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 DataTissueCerebellumChoroid PlexusWhite MatterCerebral CortexMedulla OblongataPonsThalamusAmygdalaHippocampal FormationMidbrainBasal GangliaHypothalamusSpinal CordTestisOvaryBone MarrowRNA Abundance (nTPM)2.41.71.71.61.61.61.51.41.31.31.21.21.21.50.10.1
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 ProteinsAmino AcidPro (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%1.51.51.51.11.1%1.10.80%0.4Composition of PRR23A Compared to Other Human Proteinsvery richaverageaverageaverageaverageaverageaverageaverageaverageaverageaverageaverageaverageaveragevery poorpooraverageaverageaveragevery 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 USP17L7NameBasisFunctionDEFB106A
Beta-defensin 106ATextmining and Co-expressionBelongs 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 107ATextmining and Co-expressionBelongs to the defensin family which are antimicrobial and cytotoxic peptides made by neutrophils. Enables lipid binding DEFB105A
Beta-defensin 105ATextminingBelongs to the defensin family which are antimicrobial and cytotoxic peptides made by neutrophils. Associated with Familial Hypertrophic Cardiomyopathy 12, and Familial Hypertrophic Cardiomyopathy 6DEFB106B
Beta-defensin 106BTextminingBelongs 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 JTextmining NAFAM90A10P
Putative protein FAM90A10PTextminingBelongs to the FAM90 familySPAG11B
Sperm associated antigen 11BTextminingEncodes 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 22TextminingGene 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 activityUSP17L4
Ubiquitin specific peptidase 17 like family member 4TextminingPredicted to enable cysteine-type endopeptidase activity and thiol-dependent deubiquitinaseUSP17L7
Ubiquitin specific peptidase 17 like family member 7TextminingPredicted 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 PRR23AProteinAccession numberSequence length (Amino Acids)E-valueSequence identity to Human PRR23A Protein (%)Sequence similarity to Human PRR23A Protein (%)PRR23ANP_0011281312660100100PRR23BNP_0010136722655e-14689.891.4PRR23CNP_0011281292621e-11684.686.8
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 PresentGenus and speciesCommon nameTaxonomic groupMedian Date of Divergence (Millions of Years Ago)Accession numberSequence length (Amino Acids)Sequence identity to human protein (%)Sequence similarity to human protein (%)Homo sapiensHumanPrimates0NP_001128131266100100Macaca mulattaRhesus MonkeyPrimates28.8XP_00111383328283.385.5Mus musculusMouseRodentia87NP_00112813225841.353.1Ochotona princepsAmerican PikaLagomorpha87XP_05851300927639.750.8Pteropus alectoBlack Flying FoxChiroptera94XP_0069072572736369.2Sturnira hondurensisHonduran Yellow-Shouldered BatChiroptera94XP_03691705927056.964.1Leptonychotes weddelliiWeddell SealCarnivora94XP_00673426026053.161.7Canis lupus familiarisDogCarnivora94XP_0382884142435359.8Neophocaena asiaeorientalis asiaeorientalisYangtze Finless PorpoiseCetacea94XP_0246064982615361.9Hippopotamus amphibius kibokoEast African HippopotamusHippopotamidae94XP_05759377026351.960.5Equus caballusHorsePerissodactyla94XP_02347706327959.668.1Camelus ferusWild Bactrian CamelTylopoda94XP_03234344825856.463.5Phacochoerus africanusCommon WarthogSuiformes94XP_04760813726247.357.4Moschus berezovskiiDwarf Musk DeerRuminantia94XP_05527628429145.254.2Talpa occidentalisSpanish MoleTalpidae94XP_03738256226454.164.4Sorex araneusCommon ShrewSoricidae94XP_05498076221741.646.8Erinaceus europaeusEuropean HedgehogErinaceidae94XP_06003990827427.840.6Elephas maximus indicusIndian ElephantProboscidea99XP_04972616923553.458.6Loxodonta africanaAfrican Savanna ElephantProboscidea99XP_00342000423553.458.6Orycteropus afer aferAardvarkTubulidentata99XP_00794573324352.958
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