Full text data of ARL3
ARL3
(ARFL3)
[Confidence: low (only semi-automatic identification from reviews)]
ADP-ribosylation factor-like protein 3
ADP-ribosylation factor-like protein 3
UniProt
P36405
ID ARL3_HUMAN Reviewed; 182 AA.
AC P36405; B2R6C7; Q53X83; Q5JSM2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 2.
DT 22-JAN-2014, entry version 138.
DE RecName: Full=ADP-ribosylation factor-like protein 3;
GN Name=ARL3; Synonyms=ARFL3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8034651;
RA Cavenagh M.A., Breiner M., Schurmann A., Rosenwald A.G., Terui T.,
RA Zhang C.-J., Randoazzo P.A., Adams M., Joost H.-G., Kahn R.A.;
RT "ADP-ribosylation factor (ARF)-like 3, a new member of the ARF family
RT of GTP-binding proteins cloned from human and rat tissues.";
RL J. Biol. Chem. 269:18937-18942(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-34.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 80-97 AND 128-149, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [8]
RP ABSENCE OF INTERACTION WITH TBCC.
RX PubMed=10831612; DOI=10.1083/jcb.149.5.1087;
RA Bhamidipati A., Lewis S.A., Cowan N.J.;
RT "ADP ribosylation factor-like protein 2 (Arl2) regulates the
RT interaction of tubulin-folding cofactor D with native tubulin.";
RL J. Cell Biol. 149:1087-1096(2000).
RN [9]
RP INTERACTION WITH ARL2BP; GOLGA4; PDE6D AND UNC119, AND MUTAGENESIS OF
RP GLN-71.
RX PubMed=11303027; DOI=10.1074/jbc.M102359200;
RA Van Valkenburgh H., Shern J.F., Sharer J.D., Zhu X., Kahn R.A.;
RT "ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both
RT specific and shared effectors: characterizing ARL1-binding proteins.";
RL J. Biol. Chem. 276:22826-22837(2001).
RN [10]
RP ASSOCIATION WITH MICROTUBULES, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=12417528; DOI=10.1093/hmg/11.24.3065;
RA Grayson C., Bartolini F., Chapple J.P., Willison K.R., Bhamidipati A.,
RA Lewis S.A., Luthert P.J., Hardcastle A.J., Cowan N.J., Cheetham M.E.;
RT "Localization in the human retina of the X-linked retinitis pigmentosa
RT protein RP2, its homologue cofactor C and the RP2 interacting protein
RT Arl3.";
RL Hum. Mol. Genet. 11:3065-3074(2002).
RN [11]
RP INTERACTION WITH RP2 AND ARL2BP, AND MUTAGENESIS OF THR-31 AND GLN-71.
RX PubMed=11847227; DOI=10.1074/jbc.M200128200;
RA Bartolini F., Bhamidipati A., Thomas S., Schwahn U., Lewis S.A.,
RA Cowan N.J.;
RT "Functional overlap between retinitis pigmentosa 2 protein and the
RT tubulin-specific chaperone cofactor C.";
RL J. Biol. Chem. 277:14629-14634(2002).
RN [12]
RP INTERACTION WITH SYS1, AND SUBCELLULAR LOCATION.
RX PubMed=15077113; DOI=10.1038/ncb1120;
RA Behnia R., Panic B., Whyte J.R.C., Munro S.;
RT "Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-
RT terminal acetylation and the membrane protein Sys1p.";
RL Nat. Cell Biol. 6:405-413(2004).
RN [13]
RP FUNCTION, MUTAGENESIS OF GLN-71, AND SUBCELLULAR LOCATION.
RX PubMed=16525022; DOI=10.1091/mbc.E05-10-0929;
RA Zhou C., Cunningham L., Marcus A.I., Li Y., Kahn R.A.;
RT "Arl2 and Arl3 regulate different microtubule-dependent processes.";
RL Mol. Biol. Cell 17:2476-2487(2006).
RN [14]
RP INTERACTION WITH RP2.
RX PubMed=16472755; DOI=10.1016/j.str.2005.11.008;
RA Kuehnel K., Veltel S., Schlichting I., Wittinghofer A.;
RT "Crystal structure of the human retinitis pigmentosa 2 protein and its
RT interaction with Arl3.";
RL Structure 14:367-378(2006).
RN [15]
RP FUNCTION, GTP/GDP BINDING, IDENTIFICATION IN A COMPLEX WITH UNC119 AND
RP RP2, AND SUBCELLULAR LOCATION.
RX PubMed=18588884; DOI=10.1016/j.febslet.2008.05.053;
RA Veltel S., Kravchenko A., Ismail S., Wittinghofer A.;
RT "Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-
RT effector-GAP complex.";
RL FEBS Lett. 582:2501-2507(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP FUNCTION, AND MUTAGENESIS OF THR-31 AND GLN-71.
