# PRR23A

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

## 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.
PRR23A Gene Expression Includes the Tissues that PRR23A RNA Transcript has Been Identified in Through RNA Sequencing Data :
| Tissue | Cerebellum | Choroid Plexus | White Matter | Cerebral Cortex | Medulla Oblongata | Pons | Thalamus | Amygdala | Hippocampal Formation | Midbrain | Basal Ganglia | Hypothalamus | Spinal Cord | Testis | Ovary | Bone Marrow |
| RNA Abundance (nTPM) | 2.4 | 1.7 | 1.7 | 1.6 | 1.6 | 1.6 | 1.5 | 1.4 | 1.3 | 1.3 | 1.2 | 1.2 | 1.2 | 1.5 | 0.1 | 0.1 |

## 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.
Human PRR23A Protein CompositionIncludes Percent Composition of Each Amino Acid for Human PRR23A and How that Percent Composition Compares to Other Human Proteins :
| Amino Acid | Pro (P) | Ala (A) | Leu (L) | Ser (S) | Glu (E) | Gly (G) | Val (V) | Arg (R) | Asp (D) | Phe (F) | Gln (Q) | Ile (I) | Cys (C) | His (H) | Thr (T) | Lys (K) | Met (M) | Try (Y) | Trp (W) | Asn (N) |
| Composition of Human PRR23A | 16.2% | 10.5% | 10.5% | 9.8% | 9.0% | 7.5% | 7.1% | 6.4% | 5.3% | 3.4% | 3.0% | 2.3% | 1.5 | 1.5 | 1.5 | 1.1 | 1.1% | 1.1 | 0.80% | 0.4 |
| Composition of PRR23A Compared to Other Human Proteins | very rich | average | average | average | average | average | average | average | average | average | average | average | average | average | very poor | poor | average | average | average | very poor |

### 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.
Summary of PRR23A Protein InteractionsIncludes Info About DEFB106A, DEFB107A, DEFB105A, DEFB106B, IQCJ, FAM90A10P, SPAG11B, PRSS22, USP17L4, and USP17L7 :
| Name | Basis | Function |
| DEFB106A Beta-defensin 106A | Textmining and Co-expression | Belongs to the defensin family which are antimicrobial and cytotoxic peptides made by neutrophils. Associated with Diamond-Blackfan Anemia15, Mandibulofacial with Dysostosis, and Keratomalacia. Enables lipopolysaccharide binding, protein binding, heparin binding and CCR2 chemokine receptor binding |
| DEFB107A Beta-defensin 107A | Textmining and Co-expression | Belongs to the defensin family which are antimicrobial and cytotoxic peptides made by neutrophils. Enables lipid binding |
| DEFB105A Beta-defensin 105A | Textmining | Belongs to the defensin family which are antimicrobial and cytotoxic peptides made by neutrophils. Associated with Familial Hypertrophic Cardiomyopathy 12, and Familial Hypertrophic Cardiomyopathy 6 |
| DEFB106B Beta-defensin 106B | Textmining | Belongs to the defensin family which are antimicrobial and cytotoxic peptides made by neutrophils. Associated with Diamond-Blackfan Anemia15, Mandibulofacial with Dysostosis. Enables lipopolysaccharide binding, protein binding, heparin binding and CCR2 chemokine receptor binding |
| IQCJ IQ motif containing J | Textmining | NA |
| FAM90A10P Putative protein FAM90A10P | Textmining | Belongs to the FAM90 family |
| SPAG11B Sperm associated antigen 11B | Textmining | Encodes several androgen-dependent, epididymis-specific secretory proteins. Thought to be involved in sperm maturation. Associated with Small Intestine Lymphoma and Herpes Zoster Oticus |
| PRSS22 Serine protease 22 | Textmining | Gene encodes a member of the trypsin family of serine-proteases. Preferentially cleaves the synthetic substrate H-D-Leu-Thr-Arg-pNA compared to tosyl-Gly-Pro-Arg-pNA. Enables serine-type endopeptidase activity and peptidase activator activity |
| USP17L4 Ubiquitin specific peptidase 17 like family member 4 | Textmining | Predicted to enable cysteine-type endopeptidase activity and thiol-dependent deubiquitinase |
| USP17L7 Ubiquitin specific peptidase 17 like family member 7 | Textmining | Predicted to enable cysteine-type endopeptidase activity and thiol-dependent deubiquitinase |

