TANGO2


Transport and golgi organization 2 homolog also known as chromosome 22 open reading frame 25 is a protein that in humans is encoded by the TANGO2 gene.
The function of C22orf25 is not currently known. It is characterized by the NRDE superfamily domain, which is strictly known for the conserved amino acid sequence of -Asparagine -Arginine -Aspartic Acid -Glutamic Acid. This domain is found among distantly related species from the six kingdoms: Eubacteria, Archaebacteria, Protista, Fungi, Plantae, and Animalia and is known to be involved in Golgi organization and protein secretion. It is likely that it localizes in the cytoplasm but is anchored in the cell membrane by the second amino acid. C22orf25 is also xenologous to T10 like proteins in the Fowlpox Virus and Canarypox Virus. The gene coding for C22orf25 is located on chromosome 22 and the location q11.21, so it is often associated with 22q11.2 deletion syndrome.

Protein

Gene SizeProtein Size# of exonsPromoter SequenceSignal PeptideMolecular WeightDomain Length
2271 bp276 aa9687 bpNo30.9 kDa270 aa

Gene neighborhood

The C22orf25 gene is located on the long arm of chromosome 22 in region 1, band 1, and sub-band 2 starting at 20,008,631 base pairs and ending at 20,053,447 base pairs. There is a 1.5-3.0 Mb deletion containing around 30-40 genes, spanning this region that causes the most survivable genetic deletion disorder known as 22q11.2 deletion syndrome, which is most commonly known as DiGeorge syndrome or Velocaridofacial syndrome. 22q11.2 deletion syndrome has a vast array of phenotypes and is not attributed to the loss of a single gene. The vast phenotypes arise from deletions of not only DiGeorge Syndrome Critical Region genes and disease genes but other unidentified genes as well.
C22orf25 is in close proximity to DGCR8 as well as other genes known to play a part in DiGeorge Syndrome such as armadillo repeat gene deleted in Velocardiofacial syndrome, Cathechol-O-methyltransferase and T-box 1.

Predicted mRNA features

Promoter

The promoter for the C22orf25 gene spans 687 base pairs from 20,008,092 to 20,008,878 with a predicted transcriptional start site that is 104 base pairs and spans from 20,008,591 to 20,008,694. The promoter region and beginning of the C22orf25 gene is not conserved past primates. This region was used to determine transcription factor interactions.

Transcription factors

Some of the main transcription factors that bind to the promoter are listed below.
ReferenceDetailed Family InformationStart End Strand
XBBFX-box binding factors227245-
GCMFChorion-specific transcription factors 151165-
YBXFY-box binding transcription factors158170-
RUSHSWI/SNF related nucleophosphoproteins 222232-
NEURNeuroD, Beta2, HLH domain214226-
PCBEPREB core-binding element148162-
NR2FNuclear receptor subfamily 2 factors169193-
AP1RMAF and AP1 related factors201221-
ZF02C2H2 zinc finger transcription factors 2108130-
TALETALE homeodomain class recognizing TG motifs216232-
WHNFWinged helix transcription factors271281-
FKHDForkhead domain factors119135+
MYODMyoblast determining factors218234+
AP1FAP1, activating protein 1118130+
BCL6POZ domain zinc finger expressed in B cells190206+
CARECalcium response elements196206+
EVI1EVI1 nuclear transcription factor90106+
ETSFETS transcription factor162182+
TEAFTEA/ATTS DNA binding domain factors176188+

Expression analysis

Expression data from Expressed Sequence Tag mapping, microarray and in situ hybridization show high expression for Homo sapiens in the blood, bone marrow and nerves. Expression is not restricted to these areas and low expression is seen elsewhere in the body. In Caenorhabditis elegans, the snt-1 gene was expressed in the nerve ring, ventral and dorsal cord processes, sites of neuromuscular junctions, and in neurons.

Evolutionary history

The NRDE domain, is a domain of unknown function spanning majority of the C22orf25 gene and is found among distantly related species, including viruses.
Genus and SpeciesCommon NameAccession NumberSeq.
Length		Seq.
Identity		Seq.
Similarity		KingdomTime of Divergence
Homo sapienshumans276aa--Animalia-
Pan troglodytescommon chimpanzee276aa99%100%Animalia6.4 mya
Ailuropoda melanoleucagiant panda276aa91%94%Animalia94.4 mya
Mus musculushouse mouse276aa88%95%Animalia92.4 mya
Meleagris gallopavoturkey276aa74%88%Animalia301.7 mya
Gallus gallusRed Junglefowl276aa73%88%Animalia301.7 mya
Xenopus laevisAfrican clawed frog275aa69%86%Animalia371.2 mya
Xenopus tropicalisWestern clawed frog276aa68%85%Animalia371.2 mya
Salmo salarAtlantic salmon274aa66%79%Animalia400.1 mya
Danio reriozebrafish273aa64%78%Animalia400.1 mya
Canarypoxvirus275aa50%69%--
Fowlpoxvirus273aa44%63%--
Cupriavidusproteobacteria275aa38%52%Eubacteria2313.2 mya
Burkholderiaproteobacteria273aa37%53%Eubacteria2313.2 mya
Physcomitrella patensmoss275aa37%54%Plantae1369 mya
Zea maysmaize/corn266aa33%53%Plantae1369 mya
Trichophyton rubrumfungus306aa32%47%Fungi1215.8 mya
Sporisorium reilianumPlant pathogen321aa32%43%Fungi1215.8 mya
Perkinsus marinuspathogen of oysters219aa31%48%Protista1381.2 mya
Tetrahymena thermophiliaCiliate protozoa277aa26%44%Protista1381.2 mya
Natrialba magadiiextremophile300aa25%39%Archaebacteria3556.3 mya
Halopiger xanaduensishalophilic archaeon264aa24%39%Archaebacteria3556.3 mya

Predicted protein features

Post translational modifications

Post translational modifications of the C22orf25 gene that are evolutionarily conserved in the Animalia and Plantae kingdoms as well as the Canarypox Virus include glycosylation, glycation, phosphorylation, and palmitoylation.

Predicted topology

C22orf25 localizes to the cytoplasm and is anchored to the cell membrane by the second amino acid. As mentioned previously, the second amino acid is modified by palmitoylation. Palmitoylation is known to contribute to membrane association because it contributes to enhanced hydrophobicity. Palmitoylation is known to play a role in the modulation of proteins' trafficking, stability and sorting. Palmitoylation is also involved in cellular signaling and neuronal transmission.

Protein Interactions

C22orf25 has been shown to interact with NFKB1, RELA, RELB, BTRC, RPS27A, BCL3, MAP3K8, NFKBIA, SIN3A, SUMO1, Tat.

Clinical significance

Mutations in the TANGO2 gene may cause defects in mitochondrial β-oxidation and increased endoplasmic reticulum stress and a reduction in Golgi volume density. These mutations results in early onset hypoglycemia, hyperammonemia, rhabdomyolysis, cardiac arrhythmias, and encephalopathy that later develops into cognitive impairment.