ID   TGM2_RAT                Reviewed;         686 AA.
AC   Q9WVJ6; Q6P6R6;
DT   07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   24-JAN-2024, entry version 152.
DE   RecName: Full=Protein-glutamine gamma-glutamyltransferase 2 {ECO:0000305};
DE            EC=2.3.2.13 {ECO:0000269|PubMed:16341586};
DE   AltName: Full=Isopeptidase TGM2 {ECO:0000305};
DE            EC=3.4.-.- {ECO:0000250|UniProtKB:P21980};
DE   AltName: Full=Protein G alpha(h) {ECO:0000303|PubMed:7911253};
DE            Short=Protein G(h) {ECO:0000303|PubMed:7911253};
DE   AltName: Full=Protein-glutamine deamidase TGM2 {ECO:0000305};
DE            EC=3.5.1.44 {ECO:0000250|UniProtKB:P21980};
DE   AltName: Full=Protein-glutamine dopaminyltransferase TGM2 {ECO:0000305};
DE            EC=2.3.1.- {ECO:0000250|UniProtKB:P21980};
DE   AltName: Full=Protein-glutamine histaminyltransferase TGM2 {ECO:0000305};
DE            EC=2.3.1.- {ECO:0000250|UniProtKB:P21980};
DE   AltName: Full=Protein-glutamine noradrenalinyltransferase TGM2 {ECO:0000305};
DE            EC=2.3.1.- {ECO:0000250|UniProtKB:P08587};
DE   AltName: Full=Protein-glutamine serotonyltransferase TGM2 {ECO:0000305};
DE            EC=2.3.1.- {ECO:0000250|UniProtKB:P21980};
DE   AltName: Full=Tissue transglutaminase {ECO:0000303|PubMed:11073883};
DE            Short=tTG {ECO:0000303|PubMed:11073883};
DE            Short=tTgase {ECO:0000250|UniProtKB:P21980};
DE   AltName: Full=Transglutaminase II {ECO:0000303|PubMed:7911253};
DE            Short=TGase II {ECO:0000303|PubMed:7911253};
DE   AltName: Full=Transglutaminase-2 {ECO:0000303|PubMed:16341586};
DE            Short=TGase 2 {ECO:0000303|PubMed:16341586};
DE            Short=TGase-2 {ECO:0000303|PubMed:16341586};
GN   Name=Tgm2 {ECO:0000312|RGD:621081};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND INDUCTION.
RC   STRAIN=Sprague-Dawley; TISSUE=Aortic smooth muscle;
RX   PubMed=11073883; DOI=10.1161/01.res.87.10.881;
RA   Ou H., Haendeler J., Aebly M.R., Kelly L.A., Cholewa B.C., Koike G.,
RA   Kwitek-Black A., Jacob H.J., Berk B.C., Miano J.M.;
RT   "Retinoic acid-induced tissue transglutaminase and apoptosis in vascular
RT   smooth muscle cells.";
RL   Circ. Res. 87:881-887(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Prostate;
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   [5]
RP   PROTEIN SEQUENCE OF 430-451; 634-655 AND 674-680, FUNCTION, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=7911253; DOI=10.1126/science.7911253;
RA   Nakaoka H., Perez D.M., Baek K.J., Das T., Husain A., Misono K., Im M.J.,
RA   Graham R.M.;
RT   "Gh: a GTP-binding protein with transglutaminase activity and receptor
RT   signaling function.";
RL   Science 264:1593-1596(1994).
RN   [6]
RP   FUNCTION, AND INTERACTION WITH PLCD1.
RX   PubMed=12054611; DOI=10.1016/s0006-291x(02)00197-3;
RA   Kang S.K., Kim D.K., Damron D.S., Baek K.J., Im M.J.;
RT   "Modulation of intracellular Ca(2+) via alpha(1B)-adrenoreceptor signaling
RT   molecules, G alpha(h) (transglutaminase II) and phospholipase C-delta 1.";
RL   Biochem. Biophys. Res. Commun. 293:383-390(2002).
