ID TGM2_MOUSE Reviewed; 686 AA. AC P21981; O88901; Q3TLV2; Q8C217; Q91VG9; Q9R1F7; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 18-MAR-2008, sequence version 4. DT 27-MAR-2024, entry version 200. DE RecName: Full=Protein-glutamine gamma-glutamyltransferase 2 {ECO:0000305}; DE EC=2.3.2.13 {ECO:0000250|UniProtKB:P21980}; DE AltName: Full=Isopeptidase TGM2 {ECO:0000305}; DE EC=3.4.-.- {ECO:0000250|UniProtKB:P21980}; DE AltName: Full=Protein-glutamine deamidase TGM2 {ECO:0000305}; DE EC=3.5.1.44 {ECO:0000250|UniProtKB:P21980}; DE AltName: Full=Protein-glutamine dopaminyltransferase TGM2 {ECO:0000305}; DE EC=2.3.1.- {ECO:0000250|UniProtKB:P21980}; DE AltName: Full=Protein-glutamine histaminyltransferase TGM2 {ECO:0000305}; DE EC=2.3.1.- {ECO:0000250|UniProtKB:P21980}; DE AltName: Full=Protein-glutamine noradrenalinyltransferase TGM2 {ECO:0000305}; DE EC=2.3.1.- {ECO:0000250|UniProtKB:P08587}; DE AltName: Full=Protein-glutamine serotonyltransferase TGM2 {ECO:0000305}; DE EC=2.3.1.- {ECO:0000269|PubMed:32116663}; DE AltName: Full=Tissue transglutaminase {ECO:0000303|PubMed:1670766}; DE Short=tTG {ECO:0000250|UniProtKB:P21980}; DE AltName: Full=Transglutaminase II {ECO:0000303|PubMed:11274171}; DE Short=TGase II {ECO:0000303|PubMed:11274171}; DE AltName: Full=Transglutaminase-2 {ECO:0000303|PubMed:11113189}; DE Short=TG2 {ECO:0000303|PubMed:32116663}; DE Short=TGase-2 {ECO:0000303|PubMed:11113189}; DE Short=TGase2 {ECO:0000303|PubMed:11113189, ECO:0000303|PubMed:12810961}; GN Name=Tgm2 {ECO:0000303|PubMed:10334875, ECO:0000312|MGI:MGI:98731}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Macrophage; RX PubMed=1670766; DOI=10.1016/s0021-9258(18)52460-1; RA Gentile V., Saydak M., Chiocca E.A., Akande O., Birckbichler P.J., RA Lee K.N., Stein J.P., Davies P.J.A.; RT "Isolation and characterization of cDNA clones to mouse macrophage and RT human endothelial cell tissue transglutaminases."; RL J. Biol. Chem. 266:478-483(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=129/SvJ; RX PubMed=10334875; DOI=10.1006/abbi.1999.1189; RA Nanda N., Iismaa S.E., Copeland N.G., Gilbert D.J., Jenkins N., RA Graham R.M., Sutrave P.; RT "Organization and chromosomal mapping of mouse Gh/tissue transglutaminase RT gene (Tgm2)."; RL Arch. Biochem. Biophys. 366:151-156(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10200571; DOI=10.1038/sj.cdd.4400494; RA D'Amato M., Iannicola C., Monteriu G., Piacentini M.; RT "Mapping and sequencing of the murine 'tissue' transglutaminase (Tgm2) RT gene: absence of mutations in MRLlpr/lpr mice."; RL Cell Death Differ. 6:216-217(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; RC TISSUE=Brain cortex, Dendritic cell, Embryonic heart, Heart, RC Macrophage, Mammary gland, and Spleen; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=NMRI; TISSUE=Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-3. RC STRAIN=SWR/J; RX PubMed=8626785; DOI=10.1074/jbc.271.8.4355; RA Nagy L., Saydak M., Shipley N., Lu S., Basilion J.P., Yan Z.H., Syka P., RA Chandraratna R.A.S., Stein J.P., Heyman R.A., Davies P.J.A.; RT "Identification and characterization of a versatile retinoid response RT element (retinoic acid receptor response element-retinoid X receptor RT response element) in the mouse tissue transglutaminase gene promoter."; RL J. Biol. Chem. 271:4355-4365(1996). RN [8] RP PROTEIN SEQUENCE OF 2-19; 41-74; 158-173; 215-222; 290-327; 550-561; RP 564-589; 601-609; 634-648 AND 651-671, CLEAVAGE OF INITIATOR METHIONINE, RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryonic fibroblast; RA Bienvenut W.V., Serrels B., Brunton V.G., Frame M.C.; RL Submitted (FEB-2008) to UniProtKB. RN [9] RP PROTEIN SEQUENCE OF 378-387, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=OF1; TISSUE=Hippocampus; RA Lubec G., Sunyer B., Chen W.