ID TGM2_HUMAN Reviewed; 687 AA. AC P21980; E1P5V9; Q16436; Q6B838; Q9BTN7; Q9H035; Q9UH35; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2002, sequence version 2. DT 27-MAR-2024, entry version 240. DE RecName: Full=Protein-glutamine gamma-glutamyltransferase 2 {ECO:0000305}; DE EC=2.3.2.13 {ECO:0000269|PubMed:23941696, ECO:0000269|PubMed:24349085, ECO:0000269|PubMed:31991788}; DE AltName: Full=Erythrocyte transglutaminase {ECO:0000303|PubMed:2903073}; DE AltName: Full=Heart G alpha(h) {ECO:0000303|PubMed:7592956}; DE Short=hhG alpha(h) {ECO:0000303|PubMed:7592956}; DE AltName: Full=Isopeptidase TGM2 {ECO:0000305}; DE EC=3.4.-.- {ECO:0000269|PubMed:26250429, ECO:0000269|PubMed:27131890}; DE AltName: Full=Protein G alpha(h) {ECO:0000303|PubMed:8943303}; DE Short=G(h) {ECO:0000303|PubMed:8943303}; DE AltName: Full=Protein-glutamine deamidase TGM2 {ECO:0000305}; DE EC=3.5.1.44 {ECO:0000269|PubMed:20547769, ECO:0000269|PubMed:9623982}; DE AltName: Full=Protein-glutamine dopaminyltransferase TGM2 {ECO:0000305}; DE EC=2.3.1.- {ECO:0000269|PubMed:32273471}; DE AltName: Full=Protein-glutamine histaminyltransferase TGM2 {ECO:0000305}; DE EC=2.3.1.- {ECO:0000269|PubMed:23797785}; 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:30867594}; DE AltName: Full=Tissue transglutaminase {ECO:0000303|PubMed:1358880, ECO:0000303|PubMed:1670766, ECO:0000303|PubMed:7935379, ECO:0000303|PubMed:9212111}; DE Short=tTG {ECO:0000303|PubMed:7935379, ECO:0000303|PubMed:9212111}; DE Short=tTgase {ECO:0000303|PubMed:12506096, ECO:0000303|PubMed:7649299}; DE AltName: Full=Transglutaminase C {ECO:0000303|PubMed:11390390}; DE Short=TG(C) {ECO:0000303|PubMed:11390390}; DE Short=TGC {ECO:0000303|PubMed:11390390}; DE Short=TGase C {ECO:0000303|PubMed:11390390}; DE AltName: Full=Transglutaminase H {ECO:0000303|PubMed:1358880}; DE Short=TGase H {ECO:0000303|PubMed:1358880}; DE AltName: Full=Transglutaminase II {ECO:0000303|PubMed:7592956}; DE Short=TGase II {ECO:0000303|PubMed:7592956}; DE AltName: Full=Transglutaminase-2 {ECO:0000303|PubMed:24349085, ECO:0000303|PubMed:30458214}; DE Short=TG2 {ECO:0000303|PubMed:24349085, ECO:0000303|PubMed:30458214}; DE Short=TGase-2; DE Short=hTG2 {ECO:0000303|PubMed:28858494}; GN Name=TGM2 {ECO:0000303|PubMed:17939176, ECO:0000312|HGNC:HGNC:11778}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RC TISSUE=Endothelial cell; 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] (ISOFORM 2), AND INDUCTION. RX PubMed=1358880; DOI=10.1016/s0021-9258(18)41717-6; RA Fraij B.M., Birckbichler P.J., Patterson M.K. Jr., Lee K.N., Gonzales R.A.; RT "A retinoic acid-inducible mRNA from human erythroleukemia cells encodes a RT novel tissue transglutaminase homologue."; RL J. Biol. Chem. 267:22616-22623(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RX PubMed=8611626; DOI=10.1016/0167-4781(95)00219-7; RA Fraij B.M., Gonzales R.A.; RT "A third human tissue transglutaminase homologue as a result of alternative RT gene transcripts."; RL Biochim. Biophys. Acta 1306:63-74(1996). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Colon adenocarcinoma; RA Bayardo M.P., de Urraza P., Chirdo F.G.; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-76; HIS-214; ARG-324; RP TRP-436 AND SER-536. RG NIEHS SNPs program; RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Kidney; 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 [10] RP PROTEIN SEQUENCE OF 2-9; 365-377; 565-590; 635-649 AND 664-674, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Ovarian carcinoma; RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.; RL Submitted (DEC-2008) to UniProtKB. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 448-548 (ISOFORM 2). RC TISSUE=Lymph node; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [12] RP ACTIVITY REGULATION. RX PubMed=2903073; DOI=10.1016/0014-5793(88)80928-1; RA Bergamini C.M.; RT "GTP modulates calcium binding and cation-induced conformational changes in RT erythrocyte transglutaminase."; RL FEBS Lett. 239:255-258(1988). RN [13] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=1683874; DOI=10.1002/jcp.1041490304; RA Upchurch H.F., Conway E., Patterson M.K. Jr., Maxwell M.D.; RT "Localization of cellular transglutaminase on the extracellular matrix RT after wounding: characteristics of the matrix bound enzyme."; RL J. Cell. Physiol. 149:375-382(1991). RN [14] RP FUNCTION. RX PubMed=7935379; DOI=10.1128/mcb.14.10.6584-6596.1994; RA Melino G., Annicchiarico-Petruzzelli M., Piredda L., Candi E., Gentile V., RA Davies P.J., Piacentini M.; RT "Tissue transglutaminase and apoptosis: sense and antisense transfection RT studies with human neuroblastoma cells."; RL Mol. Cell. Biol. 14:6584-6596(1994). RN [15] RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF CYS-277. RX PubMed=7649299; DOI=10.1016/0014-5793(95)00782-5; RA Mian S., el Alaoui S., Lawry J., Gentile V., Davies P.J., Griffin M.; RT "The importance of the GTP-binding protein tissue transglutaminase in the RT regulation of cell cycle progression."; RL FEBS Lett. 370:27-31(1995). RN [16] RP FUNCTION, INTERACTION WITH PHOSPHOLIPASE C, AND MUTAGENESIS OF RP 665-VAL--LYS-672. RX PubMed=7592956; DOI=10.1074/jbc.270.45.27058; RA Hwang K.C., Gray C.D., Sivasubramanian N., Im M.J.; RT "Interaction site of GTP binding Gh (transglutaminase II) with RT phospholipase C."; RL J. Biol. Chem. 270:27058-27062(1995). RN [17] RP FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF CYS-277. RX PubMed=8943303; DOI=10.1074/jbc.271.50.32385; RA Chen S., Lin F., Iismaa S., Lee K.N., Birckbichler P.J., Graham R.M.; RT "Alpha1-adrenergic receptor signaling via Gh is subtype specific and RT independent of its transglutaminase activity."; RL J. Biol. Chem. 271:32385-32391(1996). RN [18] RP FUNCTION. RX PubMed=9252372; DOI=10.1074/jbc.272.33.20577; RA Nemes