Full text data of RAN
RAN
(ARA24)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
GTP-binding nuclear protein Ran (Androgen receptor-associated protein 24; GTPase Ran; Ras-like protein TC4; Ras-related nuclear protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
GTP-binding nuclear protein Ran (Androgen receptor-associated protein 24; GTPase Ran; Ras-like protein TC4; Ras-related nuclear protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P62826
ID RAN_HUMAN Reviewed; 216 AA.
AC P62826; A8K3Z8; P17080; P28746; P28747; Q6IPB2; Q86V08; Q8NI90;
read moreAC Q9CSP3; Q9CWI7; Q9CZA2; Q9UDJ5; Q9UEU9;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=GTP-binding nuclear protein Ran;
DE AltName: Full=Androgen receptor-associated protein 24;
DE AltName: Full=GTPase Ran;
DE AltName: Full=Ras-like protein TC4;
DE AltName: Full=Ras-related nuclear protein;
GN Name=RAN; Synonyms=ARA24; ORFNames=OK/SW-cl.81;
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 TISSUE SPECIFICITY.
RC TISSUE=Teratocarcinoma;
RX PubMed=2108320;
RA Drivas G.T., Shih A., Coutavas E., Rush M.G., D'Eustachio P.;
RT "Characterization of four novel ras-like genes expressed in a human
RT teratocarcinoma cell line.";
RL Mol. Cell. Biol. 10:1793-1798(1990).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RX PubMed=1855255; DOI=10.1016/0092-8674(91)90624-8;
RA Matsumoto T., Beach D.H.;
RT "Premature initiation of mitosis in yeast lacking RCC1 or an
RT interacting GTPase.";
RL Cell 66:347-360(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLY-19 AND GLN-69.
RC TISSUE=Brain;
RX PubMed=8421051; DOI=10.1083/jcb.120.2.313;
RA Ren M., Drivas G.T., D'Eustachio P., Rush M.G.;
RT "Ran/TC4: a small nuclear GTP-binding protein that regulates DNA
RT synthesis.";
RL J. Cell Biol. 120:313-323(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH AR, AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=10400640; DOI=10.1074/jbc.274.29.20229;
RA Hsiao P.-W., Lin D.-L., Nakao R., Chang C.;
RT "The linkage of Kennedy's neuron disease to ARA24, the first
RT identified androgen receptor polyglutamine region-associated
RT coactivator.";
RL J. Biol. Chem. 274:20229-20234(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
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 [10]
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, Ovary, Skin, and Uterus;
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 [12]
RP PROTEIN SEQUENCE OF 2-23 AND 143-166, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (FEB-2006) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 39-56 AND 153-166, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 65-216.
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP PROTEIN SEQUENCE OF 65-76; 90-125; 128-147 AND 154-216, INTERACTION
RP WITH CHC1, AND SUBCELLULAR LOCATION.
RC TISSUE=Cervix carcinoma;
RX PubMed=1961752; DOI=10.1073/pnas.88.23.10830;
RA Bischoff F.R., Ponstingl H.;
RT "Mitotic regulator protein RCC1 is complexed with a nuclear ras-
RT related polypeptide.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:10830-10834(1991).
RN [16]
RP FUNCTION.
RX PubMed=8692944; DOI=10.1073/pnas.93.14.7059;
RA Moroianu J., Blobel G., Radu A.;
RT "Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta
RT heterodimer by displacing alpha from an overlapping binding site on
RT beta.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:7059-7062(1996).
RN [17]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH XPO1.
RX PubMed=9323133; DOI=10.1016/S0092-8674(00)80371-2;
RA Fornerod M., Ohno M., Yoshida M., Mattaj I.W.;
RT "CRM1 is an export receptor for leucine-rich nuclear export signals.";
RL Cell 90:1051-1060(1997).
RN [18]
RP IDENTIFICATION IN A COMPLEX WITH HIV-1 REV; HIV-1 REV RESPONSE ELEMENT
RP AND XPO1.
RX PubMed=9837918; DOI=10.1074/jbc.273.50.33414;
RA Askjaer P., Jensen T.H., Nilsson J., Englmeier L., Kjems J.;
RT "The specificity of the CRM1-Rev nuclear export signal interaction is
RT mediated by RanGTP.";
RL J. Biol. Chem. 273:33414-33422(1998).
RN [19]
RP IDENTIFICATION IN A NUCLEAR EXPORT RECEPTOR COMPLEX, AND
RP IDENTIFICATION IN A TRIMERIC EXPORT COMPLEX WITH SNUPN AND XPO1.
RX PubMed=10209022; DOI=10.1083/jcb.145.2.255;
RA Paraskeva E., Izaurralde E., Bischoff F.R., Huber J., Kutay U.,
RA Hartmann E., Luehrmann R., Goerlich D.;
RT "CRM1-mediated recycling of snurportin 1 to the cytoplasm.";
RL J. Cell Biol. 145:255-264(1999).
RN [20]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RANBP3 AND XPO1.
RX PubMed=11571268; DOI=10.1093/embo-reports/kve200;
RA Englmeier L., Fornerod M., Bischoff F.R., Petosa C., Mattaj I.W.,
RA Kutay U.;
RT "RanBP3 influences interactions between CRM1 and its nuclear protein
RT export substrates.";
RL EMBO Rep. 2:926-932(2001).
RN [21]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RANBP3 AND XPO1.
RX PubMed=11425870; DOI=10.1083/jcb.153.7.1391;
RA Lindsay M.E., Holaska J.M., Welch K., Paschal B.M., Macara I.G.;
RT "Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein
RT export.";
RL J. Cell Biol. 153:1391-1402(2001).
RN [22]
RP IDENTIFICATION IN A COMPLEX WITH COPS5; RANBP9 AND DYRK1B.
RX PubMed=14500717; DOI=10.1074/jbc.M307556200;
RA Zou Y., Lim S., Lee K., Deng X., Friedman E.;
RT "Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial
RT cell migration and is negatively regulated by the Met adaptor Ran-
RT binding protein M.";
RL J. Biol. Chem. 278:49573-49581(2003).
RN [23]
RP INTERACTION WITH TERT.
RX PubMed=12808100; DOI=10.1128/MCB.23.13.4598-4610.2003;
RA Haendeler J., Hoffmann J., Brandes R.P., Zeiher A.M., Dimmeler S.;
RT "Hydrogen peroxide triggers nuclear export of telomerase reverse
RT transcriptase via Src kinase family-dependent phosphorylation of
RT tyrosine 707.";
RL Mol. Cell. Biol. 23:4598-4610(2003).
RN [24]
RP IDENTIFICATION IN A COMPLEX WITH HTLV-1 REX; RANBP3 AND XPO1.
RX PubMed=14612415; DOI=10.1128/MCB.23.23.8751-8761.2003;
RA Hakata Y., Yamada M., Shida H.;
RT "A multifunctional domain in human CRM1 (exportin 1) mediates RanBP3
RT binding and multimerization of human T-cell leukemia virus type 1 Rex
RT protein.";
RL Mol. Cell. Biol. 23:8751-8761(2003).
RN [25]
RP INTERACTION WITH RANBP9 AND RANBP10.
RX PubMed=14684163; DOI=10.1016/j.bbrc.2003.11.124;
RA Wang D., Li Z., Schoen S.R., Messing E.M., Wu G.;
RT "A novel MET-interacting protein shares high sequence similarity with
RT RanBPM, but fails to stimulate MET-induced Ras/Erk signaling.";
RL Biochem. Biophys. Res. Commun. 313:320-326(2004).
RN [26]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH XPO1.
RX PubMed=15574331; DOI=10.1016/j.molcel.2004.11.018;
RA Petosa C., Schoehn G., Askjaer P., Bauer U., Moulin M., Steuerwald U.,
RA Soler-Lopez M., Baudin F., Mattaj I.W., Mueller C.W.;
RT "Architecture of CRM1/Exportin1 suggests how cooperativity is achieved
RT during formation of a nuclear export complex.";
RL Mol. Cell 16:761-775(2004).
RN [27]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [28]
RP FUNCTION, INTERACTION WITH BIRC5, AND MUTAGENESIS OF THR-24 AND
RP GLN-69.
RX PubMed=18591255; DOI=10.1128/MCB.02039-07;
RA Xia F., Canovas P.M., Guadagno T.M., Altieri D.C.;
RT "A survivin-ran complex regulates spindle formation in tumor cells.";
RL Mol. Cell. Biol. 28:5299-5311(2008).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH VRK1; VRK2 AND
RP VRK3.
RX PubMed=18617507; DOI=10.1074/mcp.M700586-MCP200;
RA Sanz-Garcia M., Lopez-Sanchez I., Lazo P.A.;
RT "Proteomics identification of nuclear Ran GTPase as an inhibitor of
RT human VRK1 and VRK2 (vaccinia-related kinase) activities.";
RL Mol. Cell. Proteomics 7:2199-2214(2008).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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 [31]
RP INTERACTION WITH MAD2L2, AND SUBCELLULAR LOCATION.
RX PubMed=19753112; DOI=10.1371/journal.pone.0007020;
RA Medendorp K., van Groningen J.J., Vreede L., Hetterschijt L.,
RA van den Hurk W.H., de Bruijn D.R., Brugmans L., van Kessel A.G.;
RT "The mitotic arrest deficient protein MAD2B interacts with the small
RT GTPase RAN throughout the cell cycle.";
RL PLoS ONE 4:E7020-E7020(2009).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-60; LYS-71; LYS-99 AND
RP LYS-159, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [33]
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 [34]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=7885480; DOI=10.1038/374378a0;
RA Scheffzek K., Klebe C., Fritz-Wolf K., Kabsch W., Wittinghofer A.;
RT "Crystal structure of the nuclear Ras-related protein Ran in its GDP-
RT bound form.";
RL Nature 374:378-381(1995).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF COMPLEX WITH KPNB2.
