| LSMEM2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | LSMEM2 , C3orf45, leucine rich single-pass membrane protein 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 3612240 HomoloGene: 45163 GeneCards: LSMEM2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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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]
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]
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]
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]
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]
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]
Paralogs
LSMEM2 has no known paralogs. [25]
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 |
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]
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]
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]
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.
LSMEM2 has been found to potentially interact with MEP1B, DEFA6, CYP3A43, TBC1D29, KLHL23, ZNF551, c5orf24, CWH43, and PDIA2. [36]
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]
Protein YIF1A is a Yip1 domain family proteins that in humans is encoded by the YIF1A gene.
Interferon-inducible GTPase 5 also known as immunity-related GTPase cinema 1 (IRGC1) is an enzyme that in humans is coded by the IRGC gene. It is predicted to behave like other proteins in the p47-GTPase-like and IRG families. It is most expressed in the testis.
CXorf49 is a protein, which in humans is encoded by the gene chromosome X open reading frame 49(CXorf49).
PRR29 is a protein encoded by the PRR29 gene located in humans on chromosome 17 at 17q23.
Coiled-coil domain containing protein 180 (CCDC180) is a protein that in humans is encoded by the CCDC180 gene. This protein is known to localize to the nucleus and is thought to be involved in regulation of transcription as are many proteins containing coiled-coil domains. As it is expressed most highly in the testes and is regulated by SRY and SOX transcription factors, it could be involved in sex determination.
Transmembrane and coiled-coil domains 4, TMCO4, is a protein in humans that is encoded by the TMCO4 gene. Currently, its function is not well defined. It is transmembrane protein that is predicted to cross the endoplasmic reticulum membrane three times. TMCO4 interacts with other proteins known to play a role in cancer development, hinting at a possible role in the disease of cancer.
Chromosome 16 open reading frame 46 is a protein of yet to be determined function in Homo sapiens. It is encoded by the C16orf46 gene with NCBI accession number of NM_001100873. It is a protein-coding gene with an overlapping locus.
TMEM44 is a protein that in humans is encoded by the TMEM44 gene. DKFZp686O18124 is a synonym of TMEM44.
Testis-expressed protein 9 is a protein that in humans is encoded the TEX9 gene. TEX9 that encodes a 391-long amino acid protein containing two coiled-coil regions. The gene is conserved in many species and encodes orthologous proteins in eukarya, archaea, and one species of bacteria. The function of TEX9 is not yet fully understood, but it is suggested to have ATP-binding capabilities.
Chromosome 4 open reading frame 51 (C4orf51) is a protein which in humans is encoded by the C4orf51 gene.
Cilia- and flagella-associated protein 299 (CFAP299), is a protein that in humans is encoded by the CFAP299 gene. CFAP299 is predicted to play a role in spermatogenesis and cell apoptosis.
Chromosome 1 open reading frame (C1orf167) is a protein which in humans is encoded by the C1orf167 gene. The NCBI accession number is NP_001010881. The protein is 1468 amino acids in length with a molecular weight of 162.42 kDa. The mRNA sequence was found to be 4689 base pairs in length.
Single-pass membrane and coiled-coil domain-containing protein 3 is a protein that is encoded in humans by the SMCO3 gene.
Proline-rich protein 16 (PRR16) is a protein coding gene in Homo sapiens. The protein is known by the alias Largen.
Chromosome 1 open reading frame 185, also known as C1orf185, is a protein that in humans is encoded by the C1orf185 gene. In humans, C1orf185 is a lowly expressed protein that has been found to be occasionally expressed in the circulatory system.
Chromosome 1 Opening Reading Frame 94 or C1orf94 is a protein in human coded by the C1orf94 gene. The function of this protein is still poorly understood.
C12orf24 is a gene in humans that encodes a protein known as FAM216A. This gene is primarily expressed in the testis and brain, but has constitutive expression in 25 other tissues. FAM216A is an intracellular protein that has been predicted to reside within the nucleus of cells. The exact function of C12orf24 is unknown. FAM216A is highly expressed in Sertoli cells of the testis as well as different stage spermatids.
ProteinFAM89A is a protein which in humans is encoded by the FAM89A gene. It is also known as chromosome 1 open reading frame 153 (C1orf153). Highest FAM89A gene expression is observed in the placenta and adipose tissue. Though its function is largely unknown, FAM89A is found to be differentially expressed in response to interleukin exposure, and it is implicated in immune responses pathways and various pathologies such as atherosclerosis and glioma cell expression.
TMEM275 is a protein that in humans is encoded by the TMEM275 gene. TMEM275 has two, highly-conserved, helical trans-membrane regions. It is predicted to reside within the plasma membrane or the endoplasmic reticulum's membrane.
Family with Sequence Similarity 166, member C (FAM166C), is a protein encoded by the FAM166C gene. The protein FAM166C is localized in the nucleus. It has a calculated molecular weight of 23.29 kDa. It also contains DUF2475, a protein of unknown function from amino acid 19–85. The FAM166C protein is nominally expressed in the testis, stomach, and thyroid.
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