Z. Jr., Adany R., Balazs M., Boross P., Fesues L.; RT "Identification of cytoplasmic actin as an abundant glutaminyl substrate RT for tissue transglutaminase in HL-60 and U937 cells undergoing apoptosis."; RL J. Biol. Chem. 272:20577-20583(1997). RN [19] RP IDENTIFICATION AS AUTOANTIGEN OF CELIAC DISEASE. RX PubMed=9212111; DOI=10.1038/nm0797-797; RA Dieterich W., Ehnis T., Bauer M., Donner P., Volta U., Riecken E.O., RA Schuppan D.; RT "Identification of tissue transglutaminase as the autoantigen of celiac RT disease."; RL Nat. Med. 3:797-801(1997). RN [20] RP SUBCELLULAR LOCATION. RX PubMed=9575137; DOI=10.1074/jbc.273.20.11991; RA Lesort M., Attanavanich K., Zhang J., Johnson G.V.; RT "Distinct nuclear localization and activity of tissue transglutaminase."; RL J. Biol. Chem. 273:11991-11994(1998). RN [21] RP IDENTIFICATION AS AUTOANTIGEN OF CELIAC DISEASE, FUNCTION, AND CATALYTIC RP ACTIVITY. RX PubMed=9623982; DOI=10.1038/nm0698-713; RA Molberg O., Mcadam S.N., Koerner R., Quarsten H., Kristiansen C., RA Madsen L., Fugger L., Scott H., Noren O., Roepstorff P., Lundin K.E., RA Sjoestroem H., Sollid L.M.; RT "Tissue transglutaminase selectively modifies gliadin peptides that are RT recognized by gut-derived T cells in celiac disease."; RL Nat. Med. 4:713-717(1998). RN [22] RP IDENTIFICATION. RX PubMed=11390390; DOI=10.1074/jbc.m102553200; RA Grenard P., Bates M.K., Aeschlimann D.; RT "Evolution of transglutaminase genes: identification of a transglutaminase RT gene cluster on human chromosome 15q15. Structure of the gene encoding RT transglutaminase X and a novel gene family member, transglutaminase Z."; RL J. Biol. Chem. 276:33066-33078(2001). RN [23] RP FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), SUBUNIT (ISOFORM RP 2), MUTAGENESIS OF CYS-277 (ISOFORM 2), AND MUTAGENESIS OF SER-171. RX PubMed=17116873; DOI=10.1073/pnas.0604844103; RA Antonyak M.A., Jansen J.M., Miller A.M., Ly T.K., Endo M., Cerione R.A.; RT "Two isoforms of tissue transglutaminase mediate opposing cellular fates."; RL Proc. Natl. Acad. Sci. U.S.A. 103:18609-18614(2006). RN [24] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DISULFIDE RP BONDS, AND MUTAGENESIS OF CYS-230; CYS-370 AND CYS-371. RX PubMed=20547769; DOI=10.1074/jbc.m109.097162; RA Stamnaes J., Pinkas D.M., Fleckenstein B., Khosla C., Sollid L.M.; RT "Redox regulation of transglutaminase 2 activity."; RL J. Biol. Chem. 285:25402-25409(2010). RN [25] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12506096; DOI=10.1167/iovs.02-0224; RA Priglinger S.G., May C.A., Neubauer A.S., Alge C.S., Schoenfeld C.L., RA Kampik A., Welge-Lussen U.; RT "Tissue transglutaminase as a modifying enzyme of the extracellular matrix RT in PVR membranes."; RL Invest. Ophthalmol. Vis. Sci. 44:355-364(2003). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [27] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [28] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23797785; DOI=10.1007/s00726-013-1532-y; RA Lai T.S., Greenberg C.S.; RT "Histaminylation of fibrinogen by tissue transglutaminase-2 (TGM-2): RT potential role in modulating inflammation."; RL Amino Acids 45:857-864(2013). RN [29] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF VAL-224. RX PubMed=23941696; DOI=10.1042/bj20130696; RA Kanchan K., Erguelen E., Kiraly R., Simon-Vecsei Z., Fuxreiter M., RA Fesues L.; RT "Identification of a specific one amino acid change in recombinant human RT transglutaminase 2 that regulates its activity and calcium sensitivity."; RL Biochem. J. 455:261-272(2013). RN [30] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP CYS-277. RX PubMed=24349085; DOI=10.1371/journal.pone.0081516; RA Hsieh Y.F., Liu G.Y., Lee Y.J., Yang J.J., Sandor K., Sarang Z., Bononi A., RA Pinton P., Tretter L., Szondy Z., Tsay G.J.; RT "Transglutaminase 2 contributes to apoptosis induction in Jurkat T cells by RT modulating Ca2+ homeostasis via cross-linking RAP1GDS1."; RL PLoS ONE 8:e81516-e81516(2013). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-60, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [32] RP FUNCTION, AND MUTAGENESIS OF TRP-180; TRP-241; CYS-277; TRP-278; TRP-332; RP PHE-334; TRP-337 AND TYR-516. RX PubMed=26250429; DOI=10.1007/s00726-015-2063-5; RA Kiraly R., Thangaraju K., Nagy Z., Collighan R., Nemes Z., Griffin M., RA Fesues L.; RT "Isopeptidase activity of human transglutaminase 2: disconnection from RT transamidation and characterization by kinetic parameters."; RL Amino Acids 48:31-40(2016). RN [33] RP FUNCTION. RX PubMed=27131890; DOI=10.1016/j.ab.2016.04.012; RA Thangaraju K., Biri B., Schlosser G., Kiss B., Nyitray L., Fesues L., RA Kiraly R.; RT "Real-time kinetic method to monitor isopeptidase activity of RT transglutaminase 2 on protein substrate."; RL Anal. Biochem. 505:36-42(2016). RN [34] RP REVIEW. RX PubMed=27270573; DOI=10.1007/s00726-016-2270-8; RA Lai T.S., Lin C.J., Greenberg C.S.; RT "Role of tissue transglutaminase-2 (TG2)-mediated aminylation in biological RT processes."; RL Amino Acids 49:501-515(2017). RN [35] RP ACTIVITY REGULATION. RX PubMed=28858494; DOI=10.1021/acs.jmedchem.7b01070; RA Akbar A., McNeil N.M.R., Albert M.R., Ta V., Adhikary G., Bourgeois K., RA Eckert R.L., Keillor J.W.; RT "Structure-activity relationships of potent, targeted covalent inhibitors RT that abolish both the transamidation and GTP binding activities of human RT tissue transglutaminase."; RL J. Med. Chem. 60:7910-7927(2017). RN [36] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=29618516; DOI=10.1074/jbc.ra117.001078; RA Willis W.L., Wang L., Wada T.T., Gardner M., Abdouni O., Hampton J., RA Valiente G., Young N., Ardoin S., Agarwal S., Freitas M.A., Wu L.C., RA Jarjour W.N.; RT "The proinflammatory protein HMGB1 is a substrate of transglutaminase-2 and RT forms high-molecular