TMEM248

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Transmembrane protein 248, also known as C7orf42, is a gene that in humans encodes the TMEM248 protein. This gene contains multiple transmembrane domains and is composed of seven exons.TMEM248 is predicted to be a component of the plasma membrane and be involved in vesicular trafficking. [1] [2] It has low tissue specificity, meaning it is ubiquitously expressed in tissues throughout the human body. Orthology analyses determined that TMEM248 is highly conserved, having homology with vertebrates and invertebrates. TMEM248 may play a role in cancer development. It was shown to be more highly expressed in cases of colon, breast, lung, ovarian, brain, and renal cancers. [3]

Contents

TMEM248
Identifiers
Aliases TMEM248 , C7orf42, transmembrane protein 248
External IDs MGI: 1918917 HomoloGene: 9951 GeneCards: TMEM248
Orthologs
SpeciesHumanMouse
Entrez

55069

71667

Ensembl

ENSG00000106609

ENSMUSG00000053094

UniProt

Q9NWD8

Q3TBN1

RefSeq (mRNA)

NM_017994

NM_001081394
NM_027854

RefSeq (protein)

NP_060464

NP_001074863
NP_082130

Location (UCSC) Chr 7: 66.92 – 66.96 Mb Chr 5: 130.25 – 130.27 Mb
PubMed search [6] [7]
Wikidata
View/Edit Human View/Edit Mouse

Gene

TMEM248 is located at chromosome 7 at location 7q11.21 with 37,327 base pairs, spanning from position 66,921,225 to 66,958,551. [8] [9] It has 7 exons and is located on the sense strand. [9] [10]

Transcript

Figure 1. Bird's eye view of TMEM248 promoter region and gene. Bird's Eye View of TMEM248.png
Figure 1. Bird's eye view of TMEM248 promoter region and gene.

TMEM248 contains 7 exons, seen in Figure 1. A single gene can have multiple isoforms produced by alternative splicing. TMEM248 has four isoforms summarized in Table 1.

Table 1. Isoforms of Homo Sapiens TMEM248 produced by alternative splicing.
Isoform NumberAccession NumberTranscript LengthProtein LengthMolecular Weight
1Q9NWD8-1, [11] NM_017994.5 [12] 4,22931435 kDa
X1XP_024302587.1 [13] 4,24632236 kDa
X2XM_024446821.2 [14] 4,00831435 kDa
X3XM_024446820.2 [15] 4,01031435 kDa

Messenger RNA

Figure 2. Annotated conceptual translation of human TMEM248 Conceptual Translation of Human TMEM248.pdf
Figure 2. Annotated conceptual translation of human TMEM248

An annotated conceptual translation of TMEM248 is seen in Figure 1. TMEM248 mRNA is most highly expressed in the thyroid, endometrium, prostate, testis, and ovaries, though it is ubiquitously expressed at varying levels in most tissue types. [9]

Protein

TMEM248 is a multi-pass component of the membrane and functions in protein binding and vesicular transport. [1] [2] TMEM248 has both low tissue and single cell type specificity, but single cell expression cluster is in macrophages. [16] The polypeptide chain of TMEM248 is 314 amino acids long and the molecular weight is approximately 35 kDa. TMEM248 is threonine-rich, meaning that it has a higher-than-average amount of threonine residues. [17] Additionally, it is a more acidic than basic molecule. [17] The basal isoelectric point of TMEM248 is 5.91 pH.

Subcellular localization

Immunofluorescence staining shows TMEM248 localization to vesicles.The subcellular location of TMEM248 is predicted to be the endoplasmic reticulum membrane, in vesicles, and in the plasma membrane. [18] [19]

Post-translational modifications

Predicted post-translational modifications for TMEM248 protein include glycosylation, ubiquitylation, and phosphorylation. Ubiquitylation at K228, K240, and K245, glycosylation at N80, and phosphorylation at Y13 and S300 were experimentally determined. [10] [20]

Figure 3. TMEM248 domain and post translational modification diagram. P represents phosphorylation sites, Ub represents ubiquitylation sites, and G represents glycosylation sites. TMEM (#) represents predicted transmembrane domains TMEM248 PTM diagram.png
Figure 3. TMEM248 domain and post translational modification diagram. P represents phosphorylation sites, Ub represents ubiquitylation sites, and G represents glycosylation sites. TMEM (#) represents predicted transmembrane domains

Homology and evolution

Homologs of the TMEM248 gene are found in vertebrates and invertebrates. The most distant orthologs of TMEM248 are in echinoderms, mollusks, and arthropods, which diverged approximately 680 million years ago. [22] Orthologs of TMEM248 are not found in annelids, nematodes, cnidarians, sponges, fungi, plants, or bacteria.

