RANBP2

Last updated
RANBP2
Protein RANBP2 PDB 1rrp.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases RANBP2 , ADANE, ANE1, IIAE3, NUP358, TRP1, TRP2, RAN binding protein 2
External IDs OMIM: 601181 HomoloGene: 136803 GeneCards: RANBP2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_006267

n/a

RefSeq (protein)

NP_006258

n/a

Location (UCSC) Chr 2: 108.72 – 108.79 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

RAN binding protein 2 (RANBP2) is protein which in humans is encoded by the RANBP2 gene. [3] It is also known as nucleoporin 358 (Nup358) since it is a member nucleoporin family that makes up the nuclear pore complex. RanBP2 has a mass of 358 kDa.

Function

RAN is a small GTP-binding protein of the RAS superfamily. Ran GTPase is a master regulatory switch, which among other functions, controls the shuttling of proteins between the nuclear and cytoplasm compartments of the cell. Ran GTPase controls a variety of cellular functions through its interactions with other proteins. The RanBP2 gene encodes a very large RAN-binding protein that localizes to cytoplasmic filaments emanating from the nuclear pore complex. RanBP2/Nup358 is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in controlling selective processes of the Ran-GTPase cycle. RanBP2 is composed of multiple domains. Each domain of RanBP2 selectively and directly interacts with distinct proteins such as Ran GTPase, importin-beta, exportin-1/CRM1, red opsin, subunits of the proteasome, cox11 and the kinesin-1 isoforms, KIF5B and KIF5C. Another partner of RanBP2 is the E2 enzyme UBC9. RanBP2 strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. Another target for SUMOylation is RanGAP which is the GTPase activating protein for Ran. SUMO-RanGAP interacts with a domain near the carboxyl terminus of RanBP2. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. The pleiotropic (multifunctional) role of RanBP2 reflects its interaction with multiple partners, each presenting distinct cellular or molecular functions. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on human chromosome 2q.

Clinical significance

Insufficiency of RanBP2 is directly linked to carcinogenesis, aneuploidy, and neuroprotection of photoreceptor neurons to light-elicited stress and aging. Human missense mutations in RanBP2 were identified in its leucine-rich domain and they cause autosomal dominant necrotizing encephalopathy (ADNE). [4]

Interactions

RANBP2 has been shown to interact with KPNB1 [5] [6] [7] and UBE2I. [8] [9]

Related Research Articles

<span class="mw-page-title-main">Nuclear pore</span> Openings in nuclear envelope of eukaryotic cells

A nuclear pore is a channel as part of the nuclear pore complex (NPC), a large protein complex found in the nuclear envelope in eukaryotic cells, enveloping the cell nucleus containing DNA, which facilitates the selective membrane transport of various molecules across the membrane.

A nuclear localization signalorsequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different nuclear localized proteins may share the same NLS. An NLS has the opposite function of a nuclear export signal (NES), which targets proteins out of the nucleus.

Importin is a type of karyopherin that transports protein molecules from the cell's cytoplasm to the nucleus. It does so by binding to specific recognition sequences, called nuclear localization sequences (NLS).

<span class="mw-page-title-main">Ran (protein)</span> GTPase functioning in nuclear transport

Ran also known as GTP-binding nuclear protein Ran is a protein that in humans is encoded by the RAN gene. Ran is a small 25 kDa protein that is involved in transport into and out of the cell nucleus during interphase and also involved in mitosis. It is a member of the Ras superfamily.

<span class="mw-page-title-main">Nuclear pore glycoprotein p62</span> Protein-coding gene in the species Homo sapiens

Nuclear pore glycoprotein p62 is a protein complex associated with the nuclear envelope. The p62 protein remains associated with the nuclear pore complex-lamina fraction. p62 is synthesized as a soluble cytoplasmic precursor of 61 kDa followed by modification that involve addition of N-acetylglucosamine residues, followed by association with other complex proteins. In humans it is encoded by the NUP62 gene.

<span class="mw-page-title-main">Nucleoporin</span> Family of proteins that form the nuclear pore complex

Nucleoporins are a family of proteins which are the constituent building blocks of the nuclear pore complex (NPC). The nuclear pore complex is a massive structure embedded in the nuclear envelope at sites where the inner and outer nuclear membranes fuse, forming a gateway that regulates the flow of macromolecules between the cell nucleus and the cytoplasm. Nuclear pores enable the passive and facilitated transport of molecules across the nuclear envelope. Nucleoporins, a family of around 30 proteins, are the main components of the nuclear pore complex in eukaryotic cells. Nucleoporin 62 is the most abundant member of this family. Nucleoporins are able to transport molecules across the nuclear envelope at a very high rate. A single NPC is able to transport 60,000 protein molecules across the nuclear envelope every minute.

