Protein-glutamine gamma-glutamyltransferase 2

Details

Kind

protein

Synonyms

2.3.2.13
Erythrocyte transglutaminase
G(h)
Heart G alpha(h)
hhG alpha(h)
hTG2
Isopeptidase TGM2
Protein G alpha(h)
Protein-glutamine deamidase TGM2
Protein-glutamine dopaminyltransferase TGM2
Protein-glutamine histaminyltransferase TGM2
Protein-glutamine noradrenalinyltransferase TGM2
Protein-glutamine serotonyltransferase TGM2
TG(C)
TG2
TGase C
TGase H
TGase II
TGase-2
TGC
Tissue transglutaminase
Transglutaminase C
Transglutaminase H
Transglutaminase II
Transglutaminase-2
tTG
tTgase

Gene Name

TGM2

UniProtKB Entry

P21980Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0002061|Protein-glutamine gamma-glutamyltransferase 2
MAEELVLERCDLELETNGRDHHTADLCREKLVVRRGQPFWLTLHFEGRNYEASVDSLTFS
VVTGPAPSQEAGTKARFPLRDAVEEGDWTATVVDQQDCTLSLQLTTPANAPIGLYRLSLE
ASTGYQGSSFVLGHFILLFNAWCPADAVYLDSEEERQEYVLTQQGFIYQGSAKFIKNIPW
NFGQFEDGILDICLILLDVNPKFLKNAGRDCSRRSSPVYVGRVVSGMVNCNDDQGVLLGR
WDNNYGDGVSPMSWIGSVDILRRWKNHGCQRVKYGQCWVFAAVACTVLRCLGIPTRVVTN
YNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWVESWMTRPDLQPGYEGWQALDPT
PQEKSEGTYCCGPVPVRAIKEGDLSTKYDAPFVFAEVNADVVDWIQQDDGSVHKSINRSL
IVGLKISTKSVGRDEREDITHTYKYPEGSSEEREAFTRANHLNKLAEKEETGMAMRIRVG
QSMNMGSDFDVFAHITNNTAEEYVCRLLLCARTVSYNGILGPECGTKYLLNLNLEPFSEK
SVPLCILYEKYRDCLTESNLIKVRALLVEPVINSYLLAERDLYLENPEIKIRILGEPKQK
RKLVAEVSLQNPLPVALEGCTFTVEGAGLTEEQKTVEIPDPVEAGEEVKVRMDLLPLHMG
LHKLVVNFESDKLKAVKGFRNVIIGPA

Number of residues

687

Molecular Weight

77328.21

Theoretical pI

4.86

GO Classification

Functions

protein-glutamine gamma-glutamyltransferase activity

Processes

apoptotic cell clearance / branching involved in salivary gland morphogenesis / negative regulation of endoplasmic reticulum calcium ion concentration / peptide cross-linking / positive regulation of apoptotic process / positive regulation of cell adhesion / positive regulation of mitochondrial calcium ion concentration / salivary gland cavitation

Components

cytosol / endoplasmic reticulum / extracellular exosome / focal adhesion / mitochondrion

General Function

Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono- and polyamines, thereby producing cross-linked or aminated proteins, respectively (PubMed:23941696, PubMed:31991788, PubMed:9252372). Involved in many biological processes, such as bone development, angiogenesis, wound healing, cellular differentiation, chromatin modification and apoptosis (PubMed:1683874, PubMed:27270573, PubMed:7935379, PubMed:9252372, PubMed:28198360). Acts as a protein-glutamine gamma-glutamyltransferase by mediating the cross-linking of proteins, such as ACO2, HSPB6, FN1, HMGB1, RAP1GDS1, SLC25A4/ANT1, SPP1 and WDR54 (PubMed:23941696, PubMed:24349085, PubMed:29618516, PubMed:30458214). Under physiological conditions, the protein cross-linking activity is inhibited by GTP; inhibition is relieved by Ca(2+) in response to various stresses (PubMed:18092889, PubMed:7592956, PubMed:7649299). When secreted, catalyzes cross-linking of proteins of the extracellular matrix, such as FN1 and SPP1 resulting in the formation of scaffolds (PubMed:12506096). Plays a key role during apoptosis, both by (1) promoting the cross-linking of cytoskeletal proteins resulting in condensation of the cytoplasm, and by (2) mediating cross-linking proteins of the extracellular matrix, resulting in the irreversible formation of scaffolds that stabilize the integrity of the dying cells before their clearance by phagocytosis, thereby preventing the leakage of harmful intracellular components (PubMed:7935379, PubMed:9252372). In addition to protein cross-linking, can use different monoamine substrates to catalyze a vast array of protein post-translational modifications: mediates aminylation of serotonin, dopamine, noradrenaline or histamine into glutamine residues of target proteins to generate protein serotonylation, dopaminylation, noradrenalinylation or histaminylation, respectively (PubMed:23797785, PubMed:30867594). Mediates protein serotonylation of small GTPases during activation and aggregation of platelets, leading to constitutive activation of these GTPases (By similarity). Plays a key role in chromatin organization by mediating serotonylation and dopaminylation of histone H3 (PubMed:30867594, PubMed:32273471). Catalyzes serotonylation of 'Gln-5' of histone H3 (H3Q5ser) during serotonergic neuron differentiation, thereby facilitating transcription (PubMed:30867594). Acts as a mediator of neurotransmission-independent role of nuclear dopamine in ventral tegmental area (VTA) neurons: catalyzes dopaminylation of 'Gln-5' of histone H3 (H3Q5dop), thereby regulating relapse-related transcriptional plasticity in the reward system (PubMed:32273471). Regulates vein remodeling by mediating serotonylation and subsequent inactivation of ATP2A2/SERCA2 (By similarity). Also acts as a protein deamidase by mediating the side chain deamidation of specific glutamine residues of proteins to glutamate (PubMed:20547769, PubMed:9623982). Catalyzes specific deamidation of protein gliadin, a component of wheat gluten in the diet (PubMed:9623982). May also act as an isopeptidase cleaving the previously formed cross-links (PubMed:26250429, PubMed:27131890). Also able to participate in signaling pathways independently of its acyltransferase activity: acts as a signal transducer in alpha-1 adrenergic receptor-mediated stimulation of phospholipase C-delta (PLCD) activity and is required for coupling alpha-1 adrenergic agonists to the stimulation of phosphoinositide lipid metabolism (PubMed:8943303)

