RAGP1_HUMAN
ID RAGP1_HUMAN Reviewed; 587 AA.
AC P46060; Q96JJ2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 228.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 Rna1p
RT 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. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT 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., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., 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., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., 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., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=8146159; DOI=10.1073/pnas.91.7.2587;
RA Bischoff F.R., Klebe C., Kretschmer J., Wittinghofer A., Ponstingl H.;
RT "RanGAP1 induces GTPase activity of nuclear Ras-related Ran.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:2587-2591(1994).
RN [8]
RP INTERACTION WITH RAN.
RX PubMed=7891706; DOI=10.1128/mcb.15.4.2117;
RA Ren M., Villamarin A., Shih A., Coutavas E., Moore M.S., Locurcio M.,
RA Clarke V., Oppenheim J.D., D'Eustachio P., Rush M.G.;
RT "Separate domains of the Ran GTPase interact with different factors to
RT regulate nuclear protein import and RNA processing.";
RL Mol. Cell. Biol. 15:2117-2124(1995).
RN [9]
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 of
RT mRNA for the human Ran GTPase activator RanGAP1.";
RL Gene 180:7-11(1996).
RN [10]
RP INTERACTION WITH RAN, AND FUNCTION.
RX PubMed=8896452; DOI=10.1002/j.1460-2075.1996.tb00943.x;
RA Goerlich D., Pante N., Kutay U., Aebi U., Bischoff F.R.;
RT "Identification of different roles for RanGDP and RanGTP in nuclear protein
RT import.";
RL EMBO J. 15:5584-5594(1996).
RN [11]
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 [12]
RP PHOSPHORYLATION AT THR-409; SER-428 AND SER-442, IDENTIFICATION BY MASS
RP SPECTROMETRY, SUMOYLATION, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP SUMO1; RANBP2 AND UBE2I.
RX PubMed=15037602; DOI=10.1083/jcb.200309126;
RA Swaminathan S., Kiendl F., Koerner R., Lupetti R., Hengst L., 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 [13]
RP IDENTIFICATION IN A COMPLEX WITH RANBP2; NXF1 AND NXT1.
RX PubMed=14729961; DOI=10.1128/mcb.24.3.1155-1167.2004;
RA Forler D., Rabut G., Ciccarelli F.D., Herold A., Koecher T., Niggeweg R.,
RA Bork P., Ellenberg J., Izaurralde E.;
RT "RanBP2/Nup358 provides a major binding site for NXF1-p15 dimers at the
RT nuclear pore complex and functions in nuclear mRNA export.";
RL Mol. Cell. Biol. 24:1155-1167(2004).
RN [14]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH RAN AND RANBP1, PHOSPHORYLATION
RP AT SER-358, IDENTIFICATION BY MASS SPECTROMETRY, SUMOYLATION, AND
RP MUTAGENESIS OF ARG-91; SER-356 AND SER-358.
RX PubMed=16428860; DOI=10.1247/csf.30.69;
RA Takeda E., Hieda M., Katahira J., Yoneda Y.;
RT "Phosphorylation of RanGAP1 stabilizes its interaction with Ran and
RT RanBP1.";
RL Cell Struct. Funct. 30:69-80(2005).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-442, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [16]
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., Fu L.,
RA Darnay B.G., Ford R.J.;
RT "Nuclear tumor necrosis factor receptor-associated factor 6 in lymphoid
RT cells negatively regulates c-Myb-mediated transactivation through small
RT ubiquitin-related modifier-1 modification.";
RL J. Biol. Chem. 283:5081-5089(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358; SER-428 AND SER-442, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428; SER-435; THR-436 AND
RP SER-442, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-524, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428 AND SER-442, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-442, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24; SER-301 AND SER-442, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-524, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-524, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [28]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-524, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [29]
RP INTERACTION WITH MYCBP2, AND SUMOYLATION.
RX PubMed=26304119; DOI=10.1074/jbc.m115.646901;
RA Doerr A., Pierre S., Zhang D.D., Henke M., Holland S., Scholich K.;
RT "MYCBP2 is a guanosine exchange factor for Ran protein and determines its
RT localization in neurons of dorsal root ganglia.";
RL J. Biol. Chem. 290:25620-25635(2015).
