RBCC

Full text data of ARL2

ARL2 [Confidence: low (only semi-automatic identification from reviews)]
ADP-ribosylation factor-like protein 2

UniProt P36404
ID ARL2_HUMAN Reviewed; 184 AA.
AC P36404; G3V184; Q9BUK8;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 4.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=ADP-ribosylation factor-like protein 2;
GN Name=ARL2;
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] (ISOFORM 1), AND VARIANT ALA-141.
RX PubMed=8415637; DOI=10.1073/pnas.90.19.8952;
RA Clark J., Moore L., Krasinskas A., Way J., Battey J.F., Tamkun J.W.,
RA Kahn R.A.;
RT "Selective amplification of additional members of the ADP-ribosylation
RT factor (ARF) family: cloning of additional human and Drosophila ARF-
RT like genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:8952-8956(1993).
RN [2]
RP SEQUENCE REVISION TO 11.
RA Kahn R.A.;
RL Submitted (NOV-1997) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ALA-141.
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT ALA-141.
RX PubMed=15146197; DOI=10.1038/nbt971;
RA Brandenberger R., Wei H., Zhang S., Lei S., Murage J., Fisk G.J.,
RA Li Y., Xu C., Fang R., Guegler K., Rao M.S., Mandalam R.,
RA Lebkowski J., Stanton L.W.;
RT "Transcriptome characterization elucidates signaling networks that
RT control human ES cell growth and differentiation.";
RL Nat. Biotechnol. 22:707-716(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [8]
RP INTERACTION WITH ARL2BP.
RX PubMed=10488091; DOI=10.1074/jbc.274.39.27553;
RA Sharer J.D., Kahn R.A.;
RT "The ARF-like 2 (ARL2)-binding protein, BART. Purification, cloning,
RT and initial characterization.";
RL J. Biol. Chem. 274:27553-27561(1999).
RN [9]
RP FUNCTION, INTERACTION WITH TBCD, AND MUTAGENESIS OF THR-30; THR-47;
RP PHE-50 AND GLN-70.
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 [10]
RP INTERACTION WITH ARL2BP AND PDE6D, AND MUTAGENESIS OF GLN-70.
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 [11]
RP INTERACTION WITH ARL2BP.
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 SUBCELLULAR LOCATION, AND ABSENCE OF N-MYRISTOYLATION.
RX PubMed=11809823; DOI=10.1091/mbc.01-05-0245;
RA Sharer J.D., Shern J.F., Van Valkenburgh H., Wallace D.C., Kahn R.A.;
RT "ARL2 and BART enter mitochondria and bind the adenine nucleotide
RT transporter.";
RL Mol. Biol. Cell 13:71-83(2002).
RN [13]
RP FUNCTION, MUTAGENESIS OF GLN-70, 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 ELMOD2.
RX PubMed=17452337; DOI=10.1074/jbc.M701347200;
RA Bowzard J.B., Cheng D., Peng J., Kahn R.A.;
RT "ELMOD2 is an Arl2 GTPase-activating protein that also acts on Arfs.";
RL J. Biol. Chem. 282:17568-17580(2007).
RN [15]
RP FUNCTION, AND GTP/GDP BINDING.
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 FUNCTION, INTERACTION WITH ARL2BP, MUTAGENESIS OF THR-30 AND GLN-70,
RP AND SUBCELLULAR LOCATION.
RX PubMed=18234692; DOI=10.1093/intimm/dxm154;
RA Muromoto R., Sekine Y., Imoto S., Ikeda O., Okayama T., Sato N.,
RA Matsuda T.;
RT "BART is essential for nuclear retention of STAT3.";
RL Int. Immunol. 20:395-403(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP INTERACTION WITH ARL2BP.
RX PubMed=18981177; DOI=10.1074/jbc.M806167200;
RA Bailey L.K., Campbell L.J., Evetts K.A., Littlefield K., Rajendra E.,
RA Nietlispach D., Owen D., Mott H.R.;
RT "The structure of binder of Arl2 (BART) reveals a novel G protein
RT binding domain: implications for function.";
RL J. Biol. Chem. 284:992-999(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP FUNCTION.
RX PubMed=20740604; DOI=10.1002/cm.20480;
RA Tian G., Thomas S., Cowan N.J.;
RT "Effect of TBCD and its regulatory interactor Arl2 on tubulin and
RT microtubule integrity.";
RL Cytoskeleton 67:706-714(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [23]
