Full text data of TGM2
TGM2
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Protein-glutamine gamma-glutamyltransferase 2; 2.3.2.13 (Tissue transglutaminase; Transglutaminase C; TG(C); TGC; TGase C; Transglutaminase H; TGase H; Transglutaminase-2; TGase-2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Protein-glutamine gamma-glutamyltransferase 2; 2.3.2.13 (Tissue transglutaminase; Transglutaminase C; TG(C); TGC; TGase C; Transglutaminase H; TGase H; Transglutaminase-2; TGase-2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00294578
IPI00294578 Splice Isoform 1 Of Protein-glutamine gamma-glutamyltransferase human erythroleukemia cells, Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic YLLNLNLEPFSEK, ALLVEPVINSYLLAER, DLYLENPEIK found at its expected molecular weight found at molecular weight
IPI00294578 Splice Isoform 1 Of Protein-glutamine gamma-glutamyltransferase human erythroleukemia cells, Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic YLLNLNLEPFSEK, ALLVEPVINSYLLAER, DLYLENPEIK found at its expected molecular weight found at molecular weight
UniProt
P21980
ID TGM2_HUMAN Reviewed; 687 AA.
AC P21980; E1P5V9; Q16436; Q6B838; Q9BTN7; Q9UH35;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2002, sequence version 2.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Protein-glutamine gamma-glutamyltransferase 2;
DE EC=2.3.2.13;
DE AltName: Full=Tissue transglutaminase;
DE AltName: Full=Transglutaminase C;
DE Short=TG(C);
DE Short=TGC;
DE Short=TGase C;
DE AltName: Full=Transglutaminase H;
DE Short=TGase H;
DE AltName: Full=Transglutaminase-2;
DE Short=TGase-2;
GN Name=TGM2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Endothelial cell;
RX PubMed=1670766;
RA Gentile V., Saydak M., Chiocca E.A., Akande O., Birckbichler P.J.,
RA Lee K.N., Stein J.P., Davies P.J.A.;
RT "Isolation and characterization of cDNA clones to mouse macrophage and
RT human endothelial cell tissue transglutaminases.";
RL J. Biol. Chem. 266:478-483(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1358880;
RA Fraij B.M., Birckbichler P.J., Patterson M.K. Jr., Lee K.N.,
RA Gonzales R.A.;
RT "A retinoic acid-inducible mRNA from human erythroleukemia cells
RT encodes a novel tissue transglutaminase homologue.";
RL J. Biol. Chem. 267:22616-22623(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=8611626; DOI=10.1016/0167-4781(95)00219-7;
RA Fraij B.M., Gonzales R.A.;
RT "A third human tissue transglutaminase homologue as a result of
RT alternative gene transcripts.";
RL Biochim. Biophys. Acta 1306:63-74(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Colon adenocarcinoma;
RA Bayardo M.P., de Urraza P., Chirdo F.G.;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-76; HIS-214;
RP ARG-324; TRP-436 AND SER-536.
RG NIEHS SNPs program;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-9; 365-377; 565-590; 635-649 AND 664-674,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=18092889; DOI=10.1371/journal.pbio.0050327;
RA Pinkas D.M., Strop P., Brunger A.T., Khosla C.;
RT "Transglutaminase 2 undergoes a large conformational change upon
RT activation.";
RL PLoS Biol. 5:E327-E327(2007).
RN [14]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-660.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [15]
RP VARIANTS ARG-330 AND ASN-331.
RX PubMed=17939176; DOI=10.1002/humu.9511;
RA Porzio O., Massa O., Cunsolo V., Colombo C., Malaponti M.,
RA Bertuzzi F., Hansen T., Johansen A., Pedersen O., Meschi F.,
RA Terrinoni A., Melino G., Federici M., Decarlo N., Menicagli M.,
RA Campani D., Marchetti P., Ferdaoussi M., Froguel P., Federici G.,
RA Vaxillaire M., Barbetti F.;
RT "Missense mutations in the TGM2 gene encoding transglutaminase 2 are
RT found in patients with early-onset type 2 diabetes.";
RL Hum. Mutat. 28:1150-1150(2007).
CC -!- FUNCTION: Catalyzes the cross-linking of proteins and the
CC conjugation of polyamines to proteins.
CC -!- CATALYTIC ACTIVITY: Protein glutamine + alkylamine = protein N(5)-
CC alkylglutamine + NH(3).