RN [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-524, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [31]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH XPO1; RAN; RANBP2; SUMO1 AND
RP UBE2I, AND SUMOYLATION.
RX PubMed=27160050; DOI=10.1038/ncomms11482;
RA Ritterhoff T., Das H., Hofhaus G., Schroeder R.R., Flotho A., Melchior F.;
RT "The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for
RT Crm1-dependent nuclear export complexes.";
RL Nat. Commun. 7:11482-11482(2016).
RN [32]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-8; LYS-15; LYS-279; LYS-452;
RP LYS-524 AND LYS-586, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [33] {ECO:0007744|PDB:1Z5S}
RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 418-587 IN COMPLEX WITH SUMO1;
RP 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-Nup358
RT complex.";
RL Nature 435:687-692(2005).
RN [34] {ECO:0007744|PDB:2IY0}
RP X-RAY CRYSTALLOGRAPHY (2.77 ANGSTROMS) OF 432-587 IN COMPLEX WITH SUMO1 AND
RP 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 bond.";
RL Nat. Struct. Mol. Biol. 13:1069-1077(2006).
RN [35] {ECO:0007744|PDB:3UIN, ECO:0007744|PDB:3UIO, ECO:0007744|PDB:3UIP}
RP X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF 419-587 IN COMPLEXES WITH RANBP2;
RP SUMO1; SUMO2 AND UBE2I.
RX PubMed=22194619; DOI=10.1074/jbc.m111.321141;
RA Gareau J.R., Reverter D., Lima C.D.;
RT "Determinants of small ubiquitin-like modifier 1 (SUMO1) protein
RT specificity, E3 ligase, and SUMO-RanGAP1 binding activities of nucleoporin
RT RanBP2.";
RL J. Biol. Chem. 287:4740-4751(2012).
CC -!- FUNCTION: GTPase activator for RAN (PubMed:8146159, PubMed:8896452,
CC PubMed:16428860). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN,
CC which is essential for RAN-mediated nuclear import and export
CC (PubMed:8896452, PubMed:27160050). Mediates dissociation of cargo from
CC nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear
CC export (PubMed:27160050). {ECO:0000269|PubMed:16428860,
CC ECO:0000269|PubMed:27160050, ECO:0000269|PubMed:8146159,
CC ECO:0000269|PubMed:8896452}.
CC -!- SUBUNIT: Homodimer (PubMed:8146159). Interacts with RAN
CC (PubMed:7891706, PubMed:8896452, PubMed:16428860). Forms a complex with
CC RANBP2/NUP358, NXF1 and NXT1 (PubMed:14729961). Forms a tight complex
CC in association with RANBP2/NUP358 and UBE2I/UBC9, the ubiquitin-
CC conjugating enzyme E2 (PubMed:15037602, PubMed:27160050,
CC PubMed:15931224, PubMed:22194619). Interacts with UBE2I; the
CC interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes
CC interactions of sumoylated RANGAP1 with RANBP2/NUP358 (PubMed:15037602,
CC PubMed:27160050, PubMed:15931224). The complex composed of RANBP2,
CC SUMO1, RANGAP1 and UBE2I associates with nuclear pore complexes
CC (PubMed:15037602, PubMed:15931224). Identified in a complex composed of
CC RAN, RANBP2, sumoylated RANGAP1, UBE2I and XPO1 (PubMed:27160050).
CC Identified in a complex composed of RAN, RANGAP1 and RANBP1
CC (PubMed:16428860). Interacts with TRAF6 (PubMed:18093978). Interacts
CC with SUMO1 and SENP1 (PubMed:17099698). Interacts (when sumoylated)
CC with MYCBP2; interaction inhibits MYCBP2 E3 ubiquitin-protein ligase
CC activity and promotes MYCBP2 translocation to the nucleus
CC (PubMed:26304119). {ECO:0000269|PubMed:14729961,
CC ECO:0000269|PubMed:15037602, ECO:0000269|PubMed:15931224,
CC ECO:0000269|PubMed:16428860, ECO:0000269|PubMed:17099698,
CC ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:26304119,
CC ECO:0000269|PubMed:27160050, ECO:0000269|PubMed:7891706,
CC ECO:0000269|PubMed:8146159, ECO:0000269|PubMed:8896452}.
