TGM2_CHICK
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 03-AUG-2022, entry version 137.
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; Q01841; -.
DR GeneID; 396432; -.
DR KEGG; gga:396432; -.
DR CTD; 7052; -.
DR VEuPathDB; HostDB:geneid_396432; -.
DR eggNOG; ENOG502QUSX; Eukaryota.
DR InParanoid; Q01841; -.
DR OrthoDB; 297055at2759; -.
DR PhylomeDB; Q01841; -.
DR PRO; PR:Q01841; -.
DR Proteomes; UP000000539; Unplaced.
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; -; 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 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