-Q.; RL Submitted (JAN-2009) to UniProtKB. RN [10] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=11274171; DOI=10.1074/jbc.m010846200; RA Nanda N., Iismaa S.E., Owens W.A., Husain A., Mackay F., Graham R.M.; RT "Targeted inactivation of Gh/tissue transglutaminase II."; RL J. Biol. Chem. 276:20673-20678(2001). RN [11] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=11113189; DOI=10.1128/mcb.21.1.148-155.2001; RA De Laurenzi V., Melino G.; RT "Gene disruption of tissue transglutaminase."; RL Mol. Cell. Biol. 21:148-155(2001). RN [12] RP DISRUPTION PHENOTYPE. RX PubMed=12205028; DOI=10.1096/fj.01-0689com; RA Bernassola F., Federici M., Corazzari M., Terrinoni A., Hribal M.L., RA De Laurenzi V., Ranalli M., Massa O., Sesti G., McLean W.H., Citro G., RA Barbetti F., Melino G.; RT "Role of transglutaminase 2 in glucose tolerance: knockout mice studies and RT a putative mutation in a MODY patient."; RL FASEB J. 16:1371-1378(2002). RN [13] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=12810961; DOI=10.1073/pnas.0832466100; RA Szondy Z., Sarang Z., Molnar P., Nemeth T., Piacentini M., RA Mastroberardino P.G., Falasca L., Aeschlimann D., Kovacs J., Kiss I., RA Szegezdi E., Lakos G., Rajnavolgyi E., Birckbichler P.J., Melino G., RA Fesus L.; RT "Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk RT between macrophages and apoptotic cells."; RL Proc. Natl. Acad. Sci. U.S.A. 100:7812-7817(2003). RN [14] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=15905580; DOI=10.4049/jimmunol.174.11.7330; RA Falasca L., Iadevaia V., Ciccosanti F., Melino G., Serafino A., RA Piacentini M.; RT "Transglutaminase type II is a key element in the regulation of the anti- RT inflammatory response elicited by apoptotic cell engulfment."; RL J. Immunol. 174:7330-7340(2005). RN [15] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19644512; DOI=10.1038/cdd.2009.100; RA Malorni W., Farrace M.G., Matarrese P., Tinari A., Ciarlo L., RA Mousavi-Shafaei P., D'Eletto M., Di Giacomo G., Melino G., Palmieri L., RA Rodolfo C., Piacentini M.; RT "The adenine nucleotide translocator 1 acts as a type 2 transglutaminase RT substrate: implications for mitochondrial-dependent apoptosis."; RL Cell Death Differ. 16:1480-1492(2009). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [17] RP FUNCTION, S-NITROSYLATION, AND SUBCELLULAR LOCATION. RX PubMed=20489165; DOI=10.1161/circresaha.109.215228; RA Santhanam L., Tuday E.C., Webb A.K., Dowzicky P., Kim J.H., Oh Y.J., RA Sikka G., Kuo M., Halushka M.K., Macgregor A.M., Dunn J., Gutbrod S., RA Yin D., Shoukas A., Nyhan D., Flavahan N.A., Belkin A.M., Berkowitz D.E.; RT "Decreased S-nitrosylation of tissue transglutaminase contributes to age- RT related increases in vascular stiffness."; RL Circ. Res. 107:117-125(2010). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-468, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [19] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32116663; DOI=10.3389/fphar.2019.01611; RA Liu B., Wang D., Luo E., Hou J., Qiao Y., Yan G., Wang Q., Tang C.; RT "Role of TG2-mediated SERCA2 serotonylation on hypoxic pulmonary vein RT remodeling."; RL Front. Pharmacol. 10:1611-1611(2019). CC -!- FUNCTION: Calcium-dependent acyltransferase that catalyzes the CC formation of covalent bonds between peptide-bound glutamine and various CC primary amines, such as gamma-amino group of peptide-bound lysine, or CC mono- and polyamines, thereby producing cross-linked or aminated CC proteins, respectively (By similarity). Involved in many biological CC processes, such as bone development, angiogenesis, wound healing, CC cellular differentiation, chromatin modification and apoptosis (By CC similarity). Acts as a protein-glutamine gamma-glutamyltransferase by CC mediating the cross-linking of proteins, such