RX PubMed=10353245; DOI=10.1038/20375;
RA Chook Y.M., Blobel G.;
RT "Structure of the nuclear transport complex karyopherin-beta2-Ran x
RT GppNHp.";
RL Nature 399:230-237(1999).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF COMPLEX WITH NUP358.
RX PubMed=10078529; DOI=10.1038/17969;
RA Vetter I.R., Nowak C., Nishimoto T., Kuhlmann J., Wittinghofer A.;
RT "Structure of a Ran-binding domain complexed with Ran bound to a GTP
RT analogue: implications for nuclear transport.";
RL Nature 398:39-46(1999).
CC -!- FUNCTION: GTP-binding protein involved in nucleocytoplasmic
CC transport. Required for the import of protein into the nucleus and
CC also for RNA export. Involved in chromatin condensation and
CC control of cell cycle (By similarity). The complex with BIRC5/
CC survivin plays a role in mitotic spindle formation by serving as a
CC physical scaffold to help deliver the RAN effector molecule TPX2
CC to microtubules. Acts as a negative regulator of the kinase
CC activity of VRK1 and VRK2.
CC -!- FUNCTION: Enhances AR-mediated transactivation. Transactivation
CC decreases as the poly-Gln length within AR increases.
CC -!- SUBUNIT: Monomer. Also forms a complex with CHC1 and interacts
CC with the AR N-terminal poly-Gln region. The interaction with AR is
CC inversely correlated with the poly-Gln length. Part of a complex
CC consisting of RANBP9, Ran, DYRK1B and COPS5. Found in a nuclear
CC export complex with RANBP3 and XPO1. Component of a nuclear export
CC receptor complex composed of KPNB1, Ran, SNUPN and XPO1. Found in
CC a trimeric export complex with SNUPN, Ran and XPO1. Interacts with
CC RANBP10. In case of HIV-1 infection, found in a complex with HIV-1
CC Rev, RNAs containing a Rev response element (RRE) and XPO1. Found
CC in a complex with HTLV-1 Rex, RANBP3 and XPO1. Interacts in its
CC GTP-bound form with BIRC5/survivin at S and M phases of the cell
CC cycle. Interacts with TERT; the interaction requires hydrogen
CC peroxide-mediated phosphorylation of TERT and transports TERT to
CC the nucleus. Interacts with MAD2L2. Interacts with RANBP10 (By
CC similarity). Interacts with VRK1 and VRK3. Interacts with isoform
CC 1 and isoform 2 of VRK2.
CC -!- INTERACTION:
CC O94829:IPO13; NbExp=3; IntAct=EBI-286642, EBI-747310;
CC P18754:RCC1; NbExp=6; IntAct=EBI-286642, EBI-992720;
CC Q92973:TNPO1; NbExp=2; IntAct=EBI-286642, EBI-286693;
CC Q99986:VRK1; NbExp=12; IntAct=EBI-286642, EBI-1769146;
CC Q86Y07-1:VRK2; NbExp=2; IntAct=EBI-286642, EBI-1207633;
CC Q86Y07-5:VRK2; NbExp=2; IntAct=EBI-286642, EBI-1207649;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Melanosome.
CC Note=Predominantly nuclear during interphase (By similarity).
CC Becomes dispersed throughout the cytoplasm during mitosis.
CC Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV.
CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ran family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB93486.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RANID4203912q24.html";
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DR EMBL; M31469; AAA36546.1; -; mRNA.
DR EMBL; AF052578; AAC05840.1; -; mRNA.
DR EMBL; AF054183; AAC99400.1; -; mRNA.
DR EMBL; AF501887; AAM15923.1; -; mRNA.
DR EMBL; BT007271; AAP35935.1; -; mRNA.
DR EMBL; CR450347; CAG29343.1; -; mRNA.
DR EMBL; AK290763; BAF83452.1; -; mRNA.
DR EMBL; AK312466; BAG35373.1; -; mRNA.
DR EMBL; CH471054; EAW98516.1; -; Genomic_DNA.
DR EMBL; BC004272; AAH04272.3; -; mRNA.
DR EMBL; BC014518; AAH14518.1; -; mRNA.
DR EMBL; BC014901; AAH14901.1; -; mRNA.
DR EMBL; BC016654; AAH16654.1; -; mRNA.
DR EMBL; BC051908; AAH51908.2; -; mRNA.
DR EMBL; BC072000; AAH72000.1; -; mRNA.
DR EMBL; AB062399; BAB93486.1; ALT_INIT; mRNA.
DR PIR; A44393; TVHUC3.
DR RefSeq; NP_006316.1; NM_006325.3.
DR RefSeq; XP_005253649.1; XM_005253592.1.
DR UniGene; Hs.10842; -.
DR PDB; 1I2M; X-ray; 1.76 A; A/C=1-216.
DR PDB; 1IBR; X-ray; 2.30 A; A/C=1-216.
DR PDB; 1K5D; X-ray; 2.70 A; A/D/G/J=1-216.
DR PDB; 1K5G; X-ray; 3.10 A; A/D/G/J=1-216.
DR PDB; 1QBK; X-ray; 3.00 A; C=1-216.
DR PDB; 1RRP; X-ray; 2.96 A; A/C=8-211.
DR PDB; 3CH5; X-ray; 2.10 A; A=1-216.
DR PDB; 3EA5; X-ray; 2.50 A; A/C=1-216.
DR PDB; 3GJ0; X-ray; 1.48 A; A/B=2-216.
DR PDB; 3GJ3; X-ray; 1.79 A; A=2-216.
DR PDB; 3GJ4; X-ray; 2.15 A; A/C=2-216.
DR PDB; 3GJ5; X-ray; 1.79 A; A/C=2-216.
DR PDB; 3GJ6; X-ray; 2.70 A; A=2-216.
DR PDB; 3GJ7; X-ray; 1.93 A; A/C=2-216.
DR PDB; 3GJ8; X-ray; 1.82 A; A/C=2-216.
DR PDB; 3GJX; X-ray; 2.50 A; C/F=1-216.
DR PDB; 3NBY; X-ray; 3.42 A; C/F=5-180.
DR PDB; 3NBZ; X-ray; 2.80 A; C/F=5-180.
DR PDB; 3NC0; X-ray; 2.90 A; C/F=5-180.
DR PDB; 3NC1; X-ray; 3.35 A; C=1-180.
DR PDB; 3ZJY; X-ray; 3.60 A; A/D/F=1-180.
DR PDB; 4GMX; X-ray; 2.10 A; A=1-216.
DR PDB; 4GPT; X-ray; 2.22 A; A=1-216.
DR PDB; 4HAT; X-ray; 1.78 A; A=1-216.
DR PDB; 4HAU; X-ray; 2.00 A; A=1-216.
DR PDB; 4HAV; X-ray; 2.00 A; A=1-216.
DR PDB; 4HAW; X-ray; 1.90 A; A=1-216.
DR PDB; 4HAX; X-ray; 2.28 A; A=1-216.
DR PDB; 4HAY; X-ray; 2.30 A; A=1-216.
DR PDB; 4HAZ; X-ray; 1.90 A; A=1-216.
DR PDB; 4HB0; X-ray; 2.20 A; A=1-216.
DR PDB; 4HB2; X-ray; 1.80 A; A=1-216.
DR PDB; 4HB3; X-ray; 2.80 A; A=1-216.
DR PDB; 4HB4; X-ray; 2.05 A; A=1-216.
DR PDBsum; 1I2M; -.
DR PDBsum; 1IBR; -.
DR PDBsum; 1K5D; -.
DR PDBsum; 1K5G; -.
DR PDBsum; 1QBK; -.
DR PDBsum; 1RRP; -.
DR PDBsum; 3CH5; -.
DR PDBsum; 3EA5; -.
DR PDBsum; 3GJ0; -.
DR PDBsum; 3GJ3; -.
DR PDBsum; 3GJ4; -.
DR PDBsum; 3GJ5; -.
DR PDBsum; 3GJ6; -.
DR PDBsum; 3GJ7; -.
DR PDBsum; 3GJ8; -.
DR PDBsum; 3GJX; -.
DR PDBsum; 3NBY; -.
DR PDBsum; 3NBZ; -.
DR PDBsum; 3NC0; -.
DR PDBsum; 3NC1; -.
DR PDBsum; 3ZJY; -.
DR PDBsum; 4GMX; -.
DR PDBsum; 4GPT; -.
DR PDBsum; 4HAT; -.
DR PDBsum; 4HAU; -.
DR PDBsum; 4HAV; -.
DR PDBsum; 4HAW; -.
DR PDBsum; 4HAX; -.
DR PDBsum; 4HAY; -.
DR PDBsum; 4HAZ; -.
DR PDBsum; 4HB0; -.
DR PDBsum; 4HB2; -.
DR PDBsum; 4HB3; -.
DR PDBsum; 4HB4; -.
DR ProteinModelPortal; P62826; -.
DR SMR; P62826; 8-216.
DR DIP; DIP-5929N; -.
DR IntAct; P62826; 42.
DR MINT; MINT-94188; -.