RN   [7]
RP   FUNCTION, SUBCELLULAR LOCATION, INDUCTION, ACTIVE SITE, AND MUTAGENESIS OF
RP   CYS-277.
RX   PubMed=14970202; DOI=10.1074/jbc.m314299200;
RA   Dupuis M., Levy A., Mhaouty-Kodja S.;
RT   "Functional coupling of rat myometrial alpha 1-adrenergic receptors to Gh
RT   alpha/tissue transglutaminase 2 during pregnancy.";
RL   J. Biol. Chem. 279:19257-19263(2004).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX   PubMed=16341586; DOI=10.1007/s11064-005-8796-x;
RA   Kim S.Y., Marekov L., Bubber P., Browne S.E., Stavrovskaya I., Lee J.,
RA   Steinert P.M., Blass J.P., Beal M.F., Gibson G.E., Cooper A.J.;
RT   "Mitochondrial aconitase is a transglutaminase 2 substrate:
RT   transglutamination is a probable mechanism contributing to high-molecular-
RT   weight aggregates of aconitase and loss of aconitase activity in Huntington
RT   disease brain.";
RL   Neurochem. Res. 30:1245-1255(2005).
RN   [9]
RP   ACTIVITY REGULATION, AND MUTAGENESIS OF ARG-579.
RX   PubMed=17179049; DOI=10.1073/pnas.0609283103;
RA   Begg G.E., Carrington L., Stokes P.H., Matthews J.M., Wouters M.A.,
RA   Husain A., Lorand L., Iismaa S.E., Graham R.M.;
RT   "Mechanism of allosteric regulation of transglutaminase 2 by GTP.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:19683-19688(2006).
RN   [10]
RP   FUNCTION, AND S-NITROSYLATION.
RX   PubMed=29622788; DOI=10.1038/s12276-017-0021-x;
RA   Jeong E.M., Jin C.Z., Jang J.H., Zhao Z.H., Jin C.L., Lee J.H., Lee K.B.,
RA   Kim S.J., Kim I.G., Zhang Y.H.;
RT   "S-nitrosylation of transglutaminase 2 impairs fatty acid-stimulated
RT   contraction in hypertensive cardiomyocytes.";
RL   Exp. Mol. Med. 50:9-9(2018).
CC   -!- FUNCTION: Calcium-dependent acyltransferase that catalyzes the
CC       formation of covalent bonds between peptide-bound glutamine and various
CC       primary amines, such as gamma-amino group of peptide-bound lysine, or
CC       mono- and polyamines, thereby producing cross-linked or aminated
CC       proteins, respectively (By similarity). Involved in many biological
CC       processes, such as bone development, angiogenesis, wound healing,
CC       cellular differentiation, chromatin modification and apoptosis (By
CC       similarity). Acts as a protein-glutamine gamma-glutamyltransferase by
CC       mediating the cross-linking of proteins, such as ACO2, HSPB6, FN1,
CC       HMGB1, RAP1GDS1, SLC25A4/ANT1, SPP1 and WDR54 (PubMed:16341586,
CC       PubMed:29622788). Under physiological conditions, the protein cross-
CC       linking activity is inhibited by GTP; inhibition is relieved by Ca(2+)
CC       in response to various stresses (By similarity). When secreted,
CC       catalyzes cross-linking of proteins of the extracellular matrix, such
CC       as FN1 and SPP1 resulting in the formation of scaffolds (By
CC       similarity). Plays a key role during apoptosis, both by (1) promoting
CC       the cross-linking of cytoskeletal proteins resulting in condensation of
CC       the cytoplasm, and by (2) mediating cross-linking proteins of the
CC       extracellular matrix, resulting in the irreversible formation of
CC       scaffolds that stabilize the integrity of the dying cells before their
CC       clearance by phagocytosis, thereby preventing the leakage of harmful
CC       intracellular components (By similarity). In addition to protein cross-
CC       linking, can use different monoamine substrates to catalyze a vast
CC       array of protein post-translational modifications: mediates aminylation
CC       of serotonin, dopamine, noradrenaline or histamine into glutamine
CC       residues of target proteins to generate protein serotonylation,
CC       dopaminylation, noradrenalinylation or histaminylation, respectively
CC       (By similarity). Mediates protein serotonylation of small GTPases
CC       during activation and aggregation of platelets, leading to constitutive
CC       activation of these GTPases (By similarity). Plays a key role in
CC       chromatin organization by mediating serotonylation and dopaminylation
CC       of histone H3 (By similarity). Catalyzes serotonylation of 'Gln-5' of
CC       histone H3 (H3Q5ser) during serotonergic neuron differentiation,
CC       thereby facilitating transcription (By similarity). Acts as a mediator
CC       of neurotransmission-independent role of nuclear dopamine in ventral
CC       tegmental area (VTA) neurons: catalyzes dopaminylation of 'Gln-5' of
CC       histone H3 (H3Q5dop), thereby regulating relapse-related
CC       transcriptional plasticity in the reward system (By similarity).