Table 2. Summary of selection of TMEM248 orthologs. [23]
Genus and SpeciesCommon nameOrderDoD* (MYA)AccessionLength% Similarity% Identity
Homo sapiensHumanPrimate0NP_060464.1314100100
Mus musculusHouse mouseRodentia87NP_082130.131498.794.6
Phyllostomus discolorPale spear-nosed batChiroptera94XP_02836974031499.496.5
Gallus gallusChickenGaliformes319XP_024997905.132495.290.4
Hirundo rusticaBarn swallowPasseriformes319XP_03993855831495.991.1
Mauremys muticaYellow pond turtleTestudines319XP_04484925831496.292.0
Bufo bufoCommon toadAnura353XP_04027940131594.385.1
Xenopus tropicalisWestern clawed frogAnura353NP_001007494.131593.784.1
Geotrypetes seraphiniGaboon caecilianGymnophiona353XP_03377782131393.988.5
Ictalurus punctatusChannel catfishSiluriformes431XP_01731553231592.181.0
Danio rerioZebrafish (teleost)Cypriniformes431NP_00101354831488.076.5
Triplophysa tibetanaStone loach (ray finned fish)Cypriniformes431KAA071641833288.078.0
Chiloscyllium plagiosumWhite spotted bamboo sharkOrectolobiformes (carpet)464XP_04357447832192.583.8
Carcharodon carchariasGreat white sharkLamniformes (mackerel)464XP_04105384132192.283.8
Strongylocentrotus purpuratusPacific purple sea urchinEchinoida619XP_003725226.230750.934.0
Apostichopus japonicusSea cucumberStichopodidae619PIK58986.124437.019.1
Aplysia californicaCalifornia sea hareAnaspidea680XP_005091558.137243.627.9
Blattella germanicaGerman cockroachBlattodea680PSN49789.127548.430.8
Cryptotermes secundusDrywood termiteIsoptera680XP_023712247.128145.929.8
Parasteatoda tepidariorumCommon house spiderAraneae680XP_042905814.130543.723.6
Mizuhopecten yessoensisYesso scallopPectinida680OWF5215236746.230.1
Plakobranchus ocellatusRing sap sucking slugSaccoglossa680GFO37695.140640.126.5

*DoD = date of divergence; MYA = million years ago.

Figure 4. TMEM248 evolution and corrected sequence divergence compared to fibrinogen a-chain evolution (red) and cyt c evolution (yellow). TMEM248 Evolution.png
Figure 4. TMEM248 evolution and corrected sequence divergence compared to fibrinogen a-chain evolution (red) and cyt c evolution (yellow).

TMEM248 has two paralogs in humans: TMEM219 and insulin-like growth factor binding protein 3 (IGFBP3) receptor isoform 2 precursor. The TMEM219 protein has 34.9% similarity and 21.1% identity to TMEM248. The IGFBP3 receptor isoform 2 precursor protein has 36.4% similarity and 21.9% identity to TMEM248.

TMEM219 is a death receptor that induces apoptosis (a type of programmed cell death) via a caspase-8 dependent mechanism, and the ligand for this receptor is IGFBP3. The TMEM219/IGFBP3 signaling pathway is experimentally shown to regulate pancreatic beta cell function. [24]

Table 3. Selection of Homo sapiens TMEM248 paralogs and their orthologs in other species.
Genus and SpeciesCommon nameOrderDoD (MYA)AccessionLength% Similarity% Identity
Homo sapiens TMEM219HumanPrimate0KAI2578024.121334.921.1
Homo sapiens IGFBP3HumanPrimate0P_001356618.124036.421.9
Mus musculus TMEM219House mouseRodentia87AAH46763.124034.921.1
Mus musculus IGFBP3House mouseRodentia87NP_081103.124036.821.4
Python bivittatus IGFBP3Burmese pythonSquamata319XP_00742439324240.521.8
Geotrypetes seraphini IGFBP3Gaboon caecilianGymnophiona353XP_03380258737332.619.7
Denticeps clupeoides IGFBP3Denticle herringClupeiformes431XP_02884812930040.719.8

Clinical significance

TMEM248 has proposed connections to various forms of cancer. Mutations in the gene have been recorded in tumor samples from stomach, colorectal, lung, bladder, ovarian, endometrial, and breast cancer. [16] Of the tumor samples observed, stomach tumors were most likely to contain mutations of TMEM248. There is relatively higher expression of TMEM248 in colon, breast, lung, ovarian, brain, and renal cancer. [25] Multiple myeloma (cancer of unrestricted B cell proliferation in bone marrow) progression and drug sensitivity could regulate TMEM248 expression. [26] These experimentally determined conclusions implicate TMEM248 playing a role in cell proliferation, and make expression of TMEM248 a potential candidate for more intensive studies in the development of cancer in these organs. However, the TMEM248 gene product is not prognostic for cancer with the current available research.