DR TCDB; 9.A.60.1.1; the small nuclear rna exporter (snrna-e).
DR PhosphoSite; P62826; -.
DR DMDM; 51338598; -.
DR OGP; P62826; -.
DR REPRODUCTION-2DPAGE; P62826; -.
DR UCD-2DPAGE; P62826; -.
DR PaxDb; P62826; -.
DR PRIDE; P62826; -.
DR DNASU; 5901; -.
DR Ensembl; ENST00000392369; ENSP00000376176; ENSG00000132341.
DR Ensembl; ENST00000543796; ENSP00000446215; ENSG00000132341.
DR GeneID; 5901; -.
DR KEGG; hsa:5901; -.
DR UCSC; uc001uir.3; human.
DR CTD; 5901; -.
DR GeneCards; GC12P131356; -.
DR HGNC; HGNC:9846; RAN.
DR MIM; 601179; gene.
DR neXtProt; NX_P62826; -.
DR PharmGKB; PA34205; -.
DR eggNOG; COG1100; -.
DR HOVERGEN; HBG107376; -.
DR InParanoid; P62826; -.
DR KO; K07936; -.
DR OrthoDB; EOG7C8GJ1; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_71; Gene Expression.
DR SignaLink; P62826; -.
DR ChiTaRS; RAN; human.
DR EvolutionaryTrace; P62826; -.
DR GeneWiki; Ran_(biology); -.
DR GenomeRNAi; 5901; -.
DR NextBio; 22956; -.
DR PRO; PR:P62826; -.
DR ArrayExpress; P62826; -.
DR Bgee; P62826; -.
DR Genevestigator; P62826; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005643; C:nuclear pore; NAS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0050681; F:androgen receptor binding; NAS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; TAS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; TAS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; NAS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0034629; P:cellular protein complex localization; IEA:Ensembl.
DR GO; GO:0006259; P:DNA metabolic process; TAS:UniProtKB.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0075733; P:intracellular transport of virus; TAS:Reactome.
DR GO; GO:0007067; P:mitosis; TAS:UniProtKB.
DR GO; GO:0007052; P:mitotic spindle organization; TAS:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; NAS:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; NAS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0006405; P:RNA export from nucleus; NAS:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR002041; Ran_GTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00627; GTPRANTC4.
DR SMART; SM00176; RAN; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51418; RAN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell cycle; Cell division;
KW Complete proteome; Cytoplasm; Direct protein sequencing; GTP-binding;
KW Host-virus interaction; Isopeptide bond; Mitosis; Nucleotide-binding;
KW Nucleus; Polymorphism; Protein transport; Reference proteome;
KW Transport; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 216 GTP-binding nuclear protein Ran.
FT /FTId=PRO_0000208696.
FT NP_BIND 17 24 GTP (By similarity).
FT NP_BIND 65 69 GTP (By similarity).
FT NP_BIND 122 125 GTP (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 60 60 N6-acetyllysine.
FT MOD_RES 71 71 N6-acetyllysine; alternate.
FT MOD_RES 99 99 N6-acetyllysine.
FT MOD_RES 159 159 N6-acetyllysine.
FT CROSSLNK 71 71 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate.
FT VARIANT 95 95 R -> I (in dbSNP:rs11546488).
FT /FTId=VAR_051900.
FT MUTAGEN 19 19 G->V: Blocks DNA replication; when
FT associated with L-69.
FT MUTAGEN 24 24 T->L: Has low binding affinity for GTP
FT and GDP. Almost completely abolishes
FT interaction with BIRC5.
FT MUTAGEN 69 69 Q->L: Blocks DNA replication; when
FT associated with V-19.
FT MUTAGEN 69 69 Q->N: Unable to hydrolyze GTP. Increases
FT binding to BIRC5 and promotes exaggerated
FT spindle formation.
FT CONFLICT 2 2 A -> T (in Ref. 11; AAH72000).
FT CONFLICT 181 181 A -> C (in Ref. 5; AAC99400).
FT STRAND 10 17
FT STRAND 18 22
FT HELIX 23 27
FT HELIX 31 35
FT STRAND 38 40
FT TURN 41 44
FT STRAND 45 54
FT STRAND 57 66
FT HELIX 69 71
FT HELIX 74 76
FT HELIX 77 80
FT STRAND 85 91
FT STRAND 92 94
FT HELIX 95 99
FT HELIX 101 111
FT STRAND 112 114
FT STRAND 117 122
FT STRAND 126 128
FT HELIX 133 135
FT HELIX 138 142
FT STRAND 145 148
FT TURN 151 154
FT TURN 156 158
FT HELIX 159 169
FT STRAND 176 178
FT TURN 185 187
FT HELIX 191 205
SQ SEQUENCE 216 AA; 24423 MW; D5C9B7275C34BCE0 CRC64;
MAAQGEPQVQ FKLVLVGDGG TGKTTFVKRH LTGEFEKKYV ATLGVEVHPL VFHTNRGPIK
FNVWDTAGQE KFGGLRDGYY IQAQCAIIMF DVTSRVTYKN VPNWHRDLVR VCENIPIVLC
GNKVDIKDRK VKAKSIVFHR KKNLQYYDIS AKSNYNFEKP FLWLARKLIG DPNLEFVAMP
ALAPPEVVMD PALAAQYEHD LEVAQTTALP DEDDDL
//
ID RAN_HUMAN Reviewed; 216 AA.
AC P62826; A8K3Z8; P17080; P28746; P28747; Q6IPB2; Q86V08; Q8NI90;
read moreAC Q9CSP3; Q9CWI7; Q9CZA2; Q9UDJ5; Q9UEU9;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=GTP-binding nuclear protein Ran;
DE AltName: Full=Androgen receptor-associated protein 24;
DE AltName: Full=GTPase Ran;
DE AltName: Full=Ras-like protein TC4;
DE AltName: Full=Ras-related nuclear protein;
GN Name=RAN; Synonyms=ARA24; ORFNames=OK/SW-cl.81;
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 TISSUE SPECIFICITY.
RC TISSUE=Teratocarcinoma;
RX PubMed=2108320;
RA Drivas G.T., Shih A., Coutavas E., Rush M.G., D'Eustachio P.;
RT "Characterization of four novel ras-like genes expressed in a human
RT teratocarcinoma cell line.";
RL Mol. Cell. Biol. 10:1793-1798(1990).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RX PubMed=1855255; DOI=10.1016/0092-8674(91)90624-8;
RA Matsumoto T., Beach D.H.;
RT "Premature initiation of mitosis in yeast lacking RCC1 or an
RT interacting GTPase.";
RL Cell 66:347-360(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLY-19 AND GLN-69.
RC TISSUE=Brain;
RX PubMed=8421051; DOI=10.1083/jcb.120.2.313;
RA Ren M., Drivas G.T., D'Eustachio P., Rush M.G.;
RT "Ran/TC4: a small nuclear GTP-binding protein that regulates DNA
RT synthesis.";
RL J. Cell Biol. 120:313-323(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH AR, AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=10400640; DOI=10.1074/jbc.274.29.20229;
RA Hsiao P.-W., Lin D.-L., Nakao R., Chang C.;
RT "The linkage of Kennedy's neuron disease to ARA24, the first
RT identified androgen receptor polyglutamine region-associated
RT coactivator.";
RL J. Biol. Chem. 274:20229-20234(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
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 [10]
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph, Ovary, Skin, and Uterus;
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 [12]
RP PROTEIN SEQUENCE OF 2-23 AND 143-166, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (FEB-2006) to UniProtKB.
RN [13]
RP PROTEIN SEQUENCE OF 39-56 AND 153-166, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 65-216.
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [15]
RP PROTEIN SEQUENCE OF 65-76; 90-125; 128-147 AND 154-216, INTERACTION
RP WITH CHC1, AND SUBCELLULAR LOCATION.
RC TISSUE=Cervix carcinoma;
RX PubMed=1961752; DOI=10.1073/pnas.88.23.10830;
RA Bischoff F.R., Ponstingl H.;
RT "Mitotic regulator protein RCC1 is complexed with a nuclear ras-
RT related polypeptide.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:10830-10834(1991).
RN [16]
RP FUNCTION.
RX PubMed=8692944; DOI=10.1073/pnas.93.14.7059;
RA Moroianu J., Blobel G., Radu A.;
RT "Nuclear protein import: Ran-GTP dissociates the karyopherin alphabeta
RT heterodimer by displacing alpha from an overlapping binding site on
RT beta.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:7059-7062(1996).
RN [17]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH XPO1.
RX PubMed=9323133; DOI=10.1016/S0092-8674(00)80371-2;
RA Fornerod M., Ohno M., Yoshida M., Mattaj I.W.;
RT "CRM1 is an export receptor for leucine-rich nuclear export signals.";
RL Cell 90:1051-1060(1997).
RN [18]
RP IDENTIFICATION IN A COMPLEX WITH HIV-1 REV; HIV-1 REV RESPONSE ELEMENT
RP AND XPO1.
RX PubMed=9837918; DOI=10.1074/jbc.273.50.33414;
RA Askjaer P., Jensen T.H., Nilsson J., Englmeier L., Kjems J.;
RT "The specificity of the CRM1-Rev nuclear export signal interaction is
RT mediated by RanGTP.";
RL J. Biol. Chem. 273:33414-33422(1998).
RN [19]
RP IDENTIFICATION IN A NUCLEAR EXPORT RECEPTOR COMPLEX, AND
RP IDENTIFICATION IN A TRIMERIC EXPORT COMPLEX WITH SNUPN AND XPO1.
