RBCC

Full text data of RANGAP1

RANGAP1 (KIAA1835, SD) [Confidence: low (only semi-automatic identification from reviews)]
Ran GTPase-activating protein 1; RanGAP1

UniProt P46060
ID RAGP1_HUMAN Reviewed; 587 AA.
AC P46060; Q96JJ2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1995, sequence version 1.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Ran GTPase-activating protein 1;
DE Short=RanGAP1;
GN Name=RANGAP1; Synonyms=KIAA1835, SD;
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 PARTIAL PROTEIN SEQUENCE.
RX PubMed=7878053; DOI=10.1073/pnas.92.5.1749;
RA Bischoff F.R., Krebber H., Kempf T., Hermes I., Ponstingl H.;
RT "Human RanGTPase-activating protein RanGAP1 is a homologue of yeast
RT Rna1p involved in mRNA processing and transport.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:1749-1753(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11347906; DOI=10.1093/dnares/8.2.85;
RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XX.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large proteins in vitro.";
RL DNA Res. 8:85-95(2001).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=8973340; DOI=10.1016/S0378-1119(96)00389-7;
RA Krebber H., Ponstingl H.;
RT "Ubiquitous expression and testis-specific alternative polyadenylation
RT of mRNA for the human Ran GTPase activator RanGAP1.";
RL Gene 180:7-11(1996).
RN [8]
RP SUMOYLATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-524.
RX PubMed=11854305; DOI=10.1083/jcb.200110109;
RA Joseph J., Tan S.-H., Karpova T.S., McNally J.G., Dasso M.;
RT "SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles.";
RL J. Cell Biol. 156:595-602(2002).
RN [9]
RP PHOSPHORYLATION AT THR-409; SER-428 AND SER-442, MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SUMO1; RANBP2 AND UBE2I.
RX PubMed=15037602; DOI=10.1083/jcb.200309126;
RA Swaminathan S., Kiendl F., Koerner R., Lupetti R., Hengst L.,
RA Melchior F.;
RT "RanGAP1*SUMO1 is phosphorylated at the onset of mitosis and remains
RT associated with RanBP2 upon NPC disassembly.";
RL J. Cell Biol. 164:965-971(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-442, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
RP INTERACTION WITH TRAF6.
RX PubMed=18093978; DOI=10.1074/jbc.M706307200;
RA Pham L.V., Zhou H.J., Lin-Lee Y.C., Tamayo A.T., Yoshimura L.C.,
RA Fu L., Darnay B.G., Ford R.J.;
RT "Nuclear tumor necrosis factor receptor-associated factor 6 in
RT lymphoid cells negatively regulates c-Myb-mediated transactivation
RT through small ubiquitin-related modifier-1 modification.";
RL J. Biol. Chem. 283:5081-5089(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358; SER-428 AND
RP SER-442, AND MASS SPECTROMETRY.
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428; SER-435; THR-436
RP AND SER-442, AND MASS 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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-524, 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 [16]
RP SUMOYLATION AT LYS-8 AND LYS-524, AND ACETYLATION AT ALA-2.
RC TISSUE=Cervix carcinoma;
RX PubMed=20388717; DOI=10.1074/jbc.M110.106955;
RA Blomster H.A., Imanishi S.Y., Siimes J., Kastu J., Morrice N.A.,
RA Eriksson J.E., Sistonen L.;
RT "In vivo identification of sumoylation sites by a signature tag and
RT cysteine-targeted affinity purification.";
RL J. Biol. Chem. 285:19324-19329(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428 AND SER-442, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-442, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 418-587 IN COMPLEX WITH
RP SUMO1; RANBP2 AND UBE2I.
RX PubMed=15931224; DOI=10.1038/nature03588;
RA Reverter D., Lima C.D.;
RT "Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-
RT Nup358 complex.";
RL Nature 435:687-692(2005).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.77 ANGSTROMS) OF 432-587 IN COMPLEX WITH
