TGM2_HUMAN
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 03-AUG-2022, entry version 231.
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/";
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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 SMR; P21980; -.
DR BioGRID; 112910; 140.
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 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; P21980; -.
DR PeptideAtlas; P21980; -.
DR PRIDE; P21980; -.
DR ProteomicsDB; 53947; -. [P21980-1]
DR ProteomicsDB; 53948; -. [P21980-2]
DR ProteomicsDB; 53949; -. [P21980-3]
DR ABCD; P21980; 17 sequenced antibodies.
DR Antibodypedia; 3611; 1230 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 CTD; 7052; -.
DR DisGeNET; 7052; -.
DR GeneCards; TGM2; -.
DR HGNC; HGNC:11778; TGM2.
DR HPA; ENSG00000198959; Low tissue specificity.
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; IKSVPWN; -.
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; 12 hits in 1088 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 172 other tissues.
DR ExpressionAtlas; P21980; baseline and differential.
DR Genevisible; P21980; HS.
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:UniProtKB.
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:0031226; C:intrinsic component of plasma membrane; IDA:CACAO.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
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: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; -; 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 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; unknown pathological 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; unknown pathological 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 gamma-
FT glutamyltransferase activity without affecting alpha-1
FT adrenergic receptor signaling. Abolished isopeptidase
FT 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 gamma-
FT glutamyltransferase activity without affecting cytotoxic
FT 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