<span class="mw-page-title-main">XPO1</span> Protein-coding gene in the species Homo sapiens

Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), is a eukaryotic protein that mediates the nuclear export of various proteins and RNAs.

<span class="mw-page-title-main">KPNB1</span> Protein-coding gene in the species Homo sapiens

Importin subunit beta-1 is a protein that in humans is encoded by the KPNB1 gene.

<span class="mw-page-title-main">NUP98</span> Protein-coding gene in the species Homo sapiens

Nuclear pore complex protein Nup98-Nup96 is a protein that in humans is encoded by the NUP98 gene.

<span class="mw-page-title-main">IPO5</span> Protein-coding gene in the species Homo sapiens

Importin-5 is a protein that in humans is encoded by the IPO5 gene. The protein encoded by this gene is a member of the importin beta family. Structurally, the protein adopts the shape of a right hand solenoid and is composed of 24 HEAT repeats.

<span class="mw-page-title-main">RCC1</span> Protein-coding gene in the species Homo sapiens

Regulator of chromosome condensation 1, also known as RCC1, Ran guanine nucleotide exchange factor and RanGEF, is the name for a human gene and protein.

<span class="mw-page-title-main">Nucleoporin 153</span> Protein-coding gene in the species Homo sapiens

Nucleoporin 153 (Nup153) is a protein which in humans is encoded by the NUP153 gene. It is an essential component of the basket of nuclear pore complexes (NPCs) in vertebrates, and required for the anchoring of NPCs. It also acts as the docking site of an importing karyopherin. On the cytoplasmic side of the NPC, Nup358 fulfills an analogous role.

<span class="mw-page-title-main">Transportin 1</span> Protein-coding gene in the species Homo sapiens

Transportin-1 is a protein that in humans is encoded by the TNPO1 gene.

<span class="mw-page-title-main">Nucleoporin 214</span> Protein-coding gene in the species Homo sapiens

Nucleoporin 214 (Nup2014) is a protein that in humans is encoded by the NUP214 gene.

<span class="mw-page-title-main">RANGAP1</span> Protein-coding gene in the species Homo sapiens

Ran GTPase-activating protein 1 is an enzyme that in humans is encoded by the RANGAP1 gene.

<span class="mw-page-title-main">RANBP1</span> Protein-coding gene in the species Homo sapiens

Ran-specific binding protein 1 is an enzyme that in humans is encoded by the RANBP1 gene.

<span class="mw-page-title-main">NUTF2</span> Protein-coding gene in the species Homo sapiens

Nuclear transport factor 2 is a protein that in humans is encoded by the NUTF2 gene.

<span class="mw-page-title-main">Nucleoporin 54</span> Protein-coding gene in the species Homo sapiens

Nucleoporin 54 (Nup54) is a protein that in humans is encoded by the NUP54 gene.

RanGAP is a protein involved in the transport of other proteins from the cytosol to the nucleus in eukaryotic cells.

<span class="mw-page-title-main">IPO8</span> Proteine

Importin 8 is a protein that in humans is encoded by the IPO8 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000153201 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Beddow AL, Richards SA, Orem NR, Macara IG (Apr 1995). "The Ran/TC4 GTPase-binding domain: identification by expression cloning and characterization of a conserved sequence motif". Proceedings of the National Academy of Sciences of the United States of America. 92 (8): 3328–32. Bibcode:1995PNAS...92.3328B. doi: 10.1073/pnas.92.8.3328 . PMC   42159 . PMID   7724562.
  4. "Entrez Gene: RANBP2 RAN binding protein 2".
  5. Yaseen NR, Blobel G (Sep 1999). "GTP hydrolysis links initiation and termination of nuclear import on the nucleoporin nup358". The Journal of Biological Chemistry. 274 (37): 26493–502. doi: 10.1074/jbc.274.37.26493 . PMID   10473610.
  6. Delphin C, Guan T, Melchior F, Gerace L (Dec 1997). "RanGTP targets p97 to RanBP2, a filamentous protein localized at the cytoplasmic periphery of the nuclear pore complex". Molecular Biology of the Cell. 8 (12): 2379–90. doi:10.1091/mbc.8.12.2379. PMC   25714 . PMID   9398662.
  7. Ben-Efraim I, Gerace L (Jan 2001). "Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import". The Journal of Cell Biology. 152 (2): 411–7. doi:10.1083/jcb.152.2.411. PMC   2199621 . PMID   11266456.
  8. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.
  9. Zhang H, Saitoh H, Matunis MJ (Sep 2002). "Enzymes of the SUMO modification pathway localize to filaments of the nuclear pore complex". Molecular and Cellular Biology. 22 (18): 6498–508. doi:10.1128/MCB.22.18.6498-6508.2002. PMC   135644 . PMID   12192048.

Further reading