CC -!- INTERACTION:
CC P46060; P42858: HTT; NbExp=10; IntAct=EBI-396091, EBI-466029;
CC P46060; P49792: RANBP2; NbExp=4; IntAct=EBI-396091, EBI-973138;
CC P46060; P63165: SUMO1; NbExp=14; IntAct=EBI-396091, EBI-80140;
CC P46060; P63279: UBE2I; NbExp=12; IntAct=EBI-396091, EBI-80168;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15037602,
CC ECO:0000305|PubMed:8146159}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:8146159}. Nucleus envelope
CC {ECO:0000269|PubMed:11854305, ECO:0000269|PubMed:15037602}. Chromosome,
CC centromere, kinetochore {ECO:0000269|PubMed:11854305}. Cytoplasm,
CC cytoskeleton, spindle {ECO:0000269|PubMed:11854305,
CC ECO:0000269|PubMed:15037602}. Note=Cytoplasmic during interphase.
CC Detected at the nuclear envelope during interphase (PubMed:11854305,
CC PubMed:15037602). Targeted to the nuclear pores after sumoylation
CC (PubMed:11854305). During mitosis, associates with mitotic spindles,
CC but is essentially not detected at the spindle poles (PubMed:11854305,
CC PubMed:15037602). Association with kinetochores appears soon after
CC nuclear envelope breakdown and persists until late anaphase
CC (PubMed:11854305). Mitotic location also requires sumoylation
CC (PubMed:11854305). {ECO:0000269|PubMed:11854305,
CC ECO:0000269|PubMed:15037602}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain, thymus and testis.
CC {ECO:0000269|PubMed:8973340}.
CC -!- PTM: Phosphorylation 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 UBE2I, on nuclear pore complex (NPC) diassembly and during mitosis.
CC {ECO:0000269|PubMed:15037602}.
CC -!- PTM: Sumoylated (PubMed:11854305, PubMed:15037602, PubMed:26304119,
CC PubMed:27160050). Sumoylation is necessary for targeting to the nuclear
CC envelope (NE), and for association with mitotic spindles and
CC kinetochores during mitosis (PubMed:11854305). Also required for
CC interaction with RANBP2 and is mediated by UBE2I (PubMed:27160050).
CC Desumoylated by HINT1 (By similarity). {ECO:0000250|UniProtKB:P46061,
CC ECO:0000269|PubMed:11854305, ECO:0000269|PubMed:15037602,
CC ECO:0000269|PubMed:16428860, ECO:0000269|PubMed:20388717,
CC ECO:0000269|PubMed:26304119, ECO:0000305|PubMed:27160050}.
CC -!- SIMILARITY: Belongs to the RNA1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB47464.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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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; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014044; AAH14044.1; -; mRNA.
DR EMBL; BC041396; AAH41396.1; -; mRNA.
DR CCDS; CCDS14012.1; -.
DR PIR; JC5300; JC5300.
DR RefSeq; NP_001265580.1; NM_001278651.1.
DR RefSeq; NP_001304859.1; NM_001317930.1.
DR RefSeq; NP_002874.1; NM_002883.3.
DR RefSeq; XP_006724352.1; XM_006724289.3.
DR RefSeq; XP_011528596.1; XM_011530294.2.
DR RefSeq; XP_011528597.1; XM_011530295.2.
DR RefSeq; XP_016884382.1; XM_017028893.1.
DR RefSeq; XP_016884383.1; XM_017028894.1.
DR RefSeq; XP_016884384.1; XM_017028895.1.
DR RefSeq; XP_016884385.1; XM_017028896.1.
DR RefSeq; XP_016884386.1; XM_017028897.1.
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 PDB; 5D2M; X-ray; 2.40 A; C/F=418-587.
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 PDBsum; 5D2M; -.
DR AlphaFoldDB; P46060; -.
DR BMRB; P46060; -.
DR SMR; P46060; -.
DR BioGRID; 111840; 218.
DR ComplexPortal; CPX-4747; E3 ligase (RANBP2) complex.
DR DIP; DIP-29079N; -.
DR IntAct; P46060; 88.
DR MINT; P46060; -.
DR STRING; 9606.ENSP00000401470; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR GlyGen; P46060; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P46060; -.
