ID ARL2_HUMAN Reviewed; 184 AA. AC P36404; Q9BUK8; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 4. DT 29-MAY-2013, entry version 125. 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], 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], AND VARIANT 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 [LARGE SCALE MRNA]. 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 [5] 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 [6] 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 [7] 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 [8] 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 [9] 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 [10] 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 [11] 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 [12] 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 [13] 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 [14] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-71, AND MASS RP SPECTROMETRY. RX PubMed=18781797; DOI=10.1021/pr800468j; RA Meierhofer D., Wang X., Huang L., Kaiser P.; RT "Quantitative analysis of global ubiquitination in HeLa cells by mass RT spectrometry."; RL J. Proteome Res. 7:4566-4576(2008). RN [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 -!- SUBCELLULAR LOCATION: Mitochondrion intermembrane space. CC Cytoplasm, cytoskeleton, centrosome. Nucleus. Cytoplasm. Note=The CC complex formed with ARL2BP, ARL2 and SLC25A6 is expressed in CC mitochondria. The complex formed with ARL2BP, ARL2 and SLC25A4 is CC expressed in mitochondria (By similarity). Not detected in the CC Golgi, nucleus and on the mitotic spindle. Centrosome-associated CC throughout the cell cycle. Not detected to interphase CC microtubules. CC -!- PTM: Not N-myristoylated. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Arf family. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L13687; AAC37606.1; -; mRNA. DR EMBL; AF493888; AAM12602.1; -; mRNA. DR EMBL; BC002530; AAH02530.1; -; mRNA. DR IPI; IPI00003326; -. DR PIR; A48259; A48259. DR RefSeq; NP_001186674.1; NM_001199745.1. DR RefSeq; NP_001658.2; NM_001667.3. 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 DIP; DIP-47535N; -. DR IntAct; P36404; 4. 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 GeneID; 402; -. DR KEGG; hsa:402; -. DR UCSC; uc001och.4; 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; RNYFECT; -. DR OrthoDB; EOG4K0QPF; -. DR EvolutionaryTrace; P36404; -. DR GenomeRNAi; 402; -. DR NextBio; 1685; -. DR ArrayExpress; P36404; -. DR Bgee; P36404; -. DR CleanEx; HS_ARL2; -. DR Genevestigator; P36404; -. DR GermOnline; ENSG00000110025; Homo sapiens. 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:Compara. 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; Cell cycle; Complete proteome; Cytoplasm; Cytoskeleton; KW GTP-binding; Isopeptide bond; Lipoprotein; Mitochondrion; Myristate; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Ubl conjugation. FT CHAIN 1 184 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 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 //