RANGAP1 explained

Ran GTPase-activating protein 1 is an enzyme that in humans is encoded by the RANGAP1 gene.^{[1] [2]}

Function

RanGAP1, is a homodimeric 65-kD polypeptide that specifically induces the GTPase activity of RAN, but not of RAS by over 1,000-fold. RanGAP1 is the immediate antagonist of RCC1, a regulator molecule that keeps RAN in the active, GTP-bound state. 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 Rangap1 (Fug1), the murine homolog of yeast Rna1p. RanGAP1 and RCC1 control RAN-dependent transport between the nucleus and cytoplasm. RanGAP1 is a key regulator of the RAN GTP/GDP cycle.

Interactions

RanGAP1 is a trafficking protein which helps transport other proteins from the cytoplasm to the nucleus. Small ubiquitin-related modifier needs to be associated with it before it can be localized at the nuclear pore.^[3]

RANGAP1 has been shown to interact with:

• Ran,^{[4] [5] [6]} and
• UBE2I.^{[7] [8] [9]}

References

Further reading

• Becker J, Melchior F, Gerke V, Bischoff FR, Ponstingl H, Wittinghofer A . RNA1 encodes a GTPase-activating protein specific for Gsp1p, the Ran/TC4 homologue of Saccharomyces cerevisiae . J. Biol. Chem. . 270 . 20 . 11860–5 . 1995 . 7744835 . 10.1074/jbc.270.20.11860 . free .
• Bischoff FR, Klebe C, Kretschmer J, Wittinghofer A, Ponstingl H . RanGAP1 induces GTPase activity of nuclear Ras-related Ran . Proc. Natl. Acad. Sci. U.S.A. . 91 . 7 . 2587–91 . 1994 . 8146159 . 43414 . 10.1073/pnas.91.7.2587 . 1994PNAS...91.2587B . free .
• Krebber H, Ponstingl H . Ubiquitous expression and testis-specific alternative polyadenylation of mRNA for the human Ran GTPase activator RanGAP1 . Gene . 180 . 1–2 . 7–11 . 1997 . 8973340 . 10.1016/S0378-1119(96)00389-7 .
• Matunis MJ, 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 . 6 Pt 1 . 1457–70 . 1997 . 8978815 . 2133973 . 10.1083/jcb.135.6.1457 .
• Mahajan R, Delphin C, Guan T, Gerace L, Melchior F . A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2 . Cell . 88 . 1 . 97–107 . 1997 . 9019411 . 10.1016/S0092-8674(00)81862-0 . free .
• Görlich D, Dabrowski M, Bischoff FR, Kutay U, Bork P, Hartmann E, Prehn S, Izaurralde E . A Novel Class of RanGTP Binding Proteins . J. Cell Biol. . 138 . 1 . 65–80 . 1997 . 9214382 . 2139951 . 10.1083/jcb.138.1.65 .
• Scheffzek K, Ahmadian MR, Kabsch W, Wiesmüller L, Lautwein A, Schmitz F, Wittinghofer A . The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants . Science . 277 . 5324 . 333–8 . 1998 . 9219684 . 10.1126/science.277.5324.333 .
• Mahajan R, Gerace L, Melchior F . Molecular Characterization of the SUMO-1 Modification of RanGAP1 and Its Role in Nuclear Envelope Association . J. Cell Biol. . 140 . 2 . 259–70 . 1998 . 9442102 . 2132567 . 10.1083/jcb.140.2.259 .
• Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET . Characterization of a second member of the sentrin family of ubiquitin-like proteins . J. Biol. Chem. . 273 . 18 . 11349–53 . 1998 . 9556629 . 10.1074/jbc.273.18.11349 . free .
• 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 . 3 . 693–8 . 1999 . 9920803 . 10.1006/bbrc.1998.9995 .
• Hillig RC, Renault L, Vetter IR, Drell T, Wittinghofer A, Becker J . The crystal structure of rna1p: a new fold for a GTPase-activating protein . Mol. Cell . 3 . 6 . 781–91 . 1999 . 10394366 . 10.1016/S1097-2765(01)80010-1 . free .
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP . The DNA sequence of human chromosome 22 . Nature . 402 . 6761 . 489–95 . 1999 . 10591208 . 10.1038/990031 . 1999Natur.402..489D . free .
• Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O . Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Res. . 8 . 2 . 85–95 . 2001 . 11347906 . 10.1093/dnares/8.2.85 . free .
• Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD . Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1 . Cell . 108 . 3 . 345–56 . 2002 . 11853669 . 10.1016/S0092-8674(02)00630-X . free .
• Joseph J, Tan SH, Karpova TS, McNally JG, Dasso M . SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles . J. Cell Biol. . 156 . 4 . 595–602 . 2002 . 11854305 . 2174074 . 10.1083/jcb.200110109 .
• Zhang H, Saitoh H, Matunis MJ . Enzymes of the SUMO Modification Pathway Localize to Filaments of the Nuclear Pore Complex . Mol. Cell. Biol. . 22 . 18 . 6498–508 . 2002 . 12192048 . 135644 . 10.1128/MCB.22.18.6498-6508.2002 .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proc. Natl. Acad. Sci. U.S.A. . 101 . 33 . 12130–5 . 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .
• Macauley MS, Errington WJ, Okon M, Schärpf M, Mackereth CD, Schulman BA, McIntosh LP . Structural and dynamic independence of isopeptide-linked RanGAP1 and SUMO-1 . J. Biol. Chem. . 279 . 47 . 49131–7 . 2005 . 15355965 . 10.1074/jbc.M408705200 . free .

