TMEM98
| TMEM98 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | TMEM98, NNO4, TADA1, transmembrane protein 98 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 615949; MGI: 1923457; HomoloGene: 9185; GeneCards: TMEM98; OMA:TMEM98 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Transmembrane protein 98 is a single-pass membrane protein that in humans is encoded by the TMEM98 gene.[4][5] The function of this protein is currently unknown. TMEM98 is also known as UNQ536/PRO1079.[6]
Gene
[edit]This gene is found on the plus strand of chromosome 17 at locus 17q11.2.[5] It spans from base pairs 31,254,928 to 31,272,124.[7]
Variants
[edit]There are two known transcript variants that encode for TMEM98. Variant one corresponds to the longer of the two, has 8 exons, and is 1808 bases in length.[8] Variant two codes for the same protein, but is slightly shorter at exon 2 and is missing exon 3; it is 1732 bases long.[9] This missing region corresponds to 85 base pairs near the end of the 5' UTR.[9] Variant one is more abundant than Variant two with 17 times the amount mRNA extracted in various human tissue experiments.[10]
Evolution
[edit]Paralogs
[edit]There are no known paralogs for TMEM98.[7] While not functional, there are two pseudogenes found on chromosome 6 and 14 in Homo sapiens.[11]
Orthologs
[edit]Transmembrane protein 98 is highly conserved in fish, amphibians, reptiles, birds, and other non-human mammals. It is only slightly conserved and invertebrates and insects and is not found in bacteria, archaea, protists, plants, or fungi.
| Genus and Species | Common Name | Class | Accession | Percent Identity |
|---|---|---|---|---|
| Pan paniscus | Bonobo | Mammalia | XP_003818064.1 | 99% |
| Felis catus | Common House Cat | Mammalia | XP_003996602 | 99% |
| Mus musculus | Mouse | Mammalia | NP_083813.1 | 99% |
| Myotis davidii | Mouse-Eared Bat | Mammalia | ELK33053.1 | 95% |
| Heterocephalus glaber | Naked Mole Rat | Mammalia | EHB09150.1 | 94% |
| Anolis carolinensis | Arboreal Lizard | Reptilia | XP_003222593 | 85% |
| Taeniopygia guttata | Zebra Finch | Aves | XP_002193870.1 | 78% |
| Tetraodon nigrovirdis | Green Spotten Puffer Fish | Actinopterygii | CAG07250.1 | 78% |
| Bombus impatiens | Common Eastern Bubblebee | Insecta | XP_003489307.1 | 42% |
| Harpegnathos saltator | Jumping Ant | Insecta | EFN84682.1 | 40% |
| Trichinella spiralis | Nematode Parasite | Annelida | XP_003372303.1 | 37% |
Phylogeny
[edit]The percent change over time graph was made using Time Tree.[12]
Protein
[edit]Transcript Variant one and two code for the same protein of 226 amino acids.[5] The protein is 24.6 kdal with an isoelectric point of 4.26.[13]
Domains
[edit]There is no signal peptide in this protein.[14] The transmembrane domain is 22 amino acids long and is located from amino acids 6-28. Amino acids on the N-terminus side are located outside of the cell, and amino acids on the C-terminius side are outside of the cell.[15]
The paralogous domain Grap2 and cyclin-D-interacting (pfam13324) spans from 81-151 and is highly conserved in orthologs.[16] This region is involved in the regulation of proliferation and cell differentiation using Grap2 and cyclin-d-mediated signaling pathways.[17]
Secondary Structure
[edit]TMEM98 is composed of 7 alpha helices as predicted by NCBI CBLAST with an e-value of 9x10−7.[18]
Regulation
[edit]mRNA level
[edit]The promoter region is 901 base pairs in length. The most highly conserved predicted transcription factors are shown below.[19]
| Transcription Factor | Start | End | Strand | Sequence |
|---|---|---|---|---|
| GC-box factors SP1/GC | 58 | 74 | + | gtagGGGGtgtgtgttt |
| C2H2 zinc finger transcription factor 5 | 102 | 116 | + | tgtatgGGATggagt |
| C2H2 zinc finger transcription factor 2 | 48 | 70 | - | acacaCCCCctaccctgccatcc |
| Motif composed of binding sites for pluripotency or stem cell factors | 151 | 169 | + | gggctctGCATttgtactc |
| Calcium-response element | 352 | 362 | + | agaccGAGGca |
| CP2-erythrocyte Factor released to drosophila Elf1 II B | 386 | 404 | - | cTCTGccactcactagcta |
| GC-box factors SP1/GC | 500 | 516 | + | gcccgGGGCggggcgca |
| Metal induced transcription factor | 505 | 519 | - | gcctGCGCcccgccc |
| KRAB domain zinc finger protein 57 | 543 | 555 | + | gtcTGCCgcccgg |
| Pleomorphic adenoma gene | 567 | 589 | + | cgGGGGcgcgaggaaggggtgtt |
| CTCF and BORIS gene family, transcriptional regulators | 615 | 641 | + | tgccccggccgccgGGGGgcctggcgg |
