| IED ID | IndEnz0002012474 |
| Enzyme Type ID | protease012474 |
| Protein Name |
Protein-glutamine gamma-glutamyltransferase 2 EC 2.3.2.13 Fish-derived transglutaminase FTG Isopeptidase TGM2 EC 3.4.-.- Protein-glutamine deamidase TGM2 EC 3.5.1.44 Protein-glutamine dopaminyltransferase TGM2 EC 2.3.1.- Protein-glutamine histaminyltransferase TGM2 EC 2.3.1.- Protein-glutamine noradrenalinyltransferase TGM2 EC 2.3.1.- Protein-glutamine serotonyltransferase TGM2 EC 2.3.1.- Tissue transglutaminase Tissue-type transglutaminase Transglutaminase-2 TGase-2 |
| Gene Name | tgm2 |
| Organism | Pagrus major (Red sea bream) (Chrysophrys major) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Actinopterygii Actinopteri Neopterygii Teleostei Osteoglossocephalai Clupeocephala Euteleosteomorpha Neoteleostei Eurypterygia Ctenosquamata Acanthomorphata Euacanthomorphacea Percomorphaceae Eupercaria Spariformes (porgies and others) Sparidae (porgies) Pagrus Pagrus major (Red sea bream) (Chrysophrys major) |
| Enzyme Sequence | MASYKGLIVDVNGRSHENNLAHRTREIDRERLIVRRGQPFSITLQCSDSLPPKHHLELVLHLGKRDEVVIKVQKEHGARDKWWFNQQGAQDEILLTLHSPANAVIGHYRLAVLVMSPDGHIVERADKISFHMLFNPWCRDDMVYLPDESKLQEYVMNEDGVIYMGTWDYIRSIPWNYGQFEDYVMDICFEVLDNSPAALKNSEMDIEHRSDPVYVGRTITAMVNSNGDRGVLTGRWEEPYTDGVAPYRWTGSVPILQQWSKAGVRPVKYGQCWVFAAVACTVLRCLGIPTRPITNFASAHDVDGNLSVDFLLNERLESLDSRQRSDSSWNFHCWVESWMSREDLPEGNDGWQVLDPTPQELSDGEFCCGPCPVAAIKEGNLGVKYDAPFVFAEVNADTIYWIVQKDGQRRKITEDHASVGKNISTKSVYGNHREDVTLHYKYPEGSQKEREVYKKAGRRVTEPSNEIAEQGRLQLSIKHAQPVFGTDFDVIVEVKNEGGRDAHAQLTMLAMAVTYNSLRRGECQRKTISVTVPAHKAHKEVMRLHYDDYVRCVSEHHLIRVKALLDAPGENGPIMTVANIPLSTPELLVQVPGKAVVWEPLTAYVSFTNPLPVPLKGGVFTLEGAGLLSATQIHVNGAVAPSGKVSVKLSFSPMRTGVRKLLVDFDSDRLKDVKGVTTVVVHKKYRSLITGLHTD |
| Enzyme Length | 695 |
| Uniprot Accession Number | P52181 |
| Absorption | |
| Active Site | ACT_SITE 272; /evidence="ECO:0000255|PROSITE-ProRule:PRU10024, ECO:0000305|PubMed:11080504, ECO:0007744|PDB:1G0D"; ACT_SITE 332; /evidence="ECO:0000255|PROSITE-ProRule:PRU10024, ECO:0000305|PubMed:11080504, ECO:0007744|PDB:1G0D"; ACT_SITE 355; /evidence="ECO:0000255|PROSITE-ProRule:PRU10024, ECO:0000305|PubMed:11080504, ECO:0007744|PDB:1G0D" |
| Activity Regulation | ACTIVITY REGULATION: Acyltransferase activity is regulated by the binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its closed structure, thereby obstructing the accessibility of substrates to the active sites. In contrast, Ca(2+) acts as a cofactor by inducing conformational change to the active open form. In absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and subsequent inhibition of the acyltransferase activity. {ECO:0000250|UniProtKB:P21980}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L-lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:54816, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:14005, ChEBI:CHEBI:28938, ChEBI:CHEBI:29969, ChEBI:CHEBI:30011, ChEBI:CHEBI:138370; EC=2.3.2.13; Evidence={ECO:0000250|UniProtKB:P21980, ECO:0000255|PROSITE-ProRule:PRU10024};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54817; Evidence={ECO:0000250|UniProtKB:P21980}; CATALYTIC ACTIVITY: Reaction=L-glutaminyl-[protein] + serotonin = 5-serotonyl-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:66552, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:17052, ChEBI:CHEBI:28938, ChEBI:CHEBI:30011, ChEBI:CHEBI:167174, ChEBI:CHEBI:350546; Evidence={ECO:0000250|UniProtKB:P21980};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66553; Evidence={ECO:0000250|UniProtKB:P21980}; CATALYTIC ACTIVITY: Reaction=dopamine + L-glutaminyl-[protein] = 5-dopaminyl-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:66556, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:17053, ChEBI:CHEBI:28938, ChEBI:CHEBI:30011, ChEBI:CHEBI:59905, ChEBI:CHEBI:167175; Evidence={ECO:0000250|UniProtKB:P21980};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66557; Evidence={ECO:0000250|UniProtKB:P21980}; CATALYTIC ACTIVITY: Reaction=histamine + L-glutaminyl-[protein] = 5-histaminyl-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:66564, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:17056, ChEBI:CHEBI:28938, ChEBI:CHEBI:30011, ChEBI:CHEBI:58432, ChEBI:CHEBI:167179; Evidence={ECO:0000250|UniProtKB:P21980};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66565; Evidence={ECO:0000250|UniProtKB:P21980}; CATALYTIC ACTIVITY: Reaction=(R)-noradrenaline + L-glutaminyl-[protein] = 5-(R)-noradrenalinyl-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:66560, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:17054, ChEBI:CHEBI:28938, ChEBI:CHEBI:30011, ChEBI:CHEBI:72587, ChEBI:CHEBI:167178; Evidence={ECO:0000250|UniProtKB:P08587};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66561; Evidence={ECO:0000250|UniProtKB:P08587}; CATALYTIC ACTIVITY: Reaction=H2O + L-glutaminyl-[protein] = L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:16441, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:10208, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29973, ChEBI:CHEBI:30011; EC=3.5.1.44; Evidence={ECO:0000250|UniProtKB:P21980};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16442; Evidence={ECO:0000250|UniProtKB:P21980}; |