RP SUMO1 AND SENP1.
RX PubMed=17099698; DOI=10.1038/nsmb1172;
RA Shen L., Tatham M.H., Dong C., Zagorska A., Naismith J.H., Hay R.T.;
RT "SUMO protease SENP1 induces isomerization of the scissile peptide
RT bond.";
RL Nat. Struct. Mol. Biol. 13:1069-1077(2006).
CC -!- FUNCTION: GTPase activator for the nuclear Ras-related regulatory
CC protein Ran, converting it to the putatively inactive GDP-bound
CC state.
CC -!- SUBUNIT: Homodimer. Forms a tight complex in association with
CC RANBP2/NUP358 and UBE2I/UBC9, the ubiquitin-conjugating enzyme E2.
CC Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1,
CC and subsequently stabilizes interactions of sumoylated RANGAP1
CC with RANBP2/NUP358. The SUMO1/RANGAP1/UBC9/NUP358 complex
CC associates with nuclear pore complexes. Interacts with TRAF6.
CC -!- INTERACTION:
CC P63165:SUMO1; NbExp=4; IntAct=EBI-396091, EBI-80140;
CC P63279:UBE2I; NbExp=4; IntAct=EBI-396091, EBI-80168;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus membrane; Peripheral
CC membrane protein; Cytoplasmic side. Chromosome, centromere,
CC kinetochore (By similarity). Cytoplasm, cytoskeleton, spindle pole
CC (By similarity). Note=Cytoplasmic during interphase. Targeted to
CC the nuclear rim after sumoylation. During mitosis, associates with
CC mitotic spindles. Association with kinetochores appears soon after
CC nuclear envelope breakdown and persists until late anaphase.
CC Mitotic location also requires sumoylation.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, thymus and testis.
CC -!- PTM: Phosphorylated occurs before nuclear envelope breakdown and
CC continues throughout mitosis. Phosphorylated by the M-phase kinase
CC cyclin B/Cdk1, in vitro. Differential timimg of dephosphorylation
CC occurs during phases of mitosis. The phosphorylated form remains
CC associated with RANBP2/NUP358 and the SUMO E2-conjugating enzyme,
CC UBC9, on nuclear pore complex (NPC) diassembly and during mitosis.
CC -!- PTM: Sumoylated with SUMO1. Sumoylation is necessary for targeting
CC to the nuclear envelope (NE), and for association with mitotic
CC spindles and kinetochores during mitosis. Also required for
CC interaction with RANBP2 and is mediated by UBC9.
CC -!- SIMILARITY: Belongs to the RNA1 family.
CC -!- SIMILARITY: Contains 6 LRR (leucine-rich) repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47464.1; Type=Erroneous initiation;
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DR EMBL; X82260; CAA57714.1; -; mRNA.
DR EMBL; AB058738; BAB47464.1; ALT_INIT; mRNA.
DR EMBL; CR456557; CAG30443.1; -; mRNA.
DR EMBL; AL035681; CAB63073.1; -; Genomic_DNA.
DR EMBL; BC014044; AAH14044.1; -; mRNA.
DR EMBL; BC041396; AAH41396.1; -; mRNA.
DR PIR; JC5300; JC5300.
DR RefSeq; NP_001265580.1; NM_001278651.1.
DR RefSeq; NP_002874.1; NM_002883.3.
DR UniGene; Hs.183800; -.
DR PDB; 1Z5S; X-ray; 3.01 A; C=418-587.
DR PDB; 2GRN; X-ray; 1.80 A; B=419-587.
DR PDB; 2GRO; X-ray; 1.70 A; B=419-587.
DR PDB; 2GRP; X-ray; 2.05 A; B=419-587.
DR PDB; 2GRQ; X-ray; 1.70 A; B=419-587.
DR PDB; 2GRR; X-ray; 1.30 A; B=419-587.
DR PDB; 2IO2; X-ray; 2.90 A; C=418-587.
DR PDB; 2IO3; X-ray; 3.20 A; C=418-587.
DR PDB; 2IY0; X-ray; 2.77 A; C=432-587.
DR PDB; 3UIN; X-ray; 2.60 A; C=419-587.
DR PDB; 3UIO; X-ray; 2.60 A; C=419-587.
DR PDB; 3UIP; X-ray; 2.29 A; C=419-587.
DR PDBsum; 1Z5S; -.
DR PDBsum; 2GRN; -.
DR PDBsum; 2GRO; -.
DR PDBsum; 2GRP; -.
DR PDBsum; 2GRQ; -.
DR PDBsum; 2GRR; -.
DR PDBsum; 2IO2; -.
DR PDBsum; 2IO3; -.
DR PDBsum; 2IY0; -.
DR PDBsum; 3UIN; -.
DR PDBsum; 3UIO; -.
DR PDBsum; 3UIP; -.
DR ProteinModelPortal; P46060; -.
DR SMR; P46060; 21-349, 431-587.
DR DIP; DIP-29079N; -.
DR IntAct; P46060; 17.
DR MINT; MINT-3016328; -.
DR STRING; 9606.ENSP00000348577; -.
DR PhosphoSite; P46060; -.
DR DMDM; 1172922; -.
DR PaxDb; P46060; -.
DR PRIDE; P46060; -.
DR DNASU; 5905; -.
