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SERTM2

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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.[1][2] SERTM2 expression has been linked to metastatic prostate tumors, prostate carcinomas and renal cell carcinomas.[3][4]

Gene

SERTM2 labelled at location Xq23

The SERTM2 gene in humans is located on the positive strand of the X chromosome (Xq23), spanning 10,755 base pairs.[5] The SERTM2 gene has three total exons. There is one known transcript or isoform that spans 4,612 base pairs.[6]

Aliases

SERTM2 is also known as:

  • Serine-Rich And Transmembrane Domain-Containing 2 (SERTM2) [5]
  • Long Intergenic Non-Protein Coding RNA 890 (LINC00890) [5]
  • CARDEL (Cardiac Development Long non-coding RNA)[7]

Protein

Predicted tertiary structure prediction of the SERTM2 protein in humans, Microcaecilia unicolor, alligators, and wombats. Blue = high confidence, yellow = low confidence. Made using the AlphaFold Protein Structure Database.[8][9][10]

The SERTM2 protein is 90 amino acids long. This protein has a predicted molecular weight of 10 kDa and an isoelectric point of 6.[11][12] The human SERTM2 protein structure contains two topological domains: extracellular and cytoplasmic.[13] These domains are connected by a transmembrane domain within a confirmed alpha helix.[8][9][10][12] The human protein contains a disordered region at the tail of the protein.[12] 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.[11]

Post-translational modifications

Diagram of human SERTM2 protein highlighting its transmembrane domain. The N-terminus is extracellular, and the C-terminus is intracellular. Made using Protter.[14]

The human SERTM2 protein has one confirmed post-translational modification at the 11th position.[6] The asparagine at that position undergoes N-linked glycosylation, or the attachment of an oligosaccharide to a nitrogen atom on the asparagine side chain.[15]

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.[6] 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.[7] Using knockout and overexpression experiments, it was found that 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).[7]

Homologs and evolution

The human SERTM2 has no paralogs. SERTM2 orthologs are found in mammals, birds, reptiles, amphibians, and some fish.[13] 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.[12]

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.[12]

Common Name Scientific Name Accession Number Taxonomical Group Sequence Length (amino acids) Date of Divergence

(MYA)

% identical
Primata Human Homo sapiens NP_001341402.1 Primates 90 - 100
Ring-tailed lemur Lemur catta XP_045393689.1 Primates 90 74 93
Beluga whale Delphinapterus leucas XP_030615360.1 Cetacea 90 94 92
Mouse Mus musculus NP_001341422.1 Rodentia 89 87 91
Big brown bat Eptesicus fuscus XP_054573025.1 Chiroptera 90 94 81
Common wombat Vombatus ursinus XP_027691215.1 Marsupial 90 160 81
Aves Blue tit Cyanistes caeruleus XP_023773484.1 Aves 91 319 76
Chicken Gallus gallus XP_046795767.1 Aves 92 319 73
Reptilia Alligator Alligator mississippiensis XP_059588794.1 Crocodilia 92 319 79
Burmese python Python bivittatus XP_025020345.1 Squamata 92 319 75
Softshell turtle Pelodiscus sinensis XP_025033828.1 Testudines 92 319 60
Amphibians Microcaecilia unicolor Microcaecilia unicolor XP_030065343.1 Gymnophiona 91 352 68
Two-lined caecilians Rhinatrema bivittatum XP_029463498.1 Gymnophiona 93 352 67
Common frog Rana temporaria XP_040179805.1 Anura 92 352 70
Fish/Sharks Tiger barb Puntigrus tetrazona XP_043094501.1 Osteichthyes 103 429 24
Chinese sucker fish Myxocyprinus asiaticus XP_051542736.1 Osteichthyes 108 429 21
Catshark Scyliorhinus canicula XP_038632174.1 Chondrichthyes 89 462 42

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.[3] SERTM2 overexpression has been observed in tumor microenvironment of androgen receptor pathway-positive adenocarcinoma of the prostate (ARPC).[4] In comparison to ARPC, SERTM2 expression is lower in the tumor microenvironment of neuroendocrine prostate carcinomas (NEPC), a more severe type of prostate cancer.[4]

