Agnoprotein is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

expressed by some members of the

polyomavirus ''Polyomaviridae'' is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while othe ...

family from a

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

called the agnogene. Polyomaviruses in which it occurs include two human polyomaviruses associated with disease,

BK virus The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunocompromised and the immunosuppressed. BK virus is an abb ...

and

JC virus ''Human polyomavirus 2'', commonly referred to as the JC virus or John Cunningham virus, is a type of human polyomavirus (formerly known as papovavirus). It was identified by electron microscopy in 1965 by ZuRhein and Chou, and by Silverman and ...

, as well as the

simian The simians, anthropoids, or higher primates are an infraorder (Simiiformes ) of primates containing all animals traditionally called monkeys and apes. More precisely, they consist of the parvorders New World monkeys (Platyrrhini) and Cat ...

polyomavirus

SV40 SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors in animals, but most often ...

Sequence and structure

Agnoprotein is typically quite short: examples from

, and

are 62, 71, and 66

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

residues long, respectively. Among other known polyomavirus

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...

s with a predicted agnogene, the length of the resulting predicted protein varies considerably, from as short as 30 to as long as 154 residues. It contains a highly

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, ...

central

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthesi ...

, a "bipartite"

nuclear localization sequence 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 lysines ...

at the

N-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 ami ...

, and highly basic amino acids at both termini. Comparison of the sequences of different viral agnoproteins suggests

sequence conservation In evolutionary biology, conserved sequences are identical or similar Sequence (biology), sequences in nucleic acids (DNA sequence, DNA and RNA) or peptide sequence, proteins across species (homology (biology)#Orthology, orthologous sequences), ...

toward the N-terminus with greater variability toward the C-terminus. Formation of

amphipathic An amphiphile (from the Greek αμφις amphis, both, and φιλíα philia, love, friendship), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'') properties. Such a compoun ...

alpha helices The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues earli ...

under laboratory conditions has been demonstrated for part of the sequence believed to have a role in mediating dimerization and

oligomerization In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relati ...

of the protein. The BK, JC, and SV40 agnoproteins have all been experimentally demonstrated to be

phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

''in vivo'', which appears to improve both protein stability and viral propagation, but no other

post-translational modifications Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosome ...

have been detected.

Expression

Agnoprotein is expressed from a region of the circular viral

called the agnogene, an

open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a Prokaryote, prokaryotic DNA sequence, where only one of the #Six-fra ...

contained in a region of the polyomavirus genome that codes for the

viral capsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may ...

proteins and is known as the "late region" because it is expressed late in the cycle of viral infection and replication. The agnogene and its protein product received their name (from the Greek '' agnosis'', "without knowledge") because the presence of the open reading frame and corresponding RNA was detected before the existence of the protein product was confirmed.

Cellular localization

Agnoprotein is consistently detected in the

cytoplasm 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. ...

of infected cells, with particularly high concentrations in the

perinuclear space 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 ...

. It is also detectable in the cell nucleus; in the case of JC virus, nuclear-localized agnoprotein comprises 15–20% of the total agnoprotein expressed.

Function

Agnoprotein is a

regulatory protein Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wide ...

required for efficient proliferation of the viruses in which it is present, although many polyomaviruses do not have the gene. Its functions are poorly characterized even in well-studied viruses.

Null mutant A null allele is a nonfunctional allele (a variant of a gene) caused by a genetic mutation. Such mutations can cause a complete lack of production of the associated gene product or a product that does not function properly; in either case, the alle ...

viruses without agnoprotein are generally either incapable of proliferation or are vastly impaired; some such mutants can produce

virion A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky ...

s, but they may be deficient in exiting the host cell or lack appropriately packaged genetic material. Agnoprotein null mutants can successfully proliferate if agnoprotein is present in ''trans''. Although the protein is not found in mature

s, there is some evidence that it can be

secrete 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classica ...

d from infected cells, even before viral exit, and taken up by neighboring uninfected cells. Agnoprotein has been associated with a number of processes in the viral life cycle, including

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

, replication, and

encapsidation {{Short pages monitor