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 [24]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 1-184 IN A COMPLEX WITH
RP ARL2BP; GTP AND MAGNESIUM IONS, INTERACTION WITH ARL2BP, AND
RP MUTAGENESIS OF LEU-3; LEU-4; ILE-6; LEU-7; PHE-50; TYR-76 AND TYR-80.
RX PubMed=19368893; DOI=10.1016/j.str.2009.01.014;
RA Zhang T., Li S., Zhang Y., Zhong C., Lai Z., Ding J.;
RT "Crystal structure of the ARL2-GTP-BART complex reveals a novel
RT recognition and binding mode of small GTPase with effector.";
RL Structure 17:602-610(2009).
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). GTP-binding protein that
CC does not act as an allosteric activator of the cholera toxin
CC catalytic subunit. Regulates formation of new microtubules and
CC centrosome integrity. Prevents the TBCD-induced microtubule
CC destruction. Participates in association with TBCD, in the
CC disassembly of the apical junction complexes. Antagonizes the
CC effect of TBCD on epithelial cell detachment and tight and
CC adherens junctions disassembly. Together with ARL2, plays a role
CC in the nuclear translocation, retention and transcriptional
CC activity of STAT3. Component of a regulated secretory pathway
CC involved in Ca(2+)-dependent release of acetylcholine. Required
CC for normal progress through the cell cycle.
CC -!- SUBUNIT: Found in a complex with ARL2, ARL2BP and SLC25A6. Found
CC in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E
CC and TBCD. Found in a complex with ARL2, ARL2BP and SLC25A4. The
CC GTP-bound form interacts with PDE6D. Interacts with ELMOD2. The
CC GTP-bound form interacts with ARL2BP. Interacts, preferentially in
CC its GDP-bound state, with TBCD. Interacts with UNC119.
CC -!- INTERACTION:
CC O43924:PDE6D; NbExp=4; IntAct=EBI-752365, EBI-712685;
CC Q13432:UNC119; NbExp=2; IntAct=EBI-752365, EBI-711260;
CC -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space.
CC Cytoplasm, cytoskeleton, microtubule organizing center,
CC centrosome. Nucleus. Cytoplasm. Note=The complex formed with
CC ARL2BP, ARL2 and SLC25A6 is expressed in mitochondria. The complex
CC formed with ARL2BP, ARL2 and SLC25A4 is expressed in mitochondria
CC (By similarity). Not detected in the Golgi, nucleus and on the
CC mitotic spindle. Centrosome-associated throughout the cell cycle.
CC Not detected to interphase microtubules.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P36404-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P36404-2; Sequence=VSP_047278;
CC -!- PTM: Not N-myristoylated.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family.
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DR EMBL; L13687; AAC37606.1; -; mRNA.
DR EMBL; AF493888; AAM12602.1; -; mRNA.
DR EMBL; CN338497; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AP000436; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74333.1; -; Genomic_DNA.
DR EMBL; BC002530; AAH02530.1; -; mRNA.
DR PIR; A48259; A48259.
DR RefSeq; NP_001186674.1; NM_001199745.1.
DR RefSeq; NP_001658.2; NM_001667.3.
DR RefSeq; XP_005274050.1; XM_005273993.1.
DR UniGene; Hs.502836; -.
DR PDB; 3DOE; X-ray; 2.25 A; A=1-184.
DR PDB; 3DOF; X-ray; 3.30 A; A=1-184.
DR PDBsum; 3DOE; -.
DR PDBsum; 3DOF; -.
DR ProteinModelPortal; P36404; -.
DR SMR; P36404; 2-184.
DR DIP; DIP-47535N; -.
DR IntAct; P36404; 7.
DR MINT; MINT-6602180; -.
DR STRING; 9606.ENSP00000246747; -.
DR PhosphoSite; P36404; -.
DR DMDM; 116241255; -.
DR PaxDb; P36404; -.
DR PRIDE; P36404; -.
DR DNASU; 402; -.
DR Ensembl; ENST00000246747; ENSP00000246747; ENSG00000213465.
DR Ensembl; ENST00000529384; ENSP00000436021; ENSG00000213465.
DR Ensembl; ENST00000533729; ENSP00000432971; ENSG00000213465.
DR GeneID; 402; -.
DR KEGG; hsa:402; -.
DR UCSC; uc021qlc.1; human.
DR CTD; 402; -.
DR GeneCards; GC11P064781; -.
DR H-InvDB; HIX0079396; -.
DR HGNC; HGNC:693; ARL2.
DR HPA; HPA044610; -.
DR MIM; 601175; gene.
DR neXtProt; NX_P36404; -.