RX PubMed=10209022; DOI=10.1083/jcb.145.2.255;
RA Paraskeva E., Izaurralde E., Bischoff F.R., Huber J., Kutay U.,
RA Hartmann E., Luehrmann R., Goerlich D.;
RT "CRM1-mediated recycling of snurportin 1 to the cytoplasm.";
RL J. Cell Biol. 145:255-264(1999).
RN [20]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RANBP3 AND XPO1.
RX PubMed=11571268; DOI=10.1093/embo-reports/kve200;
RA Englmeier L., Fornerod M., Bischoff F.R., Petosa C., Mattaj I.W.,
RA Kutay U.;
RT "RanBP3 influences interactions between CRM1 and its nuclear protein
RT export substrates.";
RL EMBO Rep. 2:926-932(2001).
RN [21]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH RANBP3 AND XPO1.
RX PubMed=11425870; DOI=10.1083/jcb.153.7.1391;
RA Lindsay M.E., Holaska J.M., Welch K., Paschal B.M., Macara I.G.;
RT "Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein
RT export.";
RL J. Cell Biol. 153:1391-1402(2001).
RN [22]
RP IDENTIFICATION IN A COMPLEX WITH COPS5; RANBP9 AND DYRK1B.
RX PubMed=14500717; DOI=10.1074/jbc.M307556200;
RA Zou Y., Lim S., Lee K., Deng X., Friedman E.;
RT "Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial
RT cell migration and is negatively regulated by the Met adaptor Ran-
RT binding protein M.";
RL J. Biol. Chem. 278:49573-49581(2003).
RN [23]
RP INTERACTION WITH TERT.
RX PubMed=12808100; DOI=10.1128/MCB.23.13.4598-4610.2003;
RA Haendeler J., Hoffmann J., Brandes R.P., Zeiher A.M., Dimmeler S.;
RT "Hydrogen peroxide triggers nuclear export of telomerase reverse
RT transcriptase via Src kinase family-dependent phosphorylation of
RT tyrosine 707.";
RL Mol. Cell. Biol. 23:4598-4610(2003).
RN [24]
RP IDENTIFICATION IN A COMPLEX WITH HTLV-1 REX; RANBP3 AND XPO1.
RX PubMed=14612415; DOI=10.1128/MCB.23.23.8751-8761.2003;
RA Hakata Y., Yamada M., Shida H.;
RT "A multifunctional domain in human CRM1 (exportin 1) mediates RanBP3
RT binding and multimerization of human T-cell leukemia virus type 1 Rex
RT protein.";
RL Mol. Cell. Biol. 23:8751-8761(2003).
RN [25]
RP INTERACTION WITH RANBP9 AND RANBP10.
RX PubMed=14684163; DOI=10.1016/j.bbrc.2003.11.124;
RA Wang D., Li Z., Schoen S.R., Messing E.M., Wu G.;
RT "A novel MET-interacting protein shares high sequence similarity with
RT RanBPM, but fails to stimulate MET-induced Ras/Erk signaling.";
RL Biochem. Biophys. Res. Commun. 313:320-326(2004).
RN [26]
RP IDENTIFICATION IN A NUCLEAR EXPORT COMPLEX WITH XPO1.
RX PubMed=15574331; DOI=10.1016/j.molcel.2004.11.018;
RA Petosa C., Schoehn G., Askjaer P., Bauer U., Moulin M., Steuerwald U.,
RA Soler-Lopez M., Baudin F., Mattaj I.W., Mueller C.W.;
RT "Architecture of CRM1/Exportin1 suggests how cooperativity is achieved
RT during formation of a nuclear export complex.";
RL Mol. Cell 16:761-775(2004).
RN [27]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [28]
RP FUNCTION, INTERACTION WITH BIRC5, AND MUTAGENESIS OF THR-24 AND
RP GLN-69.
RX PubMed=18591255; DOI=10.1128/MCB.02039-07;
RA Xia F., Canovas P.M., Guadagno T.M., Altieri D.C.;
RT "A survivin-ran complex regulates spindle formation in tumor cells.";
RL Mol. Cell. Biol. 28:5299-5311(2008).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH VRK1; VRK2 AND
RP VRK3.
RX PubMed=18617507; DOI=10.1074/mcp.M700586-MCP200;
RA Sanz-Garcia M., Lopez-Sanchez I., Lazo P.A.;
RT "Proteomics identification of nuclear Ran GTPase as an inhibitor of
RT human VRK1 and VRK2 (vaccinia-related kinase) activities.";
RL Mol. Cell. Proteomics 7:2199-2214(2008).
RN [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
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 [31]
RP INTERACTION WITH MAD2L2, AND SUBCELLULAR LOCATION.
RX PubMed=19753112; DOI=10.1371/journal.pone.0007020;
RA Medendorp K., van Groningen J.J., Vreede L., Hetterschijt L.,
RA van den Hurk W.H., de Bruijn D.R., Brugmans L., van Kessel A.G.;
RT "The mitotic arrest deficient protein MAD2B interacts with the small
RT GTPase RAN throughout the cell cycle.";
RL PLoS ONE 4:E7020-E7020(2009).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-60; LYS-71; LYS-99 AND
RP LYS-159, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [33]
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 [34]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX PubMed=7885480; DOI=10.1038/374378a0;
RA Scheffzek K., Klebe C., Fritz-Wolf K., Kabsch W., Wittinghofer A.;
RT "Crystal structure of the nuclear Ras-related protein Ran in its GDP-
RT bound form.";
RL Nature 374:378-381(1995).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF COMPLEX WITH KPNB2.
RX PubMed=10353245; DOI=10.1038/20375;
RA Chook Y.M., Blobel G.;
RT "Structure of the nuclear transport complex karyopherin-beta2-Ran x
RT GppNHp.";
RL Nature 399:230-237(1999).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.96 ANGSTROMS) OF COMPLEX WITH NUP358.
RX PubMed=10078529; DOI=10.1038/17969;
RA Vetter I.R., Nowak C., Nishimoto T., Kuhlmann J., Wittinghofer A.;
RT "Structure of a Ran-binding domain complexed with Ran bound to a GTP
RT analogue: implications for nuclear transport.";
RL Nature 398:39-46(1999).
CC -!- FUNCTION: GTP-binding protein involved in nucleocytoplasmic
CC transport. Required for the import of protein into the nucleus and
CC also for RNA export. Involved in chromatin condensation and
CC control of cell cycle (By similarity). The complex with BIRC5/
CC survivin plays a role in mitotic spindle formation by serving as a
CC physical scaffold to help deliver the RAN effector molecule TPX2
CC to microtubules. Acts as a negative regulator of the kinase
CC activity of VRK1 and VRK2.
CC -!- FUNCTION: Enhances AR-mediated transactivation. Transactivation
CC decreases as the poly-Gln length within AR increases.
CC -!- SUBUNIT: Monomer. Also forms a complex with CHC1 and interacts
CC with the AR N-terminal poly-Gln region. The interaction with AR is
CC inversely correlated with the poly-Gln length. Part of a complex
CC consisting of RANBP9, Ran, DYRK1B and COPS5. Found in a nuclear
CC export complex with RANBP3 and XPO1. Component of a nuclear export
CC receptor complex composed of KPNB1, Ran, SNUPN and XPO1. Found in
CC a trimeric export complex with SNUPN, Ran and XPO1. Interacts with
CC RANBP10. In case of HIV-1 infection, found in a complex with HIV-1
CC Rev, RNAs containing a Rev response element (RRE) and XPO1. Found
CC in a complex with HTLV-1 Rex, RANBP3 and XPO1. Interacts in its
CC GTP-bound form with BIRC5/survivin at S and M phases of the cell
CC cycle. Interacts with TERT; the interaction requires hydrogen
CC peroxide-mediated phosphorylation of TERT and transports TERT to
CC the nucleus. Interacts with MAD2L2. Interacts with RANBP10 (By
CC similarity). Interacts with VRK1 and VRK3. Interacts with isoform
CC 1 and isoform 2 of VRK2.
CC -!- INTERACTION:
CC O94829:IPO13; NbExp=3; IntAct=EBI-286642, EBI-747310;
CC P18754:RCC1; NbExp=6; IntAct=EBI-286642, EBI-992720;
CC Q92973:TNPO1; NbExp=2; IntAct=EBI-286642, EBI-286693;
CC Q99986:VRK1; NbExp=12; IntAct=EBI-286642, EBI-1769146;
CC Q86Y07-1:VRK2; NbExp=2; IntAct=EBI-286642, EBI-1207633;
CC Q86Y07-5:VRK2; NbExp=2; IntAct=EBI-286642, EBI-1207649;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Melanosome.
CC Note=Predominantly nuclear during interphase (By similarity).
CC Becomes dispersed throughout the cytoplasm during mitosis.
CC Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV.
CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ran family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB93486.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RANID4203912q24.html";
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DR EMBL; M31469; AAA36546.1; -; mRNA.
DR EMBL; AF052578; AAC05840.1; -; mRNA.
DR EMBL; AF054183; AAC99400.1; -; mRNA.
DR EMBL; AF501887; AAM15923.1; -; mRNA.
DR EMBL; BT007271; AAP35935.1; -; mRNA.
DR EMBL; CR450347; CAG29343.1; -; mRNA.
DR EMBL; AK290763; BAF83452.1; -; mRNA.
DR EMBL; AK312466; BAG35373.1; -; mRNA.
