RANBP2
Encyclopedia
RAN binding protein 2, also known as RANBP2 is protein
which in humans is encoded by the RANBP2 gene
.
RanBP2 is also known as Nup358 since it is a member nucleoporin family that makes-up the nuclear pore complex. RanBP2 has a 358 KDa molecular weight.
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.
, 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).
with KPNB1
and UBE2I
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the RANBP2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
RanBP2 is also known as Nup358 since it is a member nucleoporin family that makes-up the nuclear pore complex. RanBP2 has a 358 KDa molecular weight.
Function
RAN is a small GTP-binding proteinG protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
of the RAS superfamily. Ran GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
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
Nuclear pore
Nuclear pores are large protein complexes that cross the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are about on average 2000 nuclear pore complexes in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the stage in...
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
Importin
Importin is a type of protein that moves other protein molecules into the nucleus by binding to a specific recognition sequence, called the nuclear localization signal . Importin is classified as a karyopherin....
-beta, exportin
Karyopherin
Karyopherins are a group of proteins involved in transporting molecules from the cytoplasm into the nucleus of eukaryotic cells. The inside of the nucleus is called the karyoplasm . Generally, karyopherin-mediated transport occurs through the nuclear pore, which acts as a gateway into and out of...
-1/CRM1
XPO1
Exportin-1 is a protein that in humans is encoded by the XPO1 gene.-Interactions:XPO1 has been shown to interact with NMD3, CIITA, RANBP3, Nucleoporin 62, Ran, RANBP1, APC, SMARCB1 and CDKN1B.-Further reading:...
, red opsin
Opsin
Opsins are a group of light-sensitive 35–55 kDa membrane-bound G protein-coupled receptors of the retinylidene protein family found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical...
, subunits of the proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria. In eukaryotes, they are located in the nucleus and the cytoplasm. The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...
, cox11 and the kinesin-1 isoforms, KIF5B and KIF5C. Another partner of RanBP2 is the E2 enzyme
Ubiquitin-conjugating enzyme
Ubiquitin-conjugating enzymes, also known as E2 enzymes and more rarely as ubiquitin-carrier enzymes, perform the second step in the ubiquitination reaction that targets a protein for degradation via the proteasome.The ubiquitination process covalently attaches ubiquitin, a short protein of 76...
UBC9
UBE2I
SUMO-conjugating enzyme UBC9 is a protein that in humans is encoded by the UBE2I gene.-Interactions:UBE2I has been shown to interact with WT1, TOP1, RAD51, Activating transcription factor 2, PIAS1, SALL1, FHIT, RANBP2, Protein inhibitor of activated STAT2, DNMT3A, DNMT3B, Small ubiquitin-related...
. RanBP2 strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100
Sp100 nuclear antigen
Sp100 nuclear antigen is an interferon stimulated antigen found in the bile duct of primary biliary cirrhosis. Histologically sp100 'dots' regions of the cell nucleus. Viral infection and mitogens affect the expression of the Sp100 autoantigen...
. 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 carcinogenesisCarcinogenesis
Carcinogenesis or oncogenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells...
, aneuploidy
Aneuploidy
Aneuploidy is an abnormal number of chromosomes, and is a type of chromosome abnormality. An extra or missing chromosome is a common cause of genetic disorders . Some cancer cells also have abnormal numbers of chromosomes. Aneuploidy occurs during cell division when the chromosomes do not separate...
, and neuroprotection
Neuroprotection
Neuroprotection within the nervous system protects neurons from apoptosis or degeneration, for example following a brain injury or as a result of chronic neurodegenerative diseases....
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).
Interactions
RANBP2 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with KPNB1
KPNB1
Importin subunit beta-1 is a protein that in humans is encoded by the KPNB1 gene.-Interactions:KPNB1 has been shown to interact with NUP98, Karyopherin alpha 1, KPNA3, Karyopherin alpha 2, SMN1, Parathyroid hormone-related protein, Nucleoporin 62, RANBP2, Ran , RANBP1, NUP50, P53, NUP153 and...
and UBE2I
UBE2I
SUMO-conjugating enzyme UBC9 is a protein that in humans is encoded by the UBE2I gene.-Interactions:UBE2I has been shown to interact with WT1, TOP1, RAD51, Activating transcription factor 2, PIAS1, SALL1, FHIT, RANBP2, Protein inhibitor of activated STAT2, DNMT3A, DNMT3B, Small ubiquitin-related...
.