DR MetOSite; P46060; -.
DR PhosphoSitePlus; P46060; -.
DR SwissPalm; P46060; -.
DR BioMuta; RANGAP1; -.
DR DMDM; 1172922; -.
DR EPD; P46060; -.
DR jPOST; P46060; -.
DR MassIVE; P46060; -.
DR MaxQB; P46060; -.
DR PaxDb; P46060; -.
DR PeptideAtlas; P46060; -.
DR PRIDE; P46060; -.
DR ProteomicsDB; 55712; -.
DR Antibodypedia; 3803; 403 antibodies from 41 providers.
DR DNASU; 5905; -.
DR Ensembl; ENST00000356244.8; ENSP00000348577.3; ENSG00000100401.20.
DR Ensembl; ENST00000405486.5; ENSP00000385866.1; ENSG00000100401.20.
DR Ensembl; ENST00000455915.6; ENSP00000401470.2; ENSG00000100401.20.
DR GeneID; 5905; -.
DR KEGG; hsa:5905; -.
DR MANE-Select; ENST00000356244.8; ENSP00000348577.3; NM_002883.4; NP_002874.1.
DR UCSC; uc003azs.5; human.
DR CTD; 5905; -.
DR DisGeNET; 5905; -.
DR GeneCards; RANGAP1; -.
DR HGNC; HGNC:9854; RANGAP1.
DR HPA; ENSG00000100401; Low tissue specificity.
DR MIM; 602362; gene.
DR neXtProt; NX_P46060; -.
DR OpenTargets; ENSG00000100401; -.
DR PharmGKB; PA34216; -.
DR VEuPathDB; HostDB:ENSG00000100401; -.
DR eggNOG; KOG1909; Eukaryota.
DR GeneTree; ENSGT00440000039203; -.
DR HOGENOM; CLU_028747_2_0_1; -.
DR InParanoid; P46060; -.
DR OMA; WGVDELD; -.
DR OrthoDB; 1357476at2759; -.
DR PhylomeDB; P46060; -.
DR TreeFam; TF318283; -.
DR PathwayCommons; P46060; -.
DR Reactome; R-HSA-141444; Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal.
DR Reactome; R-HSA-165054; Rev-mediated nuclear export of HIV RNA.
DR Reactome; R-HSA-2467813; Separation of Sister Chromatids.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-3108232; SUMO E3 ligases SUMOylate target proteins.
DR Reactome; R-HSA-4615885; SUMOylation of DNA replication proteins.
DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR Reactome; R-HSA-68877; Mitotic Prometaphase.
DR Reactome; R-HSA-9615933; Postmitotic nuclear pore complex (NPC) reformation.
DR Reactome; R-HSA-9648025; EML4 and NUDC in mitotic spindle formation.
DR SignaLink; P46060; -.
DR SIGNOR; P46060; -.
DR BioGRID-ORCS; 5905; 798 hits in 1088 CRISPR screens.
DR ChiTaRS; RANGAP1; human.
DR EvolutionaryTrace; P46060; -.
DR GeneWiki; RANGAP1; -.
DR GenomeRNAi; 5905; -.
DR Pharos; P46060; Tbio.
DR PRO; PR:P46060; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P46060; protein.
DR Bgee; ENSG00000100401; Expressed in left testis and 188 other tissues.
DR ExpressionAtlas; P46060; baseline and differential.
DR Genevisible; P46060; HS.
DR GO; GO:0016235; C:aggresome; IDA:HPA.
DR GO; GO:1904115; C:axon cytoplasm; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:1990723; C:cytoplasmic periphery of the nuclear pore complex; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0000776; C:kinetochore; IEA:UniProtKB-KW.
DR GO; GO:0072686; C:mitotic spindle; IEA:Ensembl.
DR GO; GO:0005635; C:nuclear envelope; IDA:BHF-UCL.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005643; C:nuclear pore; TAS:ProtInc.
DR GO; GO:0044614; C:nuclear pore cytoplasmic filaments; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:FlyBase.
DR GO; GO:0106068; C:SUMO ligase complex; IPI:ComplexPortal.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:FlyBase.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0090630; P:activation of GTPase activity; IDA:UniProtKB.
DR GO; GO:1904117; P:cellular response to vasopressin; IEA:Ensembl.
