ID:RAGP1_HUMAN DESCRIPTION: RecName: Full=Ran GTPase-activating protein 1; Short=RanGAP1; FUNCTION: GTPase activator for the nuclear Ras-related regulatory protein Ran, converting it to the putatively inactive GDP-bound state. SUBUNIT: Homodimer. Forms a tight complex in association with RANBP2/NUP358 and UBE2I/UBC9, the ubiquitin-conjugating enzyme E2. Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2/NUP358. The SUMO1/RANGAP1/UBC9/NUP358 complex associates with nuclear pore complexes. Interacts with TRAF6. INTERACTION: P63165:SUMO1; NbExp=3; IntAct=EBI-396091, EBI-80140; SUBCELLULAR LOCATION: Cytoplasm. Nucleus membrane; Peripheral membrane protein; Cytoplasmic side. Chromosome, centromere, kinetochore (By similarity). Cytoplasm, cytoskeleton, spindle pole (By similarity). Note=Cytoplasmic during interphase. Targeted to the nuclear rim after sumoylation. During mitosis, associates with mitotic spindles. Association with kinetochores appears soon after nuclear envelope breakdown and persists until late anaphase. Mitotic location also requires sumoylation. TISSUE SPECIFICITY: Highly expressed in brain, thymus and testis. PTM: Phosphorylated occurs before nuclear envelope breakdown and continues throughout mitosis. Phosphorylated by the M-phase kinase cyclin B/Cdk1, in vitro. Differential timimg of dephosphorylation occurs during phases of mitosis. The phosphorylated form remains associated with RANBP2/NUP358 and the SUMO E2-conjugating enzyme, UBC9, on nuclear pore complex (NPC) diassembly and during mitosis. PTM: Sumoylated with SUMO1. Sumoylation is necessary for targeting to the nuclear envelope (NE), and for association with mitotic spindles and kinetochores during mitosis. Also required for interaction with RANBP2 and is mediated by UBC9. SIMILARITY: Belongs to the RNA1 family. SIMILARITY: Contains 6 LRR (leucine-rich) repeats. SEQUENCE CAUTION: Sequence=BAB47464.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P46060
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0007165 signal transduction GO:0046826 negative regulation of protein export from nucleus GO:0048678 response to axon injury GO:0071375 cellular response to peptide hormone stimulus GO:0090630 activation of GTPase activity GO:1904117 cellular response to vasopressin
BC048990 - Homo sapiens Ran GTPase activating protein 1, mRNA (cDNA clone IMAGE:5271569), partial cds. BC014044 - Homo sapiens Ran GTPase activating protein 1, mRNA (cDNA clone MGC:20266 IMAGE:3506039), complete cds. BC041396 - Homo sapiens Ran GTPase activating protein 1, mRNA (cDNA clone MGC:43988 IMAGE:5277434), complete cds. AK303524 - Homo sapiens cDNA FLJ61018 complete cds, highly similar to Ran GTPase-activating protein 1. BC004990 - Homo sapiens, clone IMAGE:2905857, mRNA, partial cds. BC019676 - Homo sapiens, Similar to RAN GTPase activating protein 1, clone IMAGE:4516363, mRNA, partial cds. AB058738 - Homo sapiens KIAA1835 mRNA for KIAA1835 protein. AK302222 - Homo sapiens cDNA FLJ51385 complete cds, highly similar to Ran GTPase-activating protein 1. CR456557 - Homo sapiens RANGAP1 full length open reading frame (ORF) cDNA clone (cDNA clone C22ORF:pGEM.RANGAP1). X82260 - H.sapiens mRNA for RanGTPase activating protein 1. CU013157 - Homo sapiens RANGAP1, mRNA (cDNA clone IMAGE:100000510), complete cds, with stop codon, in Gateway system. AB384305 - Synthetic construct DNA, clone: pF1KSDA1835, Homo sapiens RANGAP1 gene for Ran GTPase-activating protein 1, complete cds, without stop codon, in Flexi system. KJ897445 - Synthetic construct Homo sapiens clone ccsbBroadEn_06839 RANGAP1 gene, encodes complete protein. CU013445 - Homo sapiens RANGAP1, mRNA (cDNA clone IMAGE:100000414), complete cds, without stop codon, in Gateway system. JD020128 - Sequence 1152 from Patent EP1572962. JD028357 - Sequence 9381 from Patent EP1572962. JD019460 - Sequence 484 from Patent EP1572962. CU680754 - Synthetic construct Homo sapiens gateway clone IMAGE:100019913 5' read RANGAP1 mRNA.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_ranPathway - Cycling of Ran in nucleocytoplasmic transport h_ranMSpathway - Role of Ran in mitotic spindle regulation h_npcPathway - Mechanism of Protein Import into the Nucleus h_ranbp2Pathway - Sumoylation by RanBP2 Regulates Transcriptional Repression
Reactome (by CSHL, EBI, and GO)
Protein P46060 (Reactome details) participates in the following event(s):
R-HSA-141409 Mad1 binds kinetochore R-HSA-375302 Kinetochore capture of astral microtubules R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2 R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex R-HSA-141439 Release of activated MAD2 from kinetochores R-HSA-2467811 Separation of sister chromatids R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1 R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal R-HSA-68877 Mitotic Prometaphase R-HSA-5663220 RHO GTPases Activate Formins R-HSA-2500257 Resolution of Sister Chromatid Cohesion R-HSA-2467813 Separation of Sister Chromatids R-HSA-141424 Amplification of signal from the kinetochores R-HSA-68886 M Phase R-HSA-195258 RHO GTPase Effectors R-HSA-68882 Mitotic Anaphase R-HSA-69618 Mitotic Spindle Checkpoint R-HSA-69278 Cell Cycle (Mitotic) R-HSA-194315 Signaling by Rho GTPases R-HSA-2555396 Mitotic Metaphase and Anaphase R-HSA-69620 Cell Cycle Checkpoints R-HSA-1640170 Cell Cycle R-HSA-162582 Signal Transduction R-HSA-4615885 SUMOylation of DNA replication proteins R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins R-HSA-2990846 SUMOylation R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins