P62825 · RAN_CANLF
- ProteinGTP-binding nuclear protein Ran
- GeneRAN
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids216 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs. Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis. 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. 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. RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation. Required for normal progress through mitosis. 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. Acts as a negative regulator of the kinase activity of VRK1 and VRK2. Enhances AR-mediated transactivation.
Catalytic activity
- GTP + H2O = GDP + H+ + phosphateThis reaction proceeds in the forward direction.
Cofactor
Note: Mg2+ interacts primarily with the phosphate groups of the bound guanine nucleotide.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 18-25 | GTP (UniProtKB | ChEBI) | ||||
Sequence: DGGTGKTT | ||||||
Binding site | 36-42 | GTP (UniProtKB | ChEBI) | ||||
Sequence: EKKYVAT | ||||||
Binding site | 68 | GTP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Site | 69 | Essential for GTP hydrolysis | ||||
Sequence: Q | ||||||
Binding site | 122-125 | GTP (UniProtKB | ChEBI) | ||||
Sequence: NKVD | ||||||
Binding site | 150-152 | GTP (UniProtKB | ChEBI) | ||||
Sequence: SAK |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | melanosome | |
Cellular Component | nuclear envelope | |
Cellular Component | nucleus | |
Cellular Component | protein-containing complex | |
Cellular Component | RISC complex | |
Molecular Function | GTP binding | |
Molecular Function | GTPase activity | |
Molecular Function | magnesium ion binding | |
Molecular Function | nuclear export signal receptor activity | |
Molecular Function | pre-miRNA binding | |
Molecular Function | RISC complex binding | |
Biological Process | cell division | |
Biological Process | GTP metabolic process | |
Biological Process | mitotic sister chromatid segregation | |
Biological Process | positive regulation of protein export from nucleus | |
Biological Process | pre-miRNA export from nucleus | |
Biological Process | protein export from nucleus | |
Biological Process | protein import into nucleus | |
Biological Process | ribosomal subunit export from nucleus | |
Biological Process | snRNA import into nucleus |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameGTP-binding nuclear protein Ran
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Canidae > Canis
Accessions
- Primary accessionP62825
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Note: Predominantly nuclear during interphase. Becomes dispersed throughout the cytoplasm during mitosis (By similarity).
Identified by mass spectrometry in melanosome fractions from stage I to stage IV (By similarity).
Identified by mass spectrometry in melanosome fractions from stage I to stage IV (By similarity).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000208695 | 2-216 | GTP-binding nuclear protein Ran | |||
Sequence: AAQGEPQVQFKLVLVGDGGTGKTTFVKRHLTGEFEKKYVATLGVEVHPLVFHTNRGPIKFNVWDTAGQEKFGGLRDGYYIQAQCAIIMFDVTSRVTYKNVPNWHRDLVRVCENIPIVLCGNKVDIKDRKVKAKSIVFHRKKNLQYYDISAKSNYNFEKPFLWLARKLIGDPNLEFVAMPALAPPEVVMDPALAAQYEHDLEVAQTTALPDEDDDL | ||||||
Modified residue | 24 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 37 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 60 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 71 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Cross-link | 71 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate | ||||
Sequence: K | ||||||
Cross-link | 71 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate | ||||
Sequence: K | ||||||
Modified residue | 99 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 134 | N6-acetyllysine | ||||
Sequence: K | ||||||
Cross-link | 152 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 159 | N6-acetyllysine; alternate | ||||
Sequence: K | ||||||
Modified residue | 159 | N6-succinyllysine; alternate | ||||
Sequence: K |
Post-translational modification
Acetylation by KAT5 at Lys-134 is increased during mitosis, impairs RANGRF binding and enhances RCC1 binding. Acetylation at Lys-37 enhances the association with nuclear export components. Deacetylation of Lys-37 by SIRT7 regulates the nuclear export of NF-kappa-B subunit RELA/p65.
Keywords
- PTM
Proteomic databases
Interaction
Subunit
Monomer. Interacts with RANGAP1, which promotes RAN-mediated GTP hydrolysis. Interacts with KPNB1 (PubMed:15864302).
Interaction with KPNB1 inhibits RANGAP1-mediated stimulation of GTPase activity. Interacts with RCC1 which promotes the exchange of RAN-bound GDP by GTP. Interaction with KPNB1 inhibits RCC1-mediated exchange of RAN-bound GDP by GTP. Interacts (GTP-bound form) with TNPO1; the interaction is direct. Interacts (GTP-bound form) with TNPO3; the interaction is direct (By similarity).
