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34  structures 888  species 2  interactions 1812  sequences 32  architectures

Family: Nucleoporin_C (PF03177)

Summary: Non-repetitive/WGA-negative nucleoporin C-terminal

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Nucleoporin Edit Wikipedia article

Nucleoporin
Identifiers
Symbol Nucleoporin
Pfam PF03177
InterPro IPR004870

Nucleoporins are a family of proteins which are the constituent building blocks of the nuclear pore complex (NPC).[1] 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 in turn allow the transport of water-soluble 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.[2] 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.[3]

Function

Nucleoporins mediate transport of macromolecules between the cell nucleus and cytoplasm in eukaryotes. Certain members of the nucleoporin family form the structural scaffolding of the nuclear pore complex. However, nucleoporins primarily function by interacting with transport molecules known as karyopherins, also known as Kaps[4] These karyopherins interact with nucleoporins that contain FG peptide repeats, that is, they contain repeating sequences of the amino acids phenylalanine (F) and glycine (G).[5] In doing so, karyopherins are able to shuttle their cargo across the nuclear envelope. Nucleoporins are only required for the transport of large hydrophilic molecules above 40 kDa, as smaller molecules pass through nuclear pores via passive diffusion. Nucleoporins play an important role in the transport of mRNA from the nucleus to the cytoplasm after transcription.[6] Depending on their function, certain nucleoporins are localized to a single side of the nuclear pore complex, either cytosolic or nucleoplasmic. Other nucleoporins may be found on both faces. It has been recently shown that FG nucleoporins have specific evolutionary conserved features encoded in their sequences that provide insight into how they regulate the transport of molecules through the nuclear pore complex (NPC).[7][8]

Structure

All nucleoporins share some basic structural components. Nucleoporins aggregate to form a nuclear pore complex, an octagonal ring that traverses the nuclear envelope. There are three distinct types of nucleoporins that each have a unique structure and function. These three types are structural nucleoporins, membrane nucleoporins, and FG-nucleoporins.[3]

Structural nucleoporins form the ring portion of the NPC. They span the membrane of the nuclear envelope and are often referred to as the scaffolding of a nuclear pore. Structural nucleoporins come together to form Y-complexes that are composed of seven nucleoporins. Each nuclear pore contains sixteen Y-complexes for a total of 112 structural nucleoporins. The structure of a Y-complex is highly similar to that of COPII. The relationship of the membrane curvature of a nuclear pore with Y-complexes can be seen as analogous to the budding formation of a COPII coated vesicle.[3]

Membrane nucleoporins are localized to the curvature of a nuclear pore. These proteins are embedded within the nuclear membrane at the region where the inner and outer leaflets connect.

FG-nucleoporins are so named because they contain repeats of the amino acid residues phenylalanine and glycine. FG-repeats are small hydrophobic segments that break up long stretches of hydrophilic amino acids. These FG-repeat segments are found in long random-coil portions of the protein which stretch into the channel of nuclear pores and are primarily responsible for the selective exclusivity of nuclear pore complexes. These segments of FG-nucleoporins form a mass of chains which allow smaller molecules to diffuse through, but exclude large hydrophilic macromolecules. These large molecules are only able to cross a nuclear pore if they are accompanied by a signaling molecule that temporarily interacts with a nucleoporin's FG-repeat segment. FG-nucleoporins also contain a globular portion that serves as an anchor for attachment to the nuclear pore complex.[3]

Nucleoporins have been shown to form various subcomplexes with one another. The most common of these complexes is the p62 complex, which is an assembly composed of NUP62, NUP58, NUP54 and NUP45.[9] Another example of such a complex is the NUP107-160 complex, composed of many different nucleoporins. The NUP107-160 complex has been localized to kinetochores and plays a role in mitosis.[10]