DR PharmGKB; PA24986; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000163691; -.
DR HOVERGEN; HBG002073; -.
DR InParanoid; P36404; -.
DR KO; K07943; -.
DR OMA; EMRILFL; -.
DR OrthoDB; EOG7M98HG; -.
DR EvolutionaryTrace; P36404; -.
DR GeneWiki; ARL2; -.
DR GenomeRNAi; 402; -.
DR NextBio; 1685; -.
DR PRO; PR:P36404; -.
DR ArrayExpress; P36404; -.
DR Bgee; P36404; -.
DR CleanEx; HS_ARL2; -.
DR Genevestigator; P36404; -.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0016328; C:lateral plasma membrane; ISS:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IMP:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IMP:UniProtKB.
DR GO; GO:0005095; F:GTPase inhibitor activity; TAS:ProtInc.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051297; P:centrosome organization; IMP:UniProtKB.
DR GO; GO:0051457; P:maintenance of protein location in nucleus; IDA:UniProtKB.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; ISS:UniProtKB.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IDA:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0070830; P:tight junction assembly; ISS:UniProtKB.
DR GO; GO:0007021; P:tubulin complex assembly; TAS:ProtInc.
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 3D-structure; Alternative splicing; Cell cycle; Complete proteome;
KW Cytoplasm; Cytoskeleton; GTP-binding; Isopeptide bond; Lipoprotein;
KW Mitochondrion; Myristate; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Ubl conjugation.
FT INIT_MET 1 1 Removed (Potential).
FT CHAIN 2 184 ADP-ribosylation factor-like protein 2.
FT /FTId=PRO_0000207453.
FT NP_BIND 23 30 GTP (By similarity).
FT NP_BIND 66 70 GTP (By similarity).
FT NP_BIND 125 128 GTP (By similarity).
FT BINDING 68 68 GTP; via amide nitrogen (By similarity).
FT MOD_RES 45 45 Phosphoserine.
FT LIPID 2 2 N-myristoyl glycine (Potential).
FT CROSSLNK 71 71 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VAR_SEQ 113 139 Missing (in isoform 2).
FT /FTId=VSP_047278.
FT VARIANT 141 141 V -> A (in dbSNP:rs664226).
FT /FTId=VAR_028056.
FT MUTAGEN 3 3 L->A: Reduces interaction with ARL2BP.
FT MUTAGEN 3 3 L->D: Reduces interaction with ARL2BP.
FT MUTAGEN 4 4 L->A: Does not reduce interaction with
FT ARL2BP.
FT MUTAGEN 4 4 L->D: Reduces interaction with ARL2BP.
FT MUTAGEN 6 6 I->R: Reduces interaction with ARL2BP.
FT MUTAGEN 7 7 L->A: Does not reduce interaction with
FT ARL2BP.
FT MUTAGEN 7 7 L->D: Reduces interaction with ARL2BP.
FT MUTAGEN 30 30 T->L: Does not inhibit the interaction
FT with TBCC and rescues the TBCC-induced
FT microtubule destruction.
FT MUTAGEN 30 30 T->N: Reduces interaction with ARL2BP.
FT Inhibits accumulation of STAT3 in the
FT nucleus.
FT MUTAGEN 47 47 T->A: Does not inhibit the interaction
FT with TBCC and rescues the TBCC-induced
FT microtubule destruction.
FT MUTAGEN 50 50 F->A: Reduces interaction with ARL2BP.
FT Inhibits the interaction with TBCC and
FT rescues the TBCC-induced microtubule
FT destruction.
FT MUTAGEN 70 70 Q->L: Induces cell cycle arrest, reduces
FT ability to form microtubules and
FT centrosome fragmentation. Inhibits the
FT interaction with TBCC and does not rescue
FT the TBCC-induced microtubule destruction.
FT Interacts with ARL2BP and PDE6D.
FT MUTAGEN 76 76 Y->A: Does not reduce interaction with
FT ARL2BP.
FT MUTAGEN 80 80 Y->A: Reduces interaction with ARL2BP.
FT HELIX 3 9
FT STRAND 16 22
FT HELIX 29 37
FT STRAND 48 54
FT STRAND 60 67
FT HELIX 71 80
FT STRAND 85 92
FT HELIX 96 98
FT HELIX 99 110
FT HELIX 113 115
FT STRAND 119 125
FT HELIX 135 140
FT HELIX 141 146
FT STRAND 152 156
FT TURN 159 162
FT HELIX 165 184
SQ SEQUENCE 184 AA; 20878 MW; 0823F005719C17F9 CRC64;
MGLLTILKKM KQKERELRLL MLGLDNAGKT TILKKFNGED IDTISPTLGF NIKTLEHRGF
KLNIWDVGGQ KSLRSYWRNY FESTDGLIWV VDSADRQRMQ DCQRELQSLL VEERLAGATL
LIFANKQDLP GALSSNAIRE VLELDSIRSH HWCIQGCSAV TGENLLPGID WLLDDISSRI
FTAD
//