RX PubMed=22085962; DOI=10.1101/gad.173054.111;
RA Wright K.J., Baye L.M., Olivier-Mason A., Mukhopadhyay S., Sang L.,
RA Kwong M., Wang W., Pretorius P.R., Sheffield V.C., Sengupta P.,
RA Slusarski D.C., Jackson P.K.;
RT "An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the
RT primary cilium.";
RL Genes Dev. 25:2347-2360(2011).
CC -!- FUNCTION: Small GTP-binding protein which cycles between an
CC inactive GDP-bound and an active GTP-bound form, and the rate of
CC cycling is regulated by guanine nucleotide exchange factors (GEF)
CC and GTPase-activating proteins (GAP). Required for normal
CC cytokinesis and cilia signaling. Requires assistance from GTPase-
CC activating proteins (GAPs) like RP2 and PDE6D, in order to cycle
CC between inactive GDP-bound and active GTP-bound forms. Required
CC for targeting proteins such as NPHP3 to the ciliary membrane by
CC releasing myristoylated NPHP3 from UNC119B cargo adapter into the
CC cilium. Does not act as an allosteric activator of the cholera
CC toxin catalytic subunit.
CC -!- SUBUNIT: Interacts with RP2. The GTP-bound form interacts with
CC PDE6D. Found in a complex with ARL3, RP2 and UNC119 (or UNC119B);
CC RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the
CC release of UNC119 (or UNC119B). Interacts with SYS1. The GTP-bound
CC form interacts with ARL2BP and PDE6D. Interacts with RP2;
CC interaction is direct and stimulated with the activated GTP-bound
CC form of ARL3. Microtubule-associated protein. Does not interact
CC with TBCC. May interact with GOLGA4.
CC -!- INTERACTION:
CC O43924:PDE6D; NbExp=2; IntAct=EBI-712710, EBI-712685;
CC Q13432:UNC119; NbExp=5; IntAct=EBI-712710, EBI-711260;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Peripheral
CC membrane protein; Cytoplasmic side. Cytoplasm, cytoskeleton,
CC spindle. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome. Cytoplasm. Cell projection, cilium.
CC Note=Detected predominantly in the photoreceptor connecting
CC cilium. Present on the mitotic spindle. Centrosome-associated
CC throughout the cell cycle. Not detected to interphase
CC microtubules.
CC -!- TISSUE SPECIFICITY: Expressed in the retina. Strongly expressed in
CC connecting cilium, the myoid region of the inner segments (IS) and
CC in cone photoreceptors (at protein level).
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
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DR EMBL; U07151; AAA21654.1; -; mRNA.
DR EMBL; AF493889; AAM12603.1; -; mRNA.
DR EMBL; AK312525; BAG35424.1; -; mRNA.
DR EMBL; CR407637; CAG28565.1; -; mRNA.
DR EMBL; AL391121; CAI40862.1; -; Genomic_DNA.
DR EMBL; BC009841; AAH09841.1; -; mRNA.
DR PIR; A54869; A54869.
DR RefSeq; NP_004302.1; NM_004311.3.
DR UniGene; Hs.182215; -.
DR ProteinModelPortal; P36405; -.
DR SMR; P36405; 2-177.
DR IntAct; P36405; 10.
DR MINT; MINT-1368863; -.
DR STRING; 9606.ENSP00000260746; -.
DR PhosphoSite; P36405; -.
DR DMDM; 543851; -.
DR REPRODUCTION-2DPAGE; IPI00003327; -.
DR UCD-2DPAGE; P36405; -.
DR PaxDb; P36405; -.
DR PeptideAtlas; P36405; -.
DR PRIDE; P36405; -.
DR DNASU; 403; -.
DR Ensembl; ENST00000260746; ENSP00000260746; ENSG00000138175.
DR GeneID; 403; -.
DR KEGG; hsa:403; -.
DR UCSC; uc001kwa.3; human.
DR CTD; 403; -.
DR GeneCards; GC10M104423; -.
DR HGNC; HGNC:694; ARL3.
DR HPA; HPA036292; -.
DR MIM; 604695; gene.
DR neXtProt; NX_P36405; -.
DR PharmGKB; PA24987; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000163691; -.
DR HOVERGEN; HBG002073; -.
DR InParanoid; P36405; -.
DR KO; K07944; -.
DR OMA; PTAGFNI; -.
DR OrthoDB; EOG7M98HG; -.
DR PhylomeDB; P36405; -.
DR GeneWiki; ARL3; -.
DR GenomeRNAi; 403; -.
DR NextBio; 1689; -.
DR PRO; PR:P36405; -.
