PRR23A

Proline-Rich Protein 23A is a protein that is encoded by the Proline-Rich 23A (PRR23A) gene.

Locus
The human PRR23A gene is on chromosome 3 at position 3q23 and is located on the antisense strand. The gene is encoded from position 139,003,962 to 139,006,268. It consists on 1 exon and spans 2,307 base pairs. Other genes in the neighborhood include: FOXL2NB, FOXL2, PRR23B, and PRR23C. The FOXL2NB gene has tissue enriched expression in ovaries, and PRR23A has demonstrated expression in the ovary as well. Aliases for PRR23A include: Proline-Rich 23A, Proline-Rich Protein 23A, and UPF0572 Protein ENSP00000372650. Two of those genes, PRR23B and PRR23C, are paralogs to PRR23A.

Gene expression
PRR23A is primarily expressed at low levels in the brain and testis. There were also very low levels of PRR23A expression detected in ovary and bone marrow tissue. Genes typically show high expression in the testis during RNA sequencing since it is a highly transcriptionally active tissue due to its function of sperm production. However, some researchers have noted that this testis tissue expression of PRR23A may be legitimate since PRR23 family genes are thought to play a role in male reproduction. Furthermore, brain and testis tissue share biochemical characteristics and express a large number of common genes. This may also explain why PRR23A expression has been found at similar levels within the brain and testis.

mRNA transcript
Since PRR23A consists of 1 exon, there are no alternative splicing products. This also means that the 1 known isoform in humans has an mRNA sequence of 2,307 nucleotides which matches the length of the PRR23A gene. mRNA typically contain a 5' UTR with a median length of 170 nucleotides in humans, but the human PRR23A mRNA sequence does not contain a 5' UTR. Instead, the FASTA sequence for human PRR23A begins with the start codon ATG. Although, the 5' UTR is not translated, it plays a major regulatory role for the translation of coding sequence nucleotides to their amino acids that go on to form a protein structure. Therefore, it is unlikely that human PRR23A does not have this region, and that its upstream 5' UTR sequence could be obtained through further sequencing research.

Protein
Human PRR23A consists of 266 amino acids, has a predicted molecular weight of 28.2 kDal, and a predicted basal isoelectric point of 4.57. PRR23A, as its name implies, is enriched with the amino acid proline. Therefore, PRR23A belongs to the category of proteins called proline-rich proteins. PRR23A contains less asparagine, threonine, and lysine compared to other human proteins. This protein composition for PRR23A is generally conserved across species.

Secondary and tertiary structure
Human PRR23A is mainly a disordered protein with small stretches of beta strands and alpha helices forming. There are 2 known disordered regions at the beginning and the end of the protein. There are 6 regions from the beginning-middle of the protein sequence that are predicted to form beta strands, and when folded into the tertiary structure are in the middle of the predicted protein structure. There is 1 possible transmembrane domain that is located in 1 of these beta strands. Some proteins can create transmembrane beta barrels when a beta sheet curls on itself to make a tube that goes through a membrane, so the PRR23A could exhibit this phenomenon . There are 2 regions towards the end of the protein sequence that are predicted to form alpha helices, and when folded into a tertiary structure are in the middle of the predicted protein structure.

Subcellular localization
Antibody detection in human stomach cells has shown that PRR23A localizes in the membrane and cytoplasm. Further investigation of the PRR23A protein sequence has also identified a small transmembrane region towards the beginning of the protein, and signal sequences for the ER membrane, nucleus, and mitochondria.

Interacting proteins
PRR23A does not have very many known interactions. The most significant protein interactions for human PRR23A are DEFB106A and DEFB107A which have been determined though co-expression data and textmining. Co-expression data has also shown that DEFB106A and DEFB107A interact with one another. This means that PRR23A, DEFB106A, and DEFB107A have been observed to be correlated in expression across a large number of experiments. DEFB105A, DEFB106B, IQCJ, FAM90A10P, SPAG11B, PRSS22, USP17L4, and USP17L7 are also thought to interact with PRR23A. The basis of these interactions were determined through textmining, so further experiments such as the yeast two-hybrid assay should be conducted to increase the confidence of these protein interactions.

Post-translational modifications
Post-translational modifications for human PRR23A include: phosphorylation,  acetylation, myristoylation, sulfonation, SUMOylation, and glycosylation. The glycosylation site supports the identified transmembrane region and ER membrane subcellular localization of PRR23A since proteins that are glycosylated are typically membrane bound and expressed in the ER.

Paralogs
There are 2 known paralogs of PRR23A: PRR23B and PRR23C.

Orthologs
PRR23A orthologs are only found in placental mammals. No PRR23A orthologs have been identified in marsupials, monotremes, birds, reptiles, amphibians, fish, or invertebrates.

Evolution
PRR23A first appeared within placental mammals which evolved 78-129 million years ago. Then, placental mammals began to diversify into two the major lineages of Atlantogenata and Boreoeutheria which emerged 90-100 million years ago. PRR23A orthologs can be found within both of these major lineages, and several subgroups that evolved as well. Despite PRR23A's recent emergence in the long run of evolutionary history, it is evolving at a very rapid rate.



Function
PRR23A has demonstrated gene expression within the testis through increased mRNA levels, and so have the other PRR23 family genes. This expression indicates that PRR23A may have a role within the male reproductive system. The larger family of proline-rich proteins have a large range of functions including: energy provisions, antistress responses, calcium binding in saliva, structure support, and many others. One subgroup called small proline-rich proteins (SPRRs) are antimicrobial proteins that direct bacterial membrane disruption.

Clinical significance and pathology
Epigenetic modifications of PRR23A have been shown to impact maternal early-pregnancy serum ferritin concentrations. 2 CpG sites within human PRR23A have been identified: cg02806645 and cg06322988. When these locations are methylated, a decrease in serum ferritin concentrations during early-pregnancy was observed. Low levels of ferritin are a sign of iron deficiency which is especially important to monitor during pregnancy. Therefore, the decreased expression of PRR23A though methylation silencing is associated with iron deficiency.