TANGO2

Transport and golgi organization 2 homolog (TANGO2) also known as chromosome 22 open reading frame 25 (C22orf25) is a protein that in humans is encoded by the TANGO2 gene.

TANGO2
Identifiers
AliasesTANGO2, C22orf25, MECRCN, transport and golgi organization 2 homolog
External IDsOMIM: 616830 MGI: 101825 HomoloGene: 44029 GeneCards: TANGO2
Orthologs
SpeciesHumanMouse
Entrez

128989

27883

Ensembl

ENSG00000183597

ENSMUSG00000013539

UniProt

Q6ICL3

P54797

RefSeq (mRNA)

NM_138583

RefSeq (protein)

n/a

Location (UCSC)Chr 22: 20.02 – 20.07 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

The function of C22orf25 is not currently known. It is characterized by the NRDE superfamily domain (DUF883), which is strictly known for the conserved amino acid sequence of (N)-Asparagine (R)-Arginine (D)-Aspartic Acid (E)-Glutamic Acid. This domain is found among distantly related species from the six kingdoms:[4] Eubacteria, Archaebacteria, Protista, Fungi, Plantae, and Animalia and is known to be involved in Golgi organization and protein secretion.[5] It is likely that it localizes in the cytoplasm but is anchored in the cell membrane by the second amino acid.[6][7] 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.[8]

Protein
Gene SizeProtein Size# of exonsPromoter SequenceSignal PeptideMolecular WeightDomain Length
2271 bp276 aa9[9]687 bpNo[10]30.9 kDa[11]270 aa

Gene neighborhood

The C22orf25 gene is located on the long arm (q) of chromosome 22 in region 1, band 1, and sub-band 2 (22q11.21) starting at 20,008,631 base pairs and ending at 20,053,447 base pairs.[8] 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.[12][13] 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 (DGCR) genes and disease genes but other unidentified genes as well.[14]

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 (ARVCF), Cathechol-O-methyltransferase (COMT) and T-box 1 (TBX1).[15][16]

Gene Neighborhood of C22orf25
Gene Neighborhood of C22orf25

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.[17] The promoter region and beginning of the C22orf25 gene (20,008,263 to 20,009,250) 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.[18]

ReferenceDetailed Family InformationStart (amino acid)End (amino acid)Strand
XBBFX-box binding factors227245-
GCMFChorion-specific transcription factors (with a GCM DNA binding domain)151165-
YBXFY-box binding transcription factors158170-
RUSHSWI/SNF related nucleophosphoproteins (with a RING finger binding motif)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.[19][20][21] Expression is not restricted to these areas and low expression is seen elsewhere in the body. In Caenorhabditis elegans, the snt-1 gene (C22orf25 homologue) was expressed in the nerve ring, ventral and dorsal cord processes, sites of neuromuscular junctions, and in neurons.[22]

Evolutionary history

The NRDE (DUF883) 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 sapienshumansNP_690870.3276aa--Animalia-
Pan troglodytescommon chimpanzeeBAK62258.1276aa99%100%Animalia6.4 mya
Ailuropoda melanoleucagiant pandaXP_002920626276aa91%94%Animalia94.4 mya
Mus musculushouse mouseNP_613049.2276aa88%95%Animalia92.4 mya
Meleagris gallopavoturkeyXP_003210928276aa74%88%Animalia301.7 mya
Gallus gallusRed JunglefowlNP_001007837276aa73%88%Animalia301.7 mya
Xenopus laevisAfrican clawed frogNP_001083694275aa69%86%Animalia371.2 mya
Xenopus (Silurana) tropicalisWestern clawed frogNP_001004885.1276aa68%85%Animalia371.2 mya
Salmo salarAtlantic salmonNP_001167100274aa66%79%Animalia400.1 mya
Danio reriozebrafishNP_001003781273aa64%78%Animalia400.1 mya
CanarypoxvirusNP_955117275aa50%69%--
FowlpoxvirusNP_039033273aa44%63%--
CupriavidusproteobacteriaYP_002005507.1275aa38%52%Eubacteria2313.2 mya
BurkholderiaproteobacteriaYP_004977059273aa37%53%Eubacteria2313.2 mya
Physcomitrella patensmossXP_001781807275aa37%54%Plantae1369 mya
Zea maysmaize/cornACG35095266aa33%53%Plantae1369 mya
Trichophyton rubrumfungusXP_003236126306aa32%47%Fungi1215.8 mya
Sporisorium reilianumPlant pathogenCBQ69093321aa32%43%Fungi1215.8 mya
Perkinsus marinuspathogen of oystersXP_002787624219aa31%48%Protista1381.2 mya
Tetrahymena thermophiliaCiliate protozoaXP_001010229277aa26%44%Protista1381.2 mya
Natrialba magadiiextremophileYP_003481665300aa25%39%Archaebacteria3556.3 mya
Halopiger xanaduensishalophilic archaeonYP_004597780.1264aa24%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 (C-mannosylation),[23] glycation,[24] phosphorylation (kinase specific),[25] and palmitoylation.[26]

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[27] because it contributes to enhanced hydrophobicity.[6] Palmitoylation is known to play a role in the modulation of proteins' trafficking,[28] stability[29] and sorting.[30] Palmitoylation is also involved in cellular signaling[31] and neuronal transmission.[32]

Protein Interactions

C22orf25 has been shown to interact with NFKB1,[33] RELA,[33] RELB,[33] BTRC,[33] RPS27A,[33] BCL3,[34] MAP3K8,[33] NFKBIA,[33] SIN3A,[33] SUMO1,[33] Tat.[35]

Clinical significance

Mutations in the TANGO2 gene may cause defects in mitochondrial β-oxidation[36] and increased endoplasmic reticulum stress and a reduction in Golgi volume density.[37] These mutations results in early onset hypoglycemia, hyperammonemia, rhabdomyolysis, cardiac arrhythmias, and encephalopathy that later develops into cognitive impairment.[36][37]

References
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  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  6. "CSS-Palm".
  7. "PSORTII".
  8. "Gene (NCBI)".
  9. "ElDorado (Genomatix)".
  10. "SignalP (ExPASy)".
  11. "Statistical Analysis of Protein Sequence (Biology Workbench)".
  12. Meechan DW, Maynard TM, Tucker ES, LaMantia AS (2011). "Three phases of DiGeorge/22q11 deletion syndrome pathogenesis during brain development: Patterning, proliferation, and mitochondrial functions of 22q11 genes". International Journal of Developmental Neuroscience. 29 (3): 283–294. doi:10.1016/j.ijdevneu.2010.08.005. PMC 3770287. PMID 20833244.
  13. Kniffin C. "DiGeorge Syndrome; DGS. Retrieved April 2012, from Online Mendelian Inheritance in Man".
  14. Scambler PJ (2000). "The 22q11 deletion syndromes". Hum. Mol. Genet. 9 (16): 2421–6. doi:10.1093/hmg/9.16.2421. PMID 11005797.
  15. "22q11.2 Deletion Syndrome". University of Washington, Seattle. 1993.
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  17. "El Durado (Genomatix)".
  18. "El Durado-Genomatix".
  19. "Unigene NCBI". Archived from the original on 2013-07-12. Retrieved 2012-04-26.
  20. "GEO Profiles NCBI".
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  22. "WormBase".
  23. "NetCGly (ExPASy)".
  24. "NetGlycate (ExPASy)".
  25. "Phos (ExPASy)".
  26. "CSS Palm (ExPASy)".
  27. Resh MD (2006). "Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules". Science's STKE. 2006 (359): 14. doi:10.1126/stke.3592006re14. PMID 17077383. S2CID 25729573.
  28. Draper JM, Xia Z, Smith CD (Aug 2007). "Cellular palmitoylation and trafficking of lipated peptides". Journal of Lipid Research. 48 (8): 1873–1884. doi:10.1194/jlr.m700179-jlr200. PMC 2895159. PMID 17525474.
  29. Linder ME, Deschenes RJ (Jan 2007). "Palmitoylation: policing protein stability and traffic". Nature Reviews Molecular Cell Biology. 8 (1): 74–84. doi:10.1038/nrm2084. PMID 17183362. S2CID 26339042.
  30. Greaves J, Chamberlain LH (Jan 2007). "Palmitoylation-dependent protein sorting". The Journal of Cell Biology. 176 (3): 249–254. doi:10.1083/jcb.200610151. PMC 2063950. PMID 17242068.
  31. Casey PJ (1995). "Protein lipidation in cell signaling". Science. 268 (5208): 221–5. Bibcode:1995Sci...268..221C. doi:10.1126/science.7716512. PMID 7716512.
  32. Roth AF, Wan J, Bailey AO, Sun B, Kuchar JA, Green WN, Phinney BS, Yates JR, Davis NG (June 2006). "Global analysis of protein palmitoylation in yeast". Cell. 125 (5): 1003–1013. doi:10.1016/j.cell.2006.03.042. PMC 2246083. PMID 16751107.
  33. "Molecular Interaction Database". Archived from the original on 2006-05-06.
  34. "Molecular Interaction Database". Archived from the original on 2006-05-06.
  35. "Viral Molecular Interaction Database". Archived from the original on 2015-02-15.
  36. Kremer LS, Distelmaier F, Alhaddad B, Hempel M, Iuso A, Küpper C, et al. (2016). "Bi-allelic Truncating Mutations in TANGO2 Cause Infancy-Onset Recurrent Metabolic Crises with Encephalocardiomyopathy". American Journal of Human Genetics. 98 (2): 358–62. doi:10.1016/j.ajhg.2015.12.009. PMC 4746337. PMID 26805782.
  37. Lalani SR, Liu P, Rosenfeld JA, Watkin LB, Chiang T, Leduc MS, et al. (2016). "Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations". American Journal of Human Genetics. 98 (2): 347–57. doi:10.1016/j.ajhg.2015.12.008. PMC 4746334. PMID 26805781.
  • www.tango2.it - Disease website
  • www.tango2research.org - Research disease website -
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