DR EMBL; CH471054; EAW98516.1; -; Genomic_DNA.
DR EMBL; BC004272; AAH04272.3; -; mRNA.
DR EMBL; BC014518; AAH14518.1; -; mRNA.
DR EMBL; BC014901; AAH14901.1; -; mRNA.
DR EMBL; BC016654; AAH16654.1; -; mRNA.
DR EMBL; BC051908; AAH51908.2; -; mRNA.
DR EMBL; BC072000; AAH72000.1; -; mRNA.
DR EMBL; AB062399; BAB93486.1; ALT_INIT; mRNA.
DR PIR; A44393; TVHUC3.
DR RefSeq; NP_006316.1; NM_006325.3.
DR RefSeq; XP_005253649.1; XM_005253592.1.
DR UniGene; Hs.10842; -.
DR PDB; 1I2M; X-ray; 1.76 A; A/C=1-216.
DR PDB; 1IBR; X-ray; 2.30 A; A/C=1-216.
DR PDB; 1K5D; X-ray; 2.70 A; A/D/G/J=1-216.
DR PDB; 1K5G; X-ray; 3.10 A; A/D/G/J=1-216.
DR PDB; 1QBK; X-ray; 3.00 A; C=1-216.
DR PDB; 1RRP; X-ray; 2.96 A; A/C=8-211.
DR PDB; 3CH5; X-ray; 2.10 A; A=1-216.
DR PDB; 3EA5; X-ray; 2.50 A; A/C=1-216.
DR PDB; 3GJ0; X-ray; 1.48 A; A/B=2-216.
DR PDB; 3GJ3; X-ray; 1.79 A; A=2-216.
DR PDB; 3GJ4; X-ray; 2.15 A; A/C=2-216.
DR PDB; 3GJ5; X-ray; 1.79 A; A/C=2-216.
DR PDB; 3GJ6; X-ray; 2.70 A; A=2-216.
DR PDB; 3GJ7; X-ray; 1.93 A; A/C=2-216.
DR PDB; 3GJ8; X-ray; 1.82 A; A/C=2-216.
DR PDB; 3GJX; X-ray; 2.50 A; C/F=1-216.
DR PDB; 3NBY; X-ray; 3.42 A; C/F=5-180.
DR PDB; 3NBZ; X-ray; 2.80 A; C/F=5-180.
DR PDB; 3NC0; X-ray; 2.90 A; C/F=5-180.
DR PDB; 3NC1; X-ray; 3.35 A; C=1-180.
DR PDB; 3ZJY; X-ray; 3.60 A; A/D/F=1-180.
DR PDB; 4GMX; X-ray; 2.10 A; A=1-216.
DR PDB; 4GPT; X-ray; 2.22 A; A=1-216.
DR PDB; 4HAT; X-ray; 1.78 A; A=1-216.
DR PDB; 4HAU; X-ray; 2.00 A; A=1-216.
DR PDB; 4HAV; X-ray; 2.00 A; A=1-216.
DR PDB; 4HAW; X-ray; 1.90 A; A=1-216.
DR PDB; 4HAX; X-ray; 2.28 A; A=1-216.
DR PDB; 4HAY; X-ray; 2.30 A; A=1-216.
DR PDB; 4HAZ; X-ray; 1.90 A; A=1-216.
DR PDB; 4HB0; X-ray; 2.20 A; A=1-216.
DR PDB; 4HB2; X-ray; 1.80 A; A=1-216.
DR PDB; 4HB3; X-ray; 2.80 A; A=1-216.
DR PDB; 4HB4; X-ray; 2.05 A; A=1-216.
DR PDBsum; 1I2M; -.
DR PDBsum; 1IBR; -.
DR PDBsum; 1K5D; -.
DR PDBsum; 1K5G; -.
DR PDBsum; 1QBK; -.
DR PDBsum; 1RRP; -.
DR PDBsum; 3CH5; -.
DR PDBsum; 3EA5; -.
DR PDBsum; 3GJ0; -.
DR PDBsum; 3GJ3; -.
DR PDBsum; 3GJ4; -.
DR PDBsum; 3GJ5; -.
DR PDBsum; 3GJ6; -.
DR PDBsum; 3GJ7; -.
DR PDBsum; 3GJ8; -.
DR PDBsum; 3GJX; -.
DR PDBsum; 3NBY; -.
DR PDBsum; 3NBZ; -.
DR PDBsum; 3NC0; -.
DR PDBsum; 3NC1; -.
DR PDBsum; 3ZJY; -.
DR PDBsum; 4GMX; -.
DR PDBsum; 4GPT; -.
DR PDBsum; 4HAT; -.
DR PDBsum; 4HAU; -.
DR PDBsum; 4HAV; -.
DR PDBsum; 4HAW; -.
DR PDBsum; 4HAX; -.
DR PDBsum; 4HAY; -.
DR PDBsum; 4HAZ; -.
DR PDBsum; 4HB0; -.
DR PDBsum; 4HB2; -.
DR PDBsum; 4HB3; -.
DR PDBsum; 4HB4; -.
DR ProteinModelPortal; P62826; -.
DR SMR; P62826; 8-216.
DR DIP; DIP-5929N; -.
DR IntAct; P62826; 42.
DR MINT; MINT-94188; -.
DR TCDB; 9.A.60.1.1; the small nuclear rna exporter (snrna-e).
DR PhosphoSite; P62826; -.
DR DMDM; 51338598; -.
DR OGP; P62826; -.
DR REPRODUCTION-2DPAGE; P62826; -.
DR UCD-2DPAGE; P62826; -.
DR PaxDb; P62826; -.
DR PRIDE; P62826; -.
DR DNASU; 5901; -.
DR Ensembl; ENST00000392369; ENSP00000376176; ENSG00000132341.
DR Ensembl; ENST00000543796; ENSP00000446215; ENSG00000132341.
DR GeneID; 5901; -.
DR KEGG; hsa:5901; -.
DR UCSC; uc001uir.3; human.
DR CTD; 5901; -.
DR GeneCards; GC12P131356; -.
DR HGNC; HGNC:9846; RAN.
DR MIM; 601179; gene.
DR neXtProt; NX_P62826; -.
DR PharmGKB; PA34205; -.
DR eggNOG; COG1100; -.
DR HOVERGEN; HBG107376; -.
DR InParanoid; P62826; -.
DR KO; K07936; -.
DR OrthoDB; EOG7C8GJ1; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_71; Gene Expression.
DR SignaLink; P62826; -.
DR ChiTaRS; RAN; human.
DR EvolutionaryTrace; P62826; -.
DR GeneWiki; Ran_(biology); -.
DR GenomeRNAi; 5901; -.
DR NextBio; 22956; -.
DR PRO; PR:P62826; -.
DR ArrayExpress; P62826; -.
DR Bgee; P62826; -.
DR Genevestigator; P62826; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005643; C:nuclear pore; NAS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0050681; F:androgen receptor binding; NAS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; TAS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; TAS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; NAS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0034629; P:cellular protein complex localization; IEA:Ensembl.
DR GO; GO:0006259; P:DNA metabolic process; TAS:UniProtKB.
DR GO; GO:0010467; P:gene expression; TAS:Reactome.
DR GO; GO:0075733; P:intracellular transport of virus; TAS:Reactome.
DR GO; GO:0007067; P:mitosis; TAS:UniProtKB.
DR GO; GO:0007052; P:mitotic spindle organization; TAS:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-dependent; NAS:UniProtKB.
DR GO; GO:0006611; P:protein export from nucleus; NAS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0006405; P:RNA export from nucleus; NAS:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR002041; Ran_GTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00627; GTPRANTC4.
DR SMART; SM00176; RAN; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51418; RAN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell cycle; Cell division;
KW Complete proteome; Cytoplasm; Direct protein sequencing; GTP-binding;
KW Host-virus interaction; Isopeptide bond; Mitosis; Nucleotide-binding;
KW Nucleus; Polymorphism; Protein transport; Reference proteome;
KW Transport; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 216 GTP-binding nuclear protein Ran.
FT /FTId=PRO_0000208696.
FT NP_BIND 17 24 GTP (By similarity).
FT NP_BIND 65 69 GTP (By similarity).
FT NP_BIND 122 125 GTP (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 60 60 N6-acetyllysine.
FT MOD_RES 71 71 N6-acetyllysine; alternate.
FT MOD_RES 99 99 N6-acetyllysine.
FT MOD_RES 159 159 N6-acetyllysine.
FT CROSSLNK 71 71 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate.
FT VARIANT 95 95 R -> I (in dbSNP:rs11546488).
FT /FTId=VAR_051900.
FT MUTAGEN 19 19 G->V: Blocks DNA replication; when
FT associated with L-69.
FT MUTAGEN 24 24 T->L: Has low binding affinity for GTP
FT and GDP. Almost completely abolishes
FT interaction with BIRC5.
FT MUTAGEN 69 69 Q->L: Blocks DNA replication; when
FT associated with V-19.
FT MUTAGEN 69 69 Q->N: Unable to hydrolyze GTP. Increases
FT binding to BIRC5 and promotes exaggerated
FT spindle formation.
FT CONFLICT 2 2 A -> T (in Ref. 11; AAH72000).
FT CONFLICT 181 181 A -> C (in Ref. 5; AAC99400).
