RANGAP1

Ran GTPase activating protein 1

PDB rendering based on 1z5s.

Available structures
PDB	1Z5S, 2GRN, 2GRO, 2GRP, 2GRQ, 2GRR, 2IO2, 2IO3, 2IY0

Identifiers

Symbols

RANGAP1; Fug1; KIAA1835; MGC20266; SD

External IDs

OMIM: 602362 MGI: 103071 HomoloGene: 121881 GeneCards: RANGAP1 Gene

Gene Ontology
Molecular function	• GTPase activator activity • Ran GTPase activator activity • protein binding
Cellular component	• kinetochore • condensed chromosome kinetochore • spindle pole • soluble fraction • nucleus • nuclear pore • chromosome • cytoplasm • cytosol • cytoskeleton • membrane • nuclear membrane
Biological process	• M phase of mitotic cell cycle • mitotic prometaphase • mitotic cell cycle • signal transduction • positive regulation of Ran GTPase activity
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 22:
41.64 – 41.7 Mb

Chr 15:
81.53 – 81.56 Mb

PubMed search

[1]

[2]

For more details on RanGAP proteins in non-human species, see RanGAP.

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

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 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.^[2]

Interactions

RANGAP1 has been shown to interact with Ran (biology)^[3]^[4]^[5] and UBE2I.^[6]^[7]^[8]

References

^ Bischoff FR, Krebber H, Kempf T, Hermes I, Ponstingl H (Apr 1995). "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. doi:10.1073/pnas.92.5.1749. PMC 42597. PMID 7878053. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=42597.
^ ^a ^b "Entrez Gene: RANGAP1 Ran GTPase activating protein 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5905.
^ Hillig, R C; Renault L, Vetter I R, Drell T, Wittinghofer A, Becker J (Jun. 1999). "The crystal structure of rna1p: a new fold for a GTPase-activating protein". Mol. Cell (UNITED STATES) 3 (6): 781–91. doi:10.1016/S1097-2765(01)80010-1. ISSN 1097-2765. PMID 10394366.
^ Becker, J; Melchior F, Gerke V, Bischoff F R, Ponstingl H, Wittinghofer A (May. 1995). "RNA1 encodes a GTPase-activating protein specific for Gsp1p, the Ran/TC4 homologue of Saccharomyces cerevisiae". J. Biol. Chem. (UNITED STATES) 270 (20): 11860–5. doi:10.1074/jbc.270.20.11860. ISSN 0021-9258. PMID 7744835.
^ Bischoff, F R; Klebe C, Kretschmer J, Wittinghofer A, Ponstingl H (Mar. 1994). "RanGAP1 induces GTPase activity of nuclear Ras-related Ran". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 91 (7): 2587–91. doi:10.1073/pnas.91.7.2587. ISSN 0027-8424. PMC 43414. PMID 8146159. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43414.
^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948.
^ Tatham, Michael H; Kim Suhkmann, Yu Bin, Jaffray Ellis, Song Jing, Zheng Jian, Rodriguez Manuel S, Hay Ronald T, Chen Yuan (Aug. 2003). "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation". Biochemistry (United States) 42 (33): 9959–69. doi:10.1021/bi0345283. ISSN 0006-2960. PMID 12924945.
^ Knipscheer, Puck; Flotho Annette, Klug Helene, Olsen Jesper V, van Dijk Willem J, Fish Alexander, Johnson Erica S, Mann Matthias, Sixma Titia K, Pichler Andrea (Aug. 2008). "Ubc9 sumoylation regulates SUMO target discrimination". Mol. Cell (United States) 31 (3): 371–82. doi:10.1016/j.molcel.2008.05.022. PMID 18691969.