DR Bgee; P36405; -.
DR CleanEx; HS_ARL3; -.
DR Genevestigator; P36405; -.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005881; C:cytoplasmic microtubule; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005876; C:spindle microtubule; IDA:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0060271; P:cilium morphogenesis; IMP:UniProtKB.
DR GO; GO:0000910; P:cytokinesis; IMP:UniProtKB.
DR GO; GO:0042073; P:intraflagellar transport; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0042461; P:photoreceptor cell development; ISS:UniProtKB.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; IMP:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:UniProtKB.
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 Pfam; PF00025; Arf; 1.
DR PRINTS; PR00328; SAR1GTPBP.
DR SMART; SM00177; ARF; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51417; ARF; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cell projection; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Golgi apparatus;
KW GTP-binding; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Protein transport; Reference proteome; Transport.
FT INIT_MET 1 1 Removed (Potential).
FT CHAIN 2 182 ADP-ribosylation factor-like protein 3.
FT /FTId=PRO_0000207456.
FT NP_BIND 24 31 GTP (By similarity).
FT NP_BIND 67 71 GTP (By similarity).
FT NP_BIND 126 129 GTP (By similarity).
FT NP_BIND 159 161 GTP (By similarity).
FT METAL 31 31 Magnesium (By similarity).
FT METAL 48 48 Magnesium (By similarity).
FT BINDING 48 48 GTP (By similarity).
FT BINDING 70 70 GTP; via amide nitrogen (By similarity).
FT MOD_RES 5 5 Phosphoserine.
FT LIPID 2 2 N-myristoyl glycine (Potential).
FT VARIANT 34 34 L -> M (in dbSNP:rs1141895).
FT /FTId=VAR_014869.
FT MUTAGEN 31 31 T->N: Enhances the interaction with RP2.
FT MUTAGEN 71 71 Q->L: Enhances the interaction with RP2.
FT Does not induce a mitotic arrest
FT resulting from the loss of the
FT microtubule-based mitotic spindle.
FT Induces release of myristoylated proteins
FT from UNC119. Interacts with ARL2BP,
FT GOLGA4, PDE6D and UNC119.
SQ SEQUENCE 182 AA; 20456 MW; E5C1ACAD0BD55537 CRC64;
MGLLSILRKL KSAPDQEVRI LLLGLDNAGK TTLLKQLASE DISHITPTQG FNIKSVQSQG
FKLNVWDIGG QRKIRPYWKN YFENTDILIY VIDSADRKRF EETGQELAEL LEEEKLSCVP
VLIFANKQDL LTAAPASEIA EGLNLHTIRD RVWQIQSCSA LTGEGVQDGM NWVCKNVNAK
KK
//
ID ARL3_HUMAN Reviewed; 182 AA.
AC P36405; B2R6C7; Q53X83; Q5JSM2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1995, sequence version 2.
DT 22-JAN-2014, entry version 138.
DE RecName: Full=ADP-ribosylation factor-like protein 3;
GN Name=ARL3; Synonyms=ARFL3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8034651;
RA Cavenagh M.A., Breiner M., Schurmann A., Rosenwald A.G., Terui T.,
RA Zhang C.-J., Randoazzo P.A., Adams M., Joost H.-G., Kahn R.A.;
RT "ADP-ribosylation factor (ARF)-like 3, a new member of the ARF family
RT of GTP-binding proteins cloned from human and rat tissues.";
RL J. Biol. Chem. 269:18937-18942(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-34.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 80-97 AND 128-149, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [8]
RP ABSENCE OF INTERACTION WITH TBCC.
RX PubMed=10831612; DOI=10.1083/jcb.149.5.1087;
RA Bhamidipati A., Lewis S.A., Cowan N.J.;
RT "ADP ribosylation factor-like protein 2 (Arl2) regulates the
RT interaction of tubulin-folding cofactor D with native tubulin.";
RL J. Cell Biol. 149:1087-1096(2000).
RN [9]
RP INTERACTION WITH ARL2BP; GOLGA4; PDE6D AND UNC119, AND MUTAGENESIS OF
RP GLN-71.
RX PubMed=11303027; DOI=10.1074/jbc.M102359200;
RA Van Valkenburgh H., Shern J.F., Sharer J.D., Zhu X., Kahn R.A.;
RT "ADP-ribosylation factors (ARFs) and ARF-like 1 (ARL1) have both
RT specific and shared effectors: characterizing ARL1-binding proteins.";
RL J. Biol. Chem. 276:22826-22837(2001).