weight complexes with autoantigens."; RL J. Biol. Chem. 293:8394-8409(2018). RN [37] RP FUNCTION, AND MUTAGENESIS OF CYS-277. RX PubMed=30458214; DOI=10.1016/j.bbamcr.2018.11.009; RA Maeda A., Nishino T., Matsunaga R., Yokoyama A., Suga H., Yagi T., RA Konishi H.; RT "Transglutaminase-mediated cross-linking of WDR54 regulates EGF receptor- RT signaling."; RL Biochim. Biophys. Acta 1866:285-295(2019). RN [38] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30867594; DOI=10.1038/s41586-019-1024-7; RA Farrelly L.A., Thompson R.E., Zhao S., Lepack A.E., Lyu Y., Bhanu N.V., RA Zhang B., Loh Y.E., Ramakrishnan A., Vadodaria K.C., Heard K.J., RA Erikson G., Nakadai T., Bastle R.M., Lukasak B.J., Zebroski H. III, RA Alenina N., Bader M., Berton O., Roeder R.G., Molina H., Gage F.H., RA Shen L., Garcia B.A., Li H., Muir T.W., Maze I.; RT "Histone serotonylation is a permissive modification that enhances TFIID RT binding to H3K4me3."; RL Nature 567:535-539(2019). RN [39] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32273471; DOI=10.1126/science.aaw8806; RA Lepack A.E., Werner C.T., Stewart A.F., Fulton S.L., Zhong P., RA Farrelly L.A., Smith A.C.W., Ramakrishnan A., Lyu Y., Bastle R.M., RA Martin J.A., Mitra S., O'Connor R.M., Wang Z.J., Molina H., Turecki G., RA Shen L., Yan Z., Calipari E.S., Dietz D.M., Kenny P.J., Maze I.; RT "Dopaminylation of histone H3 in ventral tegmental area regulates cocaine RT seeking."; RL Science 368:197-201(2020). RN [40] {ECO:0007744|PDB:1KV3} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH GDP. RX PubMed=11867708; DOI=10.1073/pnas.042454899; RA Liu S., Cerione R.A., Clardy J.; RT "Structural basis for the guanine nucleotide-binding activity of tissue RT transglutaminase and its regulation of transamidation activity."; RL Proc. Natl. Acad. Sci. U.S.A. 99:2743-2747(2002). RN [41] {ECO:0007744|PDB:2Q3Z} RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), FUNCTION, ACTIVITY REGULATION, AND RP COFACTOR. RX PubMed=18092889; DOI=10.1371/journal.pbio.0050327; RA Pinkas D.M., Strop P., Brunger A.T., Khosla C.; RT "Transglutaminase 2 undergoes a large conformational change upon RT activation."; RL PLoS Biol. 5:E327-E327(2007). RN [42] {ECO:0007744|PDB:3LY6} RP X-RAY CRYSTALLOGRAPHY (3.14 ANGSTROMS) IN COMPLEX WITH ATP, AND DISULFIDE RP BOND. RX PubMed=20450932; DOI=10.1016/j.ijbiomac.2010.04.023; RA Han B.G., Cho J.W., Cho Y.D., Jeong K.C., Kim S.Y., Lee B.I.; RT "Crystal structure of human transglutaminase 2 in complex with adenosine RT triphosphate."; RL Int. J. Biol. Macromol. 47:190-195(2010). RN [43] {ECO:0007744|PDB:4PYG} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) IN COMPLEX WITH GTP, SUBUNIT, AND RP DISULFIDE BOND. RX PubMed=25192068; DOI=10.1371/journal.pone.0107005; RA Jang T.H., Lee D.S., Choi K., Jeong E.M., Kim I.G., Kim Y.W., Chun J.N., RA Jeon J.H., Park H.H.; RT "Crystal structure of transglutaminase 2 with GTP complex and amino acid RT sequence evidence of evolution of GTP binding site."; RL PLoS ONE 9:e107005-e107005(2014). RN [44] {ECO:0007744|PDB:6A8P} RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) IN COMPLEX WITH GTP. RX PubMed=30321187; DOI=10.1371/journal.pone.0204707; RA Ha H.J., Kwon S., Jeong E.M., Kim C.M., Lee K.B., Kim I.G., Park H.H.; RT "Structure of natural variant transglutaminase 2 reveals molecular basis of RT gaining stability and higher activity."; RL PLoS ONE 13:e0204707-e0204707(2018). RN [45] {ECO:0007744|PDB:6KZB} RP X-RAY CRYSTALLOGRAPHY (3.35 ANGSTROMS) IN COMPLEX WITH CALCIUM AND GDP, RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, COFACTOR, AND RP MUTAGENESIS OF GLU-437 AND GLU-539. RX PubMed=31991788; DOI=10.3390/ijms21030791; RA Jeong E.M., Lee K.B., Kim G.E., Kim C.M., Lee J.H., Kim H.J., Shin J.W., RA Kwon M.A., Park H.H., Kim I.G.; RT "Competitive binding of magnesium to calcium binding sites reciprocally RT regulates transamidase and GTP hydrolysis activity of transglutaminase 2."; RL Int. J. Mol. Sci. 21:0-0(2020). RN [46] RP VARIANT [LARGE SCALE ANALYSIS] VAL-660. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [47] RP VARIANTS ARG-330 AND ASN-331. RX PubMed=17939176; DOI=10.1002/humu.9511; RA Porzio O., Massa O., Cunsolo V., Colombo C., Malaponti M., Bertuzzi F., RA Hansen T., Johansen A., Pedersen O., Meschi F., Terrinoni A., Melino G., RA Federici M., Decarlo N., Menicagli M., Campani D., Marchetti P., RA Ferdaoussi M., Froguel P., Federici G., Vaxillaire M., Barbetti F.; RT "Missense mutations in the TGM2 gene encoding transglutaminase 2 are found RT in patients with early-onset type 2 diabetes."; RL Hum. Mutat. 28:1150-1150(2007). 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 (PubMed:9252372, PubMed:23941696, CC PubMed:31991788). Involved in many biological processes, such as bone CC development, angiogenesis, wound healing, cellular differentiation, CC chromatin modification and apoptosis (PubMed:1683874, PubMed:7935379, CC PubMed:9252372, PubMed:27270573). Acts as a protein-glutamine gamma- CC glutamyltransferase by mediating the cross-linking of proteins, such as CC ACO2, HSPB6, FN1, HMGB1, RAP1GDS1, SLC25A4/ANT1, SPP1 and WDR54 CC (PubMed:23941696, PubMed:24349085, PubMed:29618516, PubMed:30458214). CC Under physiological conditions, the protein cross-linking activity is CC inhibited by GTP; inhibition is relieved by Ca(2+) in response to CC various stresses (PubMed:7649299, PubMed:7592956, PubMed:18092889). 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 (PubMed:12506096). 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:7935379, PubMed:9252372). 