Specific Function

calcium ion binding

Pfam Domain Function

Transglut_core (PF01841)
Transglut_N (PF00868)
Transglut_C (PF00927)

Signal Regions

Not Available

Transmembrane Regions

Not Available

Cellular Location

Cytoplasm, cytosol

Gene sequence

>lcl|BSEQ0010725|Protein-glutamine gamma-glutamyltransferase 2 (TGM2)
ATGGCCGAGGAGCTGGTCTTAGAGAGGTGTGATCTGGAGCTGGAGACCAATGGCCGAGAC
CACCACACGGCCGACCTGTGCCGGGAGAAGCTGGTGGTGCGACGGGGCCAGCCCTTCTGG
CTGACCCTGCACTTTGAGGGCCGCAACTACGAGGCCAGTGTAGACAGTCTCACCTTCAGT
GTCGTGACCGGCCCAGCCCCTAGCCAGGAGGCCGGGACCAAGGCCCGTTTTCCACTAAGA
GATGCTGTGGAGGAGGGTGACTGGACAGCCACCGTGGTGGACCAGCAAGACTGCACCCTC
TCGCTGCAGCTCACCACCCCGGCCAACGCCCCCATCGGCCTGTATCGCCTCAGCCTGGAG
GCCTCCACTGGCTACCAGGGATCCAGCTTTGTGCTGGGCCACTTCATTTTGCTCTTCAAC
GCCTGGTGCCCAGCGGATGCTGTGTACCTGGACTCGGAAGAGGAGCGGCAGGAGTATGTC
CTCACCCAGCAGGGCTTTATCTACCAGGGCTCGGCCAAGTTCATCAAGAACATACCTTGG
AATTTTGGGCAGTTTGAAGATGGGATCCTAGACATCTGCCTGATCCTTCTAGATGTCAAC
CCCAAGTTCCTGAAGAACGCCGGCCGTGACTGCTCCCGCCGCAGCAGCCCCGTCTACGTG
GGCCGGGTGGTGAGTGGCATGGTCAACTGCAACGATGACCAGGGTGTGCTGCTGGGACGC
TGGGACAACAACTACGGGGACGGCGTCAGCCCCATGTCCTGGATCGGCAGCGTGGACATC
CTGCGGCGCTGGAAGAACCACGGCTGCCAGCGCGTCAAGTATGGCCAGTGCTGGGTCTTC
GCCGCCGTGGCCTGCACAGTGCTGAGGTGCCTGGGCATCCCTACCCGCGTCGTGACCAAC
TACAACTCGGCCCATGACCAGAACAGCAACCTTCTCATCGAGTACTTCCGCAATGAGTTT
GGGGAGATCCAGGGTGACAAGAGCGAGATGATCTGGAACTTCCACTGCTGGGTGGAGTCG
TGGATGACCAGGCCGGACCTGCAGCCGGGGTACGAGGGCTGGCAGGCCCTGGACCCAACG
CCCCAGGAGAAGAGCGAAGGGACGTACTGCTGTGGCCCAGTTCCAGTTCGTGCCATCAAG
GAGGGCGACCTGAGCACCAAGTACGATGCGCCCTTTGTCTTTGCGGAGGTCAATGCCGAC
GTGGTAGACTGGATCCAGCAGGACGATGGGTCTGTGCACAAATCCATCAACCGTTCCCTG
ATCGTTGGGCTGAAGATCAGCACTAAGAGCGTGGGCCGAGACGAGCGGGAGGATATCACC
CACACCTACAAATACCCAGAGGGGTCCTCAGAGGAGAGGGAGGCCTTCACAAGGGCGAAC
CACCTGAACAAACTGGCCGAGAAGGAGGAGACAGGGATGGCCATGCGGATCCGTGTGGGC
CAGAGCATGAACATGGGCAGTGACTTTGACGTCTTTGCCCACATCACCAACAACACCGCT
GAGGAGTACGTCTGCCGCCTCCTGCTCTGTGCCCGCACCGTCAGCTACAATGGGATCTTG
GGGCCCGAGTGTGGCACCAAGTACCTGCTCAACCTCAACCTGGAGCCTTTCTCTGAGAAG
AGCGTTCCTCTTTGCATCCTCTATGAGAAATACCGTGACTGCCTTACGGAGTCCAACCTC
ATCAAGGTGCGGGCCCTCCTCGTGGAGCCAGTTATCAACAGCTACCTGCTGGCTGAGAGG
GACCTCTACCTGGAGAATCCAGAAATCAAGATCCGGATCCTTGGGGAGCCCAAGCAGAAA
CGCAAGCTGGTGGCTGAGGTGTCCCTGCAGAACCCGCTCCCTGTGGCCCTGGAAGGCTGC
ACCTTCACTGTGGAGGGGGCCGGCCTGACTGAGGAGCAGAAGACGGTGGAGATCCCAGAC
CCCGTGGAGGCAGGGGAGGAAGTTAAGGTGAGAATGGACCTGCTGCCGCTCCACATGGGC
CTCCACAAGCTGGTGGTGAACTTCGAGAGCGACAAGCTGAAGGCTGTGAAGGGCTTCCGG
AATGTCATCATTGGCCCCGCCTAA