DR Ensembl; ENST00000356244; ENSP00000348577; ENSG00000100401.
DR Ensembl; ENST00000405486; ENSP00000385866; ENSG00000100401.
DR Ensembl; ENST00000455915; ENSP00000401470; ENSG00000100401.
DR GeneID; 5905; -.
DR KEGG; hsa:5905; -.
DR UCSC; uc003azs.3; human.
DR CTD; 5905; -.
DR GeneCards; GC22M041641; -.
DR HGNC; HGNC:9854; RANGAP1.
DR HPA; CAB004293; -.
DR MIM; 602362; gene.
DR neXtProt; NX_P46060; -.
DR PharmGKB; PA34216; -.
DR eggNOG; COG5238; -.
DR HOGENOM; HOG000195026; -.
DR HOVERGEN; HBG017720; -.
DR InParanoid; P46060; -.
DR KO; K14319; -.
DR OMA; AEAFGII; -.
DR OrthoDB; EOG70W3DV; -.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_21300; Mitotic M-M/G1 phases.
DR ChiTaRS; RANGAP1; human.
DR EvolutionaryTrace; P46060; -.
DR GeneWiki; RANGAP1; -.
DR GenomeRNAi; 5905; -.
DR NextBio; 22968; -.
DR PRO; PR:P46060; -.
DR ArrayExpress; P46060; -.
DR Bgee; P46060; -.
DR CleanEx; HS_RANGAP1; -.
DR Genevestigator; P46060; -.
DR GO; GO:0000777; C:condensed chromosome kinetochore; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005643; C:nuclear pore; TAS:ProtInc.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0005098; F:Ran GTPase activator activity; TAS:ProtInc.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome.
DR GO; GO:0046826; P:negative regulation of protein export from nucleus; IDA:BHF-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 1.25.40.200; -; 1.
DR InterPro; IPR009109; Ran_GTPase_activating_1_C.
DR InterPro; IPR027038; RanGap.
DR PANTHER; PTHR24113; PTHR24113; 1.
DR Pfam; PF07834; RanGAP1_C; 1.
DR SUPFAM; SSF69099; SSF69099; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Centromere; Chromosome; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; GTPase activation;
KW Isopeptide bond; Kinetochore; Leucine-rich repeat; Membrane; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 587 Ran GTPase-activating protein 1.
FT /FTId=PRO_0000056737.
FT REPEAT 48 71 LRR 1.
FT REPEAT 111 134 LRR 2.
FT REPEAT 207 230 LRR 3.
FT REPEAT 235 258 LRR 4.
FT REPEAT 292 319 LRR 5.
FT REPEAT 320 343 LRR 6.
FT MOTIF 523 526 SUMO conjugation.
FT COMPBIAS 359 399 Asp/Glu-rich (highly acidic).
FT COMPBIAS 359 397 Asp/Glu-rich (highly acidic).
FT SITE 562 562 Hydrophobic interaction with UBC9 (By
FT similarity).
FT SITE 565 565 Hydrophobic interaction with UBC9 (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 358 358 Phosphoserine.
FT MOD_RES 409 409 Phosphothreonine; by CDK2.
FT MOD_RES 428 428 Phosphoserine.
FT MOD_RES 435 435 Phosphoserine.
FT MOD_RES 436 436 Phosphothreonine.
FT MOD_RES 442 442 Phosphoserine.
FT MOD_RES 524 524 N6-acetyllysine; alternate.
FT CROSSLNK 8 8 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO-1).
FT CROSSLNK 524 524 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO-1);
FT alternate.
FT VARIANT 133 133 E -> Q (in dbSNP:rs2229752).
FT /FTId=VAR_029240.
FT MUTAGEN 524 524 K->R: No association with mitotic
FT spindles during mitosis.
FT HELIX 434 439
FT HELIX 443 448
FT HELIX 453 459
FT HELIX 466 477
FT HELIX 484 502
FT STRAND 503 507
FT HELIX 509 519
FT HELIX 536 545
FT STRAND 548 551
FT HELIX 553 555
FT HELIX 556 564
FT HELIX 568 571
FT HELIX 574 586
SQ SEQUENCE 587 AA; 63542 MW; 3C18068AAC06B98F CRC64;
MASEDIAKLA ETLAKTQVAG GQLSFKGKSL KLNTAEDAKD VIKEIEDFDS LEALRLEGNT
VGVEAARVIA KALEKKSELK RCHWSDMFTG RLRTEIPPAL ISLGEGLITA GAQLVELDLS
DNAFGPDGVQ GFEALLKSSA CFTLQELKLN NCGMGIGGGK ILAAALTECH RKSSAQGKPL
ALKVFVAGRN RLENDGATAL AEAFRVIGTL EEVHMPQNGI NHPGITALAQ AFAVNPLLRV
INLNDNTFTE KGAVAMAETL KTLRQVEVIN FGDCLVRSKG AVAIADAIRG GLPKLKELNL
SFCEIKRDAA LAVAEAMADK AELEKLDLNG NTLGEEGCEQ LQEVLEGFNM AKVLASLSDD
EDEEEEEEGE EEEEEAEEEE EEDEEEEEEE EEEEEEEPQQ RGQGEKSATP SRKILDPNTG
EPAPVLSSPP PADVSTFLAF PSPEKLLRLG PKSSVLIAQQ TDTSDPEKVV SAFLKVSSVF
KDEATVRMAV QDAVDALMQK AFNSSSFNSN TFLTRLLVHM GLLKSEDKVK AIANLYGPLM
ALNHMVQQDY FPKALAPLLL AFVTKPNSAL ESCSFARHSL LQTLYKV
//

