TMEM275

{{Short description|Protein present in humans}}TMEM275 (Transmembrane protein 275{{Cite web|title=TMEM275 Gene - GeneCards {{!}} TM275 Protein {{!}} TM275 Antibody|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM275|website=www.genecards.org|access-date=2020-05-01}}) is a protein that in humans is encoded by the TMEM275 gene.{{Cite web|title=TMEM275 transmembrane protein 275 [Homo sapiens (human)] - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=DetailsSearch&Term=105378696|website=www.ncbi.nlm.nih.gov|access-date=2020-05-01}} TMEM275 has two, highly-conserved, helical trans-membrane regions. It is predicted to reside within the plasma membrane or the endoplasmic reticulum's membrane.

Gene

= Locus =

In humans, the gene is located on chromosomal band 1p33 on the minus strand.{{Cite web|title=TMEM275 Gene - GeneCards {{!}} TM275 Protein {{!}} TM275 Antibody|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM275|website=www.genecards.org|access-date=2020-05-04}} It specifically resides on chromosome 1 at chr1:46,532,166-46,543,969. TMEM275 is 11,804bp long.

File:TMEM275 Chr 1 Location.png

= Gene neighborhood =

Upstream, on the minus strand, of TMEM275 is another gene; KNCN.{{Cite web|title=KNCN kinocilin [Homo sapiens (human)] - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene/148930|website=www.ncbi.nlm.nih.gov|access-date=2020-05-04}}

File:TMEM275_Locus.png

Transcripts

The TMEM275 gene encodes four exons, only three of which are included within the final mRNA transcript.{{Cite web|title=Genome Data Viewer|url=https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=105378696|website=www.ncbi.nlm.nih.gov|access-date=2020-05-04}} Two of those three are within the 5’ UTR and the coding sequence codes for 177 amino acids. TMEM275 is found two have two potential isoforms outside of its reference transcript. The reference isoform does not include exon 1, while isoform X1 has a shortened 5' UTR and isoform X2 has a shortened 3' UTR.{{Cite journal|date=2020-03-02|title=PREDICTED: Homo sapiens transmembrane protein 275 (TMEM275), transcript variant X1, mRNA|url=http://www.ncbi.nlm.nih.gov/nuccore/XM_024451048.1|language=en-US}}{{Cite journal|date=2020-03-02|title=PREDICTED: Homo sapiens transmembrane protein 275 (TMEM275), transcript variant X2, mRNA|url=http://www.ncbi.nlm.nih.gov/nuccore/XM_024451056.1|language=en-US}}{{Cite journal|date=2019-07-07|title=Homo sapiens transmembrane protein 275 (TMEM275), mRNA|url=http://www.ncbi.nlm.nih.gov/nuccore/NM_001357063.3|language=en-US}} However, all versions of mRNA transcripts yield the same 177 amino acid sequence.

Protein

= General properties =

The TMEM275 protein contains 177 amino acids with a predicted molecular mass of 17.2 kDa and a pI of 8.13.{{Cite web|title=ExPASy - Compute pI/Mw tool|url=https://web.expasy.org/compute_pi/|website=web.expasy.org|access-date=2020-05-01}} TMEM275 was found to have a higher presence of alanine and proline amino acid residues than most proteins.{{Cite web|title=SAPS < Sequence Statistics < EMBL-EBI|url=https://www.ebi.ac.uk/Tools/seqstats/saps/|website=www.ebi.ac.uk|access-date=2020-05-04}} When looking at orthologous proteins sequences within other species, the alanine presence was conserved throughout, but the same could not be said of the proline presence.

File:SAPS_TMEM275.png

= Primary sequence =

TMEM275's protein consists of 177 amino acids. The protein, or polypeptide chain, that is encoded by the coding sequence is made through the process of translation and is shown below among other regions of interest. There is also a poly-A, or polyadenylation signal, towards the end of the 3'UTR.