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:23797785, PubMed:30867594). CC Mediates protein serotonylation of small GTPases during activation and CC aggregation of platelets, leading to constitutive activation of these CC GTPases (By similarity). Plays a key role in chromatin organization by CC mediating serotonylation and dopaminylation of histone H3 CC (PubMed:30867594, PubMed:32273471). Catalyzes serotonylation of 'Gln-5' CC of histone H3 (H3Q5ser) during serotonergic neuron differentiation, CC thereby facilitating transcription (PubMed:30867594). Acts as a CC mediator of neurotransmission-independent role of nuclear dopamine in CC ventral tegmental area (VTA) neurons: catalyzes dopaminylation of 'Gln- CC 5' of histone H3 (H3Q5dop), thereby regulating relapse-related CC transcriptional plasticity in the reward system (PubMed:32273471). CC Regulates vein remodeling by mediating serotonylation and subsequent CC inactivation of ATP2A2/SERCA2 (By similarity). Also acts as a protein CC deamidase by mediating the side chain deamidation of specific glutamine CC residues of proteins to glutamate (PubMed:9623982, PubMed:20547769). CC Catalyzes specific deamidation of protein gliadin, a component of wheat CC gluten in the diet (PubMed:9623982). May also act as an isopeptidase CC cleaving the previously formed cross-links (PubMed:26250429, CC PubMed:27131890). 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:8943303). {ECO:0000250|UniProtKB:P08587, CC ECO:0000250|UniProtKB:P21981, ECO:0000269|PubMed:12506096, CC ECO:0000269|PubMed:1683874, ECO:0000269|PubMed:18092889, CC ECO:0000269|PubMed:20547769, ECO:0000269|PubMed:23797785, CC ECO:0000269|PubMed:23941696, ECO:0000269|PubMed:24349085, CC ECO:0000269|PubMed:26250429, ECO:0000269|PubMed:27131890, CC ECO:0000269|PubMed:29618516, ECO:0000269|PubMed:30458214, CC ECO:0000269|PubMed:30867594, ECO:0000269|PubMed:31991788, CC ECO:0000269|PubMed:32273471, ECO:0000269|PubMed:7592956, CC ECO:0000269|PubMed:7649299, ECO:0000269|PubMed:7935379, CC ECO:0000269|PubMed:8943303, ECO:0000269|PubMed:9252372, CC ECO:0000269|PubMed:9623982, ECO:0000303|PubMed:27270573}. CC -!- FUNCTION: [Isoform 2]: Has cytotoxic activity: is able to induce CC apoptosis independently of its acyltransferase activity. CC {ECO:0000269|PubMed:17116873}. 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; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10024, ECO:0000269|PubMed:23941696, CC ECO:0000269|PubMed:24349085, ECO:0000269|PubMed:31991788}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54817; CC Evidence={ECO:0000269|PubMed:23941696, ECO:0000269|PubMed:24349085, CC ECO:0000269|PubMed:31991788}; 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:30867594}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66553; CC Evidence={ECO:0000269|PubMed:30867594}; 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:0000269|PubMed:32273471}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66557; CC Evidence={ECO:0000269|PubMed:32273471}; 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:0000269|PubMed:23797785}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66565; CC Evidence={ECO:0000269|PubMed:23797785}; 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:0000269|PubMed:20547769, ECO:0000269|PubMed:9623982}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16442; CC Evidence={ECO:0000269|PubMed:20547769, ECO:0000269|PubMed:9623982}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:31991788, ECO:0000305|PubMed:18092889}; 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 (PubMed:2903073, PubMed:7592956, PubMed:18092889, CC PubMed:31991788). In contrast, Ca(2+) acts as a cofactor by inducing CC conformational change to the active open form (PubMed:2903073, CC PubMed:18092889, PubMed:31991788). In absence of Ca(2+), Mg(2+) may CC bind Ca(2+)-binding sites, promoting GTP-binding and subsequent CC inhibition of the acyltransferase activity (PubMed:31991788). CC Specifically inhibited by compound VA4 ((S)-Benzyl (6-Acrylamido-1-(4- CC ((5-(dimethylamino)naphthalen-1-yl)sulfonyl)piperazin-1-yl)-1-oxohexan- CC 2-yl)carbamate), which specifically abolishes both the transamidation CC and GTP-binding activities (PubMed:28858494). CC {ECO:0000269|PubMed:18092889, ECO:0000269|PubMed:28858494, CC ECO:0000269|PubMed:2903073, ECO:0000269|PubMed:31991788, CC ECO:0000269|PubMed:7592956}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=11.2 mM for benzyloxycarbonyl-Gln-Gly (for protein-glutamine CC deamidase activity) {ECO:0000269|PubMed:20547769}; CC Note=kcat is 11.2 min(-1) with benzyloxycarbonyl-Gln-Gly substrate CC for protein-glutamine deamidase activity. CC {ECO:0000269|PubMed:20547769}; CC -!- SUBUNIT: Monomer (PubMed:25192068). Interacts with phospholipase C; CC promoting alpha-1 adrenergic receptor signaling (PubMed:7592956). CC Interacts with PLCD1 (By similarity). {ECO:0000250|UniProtKB:Q9WVJ6, CC ECO:0000269|PubMed:25192068, ECO:0000269|PubMed:7592956}. CC -!- SUBUNIT: [Isoform 2]: Homooligomer. {ECO:0000269|PubMed:17116873}. CC -!- INTERACTION: CC P21980; Q12802: AKAP13; NbExp=4; IntAct=EBI-727668, EBI-1373806; CC P21980; PRO_0000000092 [P05067]: APP; NbExp=2; IntAct=EBI-727668, EBI-821758; CC P21980; PRO_0000005794 [P39060]: COL18A1; NbExp=2; IntAct=EBI-727668, EBI-2566375; CC P21980; P02751: FN1; NbExp=4; IntAct=EBI-727668, EBI-1220319; CC P21980; P08727: KRT19; NbExp=2; IntAct=EBI-727668, EBI-742756; CC P21980; PRO_0000018520 [P28300]: LOX; NbExp=3; IntAct=EBI-727668, EBI-20724846; CC P21980; Q04206: RELA; NbExp=3; IntAct=EBI-727668, EBI-73886; CC P21980; P40337: VHL; NbExp=10; IntAct=EBI-727668, EBI-301246; CC P21980-2; G5E9A7: DMWD; NbExp=3; IntAct=EBI-25842075, EBI-10976677; CC P21980-2; O00429-3: DNM1L; NbExp=3; IntAct=EBI-25842075, EBI-6896746; CC P21980-2; P50570-2: DNM2; NbExp=3; IntAct=EBI-25842075, EBI-10968534; CC P21980-2; P29692-2: EEF1D; NbExp=3; IntAct=EBI-25842075, EBI-5280572; CC P21980-2; Q06787-7: FMR1; NbExp=3; IntAct=EBI-25842075, EBI-25856644; CC P21980-2; P04792: HSPB1; NbExp=3; IntAct=EBI-25842075, EBI-352682; CC P21980-2; P42858: HTT; NbExp=6; IntAct=EBI-25842075, EBI-466029; CC P21980-2; O60333-2: KIF1B; NbExp=3; IntAct=EBI-25842075, EBI-10975473; CC P21980-2; D3DTS7: PMP22; NbExp=3; IntAct=EBI-25842075, EBI-25882629; CC P21980-2; P60891: PRPS1; NbExp=3; IntAct=EBI-25842075, EBI-749195; CC P21980-2; Q5T160: RARS2; NbExp=3; IntAct=EBI-25842075, EBI-1050546; CC P21980-2; Q8N488: RYBP; NbExp=3; IntAct=EBI-25842075, EBI-752324; CC P21980-2; Q14141: SEPTIN6; NbExp=3; IntAct=EBI-25842075, EBI-745901; CC P21980-2; O95416: SOX14; NbExp=3; IntAct=EBI-25842075, EBI-9087806; CC P21980-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-25842075, EBI-5235340; CC P21980-2; O14656-2: TOR1A; NbExp=3; IntAct=EBI-25842075, EBI-25847109; CC P21980-2; Q86WV8: TSC1; NbExp=3; IntAct=EBI-25842075, EBI-12806590; CC P21980-2; P02766: TTR; NbExp=3; IntAct=EBI-25842075, EBI-711909; CC P21980-2; Q9NYH9: UTP6; NbExp=3; IntAct=EBI-25842075, EBI-749211; CC P21980-2; O76024: WFS1; NbExp=3; IntAct=EBI-25842075, EBI-720609; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:24349085, CC ECO:0000269|PubMed:29618516, ECO:0000269|PubMed:9575137}. Nucleus CC {ECO:0000269|PubMed:29618516, ECO:0000269|PubMed:9575137}. Chromosome CC {ECO:0000269|PubMed:9575137}. Secreted, extracellular space, CC extracellular matrix {ECO:0000269|PubMed:12506096, CC ECO:0000269|PubMed:1683874}. Cell membrane CC {ECO:0000250|UniProtKB:Q9WVJ6}. Mitochondrion CC {ECO:0000269|PubMed:24349085}. Note=Mainly localizes to the cytosol CC (PubMed:9575137). Present at much lower level in the nucleus and CC chromatin (PubMed:9575137). Also secreted via a non-classical secretion CC pathway to the extracellular matrix (PubMed:27270573). CC {ECO:0000269|PubMed:9575137, ECO:0000303|PubMed:27270573}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:17116873}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P21980-1; Sequence=Displayed; CC Name=2; Synonyms=TGase-S {ECO:0000303|PubMed:17116873}; CC IsoId=P21980-2; Sequence=VSP_006411, VSP_006412; CC Name=3; Synonyms=TGH2; CC IsoId=P21980-3; Sequence=VSP_006413, VSP_006414; CC -!- INDUCTION: By retinoic acid. {ECO:0000269|PubMed:1358880}. CC -!- PTM: Disulfide bond formation inactivates the calcium-dependent CC acyltransferase activity (PubMed:20547769). Cys-370 can form disulfide CC bonds with both Cys-230 and Cys-371: formation of a disulfide bond CC between Cys-230 and Cys-370 facilitates formation of the disulfide CC between Cys-370 and Cys-371, which promotes inactivation of the CC acyltransferase activity (PubMed:20547769). May also form interchain CC disulfids between Cys-230 and Cys-370 (PubMed:25192068). Ca(2+) CC protects against disulfide bond formation and inactivation CC (PubMed:20547769). {ECO:0000269|PubMed:20547769, CC ECO:0000269|PubMed:25192068}. CC -!- PTM: Auto-transglutaminated: Forms covalent cross-links mediated by CC transglutaminase between Gln-633 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:0000250|UniProtKB:P21981}. CC -!- DISEASE: Note=TGM2 constitutes the major autoantigen in celiac disease, CC a multifactorial chronic disorder of the small intestine caused by CC intolerance to gluten (PubMed:9212111, PubMed:9623982). Celiac disease CC is characterized by immune-mediated enteropathy associated with failed CC intestinal absorption and malnutrition: intestinal inflammation is CC precipitated by ingestion of the protein gliadin, a component of wheat CC gluten in the diet (PubMed:9212111, PubMed:9623982). TGM2 is the main CC target for celiac disease-associated anti-endomysium autoantibodies CC (PubMed:9212111). It mediates its effect by catalyzing specific CC deamidation of gliadin; this deamidation creates an epitope that binds CC efficiently to HLA-DQ2 and is recognized by gut-derived T-cells CC (PubMed:9623982). {ECO:0000269|PubMed:9212111, CC ECO:0000269|PubMed:9623982}. CC -!- SIMILARITY: Belongs to the transglutaminase superfamily. CC Transglutaminase family. {ECO:0000305}. CC -!- CAUTION: Initial enzymatic assays were performed with a protein CC sequence containing a Gly residue instead of a Val at position 224: CC such protein displays lower Ca(2+)-binding affinity and reduced CC transglutaminase activity. {ECO:0000269|PubMed:1670766, CC ECO:0000269|PubMed:23941696}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tissue transglutaminase entry; CC URL="https://en.wikipedia.org/wiki/Tissue_transglutaminase"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/tgm2/"; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Versatile - Issue 236 of May CC 2021; CC URL="https://web.expasy.org/spotlight/back_issues/236/"; 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; M55153; AAA63261.1; -; mRNA. DR EMBL; M98478; AAA36739.1; -; mRNA. DR EMBL; S81734; AAB36379.1; -; mRNA. DR EMBL; AY675221; AAT79353.1; -; mRNA. DR EMBL; AK291714; BAF84403.1; -; mRNA. DR EMBL; AK314618; BAG37184.1; -; mRNA. DR EMBL; DQ523828; ABF47109.1; -; Genomic_DNA. DR EMBL; AL031651; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471077; EAW76040.1; -; Genomic_DNA. DR EMBL; CH471077; EAW76042.1; -; Genomic_DNA. DR EMBL; CH471077; EAW76044.1; -; Genomic_DNA. DR EMBL; BC003551; AAH03551.1; -; mRNA. DR EMBL; AL512703; CAC21649.1; -; mRNA. DR CCDS; CCDS13302.1; -. [P21980-1] DR PIR; A39045; A39045. DR PIR; A44302; A44302. DR PIR; S68092; S68092. DR RefSeq; NP_001310245.1; NM_001323316.1. [P21980-1] DR RefSeq; NP_004604.2; NM_004613.3. [P21980-1] DR RefSeq; NP_945189.1; NM_198951.2. [P21980-2] DR RefSeq; XP_011527330.1; XM_011529028.1. [P21980-1] DR PDB; 1KV3; X-ray; 2.80 A; A/B/C/D/E/F=1-687. DR PDB; 2Q3Z; X-ray; 2.00 A; A=1-687. DR PDB; 3LY6; X-ray; 3.14 A; A/B/C=1-687. DR PDB; 3S3J; X-ray; 2.25 A; A=2-687. DR PDB; 3S3P; X-ray; 2.50 A; A=2-687. DR PDB; 3S3S; X-ray; 2.30 A; A=2-687. DR PDB; 4PYG; X-ray; 