TMEM267 is a protein that in humans is encoded by the TMEM267 gene. It is a possible oncogene which encodes a transmembrane protein. The function of TMEM267 most likely involves transportation of molecules from the cytosol, as the presence of motifs and domains involved in transportation were conserved in orthologs. TMEM267 has orthologs in many species and is expressed at highest levels in the thyroid.
Gene
Known aliases for TMEM267include C5orf28, B2RDA6, and Q9H6Z2.GeneCards.org entry on TMEM267 TMEM267 is found on chromosome 5, cytoband p12 on the reverse strand between base pairs 43,444,252 and 43,485,178, meaning it has length of 40,927 base pairs.GeneCards.org entry on TMEM267 TMEM267 produces 13 distinct gt-ag introns and 12 different mRNAs, with 9 alternatively spliced variants and 3 unspliced forms. It has 2 alternative promoters and 7 validated polyadenylation sites.UniProtKB entry on Q0VDI3 (TM267_HUMAN) There are 6 predicted promoters of varying lengths.
Name Accession number Number of Exons Size (bp) Transcript Variant 1 NM_022483 3 2736 Transcript Variant 2 NM_001377394.1 4 2887 Transcript Variant X2 XM_011514075 4 3574 Transcript Variant 3 NM_001377395.1 5 3210 Transcript Variant 4 NM_001377396.1 3 2960 Transcript Variant 5 NM_001377397.1 4 3108 Transcript Variant 6 NM_001377398.1 5 3283 Transcript Variant 7 NM_001377399.1 3 3377 Transcript Variant 8 NM_001377400.1 4 3528 Transcript Variant 9 NM_001377401.1 4 2834 Transcript Variant 10 NM_001377402.1 3 2809 Transcript Variant 11 NM_001377403.1 5 2979
Protein
General information The TMEM267 protein in all isoforms is 215 amino acids in length.NCBI (National Center for Biotechnology Information) AceView entry on C5orf28 All of the isoforms have a predicted molecular mass of 24.2 kDa and theoretical isoelectric point of 8.91.GeneCards.org entry on TMEM267ExPASy Compute pI/MW predictor / There was an above average percentage of histidine and tryptophan residues. The percentage of asparagine, glutamic acid and tyrosine were below average. After analysis of Antarctic Yellowbelly Rockcod, Tropical clawed frog, Willow flycatcher, Common wall lizard, and pacific white-sided dolphin orthologs, above average percent composition of tryptophan and below average percent composition of asparagine and glutamic acid residues was conserved across amphibians, fish, mammals, birds, and reptiles.SAPS entry on TMEM267
Isoforms Name Accession number Size (aa) Transcript Variant 2 NP_001364323.1 215 Transcript Variant X2 XM_011514075 215 Transcript Variant 3 NP_001364324 215 Transcript Variant 4 NP_001364325 215 Transcript Variant 5 NP_001364326 215 Transcript Variant 6 NP_001364327 215 Transcript Variant 7 NP_001364328 215 Transcript Variant 8 NP_001364329 215 Transcript Variant 9 NP_001364330 215 Transcript Variant 10 NP_001364331 215 Transcript Variant 11 NP_001364332 215 Transcript Variant 12 NP_071928 215
Transmembrane regions The predictions surrounding the transmembrane regions of TMEM267 are unclear. Some prediction tools claim there are no transmembrane or hydrophobic regions.SAPS entry on TMEM267 Others predict between 2 and 5 transmembrane domains.ELM entry for TMEM267 Prodom entry on TMEM267 The consensus is that there is most likely at least two transmembrane regions in the amino acids in the region around 113-135 and 176–198. The helical wheel diagrams of the three transmembrane regions given by NCBI Gene indicate the presence of polar amino acid which are basic and acidic in the transmembrane regions which is unusual.
