ID   TGM2_CHICK              Reviewed;         689 AA.
AC   Q01841;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 3.
DT   24-JAN-2024, entry version 142.
DE   RecName: Full=Protein-glutamine gamma-glutamyltransferase 2 {ECO:0000305};
DE            EC=2.3.2.13 {ECO:0000250|UniProtKB:P21980};
DE   AltName: Full=Erythrocyte transglutaminase {ECO:0000303|PubMed:1357669};
DE   AltName: Full=Isopeptidase TGM2 {ECO:0000305};
DE            EC=3.4.-.- {ECO:0000250|UniProtKB:P21980};
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:0000250|UniProtKB:P21980};
DE   AltName: Full=Transglutaminase-2 {ECO:0000250|UniProtKB:P21980};
DE            Short=TGase-2 {ECO:0000250|UniProtKB:P21980};
GN   Name=TGM2 {ECO:0000250|UniProtKB:P21980};
OS   Gallus gallus (Chicken).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC   Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC   Phasianinae; Gallus.
OX   NCBI_TaxID=9031;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 9-22; 181-191; 242-262;
RP   383-401; 406-416; 430-448 AND 457-483.
RC   TISSUE=Erythrocyte;
RX   PubMed=1357669; DOI=10.1073/pnas.89.20.9804;
RA   Weraarchakul-Boonmark N., Jeong J.M., Murthy S.N.P., Engel J.D., Lorand L.;
RT   "Cloning and expression of chicken erythrocyte transglutaminase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:9804-9808(1992).
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. Involved in many biological processes, such as
CC       bone development, angiogenesis, wound healing, cellular
CC       differentiation, chromatin modification and apoptosis. Acts as a
CC       protein-glutamine gamma-glutamyltransferase by mediating the cross-
CC       linking of proteins: 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. When secreted, catalyzes cross-linking
CC       of proteins of the extracellular matrix, resulting in the formation of
CC       scaffolds. Plays a key role during apoptosis, both by (1) promoting the
CC       cross-linking of cytoskeletal proteins resulting in condensation of the
CC       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. In addition to protein cross-linking, can use
CC       different monoamine substrates to catalyze a vast array of protein
CC       post-translational modifications: mediates aminylation of serotonin,
CC       dopamine, noradrenaline or histamine into glutamine residues of target
CC       proteins to generate protein serotonylation, dopaminylation,
CC       noradrenalinylation or histaminylation, respectively (By similarity).
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. Catalyzes
CC       serotonylation of 'Gln-5' of histone H3 (H3Q5ser) during serotonergic
CC       neuron differentiation, thereby facilitating transcription. 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 (By similarity). Also
CC       acts as a protein deamidase by mediating the side chain deamidation of
CC       specific glutamine residues of proteins to glutamate. May also act as
CC       an isopeptidase cleaving the previously formed cross-links. Also able
CC       to participate in signaling pathways independently of its
CC       acyltransferase activity: acts as a signal transducer in alpha-1
CC       adrenergic receptor-mediated stimulation of phospholipase C-delta
CC       (PLCD) activity and is required for coupling alpha-1 adrenergic
CC       agonists to the stimulation of phosphoinositide lipid metabolism (By
CC       similarity). {ECO:0000250|UniProtKB:P08587,
CC       ECO:0000250|UniProtKB:P21980}.
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;
CC         Evidence={ECO:0000250|UniProtKB:P21980, ECO:0000255|PROSITE-
CC         ProRule:PRU10024};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54817;
CC         Evidence={ECO:0000250|UniProtKB:P21980};
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. In contrast, Ca(2+) acts as a cofactor by inducing
CC       conformational change to the active open form. In absence of Ca(2+),
CC       Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and
CC       subsequent inhibition of the acyltransferase activity.
CC       {ECO:0000250|UniProtKB:P21980}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P21980}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P21980}. Nucleus {ECO:0000250|UniProtKB:P21980}.
CC       Chromosome {ECO:0000250|UniProtKB:P21980}. Secreted, extracellular
CC       space, extracellular matrix {ECO:0000250|UniProtKB:P21980}. Cell
CC       membrane {ECO:0000250|UniProtKB:Q9WVJ6}. Mitochondrion
CC       {ECO:0000250|UniProtKB:P21980}. 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   -!- TISSUE SPECIFICITY: Predominates in mature erythrocytes. Also found in
CC       kidney and cardiac muscle. {ECO:0000269|PubMed:1357669}.
