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TANGO6 (Transport and Golgi Organization 6), also known as TMCO7, is a gene and protein in humans located on the 16th chromosome in section 22.1. The Function of TANGO6 is not yet well understood. TANGO6 contains two Domains of Unknown Function, DUF2435 and DUF2411, as well as one HEAT domain. These domains are all near the C-terminus and are highly conserved going back to Fruit Flies. The TANGO6 is a transmembrane protein localized within the Golgi body of the cell.

Disease Association and Clinical Significance
TANGO6 levels are shown to be underexpressed in cells with Herpes Virus 8, in cells with a Dicer Deficiency , and in ovary cells with stonewall deficiencies. Further testing also shows that TANGO6 is expressed less in cells with CD133 deletion, potentially linking TANGO6 expression levels to various types of cancer. TANGO6 is expressed at its highest levels within human cells with Leukemia, then colon cancer, osteosarcoma, non-small cell lung carcinoma, kidney cancer, Central Nervous System cancer, breast cancer, and then finally at its lowest level in healthy human cells. Certain cases of leukemia saw TANGO6 levels 27x higher than in normal cells.

Properties
The TANGO6 protein sequence is leucine rich with 15% leucine residues overall. The TANGO6 protein sequence also contains 82 multiplets, and does not have long charged segments.

Location
TANGO6 is found on Chromosome 16 at locus q22.1 with the genomic sequence starting at 68,877,456bp going through 69,117,591bp

Gene Neighborhood
TANGO6 is located on the positive strand surrounded by 12 nearby genes.

Positive Orientation On the positive strand in the 5' direction of TANGO6 lie the CDH3 and CDH1 genes. On the same strand in the 3' direction of TANGO6 lie the HAS1, CIRH1A, SNTB2 and NIP7 genes.

Negative Orientation On the negative strand the genes TERF2, TMED6, and CFTH8 are found.

Expression
TANGO6 is expressed at similar levels in virtually all human cells, with slightly increased expression in the Testes, Bronchial Epithelial Cells, Lymphoma Burkitts (Daudl), Atrioventricular Node, 721 B Lymphoblasts, and significantly more in Lymphoma Burkitts (RajI) and CD56+ NK cells.

Known Domains
The three known domains within the TANGO6 protein are all found near the C-terminus of the mature protein.

DUF2435
The largest domain both in number of amino acids and weight. With 80 amino acids, an isoelectric point of 4.39 and a molecular weight of 9.2 kDal, this domain is found within the cell and contains an alpha-helix 37 amino acids long, the function of this domain is unknown.

HEAT
Next largest of the domains is the HEAT domain with a molecular weight of 4.2 kDal and an isoelectric point of 9.74. This domain is found inside the cell and contains 37 amino acids. This domain is perhaps the most interesting of the three, it consists of a multi-helical fold made of two curved layers of alpha helices arranged in a right handed super-helix. This domain is good at binding large substrates such as proteins and nucleic acids and is found in proteins such as RNA-binding protein, Importins, Karyopherins, Exportins, and Initiation factors. It is likely that this domain binds to cargo molecules within the golgi and organizes and controls where these substrate molecules end up within the cell.

DUF2411
Finally, the smallest of the found domains is the DUF2411 domain found outside of the cell within the golgi. This domain is 36 amino acids long, has a molecular weight of 4 kDal, and has an isoelectric point of 4.47999.

Transmembrane Domains
The TANGO6 protein has four predicted transmembrane domains ranging in length from 18 to 29 amino acids.



Homologs, Orthologs, and Paralogs
TANGO6 protein homologs are found in Chimpanzees, Rhesus Monkeys, Dogs, Cows, Mice, Chicken, and Zebrafish. Orthologs are found in 73 different organisms, ranging from Mallards, Western Clawed Frogs, Starlet Sea Anemone, Acorn Worms, American Alligator, Carpenter Ants, Fruit Flies, Pacific Oysters, Purple Sea Urchin, and Human Louse. The TANGO6 gene is highly conserved through a wide variety of organisms from mammals to fruit flies and has a steady rate of change in the analyzed homologs.

Paralogs
A search of the Homo Sapien genome via BLAST yielded no paralogs with appropriate E-values for any legitimate paralogs to be found.

Post Transcriptional Modification
Protein analysis shows that the mature TANGO6 protein has 3 glycosylation sites, 1 Mannosylation site , 28 O-glycosylation sites , and 29 phosphorylation sites located on the mature TANGO6 protein.



Secondary Structure
PELE analysis of the Homo Sapien TANGO6 protein yielded 20 Alpha-Helix regions varying from 6 to 37 amino acids in length and 4 Beta-Sheet areas. Multiple Sequence Alignment between Humans, Mice, Bonobos, and Brown Bats shows that all 24 of these secondary structure sites are highly conserved between relatively closely related organisms.

Promoter
The promoter sequence of this protein is found just upstream of the short 12bp 5’ UTR and contains a variety of transcription factor binding sites ranging from Estrogen Response Factors, Fork Head Domain Factors, AT Rich Interactive Domain Factors, Octamer Binding Proteins, GLI Zink Finger Family Promoter, GC Box Factors, Activator/Repressor Binding to Transcription Initiation Site, and TATA Boxes. Overall TANGO6 has a variety of transcription factors showing the need for its expression in a wide variety of cells and situations. This is further supported by the fact that this protein is found within virtually all tissues within the human body at very similar levels.



TANGO6 Gene Structure Alternatives
There are 12 variants for the TANGO6 mRNA. Of these, 6 contain a single exon variant that is very rarely found in the cell with values between 1 and 7, vs. the normal exons with values between 83 and 580. Each of the 6 variants contain just one differing exon, while the rest remain the in the same order and sequence as the primary TANGO6 mRNA.



Protein Interactions
TANGO6 interacts with a variety of proteins in both Homo sapiens and Drosophila melanogaster, however the most important of these interactions was seen in the MACF1 protein and the PTP4A3 protein. Both of these proteins deal with Microtubules and Actin filaments. MACF1 forms crosslinks between Microtubules and filamentous Actin fibers, and could lead to the positioning and movement of the TANGO6 protein within the Golgi and its overall location within the cell. Finally, PTP4A3 makes up one of the subunits of the mature microtubule assembly. As with MACF1, this protein could lead to the controlled location and movement of the TANGO6 protein within the cell and the golgi apparatus. Other protein interactions include Ubiquitin Conjugating Enzyme E2 S, which catalyzes Lys-11 ubiquitination, which marks TANGO6 for degradation.