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Transmembrane Protein 122
TMEM122 is a protein that, in humans, is encoded by the gene Transmembrane Protein 122. TMEM122 is also known by its aliases OOSP2(oocyte secreted protein 2), USP2A(ubiquitin-specific peptidase 2), and PLAC1L(placenta-specific 1-like protein). The longest polypeptide of transmembrane protein 122 consists of 158 amino acids.

Location
TMEM122 is located on chromosome 11 minus strand at 11q12.1. The gene consists of 7636 base pairs and is flanked by OOSP4B(oocyte-secreted protein family member 4B) and MS4A3(membrane-spanning 4-domains A3).

Exons
Homo sapiens oocyte-secreted protein 2(NM_173801.5) has 4 exons.

Protein
Isoforms: Homo sapiens oocyte-secreted protein 2(NP_776162.2) consists of 158 amino acids and has no known isoforms.

Gene Level Regulation
TMEM212 is tissue specific. It is mostly found at high levels in the testis, and expressed lowly and ubiquitously in most tissue types. From sequencing RNAs of 20 human tissues TMEM122 was also found in the brain, and fetal tissues. The Illumina bodyMap2 transcriptome shows RNA expressed in a mixture of 16 tissues and more highly in testis. In fetal development, the RNA is expressed in 10 week adrenal, 20 week adrenal, and a small amount in 20 week stomach.

TMEM212 protein is less abundant than most human proteins.

The human TMEM122 promoter region was then compared to other orthologs of the protein in a multiple sequence alignment. This alignment showed high conservation across species at the FOXK1, FOXO1::FLI1, GFI1, and ETV1 binding sites. These transcription factors function in growth, metabolism, and DNA production suggesting that TMEM122 plays a similar role.

Protein Level Regulation
Motifscan predicted several TMEM122 Protein motifs, including 5 phosphorylation sites, 2 myristylation sites, and a ZP domain. The phosphorylation were included as TMEM122 has been identified as a nuclear protein, however the myristylation sites were ignored as there is no evidence of membrane association. These predicted phosphorylation sites are likely involved in regulation of function, signaling or catalytic activity through induction of conformational changes of TMEM122.

Then 20 other tools were used to analyze TMEM122 post transcriptional modifications. The tests with positive results are indicated in the figure below.

Homology / Evolution
TMEM122 has orthologs in only mammals, not including marsupials and monotremes. No orthologs were found in birds, reptiles, amphibians, bony fish, invertebrates, plants, fungi, viruses, or bacteria. Homo sapiens TMEM122 is most closely related to primates, then any other mammal(Fig. 4). Rodents seem to be the furthest orthologs regardless of their similarity, but this may be due to their shorter lifespan.



Clinical Significance
TMEM122 has been predicted to be located in extracellular region, and bioinformatics analysis suggests that this gene is associated with several biomolecular and biological processes. A recent study which used transcriptome and translatome (T&T) sequencing to examine the effect of the oocyte secreted protein, OOSP2, on human oocyte gene expression demonstrated that OOSP2 induces oocyte maturation through the translational upregulation of many downstream genes. Single-oocyte T&T-seq analyses further elucidated that OOSP2 induces specific signaling pathways, including small GTPases, through translational regulation. Additionally, when the transcriptome of human trophectoderm (TE) cells from day 5 blastocysts was compared to that of single day 3 embryos, TMEM122 was found to be among 100 genes with the highest fold upregulation. This indicates contribution to TE specification and suggests that TMEM122 might also provide new biomarkers for the selection of viable and competent blastocysts. Lastly, in 2016, restriction landmark genomic scanning was used to identify that TMEM122 is also a gene in prostate cancer that had a distinct methylation. This indicates that TMEM122 was likely to be hypomethylated, which results in increased cell proliferation.