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: Nuclear export; G protein, monomeric; Nuclear receptor co-regulator; Cell cycle regulation; Motility/polarity/chemotaxis; G protein, monomeric, Ran; G protein
Molecular Function: chromatin binding; GDP binding; GTP binding; GTPase activity; protein binding
Biological Process: DNA metabolic process; mitosis; mitotic spindle organization and biogenesis; positive regulation of protein binding; pre-microRNA export from nucleus; protein export from nucleus; protein import into nucleus, translocation; ribosomal large subunit export from nucleus; ribosomal small subunit export from nucleus; RNA-mediated gene silencing; signal transduction; tRNA export from nucleus; viral reproduction
LTP: 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.