Domains Two domains were predicted for TMEM267. First is a LaxA-binding, inner membrane-associated mutative hydrolase, which indicates that TMEM267 may be involved as a group of membrane-bound metal-dependent hydrolases that may act as phospholipases. The other is predicted to be a Vacuolar sorting protein 9 (VPS9) domain, which indicates that TMEM267 may be involved in trafficking of molecules to lysosomes and cell signaling.MotifFinder entry on TMEM267Hislop JN, Marley A, von Zastrow M. Role of Mammalian Vacuolar Protein-sorting Proteins in Endocytic Trafficking of a Non-ubiquitinated G Protein-coupled Receptor to Lysosomes. J Biol Chem 2004;279:22522–22531. Domain Location Conserved in Isoforms Conserved in Orthologs LaxA binding site 55-161 yes yes Vacuolar Sorting Protein 9 (VSP9) binding site 175-199 yes no
Motifs Motifs that were predicted are a canonical arginine-containing phosphopeptide motif, which may be involved in the transportation of the 14-3-3 proteins which are involved in many cellular processes.ELM Detail of Canonical Arginine-containing phosphopeptide motif A binding site for Interferon Regulatory Factor 3 (IRF-3) protein may be involved in the signaling pathway which actives IRF-3 in the presence of viral and microbial infections.IRF3 information Tryptophan-based motifs which enable targeting of tethering to a homology domain could mean that TMEM267 may play a role in mediating transportation form the Golgi to the ER. The coatomer subunit delta (delta-COP) is a cytosolic protein complex that binds to motifs and associates with vesicles involved in protein transport from the ER and Golgi.delta-COP protein An LC3-Interacting Region (LIR) motif was predicted, which indicates that TMEM267 may be involved in the autophagy pathway, which is involved in transferring of cytoplasmic material in autophagosomes to lysosomes as well as removal of toxic macromolecules and organelles to maintain the health of the cell.Wirth, M., Zhang, W., Razi, M. et al. Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins. Nat Commun 10, 2055 (2019). The Class 2 PDZ-binding motif predicts that TMEM267 could be involved with PDZ proteins, which are influential in trafficking, recycling, and intracellular sorting.Romero, G., von Zastrow, M., & Friedman, P. A. (2011). Role of PDZ proteins in regulating trafficking, signaling, and function of GPCRs: means, motif, and opportunity. Advances in pharmacology (San Diego, Calif.), 62, 279–314. The Wxxx[FY] motif indicates that TMEM267 could be involved in the interaction of Pex14 with Pex5 proteins.ELM Details for LIG_Pex14ELM entry for TMEM267
Motif Location Conserved in Isoforms Conserved in Orthologs Cellular Location Canonical arginine-containing phosphopeptide motif 49-56 Yes Yes cytosolInterferon Regulatory Factor 3 (IRF-3) binding site 139-146 Yes Yes cytosol Tryptophan-based motifs that enable tethering to a homology domain 144-151 Yes Yes cytosol LIR motif 64-68 Yes Yes cytosol PDZ-binding motif 210-215 Yes Yes cytosol Wxxx[FY] motif 166-170 Yes Yes cytosol
Localization and abundance
Overall, TMEM267 is most likely found in the cytoplasm. The TMEM267 protein was claimed to be localized in the nucleoplasm of cells.The Human Protein Atlas entry on TMEM267 Another tool predicted it to be found in the cytoplasm (69.6%) and mitochondrial (13%) with reliability 94.1 from Reinhardt's method for Cytoplasmic/Nuclear discrimination.PSORT prediction for TMEM267 TMEM267 is not abundant in the human body at 0.05 ppm.PaxDb protein abundance
Secondary structure predictions Secondary structure predictions were done using the transmembrane regions for TMEM267 given by NCBI Gene. The prediction servers indicate that amino acids 1-76 are helical in nature. The extracellular and intracellular regions of the TMEM267 protein are predicted to be a combination of alpha helices and beta sheets, but there is not a consensus.Chau-Fasman prediction for TMEM267GOR4 prediction for TMEM267Phyre 2 Prediction for TMEM267
Post-translational modifications
There is no evidence of post-translational modifications of the TMEM267 protein found in tissues.The Human Protein Atlas entry on TMEM267 According to protein sequence analysis, there is a prediction of one palmitoylation site, a SUMO Interaction and two sumoylation sites. There are many predicted phosphorylation sites in the non-transmembrane regions with various protein kinases including AGC, CKII, and Case kinase II.GPS for TMEM267NetPhos prediction for TMEM267 One site is predicted to be acetylated in the N-terminus of TMEM267.NetACET prediction for TMEM267 TMEM267 has four predicted glycation sites, as well as seven O-beta-GlycNAc sites.NetGlycate prediction for TMEM267YinOYang prediction for TMEM267
Expression
TMEM267 protein is expressed in over 100 tissues in the body, meaning it has low tissue specificity, but is largely present in the thyroid, pituitary gland, and pancreas. Data from NCBI Geo shows that there are higher levels of expression in mainly the thyroid but other tissues have varied expression for each sample. There seems to be, on average, highest expression levels in thyroid, ovaries, testes, pituitary gland, and pancreas. TMEM267 is not expressed at a very high level compared to Beta Actin, which has almost triple the RPKM compared to TMEM267.NCBI (National Center for Biotechnology Information) AceView entry on C5orf28 TMEM267 is expressed at 1.6 times the average gene on chromosome 5.NCBI (National Center for Biotechnology Information) AceView entry on C5orf28
Interactions Transcription factors The table below describes a curated set of transcription factors which are predicted to bind in the Genomatix predicted TMEM267 promoter region.
Transcription factor Detailed information RU49 Zinc finger proliferation 1-Zipro SORY SOX-SOY-sex/testis determining and related HMG box factors FKHD Fork head domain factors BRAC Brachyury gene, mesoderm developmental factor EVI1 EVI1-myleoid transformation protein VTBP Vertebrate TATA binding protein factor RUSH SWI/SNF related nucelophosphoproteins with RING finger DNA binding motif NKXH NKX homeodomain factors BRN5 Brn-5 POU domains PDX1 Pancreatic and intestinal homeodomain TF CEBPA/B CCAAT/Enhancer Binding Protein CAAT CCAAT binding factors SPZ1 Testis-specific bHLH-Zip TFs NFAT Nuclear factor of activated T-cells DMRT DM- domain-containing TFs ZF01 C2H2 zinc finger TF1 CREB cAMP-responsive element binding proteins XBBF X-box binding factors GCNR Germ cell nuclear receptor PLZF C2H2 zinc finger protein PLZF
Interacting proteins TMEM267 was predicted to interact with the proteins in the table below.