as ACO2, HSPB6, FN1, CC HMGB1, RAP1GDS1, SLC25A4/ANT1, SPP1 and WDR54 (PubMed:11274171, CC PubMed:11113189, PubMed:20489165). Under physiological conditions, the CC protein cross-linking activity is inhibited by GTP; inhibition is CC relieved by Ca(2+) in response to various stresses (By similarity). CC When secreted, catalyzes cross-linking of proteins of the extracellular CC matrix, such as FN1 and SPP1 resulting in the formation of scaffolds CC (By similarity). Plays a key role during apoptosis, both by (1) CC promoting the cross-linking of cytoskeletal proteins resulting in CC condensation of the cytoplasm, and by (2) mediating cross-linking CC proteins of the extracellular matrix, resulting in the irreversible CC formation of scaffolds that stabilize the integrity of the dying cells CC before their clearance by phagocytosis, thereby preventing the leakage CC of harmful intracellular components (PubMed:12810961, PubMed:15905580). CC In addition to protein cross-linking, can use different monoamine CC substrates to catalyze a vast array of protein post-translational CC modifications: mediates aminylation of serotonin, dopamine, CC noradrenaline or histamine into glutamine residues of target proteins CC to generate protein serotonylation, dopaminylation, noradrenalinylation CC or histaminylation, respectively (PubMed:32116663). Mediates protein CC serotonylation of small GTPases during activation and aggregation of CC platelets, leading to constitutive activation of these GTPases (By CC similarity). Plays a key role in chromatin organization by mediating CC serotonylation and dopaminylation of histone H3 (By similarity). CC Catalyzes serotonylation of 'Gln-5' of histone H3 (H3Q5ser) during CC serotonergic neuron differentiation, thereby facilitating transcription CC (By similarity). Acts as a mediator of neurotransmission-independent CC role of nuclear dopamine in ventral tegmental area (VTA) neurons: CC catalyzes dopaminylation of 'Gln-5' of histone H3 (H3Q5dop), thereby CC regulating relapse-related transcriptional plasticity in the reward CC system (By similarity). Regulates vein remodeling by mediating CC serotonylation and subsequent inactivation of ATP2A2/SERCA2 CC (PubMed:32116663). Also acts as a protein deamidase by mediating the CC side chain deamidation of specific glutamine residues of proteins to CC glutamate (By similarity). Catalyzes specific deamidation of protein CC gliadin, a component of wheat gluten in the diet (By similarity). May CC also act as an isopeptidase cleaving the previously formed cross-links CC (By similarity). Also able to participate in signaling pathways CC independently of its acyltransferase activity: acts as a signal CC transducer in alpha-1 adrenergic receptor-mediated stimulation of CC phospholipase C-delta (PLCD) activity and is required for coupling CC alpha-1 adrenergic agonists to the stimulation of phosphoinositide CC lipid metabolism (PubMed:11274171). {ECO:0000250|UniProtKB:P08587, CC ECO:0000250|UniProtKB:P21980, ECO:0000269|PubMed:11113189, CC ECO:0000269|PubMed:11274171, ECO:0000269|PubMed:12810961, CC ECO:0000269|PubMed:15905580, ECO:0000269|PubMed:20489165, CC ECO:0000269|PubMed:32116663}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L- CC lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:54816, CC Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:14005, CC ChEBI:CHEBI:28938, ChEBI:CHEBI:29969, ChEBI:CHEBI:30011, CC ChEBI:CHEBI:138370; EC=2.3.2.13; CC Evidence={ECO:0000250|UniProtKB:P21980, ECO:0000255|PROSITE- CC ProRule:PRU10024}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54817; CC Evidence={ECO:0000250|UniProtKB:P21980}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-glutaminyl-[protein] + serotonin = 5-serotonyl-L-glutamyl- CC [protein] + NH4(+); Xref=Rhea:RHEA:66552, Rhea:RHEA-COMP:10207, CC Rhea:RHEA-COMP:17052, ChEBI:CHEBI:28938, ChEBI:CHEBI:30011, CC ChEBI:CHEBI:167174, ChEBI:CHEBI:350546; CC Evidence={ECO:0000269|PubMed:32116663}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66553; CC Evidence={ECO:0000269|PubMed:32116663}; CC -!