TGM2_MOUSE
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 03-AUG-2022, entry version 191.
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, Macrophage,
RC 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, Pancreas,
RC 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}.
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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; 25.
DR IntAct; P21981; 3.
DR MINT; P21981; -.
DR STRING; 10090.ENSMUSP00000099411; -.
DR BindingDB; P21981; -.
DR ChEMBL; CHEMBL2079853; -.
DR iPTMnet; P21981; -.
DR PhosphoSitePlus; P21981; -.
DR SwissPalm; P21981; -.
DR EPD; P21981; -.
DR jPOST; P21981; -.
DR MaxQB; P21981; -.
DR PaxDb; P21981; -.
DR PeptideAtlas; P21981; -.
DR PRIDE; P21981; -.
DR ProteomicsDB; 262901; -.
DR Antibodypedia; 3611; 1230 antibodies from 47 providers.
DR DNASU; 21817; -.
DR Ensembl; ENSMUST00000103122; ENSMUSP00000099411; ENSMUSG00000037820.
DR GeneID; 21817; -.
DR KEGG; mmu:21817; -.
DR UCSC; uc008npr.1; mouse.
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; IKSVPWN; -.
DR OrthoDB; 297055at2759; -.
DR PhylomeDB; P21981; -.
DR TreeFam; TF324278; -.
DR BRENDA; 2.3.2.13; 3474.
DR BioGRID-ORCS; 21817; 3 hits in 74 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 268 other tissues.
DR ExpressionAtlas; P21981; baseline and differential.
DR Genevisible; P21981; MM.
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:0031226; C:intrinsic component of plasma membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; TAS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; 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: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: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: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:0007186; P:G protein-coupled receptor signaling pathway; TAS:UniProtKB.
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: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: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; -; 3.
DR Gene3D; 3.90.260.10; -; 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 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; SSF49309; SSF49309; 2.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS00547; TRANSGLUTAMINASES; 1.
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
