TGM6

Transglutaminase 6 is a protein that in humans is encoded by the TGM6 gene. [5]

TGM6
Identifiers
Aliases	TGM6, SCA35, TG6, TGM3L, TGY, dJ734P14.3, transglutaminase 6
External IDs	OMIM: 613900 MGI: 3044321 HomoloGene: 27970 GeneCards: TGM6
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20p13 Start 2,380,901 bp[1] End 2,432,753 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2|2 F1 Start 130,112,416 bp[2] End 130,154,232 bp[2]
Gene ontology Molecular function • transferase activity • transferase activity, transferring acyl groups • protein-glutamine gamma-glutamyltransferase activity • metal ion binding Cellular component • cytoplasm Biological process • peptide cross-linking Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	343641	241636
Ensembl	ENSG00000166948	ENSMUSG00000027403
UniProt	O95932	n/a
RefSeq (mRNA)	NM_198994 NM_001254734	NM_001289747 NM_001289748 NM_001289749 NM_177726
RefSeq (protein)	NP_001241663 NP_945345	n/a
Location (UCSC)	Chr 20: 2.38 – 2.43 Mb	Chr 2: 130.11 – 130.15 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function and Clinical Significance

The protein encoded by this gene belongs to the transglutaminase superfamily. It catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Mutations in this gene are associated with spinocerebellar ataxia type 35 (SCA35). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011].

Mutations in TGM6 cause acute myeloid leukaemia.[6] The presence of antibodies against TG6 is statistically related to gluten ataxia, amongst other conditions.

Model organisms

Model organisms have been used in the study of TGM6 function. A conditional knockout mouse line called Tgm6^{tm1a(KOMP)Wtsi} was generated at the Wellcome Trust Sanger Institute.[7] Male and female animals underwent a standardized phenotypic screen[8] to determine the effects of deletion.[9][10][11][12] Additional screens performed: - In-depth immunological phenotyping[13]

Tgm6 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[8][13]
Peripheral blood leukocytes 6 Weeks	Normal
Haematology 6 Weeks	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal

References

1. GRCh38: Ensembl release 89: ENSG00000166948 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027403 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Transglutaminase 6". Retrieved 2014-04-29.
6. Pan LL, Huang YM, Wang M, Zhuang XE, Luo DF, Guo SC, Zhang ZS, Huang Q, Lin SL, Wang SY (Feb 2015). "Positional cloning and next-generation sequencing identified a TGM6 mutation in a large Chinese pedigree with acute myeloid leukaemia". European Journal of Human Genetics. 23 (2): 218–23. doi:10.1038/ejhg.2014.67. PMC 4297898. PMID 24755948.
7. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
8. "International Mouse Phenotyping Consortium".
9. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
10. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
11. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
12. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
13. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• Lindfors K, Koskinen O, Laurila K, Collin P, Saavalainen P, Haimila K, Partanen J, Mäki M, Kaukinen K (Jun 2011). "IgA-class autoantibodies against neuronal transglutaminase, TG6 in celiac disease: no evidence for gluten dependency". Clinica Chimica Acta; International Journal of Clinical Chemistry. 412 (13–14): 1187–90. doi:10.1016/j.cca.2010.09.042. PMID 21453693.
• Thomas H, Beck K, Adamczyk M, Aeschlimann P, Langley M, Oita RC, Thiebach L, Hils M, Aeschlimann D (Jan 2013). "Transglutaminase 6: a protein associated with central nervous system development and motor function". Amino Acids. 44 (1): 161–77. doi:10.1007/s00726-011-1091-z. PMC 3535377. PMID 21984379.
• Sherva R, Tripodis Y, Bennett DA, Chibnik LB, Crane PK, de Jager PL, Farrer LA, Saykin AJ, Shulman JM, Naj A, Green RC (Jan 2014). "Genome-wide association study of the rate of cognitive decline in Alzheimer's disease". Alzheimer's & Dementia. 10 (1): 45–52. doi:10.1016/j.jalz.2013.01.008. PMC 3760995. PMID 23535033.
• Grenard P, Bates MK, Aeschlimann D (Aug 2001). "Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z". The Journal of Biological Chemistry. 276 (35): 33066–78. doi:10.1074/jbc.M102553200. PMID 11390390.
• Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders DS, Woodroofe N, Aeschlimann D (Sep 2008). "Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase". Annals of Neurology. 64 (3): 332–43. doi:10.1002/ana.21450. PMID 18825674.
• Stamnaes J, Dorum S, Fleckenstein B, Aeschlimann D, Sollid LM (Nov 2010). "Gluten T cell epitope targeting by TG3 and TG6; implications for dermatitis herpetiformis and gluten ataxia". Amino Acids. 39 (5): 1183–91. doi:10.1007/s00726-010-0554-y. PMID 20300788.
• Guan WJ, Wang JL, Liu YT, Ma YT, Zhou Y, Jiang H, Shen L, Guo JF, Xia K, Li JD, Tang BS (Jan 2013). "Spinocerebellar ataxia type 35 (SCA35)-associated transglutaminase 6 mutants sensitize cells to apoptosis". Biochemical and Biophysical Research Communications. 430 (2): 780–6. doi:10.1016/j.bbrc.2012.11.069. PMID 23206699.
• Scavenius C, Sanggaard KW, Nikolajsen CL, Bak S, Valnickova Z, Thøgersen IB, Jensen ON, Højrup P, Enghild JJ (Dec 2011). "Human inter-α-inhibitor is a substrate for factor XIIIa and tissue transglutaminase". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1814 (12): 1624–30. doi:10.1016/j.bbapap.2011.08.017. PMID 21939789.
• Wang JL, Yang X, Xia K, Hu ZM, Weng L, Jin X, Jiang H, Zhang P, Shen L, Guo JF, Li N, Li YR, Lei LF, Zhou J, Du J, Zhou YF, Pan Q, Wang J, Wang J, Li RQ, Tang BS (Dec 2010). "TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing". Brain. 133 (Pt 12): 3510–8. doi:10.1093/brain/awq323. PMID 21106500.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.