FT STRAND 10 17
FT STRAND 18 22
FT HELIX 23 27
FT HELIX 31 35
FT STRAND 38 40
FT TURN 41 44
FT STRAND 45 54
FT STRAND 57 66
FT HELIX 69 71
FT HELIX 74 76
FT HELIX 77 80
FT STRAND 85 91
FT STRAND 92 94
FT HELIX 95 99
FT HELIX 101 111
FT STRAND 112 114
FT STRAND 117 122
FT STRAND 126 128
FT HELIX 133 135
FT HELIX 138 142
FT STRAND 145 148
FT TURN 151 154
FT TURN 156 158
FT HELIX 159 169
FT STRAND 176 178
FT TURN 185 187
FT HELIX 191 205
SQ SEQUENCE 216 AA; 24423 MW; D5C9B7275C34BCE0 CRC64;
MAAQGEPQVQ FKLVLVGDGG TGKTTFVKRH LTGEFEKKYV ATLGVEVHPL VFHTNRGPIK
FNVWDTAGQE KFGGLRDGYY IQAQCAIIMF DVTSRVTYKN VPNWHRDLVR VCENIPIVLC
GNKVDIKDRK VKAKSIVFHR KKNLQYYDIS AKSNYNFEKP FLWLARKLIG DPNLEFVAMP
ALAPPEVVMD PALAAQYEHD LEVAQTTALP DEDDDL
//
MIM
601179
*RECORD*
*FIELD* NO
601179
*FIELD* TI
*601179 RAS-RELATED NUCLEAR PROTEIN; RAN
*FIELD* TX
CLONING
RAN (Ras-related nuclear protein) is a small GTP-binding protein
read morebelonging to the RAS superfamily (see 190020) that is essential for the
translocation of RNA and proteins through the nuclear pore complex (Ren
et al., 1993). The RAN protein is also involved in control of DNA
synthesis and of cell cycle progression. By screening a human
teratocarcinoma cDNA library with a mixed-oligonucleotide probe
corresponding to a domain conserved among RAS-like proteins, Drivas et
al. (1990) identified a cDNA, TC4, identical to RAN. Ren et al. (1993)
showed that nuclear localization of RAN requires the presence of RCC1
(179710) and that mutations in RAN expected to disrupt GTP hydrolysis
led to a disruption of DNA synthesis. Because of its many functions, it
is likely that RAN interacts with several other proteins (see 601180 and
601181).
Coutavas et al. (1994) showed that 2 distinct, but closely related, Ran
transcripts from separate loci are present in the mouse, 1 of which is
specific to the testis.
BIOCHEMICAL FEATURES
- Crystal Structure
Seewald et al. (2002) presented the 3-dimensional structure of a
Ran-RanBP1-RanGAP ternary complex in the ground state and in a
transition-state mimic. The structure and biochemical experiments showed
that RanGAP does not act through an arginine finger, that the basic
machinery for fast GTP hydrolysis is provided exclusively by Ran, and
that correct positioning of the catalytic glutamine is essential for
catalysis.
To provide a basis for understanding the crucial cargo-release step of
nuclear import, Lee et al. (2005) presented the crystal structure of
full-length yeast importin-beta (Kap95; see 602738) complexed with
RanGTP. They identified a key interaction site where the RanGTP switch I
loop binds to the carboxy-terminal arch of Kap95. This interaction
produced a change in helicoidal pitch that locks Kap95 in a conformation
that cannot bind importin-alpha (see 600685) or cargo. Lee et al. (2005)
suggested an allosteric mechanism for nuclear import complex disassembly
by RanGTP.
Monecke et al. (2009) presented the crystal structure of the
snurportin-1 (SPN1; 607902)-CRM1 (602559)-RanGTP export complex at
2.5-angstrom resolution. SPN1 is a nuclear import adapter for
cytoplasmically assembled, m3G (5-prime-2,2,7-terminal
trimethylguanosine)-capped spliceosomal U snRNPs. The structure showed
how CRM1 can specifically return the cargo-free form of SPN1 to the
cytoplasm. The extensive contact area includes 5 hydrophobic residues at
the SPN1 amino terminus that dock into a hydrophobic cleft of CRM1, as
well as numerous hydrophilic contacts of CRM1 to m3G cap-binding domain
and carboxyl-terminal residues of SPN1. Monecke et al. (2009) concluded
that RanGTP promotes cargo binding to CRM1 solely through long-range
conformational changes in the exportin.
GENE FUNCTION
Ohba et al. (1999) demonstrated that the nucleotide exchange activity of
RCC1, the only known nucleotide exchange factor for RAN, was required
for microtubule aster formation with or without demembranated sperm in
Xenopus egg extracts arrested in meiosis II. In the RCC1-depleted egg
extracts, RanGTP (see RANGAP1, 602362), but not RanGDP, induced
self-organization of microtubule asters, and the process required the
activity of dynein (see 603297). Thus, RAN was shown to regulate
formation of the microtubule network. The egg extracts used in the
experiments by Ohba et al. (1999) were prepared from unfertilized eggs
arrested in metaphase, and therefore no nuclear membrane was formed
during the experiments. Thus, RAN affects microtubule organization
independently of its role in the nucleus-cytosol exchange of
macromolecules. RANGAP1 is localized in the mitotic spindles. Wilde and
Zheng (1999) demonstrated that RanGTP, but not RanGDP, stimulated
polymerization of astral microtubules from centrosomes assembled on
Xenopus sperm. Moreover, a RAN allele with a mutation in the effector
domain (RanL43E) induced the formation of microtubule asters and spindle
assembly in the absence of sperm nuclei in a gamma-tubulin ring complex
and Xenopus microtubule-associated protein-dependent manner. The authors
suggested that RAN could be a key signaling molecule regulating
microtubule polymerization during mitosis.
Adding chromatin beads to Xenopus egg extracts causes nucleation of
microtubules, which eventually reorganize into a bipolar spindle. Using
this assay, Carazo-Salas et al. (1999) demonstrated that the activity of
chromosome-associated RCC1 protein is required for spindle formation.
When in the GTP-bound state (RanGTP), Ran itself induces microtubule
nucleation and spindle-like structures in M-phase extract. Carazo-Salas
et al. (1999) proposed that RCC1 generates a high local concentration of
RAN-GTP around chromatin which, in turn, induces the local nucleation of
microtubules.
The guanosine triphosphatase Ran stimulates assembly of microtubule
asters and spindles in mitotic Xenopus egg extracts. A carboxy-terminal
region of the nuclear mitotic apparatus protein (NUMA; 164009), a
nuclear protein required for organizing mitotic spindle poles, mimics
Ran's ability to induce asters. This NUMA fragment also specifically
interacted with the nuclear transport factor, importin-beta. Wiese et
al. (2001) showed that importin-beta is an inhibitor of microtubule
aster assembly in Xenopus egg extracts and that Ran regulates the
interaction between importin-beta and NUMA. Importin-beta therefore
links NUMA to regulation by Ran. Wiese et al. (2001) concluded that this
suggests that similar mechanisms regulate nuclear import during
interphase and spindle assembly during mitosis.
RAN-GTP becomes depleted from the nucleus bound to transport factors and
adaptors during the export of macromolecular cargo. Using an in vitro
model of nuclear import, Ribbeck et al. (1998) found evidence that
restoration of nuclear RAN concentration is not driven by a
concentration gradient across the nuclear pore, but requires interaction
between RAN-GDP with nuclear transport factor-2 (NTF2; 605813). By
mutation analysis and biochemical studies, they determined that nuclear
reaccumulation of RAN is mediated by direct interaction between the 2
proteins, and that RAN-GDP is the species bound and transported by NTF2.
Using combined experimental and computational analysis, Smith et al.
(2002) predicted that RAN transport is regulated primarily by RCC1
rather than the flux capacity of the nuclear pore complex (NPC). The
model estimated that the robust transport system allows a flux of 520
molecules per NPC per second in vivo.
Kalab et al. (2002) used fluorescence resonance energy transfer to
visualize gradients of RAN-GTP and liberated cargoes around chromosomes
in mitotic Xenopus egg extracts. During interphase, RAN-GTP was highly
enriched in the nucleoplasm, and a steep concentration difference
between nuclear and cytoplasmic RAN-GTP was established. The authors
suggested that a RAN-GTP gradient surrounds chromosomes throughout the
cell cycle.
Caudron et al. (2005) reported that the spatial cues necessary for
microtubules to reproducibly self-organize during cell division are
provided by chromosome-mediated interaction gradients between the small
guanosine triphosphatase (GTPase) Ran and importin-beta (602738). This
produces activity gradients that determine the spatial distribution of
microtubule nucleation and stabilization around chromosomes and that are
essential for the self-organization of microtubules into a bipolar
spindle.
Using Xenopus egg extracts, Walther et al. (2003) showed that RanGTP
triggers distinct steps in nuclear pore complex assembly.
Kalab et al. (2006) examined the Ran-importin-beta system in cells by
conventional and fluorescence lifetime microscopy using a biosensor,
termed Rango, that increases its fluorescence resonance energy transfer
signal when released from importin-beta by RanGTP. Rango is
predominantly free in mitotic cells, but is further liberated around
mitotic chromatin. In vitro experiments and modeling showed that this
localized increase of free cargoes corresponds to changes in RanGTP
concentration sufficient to stabilize microtubules in extracts. In
cells, the Ran-importin-beta-cargo gradient kinetically promotes spindle
formation but is largely dispensable once the spindle has been
established. Kalab et al. (2006) observed that the Ran system also
affects spindle pole formation and chromosome congression in vivo. Kalab
et al. (2006) concluded that conserved Ran-regulated pathways are
involved in multiple, parallel processes required for spindle function,
but that their relative contribution differs in chromatin- versus
centrosome/kinetochore-driven spindle assembly systems.
