TMEM143 ( Transmembrane protein 143) is a protein that in humans is encoded by TMEM143 gene. TMEM143, a dual-pass protein (two transmembrane domains), is predicted to reside in the

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

and high expression has been found in both human

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

and the heart. Interaction with other proteins indicate that TMEM143 could potentially play a role in tumor suppression/expression and cancer regulation.

Gene

Located on the

negative strand In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, ...

of human DNA, TMEM143 spans 31,882 base pairs on human chromosome 19 (19q13.33), neighbored by genes

Coiled-coil A coiled coil is a structural motif in proteins in which 2–7 alpha helix, alpha-helices are coiled together like the strands of a rope. (Protein dimer, Dimers and Protein trimer, trimers are the most common types.) Many coiled coil-type protei ...

domain containing 114 (CCDC114) and ER lumen protein-retaining receptor 1 (KDELR1).

Transcript

In humans, there are five transcript variants encoded by TMEM143 gene (1-5). Variant 1 is the longest mRNA transcript, with a coding region of 2577 nucleotides (nt) and a total of 8

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s, and possibly most indicative of function. Compared to variant 1, variant 2 (2472 nt, 424 amino acid protein) and variant 3 (2382nt, 394 amino acid protein) lack an in-frame exon in the 5' coding region while variant 4 (2277 nt, 359 amino acid protein) lacks two in-frame exons in the 5’ coding region, all leading to an N-terminally truncated protein. Transcript variant 5 is a non-coding RNA, approximately 2231 nt long, resulting in a transcript candidate for nonsense-mediated mRNA.

Protein

There are four protein isoforms, corresponding to a matching variant. Variant 1 codes for isoform a (the longest protein), and variants 2, 3, 4 code for isoforms b, c, and d, respectively. TMEM143 isoform a is 459 amino acids in length, has a molecular weight of 51.6 kDa and an isoelectric point of 9.7 in humans. A domain of unknown function (DUF3754) is present within which two transmembrane domains reside, 24 and 16 amino acids in length, both helical in nature. The transmembrane domains encompass the uncharged region present at amino acids 278 to 302. A predicted mitochondrial target peptide resides at the N-terminus spanning 52 amino acids before the cleavage site between amino acids M-51 and G-52. In addition,

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

sites, both general and

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

-specific, were predicted to be found throughout the protein, indicating the location of the protein inside the cell.

Homology

Orthologs

Orthologs have been identified in more than 85 vertebrate species. No TMEM143 orthologs have yet to be identified in birds. There are currently 85 ortholog species, however all exist as vertebrates only (with the exception of birds), the most distant being

Latimeria chalumnae The West Indian Ocean coelacanth (''Latimeria chalumnae'') (sometimes known as gombessa, African coelacanth, or simply coelacanth) is a crossopterygian, one of two extant species of coelacanth, a rare order of vertebrates more closely related to ...

(coelacanth). DUF3754 appears in a majority of the orthologs, a generally conserved region, with slight amino acid alterations to the sequence. This domain has been found in organisms as diverse as bacteria and

archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...

, however there are no known orthologs in either organismal domain.

Paralogs

There are no known paralogs for the human TMEM143 sequence.

Expression and function

Tissue presence

Possible human expression of TMEM143 protein occurs in Jurkat cells (T lymphocyte). Organelle association puts TMEM143 in the mitochondria as an integral protein in the membrane, as well as the predicted of presence in the

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

, extracellular matrix and the Golgi apparatus. High expression has been found in the heart and skeletal muscle, as indicated through human expression profiling.

Microarray A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon t ...

expression of normal human tissues also predict expression in the heart and skeletal muscle, a 95-97 percentile rank (amongst other tissues tested for normal human expression of TMEM143).

Interactions

Through text mining, TMEM143 is shown to have interactions with seven different proteins in humans: Zinc finger protein 541 (ZNF541), DNA-damage inducible 1 homolog 2 (DD12), Paraneoplastic Ma antigen family-like 2 (PNMAL2), Kelch-like 31(JLHL31), Chromosome 14 open reading frame 28 (C14orf28), Chromosome 14 open reading frame 28 (TRIN71), and Cytoplasmic polyadenylation element binding protein 2 (CPEB). ZNF541 and PNMAL2, in relation to TMEM143, have been documented as having a role in the allelic loss of q13.3 of chromosome 19. This loss results in documented cases of malignant gliomas, neuroblastomas, and

ovarian carcinoma Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different cel ...

s, all suggesting a tumor suppression gene or genes in this region. While TMEM143 is not directly referred to in research in this area, it is present in this region on the chromosome, indicating a potential functional role in humans. Interactions between TMEM143 and DD12, JLHL31, C14orf28, TRIN71, and CPEB (in humans) have been documented through microarray data. Illustrating predicted gene regulation with different microRNA (miRNA) under

ionizing radiation Ionizing radiation (or ionising radiation), including nuclear radiation, consists of subatomic particles or electromagnetic waves that have sufficient energy to ionize atoms or molecules by detaching electrons from them. Some particles can travel ...

conditions, TMEM143 and DD12, JLHL31, C14orf28, TRIN71, and CPEB all share predicted regulatory miRNAs. TMEM143 has also been found to be associated with

adipocyte Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...

differentiation. Along with other genes, TMEM143 has been documented as a PPARγ (peroxisome proliferator-activated receptor gamma) target. This indicates the possibility of TMEM143 participation in lipid metabolic pathways and lipid cell differentiation

References

{{reflist, 30em Human proteins