Transmembrane protein 53

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Identifiers
Aliases|
External IDs| GeneCards: [1]
Orthologs
Species| Human| Mouse
Entrez| |

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Ensembl| |

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UniProt| |

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RefSeq (mRNA)| |

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RefSeq (protein)| |

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Location (UCSC)| n/a| n/a
PubMed search| n/a| n/a
Wikidata
| View/Edit Human|

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transmembrane protein 53

Identifiers
Symbol| TMEM53
Alt. symbols| FLJ22353, RP4-678E16.2
Entrez| 79639
HUGO| 26186
RefSeq| NP_078863
UniProt| Q6P2H8
Other data
Locus| Chr. 1 p34.1

Transmembrane protein 53, or TMEM53, is a protein that is encoded on chromosome 1 in humans.[1] It has no paralogs but is predicted to have many orthologs across eukaryotes.

## Contents

* 1 Properties and Structure
* 1.1 General Properties[2]
* 1.2 Secondary Structure
* 1.3 Alternative Splicing
* 2 Function
* 2.1 Expression
* 2.2 Homology
* 2.3 Predicted Post-Translational Modification
* 3 References

## Properties and Structure

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### General Properties[2]

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* 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 [1]

### Secondary Structure

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The secondary structure of TMEM53 is predicted to consist of alternating pairs of alpha helices and beta sheets.[2]

### Alternative Splicing

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TMEM53 has 3 exons. Twelve alternative splice forms have been identified using 26 alternative exons.[3] The following table includes the predicted post-translational modifications for each isoform.[4]

AceView Splice Form[3] | # 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)

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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

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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

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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.[5][6][7]

More specific expression patterns have also been observed:

* Expressed in mice at higher levels in dorsal root ganglia than in the spinal cord[8]
* Expressed at lower levels in brain tissue with Huntington's disease than in normal brain tissue[9]
* Expressed at very low levels in the mouse brain, with the areas of highest detectable expression being the hypothalamus, pons, midbrain, and amygdala[10]

### Homology

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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[11] and BLAT.[12] 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

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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[2] 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

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Using bioinformatic analysis tools like MyHits Motif Scan[4] and various tools at ExPASy[13] 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.[2] This suggests high likelihood that these sites are real and important for the protein's function.

## References

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1. ↑ 1.0 1.1 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. doi:10.1126/science.1088176. PMID 12958361.
2. ↑ 2.0 2.1 2.2 2.3 SDSC Biology Workbench 2.0
3. ↑ 3.0 3.1 NCBI AceView: TMEM53
4. ↑ 4.0 4.1 MyHits Motif Scan
5. ↑ EST Profile Viewer- Human
6. ↑ EST Profile Viewer- Mouse
7. ↑ 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. doi:10.1073/pnas.0400782101. PMC 395923. PMID 15075390.
8. ↑ 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.
9. ↑ 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". Human Molecular Genetics. 15 (2): 273–85. doi:10.1093/hmg/ddi443. PMID 16330479.
10. ↑ Allen Brain Atlas
11. ↑ NCBI BLAST: Basic Local Alignment Search Tool
12. ↑ BLAT Search Genome[permanent dead link]
13. ↑ ExPASy Proteomics Server