UniProt functional annotation for P46060



	UniProt functional annotation for P46060

UniProt code: P46060.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: GTPase activator for RAN (PubMed:8146159, PubMed:8896452, PubMed:16428860). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:8896452, PubMed:27160050). Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050). {ECO:0000269|PubMed:16428860, ECO:0000269|PubMed:27160050, ECO:0000269|PubMed:8146159, ECO:0000269|PubMed:8896452}.

Subunit: Homodimer (PubMed:8146159). Interacts with RAN (PubMed:7891706, PubMed:8896452, PubMed:16428860). Forms a complex with RANBP2/NUP358, NXF1 and NXT1 (PubMed:14729961). Forms a tight complex in association with RANBP2/NUP358 and UBE2I/UBC9, the ubiquitin- conjugating enzyme E2 (PubMed:15037602, PubMed:27160050, PubMed:15931224, PubMed:22194619). Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2/NUP358 (PubMed:15037602, PubMed:27160050, PubMed:15931224). The complex composed of RANBP2, SUMO1, RANGAP1 and UBE2I associates with nuclear pore complexes (PubMed:15037602, PubMed:15931224). Identified in a complex composed of RAN, RANBP2, sumoylated RANGAP1, UBE2I and XPO1 (PubMed:27160050). Identified in a complex composed of RAN, RANGAP1 and RANBP1 (PubMed:16428860). Interacts with TRAF6 (PubMed:18093978). Interacts with SUMO1 and SENP1 (PubMed:17099698). Interacts (when sumoylated) with MYCBP2; interaction inhibits MYCBP2 E3 ubiquitin-protein ligase activity and promotes MYCBP2 translocation to the nucleus (PubMed:26304119). {ECO:0000269|PubMed:14729961, ECO:0000269|PubMed:15037602, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:16428860, ECO:0000269|PubMed:17099698, ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:26304119, ECO:0000269|PubMed:27160050, ECO:0000269|PubMed:7891706, ECO:0000269|PubMed:8146159, ECO:0000269|PubMed:8896452}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:15037602, ECO:0000305|PubMed:8146159}. Nucleus, nucleoplasm {ECO:0000269|PubMed:8146159}. Nucleus envelope {ECO:0000269|PubMed:11854305, ECO:0000269|PubMed:15037602}. Chromosome, centromere, kinetochore {ECO:0000269|PubMed:11854305}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:11854305, ECO:0000269|PubMed:15037602}. Note=Cytoplasmic during interphase. Detected at the nuclear envelope during interphase (PubMed:11854305, PubMed:15037602). Targeted to the nuclear pores after sumoylation (PubMed:11854305). During mitosis, associates with mitotic spindles, but is essentially not detected at the spindle poles (PubMed:11854305, PubMed:15037602). Association with kinetochores appears soon after nuclear envelope breakdown and persists until late anaphase (PubMed:11854305). Mitotic location also requires sumoylation (PubMed:11854305). {ECO:0000269|PubMed:11854305, ECO:0000269|PubMed:15037602}.

Tissue specificity: Highly expressed in brain, thymus and testis. {ECO:0000269|PubMed:8973340}.

Ptm: Phosphorylation occurs before nuclear envelope breakdown and continues throughout mitosis. Phosphorylated by the M-phase kinase cyclin B/Cdk1, in vitro. Differential timimg of dephosphorylation occurs during phases of mitosis. The phosphorylated form remains associated with RANBP2/NUP358 and the SUMO E2-conjugating enzyme, UBE2I, on nuclear pore complex (NPC) diassembly and during mitosis. {ECO:0000269|PubMed:15037602}.

Ptm: Sumoylated (PubMed:11854305, PubMed:15037602, PubMed:26304119, PubMed:27160050). Sumoylation is necessary for targeting to the nuclear envelope (NE), and for association with mitotic spindles and kinetochores during mitosis (PubMed:11854305). Also required for interaction with RANBP2 and is mediated by UBE2I (PubMed:27160050). {ECO:0000269|PubMed:11854305, ECO:0000269|PubMed:15037602, ECO:0000269|PubMed:16428860, ECO:0000269|PubMed:20388717, ECO:0000269|PubMed:26304119, ECO:0000305|PubMed:27160050}.

Similarity: Belongs to the RNA1 family. {ECO:0000305}.

Sequence caution: Sequence=BAB47464.1; Type=Erroneous initiation; Evidence={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:		GTPase activator for RAN (PubMed:8146159, PubMed:8896452, PubMed:16428860). Converts cytoplasmic GTP-bound RAN to GDP-bound RAN, which is essential for RAN-mediated nuclear import and export (PubMed:8896452, PubMed:27160050). Mediates dissociation of cargo from nuclear export complexes containing XPO1, RAN and RANBP2 after nuclear export (PubMed:27160050). {ECO:0000269\|PubMed:16428860, ECO:0000269\|PubMed:27160050, ECO:0000269\|PubMed:8146159, ECO:0000269\|PubMed:8896452}.