## 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.

## Homology
### Paralogs

There are 2 known paralogs of PRR23A: PRR23B and PRR23C.
Summary of PRR23 Family Proteins Found in HumansSimilarity of Human PRR23B and PRR23C to PRR23A :
| Protein | Accession Number | Sequence Length (Amino Acids) | E-value | Sequence Identity to Human PRR23A Protein (%) | Sequence Similarity to Human PRR23A Protein (%) |
| PRR23A | NP_001128131 | 266 | 0 | 100 | 100 |
| PRR23B | NP_001013672 | 265 | 5e-146 | 89.8 | 91.4 |
| PRR23C | NP_001128129 | 262 | 1e-116 | 84.6 | 86.8 |

### Orthologs

PRR23A orthologs are only found in placental mammals. No PRR23A orthologs have been identified in marsupials, monotremes, birds, reptiles, amphibians, fish, or invertebrates.
PRR23A OrthologsContains Some Select PRR23A Orthologs from Each Major Mammalian Group Where PRR23A is Present :
| Genus and Species | Common Name | Taxonomic Group | Median Date of Divergence (Millions of Years Ago) | Accession Number | Sequence Length (Amino Acids) | Sequence Identity to Human Protein (%) | Sequence Similarity to Human Protein (%) |
| Homo sapiens | Human | Primates | 0 | NP_001128131 | 266 | 100 | 100 |
| Macaca mulatta | Rhesus Monkey | Primates | 28.8 | XP_001113833 | 282 | 83.3 | 85.5 |
| Mus musculus | Mouse | Rodentia | 87 | NP_001128132 | 258 | 41.3 | 53.1 |
| Ochotona princeps | American Pika | Lagomorpha | 87 | XP_058513009 | 276 | 39.7 | 50.8 |
| Pteropus alecto | Black Flying Fox | Chiroptera | 94 | XP_006907257 | 273 | 63 | 69.2 |
| Sturnira hondurensis | Honduran Yellow-Shouldered Bat | Chiroptera | 94 | XP_036917059 | 270 | 56.9 | 64.1 |
| Leptonychotes weddellii | Weddell Seal | Carnivora | 94 | XP_006734260 | 260 | 53.1 | 61.7 |
| Canis lupus familiaris | Dog | Carnivora | 94 | XP_038288414 | 243 | 53 | 59.8 |
| Neophocaena asiaeorientalis asiaeorientalis | Yangtze Finless Porpoise | Cetacea | 94 | XP_024606498 | 261 | 53 | 61.9 |
| Hippopotamus amphibius kiboko | East African Hippopotamus | Hippopotamidae | 94 | XP_057593770 | 263 | 51.9 | 60.5 |
| Equus caballus | Horse | Perissodactyla | 94 | XP_023477063 | 279 | 59.6 | 68.1 |
| Camelus ferus | Wild Bactrian Camel | Tylopoda | 94 | XP_032343448 | 258 | 56.4 | 63.5 |
| Phacochoerus africanus | Common Warthog | Suiformes | 94 | XP_047608137 | 262 | 47.3 | 57.4 |
| Moschus berezovskii | Dwarf Musk Deer | Ruminantia | 94 | XP_055276284 | 291 | 45.2 | 54.2 |
| Talpa occidentalis | Spanish Mole | Talpidae | 94 | XP_037382562 | 264 | 54.1 | 64.4 |
| Sorex araneus | Common Shrew | Soricidae | 94 | XP_054980762 | 217 | 41.6 | 46.8 |
| Erinaceus europaeus | European Hedgehog | Erinaceidae | 94 | XP_060039908 | 274 | 27.8 | 40.6 |
| Elephas maximus indicus | Indian Elephant | Proboscidea | 99 | XP_049726169 | 235 | 53.4 | 58.6 |
| Loxodonta africana | African Savanna Elephant | Proboscidea | 99 | XP_003420004 | 235 | 53.4 | 58.6 |
| Orycteropus afer afer | Aardvark | Tubulidentata | 99 | XP_007945733 | 243 | 52.9 | 58 |

### 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.