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 PROSER2 

PROSER2, also known as proline and serine rich 2 or c10orf47, is a gene which encodes proline and serine rich 2 protein. It is found in band 14 of the short arm (p) of chromosome 10. This gene is 48,880 bases in length and is 3,360 base pairs in length after transcription to mRNA. It is oriented on the plus strand of DNA and has 5 exons. 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 13 regulatory elements including: a 2,198 bp promoter, two CTCF binding sites, five promoter flanking regions, and five enhancers, in addition to several more predicted enhancers. 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 6.74.

 PROSER2  Transcript 

 Proline and Serine rich 2 Protein 

The true function of proline and serine rich 2 protein is currently unknown. 143 organisms have orthologs with the human PROSER2. Previous experimentation through two-hybrid screens, reconstituted complex, and Affinity Capture-MS has found that PROSER2 interacts with several other genes including: ACTB, APP, EPS8, POT1, STK24, and YTHDC1. 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 

 Evolutionary History 

Orthologous Space:

The orthologous space for PROSER2 is fairly large. The most distant ortholog of the human PROSER2 is the elephant shark, ''Callorhinchus milii. The gram-negative bacteria species, Mesorhizobium loti'', also appears in a BLAST search, but has a slightly high e value (0.27) and likely does not represent a true evolutionary connection. Therefore, 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:

Text-based searches and a BLAT and BLAST against the human genome demonstrate that no paralogs exist for PROSER2. Therefore, it does not belong to a gene family.

Conserved Regions:

Multiple sequence alignments demonstrated that the 3’ end of the proline-serine rich 2 protein is highly conserved in all relatives (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 avaialble 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. This indicates that the SARG domain is responsible for a critical and potentially life-sustaining function in all primates through cartilaginous fishes. 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.

Evolutionary Pattern:

PROSER2 is a fast evolving gene, similar to Fibrinogen (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.

 Potential Function 

PROSER2 may be a biomarker of epithelial cell, breast, prostate, ovarian, lung, brain, and blood cancers as demonstrated in several US Patents.

 PROSER2  Reagents