TMEM50A

TMEM50A
Identifiers
Aliases	TMEM50A , IFNRC, SMP1, transmembrane protein 50A
External IDs	OMIM: 605348 MGI: 1919067 HomoloGene: 4469 GeneCards: TMEM50A
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1p36.11 Start 25,338,317 bp [1] End 25,362,361 bp [1]
Gene location (Mouse) Chr. Chromosome 4 (mouse) [2] Band 4 D3|4 67.14 cM Start 134,625,160 bp [2] End 134,642,335 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte palpebral conjunctiva pericardium parotid gland gums corpus epididymis lactiferous duct germinal epithelium vena cava Left adrenal gland Top expressed in adrenal gland calvaria thymus belly cord otolith organ utricle blood sciatic nerve endocardial cushion esophagus More reference expression data BioGPS More reference expression data
Orthologs Species Human Mouse Entrez 23585 71817 Ensembl ENSG00000183726 ENSMUSG00000028822 UniProt O95807 Q9CXL1 RefSeq (mRNA) NM_014313 NM_027935 RefSeq (protein) NP_055128 NP_082211 Location (UCSC) Chr 1: 25.34 – 25.36 Mb Chr 4: 134.63 – 134.64 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transmembrane protein 50A is a protein that in humans is encoded by the TMEM50A gene. ^{[5] [6] [7]}

This gene is located in the RH gene locus, between the RHD and RHCE genes. The function of its protein product is unknown; however, its sequence has potential transmembrane domains suggesting that it may be an integral membrane protein. Its position between the RH genes suggests that polymorphisms in this gene may be tightly linked to RH haplotypes and may contribute to selective pressure for or against certain RH haplotypes. ^[7]

Gene

The TMEM50A gene is located on chromosome 1 p36.11 in the human (homo sapiens) genome. Its mRNA sequence is 2284 base pairs in length and includes seven exons. The coding sequence is from base pairs 151 to 624.

Protein

The TMEM50A protein is 157 amino acids in length.

Cellular Location

PSORT II predicts that TMEM50A is most likely found in the cells plasma membrane or the endoplasmic reticulum.

Predicted properties

Through bioinformatic analysis several of TMEM50A's protein properties were predicted.

• Molecular Weight: 17.4 KDal ^[8]
• Isoelectric point: 5.483 ^[9]
• Post-translational modification: Several post-translational modifications are predicted:
  • Two serine phosphorylation sites found at amino acids 82 and 84 Residue ^[10]
  • One possibleN-Linked Glycosylation Site located at amino acid 74 ^[10]
  • One possible Tyrosine phosphorylation site

Structure

The exact structure of TMEM50A is unknown but through the use of several prediction programs, some of its most likely structural components can be assumed.

• TMHMM shows that TMEM50A has four transmembrane regions. This was further confirmed by similar results found in TMEM50A orthologs and the neutral charge found in these regions using SAPS program in Biology Workbench
• By using the PELE program in Biology Workbench along with comparing the results of known protein structures, it can be predicted that TMEM50A has:
  • Two Alpha Helix structures
  • Five Beta Sheets

Splice Sites

Alternative Splice sites were found by BLAT on the UCSC genome browser

TMEM50A has several alternative splices including:

• Removal of exon 2
• Removal of exons 2 and 3
• Removal of exons 2, 3, and 5
• Removal of exon 3
• Removal of exon 5

These alternative splice sites don't affect the reading frame of the sequence and thus may not alter the function of the protein.

Expression

TMEM50A is expressed in almost all human tissues, but evidence from EST profiles through NCBI, suggests that its expression may be slightly higher in parathyroid tissues and brain tissues. It also seems to be expressed higher during the neonate and juvenile development stages.

Interacting Proteins

There is one predicted protein that interacts with TMEM50A, C7orf43. This proteins gene is located on chromosome 7 open reading frame 43. Its function is also unknown.

Future Medical Applications

Investigation of several GEO profiles showed that TMEM50A is highly upregulated in late stage cervical cancer. This may suggest that TMEM50A has some function that may be causing or is caused directly by cervical cancer. Although few studies are available to confirm this idea, more studies may offer suggestions that use TMEM50A for treatment of late stage cervical cancer.

References

1. GRCh38: Ensembl release 89: ENSG00000183726 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028822 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Flegel WA, Wagner FF (Dec 2000). "Molecular genetics of RH". Vox Sang. 78 Suppl 2: 109–15. PMID   10938938.
6. Wagner FF, Flegel WA (Aug 2000). "RHD gene deletion occurred in the Rhesus box". Blood. 95 (12): 3662–8. doi:10.1182/blood.V95.12.3662. PMID   10845894.
7. "Entrez Gene: TMEM50A transmembrane protein 50A".
8. Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (March 1992). "Methods and algorithms for statistical analysis of protein sequences". Proceedings of the National Academy of Sciences of the United States of America. 89 (6): 2002–6. Bibcode:1992PNAS...89.2002B. doi: 10.1073/pnas.89.6.2002 . PMC   48584 . PMID   1549558.
9. "PI Program (Isoelectric Point Prediction)". Archived from the original on 2008-10-26.
10. "UniProt Database".

Further reading

• Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC   1347501 . PMID   16381901.
• Tao WA, Wollscheid B, O'Brien R, et al. (2005). "Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry". Nat. Methods. 2 (8): 591–8. doi:10.1038/nmeth776. PMID   16094384. S2CID   20475874.
• Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to Biology: A Functional Genomics Pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Clark HF, Gurney AL, Abaya E, et al. (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.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Wagner FF, Flegel WA (2002). "RHCE represents the ancestral RH position, while RHD is the duplicated gene". Blood. 99 (6): 2272–3. doi: 10.1182/blood-2001-12-0153 . PMID   11902138.
• Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC   1083732 . PMID   11256614.
• Wiemann S, Weil B, Wellenreuther R, et al. (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.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.