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LSMEM2

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LSMEM2
Identifiers
AliasesLSMEM2, C3orf45, leucine rich single-pass membrane protein 2
External IDsMGI: 3612240; HomoloGene: 45163; GeneCards: LSMEM2; OMA:LSMEM2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

132228

434436

Ensembl

ENSG00000179564

ENSMUSG00000103409

UniProt

Q8N112

n/a

RefSeq (mRNA)

NM_001304385
NM_153215

NM_001081244

RefSeq (protein)

NP_001291314
NP_694947

n/a

Location (UCSC)Chr 3: 50.28 – 50.29 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

Leucine rich single-pass membrane protein 2 is a single-pass membrane protein rich in leucine, that in humans is encoded by the LSMEM2 gene (also known as c3orf45).[4] The LSMEM2 protein is conserved in mammals, birds, and reptiles.[5] In humans, LSMEM2 is found to be highly expressed in the heart, skeletal muscle and tongue.[6][4]

Gene

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LSMEM2 is also known as c3orf45.[4] It is found at human chromosome loci 3p21 on the plus strand from bases 50,277,907-50,288,116.[4] This gene is 1,434 base pairs long and has four exon regions.[4] Nearby genes include SEMA3B and IFRD2.[4]

mRNA

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LSMEM2 has two different isoforms, isoform 1 and 2.[4] 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.[4] Isoform 1 is three base pairs and one amino acid longer than isoform 2 at the exon 2 and exon 3 junction.[7]

Protein

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The LSMEM2 protein has two isoforms.[8] Isoform 1 has an alanine added after amino acid 57, otherwise the two isoforms are identical.[7] It has a predicted MW of 17.8 kDa and isoelectric point of 5.7 pI.[9] LSMEM2 is predicted to have one transmembrane region which is composed of 50% leucine and considered leucine rich.[10] 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.[11] It is found to have one domain, Domain of unknown function 4714 (DUF4714), spanning from amino acid 13 to 161.[12]

Predicted primary sequence, regions and post-translational modifications of the LSMEM2 protein.[13]
Predicted intracellular/cytoplasmic, transmembrane, and extracellular/lumenal regions of the human LSMEM2 protein.[14]

Post-translational Modifications

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LSMEM2 is predicted to have an acetylation and palmitoylation site near the N-terminus of the protein.[15][16] It is also predicted to have various phosphorylation and O-GlcNAc sites throughout the predicted intracellular/cytosolic region of the protein.[17][18] LSMEM2 has a predicted N-glycosylation site at amino acids 155,156, and 157 in the probable extracellular/lumenal region. [19]

Schematic illustration displaying the predicted regions, domains, and post-translational modifications of the LSMEM2 protein.[20][21]

Structure

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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.[22] 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.[23]

Predicted tertiary structure of the human LSMEM2 protein by I-TASSER.[24] The structure is colored in the order of the rainbow from the N-terminus to the C-terminus.

Homology

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Paralogs

LSMEM2 has no known paralogs.[25]

Orthologs

LSMEM2 has 168 orthologs total, 131 of them being mammals, the other orthologs consist of aves and reptiles[5] The LSMEM2 protein is conserved in mammals with 71.3% chemically-similar sequences.[25] 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.[26]

Genus and Species Common Name Accession Number[27] Length (amino acids) Sequence Identity[28] Sequence Similarity[25] Date of Divergence (million years ago)[29]
Homo sapiens Human NP_001291314.1 163 100% 100% 0
Acinonyx jubatus Cheetah XP_014932576 149 84.11% 85.30% 105
Ornithorhynchus anatinus Platypus XP_028906032 172 67.97% 71.30% 177
Gallus gallus Chicken XP_015148980.1 159 50.00% 41.20% 312
Chrysemys picta Painted turtle XP_005308817 172 39.53% 44.10% 312


Evolution

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LSMEM2 was found to emerge about 312 million years ago (MYA).[29] 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.[30] LSMEM2 is predicted to change 1% every 3.9 million years.[28][29]

Expression

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LSMEM2 is found to be highly expressed in the human heart and skeletal muscle with RNA Sequencing and Microarray data.[4][31] It is also found to be highly expressed in the heart during human fetal development.[4]

Regulation of Expression

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The promoter region for LSMEM2 is predicted by El Dorado to be the 2,328 basepairs directly upstream from the LSMEM2 gene.[32] A notable transcription factor predicted to bind to this promoter is the Brachyury gene, mesoderm developmental factor.[33] This transcription factor is involved in regulating the development of the notochord.[34]

Function

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LSMEM2 has been predicted to be involved in Mitochondrial ATP synthesis coupled proton transport.[35] However, the function of LSMEM2 is still not fully understood by the scientific community.