| EGR/nerve growth factor induced protein C and release factor | 695 | 713 | + | gggcgcggGGGCgcgaggc |
| E2F-myc activator and cell cycle regulator | 663 | 679 | - | ggcccgcgcCAAAtccc |
| RNA polymerase II transcription factor | 670 | 676 | - | ccgCGCC |
| RNA polymerase II transcription factor | 696 | 702 | - | ccgCGCC |
| Nuclear respiratory factor 1 | 694 | 710 | - | tcgcGCCCccgcgcccc |
| Selenocysteine tRNA activation factor | 725 | 755 | + | ggccgcggcgcttCCCGgcatgctccgctgc |
| Nuclear respiratory factor 1 | 758 | 774 | + | gcccGCGCccgcgcccg |
| Histone nuclear factor P | 771 | 783 | + | ccCGGActttgcc |
| Nuclear respiratory factor 1 | 759 | 775 | - | ccggGCGCgggcgcggg |
| RNA polymerase II transcription factor | 886 | 892 | - | ccgCGCC |
Possible Stem Loops The 5' UTR has two possible stem loops. These are located from 279-303 and 342-372. In the 3' UTR, there is a possible stem loop located from 1487-1502.[20]
microRNA Binding Sites There is one miRNA binding site in the 3' UTR as predicted using TargetScan.[21][22] This miRNA, hsa-miR-4782-3p, may play a role in breast cancer.[23]
Protein level
[edit]TMEM98 has 4 predicted glycation sites at amino acids 44, 118, 120, and 133.[24] There are serine phosphorylation sites at 60, 122, 124, 136, 145, and 191 and threonine phosphorylation sites at 55, 105, and 160.[25] These sites are all on the N-terminus side of the transmembrane region and are inside the cytosol of the cell.
Expression
[edit]TMEM98 is expressed highly in retina, adipose tissue, embryo, ovary, umbilical cord, uterus, prostate, large and small intestines, lung, medical olfactory epithelium, nasal organ, stomach, bladder, and adrenal gland tissues. It is expressed very low in fertilized egg, oocyte, B cell, skeletal muscle, tongue epidermis, and thymus tissues.
It is also more highly expressed later embryonic stages.[26]
Clinical aspects
[edit]Mutations in TMEM98 cause autosomal dominant nanophthalmos.[27]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000006042 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Bocher M, Blocker H, Bauersachs S, Blum H, Lauber J, Dusterhoft A, Beyer A, Kohrer K, Strack N, Mewes HW, Ottenwalder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
- ^ a b c "Entrez Gene: TMEM98 transmembrane protein 98".
- ^ Clark HF, Gurney AL, Abaya E, et al. (October 2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
- ^ a b "Ensembl genome browser 75: Homo sapiens - Summary - Gene: TMEM98 (ENSG00000006042)".
- ^ "Homo sapiens transmembrane protein 98 (TMEM98), transcript variant 1, - Nucleotide - NCBI". 2018-06-23.
{{cite journal}}: Cite journal requires|journal=(help) - ^ a b "Homo sapiens transmembrane protein 98 (TMEM98), transcript variant 2, - Nucleotide - NCBI". 2018-06-23.
{{cite journal}}: Cite journal requires|journal=(help) - ^ "AceView: Gene:TMEM98, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView".
- ^ "TMEM98 Gene - GeneCards | TMM98 Protein | TMM98 Antibody".
- ^ "TimeTree :: The Timescale of Life".
- ^ "SDSC Biology Workbench".
- ^ "SignalP 4.1 Server".
- ^ "harrier.nagahama-i-bio.ac.jp".
- ^ "NCBI Conserved Domain Search".
- ^ Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S, Liu M (July 2000). "GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity". J. Biol. Chem. 275 (27): 20942–8. doi:10.1074/jbc.M002598200. PMID 10801854.
- ^ "Welcome to NCBI Related Structure Search".
- ^ "Genomatix - NGS Data Analysis & Personalized Medicine". Archived from the original on 2021-12-02. Retrieved 2014-05-10.
- ^ "The Mfold Web Server | mfold.rit.albany.edu".
- ^ "TargetScanHuman 6.2".
- ^ Agarwal, Vikram; Bell, George W.; Nam, Jin-Wu; Bartel, David P. (2015-08-12). "Predicting effective microRNA target sites in mammalian mRNAs". eLife. 4: e05005. doi:10.7554/eLife.05005. ISSN 2050-084X. PMC 4532895. PMID 26267216.
- ^ Persson H, Kvist A, Rego N, et al. (January 2011). "Identification of new microRNAs in paired normal and tumor breast tissue suggests a dual role for the ERBB2/Her2 gene". Cancer Res. 71 (1): 78–86. doi:10.1158/0008-5472.CAN-10-1869. PMID 21199797.
- ^ "NetGlycate 1.0 Server".
- ^ "NetPhos 2.0 Server".
- ^ "Home - GEO Profiles - NCBI".
- ^ Awadalla, M. S.; Burdon, K. P.; Souzeau, E; Landers, J; Hewitt, A. W.; Sharma, S; Craig, J. E. (2014). "Mutation in TMEM98 in a Large White Kindred with Autosomal Dominant Nanophthalmos Linked to 17p12-q12". JAMA Ophthalmology. 132 (8): 970–7. doi:10.1001/jamaophthalmol.2014.946. PMID 24852644.