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 (By similarity). Catalyzes specific
CC       deamidation of protein gliadin, a component of wheat gluten in the diet
CC       (By similarity). May also act as an isopeptidase cleaving the
CC       previously formed cross-links (By similarity). Also able to participate
CC       in signaling pathways independently of its acyltransferase activity:
CC       acts as a signal transducer in alpha-1 adrenergic receptor-mediated
CC       stimulation of phospholipase C-delta (PLCD) activity and is required
CC       for coupling alpha-1 adrenergic agonists to the stimulation of
CC       phosphoinositide lipid metabolism (PubMed:7911253, PubMed:12054611,
CC       PubMed:14970202). Activates alpha-1 adrenergic receptor signaling
CC       during pregnancy, promoting smooth muscle cell proliferation
CC       (PubMed:14970202). {ECO:0000250|UniProtKB:P08587,
CC       ECO:0000250|UniProtKB:P21980, ECO:0000250|UniProtKB:P21981,
CC       ECO:0000269|PubMed:12054611, ECO:0000269|PubMed:14970202,
CC       ECO:0000269|PubMed:16341586, ECO:0000269|PubMed:29622788,
CC       ECO:0000269|PubMed:7911253}.
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:16341586};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54817;
CC         Evidence={ECO:0000269|PubMed:16341586};
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:0000250|UniProtKB:P21980};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66553;
CC         Evidence={ECO:0000250|UniProtKB:P21980};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dopamine + L-glutaminyl-[protein] = 5-dopaminyl-L-glutamyl-
CC         [protein] + NH4(+); Xref=Rhea:RHEA:66556, Rhea:RHEA-COMP:10207,
CC         Rhea:RHEA-COMP:17053, ChEBI:CHEBI:28938, ChEBI:CHEBI:30011,
CC         ChEBI:CHEBI:59905, ChEBI:CHEBI:167175;
CC         Evidence={ECO:0000250|UniProtKB:P21980};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66557;
CC         Evidence={ECO:0000250|UniProtKB:P21980};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=histamine + L-glutaminyl-[protein] = 5-histaminyl-L-glutamyl-
CC         [protein] + NH4(+); Xref=Rhea:RHEA:66564, Rhea:RHEA-COMP:10207,
CC         Rhea:RHEA-COMP:17056, ChEBI:CHEBI:28938, ChEBI:CHEBI:30011,
CC         ChEBI:CHEBI:58432, ChEBI:CHEBI:167179;
CC         Evidence={ECO:0000250|UniProtKB:P21980};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66565;
CC         Evidence={ECO:0000250|UniProtKB:P21980};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(R)-noradrenaline + L-glutaminyl-[protein] = 5-(R)-
CC         noradrenalinyl-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:66560,
CC         Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:17054, ChEBI:CHEBI:28938,
CC         ChEBI:CHEBI:30011, ChEBI:CHEBI:72587, ChEBI:CHEBI:167178;
CC         Evidence={ECO:0000250|UniProtKB:P08587};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66561;
CC         Evidence={ECO:0000250|UniProtKB:P08587};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + L-glutaminyl-[protein] = L-glutamyl-[protein] + NH4(+);
CC         Xref=Rhea:RHEA:16441, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:10208,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29973,
CC         ChEBI:CHEBI:30011; EC=3.5.1.44;
