Agnoprotein is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

expressed by some members of the

polyomavirus ''Polyomaviridae'' is a family of DNA viruses whose natural hosts are mammals and birds. As of 2024, there are eight recognized genera. Fourteen species are known to infect humans, while others, such as Simian Virus 40, have been identified i ...

family from a

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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

BK virus The BK virus, also known as Human polyomavirus 1, 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 ...

and

JC virus Human polyomavirus 2, commonly referred to as the JC virus or John Cunningham virus, is a type of human polyomavirus. It was identified by electron microscopy in 1965 by ZuRhein and Chou, and by Silverman and Rubinstein. It was later isolated in ...

, 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 monkey, Platyrrhini (New World mon ...

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 is found to cause tumors in humans and animals, but most ofte ...

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 over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

residues long, respectively. Among other known polyomavirus

genome 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 genes, other functional regions of the genome such as ...

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 chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

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 biosynthe ...

, 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 amin ...

, 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 sequences in nucleic acids (DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ( ...

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

amphipathic In chemistry, an amphiphile (), or amphipath, is a chemical compound possessing both hydrophilic (''water-loving'', polar) and lipophilic (''fat-loving'', nonpolar) properties. Such a compound is called amphiphilic or amphipathic. Amphiphilic c ...

alpha helices 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 ...

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

dimerization In chemistry, dimerization is the process of joining two identical or similar molecular entities by bonds. The resulting bonds can be either strong or weak. Many symmetrical chemical species are described as dimers, even when the monomer is u ...

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 relativ ...

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

phosphorylated In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

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

post-translational modifications In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translation (biolog ...

have been detected.

Expression

Agnoprotein is expressed from a region of the circular viral

called the agnogene, an

open reading frame In molecular biology, reading frames are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible reading frames ...

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 ma ...

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 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 a ...

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 membranes ...

. It is also detectable in the

cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...

; in the case of JC virus, nuclear-localized agnoprotein comprises 15–20% of the total agnoprotein expressed.

Function

Agnoprotein is a regulatory protein 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 viruses without agnoprotein are generally either incapable of proliferation or are vastly impaired; some such mutants can produce

virion A virion (plural, ''viria'' or ''virions'') is an inert virus particle capable of invading a Cell (biology), cell. Upon entering the cell, the virion disassembles and the genetic material from the virus takes control of the cell infrastructure, t ...

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 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 classical mec ...

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, replication, and

encapsidation {{Short pages monitor