2.80 A; A/B/E=1-687. DR PDB; 6A8P; X-ray; 2.54 A; A/B/C=1-687. DR PDB; 6KZB; X-ray; 3.35 A; A/B/C=1-687. DR PDBsum; 1KV3; -. DR PDBsum; 2Q3Z; -. DR PDBsum; 3LY6; -. DR PDBsum; 3S3J; -. DR PDBsum; 3S3P; -. DR PDBsum; 3S3S; -. DR PDBsum; 4PYG; -. DR PDBsum; 6A8P; -. DR PDBsum; 6KZB; -. DR AlphaFoldDB; P21980; -. DR SASBDB; P21980; -. DR SMR; P21980; -. DR BioGRID; 112910; 211. DR CORUM; P21980; -. DR DIP; DIP-33557N; -. DR IntAct; P21980; 79. DR MINT; P21980; -. DR STRING; 9606.ENSP00000355330; -. DR BindingDB; P21980; -. DR ChEMBL; CHEMBL2730; -. DR DrugBank; DB04315; Guanosine-5'-Diphosphate. DR DrugBank; DB11254; Hexylresorcinol. DR DrugBank; DB00130; L-Glutamine. DR GuidetoPHARMACOLOGY; 3015; -. DR MoonProt; P21980; -. DR GlyGen; P21980; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P21980; -. DR MetOSite; P21980; -. DR PhosphoSitePlus; P21980; -. DR SwissPalm; P21980; -. DR BioMuta; TGM2; -. DR DMDM; 20141877; -. DR CPTAC; CPTAC-1644; -. DR CPTAC; CPTAC-280; -. DR CPTAC; CPTAC-281; -. DR EPD; P21980; -. DR jPOST; P21980; -. DR MassIVE; P21980; -. DR MaxQB; P21980; -. DR PaxDb; 9606-ENSP00000355330; -. DR PeptideAtlas; P21980; -. DR ProteomicsDB; 53947; -. [P21980-1] DR ProteomicsDB; 53948; -. [P21980-2] DR ProteomicsDB; 53949; -. [P21980-3] DR Pumba; P21980; -. DR ABCD; P21980; 17 sequenced antibodies. DR Antibodypedia; 3611; 1409 antibodies from 47 providers. DR DNASU; 7052; -. DR Ensembl; ENST00000361475.7; ENSP00000355330.2; ENSG00000198959.12. [P21980-1] DR GeneID; 7052; -. DR KEGG; hsa:7052; -. DR MANE-Select; ENST00000361475.7; ENSP00000355330.2; NM_004613.4; NP_004604.2. DR AGR; HGNC:11778; -. DR CTD; 7052; -. DR DisGeNET; 7052; -. DR GeneCards; TGM2; -. DR HGNC; HGNC:11778; TGM2. DR HPA; ENSG00000198959; Tissue enhanced (cervix). DR MIM; 190196; gene. DR neXtProt; NX_P21980; -. DR OpenTargets; ENSG00000198959; -. DR PharmGKB; PA36491; -. DR VEuPathDB; HostDB:ENSG00000198959; -. DR eggNOG; ENOG502QUSX; Eukaryota. DR GeneTree; ENSGT01050000244866; -. DR HOGENOM; CLU_013435_1_0_1; -. DR InParanoid; P21980; -. DR OMA; CTVGPGE; -. DR OrthoDB; 5344745at2759; -. DR PhylomeDB; P21980; -. DR TreeFam; TF324278; -. DR BRENDA; 2.3.2.13; 2681. DR PathwayCommons; P21980; -. DR SignaLink; P21980; -. DR SIGNOR; P21980; -. DR BioGRID-ORCS; 7052; 14 hits in 1164 CRISPR screens. DR ChiTaRS; TGM2; human. DR EvolutionaryTrace; P21980; -. DR GeneWiki; Tissue_transglutaminase; -. DR GenomeRNAi; 7052; -. DR Pharos; P21980; Tchem. DR PRO; PR:P21980; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P21980; Protein. DR Bgee; ENSG00000198959; Expressed in type B pancreatic cell and 174 other cell types or tissues. DR ExpressionAtlas; P21980; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:GOC. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0000786; C:nucleosome; IDA:UniProt. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB. DR GO; GO:0120297; F:histone dopaminyltransferase activity; IDA:UniProtKB. DR GO; GO:0120295; F:histone serotonyltransferase activity; IDA:UniProtKB. DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW. DR GO; GO:0120299; F:peptide histaminyltransferase activity; IDA:UniProtKB. DR GO; GO:0120298; F:peptide noradrenalinyltransferase activity; IEA:RHEA. DR GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; IDA:UniProtKB. DR GO; GO:0050568; F:protein-glutamine glutaminase activity; IDA:UniProtKB. DR GO; GO:0043277; P:apoptotic cell clearance; IDA:UniProtKB. DR GO; GO:0060348; P:bone development; ISS:UniProtKB. DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IEA:Ensembl. DR GO; GO:0071314; P:cellular response to cocaine; IDA:UniProtKB. DR GO; GO:1903351; P:cellular response to dopamine; IDA:UniProtKB. DR GO; GO:1904015; P:cellular response to serotonin; IDA:UniProtKB. DR GO; GO:0014046; P:dopamine secretion; IDA:UniProt. DR GO; GO:0010467; P:gene expression; IDA:UniProt. DR GO; GO:0032471; P:negative regulation of endoplasmic reticulum calcium ion concentration; IMP:UniProtKB. DR GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB. DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS: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; IDA:UniProtKB. DR GO; GO:0051057; P:positive regulation of small GTPase mediated signal transduction; ISS:UniProtKB. DR GO; GO:0018277; P:protein deamination; IDA:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:2000425; P:regulation of apoptotic cell clearance; IDA:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0060662; P:salivary gland cavitation; IEA:Ensembl. 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; P21980; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Acyltransferase; Alternative splicing; Calcium; KW Cell membrane; Chromosome; Cytoplasm; Direct protein sequencing; KW Disulfide bond; Extracellular matrix; GTP-binding; Hydrolase; KW Isopeptide bond; Membrane; Metal-binding; Mitochondrion; KW Nucleotide-binding; Nucleus; Phosphoprotein; Protease; Reference proteome; KW S-nitrosylation; Secreted; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.10, ECO:0007744|PubMed:22814378" FT CHAIN 2..687 FT /note="Protein-glutamine gamma-glutamyltransferase 2" FT /id="PRO_0000213707" FT ACT_SITE 277 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024, FT ECO:0000305|PubMed:7649299, ECO:0000305|PubMed:8943303" 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:0000305|PubMed:31991788" 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:0000269|PubMed:25192068, FT ECO:0000269|PubMed:30321187, ECO:0000269|PubMed:31991788, FT ECO:0000305|PubMed:11867708, ECO:0000305|PubMed:20450932, FT ECO:0007744|PDB:1KV3, ECO:0007744|PDB:3LY6, FT ECO:0007744|PDB:4PYG, ECO:0007744|PDB:6A8P, FT ECO:0007744|PDB:6KZB" FT BINDING 539 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000305|PubMed:31991788" FT BINDING 580..583 