Transmembrane protein 53

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
Identifiers
Aliases	TMEM53, NET4, transmembrane protein 53, CTDI
External IDs	MGI: 1916027; HomoloGene: 41573; GeneCards: TMEM53; OMA:TMEM53 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p34.1 Start 44,635,238 bp[1] End 44,674,481 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D1 Start 117,109,148 bp[2] End 117,125,779 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver mucosa of transverse colon sperm left testis right testis gonad epithelium of nasopharynx testicle apex of heart prefrontal cortex Top expressed in seminiferous tubule spermatid right kidney vestibular membrane of cochlear duct proximal tubule adrenal gland spermatocyte left lobe of liver human kidney brown adipose tissue More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 79639 68777 Ensembl ENSG00000126106 ENSMUSG00000048772 UniProt Q6P2H8 Q9D0Z3 RefSeq (mRNA) NM_001300746 NM_001300747 NM_001300748 NM_024587 NM_001285812 NM_001285814 NM_001285815 NM_001285816 NM_026837 NM_029589 RefSeq (protein) NP_001287675 NP_001287676 NP_001287677 NP_078863 NP_001272741 NP_001272743 NP_001272744 NP_001272745 NP_081113 NP_083865 Location (UCSC) Chr 1: 44.64 – 44.67 Mb Chr 4: 117.11 – 117.13 Mb PubMed search [3] [4]
Wikidata
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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
Search for Structures Swiss-model Domains InterPro

Properties and Structure

General Properties^[6]

• 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

The secondary structure of TMEM53 is predicted to consist of alternating pairs of alpha helices and beta sheets.^[6]

Alternative Splicing

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

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

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

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

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.