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 membrane ...

. The p62 protein remains associated with the

nuclear pore complex A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complexes ...

-lamina fraction. p62 is synthesized as a soluble

cytoplasmic In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. Th ...

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 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 membra ...

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 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 membra ...

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 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 repres ...

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 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 Nucleoporin 93 (Nup93) is a protein that in humans is encoded by the ''NUP93'' gene. References Further reading * * * * * * * External links PDBe-KB
provides an overview of all the structure information available in the PDB for Human ...

, 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 build ...

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 using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

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 spe ...

, *

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 with, ...

, 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 ''Schizosaccharom ...

, *