Interacting Proteins

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LSMEM2 has been found to potentially interact with MEP1B, DEFA6, CYP3A43, TBC1D29, KLHL23, ZNF551, c5orf24, CWH43, and PDIA2.[36]

Clinical Significance

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LSMEM2 was discovered to be down-regulated in the myotubes of patients with FSHD, a form of muscular dystrophy.[37] LSMEM2 was also predicted to be involved in the pathway for sepsis-induced myopathy, although more research is required to determine its exact role[38]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000179564 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ a b c d e f g h i j "LSMEM2 leucine rich single-pass membrane protein 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-04-30.
  5. ^ a b "LSMEM2 orthologs". NCBI. Retrieved 2020-05-01.
  6. ^ "LSMEM2 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 24 August 2021.
  7. ^ a b "leucine-rich single-pass membrane protein 2 isoform 1 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-04-30.
  8. ^ "leucine-rich single-pass membrane protein 2 isoform 2 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-04-30.
  9. ^ "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2020-04-30.
  10. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-04-30.
  11. ^ "TMpred Server". embnet.vital-it.ch. Archived from the original on 2019-03-05. Retrieved 2020-04-30.
  12. ^ "MOTIF: Searching Protein Sequence Motifs". www.genome.jp. Retrieved 2020-04-30.
  13. ^ "Homo sapiens leucine rich single-pass membrane protein 2 (LSMEM2), transcript variant 2, mRNA". 2019-05-31. {{cite journal}}: Cite journal requires |journal= (help)
  14. ^ "Protter - interactive protein feature visualization". wlab.ethz.ch. Retrieved 2020-05-03.
  15. ^ "CSS-Palm - Palmitoylation Site Prediction". csspalm.biocuckoo.org. Archived from the original on 2009-02-15. Retrieved 2020-05-03.
  16. ^ "NetAcet 1.0 Server". www.cbs.dtu.dk. Retrieved 2020-05-03.
  17. ^ "YinOYang 1.2 Server". www.cbs.dtu.dk. Retrieved 2020-05-03.
  18. ^ "NetPhos 3.1 Server". www.cbs.dtu.dk. Retrieved 2020-05-03.
  19. ^ "NetNGlyc 1.0 Server". www.cbs.dtu.dk. Retrieved 2020-05-01.
  20. ^ "leucine-rich single-pass membrane protein 2 isoform 2 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-05-03.
  21. ^ "ExPASy: SIB Bioinformatics Resource Portal - Categories". www.expasy.org. Retrieved 2020-05-03.
  22. ^ "PHYRE2 Protein Fold Recognition Server". www.sbg.bio.ic.ac.uk. Retrieved 2020-04-30.
  23. ^ "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2020-05-03.
  24. ^ "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2020-05-03.
  25. ^ a b c "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2020-05-01.
  26. ^ "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-05-01.
  27. ^ "Home - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-04-30.
  28. ^ a b "EMBOSS Needle < Pairwise Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2020-05-01.
  29. ^ a b c "TimeTree :: The Timescale of Life". www.timetree.org. Retrieved 2020-05-01.
  30. ^ "Home - HomoloGene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-05-01.
  31. ^ "GEO Profile Links for Gene (Select 132228) - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2020-05-01.
  32. ^ "Genomatix: Annotation & Analysis". www.genomatix.de. Retrieved 2020-05-01.
  33. ^ "Genomatix: MatInspector Input". www.genomatix.de. Retrieved 2020-05-03.
  34. ^ Reference, Genetics Home. "TBXT gene". Genetics Home Reference. Retrieved 2020-05-03.
  35. ^ "ARCHS4". amp.pharm.mssm.edu. Retrieved 2020-05-03.
  36. ^ "LSMEM2 protein (human) - STRING interaction network". string-db.org. Retrieved 2020-05-03.
  37. ^ Dmitriev P, Bou Saada Y, Dib C, Ansseau E, Barat A, Hamade A, et al. (October 2016). "DUX4-induced constitutive DNA damage and oxidative stress contribute to aberrant differentiation of myoblasts from FSHD patients" (PDF). Free Radical Biology & Medicine. 99: 244–258. doi:10.1016/j.freeradbiomed.2016.08.007. PMID 27519269. S2CID 24609856.
  38. ^ Ning YL, Yang ZQ, Xian SX, Lin JZ, Lin XF, Chen WT (February 2020). "Bioinformatics Analysis Identifies Hub Genes and Molecular Pathways Involved in Sepsis-Induced Myopathy". Medical Science Monitor. 26: e919665. doi:10.12659/MSM.919665. PMC 7009723. PMID 32008037.
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