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:25192068, FT ECO:0000269|PubMed:30321187, ECO:0000269|PubMed:31991788, FT ECO:0000305|PubMed:11867708, ECO:0000305|PubMed:20450932, FT ECO:0007744|PDB:1KV3, ECO:0007744|PDB:3LY6, FT ECO:0007744|PDB:4PYG, ECO:0007744|PDB:6A8P, FT ECO:0007744|PDB:6KZB" 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.10, ECO:0007744|PubMed:22814378" FT MOD_RES 60 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 468 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P21981" FT DISULFID 230..370 FT /note="Alternate" FT /evidence="ECO:0000269|PubMed:20450932, FT ECO:0000269|PubMed:20547769, ECO:0000269|PubMed:25192068" FT DISULFID 370..371 FT /note="Alternate" FT /evidence="ECO:0000269|PubMed:20547769" FT CROSSLNK 633 FT /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain FT with K-?)" FT /evidence="ECO:0000250|UniProtKB:P08587" FT VAR_SEQ 287..349 FT /note="VLRCLGIPTRVVTNYNSAHDQNSNLLIEYFRNEFGEIQGDKSEMIWNFHCWV FT ESWMTRPDLQP -> GELHAGMWVMSPGRGHEEHWSRNQDIPALVLPPATNTLNALCGL FT EPVTTLSGPLSNSHPSSGC (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8611626" FT /id="VSP_006413" FT VAR_SEQ 350..687 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8611626" FT /id="VSP_006414" FT VAR_SEQ 539..548 FT /note="EKSVPLCILY -> GKALCSWSIC (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1358880, FT ECO:0000303|PubMed:15489334" FT /id="VSP_006411" FT VAR_SEQ 549..687 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:1358880, FT ECO:0000303|PubMed:15489334" FT /id="VSP_006412" FT VARIANT 76 FT /note="R -> H (in dbSNP:rs41274720)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_052553" FT VARIANT 214 FT /note="R -> H (in dbSNP:rs45530133)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_055357" FT VARIANT 324 FT /note="Q -> R (in dbSNP:rs45567334)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_055358" FT VARIANT 330 FT /note="M -> R (in patients with early-onset diabetes type FT 2; uncertain significance; dbSNP:rs141603506)" FT /evidence="ECO:0000269|PubMed:17939176" FT /id="VAR_037998" FT VARIANT 331 FT /note="I -> N (in patients with early-onset diabetes type FT 2; uncertain significance)" FT /evidence="ECO:0000269|PubMed:17939176" FT /id="VAR_037999" FT VARIANT 436 FT /note="R -> W (in dbSNP:rs45629036)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_055359" FT VARIANT 536 FT /note="P -> S (in dbSNP:rs45556333)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_052554" FT VARIANT 660 FT /note="G -> V (in a colorectal cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036554" FT MUTAGEN 171 FT /note="S->E: Abolishes GTP-binding and transglutaminase FT activities. Does not have cytotoxic activity when FT overexpressed." FT /evidence="ECO:0000269|PubMed:17116873" FT MUTAGEN 180 FT /note="W->F: Abolished isopeptidase activity and reduced FT transamidase activity." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 180 FT /note="W->L: Abolished isopeptidase and transamidase FT activities." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 224 FT /note="V->G: Displays lower Ca(2+)-binding affinity and FT reduced transglutaminase activity." FT /evidence="ECO:0000269|PubMed:23941696" FT MUTAGEN 230 FT /note="C->A: Does not affect the protein-glutamine FT deamidase activity." FT /evidence="ECO:0000269|PubMed:20547769" FT MUTAGEN 241 FT /note="W->F,L: Abolished isopeptidase and transamidase FT activities." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 277 FT /note="C->S: Abolished protein-glutamine FT gamma-glutamyltransferase activity without affecting FT alpha-1 adrenergic receptor signaling. Abolished FT isopeptidase activity." FT /evidence="ECO:0000269|PubMed:24349085, FT ECO:0000269|PubMed:26250429, ECO:0000269|PubMed:7649299, FT ECO:0000269|PubMed:8943303" FT MUTAGEN 277 FT /note="C->V: Dominant negative mutant. Abolishes WDR54 FT cross-linking." FT /evidence="ECO:0000269|PubMed:30458214" FT MUTAGEN 278 FT /note="W->F: In TG2-T; strongly reduced isopeptidase FT activity without affecting the transamidase activity." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 278 FT /note="W->L: Abolished isopeptidase and transamidase FT activities." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 332 FT /note="W->F: In TG2-I; strongly reduced transamidase FT activity without affecting the isopeptidase activity." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 332 FT /note="W->L: Abolished isopeptidase and transamidase FT activities." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 334 FT /note="F->L: Abolished isopeptidase and transamidase FT activities." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 337 FT /note="W->F: Reduced isopeptidase and transamidase FT activities." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 337 FT /note="W->L: Abolished isopeptidase and transamidase FT activities." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 370 FT /note="C->A: Impaired substrate recognition for the FT protein-glutamine deamidase activity." FT /evidence="ECO:0000269|PubMed:20547769" FT MUTAGEN 371 FT /note="C->A: Impaired substrate recognition for the FT protein-glutamine deamidase activity." FT /evidence="ECO:0000269|PubMed:20547769" FT MUTAGEN 437 FT /note="E->R: Impaired Ca(2+)-binding leading to reduced FT transglutaminase activity." FT /evidence="ECO:0000269|PubMed:31991788" FT MUTAGEN 516 FT /note="Y->L: No effect on isopeptidase and transamidase FT activities." FT /evidence="ECO:0000269|PubMed:26250429" FT MUTAGEN 539 FT /note="E->R: Impaired Ca(2+)-binding leading to reduced FT transglutaminase activity." FT /evidence="ECO:0000269|PubMed:31991788" FT MUTAGEN 665..672 FT /note="VVNFESDK->IASMSSDS: Substitution with F13A1 FT sequence. Abolished interaction with phospholipase C and FT ability to promote alpha-1 adrenergic