CC -!- COFACTOR: Binds 1 calcium ion per subunit (By similarity).
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC Q12802:AKAP13; NbExp=4; IntAct=EBI-727668, EBI-1373806;
CC P39060:COL18A1; NbExp=2; IntAct=EBI-727668, EBI-2566375;
CC P02751:FN1; NbExp=3; IntAct=EBI-727668, EBI-1220319;
CC Q04206:RELA; NbExp=3; IntAct=EBI-727668, EBI-73886;
CC P40337:VHL; NbExp=10; IntAct=EBI-727668, EBI-301246;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P21980-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P21980-2; Sequence=VSP_006411, VSP_006412;
CC Name=3; Synonyms=TGH2;
CC IsoId=P21980-3; Sequence=VSP_006413, VSP_006414;
CC -!- INDUCTION: By retinoic acid.
CC -!- SIMILARITY: Belongs to the transglutaminase superfamily.
CC Transglutaminase family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tissue transglutaminase entry;
CC URL="http://en.wikipedia.org/wiki/Tissue_transglutaminase";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tgm2/";
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DR EMBL; M55153; AAA63261.1; -; mRNA.
DR EMBL; M98478; AAA36739.1; -; mRNA.
DR EMBL; S81734; AAB36379.1; -; mRNA.
DR EMBL; AY675221; AAT79353.1; -; mRNA.
DR EMBL; AK291714; BAF84403.1; -; mRNA.
DR EMBL; AK314618; BAG37184.1; -; mRNA.
DR EMBL; DQ523828; ABF47109.1; -; Genomic_DNA.
DR EMBL; AL031651; CAB66115.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76040.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76042.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76044.1; -; Genomic_DNA.
DR EMBL; BC003551; AAH03551.1; -; mRNA.
DR PIR; A39045; A39045.
DR PIR; A44302; A44302.
DR PIR; S68092; S68092.
DR RefSeq; NP_004604.2; NM_004613.2.
DR RefSeq; NP_945189.1; NM_198951.1.
DR RefSeq; XP_005260595.1; XM_005260538.1.
DR UniGene; Hs.517033; -.
DR PDB; 1FAU; Model; -; A=1-687.
DR PDB; 1KV3; X-ray; 2.80 A; A/B/C/D/E/F=1-687.
DR PDB; 2Q3Z; X-ray; 2.00 A; A=1-687.
DR PDB; 3LY6; X-ray; 3.14 A; A/B/C=1-687.
DR PDB; 3S3J; X-ray; 2.25 A; A=2-687.
DR PDB; 3S3P; X-ray; 2.50 A; A=2-687.
DR PDB; 3S3S; X-ray; 2.30 A; A=2-687.
DR PDBsum; 1FAU; -.
DR PDBsum; 1KV3; -.
DR PDBsum; 2Q3Z; -.
DR PDBsum; 3LY6; -.
DR PDBsum; 3S3J; -.
DR PDBsum; 3S3P; -.
DR PDBsum; 3S3S; -.
DR ProteinModelPortal; P21980; -.
DR SMR; P21980; 4-687.
DR DIP; DIP-33557N; -.
DR IntAct; P21980; 40.
DR MINT; MINT-88880; -.
DR STRING; 9606.ENSP00000355330; -.
DR BindingDB; P21980; -.
DR ChEMBL; CHEMBL2730; -.
DR DrugBank; DB00130; L-Glutamine.
DR PhosphoSite; P21980; -.
DR DMDM; 20141877; -.
DR PaxDb; P21980; -.
DR PeptideAtlas; P21980; -.
DR PRIDE; P21980; -.
DR Ensembl; ENST00000361475; ENSP00000355330; ENSG00000198959.
DR GeneID; 7052; -.
DR KEGG; hsa:7052; -.
DR UCSC; uc002xhr.3; human.
DR CTD; 7052; -.
DR GeneCards; GC20M036756; -.
DR HGNC; HGNC:11778; TGM2.
DR HPA; CAB002598; -.
DR HPA; HPA021019; -.
DR HPA; HPA029518; -.
DR MIM; 190196; gene.
DR neXtProt; NX_P21980; -.
DR PharmGKB; PA36491; -.
DR eggNOG; NOG80379; -.
DR HOGENOM; HOG000231695; -.
DR HOVERGEN; HBG004342; -.
DR InParanoid; P21980; -.
DR KO; K05625; -.
