PROSITE documentation PDOC50199

Zinc finger RanBP2-type signature and profile

Nucleocytoplasmic transport is mediated by large supramolecular structures that span the nuclear envelope called nuclear pore complexes (NPC). The export as well as the import pathway require three major component, the substrate, an adaptor complex and a receptor. The adaptor complex and the receptor pass through the NPC with the substrate. The nuclear transport is also dependent on the GTPase cycle of the small GTPase protein Ran and a number of Ran-binding proteins (RanBP) [1,2].

RanBP2 is one of these proteins located in the NPC on the cytoplasmic side of the ring. The function of RanBP2 is not yet well understood. It could function in coupling RanGTP hydrolysis to NPC translocation through its Ran binding domain (RanBD1) (see <PDOC50196>) [3,4]. RanBP2 contains also a cluster of zinc fingers, the RanBP2 zinc fingers. It has been shown that these zinc fingers bind RanGDP (but not RanGTP) [5] and the exportin-1 protein (a receptor of the export pathway) [6].

The RanBP2 zinc finger is also found in different proteins that are mainly involved in nuclear transport or localized to the nuclear envelope. Some of the proteins containing such a domain are listed below.

• Mammalian RanBP2/Nup358 protein. Implicated in nuclear import and export processes (8 copies).
• Human MDM2, play a central role in P53 regulation. MDM2 binds to P53 in the nucleus and the complexe is transported to the cytoplasm via a signal in MDM2 (1 copy).
• Human EWS protein. May play a role in the tumorigenic process. It may disturb gene expression by mimicking, or interfering with the normal function of CTD-polII within the transcription initiation complex (1 copy).
• FUS, probable RNA-binding protein. Exhibits diffuse staining throughout the nucleus (excluding nucleoli), together with a small number of intensely stained focal points, or granules, and punctate staining along the nuclear envelope (1 copy).
• Human nuclear pore complex protein Nup153. Possible DNA-binding subunit of the nuclear pore complex (NPC). Located to the terminal ring structure of nucleoplasmic cage (4 copies).
• Yeast asparagine-rich protein 1 (ARP1). Protein of unknown function (2 copies).

The RanBP2 zinc finger contains 4 cysteines and a conserved tryptophan upstream of the zinc finger. Our pattern starts with this tryptophan and includes the 4 cysteines. We have also developed a profile that covers a region slightly bigger than the zinc finger.