LSMEM2

LSMEM2 is also known as c3orf45. It is found at human chromosome loci 3p21 on the plus strand from bases 50,277,907-50,288,116. This gene is 1,434 base pairs long and has four exon regions. Nearby genes include SEMA3B and IFRD2.

LSMEM2 has two different isoforms, isoform 1 and 2. These two isoforms encode the same protein. Isoform 2 uses an alternate in-frame splice-site in the 5' coding region in comparison to isoform 1. Isoform 1 is three base pairs and one amino acid longer than isoform 2 at the exon 2 and exon 3 junction.{{Cite web|title=leucine-rich single-pass membrane protein 2 isoform 1 [Homo sapiens] - Protein - NCBI|url=https://www.ncbi.nlm.nih.gov/protein/23397473|website=www.ncbi.nlm.nih.gov|access-date=2020-04-30}}

The LSMEM2 protein has two isoforms.{{Cite web|title=leucine-rich single-pass membrane protein 2 isoform 2 [Homo sapiens] - Protein - NCBI|url=https://www.ncbi.nlm.nih.gov/protein/749502278|website=www.ncbi.nlm.nih.gov|access-date=2020-04-30}} Isoform 1 has an alanine added after amino acid 57, otherwise the two isoforms are identical. It has a predicted MW of 17.8 kDa and isoelectric point of 5.7 pI.{{Cite web|title=ExPASy - Compute pI/Mw tool|url=https://web.expasy.org/compute_pi/|website=web.expasy.org|access-date=2020-04-30}} LSMEM2 is predicted to have one transmembrane region which is composed of 50% leucine and considered leucine rich.{{Cite web|title=SAPS < Sequence Statistics < EMBL-EBI|url=https://www.ebi.ac.uk/Tools/seqstats/saps/|website=www.ebi.ac.uk|access-date=2020-04-30}} The N-terminus is predicted to be the cytosolic/intracellular region of the protein, while the C-terminus is predicted as the lumenal/extracellular region.{{Cite web|title=TMpred Server|url=https://embnet.vital-it.ch/software/TMPRED_form.html|website=embnet.vital-it.ch|access-date=2020-04-30|archive-date=2019-03-05|archive-url=https://web.archive.org/web/20190305234532/https://embnet.vital-it.ch/software/TMPRED_form.html|url-status=dead}} It is found to have one domain, Domain of unknown function 4714 (DUF4714), spanning from amino acid 13 to 161.{{Cite web|title=MOTIF: Searching Protein Sequence Motifs|url=https://www.genome.jp/tools/motif/|website=www.genome.jp|access-date=2020-04-30}}

File:Predicted_primary_sequence_of_the_LSMEM2_protein.png

File:Predicted_regions_of_the_human_LSMEM2_protein.png

LSMEM2 is predicted to have an acetylation and palmitoylation site near the N-terminus of the protein.{{Cite web|title=CSS-Palm - Palmitoylation Site Prediction|url=http://csspalm.biocuckoo.org/|website=csspalm.biocuckoo.org|access-date=2020-05-03|archive-date=2009-02-15|archive-url=https://web.archive.org/web/20090215130857/http://csspalm.biocuckoo.org/|url-status=dead}}{{Cite web|title=NetAcet 1.0 Server|url=http://www.cbs.dtu.dk/services/NetAcet/|website=www.cbs.dtu.dk|access-date=2020-05-03}} It is also predicted to have various phosphorylation and O-GlcNAc sites throughout the predicted intracellular/cytosolic region of the protein.{{Cite web|title=YinOYang 1.2 Server|url=http://www.cbs.dtu.dk/services/YinOYang/|website=www.cbs.dtu.dk|access-date=2020-05-03}}{{Cite web|title=NetPhos 3.1 Server|url=http://www.cbs.dtu.dk/services/NetPhos-3.1/|website=www.cbs.dtu.dk|access-date=2020-05-03}} LSMEM2 has a predicted N-glycosylation site at amino acids 155,156, and 157 in the probable extracellular/lumenal region. {{Cite web|title=NetNGlyc 1.0 Server|url=http://www.cbs.dtu.dk/services/NetNGlyc/|website=www.cbs.dtu.dk|access-date=2020-05-01}}

File:Schematic Illustration of the predicted regions and domains of the human LSMEM2 protein.png

The secondary and tertiary structure of LSMEM2 are currently unknown. The secondary structure is predicted as largely alpha-helices for the transmembrane and lumenal/extracellular region.{{Cite web|title=PHYRE2 Protein Fold Recognition Server|url=http://www.sbg.bio.ic.ac.uk/~phyre2/html/page.cgi?id=index|website=www.sbg.bio.ic.ac.uk|access-date=2020-04-30}} The cytoplasmic/intracellular region structure still remains relatively unclear. To the right is a predicted tertiary structure of the human LSMEM2 protein by the I-TASSER software.{{Cite web|title=I-TASSER server for protein structure and function prediction|url=https://zhanglab.ccmb.med.umich.edu/I-TASSER/|website=zhanglab.ccmb.med.umich.edu|access-date=2020-05-03}}