Interacts with KPNB1 and with TNPO1; both inhibit RAN GTPase activity. Interacts (via C-terminus) with RANBP1, which alleviates the inhibition of RAN GTPase activity. Interacts with RANGRF, which promotes the release of bound guanine nucleotide. RANGRF and RCC1 compete for an overlapping binding site on RAN. Identified in a complex with KPNA2 and CSE1L; interaction with RANBP1 mediates dissociation of RAN from this complex (PubMed:15602554).
Interaction with both RANBP1 and KPNA2 promotes dissociation of the complex between RAN and KPNB1. Identified in a complex composed of RAN, RANGAP1 and RANBP1. Identified in a complex that contains TNPO1, RAN and RANBP1. Identified in a nuclear export complex with XPO1. Found in a nuclear export complex with RANBP3 and XPO1. Interacts with RANBP2/NUP358. Interaction with RANBP1 or RANBP2 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1 (By similarity).
Found in a nuclear export complex with RAN, XPO5 and pre-miRNA (PubMed:19965479).
Interacts (GTP-bound form) with XPO5 (PubMed:19965479).
Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5. Interacts with RANBP9 and RANBP10. Interacts in its GTP-bound form with BIRC5/survivin at S and M phases of the cell cycle. Interacts with TERT; the interaction requires hydrogen peroxide-mediated phosphorylation of TERT and transports TERT to the nucleus. Interacts with MAD2L2. Interacts with VRK1 and VRK3. Interacts with VRK2 (By similarity).
Interacts with NEMP1 and KPNB1 (By similarity).
Interacts (GDP-bound form) with NUTF2; regulates RAN nuclear import (PubMed:9533885).
Interacts with CAPG; mediates CAPG nuclear import. Interacts with NUP153. Interacts with the AR N-terminal poly-Gln region; the interaction with AR is inversely correlated with the poly-Gln length (By similarity).
Interacts with MYCBP2, which promotes RAN-mediated GTP hydrolysis (By similarity).
Interacts with EPG5 (By similarity).
Interaction with KPNB1 inhibits RANGAP1-mediated stimulation of GTPase activity. Interacts with RCC1 which promotes the exchange of RAN-bound GDP by GTP. Interaction with KPNB1 inhibits RCC1-mediated exchange of RAN-bound GDP by GTP. Interacts (GTP-bound form) with TNPO1; the interaction is direct. Interacts (GTP-bound form) with TNPO3; the interaction is direct (By similarity).
Interacts with KPNB1 and with TNPO1; both inhibit RAN GTPase activity. Interacts (via C-terminus) with RANBP1, which alleviates the inhibition of RAN GTPase activity. Interacts with RANGRF, which promotes the release of bound guanine nucleotide. RANGRF and RCC1 compete for an overlapping binding site on RAN. Identified in a complex with KPNA2 and CSE1L; interaction with RANBP1 mediates dissociation of RAN from this complex (PubMed:15602554).
Interaction with both RANBP1 and KPNA2 promotes dissociation of the complex between RAN and KPNB1. Identified in a complex composed of RAN, RANGAP1 and RANBP1. Identified in a complex that contains TNPO1, RAN and RANBP1. Identified in a nuclear export complex with XPO1. Found in a nuclear export complex with RANBP3 and XPO1. Interacts with RANBP2/NUP358. Interaction with RANBP1 or RANBP2 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1 (By similarity).
Found in a nuclear export complex with RAN, XPO5 and pre-miRNA (PubMed:19965479).
Interacts (GTP-bound form) with XPO5 (PubMed:19965479).
Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5. Interacts with RANBP9 and RANBP10. Interacts in its GTP-bound form with BIRC5/survivin at S and M phases of the cell cycle. Interacts with TERT; the interaction requires hydrogen peroxide-mediated phosphorylation of TERT and transports TERT to the nucleus. Interacts with MAD2L2. Interacts with VRK1 and VRK3. Interacts with VRK2 (By similarity).
Interacts with NEMP1 and KPNB1 (By similarity).
Interacts (GDP-bound form) with NUTF2; regulates RAN nuclear import (PubMed:9533885).
Interacts with CAPG; mediates CAPG nuclear import. Interacts with NUP153. Interacts with the AR N-terminal poly-Gln region; the interaction with AR is inversely correlated with the poly-Gln length (By similarity).
Interacts with MYCBP2, which promotes RAN-mediated GTP hydrolysis (By similarity).
Interacts with EPG5 (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 211-216 | Interaction with RANBP1 | ||||
Sequence: DEDDDL |
Sequence similarities
Belongs to the small GTPase superfamily. Ran family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length216
- Mass (Da)24,423
- Last updated2007-01-23 v3
- ChecksumD5C9B7275C34BCE0
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z11922 EMBL· GenBank· DDBJ | CAA77980.1 EMBL· GenBank· DDBJ | mRNA |