RN [10]
RP ASSOCIATION WITH MICROTUBULES, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=12417528; DOI=10.1093/hmg/11.24.3065;
RA Grayson C., Bartolini F., Chapple J.P., Willison K.R., Bhamidipati A.,
RA Lewis S.A., Luthert P.J., Hardcastle A.J., Cowan N.J., Cheetham M.E.;
RT "Localization in the human retina of the X-linked retinitis pigmentosa
RT protein RP2, its homologue cofactor C and the RP2 interacting protein
RT Arl3.";
RL Hum. Mol. Genet. 11:3065-3074(2002).
RN [11]
RP INTERACTION WITH RP2 AND ARL2BP, AND MUTAGENESIS OF THR-31 AND GLN-71.
RX PubMed=11847227; DOI=10.1074/jbc.M200128200;
RA Bartolini F., Bhamidipati A., Thomas S., Schwahn U., Lewis S.A.,
RA Cowan N.J.;
RT "Functional overlap between retinitis pigmentosa 2 protein and the
RT tubulin-specific chaperone cofactor C.";
RL J. Biol. Chem. 277:14629-14634(2002).
RN [12]
RP INTERACTION WITH SYS1, AND SUBCELLULAR LOCATION.
RX PubMed=15077113; DOI=10.1038/ncb1120;
RA Behnia R., Panic B., Whyte J.R.C., Munro S.;
RT "Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-
RT terminal acetylation and the membrane protein Sys1p.";
RL Nat. Cell Biol. 6:405-413(2004).
RN [13]
RP FUNCTION, MUTAGENESIS OF GLN-71, AND SUBCELLULAR LOCATION.
RX PubMed=16525022; DOI=10.1091/mbc.E05-10-0929;
RA Zhou C., Cunningham L., Marcus A.I., Li Y., Kahn R.A.;
RT "Arl2 and Arl3 regulate different microtubule-dependent processes.";
RL Mol. Biol. Cell 17:2476-2487(2006).
RN [14]
RP INTERACTION WITH RP2.
RX PubMed=16472755; DOI=10.1016/j.str.2005.11.008;
RA Kuehnel K., Veltel S., Schlichting I., Wittinghofer A.;
RT "Crystal structure of the human retinitis pigmentosa 2 protein and its
RT interaction with Arl3.";
RL Structure 14:367-378(2006).
RN [15]
RP FUNCTION, GTP/GDP BINDING, IDENTIFICATION IN A COMPLEX WITH UNC119 AND
RP RP2, AND SUBCELLULAR LOCATION.
RX PubMed=18588884; DOI=10.1016/j.febslet.2008.05.053;
RA Veltel S., Kravchenko A., Ismail S., Wittinghofer A.;
RT "Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-
RT effector-GAP complex.";
RL FEBS Lett. 582:2501-2507(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP FUNCTION, AND MUTAGENESIS OF THR-31 AND GLN-71.
RX PubMed=22085962; DOI=10.1101/gad.173054.111;
RA Wright K.J., Baye L.M., Olivier-Mason A., Mukhopadhyay S., Sang L.,
RA Kwong M., Wang W., Pretorius P.R., Sheffield V.C., Sengupta P.,
RA Slusarski D.C., Jackson P.K.;
RT "An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the
RT primary cilium.";
RL Genes Dev. 25:2347-2360(2011).
CC -!- FUNCTION: Small GTP-binding protein which cycles between an
CC inactive GDP-bound and an active GTP-bound form, and the rate of
CC cycling is regulated by guanine nucleotide exchange factors (GEF)
CC and GTPase-activating proteins (GAP). Required for normal
CC cytokinesis and cilia signaling. Requires assistance from GTPase-
CC activating proteins (GAPs) like RP2 and PDE6D, in order to cycle
CC between inactive GDP-bound and active GTP-bound forms. Required
CC for targeting proteins such as NPHP3 to the ciliary membrane by
CC releasing myristoylated NPHP3 from UNC119B cargo adapter into the
CC cilium. Does not act as an allosteric activator of the cholera
CC toxin catalytic subunit.
CC -!- SUBUNIT: Interacts with RP2. The GTP-bound form interacts with
CC PDE6D. Found in a complex with ARL3, RP2 and UNC119 (or UNC119B);
CC RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the
CC release of UNC119 (or UNC119B). Interacts with SYS1. The GTP-bound
CC form interacts with ARL2BP and PDE6D. Interacts with RP2;
CC interaction is direct and stimulated with the activated GTP-bound
CC form of ARL3. Microtubule-associated protein. Does not interact
CC with TBCC. May interact with GOLGA4.
CC -!- INTERACTION:
CC O43924:PDE6D; NbExp=2; IntAct=EBI-712710, EBI-712685;
CC Q13432:UNC119; NbExp=5; IntAct=EBI-712710, EBI-711260;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Peripheral
CC membrane protein; Cytoplasmic side. Cytoplasm, cytoskeleton,
CC spindle. Nucleus. Cytoplasm, cytoskeleton, microtubule organizing
CC center, centrosome. Cytoplasm. Cell projection, cilium.