DR GO; GO:0046826; P:negative regulation of protein export from nucleus; IDA:BHF-UCL.
DR GO; GO:0051168; P:nuclear export; IC:ComplexPortal.
DR GO; GO:0006913; P:nucleocytoplasmic transport; IBA:GO_Central.
DR GO; GO:0016925; P:protein sumoylation; IDA:ComplexPortal.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 1.25.40.200; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR009109; Ran_GTPase_activating_1_C.
DR InterPro; IPR036720; RanGAP1_C_sf.
DR Pfam; PF13516; LRR_6; 4.
DR Pfam; PF07834; RanGAP1_C; 1.
DR SUPFAM; SSF69099; SSF69099; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Centromere; Chromosome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; GTPase activation; Isopeptide bond; Kinetochore;
KW Leucine-rich repeat; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:20388717"
FT CHAIN 2..587
FT /note="Ran GTPase-activating protein 1"
FT /id="PRO_0000056737"
FT REPEAT 48..71
FT /note="LRR 1"
FT REPEAT 111..134
FT /note="LRR 2"
FT REPEAT 207..230
FT /note="LRR 3"
FT REPEAT 235..258
FT /note="LRR 4"
FT REPEAT 292..319
FT /note="LRR 5"
FT REPEAT 320..343
FT /note="LRR 6"
FT REGION 357..430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 523..526
FT /note="SUMO conjugation"
FT COMPBIAS 358..398
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 562
FT /note="Hydrophobic interaction with UBE2I"
FT /evidence="ECO:0000250"
FT SITE 565
FT /note="Hydrophobic interaction with UBE2I"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:20388717"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16428860,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 409
FT /note="Phosphothreonine; by CDK2"
FT /evidence="ECO:0000269|PubMed:15037602"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15037602,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 436
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15037602,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 524
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 8
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT CROSSLNK 8
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 15
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 279
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 452
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 524
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0000269|PubMed:11854305,
FT ECO:0007744|PubMed:25114211"
FT CROSSLNK 524
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:25114211,
FT ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT CROSSLNK 586
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 133
FT /note="E -> Q (in dbSNP:rs2229752)"
FT /id="VAR_029240"
FT MUTAGEN 91
FT /note="R->A: Abolishes RAN GTPase activation."
FT /evidence="ECO:0000269|PubMed:16428860"
FT MUTAGEN 356
FT /note="S->A: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:16428860"
FT MUTAGEN 358
FT /note="S->A: Strongly decreased phosphorylation. No effect
FT on sumoylation."
FT /evidence="ECO:0000269|PubMed:16428860"
FT MUTAGEN 524
FT /note="K->R: Loss of cross-link to SUMO1. Abolishes
FT association with nuclear pores during interphase, and with
FT mitotic spindles during mitosis."
FT /evidence="ECO:0000269|PubMed:11854305"
FT HELIX 434..439
FT /evidence="ECO:0007829|PDB:2GRR"
FT HELIX 443..448
FT /evidence="ECO:0007829|PDB:2GRR"
FT HELIX 450..452
FT /evidence="ECO:0007829|PDB:2IO2"
FT HELIX 453..459
FT /evidence="ECO:0007829|PDB:2GRR"
FT HELIX 466..477
FT /evidence="ECO:0007829|PDB:2GRR"
FT HELIX 484..502
FT /evidence="ECO:0007829|PDB:2GRR"
FT STRAND 503..507
FT /evidence="ECO:0007829|PDB:1Z5S"
FT HELIX 509..519
FT /evidence="ECO:0007829|PDB:2GRR"
FT STRAND 522..526
FT /evidence="ECO:0007829|PDB:2IO2"
FT HELIX 536..545
FT /evidence="ECO:0007829|PDB:2GRR"
FT STRAND 548..551
FT /evidence="ECO:0007829|PDB:1Z5S"
FT HELIX 553..555
FT /evidence="ECO:0007829|PDB:2GRR"
FT HELIX 556..564
FT /evidence="ECO:0007829|PDB:2GRR"
FT HELIX 568..571
FT /evidence="ECO:0007829|PDB:2GRR"
FT HELIX 574..586
FT /evidence="ECO:0007829|PDB:2GRR"
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
