Proline-rich protein 21 (PRR21) is a protein of the family of

proline-rich proteins Proline-rich proteins (PRPs) is a class of intrinsically unstructured proteins (IUP) containing several repeats of a short proline-rich sequence. Many tannin-consuming animals secrete a tannin-binding protein (mucin) in their saliva. Tannin-bindin ...

. It is encoded by the PRR21 gene, which is found on human

chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost e ...

, band 2q37.3. The gene exists in several species, both

vertebrates Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

and

invertebrates Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...

, including humans. However, the protein have few conserved regions among species.

Structure

PRR21 consists of 389

amino acids 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 am ...

or 1170

base pairs A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

, all found within one

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

. Like other proline-rich proteins, it contains a repeated sequence of amino acids that contains several

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

residues. The tandemly repeated sequence of PRR21 is 28 amino acids long and is repeated in full 11 times, with few variations. A logo displaying the variances of the repeat is shown below. The repeat constitute almost the entire protein, except for the very beginning and a short tail. Repeated sequences of PRR21

Polymorphism

Many

single-nucleotide polymorphism In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently lar ...

s (SNPs) are predicted for the gene, and several of these cause

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense m ...

s. This allows for personal variances within the population, and contribution to the "uniqueness" of each individual.

Post-translational modifications

PRR21 has 28 possible

phosphorylation 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 ...

sites. These follow the patterns of the repeated sequence. 22 out of 28 phosphorylation sites occur at

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 − form un ...

s at positions 9 and 24 in the repeat, both of which are highly conserved. Though, these serines can be changed by SNPs. Phosphorylation generally either activates or inactivates a protein. The protein has a no potential GPI-modification sites. PRR21 is not predicted to interact with any other proteins.

Homology

PRR21 have no

paralogs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

, and few

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

. The orthologs are poorly conserved, as proline-rich proteins lack the need for specificity. Most important is that they have a loose structure and contain many prolines. The repeats often work as spacers only to make the protein big enough to interact with other proteins. Thus, orthologs often look dissimilar.

Functions

There is 99.97% likelihood that PRR21 enters the

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

. PRR21 may be involved in stress responses that are related to phosphorylation of mitochondrial proteins. The gene is ubiquitously expressed, as nearly all

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

cells contain mitochondria. PRR21 may be a salivary protein, as the tandemly repeated sequence constitute almost the entire protein, which is a common feature of salivary proline-rich proteins.

Other proline-rich proteins

There are several kinds of proline-rich proteins, which can include either ''repetitive short sequences'' or ''tandemly repeated sequences''. They have in common that the repeats, and the repeats only, contain unusual amounts of proline. They have a loose structure, which is caused by several features; the prolines have a shape that causes to chain to turn, and especially prevents

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 ear ...

. Also, the proteins contain many positively charged residues that repel each other. This results in loose proteins that are suitable as binding proteins. These binding interactions can be

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, th ...

interactions as proline-rich proteins tend to have exposed hydrophobic regions. The prolines themselves work as additional binding sites for

hydrogen bonds In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a ...

by being strong hydrogen acceptors.

References

{{reflist, 33em Salivary proline-rich proteins