Transport Mechanism

Nucleoporins regulate the transport of macromolecules through the nuclear envelope via interactions with the transporter molecules karyopherins. Karyopherins will bind to their cargo, and reversibly interact with the FG-repeats in nucleoporins. Karyopherins and their cargo are passed between FG-repeats until they diffuse down their concentration gradient and through the nuclear pore complex. Karyopherins can serve as an importin (transporting proteins into the nucleus) or an exportin (transporting proteins out of the nucleus).[3] Karyopherins release of their cargo is driven by Ran, a G protein. Ran is small enough that it can diffuse through nuclear pores down its concentration gradient without interacting with nucleoporins. Ran will bind to either GTP or GDP and has the ability to change a karyopherin's affinity for its cargo. Inside the nucleus, RanGTP causes an importin karyopherin to change conformation, allowing its cargo to be released. RanGTP can also bind to exportin karyopherins and pass through the nuclear pore. Once it has reached the cytosol, RanGTP can be hydrolyzed to RanGDP, allowing the exportin's cargo to be released.[11]

Pathology

Several diseases have been linked to pathologies of nucleoporins, notably diabetes, primary biliary cirrhosis, Parkinson's Disease and Alzheimer's disease. Overexpression of the genes that encode for different nucleoporins also have been shown to be related to the formation of cancerous tumors.

Nucleoporins have been shown to be highly sensitive to glucose concentration changes. Therefore, individuals affected by diabetes often exhibit increased glycosylation of nucleoporins, particularly nucleoporin 62.[2]

Autoimmune conditions such as anti-p62 antibodies, which inhibit p62 complexes have links to primary biliary cirrhosis which destroys the bile ducts of the liver.[9]

Decreases in the production of the p62 complex are common to many neurodegenerative diseases. Modification of the p62 promoter by oxidation is correlated with Alzheimer's disease, Huntington's Disease, and Parkinson's disease among other neurodegenerative disorders.[12]

Increased expression of the NUP88 gene, which encodes for nucleoporin 88, is commonly found in precancerous dysplasias and malignant neoplasms.[13]

Examples

Each individual nucleoporin is named according to its molecular weight (in kilo Daltons). Below are several examples of proteins in the nucleoporin family:

References

  1. ^ Doye V, Hurt E (June 1997). "From nucleoporins to nuclear pore complexes". Current Opinion in Cell Biology. 9 (3): 401–11. doi:10.1016/S0955-0674(97)80014-2. PMID 9159086. 
  2. ^ a b Han I, Oh ES, Kudlow JE (August 2000). "Responsiveness of the state of O-linked N-acetylglucosamine modification of nuclear pore protein p62 to the extracellular glucose concentration". The Biochemical Journal. 350 Pt 1: 109–14. doi:10.1042/0264-6021:3500109. PMC 1221231Freely accessible. PMID 10926833. 
  3. ^ a b c d e Lodish H (2013). Molecular Cell Biology (Seventh ed.). New York: Worth Publ. ISBN 1-4292-3413-X. 
  4. ^ Allen NP, Patel SS, Huang L, Chalkley RJ, Burlingame A, Lutzmann M, Hurt EC, Rexach M (December 2002). "Deciphering networks of protein interactions at the nuclear pore complex". Molecular & Cellular Proteomics. 1 (12): 930–46. doi:10.1074/mcp.t200012-mcp200. PMID 12543930. 
  5. ^ Peters R (2006). "Introduction to nucleocytoplasmic transport: molecules and mechanisms". Methods in Molecular Biology. 322: 235–58. doi:10.1007/978-1-59745-000-3_17. PMID 16739728. 
  6. ^ Marfori M, Mynott A, Ellis JJ, Mehdi AM, Saunders NF, Curmi PM, Forwood JK, Bodén M, Kobe B (September 2011). "Molecular basis for specificity of nuclear import and prediction of nuclear localization". Biochimica et Biophysica Acta. 1813 (9): 1562–77. doi:10.1016/j.bbamcr.2010.10.013. PMID 20977914. 
  7. ^ Peyro M, Soheilypour M, Lee BL, Mofrad MR (November 2015). "Evolutionarily Conserved Sequence Features Regulate the Formation of the FG Network at the Center of the Nuclear Pore Complex". Scientific Reports. 5: 15795. doi:10.1038/srep15795. PMID 26541386. 
  8. ^ Ando D, Colvin M, Rexach M, Gopinathan A (2013-09-16). "Physical motif clustering within intrinsically disordered nucleoporin sequences reveals universal functional features". PLOS One. 8 (9): e73831. doi:10.1371/journal.pone.0073831. PMC 3774778Freely accessible. PMID 24066078. 
  9. ^ a b Miyachi K, Hankins RW, Matsushima H, Kikuchi F, Inomata T, Horigome T, Shibata M, Onozuka Y, Ueno Y, Hashimoto E, Hayashi N, Shibuya A, Amaki S, Miyakawa H (May 2003). "Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study". Journal of Autoimmunity. 20 (3): 247–54. doi:10.1016/S0896-8411(03)00033-7. PMID 12753810. 
  10. ^ Loïodice I, Alves A, Rabut G, Van Overbeek M, Ellenberg J, Sibarita JB, Doye V (July 2004). "The entire Nup107-160 complex, including three new members, is targeted as one entity to kinetochores in mitosis". Molecular Biology of the Cell. 15 (7): 3333–44. doi:10.1091/mbc.E03-12-0878. PMID 15146057. 
  11. ^ Avis JM, Clarke PR (October 1996). "Ran, a GTPase involved in nuclear processes: its regulators and effectors". Journal of Cell Science. 109 ( Pt 10): 2423–7. PMID 8923203. 
  12. ^ Du Y, Wooten MC, Wooten MW (August 2009). "Oxidative damage to the promoter region of SQSTM1/p62 is common to neurodegenerative disease". Neurobiology of Disease. 35 (2): 302–10. doi:10.1016/j.nbd.2009.05.015. PMID 19481605. 
  13. ^ "Entrez Gene: NUP88 nucleoporin 88kDa"

