TANGO2

Last updated

TANGO2
Identifiers
Aliases TANGO2 , C22orf25, MECRCN, transport and golgi organization 2 homolog
External IDs OMIM: 616830; MGI: 101825; HomoloGene: 44029; GeneCards: TANGO2; OMA:TANGO2 - orthologs
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 Mb n/a
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

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.

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.gif
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-
WHNF Winged helix transcription factors 271281-
FKHDForkhead domain factors119135+
MYODMyoblast determining factors218234+
AP1F AP1, activating protein 1 118130+
BCL6POZ domain zinc finger expressed in B cells190206+
CARECalcium response elements196206+
EVI1 EVI1 nuclear transcription factor 90106+
ETSF ETS transcription factor 162182+
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 sapiens humans NP_690870.3 276aa--Animalia-
Pan troglodytes common chimpanzee BAK62258.1 276aa99%100%Animalia6.4 mya
Ailuropoda melanoleuca giant panda XP_002920626 276aa91%94%Animalia94.4 mya
Mus musculus house mouse NP_613049.2 276aa88%95%Animalia92.4 mya
Meleagris gallopavo turkey XP_003210928 276aa74%88%Animalia301.7 mya
Gallus gallus Red Junglefowl NP_001007837 276aa73%88%Animalia301.7 mya
Xenopus laevis African clawed frog NP_001083694 275aa69%86%Animalia371.2 mya
Xenopus (Silurana) tropicalis Western clawed frog NP_001004885.1 276aa68%85%Animalia371.2 mya
Salmo salar Atlantic salmon NP_001167100 274aa66%79%Animalia400.1 mya
Danio rerio zebrafish NP_001003781 273aa64%78%Animalia400.1 mya
Canarypox virus NP_955117 275aa50%69%--
Fowlpox virus NP_039033 273aa44%63%--
Cupriavidus proteobacteria YP_002005507.1 275aa38%52%Eubacteria2313.2 mya
Burkholderia proteobacteria YP_004977059 273aa37%53%Eubacteria2313.2 mya
Physcomitrella patens moss XP_001781807 275aa37%54%Plantae1369 mya
Zea mays maize/corn ACG35095 266aa33%53%Plantae1369 mya
Trichophyton rubrum fungus XP_003236126 306aa32%47%Fungi1215.8 mya
Sporisorium reilianum Plant pathogen CBQ69093 321aa32%43%Fungi1215.8 mya
Perkinsus marinus pathogen of oysters XP_002787624 219aa31%48%Protista1381.2 mya
Tetrahymena thermophilia Ciliate protozoa XP_001010229 277aa26%44%Protista1381.2 mya
Natrialba magadii extremophile YP_003481665 300aa25%39%Archaebacteria3556.3 mya
Halopiger xanaduensis halophilic archaeon YP_004597780.1 264aa24%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, [33] MAP3K8, [33] NFKBIA, [33] SIN3A, [33] SUMO1, [33] Tat. [34]

Clinical significance

Mutations in the TANGO2 gene may cause defects in mitochondrial β-oxidation [35] and increased endoplasmic reticulum stress and a reduction in Golgi volume density. [36] These mutations results in early onset hypoglycemia, hyperammonemia, rhabdomyolysis, cardiac arrhythmias, and encephalopathy that later develops into cognitive impairment. [35] [36] Abnormal autophagy and mitophagy have been associated with TANGO2-related disease and may explain the varying presentation in muscle biopsies, including secondary abnormal fatty acid and mitochondrial metabolism. [37]

Related Research Articles

<span class="mw-page-title-main">Mitochondrial myopathy</span> Muscle disorders caused by mitochondrial dysfunction

Mitochondrial myopathies are types of myopathies associated with mitochondrial disease. Adenosine triphosphate (ATP), the chemical used to provide energy for the cell, cannot be produced sufficiently by oxidative phosphorylation when the mitochondrion is either damaged or missing necessary enzymes or transport proteins. With ATP production deficient in mitochondria, there is an over-reliance on anaerobic glycolysis which leads to lactic acidosis either at rest or exercise-induced.