*FIELD* RF
1. Carazo-Salas, R. E.; Guarguaglini, G.; Gruss, O. J.; Segref, A.;
Karsenti, E.; Mattaj, I. W.: Generation of GTP-bound Ran by RCC1
is required for chromatin-induced mitotic spindle formation. Nature 400:
178-181, 1999.
2. Caudron, M.; Bunt, G.; Bastiaens, P.; Karsenti, E.: Spatial coordination
of spindle assembly by chromosome-mediated signaling gradients. Science 309:
1373-1376, 2005.
3. Coutavas, E. E.; Hsieh, C. M.; Ren, M.; Drivas, G. T.; Rush, M.
G.; D'Eustachio, P.: Tissue-specific expression of Ran isoforms in
the mouse. Mammalian Genome 5: 623-628, 1994.
4. Drivas, G. T.; Shih, A.; Coutavas, E.; Rush, M. G.; D'Eustachio,
P.: Characterization of four novel ras-like genes expressed in a
human teratocarcinoma cell line. Molec. Cell. Biol. 10: 1793-1797,
1990.
5. Kalab, P.; Pralle, A.; Isacoff, E. Y.; Heald, R.; Weis, K.: Analysis
of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440:
697-701, 2006.
6. Kalab, P.; Weis, K.; Heald, R.: Visualization of a Ran-GTP gradient
in interphase and mitotic Xenopus egg extracts. Science 295: 2452-2456,
2002.
7. Lee, S. J.; Matsuura, Y.; Liu, S. M.; Stewart, M.: Structural
basis for nuclear import complex dissociation by RanGTP. (Letter) Nature 435:
693-696, 2005.
8. Monecke, T.; Guttler, T.; Neumann, P.; Dickmanns, A.; Gorlich,
D.; Ficner, R.: Crystal structure of the nuclear export receptor
CRM1 in complex with snurportin 1 and RanGTP. Science 324: 1087-1091,
2009.
9. Ohba, T.; Nakamura, M.; Nishitani, H.; Nishimoto, T.: Self-organization
of microtubule asters induced in Xenopus egg extracts by GTP-bound
Ran. Science 284: 1356-1358, 1999.
10. Ren, M.; Drivas, G.; D'Eustachio, P.; Rush, M. G.: Ran/TC4: a
small nuclear GTP-binding protein that regulates DNA synthesis. J.
Cell Biol. 120: 313-323, 1993.
11. Ribbeck, K.; Lipowsky, G.; Kent, H. M.; Stewart, M.; Gorlich,
D.: NTF2 mediates nuclear import of Ran. EMBO J. 17: 6587-6598,
1998.
12. Seewald, M. J.; Korner, C.; Wittinghofer, A.; Vetter, I. R.:
RanGAP mediates GTP hydrolysis without an arginine finger. Nature 415:
662-666, 2002.
13. Smith, A. E.; Slepchenko, B. M.; Schaff, J. C.; Loew, L. M.; Macara,
I. G.: Systems analysis of Ran transport. Science 295: 488-491,
2002.
14. Walther, T. C.; Askjaer, P.; Gentzel, M.; Habermann, A.; Griffiths,
G.; Wilm, M.; Mattaj, I. W.; Hetzer, M.: RanGTP mediates nuclear
pore complex assembly. Nature 424: 689-694, 2003.
15. Wiese, C.; Wilde, A.; Moore, M. S.; Adam, S. A.; Merdes, A.; Zheng,
Y.: Role of importin-beta in coupling Ran to downstream targets in
microtubule assembly. Science 291: 653-656, 2001.
16. Wilde, A.; Zheng, Y.: Stimulation of microtubule aster formation
and spindle assembly by the small GTPase Ran. Science 284: 1359-1362,
1999.
*FIELD* CN
Ada Hamosh - updated: 6/17/2009
Ada Hamosh - updated: 5/26/2006
Patricia A. Hartz - updated: 1/26/2006
Ada Hamosh - updated: 10/10/2005
Ada Hamosh - updated: 6/15/2005
Ada Hamosh - updated: 12/29/2004
Patricia A. Hartz - updated: 4/26/2002
Paul J. Converse - updated: 4/3/2002
Ada Hamosh - updated: 2/4/2002
Paul J. Converse - updated: 1/18/2002
Ada Hamosh - updated: 4/5/2001
Ada Hamosh - updated: 8/25/1999
Ada Hamosh - updated: 5/20/1999
*FIELD* CD
Alan F. Scott: 4/4/1996
*FIELD* ED
alopez: 06/23/2009
alopez: 6/23/2009
terry: 6/17/2009
alopez: 6/6/2006
terry: 5/26/2006
mgross: 2/2/2006
terry: 1/26/2006
alopez: 10/12/2005
terry: 10/10/2005
alopez: 6/16/2005
terry: 6/15/2005
alopez: 12/30/2004
terry: 12/29/2004
carol: 4/29/2002
terry: 4/26/2002
mgross: 4/3/2002
alopez: 2/7/2002
terry: 2/4/2002
mgross: 1/18/2002
alopez: 4/19/2001
alopez: 4/6/2001
terry: 4/5/2001
alopez: 8/25/1999
alopez: 5/20/1999
terry: 5/20/1999
mark: 4/5/1996
terry: 4/4/1996
mark: 4/4/1996
*RECORD*
*FIELD* NO
601179
*FIELD* TI
*601179 RAS-RELATED NUCLEAR PROTEIN; RAN
*FIELD* TX
CLONING
RAN (Ras-related nuclear protein) is a small GTP-binding protein
read morebelonging to the RAS superfamily (see 190020) that is essential for the
translocation of RNA and proteins through the nuclear pore complex (Ren
et al., 1993). The RAN protein is also involved in control of DNA
synthesis and of cell cycle progression. By screening a human
teratocarcinoma cDNA library with a mixed-oligonucleotide probe
corresponding to a domain conserved among RAS-like proteins, Drivas et
al. (1990) identified a cDNA, TC4, identical to RAN. Ren et al. (1993)
showed that nuclear localization of RAN requires the presence of RCC1
(179710) and that mutations in RAN expected to disrupt GTP hydrolysis
led to a disruption of DNA synthesis. Because of its many functions, it
is likely that RAN interacts with several other proteins (see 601180 and
601181).
Coutavas et al. (1994) showed that 2 distinct, but closely related, Ran
transcripts from separate loci are present in the mouse, 1 of which is
specific to the testis.
BIOCHEMICAL FEATURES
- Crystal Structure
Seewald et al. (2002) presented the 3-dimensional structure of a
Ran-RanBP1-RanGAP ternary complex in the ground state and in a
transition-state mimic. The structure and biochemical experiments showed
that RanGAP does not act through an arginine finger, that the basic
machinery for fast GTP hydrolysis is provided exclusively by Ran, and
that correct positioning of the catalytic glutamine is essential for
catalysis.
To provide a basis for understanding the crucial cargo-release step of
nuclear import, Lee et al. (2005) presented the crystal structure of
full-length yeast importin-beta (Kap95; see 602738) complexed with
RanGTP. They identified a key interaction site where the RanGTP switch I
loop binds to the carboxy-terminal arch of Kap95. This interaction
produced a change in helicoidal pitch that locks Kap95 in a conformation
that cannot bind importin-alpha (see 600685) or cargo. Lee et al. (2005)
suggested an allosteric mechanism for nuclear import complex disassembly
by RanGTP.
Monecke et al. (2009) presented the crystal structure of the
snurportin-1 (SPN1; 607902)-CRM1 (602559)-RanGTP export complex at
2.5-angstrom resolution. SPN1 is a nuclear import adapter for
cytoplasmically assembled, m3G (5-prime-2,2,7-terminal
trimethylguanosine)-capped spliceosomal U snRNPs. The structure showed
how CRM1 can specifically return the cargo-free form of SPN1 to the
cytoplasm. The extensive contact area includes 5 hydrophobic residues at
the SPN1 amino terminus that dock into a hydrophobic cleft of CRM1, as
well as numerous hydrophilic contacts of CRM1 to m3G cap-binding domain
and carboxyl-terminal residues of SPN1. Monecke et al. (2009) concluded
that RanGTP promotes cargo binding to CRM1 solely through long-range
conformational changes in the exportin.
GENE FUNCTION
Ohba et al. (1999) demonstrated that the nucleotide exchange activity of
RCC1, the only known nucleotide exchange factor for RAN, was required
for microtubule aster formation with or without demembranated sperm in
Xenopus egg extracts arrested in meiosis II. In the RCC1-depleted egg
extracts, RanGTP (see RANGAP1, 602362), but not RanGDP, induced
self-organization of microtubule asters, and the process required the
activity of dynein (see 603297). Thus, RAN was shown to regulate
formation of the microtubule network. The egg extracts used in the
experiments by Ohba et al. (1999) were prepared from unfertilized eggs
arrested in metaphase, and therefore no nuclear membrane was formed
during the experiments. Thus, RAN affects microtubule organization
independently of its role in the nucleus-cytosol exchange of
macromolecules. RANGAP1 is localized in the mitotic spindles. Wilde and
Zheng (1999) demonstrated that RanGTP, but not RanGDP, stimulated
polymerization of astral microtubules from centrosomes assembled on
Xenopus sperm. Moreover, a RAN allele with a mutation in the effector
domain (RanL43E) induced the formation of microtubule asters and spindle
assembly in the absence of sperm nuclei in a gamma-tubulin ring complex
and Xenopus microtubule-associated protein-dependent manner. The authors
suggested that RAN could be a key signaling molecule regulating
microtubule polymerization during mitosis.