CC         Evidence={ECO:0000250|UniProtKB:P21980};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16442;
CC         Evidence={ECO:0000250|UniProtKB:P21980};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000250|UniProtKB:P21980};
CC   -!- ACTIVITY REGULATION: Acyltransferase activity is regulated by the
CC       binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its
CC       closed structure, thereby obstructing the accessibility of substrates
CC       to the active sites (PubMed:17179049). In contrast, Ca(2+) acts as a
CC       cofactor by inducing conformational change to the active open form. In
CC       absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-
CC       binding and subsequent inhibition of the acyltransferase activity (By
CC       similarity). {ECO:0000250|UniProtKB:P21980,
CC       ECO:0000269|PubMed:17179049}.
CC   -!- SUBUNIT: Monomer (By similarity). Interacts with phospholipase C;
CC       promoting alpha-1 adrenergic receptor signaling (By similarity).
CC       Interacts with PLCD1 (PubMed:12054611). {ECO:0000250|UniProtKB:P21980,
CC       ECO:0000269|PubMed:12054611}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11073883,
CC       ECO:0000269|PubMed:7911253}. Nucleus {ECO:0000269|PubMed:11073883}.
CC       Chromosome {ECO:0000250|UniProtKB:P21980}. Secreted, extracellular
CC       space, extracellular matrix {ECO:0000250|UniProtKB:P21980}. Cell
CC       membrane {ECO:0000269|PubMed:14970202}. Mitochondrion
CC       {ECO:0000269|PubMed:16341586}. Note=Mainly localizes to the cytosol.
CC       Present at much lower level in the nucleus and chromatin. Also secreted
CC       via a non-classical secretion pathway to the extracellular matrix.
CC       {ECO:0000250|UniProtKB:P21980}.
CC   -!- INDUCTION: By retinoic acid (PubMed:11073883). Up-regulated during
CC       pregnancy (PubMed:14970202). {ECO:0000269|PubMed:11073883,
CC       ECO:0000269|PubMed:14970202}.
CC   -!- PTM: Disulfide bond formation inactivates the calcium-dependent
CC       acyltransferase activity. Cys-370 can form disulfide bonds with both
CC       Cys-230 and Cys-371: formation of a disulfide bond between Cys-230 and
CC       Cys-370 facilitates formation of the disulfide between Cy-370 and Cys-
CC       371, which promotes inactivation of the acyltransferase activity. May
CC       also form interchain disulfids between Cys-230 and Cys-370. Ca(2+)
CC       protects against disulfide bond formation and inactivation.
CC       {ECO:0000250|UniProtKB:P21980}.
CC   -!- PTM: Auto-transglutaminated: Forms covalent cross-links mediated by
CC       transglutaminase between Gln-632 and the epsilon-amino group of a
CC       lysine residue of itself or HMGB1, forming homopolymers and
CC       heteropolymers, respectively. {ECO:0000250|UniProtKB:P08587}.
CC   -!- PTM: S-nitrosylated, leading to its inactivate the acyltransferase
CC       activity. {ECO:0000269|PubMed:29622788}.
CC   -!- SIMILARITY: Belongs to the transglutaminase superfamily.
CC       Transglutaminase family. {ECO:0000305}.
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DR   EMBL; AABR07054457; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF106325; AAD42046.1; -; mRNA.
DR   EMBL; CH474005; EDL96658.1; -; Genomic_DNA.
DR   EMBL; BC062062; AAH62062.1; -; mRNA.