- CATALYTIC ACTIVITY: CC Reaction=dopamine + L-glutaminyl-[protein] = 5-dopaminyl-L-glutamyl- CC [protein] + NH4(+); Xref=Rhea:RHEA:66556, Rhea:RHEA-COMP:10207, CC Rhea:RHEA-COMP:17053, ChEBI:CHEBI:28938, ChEBI:CHEBI:30011, CC ChEBI:CHEBI:59905, ChEBI:CHEBI:167175; CC Evidence={ECO:0000250|UniProtKB:P21980}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66557; CC Evidence={ECO:0000250|UniProtKB:P21980}; CC -!- CATALYTIC ACTIVITY: CC Reaction=histamine + L-glutaminyl-[protein] = 5-histaminyl-L-glutamyl- CC [protein] + NH4(+); Xref=Rhea:RHEA:66564, Rhea:RHEA-COMP:10207, CC Rhea:RHEA-COMP:17056, ChEBI:CHEBI:28938, ChEBI:CHEBI:30011, CC ChEBI:CHEBI:58432, ChEBI:CHEBI:167179; CC Evidence={ECO:0000250|UniProtKB:P21980}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66565; CC Evidence={ECO:0000250|UniProtKB:P21980}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(R)-noradrenaline + L-glutaminyl-[protein] = 5-(R)- CC noradrenalinyl-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:66560, CC Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:17054, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:30011, ChEBI:CHEBI:72587, ChEBI:CHEBI:167178; CC Evidence={ECO:0000250|UniProtKB:P08587}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66561; CC Evidence={ECO:0000250|UniProtKB:P08587}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + L-glutaminyl-[protein] = L-glutamyl-[protein] + NH4(+); CC Xref=Rhea:RHEA:16441, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:10208, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29973, CC ChEBI:CHEBI:30011; EC=3.5.1.44; CC Evidence={ECO:0000250|UniProtKB:P21980}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16442; CC Evidence={ECO:0000250|UniProtKB:P21980}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000250|UniProtKB:P21980}; CC -!- ACTIVITY REGULATION: Acyltransferase activity is regulated by the CC binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its CC closed structure, thereby obstructing the accessibility of substrates CC to the active sites. In contrast, Ca(2+) acts as a cofactor by inducing CC conformational change to the active open form. In absence of Ca(2+), CC Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and CC subsequent inhibition of the acyltransferase activity. CC {ECO:0000250|UniProtKB:P21980}. CC -!- SUBUNIT: Monomer. Interacts with phospholipase C; promoting alpha-1 CC adrenergic receptor signaling (By similarity). Interacts with PLCD1 (By CC similarity). {ECO:0000250|UniProtKB:P21980, CC ECO:0000250|UniProtKB:Q9WVJ6}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19644512}. CC Nucleus {ECO:0000250|UniProtKB:P21980}. Chromosome CC {ECO:0000250|UniProtKB:P21980}. Secreted, extracellular space, CC extracellular matrix {ECO:0000269|PubMed:20489165}. Cell membrane CC {ECO:0000250|UniProtKB:Q9WVJ6}. Mitochondrion CC {ECO:0000269|PubMed:19644512}. Note=Mainly localizes to the cytosol. CC Present at much lower level in the nucleus and chromatin. Also secreted CC via a non-classical secretion pathway to the extracellular matrix. CC {ECO:0000250|UniProtKB:P21980}. CC -!- PTM: Disulfide bond formation inactivates the calcium-dependent CC acyltransferase activity. Cys-370 can form disulfide bonds with both CC Cys-230 and Cys-371: formation of a disulfide bond between Cys-230 and CC Cys-370 facilitates formation of the disulfide between Cys-370 and Cys- CC 371, which promotes inactivation of the acyltransferase activity. May CC also form interchain disulfids between Cys-230 and Cys-370. Ca(2+) CC protects against disulfide bond formation and inactivation. CC {ECO:0000250|UniProtKB:P21980}. CC -!