MIM 601175
*RECORD*
*FIELD* NO
601175
*FIELD* TI
*601175 ADP-RIBOSYLATION FACTOR-LIKE 2; ARL2
*FIELD* TX

CLONING

The ARFs are small GTP-binding proteins of the RAS superfamily (see
read moreARF1, 103180). Clark et al. (1993) used degenerate PCR to clone human
ARL2, a member of a functionally distinct group of ARF-like genes. ARL2
encodes a 184-amino acid predicted protein that is 76% identical to ARF1
and about 40 to 45% identical to the Drosophila ARL proteins. Northern
blot analysis suggested ubiquitous transcription.

By immunohistochemical analysis of several mammalian cell lines,
including human, Zhou et al. (2006) found that ARL2 was expressed at
centrosomes, in cytoplasmic punctae, and in the nucleus. ARL2 localized
to centrosomes throughout the cell cycle, and its expression in other
structures was cell type specific.

GENE FUNCTION

Clark et al. (1993) found that recombinant ARL2 bound GTP rapidly.
However, guanine nucleotide exchange did not require phospholipids, a
characteristic of ARF proteins.

Bowzard et al. (2007) showed that both human ELMOD1 (615456) and ELMOD2
(610196), but not other ELMO domain-containing proteins, had GAP
activity toward ARL2.

Zhou et al. (2006) stated that ARL2 and ARL3 (604695) arose from a
common ancestor early in eukaryotic evolution and that they remain
highly related. However, they found that the 2 GTPases had distinct
effects on microtubule function in mammalian cells. Knockdown of ARL2 in
HeLa cells via RNA interference had 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. In contrast,
knockdown of ARL3 using RNA interference changed HeLa cell morphology,
caused Golgi fragmentation, and increased acetylation of alpha-tubulin
(see 602259), which resulted in failure of cytokinesis and an elevated
number of binucleated cells. Overexpression of ARL3 had little effect.

The assembly of alpha/beta tubulin heterodimers requires the
participation of a series of chaperone proteins, some of which can
participate in the reverse microtubule-depolymerizing reaction. Using
HeLa cells, Tian et al. (2010) found that overexpression of the tubulin
chaperone TBCD (604649) caused microtubule depolymerization.
Coexpression of ARL2 inhibited microtubule depolymerization by
sequestering TBCD in an ARL2-TBCD interaction.

Using microarray analysis, quantitative PCR, and overexpression and
knockdown studies, Wang et al. (2011) found that binding of the microRNA
MIR16 (see 609704) to the 3-prime UTR of ARL2 caused downregulation of
ARL2 mRNA and protein expression in several human cell lines. MIR16
reduced proliferation and caused G0/G1 cell cycle arrest, at least in
part, through ARL2 downregulation. MIR16 also reduced cell migration,
but this effect was not mimicked by small interfering RNA directed
against ARL2.

Ismail et al. (2011) stated that PDE-delta (PDE6D; 602676) 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.

MAPPING

Hartz (2013) mapped the ARL2 gene to chromosome 11q13.1 based on an
alignment of the ARL2 sequence (GenBank GENBANK L13687) with the genomic
sequence (GRCh37).

*FIELD* RF
1. Bowzard, J. B.; Cheng, D.; Peng, J.; Kahn, R. A.: ELMOD2 is an
Arl2 GTPase-activating protein that also acts on Arfs. J. Biol. Chem. 282:
17568-17580, 2007.

2. Clark, J.; Moore, L.; Krasinskas, A.; Way, J.; Battey, J.; Tamkun,
J.; Kahn, R. A.: Selective amplification of additional members of
the ADP-ribosylation factor (ARF) family: cloning of additional human
and Drosophila ARF-like genes. Proc. Nat. Acad. Sci. 90: 8952-8956,
1993.

3. Hartz, P. A.: Personal Communication. Baltimore, Md. 9/23/2013.

4. 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.

5. Tian, G.; Thomas, S.; Cowan, N. J.: Effect of TBCD and its regulatory
interactor Arl2 on tubulin and microtubule integrity. Cytoskeleton 67:
706-714, 2010.

6. Wang, K.; Li, P.; Dong, Y.; Cai, X.; Hou, D.; Guo, J.; Yin, Y.;
Zhang, Y.; Li, J.; Liang, H.; Yu, B.; Chen, J.; Zen, K.; Zhang, J.;
Zhang, C.-Y.; Chen, X.: A microarray-based approach identifies ADP
ribosylation factor-like protein 2 as a target of microRNA-16. J.
Biol. Chem. 286: 9468-9476, 2011.

7. 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: 9/23/2013

*FIELD* CD
Alan F. Scott: 4/4/1996

*FIELD* ED
mgross: 10/23/2013
tpirozzi: 10/2/2013
mgross: 9/24/2013
tpirozzi: 9/23/2013
mark: 4/4/1996
terry: 4/4/1996
mark: 4/4/1996

RBCC Red Blood Cell Collection

Full text data of ARL2