DR   RefSeq; NP_062259.2; NM_019386.2.
DR   AlphaFoldDB; Q9WVJ6; -.
DR   SMR; Q9WVJ6; -.
DR   CORUM; Q9WVJ6; -.
DR   STRING; 10116.ENSRNOP00000018328; -.
DR   GlyGen; Q9WVJ6; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9WVJ6; -.
DR   PhosphoSitePlus; Q9WVJ6; -.
DR   PaxDb; 10116-ENSRNOP00000018328; -.
DR   Ensembl; ENSRNOT00000018328.6; ENSRNOP00000018328.5; ENSRNOG00000012956.7.
DR   Ensembl; ENSRNOT00060044772; ENSRNOP00060037125; ENSRNOG00060025818.
DR   GeneID; 56083; -.
DR   KEGG; rno:56083; -.
DR   UCSC; RGD:621081; rat.
DR   AGR; RGD:621081; -.
DR   CTD; 7052; -.
DR   RGD; 621081; Tgm2.
DR   eggNOG; ENOG502QUSX; Eukaryota.
DR   GeneTree; ENSGT01050000244866; -.
DR   HOGENOM; CLU_013435_1_0_1; -.
DR   InParanoid; Q9WVJ6; -.
DR   OrthoDB; 5344745at2759; -.
DR   PhylomeDB; Q9WVJ6; -.
DR   TreeFam; TF324278; -.
DR   PRO; PR:Q9WVJ6; -.
DR   Proteomes; UP000002494; Chromosome 3.
DR   Proteomes; UP000234681; Chromosome 3.
DR   Bgee; ENSRNOG00000012956; Expressed in lung and 19 other cell types or tissues.
DR   GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:GOC.
DR   GO; GO:0031012; C:extracellular matrix; ISO:RGD.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR   GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR   GO; GO:0000786; C:nucleosome; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0019899; F:enzyme binding; IC:RGD.
DR   GO; GO:0005525; F:GTP binding; IDA:RGD.
DR   GO; GO:0120297; F:histone dopaminyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0120295; F:histone serotonyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR   GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0120299; F:peptide histaminyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0043274; F:phospholipase binding; IPI:RGD.
DR   GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR   GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; ISO:RGD.
DR   GO; GO:0050568; F:protein-glutamine glutaminase activity; ISS:UniProtKB.
DR   GO; GO:0043277; P:apoptotic cell clearance; ISO:RGD.
DR   GO; GO:0001974; P:blood vessel remodeling; IMP:RGD.
DR   GO; GO:0060348; P:bone development; ISS:UniProtKB.
DR   GO; GO:0060445; P:branching involved in salivary gland morphogenesis; ISO:RGD.
DR   GO; GO:0071314; P:cellular response to cocaine; ISO:RGD.
DR   GO; GO:1903351; P:cellular response to dopamine; ISS:UniProtKB.
DR   GO; GO:1904015; P:cellular response to serotonin; ISS:UniProtKB.
DR   GO; GO:0014046; P:dopamine secretion; ISO:RGD.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR   GO; GO:0010467; P:gene expression; ISO:RGD.
DR   GO; GO:0032471; P:negative regulation of endoplasmic reticulum calcium ion concentration; ISO:RGD.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IDA:MGI.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:RGD.
DR   GO; GO:0045785; P:positive regulation of cell adhesion; ISO:RGD.
DR   GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR   GO; GO:0051561; P:positive regulation of mitochondrial calcium ion concentration; ISO:RGD.
DR   GO; GO:0050769; P:positive regulation of neurogenesis; ISO:RGD.
DR   GO; GO:0051057; P:positive regulation of small GTPase mediated signal transduction; ISS:UniProtKB.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:RGD.
DR   GO; GO:0018277; P:protein deamination; ISS:UniProtKB.
DR   GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:2000425; P:regulation of apoptotic cell clearance; ISS:UniProtKB.
DR   GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0060662; P:salivary gland cavitation; ISO:RGD.
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.
