Biology:PROB1

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Short description: Protein-coding gene in the species Homo sapiens

Proline-rich basic protein 1 (PROB1) is a protein encoded by the PROB1 gene located on human chromosome 5, open reading frame 65. PROB1 is also known as C5orf65 and weakly similar to basic proline-rich protein.[1][2]

Gene

Characteristics

The PROB1 gene is 3251 bp long and contains a single exon.[2]

Location

The PROB1 gene is located on human chromosome 5, cytogenetic band 5q31.2.[3]

mRNA

Expression

PROB1 is expressed in 89 types of tissue in the human body,[4] with highest expression in the skeletal muscle of the leg and cardiac muscle of the heart.[5] While mRNA expression is somewhat ubiquitous and was also elevated in the spinal cord, cerebrum, and lymphocytes, measurable protein expression was only recorded in cardiac and skeletal muscle.[6]

Protein

PROB1 is composed of 1015 amino acids. It contains two proline-rich regions, which compose the majority of the protein, and a domain of unknown function (DUF).[3]

Structure

Predicted tertiary structure of PROB1 generated by I-Tasser[7] and rendered in PyMOL.[8] The dark blue indicates prolines and yellow marks the DUF. The alpha helices are colored green, beta sheets are colored light blue, and random coils are colored pink.

Predicted secondary structures for PROB1 reveal that the protein is mostly composed of random coils, with a small percentage of alpha helices and beta sheets present.[9] This is likely due to the properties of proline; its large size, ring structure, and confined phi angle cause it to disrupt secondary structure formation. The DUF, which resides in the second proline-rich region of the protein, is also predicted to be completely composed of random coils. A tertiary structure prediction for PROB1 was generated using I-Tasser[7] and rendered in PyMOL;[8] overall, the protein displays an elongated structure.

Sub-cellular Localization

Analysis of protein structure, post-translational modifications, and localization signals reveals that PROB1 has no transmembrane domains and is an intracellular protein. Immunohistochemistry indicates its localization to the nucleoplasm of the cell.[10]

Post-translational Modifications

An array of post-translational modifications were found for PROB1, including an S-palmitolyation site[11] and a multitude of overlapping O-GlcNAcylation[12] and phosphorylation sites.[13] A representation containing a subset of the predicted modifications was generated using Dog 2.0[14] and is shown below.

Schematic of the PROB1 protein annotated with predicted post-translational modifications, created using Dog 2.0.[14]














Interactions

PROB1 has been found to be coexpressed with proteins SPATA24 and JADE2, but no notable functional protein interactions with PROB1 are known at this time.[15]

Homology

A subset of the mammalian orthologs of PROB1 predicted by BLAST.

Paralogs

There are no known human paralogs of PROB1 to date.[16][17]

Orthologs

PROB1 has only mammalian orthologs. Its most distant ortholog is the marsupial Vombatus ursinus (common wombat), which is estimated to have diverged about 159 million years ago as dated by TimeTree.[18] A subset of the multitude of orthologs produced by BLAST[16] is shown in the accompanying table.

Clinical Significance

PROB1 is implicated in keratoconus, which causes collagen-related degeneration of the cornea. Variants of PROB1 in the 5q31.1-q35.3 linkage region completely segregated with the keratoconus phenotype in a study utilizing segregation analysis methodology.[19] Additionally, PROB1 expression is shown to be significantly elevated in several disease states, including head and neck cancer[20] and prostate inflammation.[21]

References

  1. ↑ European Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics. (2019, January 16). Proline-rich basic protein 1. Retrieved from https://www.uniprot.org/uniprot/E7EW31
  2. ↑ 2.0 2.1 Proline-rich basic protein 1 [Homo sapiens]. (2018, June 24). Retrieved from https://www.ncbi.nlm.nih.gov/protein/NP_001155018.1.
  3. ↑ 3.0 3.1 "PROB1 Gene". https://genecards.weizmann.ac.il/v3/cgi-bin/carddisp.pl?gene=PROB1. 
  4. ↑ CALIPHO Team - SIB - Swiss Institute of Bioinformatics. (2018, September 3). PROB1 - Proteomics. Retrieved from https://www.nextprot.org/entry/NX_E7EW31/proteomics
  5. ↑ The Human Protein Atlas. (2015). PROB1. Retrieved from https://www.proteinatlas.org/ENSG00000228672-PROB1/tissue
  6. ↑ "Gene expression for PROB1". 2019. https://gtexportal.org/home/gene/PROB1. 
  7. ↑ 7.0 7.1 Zhang, Yang. "I-TASSER server for protein structure and function prediction.". https://zhanglab.ccmb.med.umich.edu/I-TASSER/. 
  8. ↑ 8.0 8.1 The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC.
  9. ↑ "Predicted secondary structure of PROB1". 2016. https://npsa-prabi.ibcp.fr/cgi-bin/npsa_automat.pl?page=/NPSA/npsa_sopma.html. 
  10. ↑ Atlas Antibodies. Anti-PROB1 Antibody (HPA060103). Retrieved from https://atlasantibodies.com/products/PROB1-antibody-HPA060103   
  11. ↑ The CUCKOO Workgroup. (2019, May 1). GPS-Lipid - Prediction of Lipid Modifications (S-Palmitoylation, N-Myristoylation, S-Farnesylation, S-Geranylgeranylation). Retrieved from http://lipid.biocuckoo.org/presult.php
  12. ↑ DTU Bioinformatics. (2017, January 2). YinOYang 1.2. Retrieved from http://www.cbs.dtu.dk/services/YinOYang/
  13. ↑ MyHits. Sigrist CJ, Cerutti L, de Castro E, Langendijk-Genevaux PS, Bulliard V, Bairoch A, Hulo N. PROSITE, a protein domain database for functional characterization and annotation. Nucleic Acids Res. 2010; 38(Database issue):D161-6
  14. ↑ 14.0 14.1 The CUCKOO Workgroup. (2014, February 26). DOG 2.0 - Protein Domain Structure Visualization. Retrieved from http://dog.biocuckoo.org/
  15. ↑ STRING Consortium. (2019). STRING. Retrieved from https://string db.org/cgi/input.pl?sessionId=AQ4nteBhjSOX&input_page_show_search=on EMBL-EBI. (2019).
  16. ↑ 16.0 16.1 BLAST, https://blast.ncbi.nlm.nih.gov/Blast.cgi
  17. ↑ Kent WJ. BLAT - the BLAST-like alignment tool. Genome Res. 2002 Apr;12(4):656-64.
  18. ↑ Institute for Genomics and Evolutionary Medicine. The Timescale of Life. Retrieved from http://www.timetree.org/
  19. ↑ Karolak, J. A., Gambin, T., Pitarque, J. A., Molinari, A., Jhangiani, S., Stankiewicz, P., . . . Gajecka, M. (2016). Variants in SKP1, PROB1 and IL17B genes at keratoconus 5q31.1–q35.3 susceptibility locus identified by whole-exome sequencing. European Journal of Human Genetics,25(1), 73-78. doi:10.1038/ejhg.2016.130
  20. ↑ Lachmann, A. Retrieved from https://amp.pharm.mssm.edu/archs4/gene/PROB1#tissueexpression
  21. ↑ Prob1 - Model for inflammatory signaling in prostate epithelium based on expression of a constitutively active version of IκB kinase 2 (IKK2ca). Retrieved from https://www.ncbi.nlm.nih.gov/geoprofiles/79454671



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