Chromosome Location

Locus

20q11.23

External Identifiers

Resource	Link
UniProtKB ID	P21980
UniProtKB Entry Name	TGM2_HUMAN
GenBank Protein ID	339521
GenBank Gene ID	M55153
GeneCard ID	TGM2
GenAtlas ID	TGM2
HGNC ID	HGNC:11778
PDB ID(s)	1KV3, 2Q3Z, 3LY6, 3S3J, 3S3P, 3S3S, 4PYG, 6A8P, 6KZB
KEGG ID	hsa:7052
IUPHAR/Guide To Pharmacology ID	3015
NCBI Gene ID	7052

General References

Gentile V, Saydak M, Chiocca EA, Akande O, Birckbichler PJ, Lee KN, Stein JP, Davies PJ: Isolation and characterization of cDNA clones to mouse macrophage and human endothelial cell tissue transglutaminases. J Biol Chem. 1991 Jan 5;266(1):478-83. [Article]
Fraij BM, Birckbichler PJ, Patterson MK Jr, Lee KN, Gonzales RA: A retinoic acid-inducible mRNA from human erythroleukemia cells encodes a novel tissue transglutaminase homologue. J Biol Chem. 1992 Nov 5;267(31):22616-23. [Article]
Fraij BM, Gonzales RA: A third human tissue transglutaminase homologue as a result of alternative gene transcripts. Biochim Biophys Acta. 1996 Apr 10;1306(1):63-74. [Article]
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [Article]
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
Pinkas DM, Strop P, Brunger AT, Khosla C: Transglutaminase 2 undergoes a large conformational change upon activation. PLoS Biol. 2007 Dec;5(12):e327. [Article]
Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [Article]
Porzio O, Massa O, Cunsolo V, Colombo C, Malaponti M, Bertuzzi F, Hansen T, Johansen A, Pedersen O, Meschi F, Terrinoni A, Melino G, Federici M, Decarlo N, Menicagli M, Campani D, Marchetti P, Ferdaoussi M, Froguel P, Federici G, Vaxillaire M, Barbetti F: Missense mutations in the TGM2 gene encoding transglutaminase 2 are found in patients with early-onset type 2 diabetes. Mutation in brief no. 982. Online. Hum Mutat. 2007 Nov;28(11):1150. [Article]

Associated Data

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
Guanosine-5'-Diphosphate	experimental	yes	target	inhibitor	Details
L-Glutamine	approved, investigational, nutraceutical	unknown	enzyme	substrate	Details
Hexylresorcinol	approved	unknown	target	inhibitor	Details
Oltipraz	investigational	yes	target	inhibitor	Details
Epigallocatechin gallate	investigational	yes	target	inhibitor	Details
Anethole trithione	approved, experimental	yes	target	inhibitor	Details