Related Research Articles

<span class="mw-page-title-main">TMEM98</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 98 is a single-pass membrane protein that in humans is encoded by the TMEM98 gene. The function of this protein is currently unknown. TMEM98 is also known as UNQ536/PRO1079.

<span class="mw-page-title-main">KIAA0922</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 131-like, alternatively named uncharacterized protein KIAA0922, is an integral transmembrane protein encoded by the human gene KIAA0922 that is significantly conserved in eukaryotes, at least through protists. Although the function of this gene is not yet fully elucidated, initial microarray evidence suggests that it may be involved in immune responses. Furthermore, its paralog, prolyl endopeptidase (PREP) whose function is known, provides clues as to the function of TMEM131L.

<span class="mw-page-title-main">Transmembrane protein 151b</span> Transmembrane protein

Transmembrane protein 151B is a protein that in humans is encoded by the TMEM151B gene.

TMEM143 is a protein that in humans is encoded by TMEM143 gene. TMEM143, a dual-pass protein, is predicted to reside in the mitochondria and high expression has been found in both human skeletal muscle and the heart. Interaction with other proteins indicate that TMEM143 could potentially play a role in tumor suppression/expression and cancer regulation.

TMEM156 is a gene that encodes the transmembrane protein 156 (TMEM156) in Homo sapiens. It has the clone name of FLJ23235.

<span class="mw-page-title-main">Transmembrane protein 255A</span> Mammalian protein found in Homo sapiens

Transmembrane protein 255A is a protein that is encoded by the TMEM255A gene. TMEM255A is often referred to as family with sequence similarity 70, member A (FAM70A). The TMEM255A protein is transmembrane and is predicted to be located the nuclear envelope of eukaryote organisms.

<span class="mw-page-title-main">Transmembrane protein 44</span>

Transmembrane protein 44 is a protein that in humans is encoded by the TMEM44 gene.

<span class="mw-page-title-main">TMEM44</span> Protein-coding gene in the species Homo sapiens

TMEM44 is a protein that in humans is encoded by the TMEM44 gene. DKFZp686O18124 is a synonym of TMEM44.

<span class="mw-page-title-main">TMEM171</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 171 (TMEM171) is a protein that in humans is encoded by the TMEM171 gene.

<span class="mw-page-title-main">TMEM125</span> Protein

Transmembrane protein 125 is a protein that, in humans, is encoded by the TMEM125 gene. It has 4 transmembrane domains and is expressed in the lungs, thyroid, pancreas, intestines, spinal cord, and brain. Though its function is currently poorly understood by the scientific community, research indicates it may be involved in colorectal and lung cancer networks. Additionally, it was identified as a cell adhesion molecule in oligodendrocytes, suggesting it may play a role in neuron myelination.

<span class="mw-page-title-main">TMEM128</span>

TMEM128, also known as Transmembrane Protein 128, is a protein that in humans is encoded by the TMEM128 gene. TMEM128 has three variants, varying in 5' UTR's and start codon location. TMEM128 contains four transmembrane domains and is localized in the Endoplasmic Reticulum membrane. TMEM128 contains a variety of regulation at the gene, transcript, and protein level. While the function of TMEM128 is poorly understood, it interacts with several proteins associated with the cell cycle, signal transduction, and memory.

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.

<span class="mw-page-title-main">TMEM101</span>

Transmembrane protein 101 (TMEM101) is a protein that in humans is encoded by the TMEM101 gene. The TMEM101 protein has been demonstrated to activate the NF-κB signaling pathway. High levels of expression of TMEM101 have been linked to breast cancer.

<span class="mw-page-title-main">TMEM212</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 212 is a protein that in humans is encoded by the TMEM212 gene. The protein consists of 5 transmembrane domains and localizes in the plasma membrane and endoplasmic reticulum. TMEM212 has orthologs in vertebrates but not invertebrates. TMEM212 has been associated with sporadic Parkinson's disease, facial processing, and adiposity in African Americans.

<span class="mw-page-title-main">TEDDM1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">TMEM104</span> TMEM104 protein encoding gene

Transmembrane protein 104 (TMEM104) is a protein that in humans is encoded by the TMEM104 gene. The aliases of TMEM104 are FLJ00021 and FLJ20255. Humans have a 163,255 base pair long gene coding sequence, 4703 base pair long mRNA, and 496 amino acid long protein sequence. In Eukaryotes, the TMEM104 gene is conserved.

<span class="mw-page-title-main">TMEM144</span> Transmembrane Protein 144

Transmembrane Protein 144 (TMEM144) is a protein in humans encoded by the TMEM144 gene.