Becker J, Melchior F, Gerke V et al. (1995). "RNA1 encodes a GTPase-activating protein specific for Gsp1p, the Ran/TC4 homologue of Saccharomyces cerevisiae". J. Biol. Chem. 270 (20): 11860–5. doi:10.1074/jbc.270.20.11860. PMID 7744835.
Bischoff FR, Klebe C, Kretschmer J et al. (1994). "RanGAP1 induces GTPase activity of nuclear Ras-related Ran". Proc. Natl. Acad. Sci. U.S.A. 91 (7): 2587–91. doi:10.1073/pnas.91.7.2587. PMC 43414. PMID 8146159. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=43414.
Krebber H, Ponstingl H (1997). "Ubiquitous expression and testis-specific alternative polyadenylation of mRNA for the human Ran GTPase activator RanGAP1". Gene 180 (1–2): 7–11. doi:10.1016/S0378-1119(96)00389-7. PMID 8973340.
Matunis MJ, Coutavas E, Blobel G (1997). "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. doi:10.1083/jcb.135.6.1457. PMC 2133973. PMID 8978815. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2133973.
Mahajan R, Delphin C, Guan T et al. (1997). "A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2". Cell 88 (1): 97–107. doi:10.1016/S0092-8674(00)81862-0. PMID 9019411.
Görlich D, Dabrowski M, Bischoff FR et al. (1997). "A Novel Class of RanGTP Binding Proteins". J. Cell Biol. 138 (1): 65–80. doi:10.1083/jcb.138.1.65. PMC 2139951. PMID 9214382. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2139951.
Scheffzek K, Ahmadian MR, Kabsch W et al. (1998). "The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants". Science 277 (5324): 333–8. doi:10.1126/science.277.5324.333. PMID 9219684.
Mahajan R, Gerace L, Melchior F (1998). "Molecular Characterization of the SUMO-1 Modification of RanGAP1 and Its Role in Nuclear Envelope Association". J. Cell Biol. 140 (2): 259–70. doi:10.1083/jcb.140.2.259. PMC 2132567. PMID 9442102. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2132567.
Kamitani T, Kito K, Nguyen HP et al. (1998). "Characterization of a second member of the sentrin family of ubiquitin-like proteins". J. Biol. Chem. 273 (18): 11349–53. doi:10.1074/jbc.273.18.11349. PMID 9556629.
Okuma T, Honda R, Ichikawa G et al. (1999). "In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2". Biochem. Biophys. Res. Commun. 254 (3): 693–8. doi:10.1006/bbrc.1998.9995. PMID 9920803.
Hillig RC, Renault L, Vetter IR et al. (1999). "The crystal structure of rna1p: a new fold for a GTPase-activating protein". Mol. Cell 3 (6): 781–91. doi:10.1016/S1097-2765(01)80010-1. PMID 10394366.
Dunham I, Shimizu N, Roe BA et al. (1999). "The DNA sequence of human chromosome 22". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
Nagase T, Nakayama M, Nakajima D et al. (2001). "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. doi:10.1093/dnares/8.2.85. PMID 11347906.
Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD (2002). "Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1". Cell 108 (3): 345–56. doi:10.1016/S0092-8674(02)00630-X. PMID 11853669.
Joseph J, Tan SH, Karpova TS et al. (2002). "SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles". J. Cell Biol. 156 (4): 595–602. doi:10.1083/jcb.200110109. PMC 2174074. PMID 11854305. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2174074.
Zhang H, Saitoh H, Matunis MJ (2002). "Enzymes of the SUMO Modification Pathway Localize to Filaments of the Nuclear Pore Complex". Mol. Cell. Biol. 22 (18): 6498–508. doi:10.1128/MCB.22.18.6498-6508.2002. PMC 135644. PMID 12192048. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=135644.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Beausoleil SA, Jedrychowski M, Schwartz D et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=514446.
Macauley MS, Errington WJ, Okon M et al. (2005). "Structural and dynamic independence of isopeptide-linked RanGAP1 and SUMO-1". J. Biol. Chem. 279 (47): 49131–7. doi:10.1074/jbc.M408705200. PMID 15355965.

PDB gallery

1z5s: Crystal structure of a complex between UBC9, SUMO-1, RANGAP1 and NUP358/RANBP2

2grn: Crystal Structure of human RanGAP1-Ubc9

2gro: Crystal Structure of human RanGAP1-Ubc9-N85Q

2grp: Crystal Structure of human RanGAP1-Ubc9-Y87A

2grq: Crystal Structure of human RanGAP1-Ubc9-D127A

2grr: Crystal Structure of human RanGAP1-Ubc9-D127S

2io2: Crystal structure of human Senp2 in complex with RanGAP1-SUMO-1

2io3: Crystal structure of human Senp2 in complex with RanGAP1-SUMO-2

2iy0: SENP1 (MUTANT) SUMO1 RANGAP

RANGAP1

Interactions

References

Further reading