SERTM2, also known as the Serine Rich And Transmembrane Domain Containing 2, is a protein which in humans is encoded by the SERTM2 gene. The SERTM2 protein is a transmembrane protein located in the intracellular membrane and active in membrane-bound organelles. SERTM2 expression has been linked to metastatic prostate tumors, prostate carcinomas and renal cell carcinomas.
Gene
The SERTM2 gene in humans is located on the positive strand of the X chromosome (Xq23), spanning 10,755 base pairs. The SERTM2 gene has three total exons. There is one known transcript or isoform that spans 4,612 base pairs.
Aliases SERTM2 is also known as:
Serine-Rich And Transmembrane Domain-Containing 2 (SERTM2) Long Intergenic Non-Protein Coding RNA 890 (LINC00890) CARDEL (Cardiac Development Long non-coding RNA)
Protein
The SERTM2 protein is 90 amino acids long. This protein has a predicted molecular weight of 10 kDa and an isoelectric point of 6. The human SERTM2 protein structure contains two topological domains: extracellular and cytoplasmic.SERTM2 (SERTM2 - serine rich and transmembrane domain containing 2) [https://www.ncbi.nlm.nih.gov/gene/401613] These domains are connected by a transmembrane domain within a confirmed alpha helix. The human protein contains a disordered region at the tail of the protein. Despite having serine-rich in its common name, the protein was not found to have abundance of serine or any other amino acid when compared to other human proteins.
Post-translational modifications
The human SERTM2 protein has one confirmed post-translational modification at the 11th position. The asparagine at that position undergoes N-linked glycosylation, or the attachment of an oligosaccharide to a nitrogen atom on the asparagine side chain.
Expression RNA-sequencing and human tissue profiling has found that SERTM2 is expressed primarily in the endometrium prostate, and liver of humans at moderate level. SERTM2 is found to be upregulated in cardiac progenitor cells compared to mesoderm cells and in fetal cells versus adult heart tissue using RNA-sequencing data. Using knockout and overexpression experiments, it was found that both the knockout and overexpression of SERTM2 results in low cardiomyocyte yield, suggesting that expression must be carefully regulated during cellular differentiation for normal cardiac development to occur and resulted in the nickname CARDEL (Cardiac Development Long non-coding RNA).
Homologs and evolution The human SERTM2 has no paralogs. SERTM2 orthologs are found in mammals, birds, reptiles, amphibians, and some fish. The earliest known SERTM2 gene appeared 462 million years ago in the catshark, a cartilaginous fish. The gene is hard to find in fish, with only two other known appearances in the tiger barb and the Chinese sucker fish, two bony fish. SERTM2 became more established in amphibians 352 million years ago, and its orthologs are found throughout modern reptiles, birds, mammals, and primates.
Table 1: Human serine-rich and transmembrane-domain containing 2 (SERTM2) gene orthologs. Orthologs are sorted first by date of divergence from the human gene, then by similarity to the human sequence. Common NameScientific NameAccession NumberTaxonomical GroupSequence Length (amino acids)Date of Divergence (MYA)% identicalPrimataHumanHomo sapiensNP_001341402.1Primates90-100Ring-tailed lemurLemur cattaXP_045393689.1Primates907493Beluga whaleDelphinapterus leucasXP_030615360.1Cetacea909492MouseMus musculusNP_001341422.1Rodentia898791Big brown batEptesicus fuscusXP_054573025.1Chiroptera909481Common wombatVombatus ursinusXP_027691215.1Marsupial9016081AvesBlue titCyanistes caeruleusXP_023773484.1Aves9131976ChickenGallus gallusXP_046795767.1Aves9231973ReptiliaAlligatorAlligator mississippiensisXP_059588794.1Crocodilia9231979Burmese pythonPython bivittatusXP_025020345.1Squamata9231975Softshell turtlePelodiscus sinensisXP_025033828.1Testudines9231960AmphibiansMicrocaecilia unicolorMicrocaecilia unicolorXP_030065343.1Gymnophiona9135268Two-lined caeciliansRhinatrema bivittatumXP_029463498.1Gymnophiona9335267Common frogRana temporariaXP_040179805.1Anura9235270Fish/SharksTiger barbPuntigrus tetrazonaXP_043094501.1Osteichthyes10342924Chinese sucker fishMyxocyprinus asiaticusXP_051542736.1Osteichthyes10842921CatsharkScyliorhinus caniculaXP_038632174.1Chondrichthyes8946242
Clinical significance Metastatic tumors in the prostate have been shown to have 3-fold more expression of SERTM2 than primary tumors, suggesting that overexpression of SERTM2 may be linked to the metastatic nature of prostate tumors. SERTM2 overexpression has been observed in tumor microenvironment of androgen receptor pathway-positive adenocarcinoma of the prostate (ARPC). In comparison to ARPC, SERTM2 expression is lower in the tumor microenvironment of neuroendocrine prostate carcinomas (NEPC), a more severe type of prostate cancer.
References