Transmembrane protein 53, or TMEM53, is a protein that is encoded on chromosome 1 in humans.[5] It has no paralogs but is predicted to have many orthologs across eukaryotes.
| TMEM53 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | TMEM53, NET4, transmembrane protein 53, CTDI | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | MGI: 1916027; HomoloGene: 41573; GeneCards: TMEM53; OMA:TMEM53 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| transmembrane protein 53 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | TMEM53 | ||||||
| Alt. symbols | FLJ22353, RP4-678E16.2 | ||||||
| NCBI gene | 79639 | ||||||
| HGNC | 26186 | ||||||
| RefSeq | NP_078863 | ||||||
| UniProt | Q6P2H8 | ||||||
| Other data | |||||||
| Locus | Chr. 1 p34.1 | ||||||
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Properties and Structure
edit- DUF829 makes up 87% of TMEM53's length
- Contains a transmembrane domain but lacks a signal peptide
- Molecular weight 31.6 kilodaltons
- Isoelectric point 8.56
- Leucine-rich (14.4% of amino acids are leucines)
- Predicted to be localized to the nucleus [5]
Secondary Structure
editThe secondary structure of TMEM53 is predicted to consist of alternating pairs of alpha helices and beta sheets.[6]
Alternative Splicing
editTMEM53 has 3 exons. Twelve alternative splice forms have been identified using 26 alternative exons.[7] The following table includes the predicted post-translational modifications for each isoform.[8]
| AceView Splice Form[7] | # Amino Acids | % ID with RefSeq | # of Clones Found | DUF829 | CK2 sites | PKC sites | Tyr sites | Pumilio site | N-Myristoylation sites | Extras (not comparable to RefSeq) |
|---|---|---|---|---|---|---|---|---|---|---|
| a | 277 | RefSeq | 64 | X | 2 | 3 | 1 | 1 | 2 | |
| b | 247 | 88.8% | 6 | X | 2 | 2 | 1 | 1 | 2 | |
| c | 204 | 64.4% | 1 | X | 2 | 1 | 1 | 1 | 2 | Microbody C-terminal targeting signal |
| d | 204 | 73.6% | 10 | X | 2 | 2 | 1 | 1 | 1 | |
| e | 223 | 57.5% | 2 | X | 1 | 4 | 3 | |||
| f | 143 | 21.4% | 1 | X | 1 | 3 | 3 | Amidation site, Asn glycosylation site, cAMP-dependent phosphorylation site | ||
| g | 142 | n/a | 1 | 1 | 3 | 1 | ||||
| h | 137 | 45.1% | 2 | X | 1 | 3 | 2 | Protein prenyltransferase repeat | ||
| i | 129 | 32.1% | 1 | X | 4 | 2 | ||||
| j | 139 | 27.2% | 21 | X | 2 | 3 | ||||
| k | 110 | n/a | 1 | 1 | 4 | 3 | Amidation site, Asn glycosylation site, cAMP-dependent phosphorylation site | |||
| l | 106 | n/a | 5 | 3 |
Function
editThe function of TMEM53 is not fully understood. It contains a domain of unknown function, DUF829, which is approximately 240 amino acids long. This domain has not been found in proteins other than TMEM53 and its orthologs.
Expression
editBased on human and mouse EST profiles and a human tissue GEO profile, TMEM53 appears to be expressed ubiquitously at low levels in both normal and cancerous tissues.[9][10][11]
More specific expression patterns have also been observed:
- Expressed in mice at higher levels in dorsal root ganglia than in the spinal cord[12]
- Expressed at lower levels in brain tissue with Huntington's disease than in normal brain tissue[13]
- Expressed at very low levels in the mouse brain, with the areas of highest detectable expression being the hypothalamus, pons, midbrain, and amygdala[14]
Homology
editTransmembrane protein 53 has no paralogs. It does, however, have orthologs extending throughout eukaryotes, from primates to amoeba. The following table presents a selection of orthologs found using searches in BLAST[15] and BLAT.[16] It is not a comprehensive list, but rather a small selection meant to display the diversity of species in which orthologs are found.