MIM 602362
*RECORD*
*FIELD* NO
602362
*FIELD* TI
*602362 GTPase-ACTIVATING PROTEIN, RAN, 1; RANGAP1
;;RAN GTPase-ACTIVATING PROTEIN 1
read more*FIELD* TX

CLONING

RAS-related small GTP-binding proteins (GTPBPs), such as RAN (601179),
participate in various intracellular signal transduction pathways. The
GTP-bound form usually represents the active signaling form of the
protein. Hydrolysis of GTP to GDP and phosphate occurs upon activation
of a latent GTPase activity in the GTPBP and returns it to its inactive,
GDP-bound state. This latent GTPase activity is induced upon interaction
of GTP-bound GTPBPs with GTPase-activating proteins (GAPs). Bischoff et
al. (1994) purified a GAP from a HeLa cell extract. The protein,
designated RanGAP1, is a homodimeric 65-kD polypeptide. RanGAP1
specifically induced the GTPase activity of RAN, but not of RAS
(190020), by over 1,000-fold. Bischoff et al. (1994) believed RanGAP1 to
be the immediate antagonist of RCC1 (179710), a regulator molecule that
keeps RAN in the active, GTP-bound state.

Bischoff et al. (1995) purified the 65-kD RanGAP1 protein from human
HeLa cells. Using PCR with degenerate primers based on RanGAP1 peptide
sequences, they cloned the corresponding cDNA from a HeLa cell library.
The RANGAP1 gene encodes a 587-amino acid polypeptide. The sequence is
unrelated to that of GTPase activators for other RAS-related proteins,
but is 88% identical to Fug1, the murine homolog of yeast Rna1p.
Bischoff et al. (1995) proposed that RanGAP1 and RCC1 control
RAN-dependent transport between the nucleus and cytoplasm.

GENE FUNCTION

RAN is a nuclear RAS-like GTPase that is required for the bidirectional
transport of proteins and ribonucleoproteins across the nuclear pore
complex (NPC). RanGAP1 is a key regulator of the RAN GTP/GDP cycle.
Matunis et al. (1996) reported the identification and localization of a
novel form of RanGAP1. They showed that the 70-kD unmodified form of
RanGAP1 is exclusively cytoplasmic, whereas the 90-kD modified form is
associated with the cytoplasmic fibers of the NPC. The modified form
also appeared to associate with the mitotic spindle apparatus during
mitosis. These findings had specific implications for RAN function and
broad implications for protein regulation by ubiquitin-like
modifications.