| DNA Binding | |
| EC Number | 2.3.2.13; 3.4.-.-; 3.5.1.44; 2.3.1.- |
| Enzyme Function | FUNCTION: Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono- and polyamines, thereby producing cross-linked or aminated proteins, respectively. Involved in many biological processes, such as bone development, angiogenesis, wound healing, cellular differentiation, chromatin modification and apoptosis. Acts as a protein-glutamine gamma-glutamyltransferase by mediating the cross-linking of proteins: under physiological conditions, the protein cross-linking activity is inhibited by GTP; inhibition is relieved by Ca(2+) in response to various stresses. When secreted, catalyzes cross-linking of proteins of the extracellular matrix, resulting in the formation of scaffolds. Plays a key role during apoptosis, both by (1) promoting the cross-linking of cytoskeletal proteins resulting in condensation of the cytoplasm, and by (2) mediating cross-linking proteins of the extracellular matrix, resulting in the irreversible formation of scaffolds that stabilize the integrity of the dying cells before their clearance by phagocytosis, thereby preventing the leakage of harmful intracellular components. In addition to protein cross-linking, can use different monoamine substrates to catalyze a vast array of protein post-translational modifications: mediates aminylation of serotonin, dopamine, noradrenaline or histamine into glutamine residues of target proteins to generate protein serotonylation, dopaminylation, noradrenalinylation or histaminylation, respectively (By similarity). Mediates protein serotonylation of small GTPases during activation and aggregation of platelets, leading to constitutive activation of these GTPases (By similarity). Plays a key role in chromatin organization by mediating serotonylation and dopaminylation of histone H3. Catalyzes serotonylation of 'Gln-5' of histone H3 (H3Q5ser) during serotonergic neuron differentiation, thereby facilitating transcription. Acts as a mediator of neurotransmission-independent role of nuclear dopamine in ventral tegmental area (VTA) neurons: catalyzes dopaminylation of 'Gln-5' of histone H3 (H3Q5dop), thereby regulating relapse-related transcriptional plasticity in the reward system. Also acts as a protein deamidase by mediating the side chain deamidation of specific glutamine residues of proteins to glutamate. May also act as an isopeptidase cleaving the previously formed cross-links. Also able to participate in signaling pathways independently of its acyltransferase activity: acts as a signal transducer in alpha-1 adrenergic receptor-mediated stimulation of phospholipase C-delta (PLCD) activity and is required for coupling alpha-1 adrenergic agonists to the stimulation of phosphoinositide lipid metabolism (By similarity). {ECO:0000250|UniProtKB:P08587, ECO:0000250|UniProtKB:P21980}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 476..482; /note=GTP; /evidence=ECO:0000250|UniProtKB:P21980; NP_BIND 578..581; /note=GTP; /evidence=ECO:0000250|UniProtKB:P21980 |
| Features | Active site (3); Beta strand (46); Chain (1); Helix (14); Metal binding (5); Nucleotide binding (2); Site (1); Turn (7) |
| Keywords | 3D-structure;Acyltransferase;Calcium;Cell membrane;Chromosome;Cytoplasm;Direct protein sequencing;Extracellular matrix;GTP-binding;Hydrolase;Membrane;Metal-binding;Mitochondrion;Nucleotide-binding;Nucleus;Protease;Secreted;Transferase |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P21980}. Nucleus {ECO:0000250|UniProtKB:P21980}. Chromosome {ECO:0000250|UniProtKB:P21980}. Secreted, extracellular space, extracellular matrix {ECO:0000250|UniProtKB:P21980}. Cell membrane {ECO:0000250|UniProtKB:Q9WVJ6}. Mitochondrion {ECO:0000250|UniProtKB:P21980}. Note=Mainly localizes to the cytosol. Present at much lower level in the nucleus and chromatin. Also secreted via a non-classical secretion pathway to the extracellular matrix. {ECO:0000250|UniProtKB:P21980}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 1G0D; |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 78,216 |
| Kinetics | |
| Metal Binding | METAL 395; /note=Calcium; /evidence=ECO:0000250|UniProtKB:P00488; METAL 397; /note=Calcium; /evidence=ECO:0000250|UniProtKB:P00488; METAL 434; /note=Calcium; /evidence=ECO:0000250|UniProtKB:P21980; METAL 444; /note=Calcium; /evidence=ECO:0000250|UniProtKB:P00488; METAL 449; /note=Calcium; /evidence=ECO:0000250|UniProtKB:P00488 |
| Rhea ID | RHEA:54816; RHEA:54817; RHEA:66552; RHEA:66553; RHEA:66556; RHEA:66557; RHEA:66564; RHEA:66565; RHEA:66560; RHEA:66561; RHEA:16441; RHEA:16442 |
| Cross Reference Brenda |