UniProt functional annotation for P49792

UniProt code: P49792.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Function: E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. 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. Binds single- stranded RNA (in vitro). May bind DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1. Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB. {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:22194619}.
Pathway: Protein modification; protein sumoylation.
Subunit: Forms a tight complex with RANBP1 and UBE2I. Interacts with SUMO1 but not SUMO2. Interacts with PARK2. Interacts with sumoylated RANGAP1. Interacts with CDCA8. Interacts with PML (isoform PML-4). {ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15388847, ECO:0000269|PubMed:15608651, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:16332688, ECO:0000269|PubMed:18946085, ECO:0000269|PubMed:22194619}.
Subcellular location: Nucleus. Nucleus membrane. Nucleus, nuclear pore complex. Note=Detected in diffuse and discrete intranuclear foci. Cytoplasmic filaments.
Domain: Contains a dozen F-X-F-G repeats in the C-terminal half. {ECO:0000269|PubMed:23353830}.
Domain: The PPIase cyclophilin-type domain has high structural similarity with PPIA, but has extremely low and barely detectable proline isomerase activity (in vitro) (PubMed:23353830). Only about half of the residues that surround the PPIA active site cleft are conserved. {ECO:0000269|PubMed:23353830}.
Ptm: Polyubiquitinated by PARK2, which leads to proteasomal degradation. {ECO:0000269|PubMed:16332688}.
Ptm: The 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. {ECO:0000250}.
Disease: Encephalopathy, acute, infection-induced, 3 (IIAE3) [MIM:608033]: 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. {ECO:0000269|PubMed:19118815}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required (PubMed:19118815). {ECO:0000269|PubMed:19118815}.
Similarity: Contains 1 PPIase cyclophilin-type domain. {ECO:0000255|PROSITE-ProRule:PRU00156}.
Similarity: Contains 4 RanBD1 domains. {ECO:0000255|PROSITE- ProRule:PRU00164}.
Similarity: Contains 8 RanBP2-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00322}.
Similarity: Contains 7 TPR repeats. {ECO:0000255|PROSITE- ProRule:PRU00339}.

Annotations taken from UniProtKB at the EBI.