UniProt functional annotation for P49792



	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 (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). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}.

Pathway: Protein modification; protein sumoylation.

Subunit: Part of the nuclear pore complex (PubMed:11839768, PubMed:20386726, PubMed:23353830, PubMed:7603572). Forms a complex with NXT1, NXF1 and RANGAP1 (PubMed:14729961). Forms a tight complex with RANBP1 and UBE2I (PubMed:15388847, PubMed:10078529, PubMed:15826666). Interacts with SUMO1 but not SUMO2 (PubMed:15388847, PubMed:10078529, PubMed:15826666). Interacts with PRKN (PubMed:16332688). Interacts with sumoylated RANGAP1 (PubMed:15378033, PubMed:10078529, PubMed:15826666). Interacts with CDCA8 (PubMed:19413330). Interacts with PML (isoform PML-4) (PubMed:22155184). Interacts with BICD2 (PubMed:20386726). Interacts with MCM3AP isoform GANP (PubMed:20005110). {ECO:0000269|PubMed:10078529, ECO:0000269|PubMed:11839768, ECO:0000269|PubMed:14729961, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15388847, ECO:0000269|PubMed:15826666, ECO:0000269|PubMed:16332688, ECO:0000269|PubMed:20005110, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7603572}.

Subcellular location: Nucleus {ECO:0000269|PubMed:7775481}. Nucleus membrane {ECO:0000269|PubMed:11839768}. Nucleus, nuclear pore complex {ECO:0000269|PubMed:11839768, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7603572}. Nucleus envelope {ECO:0000269|PubMed:20386726}. Note=Detected in diffuse and discrete intranuclear foci (PubMed:11839768). Cytoplasmic filaments (PubMed:7775481). {ECO:0000269|PubMed:11839768, ECO:0000269|PubMed:7775481}.

Domain: Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited. {ECO:0000305}.

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 PRKN, which leads to proteasomal degradation. {ECO:0000269|PubMed:16332688}.

Ptm: 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|UniProtKB:Q9ERU9}.

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 variants 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}.

Disease: Note=A chromosomal aberration involving RANBP2 is a cause of chromosome 8p11 myeloproliferative syndrome. Translocation t(2;8)(q12;p11) with FGFR1. Chromosome 8p11 myeloproliferative syndrome is characterized by myeloid hyperplasia, eosinophilia and T-cell or B- cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. {ECO:0000269|PubMed:23041776}.

Similarity: Belongs to the RanBP2 E3 ligase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


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 (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). {ECO:0000269\|PubMed:11792325, ECO:0000269\|PubMed:12032081, ECO:0000269\|PubMed:15378033, ECO:0000269\|PubMed:15931224, ECO:0000269\|PubMed:20386726, ECO:0000269\|PubMed:20676357, ECO:0000269\|PubMed:22155184, ECO:0000269\|PubMed:22194619, ECO:0000269\|PubMed:23353830, ECO:0000269\|PubMed:7775481, ECO:0000303\|PubMed:10078529}.


Pathway:		Protein modification; protein sumoylation.
Subunit:		Part of the nuclear pore complex (PubMed:11839768, PubMed:20386726, PubMed:23353830, PubMed:7603572). Forms a complex with NXT1, NXF1 and RANGAP1 (PubMed:14729961). Forms a tight complex with RANBP1 and UBE2I (PubMed:15388847, PubMed:10078529, PubMed:15826666). Interacts with SUMO1 but not SUMO2 (PubMed:15388847, PubMed:10078529, PubMed:15826666). Interacts with PRKN (PubMed:16332688). Interacts with sumoylated RANGAP1 (PubMed:15378033, PubMed:10078529, PubMed:15826666). Interacts with CDCA8 (PubMed:19413330). Interacts with PML (isoform PML-4) (PubMed:22155184). Interacts with BICD2 (PubMed:20386726). Interacts with MCM3AP isoform GANP (PubMed:20005110). {ECO:0000269\|PubMed:10078529, ECO:0000269\|PubMed:11839768, ECO:0000269\|PubMed:14729961, ECO:0000269\|PubMed:15378033, ECO:0000269\|PubMed:15388847, ECO:0000269\|PubMed:15826666, ECO:0000269\|PubMed:16332688, ECO:0000269\|PubMed:20005110, ECO:0000269\|PubMed:20386726, ECO:0000269\|PubMed:22155184, ECO:0000269\|PubMed:23353830, ECO:0000269\|PubMed:7603572}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:7775481}. Nucleus membrane {ECO:0000269\|PubMed:11839768}. Nucleus, nuclear pore complex {ECO:0000269\|PubMed:11839768, ECO:0000269\|PubMed:20386726, ECO:0000269\|PubMed:23353830, ECO:0000269\|PubMed:7603572}. Nucleus envelope {ECO:0000269\|PubMed:20386726}. Note=Detected in diffuse and discrete intranuclear foci (PubMed:11839768). Cytoplasmic filaments (PubMed:7775481). {ECO:0000269\|PubMed:11839768, ECO:0000269\|PubMed:7775481}.
Domain:		Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited. {ECO:0000305}.
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 PRKN, which leads to proteasomal degradation. {ECO:0000269\|PubMed:16332688}.
Ptm:		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\|UniProtKB:Q9ERU9}.
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 variants 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}.
Disease:		Note=A chromosomal aberration involving RANBP2 is a cause of chromosome 8p11 myeloproliferative syndrome. Translocation t(2;8)(q12;p11) with FGFR1. Chromosome 8p11 myeloproliferative syndrome is characterized by myeloid hyperplasia, eosinophilia and T-cell or B- cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. {ECO:0000269\|PubMed:23041776}.
Similarity:		Belongs to the RanBP2 E3 ligase family. {ECO:0000305}.