References

  1. ^ Alliance of Genome Resources. "SERTM2". Retrieved 28 September 2023.
  2. ^ Watanabe, Ryuta; Miura, Noriyoshi; Kurata, Mie; Kitazawa, Riko; Kikugawa, Tadahiko; Saika, Takashi (January 2023). "Spatial Gene Expression Analysis Reveals Characteristic Gene Expression Patterns of De Novo Neuroendocrine Prostate Cancer Coexisting with Androgen Receptor Pathway Prostate Cancer". International Journal of Molecular Sciences. 24 (10): 8955. doi:10.3390/ijms24108955. ISSN 1422-0067. PMC 10219300. PMID 37240308.
  3. ^ a b Chandran, Uma R.; Ma, Changqing; Dhir, Rajiv; Bisceglia, Michelle; Lyons-Weiler, Maureen; Liang, Wenjing; Michalopoulos, George; Becich, Michael; Monzon, Federico A. (2007-04-12). "Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process". BMC Cancer. 7 (1): 64. doi:10.1186/1471-2407-7-64. ISSN 1471-2407. PMC 1865555. PMID 17430594.
  4. ^ a b c Watanabe, Ryuta; Miura, Noriyoshi; Kurata, Mie; Kitazawa, Riko; Kikugawa, Tadahiko; Saika, Takashi (2023-05-18). "Spatial Gene Expression Analysis Reveals Characteristic Gene Expression Patterns of De Novo Neuroendocrine Prostate Cancer Coexisting with Androgen Receptor Pathway Prostate Cancer". International Journal of Molecular Sciences. 24 (10): 8955. doi:10.3390/ijms24108955. ISSN 1422-0067. PMC 10219300. PMID 37240308.
  5. ^ a b c GeneCards (Aug 2, 2023). "SERTM2 Gene - Serine Rich And Transmembrane Domain Containing 2". Retrieved 28 September 2023.
  6. ^ a b c National Library of Medicine. "Serine rich and transmembrane domain containing 2 (SERTM2) [Homo sapiens (human)], Gene". Retrieved 28 September 2023.
  7. ^ a b c Pereira, Isabela T.; Gomes-Júnior, Rubens; Hansel-Frose, Aruana; Liu, Man; Soliman, Hossam A.N.; Chan, Sunny S.K.; Dudley, Samuel C.; Kyba, Michael; Dallagiovanna, Bruno (19 February 2023). "Cardiac Development Long non-coding RNA (CARDEL) is activated during human heart development and contributes to cardiac specification and homeostasis". doi:10.1101/2023.02.19.529122. S2CID 257052580.
  8. ^ a b "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk. Retrieved 2023-12-14.
  9. ^ a b Jumper, John; Evans, Richard; Pritzel, Alexander; Green, Tim; Figurnov, Michael; Ronneberger, Olaf; Tunyasuvunakool, Kathryn; Bates, Russ; Žídek, Augustin; Potapenko, Anna; Bridgland, Alex; Meyer, Clemens; Kohl, Simon A. A.; Ballard, Andrew J.; Cowie, Andrew (August 2021). "Highly accurate protein structure prediction with AlphaFold". Nature. 596 (7873): 583–589. Bibcode:2021Natur.596..583J. doi:10.1038/s41586-021-03819-2. ISSN 1476-4687. PMC 8371605. PMID 34265844.
  10. ^ a b Varadi, Mihaly; Anyango, Stephen; Deshpande, Mandar; Nair, Sreenath; Natassia, Cindy; Yordanova, Galabina; Yuan, David; Stroe, Oana; Wood, Gemma; Laydon, Agata; Žídek, Augustin; Green, Tim; Tunyasuvunakool, Kathryn; Petersen, Stig; Jumper, John (2022-01-07). "AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models". Nucleic Acids Research. 50 (D1): D439–D444. doi:10.1093/nar/gkab1061. ISSN 0305-1048. PMC 8728224. PMID 34791371.
  11. ^ a b "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2023-12-07.
  12. ^ a b c d e "Home - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-10-23.
  13. ^ a b SERTM2 (SERTM2 - serine rich and transmembrane domain containing 2) [https://www.ncbi.nlm.nih.gov/gene/401613]
  14. ^ Wollscheid Lab (2018). Protter [Computer Software]. https://wlab.ethz.ch/protter/
  15. ^ Lowenthal, Mark S.; Davis, Kiersta S.; Formolo, Trina; Kilpatrick, Lisa E.; Phinney, Karen W. (2016-07-01). "Identification of novel N-glycosylation sites at non-canonical protein consensus motifs". Journal of Proteome Research. 15 (7): 2087–2101. doi:10.1021/acs.jproteome.5b00733. ISSN 1535-3893. PMC 5100817. PMID 27246700.
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