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RAN (P62826) - Overview - Molecular Target Synopsis

Protein


RAN, GTP-binding nuclear protein Ran
UniProt P62826

Also Known as RAN_HUMAN, RAN, ARA24

GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs (PubMed:10400640, PubMed:8276887, PubMed:8896452, PubMed:8636225, PubMed:8692944, PubMed:9351834, PubMed:9428644, PubMed:9822603, PubMed:26272610). Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis (PubMed:7819259, PubMed:8896452, PubMed:8636225, PubMed:8692944, PubMed:9351834, PubMed:9428644, PubMed:9822603, PubMed:29040603, PubMed:11336674, PubMed:26272610). 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 (PubMed:8896452, PubMed:9351834, PubMed:9428644). 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 (PubMed:20485264). RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation (PubMed:10408446, PubMed:29040603). Required for normal progress through mitosis (PubMed:8421051, PubMed:12194828, PubMed:29040603). 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 (PubMed:18591255). Acts as a negative regulator of the kinase activity of VRK1 and VRK2 (PubMed:18617507). Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases (PubMed:10400640). Monomer. Interacts with RANGAP1, which promotes RAN-mediated GTP hydrolysis (PubMed:7819259, PubMed:9428644). Interacts with KPNB1 (PubMed:8896452, PubMed:9428644, PubMed:10367892). Interaction with KPNB1 inhibits RANGAP1-mediated stimulation of GTPase activity (PubMed:9428644). Interacts with RCC1 which promotes the exchange of RAN-bound GDP by GTP (PubMed:1961752, PubMed:7819259, PubMed:12194828, PubMed:11336674). Interaction with KPNB1 inhibits RCC1-mediated exchange of RAN-bound GDP by GTP (PubMed:8896452). Interacts (GTP-bound form) with TNPO1; the interaction is direct (PubMed:9351834). Interacts with KPNB1 and with TNPO1; both inhibit RAN GTPase activity (PubMed:8896452, PubMed:9428644). Interacts (via C-terminus) with RANBP1, which alleviates the inhibition of RAN GTPase activity (PubMed:7891706, PubMed:8896452, PubMed:9428644, PubMed:11832950). Interacts with RANGRF, which promotes the release of bound guanine nucleotide (PubMed:29040603). RANGRF and RCC1 compete for an overlapping binding site on RAN (PubMed:29040603). Identified in a complex with KPNA2 and CSE1L; interaction with RANBP1 mediates dissociation of RAN from this complex (PubMed:9428644). Interaction with both RANBP1 and KPNA2 promotes dissociation of the complex between RAN and KPNB1 (PubMed:9428644). Identified in a complex composed of RAN, RANGAP1 and RANBP1 (PubMed:16428860). Identified in a complex that contains TNPO1, RAN and RANBP1 (PubMed:9428644). Identified in a nuclear export complex with XPO1 (PubMed:9323133, PubMed:15574331, PubMed:10209022). Found in a nuclear export complex with RANBP3 and XPO1 (PubMed:11571268, PubMed:11425870). Interacts with RANBP2/NUP358 (PubMed:10078529, PubMed:26272610). 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 (PubMed:20485264). Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1 (PubMed:10209022, PubMed:19389996). Found in a nuclear export complex with RAN, XPO5 and pre-miRNA (By similarity). Interacts (GTP-bound form) with XPO5 (By similarity). Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5 (PubMed:14500717). Interacts with RANBP9 and RANBP10 (PubMed:14684163). Interacts in its GTP-bound form with BIRC5/survivin at S and M phases of the cell cycle (PubMed:18591255). Interacts with TERT; the interaction requires hydrogen peroxide-mediated phosphorylation of TERT and transports TERT to the nucleus (PubMed:12808100). Interacts with MAD2L2 (PubMed:19753112). Interacts with VRK1 and VRK3 (PubMed:18617507). Interacts with isoform 1 and isoform 2 of VRK2 (PubMed:18617507). Interacts with NEMP1 and KPNB1 (By similarity). Interacts (GDP-bound form) with NUTF2; regulates RAN nuclear import (PubMed:9822603, PubMed:10679025, PubMed:18266911). Interacts with CAPG; mediates CAPG nuclear import (PubMed:10679025, PubMed:18266911). Interacts with NUP153 (PubMed:18611384, PubMed:19505478). Interacts with the AR N-terminal poly-Gln region; the interaction with AR is inversely correlated with the poly-Gln length (PubMed:10400640). Interacts with MYCBP2, which promotes RAN-mediated GTP hydrolysis (PubMed:26304119).

5YST
RANM189D IN COMPLEX WITH RANBP1-CRM1
RCSB/PDB
Inspect Structure
See all 3D Structures for RAN

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: RAN is active in the following subcellular-locations: cytoplasm, cytosol, melanosome, nucleus, nucleus envelope.
GO terms: RAN is active in the following subcellular-locations: centriole, cytoplasm, cytosol, extracellular exosome, host cell, melanosome, membrane, midbody, nuclear envelope, nuclear pore, nucleolus, nucleoplasm, nucleus, protein-containing complex, recycling endosome, RNA nuclear export complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project RAN has gain in 2 cell-lines, loss in 0 cell-lines and no signal in 1003 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: PC_3, ACHN, KM12

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MKN-74, OVCAR-8, SK-MEL-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: A549, HSMM, NHLF

(see details)

3D Structures


For RAN there are:
77 structures (119 chains) solved
73 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


RAN has been screened with compounds ( bioactivities). (see details)