Proline-rich protein 30 explained

Proline-rich protein 30 (PRR30 or C2orf53) is a protein in humans that is encoded for by the PRR30 gene.[1] PRR30 is a member in the family of Proline-rich proteins characterized by their intrinsic lack of structure. Copy number variations in the PRR30 gene have been associated with an increased risk for neurofibromatosis.

Gene

The PRR30 gene is located on the short arm of human chromosome 2 at band 2p23.3. It flanked by Prolactin regulatory element binding (PREB) and Transcription Factor 23 (TCF23). The gene has three Exons in total. PRR30 has a length of 2618 base pairs of linear DNA.[2]

Promoter Region

The PRR30 promoter directly flanks the gene and is 1162 base pairs in length.[3]

Transcript

The PRR30 mRNA transcript is 2063 base pairs in length. There are four splice sites total all of which are in the 5’ UTR. There are no known isoforms or alternative splicing of PRR30.

Protein

Human protein PRR30 consists of 412 amino acid residues. It has a molecular weight of 44.7 kdal and an isoelectric point of 10.7.[4] [5] It is proline rich and composed primarily of non-essential amino acids. There is a region of extreme conservation across orthologs spanning from residues 187 to 321.[6] PRR30 appears to be subcellularly localized to the cell nucleus.[7] NetNES predicts a nuclear export signal from residues 213 to 216.[8] IntAct predicts that PRR30 interacts with Human Testis Protein 37 or TEX37, Cystiene Rich Tail Protein 1 (CYSRT1), and Keratin Associated Protein 6-2 (KRTAP6-2).[9] PRR30 is predicted to undergo post-translational modifications in the form of glycosylation and phosphorylation.[10] [11] [12]

Structure

PRR30 is an intrinsically disordered protein (IDP) and lacks any formal tertiary structure or quaternary structure. I-Tasser and Phyre predict minimal coiling throughout PRR30 as a whole. In the region of high conservation, there are predicted alpha helices & beta sheets.[13]

Function

Unstructured proteins like PRR30 are highly variable in function.[14] Other Proline-Rich Proteins have been shown to have an affinity for binding calcium across different tissues in the human body.[15] [16] COACH predicts several ligand binding domains associated with calcium across PRR30. The highest confidence predicted calcium binding domain resides in the area of greatest conservation.[17] [18]

Expression

NCBI EST profiles have shown differential expression across many tissues but increased levels in the human testes and pharynx.[19]

Homology

PRR30 is exclusive to mammals but is not present in all mammals. PRR30 is highly conserved across Primates but shows loss of the gene in members of Rodents and Laurasiatheria.[20] The most distant known ortholog of PRR30 is found in S. harrisii, Tasmanian Devil. The PRR30 gene appears to be evolving relatively fast rate.[21]

Paralogs

There are no known paralogs for PRR30.[22]

Orthologs

Genus & Species[23] Sequence IdentityDate of Divergence (MYA)Sequence Length
Homo sapiens/Human100%0412
Pan paniscus99%6.4412
Pan troglodytes/Chimpanzee99%6.4412
Pongo pygmaeus/Bornean orangutan93%15.2413
Nomascus leucogenys94%19.43412
Gorilla gorilla/Western gorilla96%8.61412
Macaca fascicularis93%28.1412
Papio anubis93%28.1412
Macaca nemestrina93%28.1412
Acinonyx jubatus66%94394
Bos taurus65%94396
Bos indicus65%94396
Heterocephalus glaber57%88373
Cavia porcellus54%88391
Octodon degus61%88402
Mus musculus52%88399
Echinops telfairi61%102313
Erinaceus europaeus57%94375
Tupaia chinensis68%85410
Sorex araneus59%94298
Elephantulus edwardii51%102286
Rhinolophus sinicus68%94359
Miniopterus natalensis63%94396
Myotis brandtii64%94239
Sarcophilus harrisii57%160376

Clinical significance

In recent 2015 study, copy number variation of PRR30 gene was linked to an increase risk for neurofibromatosis. 78% of the patients displaying type 1-associated cutaneous neurofibromas carried an extra copy of the PRR30 gene. No mechanism was described illuminating the correlation.