CC Note=Detected predominantly in the photoreceptor connecting
CC cilium. Present on the mitotic spindle. Centrosome-associated
CC throughout the cell cycle. Not detected to interphase
CC microtubules.
CC -!- TISSUE SPECIFICITY: Expressed in the retina. Strongly expressed in
CC connecting cilium, the myoid region of the inner segments (IS) and
CC in cone photoreceptors (at protein level).
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
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DR EMBL; U07151; AAA21654.1; -; mRNA.
DR EMBL; AF493889; AAM12603.1; -; mRNA.
DR EMBL; AK312525; BAG35424.1; -; mRNA.
DR EMBL; CR407637; CAG28565.1; -; mRNA.
DR EMBL; AL391121; CAI40862.1; -; Genomic_DNA.
DR EMBL; BC009841; AAH09841.1; -; mRNA.
DR PIR; A54869; A54869.
DR RefSeq; NP_004302.1; NM_004311.3.
DR UniGene; Hs.182215; -.
DR ProteinModelPortal; P36405; -.
DR SMR; P36405; 2-177.
DR IntAct; P36405; 10.
DR MINT; MINT-1368863; -.
DR STRING; 9606.ENSP00000260746; -.
DR PhosphoSite; P36405; -.
DR DMDM; 543851; -.
DR REPRODUCTION-2DPAGE; IPI00003327; -.
DR UCD-2DPAGE; P36405; -.
DR PaxDb; P36405; -.
DR PeptideAtlas; P36405; -.
DR PRIDE; P36405; -.
DR DNASU; 403; -.
DR Ensembl; ENST00000260746; ENSP00000260746; ENSG00000138175.
DR GeneID; 403; -.
DR KEGG; hsa:403; -.
DR UCSC; uc001kwa.3; human.
DR CTD; 403; -.
DR GeneCards; GC10M104423; -.
DR HGNC; HGNC:694; ARL3.
DR HPA; HPA036292; -.
DR MIM; 604695; gene.
DR neXtProt; NX_P36405; -.
DR PharmGKB; PA24987; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000163691; -.
DR HOVERGEN; HBG002073; -.
DR InParanoid; P36405; -.
DR KO; K07944; -.
DR OMA; PTAGFNI; -.
DR OrthoDB; EOG7M98HG; -.
DR PhylomeDB; P36405; -.
DR GeneWiki; ARL3; -.
DR GenomeRNAi; 403; -.
DR NextBio; 1689; -.
DR PRO; PR:P36405; -.
DR Bgee; P36405; -.
DR CleanEx; HS_ARL3; -.
DR Genevestigator; P36405; -.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005881; C:cytoplasmic microtubule; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005876; C:spindle microtubule; IDA:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB.
DR GO; GO:0060271; P:cilium morphogenesis; IMP:UniProtKB.
DR GO; GO:0000910; P:cytokinesis; IMP:UniProtKB.
DR GO; GO:0042073; P:intraflagellar transport; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0042461; P:photoreceptor cell development; ISS:UniProtKB.
DR GO; GO:0006892; P:post-Golgi vesicle-mediated transport; IMP:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:UniProtKB.
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 Pfam; PF00025; Arf; 1.
DR PRINTS; PR00328; SAR1GTPBP.
DR SMART; SM00177; ARF; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51417; ARF; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Cell projection; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Golgi apparatus;
KW GTP-binding; Lipoprotein; Magnesium; Membrane; Metal-binding;
KW Myristate; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Protein transport; Reference proteome; Transport.
FT INIT_MET 1 1 Removed (Potential).
FT CHAIN 2 182 ADP-ribosylation factor-like protein 3.
FT /FTId=PRO_0000207456.
FT NP_BIND 24 31 GTP (By similarity).
FT NP_BIND 67 71 GTP (By similarity).
FT NP_BIND 126 129 GTP (By similarity).
FT NP_BIND 159 161 GTP (By similarity).
FT METAL 31 31 Magnesium (By similarity).
FT METAL 48 48 Magnesium (By similarity).
FT BINDING 48 48 GTP (By similarity).
FT BINDING 70 70 GTP; via amide nitrogen (By similarity).
FT MOD_RES 5 5 Phosphoserine.
FT LIPID 2 2 N-myristoyl glycine (Potential).
FT VARIANT 34 34 L -> M (in dbSNP:rs1141895).
FT /FTId=VAR_014869.
FT MUTAGEN 31 31 T->N: Enhances the interaction with RP2.
FT MUTAGEN 71 71 Q->L: Enhances the interaction with RP2.
