TMEM249

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External IDs	GeneCards: [1]
Orthologs
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	Wikidata
View/Edit Human

TMEM 249 is a protein that in humans is encoded by the C8orfk29 gene.

Gene

Locus

TMEM 249 is located near the end of the long arm of chromosome 8 in humans.^[1]

File:TMEM249 chromosomal location.png

The chromosomal neighborhood of TMEM 249 on human chromosome 8.

File:TMEM249 Chromosomal position.png

General position of TMEM 249 on human chromosome 8 marked by a red line.

Common aliases

TMEM 249 is also known as C8orfk29.^[2]

Primary sequence & variants/isoforms

File:TMEM249 Isoforms and Splice Variants.png

Isoforms and Splice variants of TMEM249 provided by NCBI's Aceview and Softberry.

The primary sequence found at NCBI^[3] and Aceview on NCBI predicts there are five spliceforms, with four closely resembling one another and the fifth missing a large 5' intron region. Softberry reinforces the Aceview data by predicting five exons, which are seen in four of the five spliceforms of Aceview.

The general structure of the TMEM 249 transcript has a large 5' UTR followed by exon 1, then a large intron followed by exon 2, a small intron then exon 3. The rest of the protein follows exon 3 with a large intron, exon 4 a small intron then exon 5, the 3' UTR.

The primary transcript contains all five exons and produces a protein that is 235 Amino Acids long. Transcript 1 and 2 are translated in the 3' to 5' direction while transcripts 3 through 5 are translated in the 5' to 3' direction. Note that the gene is encoded on the minus strand within the chromosome.

Homology / Evolution

Paralogs

File:TMEM 249 Ortholog Sequence Similarity graph.png

20 of TMEM 249's orthologs graphed by sequence similarity and date of divergence (MYA).

The only known paralog of human TMEM 249 is found in the second isoform of the protein in Gorillas. Of the 217 amino acids aligned between gorilla and human TMEM 249, 96% are in complete consensus and 99% are conserved.

Orthologs

TMEM 249 orthologs includes all groups of life except birds, fungi, archea, protists, and plants. The most distant ortholog, Rozella allomycis, was the most diverged species that qualified as an ortholog. The last shared ancestor between Rozella allomycis and Homo sapiens is the Opisthokonts.

Homologs

No homologs or homologous domains exist within TMEM 249.

Phylogeny

No fungi orthologs were found in the search for similar sequences, so it could be assumed that the gene may have arisen in Opisthokonts and proliferated down the animal tree. This would mean the protein diverged too late to evolve through the fungi tree. This would explain why there are no found plant orthologs as the gene would have arose after animals and plants diverged evolutionarily.^{[citation needed]}

Protein

Domains and motifs

File:TMEM249 predicted transmembrane domains.png

Predicted transmembrane domains of human TMEM249.

There are three predicted transmembrane domains. It is unknown whether these transmembrane domains affect the larger structure of the protein complex once properly expressed in tissue. Evolutionary analysis showed that these transmembrane domains are highly conserved across all ortholog taxa.

Post-translational modifications

File:TMEM249 predicted Serine Phosphorylations.png

TMEM249 predicted serine phosphorylations at the C-terminus of the protein.

There is an area near the 3’ end of the protein that is predicted to be heavily serine phosphorylated. This end of the protein is likely on the cytosolic half of the protein and serves in some activation function of a pathway.

Secondary structure

File:Secondary Structure prediction of human TMEM 249 isoform 1.png

Conceptual translation showing the predicted secondary structure of human TMEM249 isoform 1.

TMEM249 has a highly varied structure. Prediction data supports alternating regions of beta sheets and alpha helices. These predictions may support a beta barrel or "helix barrel" through the membrane made up of multiple protein monomers of TMEM249.

Expression

Promoter

File:TMEM249 Promoter Transcription Factor Binding Sites.png

The TMEM249 promoter region annotated for predicted transcription factor binding sites.

The promoter region was found using Eldorado from Genomatix.de (source), the region occupies a region upstream of the 5’ region of TMEM 249 on the minus strand of chromosome 8. This promoter binds a number of transcription factors as determined by Eldorado at Genomatix.de.

Tissue Expression

File:TMEM249 GEO Tissue Profile.png

The GEO profile taken from NCBI showing a wide variety of tissues that TMEM 249 is present in.

TMEM 249 expression is present at a high level in a wide variety of human tissues. GEO tissue profiles for this protein show that this protein is present in a wide variety of locations within the human body. The human protein atlas claims an even wider expression scope for this protein(source).

Function / Biochemistry

Interacting Proteins

There were no known protein interactions for TMEM 249.

Clinical Significance

TMEM249 has no known link to medical disease.

Mutations

File:TMEM249 SNPs.png

Single nucleotide polymorphisms of TMEM249 as collected by the SNP database on NCBI.

There exist a number of SNPs for TMEM 249 in humans. The mutations are scattered for the most part, with the largest changes in amino acids occurring in the domain of unknown function.

References

External links

1. San Diego Supercomputing Center. SDSC Biology Workbench. Available from: http://seqtool.sdsc.edu/CGI/BW.cgi^{[permanent dead link]}

2. Strausberg, RL; Feingold; Grouse, LH; Derge, JG; Klausner, RD; Collins, FS; Wagner, L; Shenmen, CM; Schuler, GD; Altschul, SF; et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.

3. NCBI - BLAST. [cited 2015 April 3]. Available from: http://blast.ncbi.nlm.nih.gov/Blast.cgi

4. Softberry. Available from: http://www.softberry.com/

5. Genomatix. Available from: https://www.genomatix.de/

6. Expasy. Available from: http://www.expasy.org/