a small GTPase belonging to the RAS superfamily that regulates the nucleo-cytoplasmic traffic through the nuclear pore complex, the condensation of chromatin, spindle assembly and cytokinesis, as well as the organization of non-centrosomal microtubules. A major regulator of mitosis and a potential therapeutic target in cancers expressing higher Ras/MEK/ERK and PI3K/Akt/mTORC1 activities. Required for the import of protein into and RNA export from the nucleus. Cycles between the nucleus and cytoplasm in this process. The Ran guanine nucleotide-exchange factor (RanGEF) is nuclear, promoting the GTP-bound state, while the Ran GTPase activating protein (RanGAP) is cytoplasmic, promoting GDP-bound state. RanGDP is imported into the nucleus by nuclear transport factor-2 (NUTF2), where RanGEF catalyses nucleotide exchange and generates RanGTP. RanGTP then binds to transport factors, such as KPNB1 and CAS, and is exported to the cytoplasm, where RanGAP stimulates GTP hydrolysis. Regulates microtubule polymerization during mitosis; micritubule localization of RAN requires the presence of regulator of chromosome condensation 1 (RCC1), a Ran-GEF. RCC1 generates a high local concentration of RAN-GTP around chromatin which, in turn, induces the local nucleation of microtubules. Regulates the formation and organization of the microtubule network independently of its role in the nucleus-cytosol exchange of macromolecules. GTP-Ran interacts with survivin at S and M phases of the cell cycle. Ran-survivin complexes play a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2. Interacts with TERT following the tyrosine phosphorylation of TERT induced by H2O2, inducing nuclear export of TERT. Interacts with MAD2L2. Predominantly nuclear during interphase. Becomes dispersed throughout the cytoplasm during mitosis. Note: This description may include information from UniProtKB.
Protein type: Cell cycle regulation; G protein; Nuclear export; G protein, monomeric, Ran; Motility/polarity/chemotaxis; Nuclear receptor co-regulator; G protein, monomeric
Molecular Function: GTPase activity; protein domain specific binding; protein binding; GDP binding; androgen receptor binding; GTP binding; transcription coactivator activity; chromatin binding
Biological Process: ribosomal small subunit export from nucleus; mitosis; positive regulation of protein binding; viral reproduction; positive regulation of transcription, DNA-dependent; viral infectious cycle; signal transduction; ribosomal large subunit export from nucleus; mitotic spindle organization and biogenesis; protein import into nucleus; cell division; small GTPase mediated signal transduction; androgen receptor signaling pathway; gene expression; protein export from nucleus; actin cytoskeleton organization and biogenesis; DNA metabolic process; spermatid development
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.