FT Does not induce a mitotic arrest
FT resulting from the loss of the
FT microtubule-based mitotic spindle.
FT Induces release of myristoylated proteins
FT from UNC119. Interacts with ARL2BP,
FT GOLGA4, PDE6D and UNC119.
SQ SEQUENCE 182 AA; 20456 MW; E5C1ACAD0BD55537 CRC64;
MGLLSILRKL KSAPDQEVRI LLLGLDNAGK TTLLKQLASE DISHITPTQG FNIKSVQSQG
FKLNVWDIGG QRKIRPYWKN YFENTDILIY VIDSADRKRF EETGQELAEL LEEEKLSCVP
VLIFANKQDL LTAAPASEIA EGLNLHTIRD RVWQIQSCSA LTGEGVQDGM NWVCKNVNAK
KK
//
MIM
604695
*RECORD*
*FIELD* NO
604695
*FIELD* TI
*604695 ADP-RIBOSYLATION FACTOR-LIKE 3; ARL3
;;ARFL3
*FIELD* TX
CLONING
ADP-ribosylation factors (ARFs) are low molecular weight GTP-binding
read moreproteins 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 function in mammalian cells. Knockdown
of ARL3 using RNA interference changed HeLa cell morphology, caused
Golgi fragmentation, and increased acetylation of alpha-tubulin (see
602529), which resulted in failure of cytokinesis, with increased number
of binucleated cells. Overexpression of ARL3 had little effect. In
contrast, knockdown of ARL2 in HeLa cells showed little effect, but
expression of ARL2 with a dominant activating mutation caused failure of
tubulin polymerization, with loss of microtubules and microtubule-based
mitotic spindle, resulting in cell cycle arrest in M phase.
Ismail et al. (2011) stated that PDE-delta binds to farnesylated small G
proteins. They presented the 1.7-angstrom structure of human PDE-delta
in complex with C-terminally farnesylated human RHEB (601293). PDE-delta
interacted almost exclusively with the C-terminal farnesyl moiety of
RHEB, which was inserted within the farnesyl-binding pocket of
PDE-delta. The interaction did not require guanine nucleotide, which
bound RHEB on a surface nearly opposite to the PDE-delta-binding site.
PDE-delta also interacted with mouse Arl2. The interaction of PDE-delta
with Arl2 was dependent upon GTP and caused a conformational change in
PDE-delta that closed its farnesyl-binding pocket. In solution, addition
of Arl2-GTP dissociated the PDE-delta-farnesylated RHEB complex.
Addition of Arl3-GTP also caused release of farnesylated RHEB from
PDE-delta. In transfected canine kidney cells, fluorescence-labeled RHEB
showed endoplasmic reticulum (ER) and Golgi localization. Addition of
PDE-delta relocalized RHEB into a cytoplasmic and nuclear distribution,
and subsequent addition of Arl2-GTP restored RHEB localization to ER and
Golgi membranes. Ismail et al. (2011) concluded that PDE-delta functions
as a solubilization factor for farnesylated RHEB and that ARL2 and ARL3
act in a GTP-dependent manner as allosteric release factors for
farnesylated RHEB.
BIOCHEMICAL FEATURES
Veltel et al. (2008) solved the crystal structure of the central G
domain of mouse Arl3 bound to a GTP analog and human RP2 to 2.6-angstrom
resolution. Both switch regions of Arl3 interacted with the N-terminal
beta-helix domain of RP2. Biochemical analysis showed that Arl3 had a
slow intrinsic rate of GTP hydrolysis, which was accelerated more than
1,400-fold by catalytic amounts of RP2. Veltel et al. (2008) also
determined that arg118 of RP2 and gln71 of Arl3 were crucial active site
catalytic residues. They concluded that RP2 is a GTPase-activating
protein (GAP) for ARL3.
ANIMAL MODEL
Schrick et al. (2006) found that while Arl3 +/- mice appeared normal,
Arl3 -/- mice were obtained at a submendelian ratio, were small and
sickly, and had markedly swollen abdomens. Arl3 -/- mice failed to
thrive and all died by 3 weeks of age. They exhibited abnormal
development of renal, hepatic, and pancreatic epithelial tubule
structures, with abnormal epithelial cell proliferation and cyst
formation characteristic of ARPKD (263200). Moreover, mice lacking Arl3
exhibited photoreceptor degeneration as early as postnatal day 14.
Schrick et al. (2006) concluded that absence of Arl3 causes a ciliary
disease affecting the kidney, biliary tract, pancreas, and retina.
*FIELD* RF
1. Cavenagh, M. M.; Breiner, M.; Schurmann, A.; Rosenwald, A. G.;
Terui, T.; Zhang, C.; Randazzo, P. A.; Adams, M.; Joost, H. G.; Kahn,
R. A.: ADP-ribosylation factor (ARF)-like 3, a new member of the
ARF family of GTP-binding proteins cloned from human and rat tissues. J.
Biol. Chem. 269: 18937-18942, 1994.
2. Grayson, C.; Bartolini, F.; Chapple, J. P.; Willison, K. R.; Bhamidipati,
A.; Lewis, S. A.; Luthert, P. J.; Hardcastle, A. J.; Cowan, N. J.;
Cheetham, M. E.: Localization in the human retina of the X-linked
retinitis pigmentosa protein RP2, its homologue cofactor C and the
RP2 interacting protein Arl3. Hum. Molec. Genet. 11: 3065-3074,
2002.
3. Ismail, S. A.; Chen, Y.-X.; Rusinova, A.; Chandra, A.; Bierbaum,
M.; Gremer, L.; Triola, G.; Waldmann, H.; Bastiaens, P. I. H.; Wittinghofer,
A.: Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for
farnesylated cargo. Nature Chem. Biol. 7: 942-949, 2011.
4. Kim, H.-S.: Assignment of the human ADP-ribosylation factor-like
3 (ARL3) gene to chromosome 10 band q23.3 by radiation hybrid mapping. Cytogenet.
Cell Genet. 83: 246 only, 1998.
5. Schrick, J. J.; Vogel, P.; Abuin, A.; Hampton, B.; Rice, D. S.
: ADP-ribosylation factor-like 3 is involved in kidney and photoreceptor
development. Am. J. Path. 168: 1288-1298, 2006.
6. Veltel, S.; Gasper, R.; Eisenacher, E.; Wittinghofer, A.: The
retinitis pigmentosa 2 gene product is a GTPase-activating protein
for Arf-like 3. Nature Struct. Molec. Biol. 15: 373-380, 2008.
7. Veltel, S.; Kravchenko, A.; Ismail, S.; Wittinghofer, A.: Specificity
of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-GAP
complex. FEBS Letters 582: 2501-2507, 2008.
8. Zhou, C.; Cunningham, L.; Marcus, A. I.; Li, Y.; Kahn, R. A.:
Arl2 and Arl3 regulate different microtubule-dependent processes. Molec.
Biol. Cell 17: 2476-2487, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 10/2/2013
Patricia A. Hartz - updated: 6/30/2009
George E. Tiller - updated: 8/25/2004
*FIELD* CD
Paul J. Converse: 3/17/2000
*FIELD* ED
mgross: 10/23/2013
tpirozzi: 10/2/2013
alopez: 7/6/2009
terry: 6/30/2009
alopez: 2/16/2009
tkritzer: 8/25/2004
mgross: 3/21/2000
mgross: 3/20/2000
mgross: 3/17/2000
*RECORD*
*FIELD* NO
604695
*FIELD* TI
*604695 ADP-RIBOSYLATION FACTOR-LIKE 3; ARL3
;;ARFL3
*FIELD* TX
CLONING
ADP-ribosylation factors (ARFs) are low molecular weight GTP-binding
read moreproteins 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 function in mammalian cells. Knockdown
of ARL3 using RNA interference changed HeLa cell morphology, caused
Golgi fragmentation, and increased acetylation of alpha-tubulin (see
602529), which resulted in failure of cytokinesis, with increased number
of binucleated cells. Overexpression of ARL3 had little effect. In
contrast, knockdown of ARL2 in HeLa cells showed little effect, but
expression of ARL2 with a dominant activating mutation caused failure of
tubulin polymerization, with loss of microtubules and microtubule-based
mitotic spindle, resulting in cell cycle arrest in M phase.
Ismail et al. (2011) stated that PDE-delta binds to farnesylated small G
proteins. They presented the 1.7-angstrom structure of human PDE-delta
in complex with C-terminally farnesylated human RHEB (601293). PDE-delta
interacted almost exclusively with the C-terminal farnesyl moiety of
RHEB, which was inserted within the farnesyl-binding pocket of
PDE-delta. The interaction did not require guanine nucleotide, which
bound RHEB on a surface nearly opposite to the PDE-delta-binding site.
PDE-delta also interacted with mouse Arl2. The interaction of PDE-delta
with Arl2 was dependent upon GTP and caused a conformational change in
PDE-delta that closed its farnesyl-binding pocket. In solution, addition
of Arl2-GTP dissociated the PDE-delta-farnesylated RHEB complex.
Addition of Arl3-GTP also caused release of farnesylated RHEB from
PDE-delta. In transfected canine kidney cells, fluorescence-labeled RHEB
showed endoplasmic reticulum (ER) and Golgi localization. Addition of
PDE-delta relocalized RHEB into a cytoplasmic and nuclear distribution,
and subsequent addition of Arl2-GTP restored RHEB localization to ER and
Golgi membranes. Ismail et al. (2011) concluded that PDE-delta functions
as a solubilization factor for farnesylated RHEB and that ARL2 and ARL3
act in a GTP-dependent manner as allosteric release factors for
farnesylated RHEB.