Adding chromatin beads to Xenopus egg extracts causes nucleation of
microtubules, which eventually reorganize into a bipolar spindle. Using
this assay, Carazo-Salas et al. (1999) demonstrated that the activity of
chromosome-associated RCC1 protein is required for spindle formation.
When in the GTP-bound state (RanGTP), Ran itself induces microtubule
nucleation and spindle-like structures in M-phase extract. Carazo-Salas
et al. (1999) proposed that RCC1 generates a high local concentration of
RAN-GTP around chromatin which, in turn, induces the local nucleation of
microtubules.
The guanosine triphosphatase Ran stimulates assembly of microtubule
asters and spindles in mitotic Xenopus egg extracts. A carboxy-terminal
region of the nuclear mitotic apparatus protein (NUMA; 164009), a
nuclear protein required for organizing mitotic spindle poles, mimics
Ran's ability to induce asters. This NUMA fragment also specifically
interacted with the nuclear transport factor, importin-beta. Wiese et
al. (2001) showed that importin-beta is an inhibitor of microtubule
aster assembly in Xenopus egg extracts and that Ran regulates the
interaction between importin-beta and NUMA. Importin-beta therefore
links NUMA to regulation by Ran. Wiese et al. (2001) concluded that this
suggests that similar mechanisms regulate nuclear import during
interphase and spindle assembly during mitosis.
RAN-GTP becomes depleted from the nucleus bound to transport factors and
adaptors during the export of macromolecular cargo. Using an in vitro
model of nuclear import, Ribbeck et al. (1998) found evidence that
restoration of nuclear RAN concentration is not driven by a
concentration gradient across the nuclear pore, but requires interaction
between RAN-GDP with nuclear transport factor-2 (NTF2; 605813). By
mutation analysis and biochemical studies, they determined that nuclear
reaccumulation of RAN is mediated by direct interaction between the 2
proteins, and that RAN-GDP is the species bound and transported by NTF2.
Using combined experimental and computational analysis, Smith et al.
(2002) predicted that RAN transport is regulated primarily by RCC1
rather than the flux capacity of the nuclear pore complex (NPC). The
model estimated that the robust transport system allows a flux of 520
molecules per NPC per second in vivo.
Kalab et al. (2002) used fluorescence resonance energy transfer to
visualize gradients of RAN-GTP and liberated cargoes around chromosomes
in mitotic Xenopus egg extracts. During interphase, RAN-GTP was highly
enriched in the nucleoplasm, and a steep concentration difference
between nuclear and cytoplasmic RAN-GTP was established. The authors
suggested that a RAN-GTP gradient surrounds chromosomes throughout the
cell cycle.
Caudron et al. (2005) reported that the spatial cues necessary for
microtubules to reproducibly self-organize during cell division are
provided by chromosome-mediated interaction gradients between the small
guanosine triphosphatase (GTPase) Ran and importin-beta (602738). This
produces activity gradients that determine the spatial distribution of
microtubule nucleation and stabilization around chromosomes and that are
essential for the self-organization of microtubules into a bipolar
spindle.
Using Xenopus egg extracts, Walther et al. (2003) showed that RanGTP
triggers distinct steps in nuclear pore complex assembly.
Kalab et al. (2006) examined the Ran-importin-beta system in cells by
conventional and fluorescence lifetime microscopy using a biosensor,
termed Rango, that increases its fluorescence resonance energy transfer
signal when released from importin-beta by RanGTP. Rango is
predominantly free in mitotic cells, but is further liberated around
mitotic chromatin. In vitro experiments and modeling showed that this
localized increase of free cargoes corresponds to changes in RanGTP
concentration sufficient to stabilize microtubules in extracts. In
cells, the Ran-importin-beta-cargo gradient kinetically promotes spindle
formation but is largely dispensable once the spindle has been
established. Kalab et al. (2006) observed that the Ran system also
affects spindle pole formation and chromosome congression in vivo. Kalab
et al. (2006) concluded that conserved Ran-regulated pathways are
involved in multiple, parallel processes required for spindle function,
but that their relative contribution differs in chromatin- versus
centrosome/kinetochore-driven spindle assembly systems.
*FIELD* RF
1. Carazo-Salas, R. E.; Guarguaglini, G.; Gruss, O. J.; Segref, A.;
Karsenti, E.; Mattaj, I. W.: Generation of GTP-bound Ran by RCC1
is required for chromatin-induced mitotic spindle formation. Nature 400:
178-181, 1999.
2. Caudron, M.; Bunt, G.; Bastiaens, P.; Karsenti, E.: Spatial coordination
of spindle assembly by chromosome-mediated signaling gradients. Science 309:
1373-1376, 2005.
3. Coutavas, E. E.; Hsieh, C. M.; Ren, M.; Drivas, G. T.; Rush, M.
G.; D'Eustachio, P.: Tissue-specific expression of Ran isoforms in
the mouse. Mammalian Genome 5: 623-628, 1994.
4. Drivas, G. T.; Shih, A.; Coutavas, E.; Rush, M. G.; D'Eustachio,
P.: Characterization of four novel ras-like genes expressed in a
human teratocarcinoma cell line. Molec. Cell. Biol. 10: 1793-1797,
1990.
5. Kalab, P.; Pralle, A.; Isacoff, E. Y.; Heald, R.; Weis, K.: Analysis
of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440:
697-701, 2006.
6. Kalab, P.; Weis, K.; Heald, R.: Visualization of a Ran-GTP gradient
in interphase and mitotic Xenopus egg extracts. Science 295: 2452-2456,
2002.
7. Lee, S. J.; Matsuura, Y.; Liu, S. M.; Stewart, M.: Structural
basis for nuclear import complex dissociation by RanGTP. (Letter) Nature 435:
693-696, 2005.
8. Monecke, T.; Guttler, T.; Neumann, P.; Dickmanns, A.; Gorlich,
D.; Ficner, R.: Crystal structure of the nuclear export receptor
CRM1 in complex with snurportin 1 and RanGTP. Science 324: 1087-1091,
2009.
9. Ohba, T.; Nakamura, M.; Nishitani, H.; Nishimoto, T.: Self-organization
of microtubule asters induced in Xenopus egg extracts by GTP-bound
Ran. Science 284: 1356-1358, 1999.
10. Ren, M.; Drivas, G.; D'Eustachio, P.; Rush, M. G.: Ran/TC4: a
small nuclear GTP-binding protein that regulates DNA synthesis. J.
Cell Biol. 120: 313-323, 1993.
11. Ribbeck, K.; Lipowsky, G.; Kent, H. M.; Stewart, M.; Gorlich,
D.: NTF2 mediates nuclear import of Ran. EMBO J. 17: 6587-6598,
1998.
12. Seewald, M. J.; Korner, C.; Wittinghofer, A.; Vetter, I. R.:
RanGAP mediates GTP hydrolysis without an arginine finger. Nature 415:
662-666, 2002.
13. Smith, A. E.; Slepchenko, B. M.; Schaff, J. C.; Loew, L. M.; Macara,
I. G.: Systems analysis of Ran transport. Science 295: 488-491,
2002.
14. Walther, T. C.; Askjaer, P.; Gentzel, M.; Habermann, A.; Griffiths,
G.; Wilm, M.; Mattaj, I. W.; Hetzer, M.: RanGTP mediates nuclear
pore complex assembly. Nature 424: 689-694, 2003.
15. Wiese, C.; Wilde, A.; Moore, M. S.; Adam, S. A.; Merdes, A.; Zheng,
Y.: Role of importin-beta in coupling Ran to downstream targets in
microtubule assembly. Science 291: 653-656, 2001.
16. Wilde, A.; Zheng, Y.: Stimulation of microtubule aster formation
and spindle assembly by the small GTPase Ran. Science 284: 1359-1362,
1999.
*FIELD* CN
Ada Hamosh - updated: 6/17/2009
Ada Hamosh - updated: 5/26/2006
Patricia A. Hartz - updated: 1/26/2006
Ada Hamosh - updated: 10/10/2005
Ada Hamosh - updated: 6/15/2005
Ada Hamosh - updated: 12/29/2004
Patricia A. Hartz - updated: 4/26/2002
Paul J. Converse - updated: 4/3/2002
Ada Hamosh - updated: 2/4/2002
Paul J. Converse - updated: 1/18/2002
Ada Hamosh - updated: 4/5/2001
Ada Hamosh - updated: 8/25/1999
Ada Hamosh - updated: 5/20/1999
*FIELD* CD
Alan F. Scott: 4/4/1996
*FIELD* ED
alopez: 06/23/2009
alopez: 6/23/2009
terry: 6/17/2009
alopez: 6/6/2006
terry: 5/26/2006
mgross: 2/2/2006
terry: 1/26/2006
alopez: 10/12/2005
terry: 10/10/2005
alopez: 6/16/2005
terry: 6/15/2005
alopez: 12/30/2004
terry: 12/29/2004
carol: 4/29/2002
terry: 4/26/2002
mgross: 4/3/2002
alopez: 2/7/2002
terry: 2/4/2002
mgross: 1/18/2002
alopez: 4/19/2001
alopez: 4/6/2001
terry: 4/5/2001
alopez: 8/25/1999
alopez: 5/20/1999
terry: 5/20/1999
mark: 4/5/1996
terry: 4/4/1996
mark: 4/4/1996