TMEM98

Last updated
TMEM98
Identifiers
Aliases TMEM98 , NNO4, TADA1, transmembrane protein 98
External IDs OMIM: 615949 MGI: 1923457 HomoloGene: 9185 GeneCards: TMEM98
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_015544
NM_001033504
NM_001301746

NM_029537

RefSeq (protein)

NP_001028676
NP_001288675
NP_056359

NP_083813

Location (UCSC) Chr 17: 32.93 – 32.95 Mb n/a
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

Gene

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

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

Paralogs

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

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 SpeciesCommon NameClassAccessionPercent Identity
Pan paniscus Bonobo MammaliaXP_003818064.199%
Felis catusCommon House CatMammaliaXP_00399660299%
Mus musculusMouseMammaliaNP_083813.199%
Myotis davidii Mouse-Eared Bat MammaliaELK33053.195%
Heterocephalus glaber Naked Mole Rat MammaliaEHB09150.194%
Anolis carolinensisArboreal LizardReptiliaXP_00322259385%
Taeniopygia guttata Zebra Finch AvesXP_002193870.178%
Tetraodon nigrovirdisGreen Spotten Puffer Fish ActinopterygiiCAG07250.178%
Bombus impatiens Common Eastern Bubblebee InsectaXP_003489307.142%
Harpegnathos saltator Jumping Ant InsectaEFN84682.140%
Trichinella spiralis Nematode ParasiteAnnelidaXP_003372303.137%

Phylogeny

The percent change over time graph was made using Time Tree. [12]

Percent Change Over Time Phylogenetic Change Over Time of TMEM98.png
Percent Change Over Time

Protein

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

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

TMEM98 is composed of 7 alpha helices as predicted by NCBI CBLAST with an e-value of 9x10−7. [18]

Regulation

mRNA level

The promoter region is 901 base pairs in length. The most highly conserved predicted transcription factors are shown below. [19]

Transcription FactorStartEndStrandSequence
GC-box factors SP1/GC5874+gtagGGGGtgtgtgttt
C2H2 zinc finger transcription factor 5102116+tgtatgGGATggagt
C2H2 zinc finger transcription factor 24870-acacaCCCCctaccctgccatcc
Motif composed of binding sites for pluripotency or stem cell factors151169+gggctctGCATttgtactc
Calcium-response element352362+agaccGAGGca
CP2-erythrocyte Factor released to drosophila Elf1 II B386404-cTCTGccactcactagcta
GC-box factors SP1/GC500516+gcccgGGGCggggcgca
Metal induced transcription factor505519-gcctGCGCcccgccc
KRAB domain zinc finger protein 57543555+gtcTGCCgcccgg
Pleomorphic adenoma gene567589+cgGGGGcgcgaggaaggggtgtt
CTCF and BORIS gene family, transcriptional regulators615641+tgccccggccgccgGGGGgcctggcgg
EGR/nerve growth factor induced protein C and release factor695713+gggcgcggGGGCgcgaggc
E2F-myc activator and cell cycle regulator663679-ggcccgcgcCAAAtccc
RNA polymerase II transcription factor670676-ccgCGCC
RNA polymerase II transcription factor696702-ccgCGCC
Nuclear respiratory factor 1694710-tcgcGCCCccgcgcccc
Selenocysteine tRNA activation factor725755+ggccgcggcgcttCCCGgcatgctccgctgc
Nuclear respiratory factor 1758774+gcccGCGCccgcgcccg
Histone nuclear factor P771783+ccCGGActttgcc
Nuclear respiratory factor 1759775-ccggGCGCgggcgcggg
RNA polymerase II transcription factor886892-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

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

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

Mutations in TMEM98 cause autosomal dominant nanophthalmos. [27]

Related Research Articles

<span class="mw-page-title-main">TMEM242</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 242 (TMEM242) is a protein that in humans is encoded by the TMEM242 gene. The tmem242 gene is located on chromosome 6, on the long arm, in band 2 section 5.3. This protein is also commonly called C6orf35, BM033, and UPF0463 Transmembrane Protein C6orf35. The tmem242 gene is 35,238 base pairs long, and the protein is 141 amino acids in length. The tmem242 gene contains 4 exons. The function of this protein is not well understood by the scientific community. This protein contains a DUF1358 domain.

<span class="mw-page-title-main">TMEM229B</span> Gene of the species Homo sapiens

Transmembrane protein 229b is a protein that in humans is encoded by the TMEM229b gene.

<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.