DR OMA; ANGRDHH; -.
DR OrthoDB; EOG7WT40M; -.
DR PhylomeDB; P21980; -.
DR SignaLink; P21980; -.
DR ChiTaRS; TGM2; human.
DR EvolutionaryTrace; P21980; -.
DR GeneWiki; Tissue_transglutaminase; -.
DR GenomeRNAi; 7052; -.
DR NextBio; 27573; -.
DR PMAP-CutDB; P21980; -.
DR PRO; PR:P21980; -.
DR ArrayExpress; P21980; -.
DR Bgee; P21980; -.
DR CleanEx; HS_TGM2; -.
DR Genevestigator; P21980; -.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; ISS:UniProtKB.
DR GO; GO:0043277; P:apoptotic cell clearance; IDA:UniProtKB.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IEA:Ensembl.
DR GO; GO:0018153; P:isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine; IEA:Ensembl.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl.
DR GO; GO:0060662; P:salivary gland cavitation; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.90.260.10; -; 1.
DR InterPro; IPR023608; Gln_gamma-glutamylTfrase_euk.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002931; Transglutaminase-like.
DR InterPro; IPR008958; Transglutaminase_C.
DR InterPro; IPR013808; Transglutaminase_CS.
DR InterPro; IPR001102; Transglutaminase_N.
DR PANTHER; PTHR11590; PTHR11590; 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; SSF49309; SSF49309; 2.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS00547; TRANSGLUTAMINASES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Acyltransferase; Alternative splicing;
KW Calcium; Complete proteome; Direct protein sequencing; Metal-binding;
KW Polymorphism; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 687 Protein-glutamine gamma-
FT glutamyltransferase 2.
FT /FTId=PRO_0000213707.
FT ACT_SITE 277 277 By similarity.
FT ACT_SITE 335 335 By similarity.
FT ACT_SITE 358 358 By similarity.
FT METAL 398 398 Calcium (By similarity).
FT METAL 400 400 Calcium (By similarity).
FT METAL 447 447 Calcium (By similarity).
FT METAL 452 452 Calcium (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 287 349 VLRCLGIPTRVVTNYNSAHDQNSNLLIEYFRNEFGEIQGDK
FT SEMIWNFHCWVESWMTRPDLQP -> GELHAGMWVMSPGRG
FT HEEHWSRNQDIPALVLPPATNTLNALCGLEPVTTLSGPLSN
FT SHPSSGC (in isoform 3).
FT /FTId=VSP_006413.
FT VAR_SEQ 350 687 Missing (in isoform 3).
FT /FTId=VSP_006414.
FT VAR_SEQ 539 548 EKSVPLCILY -> GKALCSWSIC (in isoform 2).
FT /FTId=VSP_006411.
FT VAR_SEQ 549 687 Missing (in isoform 2).
FT /FTId=VSP_006412.
FT VARIANT 76 76 R -> H (in dbSNP:rs41274720).
FT /FTId=VAR_052553.
FT VARIANT 214 214 R -> H (in dbSNP:rs45530133).
FT /FTId=VAR_055357.
FT VARIANT 324 324 Q -> R (in dbSNP:rs45567334).
FT /FTId=VAR_055358.
FT VARIANT 330 330 M -> R (in patients with early-onset
FT diabetes type 2; pathological
FT significance unknown).
FT /FTId=VAR_037998.
FT VARIANT 331 331 I -> N (in patients with early-onset
FT diabetes type 2; pathological
FT significance unknown).
FT /FTId=VAR_037999.
FT VARIANT 436 436 R -> W (in dbSNP:rs45629036).
FT /FTId=VAR_055359.
FT VARIANT 536 536 P -> S (in dbSNP:rs45556333).
FT /FTId=VAR_052554.
FT VARIANT 660 660 G -> V (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036554.
FT CONFLICT 51 51 E -> Q (in Ref. 1; AAA63261).
FT CONFLICT 186 186 E -> Q (in Ref. 1; AAA63261).
FT CONFLICT 224 224 V -> G (in Ref. 1; AAA63261).
FT CONFLICT 533 533 N -> T (in Ref. 1; AAA63261).
FT CONFLICT 655 655 L -> V (in Ref. 1; AAA63261).