File:TMEM275_Conceptual_Translation.png

= Domains =

TMEM275 has two, highly-conserved, helical trans-membrane regions.{{Cite web|title=Protter - interactive protein feature visualization|url=http://wlab.ethz.ch/protter/start/|website=wlab.ethz.ch|access-date=2020-05-04}}{{Cite web|title=TMEM275 transmembrane protein 275 [Homo sapiens (human)] - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene/105378696|website=www.ncbi.nlm.nih.gov|access-date=2020-05-04}} The regions can be seem within the amino acid sequence above within the conceptual translation in purple. Evolutionary analysis showed that these trans-membrane domains are highly conserved across all ortholog taxa.

File:TMEM275_Domains.png

= Secondary structure =

Many programs were used to analyze the predicted secondary structure for TMEM275. It was found to have a highly varied structure. However, prediction data supports the alpha helical structure of the two transmembrane domains.{{Cite web|title=PHYRE2 Protein Fold Recognition Server|url=http://www.sbg.bio.ic.ac.uk/~phyre2/html/page.cgi?id=index|website=www.sbg.bio.ic.ac.uk|access-date=2020-05-05}}{{Cite web|title=NPS@ : CONSENSUS secondary structure prediction|url=https://npsa-prabi.ibcp.fr/cgi-bin/npsa_automat.pl?page=/NPSA/npsa_seccons.html|website=npsa-prabi.ibcp.fr|access-date=2020-05-05}}{{Cite web|title=CFSSP: Chou & Fasman Secondary Structure Prediction Server|url=http://www.biogem.org/tool/chou-fasman/|website=www.biogem.org|access-date=2020-05-05}}{{Cite web|title=JPred: A Protein Secondary Structure Prediction Server|url=http://www.compbio.dundee.ac.uk/jpred/|website=www.compbio.dundee.ac.uk|language=en|access-date=2020-05-05}}{{Cite web|title=Bioinformatics Toolkit|url=https://toolkit.tuebingen.mpg.de/tools/ali2d|website=toolkit.tuebingen.mpg.de|access-date=2020-05-05}}

Regulation

= Gene level regulation =

== Promoter ==

The predicted promoter region is 1116 bp long and located on chromosome 1 on the minus strand and extends from 46535401- 46536515.{{Cite web|title=Genomatix: Annotation & Analysis|url=https://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=c7d107de46aed9df9a007315eba26f99;SHOW_ANNOTATION=TMEM275;ELDORADO_VERSION=E35R1911|website=www.genomatix.de|access-date=2020-05-01}}

File:Promoter_Birdseye.png

== Transcription factor binding sites ==

ElDorado through Genomatix was used to analyze the top 20 transcription factor binding sites within the promoter.{{Cite web|title=TMEM275 - ElDorado - GenoMatix|url=https://www.genomatix.de/cgi-bin/sessions/login.pl?s=e86f04e08754a5c6dc7214fe2db70f57|last=|first=|date=|website=www.genomatix.de|archive-url=|archive-date=|access-date=2020-05-05}}

File:Top_20_TFs_on_TMEM275_Promoter.png, labelled with the top 20 TF binding site matches found by Genomatix and decided by high matrix similarity scores, proximity to possible transcription start sites, and/or high conservation through primates. ]]

== Expression pattern ==

TMEM275's RNA levels are very high at around 11 weeks of gestation within the intestines.{{Cite web|title=Tissue-specific circular RNA induction during human fetal development|url=https://www.ncbi.nlm.nih.gov/gene/105378696?report=expression&bioproject=PRJNA270632|last=|first=|date=|website=www.ncbi.nlm.nih.gov|archive-url=|archive-date=|access-date=2020-05-05}} Some other notable peaks include the lungs, kidneys, and adrenal tissues at 10, 16, and 20 weeks, respectively.{{Cite web|title=TMEM275 Gene Expression - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene/105378696?report=expression&bioproject=PRJNA270632|website=www.ncbi.nlm.nih.gov|access-date=2020-05-05}} It has also been found that of the 20 human tissues tested, RNA was notably present within fetal brain tissue.{{Cite web|title=RNA sequencing of total RNA from 20 human tissues - TMEM275 Gene Expression - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene/105378696?report=expression&bioproject=PRJNA280600|last=|first=|date=|website=www.ncbi.nlm.nih.gov|archive-url=|archive-date=|access-date=2020-05-05}} Further testing on tissue types lead to the discovery that TMEM275 may have tissue-specificity with the testis, the brain, and the prostate.{{Cite web|title=HPA RNA-seq normal tissues - TMEM275 Gene Expression - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene/105378696?report=expression&bioproject=PRJEB4337|last=|first=|date=|website=www.ncbi.nlm.nih.gov|archive-url=|archive-date=|access-date=2020-05-05}} Along with the thyroid and ovaries.{{Cite web|title=Illumina bodyMap2 transcriptome - TMEM275 Gene Expression - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene/105378696?report=expression&bioproject=PRJEB2445|last=|first=|date=|website=www.ncbi.nlm.nih.gov|archive-url=|archive-date=|access-date=2020-05-05}}