File:Predicted_tertiary_structure_of_the_human_LSMEM2_protein.jpg

Paralogs

LSMEM2 has no known paralogs.{{Cite web|title=BLAST: Basic Local Alignment Search Tool|url=https://blast.ncbi.nlm.nih.gov/Blast.cgi|website=blast.ncbi.nlm.nih.gov|access-date=2020-05-01}}

Orthologs

LSMEM2 has 168 orthologs total, 131 of them being mammals, the other orthologs consist of aves and reptiles The LSMEM2 protein is conserved in mammals with 71.3% chemically-similar sequences. The table below displays features of select orthologs of LSMEM2 of varying evolutionary distance. The predicted transmembrane domain of LSMEM2 is found to be highly conserved in its orthologs.{{Cite web|title=Clustal Omega < Multiple Sequence Alignment < EMBL-EBI|url=https://www.ebi.ac.uk/Tools/msa/clustalo/|website=www.ebi.ac.uk|access-date=2020-05-01}}

LSMEM2 was found to emerge about 312 million years ago (MYA). It has been found to evolve at an intermediate rate when compared to a quickly evolving protein, Fibronectin, and a slowly evolving protein, Cytochrome C.{{Cite web|title=Home - HomoloGene - NCBI|url=https://www.ncbi.nlm.nih.gov/homologene/?term=|website=www.ncbi.nlm.nih.gov|access-date=2020-05-01}} LSMEM2 is predicted to change 1% every 3.9 million years.

LSMEM2 is found to be highly expressed in the human heart and skeletal muscle with RNA Sequencing and Microarray data.{{Cite web|title=GEO Profile Links for Gene (Select 132228) - GEO Profiles - NCBI|url=https://www.ncbi.nlm.nih.gov/geoprofiles?LinkName=gene_geoprofiles&from_uid=132228|website=www.ncbi.nlm.nih.gov|access-date=2020-05-01}} It is also found to be highly expressed in the heart during human fetal development.

The promoter region for LSMEM2 is predicted by El Dorado to be the 2,328 basepairs directly upstream from the LSMEM2 gene.{{Cite web|title=Genomatix: Annotation & Analysis|url=https://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=c39121bfaec685d0f2d3eab437feff44;SHOW_ANNOTATION=LSMEM2;ELDORADO_VERSION=E35R1911|website=www.genomatix.de|access-date=2020-05-01}} A notable transcription factor predicted to bind to this promoter is the Brachyury gene, mesoderm developmental factor.{{Cite web|title=Genomatix: MatInspector Input|url=https://www.genomatix.de/cgi-bin/matinspector_prof/mat_fam.pl?s=e11b995274dcd78b20b2e2dc9b38c815|website=www.genomatix.de|access-date=2020-05-03}} This transcription factor is involved in regulating the development of the notochord.{{Cite web|title=TBXT gene|url=https://ghr.nlm.nih.gov/gene/TBXT|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2020-05-03}}

LSMEM2 has been predicted to be involved in Mitochondrial ATP synthesis coupled proton transport.{{Cite web|title=ARCHS4|url=https://maayanlab.cloud/archs4/gene/LSMEM2|website=amp.pharm.mssm.edu|access-date=2020-05-03}} However, the function of LSMEM2 is still not fully understood by the scientific community.

LSMEM2 has been found to potentially interact with MEP1B, DEFA6, CYP3A43, TBC1D29, KLHL23, ZNF551, c5orf24, CWH43, and PDIA2.{{Cite web|title=LSMEM2 protein (human) - STRING interaction network|url=https://string-db.org/cgi/network.pl?taskId=qR3l0GbziIub|website=string-db.org|access-date=2020-05-03}}

LSMEM2 was discovered to be down-regulated in the myotubes of patients with FSHD, a form of muscular dystrophy.{{cite journal | vauthors = Dmitriev P, Bou Saada Y, Dib C, Ansseau E, Barat A, Hamade A, Dessen P, Robert T, Lazar V, Louzada RA, Dupuy C, Zakharova V, Carnac G, Lipinski M, Vassetzky YS | display-authors = 6 | title = DUX4-induced constitutive DNA damage and oxidative stress contribute to aberrant differentiation of myoblasts from FSHD patients | journal = Free Radical Biology & Medicine | volume = 99 | pages = 244–258 | date = October 2016 | pmid = 27519269 | doi = 10.1016/j.freeradbiomed.2016.08.007 | s2cid = 24609856 | url = https://hal.umontpellier.fr/hal-01804819/file/2016%20Dimitriev%20et%20al.%2C%20DUX4%20induced.pdf }} LSMEM2 was also predicted to be involved in the pathway for sepsis-induced myopathy, although more research is required to determine its exact role{{cite journal | vauthors = Ning YL, Yang ZQ, Xian SX, Lin JZ, Lin XF, Chen WT | title = Bioinformatics Analysis Identifies Hub Genes and Molecular Pathways Involved in Sepsis-Induced Myopathy | journal = Medical Science Monitor | volume = 26 | pages = e919665 | date = February 2020 | pmid = 32008037 | pmc = 7009723 | doi = 10.12659/MSM.919665 | url = https://www.medscimonit.com/abstract/index/idArt/919665 }}

{{reflist}}