Nuclear pore glycoprotein p62 is a protein complex associated with the

nuclear envelope The nuclear envelope, also known as the nuclear membrane, is made up of two lipid bilayer membranes that in eukaryotic cells surround the nucleus, which encloses the genetic material. The nuclear envelope consists of two lipid bilayer membran ...

. The p62 protein remains associated with the

nuclear pore complex The nuclear pore complex (NPC), is a large protein complex giving rise to the nuclear pore. A great number of nuclear pores are studded throughout the nuclear envelope that surrounds the eukaryote cell nucleus. The pores enable the nuclear tra ...

-lamina fraction. p62 is synthesized as a soluble

cytoplasmic The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell and ...

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. The

is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the

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

alpha/beta complex which is involved in the import of proteins containing

nuclear localization signal A nuclear localization signal ''or'' sequence (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 lysin ...

s. Multiple transcript variants of this gene encode a single protein isoform.

Structure

P62 is a

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form when dissolved in water), a carboxyl group (which is in the deprotonated −COO− ...

rich protein of ~520 amino acids, with tetrapeptide repeats on the

amino terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

and a series of

alpha-helical An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the secondary structure of proteins. It is also the most extreme type of l ...

regions with hydrophobic

heptad repeat The heptad repeat is an example of a structural motif that consists of a repeating pattern of seven amino acids: ''a b c d e f g'' H P P H C P C where H represents hydrophobic residues, C represents, typically, charged residues, and P repre ...

s forming

beta-propeller In structural biology, a beta-propeller (β-propeller) is a type of all-β protein architecture characterized by 4 to 8 highly symmetrical blade-shaped beta sheets arranged toroidally around a central axis. Together the beta-sheets form a funnel- ...

domain. P62 assembles into a complex containing 3 addition proteins, p60, p54 and p45 forming the p62 complex of ~235 kDa. ''O''-GlcNAcylation appears to be involved in the assembly and disassembly of p62 into higher order complexes, and a serine/threonine rich linker region between Ser270 to Thr294 appear to be regulatory. The p62 complex is localized to both the nucleoplasmic and cytoplasmic sides of the pore complex and the relative diameter of p62 complex relative to the nuclear pore complex suggests it interacts in pore gating.

Function

P62 appears to interact with

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

during transport out of the nucleus. P62 also interacts with a nuclear transport factor ( NTF2) protein that is involved in trafficking proteins between cytoplasm and nucleus. Another protein, importin (beta) binds to the helical rod section of p62, which also binds NTF2 suggesting the formation of a higher order gating complex. Karyopherin beta2 (transportin), a riboprotein transporter also interacts with p62. P62 also interacts with Nup93, and when Nup98 is depleted p62 fails to assemble with nuclear pore complexes. Mutant pores could not dock/transport proteins with nuclear localization signals or M9 import signals.

Pathology

Antibodies to p62 complex are involved in one or more autoimmune diseases. P62 glycosylation is increased in diabetes and may influence its association with other diseases. p62 is also more frequent in Stage IV

primary biliary cirrhosis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to buil ...

and is prognostic for severe disease.

Interactions

Nucleoporin 62 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with: *

HSF2 Heat shock factor protein 2 is a protein that in humans is encoded by the ''HSF2'' gene. Function HSF2, as well as the related gene HSF1, encodes a protein that binds specifically to the heat-shock element and has homology to HSFs of other sp ...

, *

KPNB1 Importin subunit beta-1 is a protein that in humans is encoded by the ''KPNB1'' gene. Function Nucleocytoplasmic transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. T ...

, *

NUTF2 Nuclear transport factor 2 is a protein that in humans is encoded by the ''NUTF2'' gene. Function The protein encoded by this gene is a cytosolic factor that facilitates protein transport into the nucleus. It interacts with the nuclear pore co ...

, *

TRAF3 TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor ( TRAF) protein family. TRAF proteins associate wit ...

, and *

XPO1 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. History XPO1 (CRM1) originally was identified in the fission yeast ''Schizosacchar ...

, * Nup93.

Structure

Function

Pathology

Interactions

References

Further reading