Notes and References

1. Bischoff FR, 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 Natl Acad Sci U S A . 92 . 5 . 1749–53 . Apr 1995 . 7878053 . 42597 . 10.1073/pnas.92.5.1749 . 1995PNAS...92.1749B . free .
2. Web site: Entrez Gene: RANGAP1 Ran GTPase activating protein 1.
3. Hochstrasser M . Biochemistry. All in the ubiquitin family . Science . 289 . 5479 . 563–4 . 2000 . 10939967 . 10.1126/science.289.5479.563. 32469429 .
4. Hillig RC, Renault L, Vetter IR, Drell T, Wittinghofer A, Becker J . The crystal structure of rna1p: a new fold for a GTPase-activating protein . Mol. Cell . 3 . 6 . 781–91 . Jun 1999 . 10394366 . 10.1016/S1097-2765(01)80010-1. free .
5. Becker J, Melchior F, Gerke V, Bischoff FR, Ponstingl H, Wittinghofer A . RNA1 encodes a GTPase-activating protein specific for Gsp1p, the Ran/TC4 homologue of Saccharomyces cerevisiae . J. Biol. Chem. . 270 . 20 . 11860–5 . May 1995 . 7744835 . 10.1074/jbc.270.20.11860. free .
6. Bischoff FR, Klebe C, Kretschmer J, Wittinghofer A, Ponstingl H . RanGAP1 induces GTPase activity of nuclear Ras-related Ran . Proc. Natl. Acad. Sci. U.S.A. . 91 . 7 . 2587–91 . Mar 1994 . 8146159 . 43414 . 10.1073/pnas.91.7.2587. 1994PNAS...91.2587B . free .
7. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 89 . 17353931 . 1847948 . 10.1038/msb4100134 . 2007 .
8. Tatham MH, Kim S, Yu B, Jaffray E, Song J, Zheng J, Rodriguez MS, Hay RT, Chen Y . Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation . Biochemistry . 42 . 33 . 9959–69 . Aug 2003 . 12924945 . 10.1021/bi0345283 .
9. Knipscheer P, Flotho A, Klug H, Olsen JV, van Dijk WJ, Fish A, Johnson ES, Mann M, Sixma TK, Pichler A . Ubc9 sumoylation regulates SUMO target discrimination . Mol. Cell . 31 . 3 . 371–82 . Aug 2008 . 18691969 . 10.1016/j.molcel.2008.05.022 . free .