| Scientific Name | Common Name | Accession Number | Sequence Length | Percent Identity | Percent Similarity |
|---|---|---|---|---|---|
| Homo sapiens | Human | NP_078863 | 277 aa | - | - |
| Macaca mulatta | Rhesus monkey | XP_001093396.1 | 204 aa | 97% | 98% |
| Canis lupus familiaris | Dog | XP_539639.2 | 278 aa | 88% | 92% |
| Mus musculus | Mouse | NP_081113.1 | 276 aa | 86% | 91% |
| Monodelphis domestica | Opossum | XP_001376124.1 | 405 aa | 69% | 82% |
| Gallus gallus | Chicken | XP_422420.1 | 276 aa | 56% | 70% |
| Xenopus laevis | Frog | NP_001086490.1 | 285 aa | 54% | 69% |
| Danio rerio | Zebrafish | NP_001002637.1 | 281 aa | 47% | 66% |
| Ciona intestinalis | Sea squirt | XP_002127410.1 | 290 aa | 37% | 51% |
| Drosophila melanogaster | Fruit fly | NP_610178.2 | 368 aa | 35% | 56% |
| Apis mellifera | Honey bee | XP_392954.1 | 326 aa | 32% | 52% |
| Strongylocentrotus purpuratus | Purple sea urchin | XP_788598.1 | 287 aa | 32% | 52% |
| Oryza sativa | Rice | EEC81354.1 | 412 aa | 31% | 45% |
| Nematostella vectensis | Sea anemone | XP_001628968.1 | 242 aa | 29% | 52% |
| Populus trichocarpa | Black cottonwood | XP_002306371.1 | 443 aa | 29% | 45% |
| Aspergillus nidulans | Fungus | XP_657927.1 | 285 aa | 27% | 44% |
| Dictyostelium discoideum | Amoeba | XP_644630.1 | 354 aa | 27% | 44% |
Based on ClustalW[6] multiple sequence alignments of 38 orthologs, including the ones above, 11 amino acids are completely conserved throughout all species with this protein.
Predicted Post-Translational Modification
editUsing bioinformatic analysis tools like MyHits Motif Scan[8] and various tools at ExPASy[17] and comparing to multiple sequence alignments, highly conserved potential sites of post-translational modification were identified. The following is not a comprehensive list of predicted modification sites; it includes only the ones that use highly conserved amino acids.
- CK2 phosphorylation sites 140-143, 217-220
- Tyrosine phosphorylation sites 209-216, 263
- PKC phosphorylation site 19-21 conserved in mammals
- N-myristoylation site 27-32 conserved in mammals
- N-myristoylation site 153-158 conserved in vertebrates
T216, the tyrosine for a tyrosine phosphorylation site, and S217, the serine for a predicted CK2 phosphorylation site, are completely conserved throughout the protein's evolutionary history.[6] This suggests high likelihood that these sites are real and important for the protein's function.
References
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000126106 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048772 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Schirmer EC, Florens L, Guan T, Yates JR, Gerace L (September 2003). "Nuclear membrane proteins with potential disease links found by subtractive proteomics". Science. 301 (5638): 1380–2. Bibcode:2003Sci...301.1380S. doi:10.1126/science.1088176. PMID 12958361. S2CID 23832536.
- ^ a b c d SDSC Biology Workbench 2.0
- ^ a b NCBI AceView: TMEM53
- ^ a b MyHits Motif Scan
- ^ EST Profile Viewer- Human
- ^ EST Profile Viewer- Mouse
- ^ Su AI, Wiltshire T, Batalov S, Lapp H, et al. (April 2004). "A gene atlas of the mouse and human protein-encoding transcriptomes". Proceedings of the National Academy of Sciences, USA. 101 (16): 6062–7. Bibcode:2004PNAS..101.6062S. doi:10.1073/pnas.0400782101. PMC 395923. PMID 15075390.
- ^ LeDoux MS, Xu L, Xiao J, Ferrell B, et al. (Aug 2006). "Murine central and peripheral nervous system transcriptomes: comparative expression". Brain Res. 1107 (1): 24–41. doi:10.1016/j.brainres.2006.05.101. PMID 16824496. S2CID 18764761.
- ^ Apostol BL, Illes K, Pallos J, Bodai L, et al. (Jan 2006). "Mutant huntingtin alters MAPK signaling pathways in PC12 and striatal cells: ERK1/2 protects against mutant huntingtin-associated toxicity" (PDF). Human Molecular Genetics. 15 (2): 273–85. doi:10.1093/hmg/ddi443. PMID 16330479.
- ^ Allen Brain Atlas
- ^ NCBI BLAST: Basic Local Alignment Search Tool
- ^ BLAT Search Genome[permanent dead link]
- ^ ExPASy Proteomics Server