PROSER2, also known as proline and serine rich 2, is a protein that in humans is encoded by the PROSER2 gene. PROSER2, or c10orf47 (Chromosome 10 open reading frame 47), is found in band 14 of the short arm of chromosome 10 (10p14) and contains a highly conserved SARG domain. It is a fast evolving gene with two paralogs, c1orf116 and specifically androgen-regulated gene protein isoform 1. The PROSER2 protein has a currently uncharacterized function however, in humans, it may play a role in cell cycle regulation, reproductive functioning, and is a potential biomarker of cancer.
Gene
This gene is 48,880 bases in length and is 3,360 base pairs in length after transcription to mRNA. PROSER2 has 5 splice variants, 3 of which are alternatively spliced and 2 of which are unspliced forms. It contains an upstream in-frame stop codon and a 2,000 bp promoter.
Locus
PROSER2 is located on the tenth chromosome (10p14). It is oriented on the plus strand of DNA and has 5 exons.
PROSER2 Transcript
Homology and Evolution
Orthologous Space
The orthologous space for PROSER2 is fairly large, as 143 organisms are reported to have orthologs with the human PROSER2. The most distant ortholog of the human PROSER2 is the elephant shark, Callorhinchus milii. The most distant relatives of humans with PROSER2 are fish and sharks (cartilaginous fishes). For this same reason, it can be inferred that PROSER2 originated in vertebrates.
Paralogous Space
The human PROSER2 gene has two paralogs: c1orf116 and specifically androgen-regulated gene protein isoform 1.
Conserved Regions
Multiple sequence alignments demonstrated that the 3’ end of the proline-serine rich 2 protein is highly conserved in both distant and close homologs. These widely conserved amino acids found in all primates, mammals, reptiles, birds, amphibians, fish, and sharks for which sequences are available include: R421, G406, V409, A424, L425, L428, G429, and L430. It can be noted that these highly conserved amino acids comprise much of the 3’ end of the specifically androgen-regulated gene protein (SARG) domain. The 5’ end of the proline-serine rich 2 protein is highly conserved in close relatives of humans including all primates, mammals, reptiles, and birds for which sequences are available. PROSER2 has an even balance of basic and acidic residues which are conserved throughout all homologs.
Evolutionary Pattern
PROSER2 is a fast evolving gene, similar to Fibrinogen alpha subunit (FGA). It aligns almost perfectly with Fibrinogen’s evolutionary history and is much farther away from the evolutionary timeline of Cytochrome C (CYCS) which is evolving more slowly than PROSER2 or FGA. Gene duplication of PROSER2 occurred approximately in fish which diverged from humans 436.8 MYA.
Proline and Serine Rich 2 Protein
In Homo sapiens, PROSER2 encodes the proline and serine-rich protein 2 which is 435 amino acids in length and has a molecular weight of 45,802 Da. This protein has a fairly neutral basal isoelectric point of 6.81. The proline and serine rich 2 protein contains a conserved SARG (specifically androgen-regulated gene protein) domain that spans 388 amino acids within PROSER2. The SARG domain belongs to the pfam15385 family of genes. Its true function has yet to be elucidated, but it is a suspected androgen receptor because it is up-regulated in the presence of androgens, but not glucocorticoids. The SARG domain is highly expressed in the prostate where PROSER2 has also been reported.
Protein Internal Structure
Post-Translational Modifications
PROSER2 contains 35 predicted Serine phosphorylation sites, as well as 2 predicted Threonine phosphorylation sites on conserved residues. It is also predicted to contain 2 SUMO Interaction Motifs, 2 S-Palmitoylation sites, as well as 2 GalNac O-glycosylation sites all located on or near highly conserved amino acids. These modifications may change the folding and function of the protein which is predicted to be localized to the nucleus.
Predicted Secondary Structure
PROSER2’s structure is currently uncharacterized. However, it is likely to contain 4 alpha helices and 5 domains of beta sheets which are conserved across all mammalian homologs. Based on its structural features and post-translational modifications, it is predicted to be a soluble protein secreted from the nucleus via a non-classical secretion pathway.
Function
The function of proline and serine rich 2 protein is currently unknown. However, it is listed in several U.S. patents as a potential biomarker of cancer.