- PTM: Auto-transglutaminated: Forms covalent cross-links mediated by CC transglutaminase between Gln-632 and the epsilon-amino group of a CC lysine residue of itself or HMGB1, forming homopolymers and CC heteropolymers, respectively. {ECO:0000250|UniProtKB:P08587}. CC -!- PTM: S-nitrosylated, leading to inactivation of the acyltransferase CC activity. {ECO:0000269|PubMed:20489165}. CC -!- DISRUPTION PHENOTYPE: No visible phenotype in normal conditions CC (PubMed:11274171, PubMed:11113189). During apoptosis, mice display CC defective clearance of apoptotic cells in the thymus (PubMed:12810961). CC Moreover, inflammatory as well as autoimmune reactions develop CC spontaneously with age (PubMed:12810961). Defective clearance of CC apoptotic cells is caused by an impaired capacity of macrophages to CC engulf, but not to bind, apoptotic cells (PubMed:15905580). Mice also CC show glucose intolerance after intraperitoneal glucose loading: mice CC manifest a tendency to develop hypoglycemia after administration of CC exogenous insulin as a consequence of enhanced IRS2 phosphorylation CC (PubMed:12205028). {ECO:0000269|PubMed:11113189, CC ECO:0000269|PubMed:11274171, ECO:0000269|PubMed:12205028, CC ECO:0000269|PubMed:12810961, ECO:0000269|PubMed:15905580}. CC -!- SIMILARITY: Belongs to the transglutaminase superfamily. CC Transglutaminase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M55154; AAA40420.1; -; mRNA. DR EMBL; AF114266; AAD37501.1; -; mRNA. DR EMBL; AF076928; AAC62014.1; -; mRNA. DR EMBL; AK052912; BAC35200.1; -; mRNA. DR EMBL; AK080224; BAC37852.1; -; mRNA. DR EMBL; AK080593; BAC37952.1; -; mRNA. DR EMBL; AK089481; BAC40899.1; -; mRNA. DR EMBL; AK143712; BAE25511.1; -; mRNA. DR EMBL; AK151776; BAE30682.1; -; mRNA. DR EMBL; AK152152; BAE30987.1; -; mRNA. DR EMBL; AK152627; BAE31370.1; -; mRNA. DR EMBL; AK159255; BAE34936.1; -; mRNA. DR EMBL; AK166302; BAE38690.1; -; mRNA. DR EMBL; AK168990; BAE40790.1; -; mRNA. DR EMBL; AK169356; BAE41105.1; -; mRNA. DR EMBL; AL669824; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC016492; AAH16492.1; -; mRNA. DR EMBL; U24148; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS16985.1; -. DR PIR; B39045; B39045. DR RefSeq; NP_033399.1; NM_009373.3. DR AlphaFoldDB; P21981; -. DR SMR; P21981; -. DR BioGRID; 204168; 26. DR IntAct; P21981; 4. DR MINT; P21981; -. DR STRING; 10090.ENSMUSP00000099411; -. DR BindingDB; P21981; -. DR ChEMBL; CHEMBL2079853; -. DR MoonProt; P21981; -. DR GlyGen; P21981; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P21981; -. DR PhosphoSitePlus; P21981; -. DR SwissPalm; P21981; -. DR EPD; P21981; -. DR jPOST; P21981; -. DR MaxQB; P21981; -. DR PaxDb; 10090-ENSMUSP00000099411; -. DR PeptideAtlas; P21981; -. DR ProteomicsDB; 262901; -. DR Pumba; P21981; -. DR Antibodypedia; 3611; 1409 antibodies from 47 providers. DR DNASU; 21817; -. DR Ensembl; ENSMUST00000103122.10; ENSMUSP00000099411.4; ENSMUSG00000037820.16. DR GeneID; 21817; -. DR KEGG; mmu:21817; -. DR UCSC; uc008npr.1; mouse. DR AGR; MGI:98731; -. DR CTD; 7052; -. DR MGI; MGI:98731; Tgm2. DR VEuPathDB; HostDB:ENSMUSG00000037820; -. DR eggNOG; ENOG502QUSX; Eukaryota. DR GeneTree; ENSGT01050000244866; -. DR HOGENOM; CLU_013435_1_0_1; -. DR InParanoid; P21981; -. DR OMA; CTVGPGE; -. DR OrthoDB; 5344745at2759; -. DR PhylomeDB; P21981; -. DR TreeFam; TF324278; -. DR BRENDA; 2.3.2.13; 3474. DR BioGRID-ORCS; 21817; 3 hits in 79 CRISPR screens. DR ChiTaRS; Tgm2; mouse. DR PRO; PR:P21981; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; P21981; Protein. DR Bgee; ENSMUSG00000037820; Expressed in conjunctival fornix and 270 other cell types or tissues. DR ExpressionAtlas; P21981; baseline and differential. DR GO; GO:0000785; C:chromatin; ISS:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; ISA:MGI. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:GOC. DR GO; GO:0031012; C:extracellular matrix; ISO:MGI. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW. DR GO; GO:0016020; C:membrane; TAS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; ISO:MGI. DR GO; GO:0000786; C:nucleosome; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB. DR GO; GO:0120297; F:histone dopaminyltransferase activity; ISS:UniProtKB. DR GO; GO:0120295; F:histone serotonyltransferase activity; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0120299; F:peptide histaminyltransferase activity; ISS:UniProtKB. DR GO; GO:0120298; F:peptide noradrenalinyltransferase activity; IEA:RHEA. DR GO; GO:0043274; F:phospholipase binding; ISO:MGI. DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI. DR GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; IMP:UniProtKB. DR GO; GO:0050568; F:protein-glutamine glutaminase activity; ISS:UniProtKB. DR GO; GO:0008483; F:transaminase activity; ISO:MGI. DR GO; GO:0043277; P:apoptotic cell clearance; ISO:MGI. DR GO; GO:0001974; P:blood vessel remodeling; ISO:MGI. DR GO; GO:0060348; P:bone development; ISS:UniProtKB. DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IMP:MGI. DR GO; GO:0071314; P:cellular response to cocaine; ISO:MGI. DR GO; GO:1903351; P:cellular response to dopamine; ISS:UniProtKB. DR GO; GO:1904015; P:cellular response to serotonin; ISS:UniProtKB. DR GO; GO:0014046; P:dopamine secretion; ISO:MGI. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:UniProtKB. DR GO; GO:0010467; P:gene expression; ISO:MGI. DR GO; GO:0032471; P:negative regulation of endoplasmic reticulum calcium ion concentration; IMP:UniProtKB. DR GO; GO:0018149; P:peptide cross-linking; ISS:UniProtKB. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:MGI. DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB. DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB. DR GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; IMP:UniProtKB. DR GO; GO:0050769; P:positive regulation of neurogenesis; ISO:MGI. DR GO; GO:0051057; P:positive regulation of small GTPase mediated signal transduction; ISS:UniProtKB. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI. DR GO; GO:0018277; P:protein deamination; ISS:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:2000425; P:regulation of apoptotic cell clearance; IMP:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0060662; P:salivary gland cavitation; IMP:MGI. DR Gene3D; 2.60.40.10; Immunoglobulins; 3. DR Gene3D; 3.90.260.10; Transglutaminase-like; 1. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR002931; Transglutaminase-like. DR InterPro; IPR036985; Transglutaminase-like_sf. DR InterPro; IPR023608; Transglutaminase_animal. DR InterPro; IPR013808; Transglutaminase_AS. DR InterPro; IPR008958; Transglutaminase_C. DR InterPro; IPR036238; Transglutaminase_C_sf. DR InterPro; IPR001102; Transglutaminase_N. DR PANTHER; PTHR11590; PROTEIN-GLUTAMINE GAMMA-GLUTAMYLTRANSFERASE; 1. DR PANTHER; PTHR11590:SF6; PROTEIN-GLUTAMINE GAMMA-GLUTAMYLTRANSFERASE 2; 1. DR Pfam; PF00927; Transglut_C; 2. DR Pfam; PF01841; Transglut_core; 1. DR Pfam; PF00868; Transglut_N; 1. DR PIRSF; PIRSF000459; TGM_EBP42; 1. DR SMART; SM00460; TGc; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF81296; E set domains; 1. DR SUPFAM; SSF49309; Transglutaminase, two C-terminal domains; 2. DR PROSITE; PS00547; TRANSGLUTAMINASES; 1. DR Genevisible; P21981; MM. PE 1: Evidence at protein level; KW Acetylation; Acyltransferase; Calcium; Cell membrane; Chromosome; KW Cytoplasm; Direct protein sequencing; Disulfide bond; Extracellular matrix; KW GTP-binding; Hydrolase; Isopeptide bond; Membrane; Metal-binding; KW