RANGAP1 is modified by the conjugation of SUMO1 (601912), and this
modification is required for association of RANGAP1 with the nuclear
pore complex. Okuma et al. (1999) showed that human SUA1 (SAE1; 613294),
UBA2 (613295), and UBC9 (UBE2I; 601661) catalyzed in vitro sumoylation
of RANGAP1 in a 2-step reaction.

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.

Bernier-Villamor et al. (2002) performed crystallographic analysis of a
complex between mammalian UBC9 and a C-terminal domain of RANGAP1 at 2.5
angstroms. These experiments revealed structural determinants for
recognition of consensus SUMO modification sequences found within
SUMO-conjugated proteins. Structure-based mutagenesis and biochemical
analysis of UBC9 and RANGAP1 revealed distinct motifs required for
substrate binding and SUMO modification of p53 (191170), NFKBIA
(164008), and RANGAP1.

Reverter and Lima (2005) described the 3.0-angstrom crystal structure of
a 4-protein complex of UBC9, a NUP358/RANBP2 (601181) E3 ligase domain
(IR1-M), and SUMO1 conjugated to the carboxy-terminal domain of RANGAP1.
Structural insights, combined with biochemical and kinetic data obtained
with additional substrates, supported a model in which NUP358/RANBP2
acts as an E3 by binding both SUMO and UBC9 to position the
SUMO-E2-thioester in an optimal orientation to enhance conjugation.

*FIELD* RF
1. Bernier-Villamor, V.; Sampson, D. A.; Matunis, M. J.; Lima, C.
D.: Structural basis for E2-mediated SUMO conjugation revealed by
a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell 108:
345-356, 2002.

2. Bischoff, F. R.; Klebe, C.; Kretschmer, J.; Wittinghofer, A.; Ponstingl,
H.: RanGAP1 induces GTPase activity of nuclear Ras-related Ran. Proc.
Nat. Acad. Sci. 91: 2587-2591, 1994.

3. Bischoff, F. R.; Krebber, H.; Kempf, T.; Hermes, I.; Ponstingl,
H.: Human RanGTPase-activating protein RanGAP1 is a homologue of
yeast Rna1p involved in mRNA processing and transport. Proc. Nat.
Acad. Sci. 92: 1749-1753, 1995.

4. Matunis, M. J.; Coutavas, E.; Blobel, G.: A novel ubiquitin-like
modification modulates the partitioning of the Ran-GTPase-activating
protein RanGAP1 between the cytosol and the nuclear pore complex. J.
Cell Biol. 135: 1457-1470, 1996.

5. Okuma, T.; Honda, R.; Ichikawa, G.; Tsumagari, N.; Yasuda, H.:
In vitro SUMO-1 modification requires two enzymatic steps, E1 and
E2. Biochem. Biophys. Res. Commun. 254: 693-698, 1999.

6. Reverter, D.; Lima, C. D.: Insights into E3 ligase activity revealed
by a SUMO-RanGAP1-Ubc9-Nup358 complex. (Letter) Nature 435: 687-692,
2005.

7. Seewald, M. J.; Korner, C.; Wittinghofer, A.; Vetter, I. R.: RanGAP
mediates GTP hydrolysis without an arginine finger. Nature 415:
662-666, 2002.

*FIELD* CN
Patricia A. Hartz - updated: 3/4/2010
Ada Hamosh - updated: 6/15/2005
Stylianos E. Antonarakis - updated: 3/22/2002
Ada Hamosh - updated: 2/4/2002
Jennifer P. Macke - updated: 7/12/1999
Victor A. McKusick - updated: 2/16/1999

*FIELD* CD
Mark H. Paalman: 2/17/1998

*FIELD* ED
mgross: 03/04/2010
terry: 3/4/2010
alopez: 6/16/2005
terry: 6/15/2005
mgross: 3/22/2002
alopez: 2/7/2002
terry: 2/4/2002
alopez: 7/12/1999
mgross: 2/22/1999
mgross: 2/18/1999
terry: 2/16/1999
psherman: 6/3/1998
alopez: 2/17/1998

RBCC Red Blood Cell Collection

Full text data of RANGAP1