<span class="mw-page-title-main">TBX1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">VPS13B</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">YIF1A</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">KIAA1109</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">LZTR1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">DHHC domain</span>

In molecular biology the DHHC domain is a protein domain that acts as an enzyme, which adds a palmitoyl chemical group to proteins in order to anchor them to cell membranes. The DHHC domain was discovered in 1999 and named after a conserved sequence motif found in its protein sequence. Roth and colleagues showed that the yeast Akr1p protein could palmitoylate Yck2p in vitro and inferred that the DHHC domain defined a large family of palmitoyltransferases. In mammals twenty three members of this family have been identified and their substrate specificities investigated. Some members of the family such as ZDHHC3 and ZDHHC7 enhance palmitoylation of proteins such as PSD-95, SNAP-25, GAP43, Gαs. Others such as ZDHHC9 showed specificity only toward the H-Ras protein. However, a recent study questions the involvement of classical enzyme-substrate recognition and specificity in the palmitoylation reaction. Several members of the family have been implicated in human diseases.

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<span class="mw-page-title-main">Coiled-coil domain containing protein 120</span> Protein-coding gene in humans

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<span class="mw-page-title-main">FAM214A</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Proser2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">ZCCHC18</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">TMEM171</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">C22orf23</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">LSMEM2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CCDC188</span> Protein found in humans

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<span class="mw-page-title-main">DiGeorge syndrome</span> Medical condition caused by chromosomal abnormality

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent infections, developmental disability, intellectual disability and cleft palate. Associated conditions include kidney problems, schizophrenia, hearing loss and autoimmune disorders such as rheumatoid arthritis or Graves' disease.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000183597 – Ensembl, May 2017
  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.
  4. ↑ "BLAST (NCBI)".
  5. ↑ "Conserved Domains (NCBI)".
  6. 1 2 "CSS-Palm". Archived from the original on 2009-02-15. Retrieved 2012-05-08.
  7. ↑ "PSORTII".
  8. 1 2 "Gene (NCBI)".
  9. ↑ "ElDorado (Genomatix)". Archived from the original on 2021-12-02. Retrieved 2012-04-27.
  10. ↑ "SignalP (ExPASy)". Archived from the original on 2012-04-24. Retrieved 2012-04-28.
  11. ↑ "Statistical Analysis of Protein Sequence (Biology Workbench)".[ permanent dead link ]
  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. ↑ Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, McDonald-Mcginn DM, Hain HS, Emanuel BS, Zackai EH (1993). "22q11.2 Deletion Syndrome". University of Washington, Seattle. PMID   20301696.
  16. ↑ "BLAT UCSC Genome Browser".
  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".
  21. ↑ "Bio GPS".
  22. ↑ "WormBase".
  23. ↑ "NetCGly (ExPASy)". Archived from the original on 2012-04-24. Retrieved 2012-04-28.
  24. ↑ "NetGlycate (ExPASy)". Archived from the original on 2012-04-24. Retrieved 2012-04-28.
  25. ↑ "Phos (ExPASy)". Archived from the original on 2012-04-24. Retrieved 2012-04-28.
  26. ↑ "CSS Palm (ExPASy)". Archived from the original on 2012-04-24. Retrieved 2012-04-28.
  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. 1 2 3 4 5 6 7 8 9 10 "Molecular Interaction Database". Archived from the original on 2006-05-06.
  34. ↑ "Viral Molecular Interaction Database". Archived from the original on 2015-02-15.
  35. 1 2 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.
  36. 1 2 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.
  37. ↑ de Calbiac H, Montealegre S, Straube M, Renault S, Debruge H, Chentout L, Ciura S, Imbard A, Le Guillou E, Marian A, Goudin N, Caccavelli L, Fabrega S, Hubas A, van Endert P (February 2024). "TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning". Autophagy Reports. 3 (1). doi:10.1080/27694127.2024.2306766. ISSN   2769-4127.
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