Mitochondrion; Nucleotide-binding; Nucleus; Protease; Reference proteome; KW S-nitrosylation; Secreted; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.8" FT CHAIN 2..686 FT /note="Protein-glutamine gamma-glutamyltransferase 2" FT /id="PRO_0000213708" FT ACT_SITE 277 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024" FT ACT_SITE 335 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024" FT ACT_SITE 358 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024" FT BINDING 398 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P00488" FT BINDING 400 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P00488" FT BINDING 437 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P21980" FT BINDING 447 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P00488" FT BINDING 452 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P00488" FT BINDING 476..483 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P21980" FT BINDING 538 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:P21980" FT BINDING 579..582 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250|UniProtKB:P21980" FT SITE 516 FT /note="Important for catalytic activity" FT /evidence="ECO:0000250|UniProtKB:P52181" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.8" FT MOD_RES 468 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT DISULFID 230..370 FT /note="Alternate" FT /evidence="ECO:0000250|UniProtKB:P21980" FT DISULFID 370..371 FT /note="Alternate" FT /evidence="ECO:0000250|UniProtKB:P21980" FT CROSSLNK 632 FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain FT with K-?)" FT /evidence="ECO:0000250|UniProtKB:P08587" FT CONFLICT 32..33 FT /note="VL -> LV (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" FT CONFLICT 51 FT /note="E -> Q (in Ref. 1; AAA40420 and 2; AAD37501)" FT /evidence="ECO:0000305" FT CONFLICT 186 FT /note="E -> Q (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" FT CONFLICT 226 FT /note="A -> D (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" FT CONFLICT 325 FT /note="S -> T (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" FT CONFLICT 357 FT /note="I -> L (in Ref. 1; AAA40420 and 2; AAD37501)" FT /evidence="ECO:0000305" FT CONFLICT 396 FT /note="E -> K (in Ref. 4; BAC40899)" FT /evidence="ECO:0000305" FT CONFLICT 408..409 FT /note="ED -> DE (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" FT CONFLICT 415..416 FT /note="SI -> WM (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" FT CONFLICT 421 FT /note="V -> I (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" FT CONFLICT 481..485 FT /note="DSMSM -> QYEH (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" FT CONFLICT 539 FT /note="N -> K (in Ref. 4; BAE38690)" FT /evidence="ECO:0000305" FT CONFLICT 552 FT /note="G -> D (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" FT CONFLICT 583 FT /note="L -> V (in Ref. 1; AAA40420 and 2; AAD37501)" FT /evidence="ECO:0000305" FT CONFLICT 654 FT /note="F -> S (in Ref. 1; AAA40420)" FT /evidence="ECO:0000305" SQ SEQUENCE 686 AA; 77061 MW; 9B64B074D3F837DE CRC64; MAEELLLERC DLEIQANGRD HHTADLCQEK LVLRRGQRFR LTLYFEGRGY EASVDSLTFG AVTGPDPSEE AGTKARFSLS DNVEEGSWSA SVLDQQDNVL SLQLCTPANA PIGLYRLSLE ASTGYQGSSF VLGHFILLYN AWCPADDVYL DSEEERREYV LTQQGFIYQG SVKFIKSVPW NFGQFEDGIL DTCLMLLDMN PKFLKNRSRD CSRRSSPIYV GRVVSAMVNC NDDQGVLLGR WDNNYGDGIS PMAWIGSVDI LRRWKEHGCQ QVKYGQCWVF AAVACTVLRC LGIPTRVVTN YNSAHDQNSN LLIEYFRNEF GELESNKSEM IWNFHCWVES WMTRPDLQPG YEGWQAIDPT PQEKSEGTYC CGPVSVRAIK EGDLSTKYDA PFVFAEVNAD VVDWIRQEDG SVLKSINRSL VVGQKISTKS VGRDDREDIT HTYKYPEGSP EEREVFTKAN HLNKLAEKEE TGVAMRIRVG DSMSMGNDFD VFAHIGNDTS ETRECRLLLC ARTVSYNGVL GPECGTEDIN LTLDPYSENS IPLRILYEKY SGCLTESNLI KVRGLLIEPA ANSYLLAERD LYLENPEIKI RVLGEPKQNR KLVAEVSLKN PLSDPLYDCI FTVEGAGLTK EQKSVEVSDP VPAGDLVKAR VDLFPTDIGL HKLVVNFQCD KLKSVKGYRN VIIGPA //