External links

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Non-repetitive/WGA-negative nucleoporin C-terminal Provide feedback

This is the C-termainl half of a family of nucleoporin proteins. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells, and mediate bidirectional nucleocytoplasmic transport, especially of mRNA and proteins. Two nucleoporin classes are known: one is characterised by the FG repeat PF03093; the other is represented by this family, and lacks any repeats. RNA undergoing nuclear export first encounters the basket of the nuclear pore and many nucleoporins are accessible on the basket side of the pore [2].

Literature references

  1. Zhang X, Yang H, Corydon MJ, Zhang X, Pedersen S, Korenberg JR, Chen XN, Laporte J, Gregersen N, Niebuhr E, Liu G, Bolund L; , Genomics 1999;57:144-151.: Localization of a human nucleoporin 155 gene (NUP155) to the 5p13 region and cloning of its cDNA. PUBMED:10191094 EPMC:10191094

  2. Vasu S, Shah S, Orjalo A, Park M, Fischer WH, Forbes DJ; , J Cell Biol 2001;155:339-354.: Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. PUBMED:11684705 EPMC:11684705


This tab holds annotation information from the InterPro database.

InterPro entry IPR007187

This is the C-terminal half of a family of nucleoporin proteins. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells, and mediate bidirectional nucleocytoplasmic transport, especially of mRNA and proteins. Two nucleoporin classes are known: one is characterised by the FG repeat and the other is represented by this family, which lacks any repeats. RNA undergoing nuclear export first encounters the basket of the nuclear pore and many nucleoporins are accessible on the basket side of the pore [PUBMED:10191094, PUBMED:11684705].

Domain organisation

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  Seed
(63)
Full
(1812)
Representative proteomes UniProt
(2626)
NCBI
(3417)
Meta
(1)
RP15
(454)
RP35
(983)
RP55
(1435)
RP75
(1771)
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  Seed
(63)
Full
(1812)
Representative proteomes UniProt
(2626)
NCBI
(3417)
Meta
(1)
RP15
(454)
RP35
(983)
RP55
(1435)
RP75
(1771)
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Curation View help on the curation process

Seed source: Pfam-B_1212 (release 6.5)
Previous IDs: Nucleoporin;
Type: Family
Sequence Ontology: SO:0100021
Author: Mifsud W
Number in seed: 63
Number in full: 1812
Average length of the domain: 460.90 aa
Average identity of full alignment: 16 %
Average coverage of the sequence by the domain: 37.20 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.9 25.9
Trusted cut-off 25.9 25.9
Noise cut-off 25.8 25.7
Model length: 596
Family (HMM) version: 14
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Interactions

There are 2 interactions for this family. More...

Nup84_Nup100 Nucleoporin_C

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Nucleoporin_C domain has been found. There are 34 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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