RANBP2

RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]

Full Name

RAN Binding Protein 2

Function

E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:22194619, PubMed:15931224).
Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481).
Binds single-stranded RNA (in vitro) (PubMed:7775481).
May bind DNA (PubMed:7775481).
Component of the nuclear export pathway (PubMed:10078529).
Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529).
Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184).
Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726).
Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830).

Biological Process

Biological Process centrosome localizationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process mRNA transportIEA:UniProtKB-KW
Biological Process NLS-bearing protein import into nucleusManual Assertion Based On ExperimentIMP:GO_Central
Biological Process nuclear export1 PublicationIC:ComplexPortal
Biological Process nucleocytoplasmic transport1 PublicationIC:ComplexPortal
Biological Process positive regulation of glucokinase activityIEA:Ensembl
Biological Process protein foldingIEA:InterPro
Biological Process protein peptidyl-prolyl isomerizationIEA:InterPro
Biological Process protein sumoylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of gluconeogenesisIEA:Ensembl

Cellular Location

Nucleus
Nucleus membrane
Nucleus, nuclear pore complex
Nucleus envelope
Detected in diffuse and discrete intranuclear foci (PubMed:11839768).
Cytoplasmic filaments (PubMed:7775481).

Involvement in disease

Encephalopathy, acute, infection-induced, 3 (IIAE3):
A rapidly progressive encephalopathy manifesting in susceptible individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem.

PTM

Polyubiquitinated by PRKN, which leads to proteasomal degradation.
The inner channel of the NPC has a different redox environment from the cytoplasm and allows the formation of interchain disulfide bonds between some nucleoporins, the significant increase of these linkages upon oxidative stress reduces the permeability of the NPC.