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
Aliases	TANGO2, C22orf25, MECRCN, transport and golgi organization 2 homolog
External IDs	OMIM: 616830 MGI: 101825 HomoloGene: 44029 GeneCards: TANGO2
Gene location (Human) Chr. Chromosome 22 (human)^[1] Band 22q11.21 Start 20,017,014 bp^[1] End 20,067,164 bp^[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood monocyte right lobe of thyroid gland right coronary artery left lobe of thyroid gland spleen body of stomach popliteal artery ascending aorta right adrenal gland n/a More reference expression data BioGPS n/a
Orthologs Species Human Mouse Entrez 128989 27883 Ensembl ENSG00000183597 ENSMUSG00000013539 UniProt Q6ICL3 P54797 RefSeq (mRNA) NM_001283106 NM_001283116 NM_001283129 NM_001283148 NM_001283154 NM_001283179 NM_001283186 NM_001283199 NM_001283215 NM_001283235 NM_001283248 NM_152906 NM_001322141 NM_001322142 NM_001322143 NM_001322144 NM_001322145 NM_001322146 NM_001322147 NM_001322148 NM_001322149 NM_001322150 NM_001322153 NM_001322155 NM_001322160 NM_001322163 NM_001322166 NM_001322167 NM_001322169 NM_001322171 NM_001322172 NM_001322173 NM_001322174 NM_001322175 NM_138583 RefSeq (protein) NP_001270035 NP_001270045 NP_001270058 NP_001270077 NP_001270083 NP_001270108 NP_001270115 NP_001270128 NP_001270144 NP_001270164 NP_001270177 NP_001309070 NP_001309071 NP_001309072 NP_001309073 NP_001309074 NP_001309075 NP_001309076 NP_001309077 NP_001309078 NP_001309079 NP_001309082 NP_001309084 NP_001309089 NP_001309092 NP_001309095 NP_001309096 NP_001309098 NP_001309100 NP_001309101 NP_001309102 NP_001309103 NP_001309104 NP_690870 n/a Location (UCSC) Chr 22: 20.02 – 20.07 Mb n/a PubMed search ^[2] ^[3]
Wikidata
View/Edit Human View/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 Size	Protein Size	# of exons	Promoter Sequence	Signal Peptide	Molecular Weight	Domain Length
2271 bp	276 aa	9^[9]	687 bp	No^[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

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]

Reference	Detailed Family Information	Start (amino acid)	End (amino acid)	Strand
XBBF	X-box binding factors	227	245	-
GCMF	Chorion-specific transcription factors (with a GCM DNA binding domain)	151	165	-
YBXF	Y-box binding transcription factors	158	170	-
RUSH	SWI/SNF related nucleophosphoproteins (with a RING finger binding motif)	222	232	-
NEUR	NeuroD, Beta2, HLH domain	214	226	-
PCBE	PREB core-binding element	148	162	-
NR2F	Nuclear receptor subfamily 2 factors	169	193	-
AP1R	MAF and AP1 related factors	201	221	-
ZF02	C2H2 zinc finger transcription factors 2	108	130	-
TALE	TALE homeodomain class recognizing TG motifs	216	232	-
WHNF	Winged helix transcription factors	271	281	-
FKHD	Forkhead domain factors	119	135	+
MYOD	Myoblast determining factors	218	234	+
AP1F	AP1, activating protein 1	118	130	+
BCL6	POZ domain zinc finger expressed in B cells	190	206	+
CARE	Calcium response elements	196	206	+
EVI1	EVI1 nuclear transcription factor	90	106	+
ETSF	ETS transcription factor	162	182	+
TEAF	TEA/ATTS DNA binding domain factors	176	188	+

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 Species	Common Name	Accession Number	Seq. Length	Seq. Identity	Seq. Similarity	Kingdom	Time of Divergence
Homo sapiens	humans	NP_690870.3	276aa	-	-	Animalia	-
Pan troglodytes	common chimpanzee	BAK62258.1	276aa	99%	100%	Animalia	6.4 mya
Ailuropoda melanoleuca	giant panda	XP_002920626	276aa	91%	94%	Animalia	94.4 mya
Mus musculus	house mouse	NP_613049.2	276aa	88%	95%	Animalia	92.4 mya
Meleagris gallopavo	turkey	XP_003210928	276aa	74%	88%	Animalia	301.7 mya
Gallus gallus	Red Junglefowl	NP_001007837	276aa	73%	88%	Animalia	301.7 mya
Xenopus laevis	African clawed frog	NP_001083694	275aa	69%	86%	Animalia	371.2 mya
Xenopus (Silurana) tropicalis	Western clawed frog	NP_001004885.1	276aa	68%	85%	Animalia	371.2 mya
Salmo salar	Atlantic salmon	NP_001167100	274aa	66%	79%	Animalia	400.1 mya
Danio rerio	zebrafish	NP_001003781	273aa	64%	78%	Animalia	400.1 mya
Canarypox	virus	NP_955117	275aa	50%	69%	-	-
Fowlpox	virus	NP_039033	273aa	44%	63%	-	-
Cupriavidus	proteobacteria	YP_002005507.1	275aa	38%	52%	Eubacteria	2313.2 mya
Burkholderia	proteobacteria	YP_004977059	273aa	37%	53%	Eubacteria	2313.2 mya
Physcomitrella patens	moss	XP_001781807	275aa	37%	54%	Plantae	1369 mya
Zea mays	maize/corn	ACG35095	266aa	33%	53%	Plantae	1369 mya
Trichophyton rubrum	fungus	XP_003236126	306aa	32%	47%	Fungi	1215.8 mya
Sporisorium reilianum	Plant pathogen	CBQ69093	321aa	32%	43%	Fungi	1215.8 mya
Perkinsus marinus	pathogen of oysters	XP_002787624	219aa	31%	48%	Protista	1381.2 mya
Tetrahymena thermophilia	Ciliate protozoa	XP_001010229	277aa	26%	44%	Protista	1381.2 mya
Natrialba magadii	extremophile	YP_003481665	300aa	25%	39%	Archaebacteria	3556.3 mya
Halopiger xanaduensis	halophilic archaeon	YP_004597780.1	264aa	24%	39%	Archaebacteria	3556.3 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]

References

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2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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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".
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20. "GEO Profiles NCBI".
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24. . Archived from the original on 2012-04-24. Retrieved 2012-04-28.
25. . Archived from the original on 2012-04-24. Retrieved 2012-04-28.
26. . 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. . Archived from the original on 2006-05-06.
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35. 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. 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.

External links

• [1] 2017-11-07 at the Wayback Machine www.tango2.it - Disease website
• [2] www.tango2research.org - Research disease website -