CC   -!- SIMILARITY: Belongs to the transglutaminase superfamily.
CC       Transglutaminase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA49104.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; L02270; AAA49104.1; ALT_INIT; mRNA.
DR   PIR; A47203; A47203.
DR   RefSeq; NP_990779.1; NM_205448.1.
DR   AlphaFoldDB; Q01841; -.
DR   SMR; Q01841; -.
DR   STRING; 9031.ENSGALP00000038435; -.
DR   PaxDb; 9031-ENSGALP00000038435; -.
DR   KEGG; gga:396432; -.
DR   VEuPathDB; HostDB:geneid_396432; -.
DR   eggNOG; ENOG502QUSX; Eukaryota.
DR   InParanoid; Q01841; -.
DR   PhylomeDB; Q01841; -.
DR   PRO; PR:Q01841; -.
DR   Proteomes; UP000000539; Unassembled WGS sequence.
DR   GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR   GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR   GO; GO:0120297; F:histone dopaminyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0120295; F:histone serotonyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0120299; F:peptide histaminyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0120298; F:peptide noradrenalinyltransferase activity; IEA:RHEA.
DR   GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; IBA:GO_Central.
DR   GO; GO:0050568; F:protein-glutamine glutaminase activity; ISS:UniProtKB.
DR   GO; GO:0060348; P:bone development; ISS:UniProtKB.
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:0018149; P:peptide cross-linking; ISS:UniProtKB.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR   GO; GO:0051057; P:positive regulation of small GTPase mediated signal transduction; ISS:UniProtKB.
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   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   Acyltransferase; Calcium; Cell membrane; Chromosome; Cytoplasm;
KW   Direct protein sequencing; Extracellular matrix; GTP-binding; Hydrolase;
KW   Membrane; Metal-binding; Mitochondrion; Nucleotide-binding; Nucleus;
KW   Protease; Reference proteome; Secreted; Transferase.
FT   CHAIN           1..689
FT                   /note="Protein-glutamine gamma-glutamyltransferase 2"
FT                   /id="PRO_0000213709"
FT   REGION          427..453
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        430..453
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        278
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10024"
FT   ACT_SITE        336
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10024"
FT   ACT_SITE        359
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10024"
FT   BINDING         399
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P00488"
FT   BINDING         401
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         539
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000250|UniProtKB:P21980"
FT   BINDING         580..583
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"
SQ   SEQUENCE   689 AA;  77970 MW;  ACA3FA84B48A5AB3 CRC64;
     MAEELVLETC DLQCERNGRE HRTEEMGSQQ LVVRRGQPFT ITLNFAGRGY EEGVDKLAFD
     VETGPCPVET SGTRSHFTLT DCPEEGTWSA VLQQQDGATL CVSLCSPSIA RVGRYRLTLE
     ASTGYQGSSF HLGDFVLLFN AWHPEDAVYL KEEDERREYV LSQQGLIYMG SRDYITSTPW
     NFGQFEDEIL AICLEMLDIN PKFLRDQNLD CSRRNDPVYI GRVVSAMVNC NDEDHGVLLG
     RWDNHYEDGM SPMAWIGSVD ILKRWRRLGC QPVKYGQCWV FAAVACTVMR CLGVPSRVVT
     NYNSAHDTNG NLVIDRYLSE TGMEERRSTD MIWNFHCWVE CWMTRPDLAP GYDGWQALDP
     TPQEKSEGVY CCGPAPVKAI KEGDLQVQYD IPFVFAEVNA DVVYWIVQSD GEKKKSTHSS
     VVGKNISTKS VGRDSREDIT HTYKYPEGSE KEREVFSKAE HEKSSLGEQE EGLHMRIKLS
     EGANNGSDFD VFAFISNDTD KERECRLRLC ARTASYNGEV GPQCGFKDLL NLSLQPHMEQ
     SVPLRILYEQ YGPNLTQDNM IKVVALLTEY ETGDSVVAIR DVYIQNPEIK IRILGEPMQE
     RKLVAEIRLV NPLAEPLNNC IFVVEGAGLT EGQRIEELED PVEPQAEAKF RMEFVPRQAG
     LHKLMVDFES DKLTGVKGYR NVIIAPLPK
//