TMEM252 or transmembrane protein 252 is a protein that, in humans, is encoded by the TMEM252 gene.

<span class="mw-page-title-main">TMEM82</span> Transmembrane Protein 82

Transmembrane protein 82 (TMEM82) is a protein encoded by the TMEM82 gene in humans.

<span class="mw-page-title-main">TMEM271</span> TMEM271 gene and protein

Transmembrane protein 271, or TMEM271 is a protein in Homo sapiens encoded by the TMEM271 gene, located at 4p16.3 on the minus strand. The protein is located on the plasma membrane of cells and highly expressed in several regions of the brain.

References

  1. 1 2 "TMEM248 transmembrane protein 248 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-09-20.
  2. 1 2 "TMEM248 Polyclonal Antibody (PA5-53435)". www.thermofisher.com. Retrieved 2022-12-15.
  3. ↑ Sehovic, Emir; Hadrovic, Adem; Dogan, Senol (2019-11-10). "Detection and analysis of stable and flexible genes towards a genome signature framework in cancer". Bioinformation. 15 (10): 772–779. doi:10.6026/97320630015772. ISSN   0973-2063. PMC   6900328 . PMID   31831960.
  4. 1 2 3 GRCh38: Ensembl release 89: ENSG00000106609 - Ensembl, May 2017
  5. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000053094 - Ensembl, May 2017
  6. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  7. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  8. ↑ "TMEM248". UCSC Genome Browser. University of California, Santa Cruz. Retrieved 3 August 2022.
  9. 1 2 3 "TMEM248 transmembrane protein 248 [ Homo sapiens (human) ]". National Library of Medicine. NCBI. Retrieved 30 July 2022.
  10. 1 2 "TMEM248 Gene - Transmembrane Protein 248". GeneCards. Weizmann Institute of Science. Retrieved 3 August 2022.
  11. ↑ "UniProt". www.uniprot.org. Retrieved 2022-12-15.
  12. ↑ "Homo sapiens transmembrane protein 248 (TMEM248), mRNA". 2021-06-26.{{cite journal}}: Cite journal requires |journal= (help)
  13. ↑ "transmembrane protein 248 isoform X1 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-12-15.
  14. ↑ "PREDICTED: Homo sapiens transmembrane protein 248 (TMEM248), transcript variant X2, mRNA". 2022-04-05.{{cite journal}}: Cite journal requires |journal= (help)
  15. ↑ "PREDICTED: Homo sapiens transmembrane protein 248 (TMEM248), transcript variant X3, mRNA". 2022-04-05.{{cite journal}}: Cite journal requires |journal= (help)
  16. 1 2 "Tissue expression of TMEM248 - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2022-12-15.
  17. 1 2 "EBI Tools: Job not available". www.ebi.ac.uk. Retrieved 2022-12-15.
  18. ↑ "PSORT WWW Server". psort.hgc.jp. Retrieved 2022-12-15.
  19. ↑ "{{ngMeta['og:title']}}". bio.tools. Retrieved 2022-12-15.
  20. ↑ "TMEM248 (human)". www.phosphosite.org. Retrieved 2022-12-15.
  21. ↑ "IBS - Online". ibs.biocuckoo.org. Retrieved 2022-12-15.
  22. ↑ "TimeTree of Life". TimeTree 5, The TimeScale of Life. Institute for Genomics and Evolutionary Medicine Center of Biodiversity Temple University. Retrieved 3 August 2022.
  23. ↑ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2022-12-15.
  24. ↑ D’Addio, Francesca; Maestroni, Anna; Assi, Emma; Ben Nasr, Moufida; Amabile, Giovanni; Usuelli, Vera; Loretelli, Cristian; Bertuzzi, Federico; Antonioli, Barbara; Cardarelli, Francesco; El Essawy, Basset; Solini, Anna; Gerling, Ivan C.; Bianchi, Cristina; Becchi, Gabriella (2022-02-03). "The IGFBP3/TMEM219 pathway regulates beta cell homeostasis". Nature Communications. 13 (1): 684. Bibcode:2022NatCo..13..684D. doi:10.1038/s41467-022-28360-2. ISSN   2041-1723. PMC   8813914 . PMID   35115561.
  25. ↑ Sehovic, Emir; Hadrovic, Adem; Dogan, Senol (2019-11-10). "Detection and analysis of stable and flexible genes towards a genome signature framework in cancer". Bioinformation. 15 (10): 772–779. doi:10.6026/97320630015772. ISSN   0973-2063. PMC   6900328 . PMID   31831960.
  26. ↑ Ida, Vänttinen (2020). "Drug Response and Disease Progression Associated MicroRNAs in Multiple Myeloma".{{cite journal}}: Cite journal requires |journal= (help)
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