receptor signaling." FT /evidence="ECO:0000269|PubMed:7592956" FT CONFLICT 51 FT /note="E -> Q (in Ref. 1; AAA63261)" FT /evidence="ECO:0000305" FT CONFLICT 186 FT /note="E -> Q (in Ref. 1; AAA63261)" FT /evidence="ECO:0000305" FT CONFLICT 224 FT /note="V -> G (in Ref. 1; AAA63261)" FT /evidence="ECO:0000305" FT CONFLICT 533 FT /note="N -> T (in Ref. 1; AAA63261)" FT /evidence="ECO:0000305" FT CONFLICT 655 FT /note="L -> V (in Ref. 1; AAA63261)" FT /evidence="ECO:0000305" FT STRAND 7..11 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 14..20 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 24..26 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 28..30 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 39..48 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 52..54 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 55..66 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 69..72 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 73..79 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 85..87 FT /evidence="ECO:0007829|PDB:4PYG" FT STRAND 89..95 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 97..105 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 113..123 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 126..138 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 153..159 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 164..170 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 172..181 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 189..198 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 201..205 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 207..213 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 217..226 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 227..229 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 231..234 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 235..239 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 251..253 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 255..257 FT /evidence="ECO:0007829|PDB:4PYG" FT HELIX 258..266 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 267..269 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 272..275 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 277..291 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 295..304 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 306..309 FT /evidence="ECO:0007829|PDB:1KV3" FT HELIX 311..317 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 332..342 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 347..350 FT /evidence="ECO:0007829|PDB:3LY6" FT STRAND 353..357 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 365..369 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 376..380 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 387..389 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 390..397 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 400..404 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 412..414 FT /evidence="ECO:0007829|PDB:6A8P" FT STRAND 419..429 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 433..438 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 440..443 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 447..449 FT /evidence="ECO:0007829|PDB:3LY6" FT HELIX 450..460 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 468..471 FT /evidence="ECO:0007829|PDB:3LY6" FT STRAND 473..478 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 489..497 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 499..501 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 503..514 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 520..534 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 538..546 FT /evidence="ECO:0007829|PDB:2Q3Z" FT HELIX 548..551 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 552..554 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 560..569 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 570..573 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 574..583 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 590..595 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 598..601 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 603..610 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 613..615 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 619..625 FT /evidence="ECO:0007829|PDB:2Q3Z" FT TURN 627..629 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 634..638 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 647..654 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 658..660 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 662..669 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 671..673 FT /evidence="ECO:0007829|PDB:2Q3Z" FT STRAND 676..682 FT /evidence="ECO:0007829|PDB:2Q3Z" FT MUTAGEN P21980-2:277 FT /note="C->V: Abolished protein-glutamine FT gamma-glutamyltransferase activity without affecting FT cytotoxic activity." FT /evidence="ECO:0000269|PubMed:17116873" SQ SEQUENCE 687 AA; 77329 MW; 7DA33FF335DE7B37 CRC64; MAEELVLERC DLELETNGRD HHTADLCREK LVVRRGQPFW LTLHFEGRNY EASVDSLTFS VVTGPAPSQE AGTKARFPLR DAVEEGDWTA TVVDQQDCTL SLQLTTPANA PIGLYRLSLE ASTGYQGSSF VLGHFILLFN AWCPADAVYL DSEEERQEYV LTQQGFIYQG SAKFIKNIPW NFGQFEDGIL DICLILLDVN PKFLKNAGRD CSRRSSPVYV GRVVSGMVNC NDDQGVLLGR WDNNYGDGVS PMSWIGSVDI LRRWKNHGCQ RVKYGQCWVF AAVACTVLRC LGIPTRVVTN YNSAHDQNSN LLIEYFRNEF GEIQGDKSEM IWNFHCWVES WMTRPDLQPG YEGWQALDPT PQEKSEGTYC CGPVPVRAIK EGDLSTKYDA PFVFAEVNAD VVDWIQQDDG SVHKSINRSL IVGLKISTKS VGRDEREDIT HTYKYPEGSS EEREAFTRAN HLNKLAEKEE TGMAMRIRVG QSMNMGSDFD VFAHITNNTA EEYVCRLLLC ARTVSYNGIL GPECGTKYLL NLNLEPFSEK SVPLCILYEK YRDCLTESNL IKVRALLVEP VINSYLLAER DLYLENPEIK IRILGEPKQK RKLVAEVSLQ NPLPVALEGC TFTVEGAGLT EEQKTVEIPD PVEAGEEVKV RMDLLPLHMG LHKLVVNFES DKLKAVKGFR NVIIGPA //