FT STRAND 7 11
FT HELIX 14 20
FT HELIX 24 26
FT STRAND 28 30
FT STRAND 32 34
FT STRAND 39 48
FT TURN 52 54
FT STRAND 55 66
FT TURN 69 72
FT STRAND 73 79
FT STRAND 89 95
FT STRAND 97 105
FT STRAND 113 123
FT STRAND 126 138
FT HELIX 153 159
FT STRAND 164 170
FT STRAND 172 181
FT HELIX 189 198
FT HELIX 201 205
FT HELIX 207 213
FT HELIX 217 226
FT TURN 227 229
FT TURN 231 234
FT STRAND 235 239
FT TURN 251 253
FT HELIX 258 266
FT TURN 267 269
FT STRAND 272 275
FT HELIX 277 291
FT STRAND 295 304
FT STRAND 306 309
FT HELIX 311 317
FT STRAND 332 342
FT STRAND 347 350
FT STRAND 353 357
FT STRAND 365 369
FT HELIX 376 380
FT TURN 387 389
FT HELIX 390 397
FT STRAND 400 404
FT STRAND 412 414
FT STRAND 419 429
FT STRAND 433 438
FT HELIX 440 443
FT STRAND 447 449
FT HELIX 450 460
FT TURN 468 471
FT STRAND 473 478
FT STRAND 489 497
FT STRAND 499 501
FT STRAND 503 514
FT STRAND 520 534
FT STRAND 538 546
FT HELIX 548 551
FT TURN 552 554
FT STRAND 560 569
FT TURN 570 573
FT STRAND 574 583
FT STRAND 590 595
FT STRAND 598 601
FT STRAND 603 610
FT STRAND 613 615
FT STRAND 619 625
FT TURN 627 629
FT STRAND 634 638
FT STRAND 647 654
FT STRAND 658 660
FT STRAND 662 669
FT STRAND 671 673
FT STRAND 676 682
SQ SEQUENCE 687 AA; 77329 MW; 7DA33FF335DE7B37 CRC64;
MAEELVLERC DLELETNGRD HHTADLCREK LVVRRGQPFW LTLHFEGRNY EASVDSLTFS
VVTGPAPSQE AGTKARFPLR DAVEEGDWTA TVVDQQDCTL SLQLTTPANA PIGLYRLSLE
ASTGYQGSSF VLGHFILLFN AWCPADAVYL DSEEERQEYV LTQQGFIYQG SAKFIKNIPW
NFGQFEDGIL DICLILLDVN PKFLKNAGRD CSRRSSPVYV GRVVSGMVNC NDDQGVLLGR
WDNNYGDGVS PMSWIGSVDI LRRWKNHGCQ RVKYGQCWVF AAVACTVLRC LGIPTRVVTN
YNSAHDQNSN LLIEYFRNEF GEIQGDKSEM IWNFHCWVES WMTRPDLQPG YEGWQALDPT
PQEKSEGTYC CGPVPVRAIK EGDLSTKYDA PFVFAEVNAD VVDWIQQDDG SVHKSINRSL
IVGLKISTKS VGRDEREDIT HTYKYPEGSS EEREAFTRAN HLNKLAEKEE TGMAMRIRVG
QSMNMGSDFD VFAHITNNTA EEYVCRLLLC ARTVSYNGIL GPECGTKYLL NLNLEPFSEK
SVPLCILYEK YRDCLTESNL IKVRALLVEP VINSYLLAER DLYLENPEIK IRILGEPKQK
RKLVAEVSLQ NPLPVALEGC TFTVEGAGLT EEQKTVEIPD PVEAGEEVKV RMDLLPLHMG
LHKLVVNFES DKLKAVKGFR NVIIGPA
//
ID TGM2_HUMAN Reviewed; 687 AA.
AC P21980; E1P5V9; Q16436; Q6B838; Q9BTN7; Q9UH35;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2002, sequence version 2.
DT 22-JAN-2014, entry version 158.
