TGM2_RAT
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 03-AUG-2022, entry version 145.
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 iPTMnet; Q6P6R6; -.
DR PhosphoSitePlus; Q9WVJ6; -.
DR PaxDb; Q9WVJ6; -.
DR PRIDE; Q9WVJ6; -.
DR Ensembl; ENSRNOT00000018328; ENSRNOP00000018328; ENSRNOG00000012956.
DR GeneID; 56083; -.
DR KEGG; rno:56083; -.
DR UCSC; RGD:621081; rat.
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 OMA; IKSVPWN; -.
DR OrthoDB; 297055at2759; -.
DR PhylomeDB; Q9WVJ6; -.
DR TreeFam; TF324278; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Proteomes; UP000234681; Chromosome 3.
DR Bgee; ENSRNOG00000012956; Expressed in lung and 19 other 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:0031226; C:intrinsic component of plasma membrane; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA: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: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:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0018153; P:isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine; IDA:RGD.
DR GO; GO:0032471; P:negative regulation of endoplasmic reticulum calcium ion concentration; ISO:RGD.
DR GO; GO:0018149; P:peptide cross-linking; 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:0045785; P:positive regulation of cell adhesion; ISO:RGD.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; IMP:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:RGD.
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; -; 3.
DR Gene3D; 3.90.260.10; -; 1.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR002931; Transglutaminase-like.
DR InterPro; IPR036985; Transglutaminase-like_sf.
DR InterPro; IPR023608; Transglutaminase_animal.
DR InterPro; IPR013808; Transglutaminase_AS.
DR InterPro; IPR008958; Transglutaminase_C.
DR InterPro; IPR036238; Transglutaminase_C_sf.
DR InterPro; IPR001102; Transglutaminase_N.
DR Pfam; PF00927; Transglut_C; 2.
DR Pfam; PF01841; Transglut_core; 1.
DR Pfam; PF00868; Transglut_N; 1.
DR PIRSF; PIRSF000459; TGM_EBP42; 1.
DR SMART; SM00460; TGc; 1.
DR SUPFAM; SSF49309; SSF49309; 2.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS00547; TRANSGLUTAMINASES; 1.
PE 1: Evidence at protein level;
KW Acetylation; Acyltransferase; Calcium; Cell membrane; Chromosome;
KW Cytoplasm; Direct protein sequencing; Disulfide bond; Extracellular matrix;
KW GTP-binding; Hydrolase; Isopeptide bond; Membrane; Metal-binding;
KW Mitochondrion; Nucleotide-binding; Nucleus; 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 gamma-
FT glutamyltransferase activity without affecting alpha-1
FT 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