Transmembrane protein 241 is a ubiquitous sugar transporter protein which in humans is encoded by the TMEM241 gene.

Transmembrane protein 33 is a protein that in humans, is encoded by the TMEM33 gene, also known as SHINC3. Another name for the TMEM33 protein is DB83.

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.

Transmembrane protein 251, also known as C14orf109 or UPF0694, is a protein that in humans is encoded by the TMEM251 gene. One notable feature of this protein is the presence of proline residues on one of its predicted transmembrane domains., which is a determinant of the intramitochondrial sorting of inner membrane proteins.

<span class="mw-page-title-main">TMEM249</span> Protein-coding gene in the species Homo sapiens

TMEM249 is a protein that in humans is encoded by the C8orfk29 gene.

<span class="mw-page-title-main">Transmembrane protein 268</span>

Transmembrane protein 268 is a protein that in humans is encoded by TMEM268 gene. The protein is a transmembrane protein of 342 amino acids long with eight alternative splice variants. The protein has been identified in organisms from the common fruit fly to primates. To date, there has been no protein expression found in organisms simpler than insects.

<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.

Transmembrane Protein 217 is a protein encoded by the gene TMEM217. TMEM217 has been found to have expression correlated with the lymphatic system and endothelial tissues and has been predicted to have a function linked to the cytoskeleton.

<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">C9orf50</span> Protein-coding gene in the species Homo sapiens

Chromosome 9 open reading frame 50 is a protein that in humans is encoded by the C9orf50 gene. C9orf50 has one other known alias, FLJ35803. In humans the gene coding sequence is 10,051 base pairs long, transcribing an mRNA of 1,624 bases that encodes a 431 amino acid protein.

<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.

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.

Transmembrane protein 39B (TMEM39B) is a protein that in humans is encoded by the gene TMEM39B. TMEM39B is a multi-pass membrane protein with eight transmembrane domains. The protein localizes to the plasma membrane and vesicles. The precise function of TMEM39B is not yet well-understood by the scientific community, but differential expression is associated with survival of B cell lymphoma, and knockdown of TMEM39B is associated with decreased autophagy in cells infected with the Sindbis virus. Furthermore, the TMEM39B protein been found to interact with the SARS-CoV-2 ORF9C protein. TMEM39B is expressed at moderate levels in most tissues, with higher expression in the testis, placenta, white blood cells, adrenal gland, thymus, and fetal brain.

<span class="mw-page-title-main">TMEM169</span> Gene

Transmembrane protein 169 (TMEM169) in humans is encoded by TMEM169 gene. The aliases of TMEM169 include FLJ34263, DKFZp781L2456, and LOC92691. TMEM169 has the highest expression in the brain, particularly the fetal brain. TMEM169 has homologs mammals, reptiles, amphibians, birds, fish, chordates and invertebrates. The most distantly related homolog of TMEM169 is Anopheles albimanus.

<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">TMEM248</span> Transmembrane protein 248/TMEM248 gene

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. 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.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000006042 - 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. 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.
  5. 1 2 3 "Entrez Gene: TMEM98 transmembrane protein 98".
  6. 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.
  7. 1 2 "Ensembl genome browser 75: Homo sapiens - Summary - Gene: TMEM98 (ENSG00000006042)".
  8. "Homo sapiens transmembrane protein 98 (TMEM98), transcript variant 1, - Nucleotide - NCBI". 2018-06-23.{{cite journal}}: Cite journal requires |journal= (help)
  9. 1 2 "Homo sapiens transmembrane protein 98 (TMEM98), transcript variant 2, - Nucleotide - NCBI". 2018-06-23.{{cite journal}}: Cite journal requires |journal= (help)
  10. "AceView: Gene:TMEM98, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView".
  11. "TMEM98 Gene - GeneCards | TMM98 Protein | TMM98 Antibody".
  12. "TimeTree :: The Timescale of Life".
  13. "SDSC Biology Workbench".
  14. "SignalP 4.1 Server".
  15. "harrier.nagahama-i-bio.ac.jp".
  16. "NCBI Conserved Domain Search".
  17. 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.
  18. "Welcome to NCBI Related Structure Search".
  19. "Genomatix - NGS Data Analysis & Personalized Medicine".
  20. "The Mfold Web Server | mfold.rit.albany.edu".
  21. "TargetScanHuman 6.2".
  22. 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.
  23. 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.
  24. "NetGlycate 1.0 Server".
  25. "NetPhos 2.0 Server".
  26. "Home - GEO Profiles - NCBI".
  27. 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.