RAN

RAN

Target · Small GTPase

RAN GTP-binding nuclear protein Ran · ras-related nuclear protein

RAN (RAN, member RAS oncogene family; also known as ARA24, TC4 and Gsp1) is a small GTPase of the RAS superfamily. It drives nucleocytoplasmic transport of proteins and RNAs and also contributes to mitotic spindle assembly and cell cycle progression. Browse Assay Genie's current range of RAN research reagents below, or read on for the biology behind the target.

Nuclear and cytosolicNucleocytoplasmic transport GTPaseAndrogen receptor coactivator
216 aa
Protein length
~24 kDa
Molecular weight
12q24.33
Gene locus
EC 3.6.5.-
Enzyme class
Target information

What is RAN (RAN, member RAS oncogene family)?

RAN is a GTPase that participates in both the import and the export of proteins and RNAs through the nuclear pore complex. It cycles between a cytoplasmic GDP-bound state and a nuclear GTP-bound state through nucleotide exchange and GTP hydrolysis. This gradient sets the directionality of transport: nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them when they interact with GTP-bound RAN, while export receptors behave in the opposite way. RAN therefore controls cargo loading and release in the correct compartment. Interaction with RANBP1 changes the conformation of the XPO1-RAN complex and triggers release of the nuclear export signal of cargo proteins.

The RAN gene encodes a member of the small GTPase superfamily and the Ran family, classed by HGNC among the RAN family GTPases. The protein is found in the nucleus, nuclear envelope and cytosol, and nuclear localisation of RAN requires regulator of chromosome condensation 1 (RCC1). Mouse and rat both have a Ran ortholog. Because RAN has so many functions, it is likely to interact with a number of other proteins, and mutations in RAN disrupt DNA synthesis.

Beyond transport, GTP-bound RAN triggers microtubule assembly at mitotic chromosomes and is required for normal spindle assembly, chromosome segregation and progression through mitosis. RCC1 generates a high local concentration of RAN-GTP around chromatin, which induces local microtubule nucleation. The RAN complex with BIRC5/survivin helps deliver the RAN effector TPX2 to microtubules. RAN also negatively regulates the kinase activity of VRK1 and VRK2, and acts as an androgen receptor (AR) coactivator. Its coactivation diminishes as the polyglutamine tract in AR expands, which may contribute to partial androgen insensitivity in Kennedy's disease.

Nucleocytoplasmic transport

RAN-GTP and RAN-GDP states set the directionality of nuclear import and export, making RAN central to studies of transport receptors and cargo release.

Mitosis and spindle assembly

GTP-bound RAN triggers microtubule assembly at chromosomes and is required for spindle formation and chromosome segregation.

Cell cycle and DNA synthesis

RAN is involved in control of DNA synthesis and cell cycle progression, and mutations in RAN disrupt DNA synthesis.

Androgen receptor and Kennedy's disease

RAN coactivates AR, and this coactivation weakens with polyglutamine expansion, a feature linked to Kennedy's disease.

Background

RAN frequently asked questions

What does RAN do?

RAN is a small GTPase that controls nuclear import and export of proteins and RNAs. Its GTP-bound nuclear state and GDP-bound cytoplasmic state regulate cargo binding and release by transport receptors. It also drives microtubule assembly at mitotic chromosomes and supports spindle formation.

What other names does RAN go by?

RAN is the HGNC symbol for RAN, member RAS oncogene family. UniProt names the protein GTP-binding nuclear protein Ran, and NCBI describes it as ras-related nuclear protein. Aliases include ARA24, TC4 and Gsp1.

Is RAN linked to disease or conserved in other species?

Mouse and rat each have a Ran ortholog. RAN is an androgen receptor coactivator whose effect diminishes as AR polyglutamine repeats expand, which may contribute to partial androgen insensitivity in Kennedy's disease. Check the datasheet of any product for its validated reactivity.

Explore

Related targets

Other RAN-binding proteins, transport receptors and mitotic spindle factors that act alongside RAN.

Gene and protein annotations from HGNC, NCBI Gene and UniProt P62826; product specifications from Assay Genie datasheets.

RAN Product listing