Notes and References

  1. Lamesch P, Li N, Milstein S, Fan C, Hao T, Szabo G, Hu Z, Venkatesan K, Bethel G, Martin P, Rogers J, Lawlor S, McLaren S, Dricot A, Borick H, Cusick ME, Vandenhaute J, Dunham I, Hill DE, Vidal M . 6 . hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes . Genomics . 89 . 3 . 307–315 . March 2007 . 17207965 . 4647941 . 10.1016/j.ygeno.2006.11.012 .
  2. 7. NCBI (National Center for Biotechnology Information) entry on PRR30 https://www.ncbi.nlm.nih.gov/nuccore/148236530
  3. Web site: Genomatix: Genomatix Genome Browser. www.genomatix.de. en-US. 2017-04-27.
  4. Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S . Methods and algorithms for statistical analysis of protein sequences . Proceedings of the National Academy of Sciences of the United States of America . 89 . 6 . 2002–2006 . March 1992 . 1549558 . 48584 . 10.1073/pnas.89.6.2002 . free . 1992PNAS...89.2002B .
  5. [Volker Brendel]
  6. Thompson JD, Higgins DG, Gibson TJ . CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice . Nucleic Acids Research . 22 . 22 . 4673–4680 . November 1994 . 7984417 . 308517 . 10.1093/nar/22.22.4673 .
  7. Web site: PredictProtein - Protein Sequence Analysis, Prediction of Structural and Functional Features. Rost B . www.predictprotein.org. en. 2017-04-28.
  8. la Cour T, Kiemer L, Mølgaard A, Gupta R, Skriver K, Brunak S . Analysis and prediction of leucine-rich nuclear export signals . Protein Engineering, Design & Selection . 17 . 6 . 527–536 . June 2004 . 15314210 . 10.1093/protein/gzh062 . free .
  9. Orchard S, Ammari M, Aranda B, Breuza L, Briganti L, Broackes-Carter F, Campbell NH, Chavali G, Chen C, del-Toro N, Duesbury M, Dumousseau M, Galeota E, Hinz U, Iannuccelli M, Jagannathan S, Jimenez R, Khadake J, Lagreid A, Licata L, Lovering RC, Meldal B, Melidoni AN, Milagros M, Peluso D, Perfetto L, Porras P, Raghunath A, Ricard-Blum S, Roechert B, Stutz A, Tognolli M, van Roey K, Cesareni G, Hermjakob H . 6 . The MIntAct project--IntAct as a common curation platform for 11 molecular interaction databases . Nucleic Acids Research . 42 . Database issue . D358–D363 . January 2014 . 24234451 . 3965093 . 10.1093/nar/gkt1115 .
  10. Blom N, Sicheritz-Pontén T, Gupta R, Gammeltoft S, Brunak S . Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence . Proteomics . 4 . 6 . 1633–1649 . June 2004 . 15174133 . 10.1002/pmic.200300771 . 18810164 .
  11. Blom N, Gammeltoft S, Brunak S . Sequence and structure-based prediction of eukaryotic protein phosphorylation sites . Journal of Molecular Biology . 294 . 5 . 1351–1362 . December 1999 . 10600390 . 10.1006/jmbi.1999.3310 .
  12. Gupta R, Jung E, Brunak S . Prediction of N-glycosylation sites in human proteins.. 2004 .
  13. Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ . The Phyre2 web portal for protein modeling, prediction and analysis . Nature Protocols . 10 . 6 . 845–858 . June 2015 . 25950237 . 5298202 . 10.1038/nprot.2015.053 .
  14. Dunker AK, Lawson JD, Brown CJ, Williams RM, Romero P, Oh JS, Oldfield CJ, Campen AM, Ratliff CM, Hipps KW, Ausio J, Nissen MS, Reeves R, Kang C, Kissinger CR, Bailey RW, Griswold MD, Chiu W, Garner EC, Obradovic Z . 6 . Intrinsically disordered protein . Journal of Molecular Graphics & Modelling . 19 . 1 . 26–59 . 2001 . 11381529 . 10.1016/s1093-3263(00)00138-8 .
  15. Wong RS, Bennick A . The primary structure of a salivary calcium-binding proline-rich phosphoprotein (protein C), a possible precursor of a related salivary protein A . The Journal of Biological Chemistry . 255 . 12 . 5943–5948 . June 1980 . 7380845 . 10.1016/S0021-9258(19)70721-2 . free .
  16. Bennick A . Salivary proline-rich proteins . Molecular and Cellular Biochemistry . 45 . 2 . 83–99 . June 1982 . 6810092 . 10.1007/bf00223503 . 31373141 .
  17. Yang J, Roy A, Zhang Y . BioLiP: a semi-manually curated database for biologically relevant ligand-protein interactions . Nucleic Acids Research . 41 . Database issue . D1096–D1103 . January 2013 . 23087378 . 3531193 . 10.1093/nar/gks966 .
  18. Yang J, Roy A, Zhang Y . Protein-ligand binding site recognition using complementary binding-specific substructure comparison and sequence profile alignment . Bioinformatics . 29 . 20 . 2588–2595 . October 2013 . 23975762 . 3789548 . 10.1093/bioinformatics/btt447 .
  19. Web site: EST Profile - Hs.136555. Group. Schuler. www.ncbi.nlm.nih.gov. 2017-05-04.
  20. Web site: Gene: PRR30 (ENSG00000186143) - Gene gain/loss tree - Homo sapiens - Ensembl genome browser 88. www.ensembl.org. en-gb. 2017-05-06.
  21. Web site: Ortholog Search cegg.unige.ch Computational Evolutionary Genomics Group. www.orthodb.org. 2017-05-06.
  22. Web site: PRR30 Gene - GeneCards PRR30 Protein PRR30 Antibody . GeneCards Human Gene Databas . 2017-04-27.
  23. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ . Basic local alignment search tool . Journal of Molecular Biology . 215 . 3 . 403–410 . October 1990 . 2231712 . 10.1006/jmbi.1990.9999 .

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