= Protein level regulation =

== [[Subcellular localization|Subcellular Localization]] ==

TMEM275 is predicted to be within the plasma membrane or the endoplasmic reticulum's membrane.{{Cite web|title=PSORT II Prediction|url=https://psort.hgc.jp/form2.html|website=psort.hgc.jp|access-date=2020-05-05}}

== Post-translational modifications ==

Various PTMs were analyzed for association with TMEM275. This includes looking for the presence of a SUMO-motif, acetylation sites, the presence of signal peptides, and any O-GlcNAc site and N-myristylation predictions.{{Cite web|title=TERMINUS - Welcome to terminus|url=http://terminus.unige.ch/|website=terminus.unige.ch|access-date=2020-05-05}}{{Cite web|title=SignalP-5.0|url=http://www.cbs.dtu.dk/services/SignalP/|website=www.cbs.dtu.dk|access-date=2020-05-05}}{{Cite web|title=SUMOplot™ Analysis Program {{!}} Abcepta|url=http://www.abcepta.com/sumoplot|website=www.abcepta.com|access-date=2020-05-05}}

=== Cleavage site ===

File:Methionine Cleavage Site within TMEM275.png of methionine shown within the amino acid sequence of TMEM275.]]{{clear}}

=== [[Phosphorylation]] ===

File:Phosphorylation Prediction of TMEM275.png. Analysis was conducted through NetPhos server and scores are included the bolded locations of possible sites.]]{{clear}}

Homology

= Paralogs =

There are no known paralogs for TMEM275.

= Homologs =

No homologs or homologous domains exist within TMEM275.

= Orthologs =

A total of 105 organisms are found to have orthologs with the human TMEM275 genes, all of which are a part of the Teleostomi, or jawed vertebrates, clade.{{Cite web|title=TMEM275 orthologs|url=https://www.ncbi.nlm.nih.gov/gene/105378696/ortholog/|website=NCBI|language=en|access-date=2020-05-01}} Of the 105 organisms that have an orthologous TMEM275: 49 are mammals, 27 are birds, 3 are turtles, 3 are lizards, 3 are amphibians, 19 are bony fishes, and 1 is an alligator.

The group with the most similar sequences by percent identity was unsurprisingly Mammalia. The percent identities of those orthologous proteins in relation to humans ranged from 52.1% to 70.9%. The group that had the orthologous TMEM275, but was the least similar was Actinopterygii or Bony Fishes. Their percent similarities ranged from 38.5% to 47.6%. Percent similarities were found by conducting a pairwise analysis of each orthologous protein within each species against the human protein.{{Cite web|title=EMBOSS Needle < Pairwise Sequence Alignment < EMBL-EBI|url=https://www.ebi.ac.uk/Tools/psa/emboss_needle/|website=www.ebi.ac.uk|access-date=2020-05-01}}

File:TMEM275_Ortholog_Table.png

Phylogeny

= Gene appearance =

TMEM275 seems to have appeared 435 MYA within the Bony fishes or Actinopterygii.

Interacting proteins

There were no known protein interactions for TMEM275.

Clinical significance

TMEM275 has no known link to medical disease.

References