TMEM98

This gene is found on the plus strand of chromosome 17 at locus 17q11.2. It spans from base pairs 31,254,928 to 31,272,124.{{cite web |url=http://useast.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000006042;r=17:31254928-31272124 |title=Ensembl genome browser 75: Homo sapiens - Summary - Gene: TMEM98 (ENSG00000006042) }}

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.{{cite journal |url=https://www.ncbi.nlm.nih.gov/nuccore/NM_015544.2 |title=Homo sapiens transmembrane protein 98 (TMEM98), transcript variant 1, - Nucleotide - NCBI |date=2018-06-23 }} Variant two codes for the same protein, but is slightly shorter at exon 2 and is missing exon 3; it is 1732 bases long.{{cite journal |url=https://www.ncbi.nlm.nih.gov/nuccore/NM_001033504.1 |title=Homo sapiens transmembrane protein 98 (TMEM98), transcript variant 2, - Nucleotide - NCBI |date=2018-06-23 }} This missing region corresponds to 85 base pairs near the end of the 5' UTR. Variant one is more abundant than Variant two with 17 times the amount mRNA extracted in various human tissue experiments.{{cite web |url=https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=tmem98&submit=Go |title=AceView: Gene:TMEM98, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView. }}

There are no known paralogs for TMEM98. While not functional, there are two pseudogenes found on chromosome 6 and 14 in Homo sapiens.{{cite web |url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM98 |title=TMEM98 Gene - GeneCards | TMM98 Protein | TMM98 Antibody }}

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.

The percent change over time graph was made using Time Tree.{{cite web |url=http://www.timetree.org/ |title=TimeTree :: The Timescale of Life }}

File:Phylogenetic Change Over Time of TMEM98.png

Transcript Variant one and two code for the same protein of 226 amino acids. The protein is 24.6 kdal with an isoelectric point of 4.26.{{cite web |url=http://workbench.sdsc.edu/ |title=SDSC Biology Workbench }}

There is no signal peptide in this protein.{{cite web |url=http://www.cbs.dtu.dk/services/SignalP/ |title=SignalP 4.1 Server }} 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.{{cite web |url=http://harrier.nagahama-i-bio.ac.jp/sosui/sosui_submit.html |title=harrier.nagahama-i-bio.ac.jp }}

The paralogous domain Grap2 and cyclin-D-interacting (pfam13324) spans from 81-151 and is highly conserved in orthologs.{{cite web |url=https://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi |title=NCBI Conserved Domain Search }} This region is involved in the regulation of proliferation and cell differentiation using Grap2 and cyclin-d-mediated signaling pathways.{{cite journal | date = July 2000 |vauthors=Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S, Liu M | title = GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity | journal = J. Biol. Chem. | volume = 275 | issue = 27 | pages = 20942–8 | pmid = 10801854 | doi = 10.1074/jbc.M002598200| doi-access = free }}

TMEM98 is composed of 7 alpha helices as predicted by NCBI CBLAST with an e-value of 9x10⁻⁷.{{cite web |url=https://www.ncbi.nlm.nih.gov/Structure/cblast/cblast.cgi |title=Welcome to NCBI Related Structure Search }}

The promoter region is 901 base pairs in length. The most highly conserved predicted transcription factors are shown below.{{cite web |url=http://www.genomatix.de/ |title=Genomatix - NGS Data Analysis & Personalized Medicine |access-date=2014-05-10 |archive-date=2021-12-02 |archive-url=https://web.archive.org/web/20211202010908/https://www.genomatix.de/ |url-status=dead }}

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.{{cite web |url=http://mfold.rna.albany.edu/?q=mfold |title=The Mfold Web Server | mfold.rit.albany.edu }}

microRNA Binding Sites

There is one miRNA binding site in the 3' UTR as predicted using TargetScan.{{cite web |url=http://www.targetscan.org/ |title=TargetScanHuman 6.2 }}{{Cite journal|title = Predicting effective microRNA target sites in mammalian mRNAs|journal = eLife|date = 2015-08-12|issn = 2050-084X|pmc = 4532895|pmid = 26267216|pages = e05005|volume = 4|doi = 10.7554/eLife.05005|language = en|first1 = Vikram|last1 = Agarwal|first2 = George W.|last2 = Bell|first3 = Jin-Wu|last3 = Nam|first4 = David P.|last4 = Bartel | doi-access=free }} This miRNA, hsa-miR-4782-3p, may play a role in breast cancer.{{cite journal |vauthors=Persson H, Kvist A, Rego N, etal |title=Identification of new microRNAs in paired normal and tumor breast tissue suggests a dual role for the ERBB2/Her2 gene |journal=Cancer Res. |volume=71 |issue=1 |pages=78–86 |date=January 2011 |pmid=21199797 |doi=10.1158/0008-5472.CAN-10-1869 |doi-access=free }}

TMEM98 has 4 predicted glycation sites at amino acids 44, 118, 120, and 133.{{cite web |url=http://www.cbs.dtu.dk/services/NetGlycate/ |title=NetGlycate 1.0 Server }} There are serine phosphorylation sites at 60, 122, 124, 136, 145, and 191 and threonine phosphorylation sites at 55, 105, and 160.{{cite web |url=http://www.cbs.dtu.dk/services/NetPhos/ |title=NetPhos 2.0 Server }} These sites are all on the N-terminus side of the transmembrane region and are inside the cytosol of the cell.

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.{{cite web |url=https://www.ncbi.nlm.nih.gov/geoprofiles/ |title=Home - GEO Profiles - NCBI }}

Mutations in TMEM98 cause autosomal dominant nanophthalmos.{{Cite journal

| pmid = 24852644

| year = 2014

| last1 = Awadalla

| first1 = M. S.

| title = Mutation in TMEM98 in a Large White Kindred with Autosomal Dominant Nanophthalmos Linked to 17p12-q12

| journal = JAMA Ophthalmology

| last2 = Burdon

| first2 = K. P.

| last3 = Souzeau

| first3 = E

| last4 = Landers

| first4 = J

| last5 = Hewitt

| first5 = A. W.

| last6 = Sharma

| first6 = S

| last7 = Craig

| first7 = J. E.

| doi = 10.1001/jamaophthalmol.2014.946

| volume=132

| issue = 8

| pages=970–7

| doi-access = free

}}

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