO:0000269|PubMed:18376416"
FT MUTAGEN 71
FT /note="Q->L: Inhibits RP2-dependent GTP-hydrolysis rate."
FT /evidence="ECO:0000269|PubMed:10518933,
FT ECO:0000269|PubMed:18376416"
FT MUTAGEN 98
FT /note="K->Q: Does not reduce the interaction with RP2."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 164
FT /note="E->A: Reduces the interaction with RP2; when
FT associated with A-168."
FT /evidence="ECO:0000269|PubMed:18376416"
FT MUTAGEN 168
FT /note="D->A: Reduces the interaction with RP2; when
FT associated with A-164."
FT /evidence="ECO:0000269|PubMed:18376416"
FT HELIX 6..9
FT /evidence="ECO:0007829|PDB:1FZQ"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:4ZI2"
FT HELIX 14..16
FT /evidence="ECO:0007829|PDB:4ZI2"
FT STRAND 18..25
FT /evidence="ECO:0007829|PDB:1FZQ"
FT HELIX 30..37
FT /evidence="ECO:0007829|PDB:1FZQ"
FT STRAND 43..48
FT /evidence="ECO:0007829|PDB:1FZQ"
FT STRAND 51..58
FT /evidence="ECO:0007829|PDB:1FZQ"
FT STRAND 61..67
FT /evidence="ECO:0007829|PDB:1FZQ"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:1FZQ"
FT HELIX 75..82
FT /evidence="ECO:0007829|PDB:1FZQ"
FT STRAND 86..93
FT /evidence="ECO:0007829|PDB:1FZQ"
FT HELIX 97..99
FT /evidence="ECO:0007829|PDB:1FZQ"
FT HELIX 100..110
FT /evidence="ECO:0007829|PDB:1FZQ"
FT HELIX 114..116
FT /evidence="ECO:0007829|PDB:1FZQ"
FT STRAND 121..126
FT /evidence="ECO:0007829|PDB:1FZQ"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:3BH6"
FT HELIX 136..142
FT /evidence="ECO:0007829|PDB:1FZQ"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:1FZQ"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:1FZQ"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:1FZQ"
FT HELIX 166..175
FT /evidence="ECO:0007829|PDB:1FZQ"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:4ZI2"
FT HELIX 179..182
FT /evidence="ECO:0007829|PDB:4ZI3"
SQ SEQUENCE 182 AA; 20487 MW; 16B85B2268ADB9DE CRC64;
MGLLSILRKL KSAPDQEVRI LLLGLDNAGK TTLLKQLASE DISHITPTQG FNIKSVQSQG
FKLNVWDIGG QRKIRPYWRS YFENTDILIY VIDSADRKRF EETGQELTEL LEEEKLSCVP
VLIFANKQDL LTAAPASEIA EGLNLHTIRD RVWQIQSCSA LTGEGVQDGM NWVCKNVNAK
KK