PE   1: Evidence at protein level;
KW   Acetylation; Acyltransferase; Calcium; Cell membrane; Chromosome;
KW   Cytoplasm; Direct protein sequencing; Disulfide bond; Extracellular matrix;
KW   GTP-binding; Hydrolase; Isopeptide bond; Membrane; Metal-binding;
KW   Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; Protease;
KW   Reference proteome; S-nitrosylation; Secreted; Transferase.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P21980"
FT   CHAIN           2..686
FT                   /note="Protein-glutamine gamma-glutamyltransferase 2"
FT                   /id="PRO_0000452473"
FT   ACT_SITE        277
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10024,
FT                   ECO:0000305|PubMed:14970202"
FT   ACT_SITE        335
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10024"
FT   ACT_SITE        358
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10024"
FT   BINDING         398
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P00488"
FT   BINDING         400
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P00488"
FT   BINDING         437
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P21980"
FT   BINDING         447
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P00488"
FT   BINDING         452
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P00488"
FT   BINDING         476..483
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P21980"
FT   BINDING         538
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P21980"
FT   BINDING         579..582
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:P21980"
FT   SITE            516
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P52181"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P21980"
FT   MOD_RES         468
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P21981"
FT   DISULFID        230..370
FT                   /note="Alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P21980"
FT   DISULFID        370..371
FT                   /note="Alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P21980"
FT   CROSSLNK        632
FT                   /note="Isoglutamyl lysine isopeptide (Gln-Lys) (interchain
FT                   with K-?)"
FT                   /evidence="ECO:0000250|UniProtKB:P08587"
FT   MUTAGEN         277
FT                   /note="C->S: Abolished protein-glutamine
FT                   gamma-glutamyltransferase activity without affecting
FT                   alpha-1 adrenergic receptor signaling."
FT                   /evidence="ECO:0000269|PubMed:14970202"
FT   MUTAGEN         579
FT                   /note="R->A: Destabilizes the compact conformation in
FT                   presence of GTP."
FT                   /evidence="ECO:0000269|PubMed:17179049"
FT   CONFLICT        29
FT                   /note="Q -> E (in Ref. 4; AAH62062)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   686 AA;  76935 MW;  4CD3D377FA86EC1A CRC64;
     MAEELNLERC DLEIQANGRD HHTADLCQQK LVLRRGQRFR LTLYFEGRGY EASVDRLTFG
     AVTGPDPSEE AGTKARFSLS DDVEEGSWSA SVLDQQDNVL SLQLCTPANA PVGQYRLSLE
     TSTGYQGSSF MLGHFILLFN AWCPADDVYL DSEAERREYV LTQQGFIYQG SVKFIKSVPW
     NFGQFEDGIL DACLMLLDVN PKFLKDRSRD CSRRSSPIYV GRVVSGMVNC NDDQGVLLGR
     WDNNYGDGIS PMAWIGSVDI LRRWKEHGCQ QVKYGQCWVF AAVACTVLRC LGIPTRVVTN
     YNSAHDQNSN LLIEYFRNEY GELESNKSEM IWNFHCWVES WMTRPDLQPG YEGWQAIDPT
     PQEKSEGTYC CGPVSVRAIK EGDLSTKYDA SFVFAEVNAD VVDWIRQSDG SVLKSINNSL
     VVGQKISTKS VGRDDREDIT YTYKYPEGSP EEREVFTRAN HLNKLAEKEE TGVAMRIRVG
     DGMSLGNDFD VFAHIGNDTS ESRECRLLLC ARTVSYNGVL GPECGTEDIN LTLDPYSENS
     IPLRILYEKY SGCLTESNLI KVRGLLVEPA ANSYLLAERD LYLENPEIKI RILGEPKQNR
     KLVAEVSLKN PLSDSLYDCV FTVEGAGLTK EQKSVEVSDP VPAGDAVKVR VDLFPTDIGL
     HKLVVNFQCD KLKSVKGYRN IIIGPA
//