RAN

RAN (ras-related nuclear protein) is a small GTP binding protein belonging to the RAS superfamily that is essential for the translocation of RNA and proteins through the nuclear pore complex. The RAN protein is also involved in control of DNA synthesis and cell cycle progression. Nuclear localization of RAN requires the presence of regulator of chromosome condensation 1 (RCC1). Mutations in RAN disrupt DNA synthesis. Because of its many functions, it is likely that RAN interacts with several other proteins. RAN regulates formation and organization of the microtubule network independently of its role in the nucleus-cytosol exchange of macromolecules. RAN could be a key signaling molecule regulating microtubule polymerization during mitosis. RCC1 generates a high local concentration of RAN-GTP around chromatin which, in turn, induces the local nucleation of microtubules. RAN is an androgen receptor (AR) coactivator that binds differentially with different lengths of polyglutamine within the androgen receptor. Polyglutamine repeat expansion in the AR is linked to Kennedy's disease (X-linked spinal and bulbar muscular atrophy). RAN coactivation of the AR diminishes with polyglutamine expansion within the AR, and this weak coactivation may lead to partial androgen insensitivity during the development of Kennedy's disease. [provided by RefSeq, Jul 2008]

RAN, member RAS oncogene family

GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs (PubMed:10400640, PubMed:8276887, PubMed:8896452, PubMed:8636225, PubMed:8692944, PubMed:9351834, PubMed:9428644, PubMed:9822603, PubMed:17209048, PubMed:26272610, PubMed:27306458).
Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis (PubMed:7819259, PubMed:8896452, PubMed:8636225, PubMed:8692944, PubMed:9351834, PubMed:9428644, PubMed:9822603, PubMed:29040603, PubMed:11336674, PubMed:26272610).
Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport (PubMed:8896452, PubMed:9351834, PubMed:9428644).
Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins (PubMed:20485264).
RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation (PubMed:10408446, PubMed:29040603).
Required for normal progress through mitosis (PubMed:8421051, PubMed:12194828, PubMed:29040603).
The complex with BIRC5/survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules (PubMed:18591255).
Acts as a negative regulator of the kinase activity of VRK1 and VRK2 (PubMed:18617507).
Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases (PubMed:10400640).

Biological Process actin cytoskeleton organizationIEA:Ensembl
Biological Process cell divisionIEA:UniProtKB-KW
Biological Process DNA metabolic processManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process GTP metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process mitotic cell cycleManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process mitotic sister chromatid segregationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process mitotic spindle organizationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process positive regulation of protein bindingManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of protein import into nucleusManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process pre-miRNA export from nucleus1 PublicationIC:BHF-UCL
Biological Process protein export from nucleusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein import into nucleusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein localization to nucleolusManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process ribosomal large subunit export from nucleusManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process ribosomal small subunit export from nucleusManual Assertion Based On ExperimentIMP:ParkinsonsUK-UCL
Biological Process ribosomal subunit export from nucleusManual Assertion Based On ExperimentIBA:GO_Central
Biological Process snRNA import into nucleusManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process viral processTAS:Reactome

Nucleus
Nucleus envelope
Cytoplasm, cytosol
Cytoplasm
Melanosome
Predominantly nuclear during interphase (PubMed:8421051, PubMed:12194828, PubMed:10679025).
Becomes dispersed throughout the cytoplasm during mitosis (PubMed:8421051, PubMed:12194828).
Identified by mass spectrometry in melanosome fractions from stage I to stage IV (PubMed:17081065).

Acetylation by KAT5 at Lys-134 is increased during mitosis, impairs RANGRF binding and enhances RCC1 binding (PubMed:29040603).
Acetylation at Lys-37 enhances the association with nuclear export components (PubMed:31075303).
Deacetylation of Lys-37 by SIRT7 regulates the nuclear export of NF-kappa-B subunit RELA/p65 (PubMed:31075303).