BIOCHEMICAL FEATURES
Veltel et al. (2008) solved the crystal structure of the central G
domain of mouse Arl3 bound to a GTP analog and human RP2 to 2.6-angstrom
resolution. Both switch regions of Arl3 interacted with the N-terminal
beta-helix domain of RP2. Biochemical analysis showed that Arl3 had a
slow intrinsic rate of GTP hydrolysis, which was accelerated more than
1,400-fold by catalytic amounts of RP2. Veltel et al. (2008) also
determined that arg118 of RP2 and gln71 of Arl3 were crucial active site
catalytic residues. They concluded that RP2 is a GTPase-activating
protein (GAP) for ARL3.
ANIMAL MODEL
Schrick et al. (2006) found that while Arl3 +/- mice appeared normal,
Arl3 -/- mice were obtained at a submendelian ratio, were small and
sickly, and had markedly swollen abdomens. Arl3 -/- mice failed to
thrive and all died by 3 weeks of age. They exhibited abnormal
development of renal, hepatic, and pancreatic epithelial tubule
structures, with abnormal epithelial cell proliferation and cyst
formation characteristic of ARPKD (263200). Moreover, mice lacking Arl3
exhibited photoreceptor degeneration as early as postnatal day 14.
Schrick et al. (2006) concluded that absence of Arl3 causes a ciliary
disease affecting the kidney, biliary tract, pancreas, and retina.
*FIELD* RF
1. Cavenagh, M. M.; Breiner, M.; Schurmann, A.; Rosenwald, A. G.;
Terui, T.; Zhang, C.; Randazzo, P. A.; Adams, M.; Joost, H. G.; Kahn,
R. A.: ADP-ribosylation factor (ARF)-like 3, a new member of the
ARF family of GTP-binding proteins cloned from human and rat tissues. J.
Biol. Chem. 269: 18937-18942, 1994.
2. Grayson, C.; Bartolini, F.; Chapple, J. P.; Willison, K. R.; Bhamidipati,
A.; Lewis, S. A.; Luthert, P. J.; Hardcastle, A. J.; Cowan, N. J.;
Cheetham, M. E.: Localization in the human retina of the X-linked
retinitis pigmentosa protein RP2, its homologue cofactor C and the
RP2 interacting protein Arl3. Hum. Molec. Genet. 11: 3065-3074,
2002.
3. Ismail, S. A.; Chen, Y.-X.; Rusinova, A.; Chandra, A.; Bierbaum,
M.; Gremer, L.; Triola, G.; Waldmann, H.; Bastiaens, P. I. H.; Wittinghofer,
A.: Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for
farnesylated cargo. Nature Chem. Biol. 7: 942-949, 2011.
4. Kim, H.-S.: Assignment of the human ADP-ribosylation factor-like
3 (ARL3) gene to chromosome 10 band q23.3 by radiation hybrid mapping. Cytogenet.
Cell Genet. 83: 246 only, 1998.
5. Schrick, J. J.; Vogel, P.; Abuin, A.; Hampton, B.; Rice, D. S.
: ADP-ribosylation factor-like 3 is involved in kidney and photoreceptor
development. Am. J. Path. 168: 1288-1298, 2006.
6. Veltel, S.; Gasper, R.; Eisenacher, E.; Wittinghofer, A.: The
retinitis pigmentosa 2 gene product is a GTPase-activating protein
for Arf-like 3. Nature Struct. Molec. Biol. 15: 373-380, 2008.
7. Veltel, S.; Kravchenko, A.; Ismail, S.; Wittinghofer, A.: Specificity
of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-GAP
complex. FEBS Letters 582: 2501-2507, 2008.
8. Zhou, C.; Cunningham, L.; Marcus, A. I.; Li, Y.; Kahn, R. A.:
Arl2 and Arl3 regulate different microtubule-dependent processes. Molec.
Biol. Cell 17: 2476-2487, 2006.
*FIELD* CN
Patricia A. Hartz - updated: 10/2/2013
Patricia A. Hartz - updated: 6/30/2009
George E. Tiller - updated: 8/25/2004
*FIELD* CD
Paul J. Converse: 3/17/2000
*FIELD* ED
mgross: 10/23/2013
tpirozzi: 10/2/2013
alopez: 7/6/2009
terry: 6/30/2009
alopez: 2/16/2009
tkritzer: 8/25/2004
mgross: 3/21/2000
mgross: 3/20/2000
mgross: 3/17/2000