Nucleoporin 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.

The nuclear pore complex 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 alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform.

Structure

P62 is a serine/threonine rich protein of ~520 amino acids, with tetrapeptide repeats on the amino terminus and a series of alpha-helical regions with hydrophobic heptad repeat

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...

s. P62 assembles into a complex containing 3 addition proteins, p60, p54 and p45 forming the p62 complex of ~235 kDa. Glycosylation

Glycosylation

Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...

 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 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 nucleoporin-93kDa, 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

Anti-p62 antibodies

Anti-p62 antibodies are found in a primary biliary cirrhosis. p62 is also more frequent in Stage IV primary biliary cirrhosis and is prognostic for severe disease. The autoantigen is the nucleoporin 62kDA protein....

 complex are involved in 1 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 cirrhosis

Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...

 and is prognostic for severe disease.

Interactions

Nucleoporin 62 has been shown to interact

Protein-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 XPO1

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:...

, 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...

, TRAF3

TRAF3

TNF receptor-associated factor 3 is a protein that in humans is encoded by the TRAF3 gene.-Interactions:TRAF3 has been shown to interact with CD30, CD27, Lymphotoxin beta receptor, Nucleoporin 62, CD40, TNFSF14, RANK, Caspase 3 and TANK....

, HSF2

HSF2

Heat shock factor protein 2 is a protein that in humans is encoded by the HSF2 gene.-Interactions:HSF2 has been shown to interact with Nucleoporin 62 and HSF1....

 and NUTF2

NUTF2

Nuclear transport factor 2 is a protein that in humans is encoded by the NUTF2 gene.-Interactions:NUTF2 has been shown to interact with Nucleoporin 62 and Ran .-Further reading:...

.

Further reading