Subunit:		Homodimer (PubMed:8146159). Interacts with RAN (PubMed:7891706, PubMed:8896452, PubMed:16428860). Forms a complex with RANBP2/NUP358, NXF1 and NXT1 (PubMed:14729961). Forms a tight complex in association with RANBP2/NUP358 and UBE2I/UBC9, the ubiquitin- conjugating enzyme E2 (PubMed:15037602, PubMed:27160050, PubMed:15931224, PubMed:22194619). Interacts with UBE2I; the interaction conjugates SUMO1 to RANGAP1, and subsequently stabilizes interactions of sumoylated RANGAP1 with RANBP2/NUP358 (PubMed:15037602, PubMed:27160050, PubMed:15931224). The complex composed of RANBP2, SUMO1, RANGAP1 and UBE2I associates with nuclear pore complexes (PubMed:15037602, PubMed:15931224). Identified in a complex composed of RAN, RANBP2, sumoylated RANGAP1, UBE2I and XPO1 (PubMed:27160050). Identified in a complex composed of RAN, RANGAP1 and RANBP1 (PubMed:16428860). Interacts with TRAF6 (PubMed:18093978). Interacts with SUMO1 and SENP1 (PubMed:17099698). Interacts (when sumoylated) with MYCBP2; interaction inhibits MYCBP2 E3 ubiquitin-protein ligase activity and promotes MYCBP2 translocation to the nucleus (PubMed:26304119). {ECO:0000269\|PubMed:14729961, ECO:0000269\|PubMed:15037602, ECO:0000269\|PubMed:15931224, ECO:0000269\|PubMed:16428860, ECO:0000269\|PubMed:17099698, ECO:0000269\|PubMed:18093978, ECO:0000269\|PubMed:26304119, ECO:0000269\|PubMed:27160050, ECO:0000269\|PubMed:7891706, ECO:0000269\|PubMed:8146159, ECO:0000269\|PubMed:8896452}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:15037602, ECO:0000305\|PubMed:8146159}. Nucleus, nucleoplasm {ECO:0000269\|PubMed:8146159}. Nucleus envelope {ECO:0000269\|PubMed:11854305, ECO:0000269\|PubMed:15037602}. Chromosome, centromere, kinetochore {ECO:0000269\|PubMed:11854305}. Cytoplasm, cytoskeleton, spindle {ECO:0000269\|PubMed:11854305, ECO:0000269\|PubMed:15037602}. Note=Cytoplasmic during interphase. Detected at the nuclear envelope during interphase (PubMed:11854305, PubMed:15037602). Targeted to the nuclear pores after sumoylation (PubMed:11854305). During mitosis, associates with mitotic spindles, but is essentially not detected at the spindle poles (PubMed:11854305, PubMed:15037602). Association with kinetochores appears soon after nuclear envelope breakdown and persists until late anaphase (PubMed:11854305). Mitotic location also requires sumoylation (PubMed:11854305). {ECO:0000269\|PubMed:11854305, ECO:0000269\|PubMed:15037602}.
Tissue specificity:		Highly expressed in brain, thymus and testis. {ECO:0000269\|PubMed:8973340}.
Ptm:		Phosphorylation occurs before nuclear envelope breakdown and continues throughout mitosis. Phosphorylated by the M-phase kinase cyclin B/Cdk1, in vitro. Differential timimg of dephosphorylation occurs during phases of mitosis. The phosphorylated form remains associated with RANBP2/NUP358 and the SUMO E2-conjugating enzyme, UBE2I, on nuclear pore complex (NPC) diassembly and during mitosis. {ECO:0000269\|PubMed:15037602}.
Ptm:		Sumoylated (PubMed:11854305, PubMed:15037602, PubMed:26304119, PubMed:27160050). Sumoylation is necessary for targeting to the nuclear envelope (NE), and for association with mitotic spindles and kinetochores during mitosis (PubMed:11854305). Also required for interaction with RANBP2 and is mediated by UBE2I (PubMed:27160050). {ECO:0000269\|PubMed:11854305, ECO:0000269\|PubMed:15037602, ECO:0000269\|PubMed:16428860, ECO:0000269\|PubMed:20388717, ECO:0000269\|PubMed:26304119, ECO:0000305\|PubMed:27160050}.
Similarity:		Belongs to the RNA1 family. {ECO:0000305}.
Sequence caution:		Sequence=BAB47464.1; Type=Erroneous initiation; Evidence={ECO:0000305};