Transmembrane protein 53
| 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 | |||||||
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| 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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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.
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
[edit]The secondary structure of TMEM53 is predicted to consist of alternating pairs of alpha helices and beta sheets.[6]
Alternative Splicing
[edit]TMEM53 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
[edit]The 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
[edit]Based 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
[edit]Transmembrane 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
[edit]Using 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