DE RecName: Full=Protein-glutamine gamma-glutamyltransferase 2;
DE EC=2.3.2.13;
DE AltName: Full=Tissue transglutaminase;
DE AltName: Full=Transglutaminase C;
DE Short=TG(C);
DE Short=TGC;
DE Short=TGase C;
DE AltName: Full=Transglutaminase H;
DE Short=TGase H;
DE AltName: Full=Transglutaminase-2;
DE Short=TGase-2;
GN Name=TGM2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Endothelial cell;
RX PubMed=1670766;
RA Gentile V., Saydak M., Chiocca E.A., Akande O., Birckbichler P.J.,
RA Lee K.N., Stein J.P., Davies P.J.A.;
RT "Isolation and characterization of cDNA clones to mouse macrophage and
RT human endothelial cell tissue transglutaminases.";
RL J. Biol. Chem. 266:478-483(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1358880;
RA Fraij B.M., Birckbichler P.J., Patterson M.K. Jr., Lee K.N.,
RA Gonzales R.A.;
RT "A retinoic acid-inducible mRNA from human erythroleukemia cells
RT encodes a novel tissue transglutaminase homologue.";
RL J. Biol. Chem. 267:22616-22623(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=8611626; DOI=10.1016/0167-4781(95)00219-7;
RA Fraij B.M., Gonzales R.A.;
RT "A third human tissue transglutaminase homologue as a result of
RT alternative gene transcripts.";
RL Biochim. Biophys. Acta 1306:63-74(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Colon adenocarcinoma;
RA Bayardo M.P., de Urraza P., Chirdo F.G.;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-76; HIS-214;
RP ARG-324; TRP-436 AND SER-536.
RG NIEHS SNPs program;
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PROTEIN SEQUENCE OF 2-9; 365-377; 565-590; 635-649 AND 664-674,
RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS
RP SPECTROMETRY.
RC TISSUE=Ovarian carcinoma;
RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=18092889; DOI=10.1371/journal.pbio.0050327;
RA Pinkas D.M., Strop P., Brunger A.T., Khosla C.;
RT "Transglutaminase 2 undergoes a large conformational change upon
RT activation.";
RL PLoS Biol. 5:E327-E327(2007).
RN [14]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-660.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [15]
RP VARIANTS ARG-330 AND ASN-331.
RX PubMed=17939176; DOI=10.1002/humu.9511;
RA Porzio O., Massa O., Cunsolo V., Colombo C., Malaponti M.,
RA Bertuzzi F., Hansen T., Johansen A., Pedersen O., Meschi F.,
RA Terrinoni A., Melino G., Federici M., Decarlo N., Menicagli M.,
RA Campani D., Marchetti P., Ferdaoussi M., Froguel P., Federici G.,
RA Vaxillaire M., Barbetti F.;
RT "Missense mutations in the TGM2 gene encoding transglutaminase 2 are
RT found in patients with early-onset type 2 diabetes.";
RL Hum. Mutat. 28:1150-1150(2007).
CC -!- FUNCTION: Catalyzes the cross-linking of proteins and the
CC conjugation of polyamines to proteins.
CC -!- CATALYTIC ACTIVITY: Protein glutamine + alkylamine = protein N(5)-
CC alkylglutamine + NH(3).
CC -!- COFACTOR: Binds 1 calcium ion per subunit (By similarity).
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC Q12802:AKAP13; NbExp=4; IntAct=EBI-727668, EBI-1373806;
CC P39060:COL18A1; NbExp=2; IntAct=EBI-727668, EBI-2566375;
CC P02751:FN1; NbExp=3; IntAct=EBI-727668, EBI-1220319;
CC Q04206:RELA; NbExp=3; IntAct=EBI-727668, EBI-73886;
CC P40337:VHL; NbExp=10; IntAct=EBI-727668, EBI-301246;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P21980-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P21980-2; Sequence=VSP_006411, VSP_006412;
CC Name=3; Synonyms=TGH2;
CC IsoId=P21980-3; Sequence=VSP_006413, VSP_006414;
CC -!- INDUCTION: By retinoic acid.
CC -!- SIMILARITY: Belongs to the transglutaminase superfamily.
CC Transglutaminase family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tissue transglutaminase entry;
CC URL="http://en.wikipedia.org/wiki/Tissue_transglutaminase";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tgm2/";
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DR EMBL; M55153; AAA63261.1; -; mRNA.
DR EMBL; M98478; AAA36739.1; -; mRNA.
DR EMBL; S81734; AAB36379.1; -; mRNA.
DR EMBL; AY675221; AAT79353.1; -; mRNA.
DR EMBL; AK291714; BAF84403.1; -; mRNA.
DR EMBL; AK314618; BAG37184.1; -; mRNA.
DR EMBL; DQ523828; ABF47109.1; -; Genomic_DNA.
DR EMBL; AL031651; CAB66115.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76040.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76042.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76044.1; -; Genomic_DNA.
DR EMBL; BC003551; AAH03551.1; -; mRNA.
DR PIR; A39045; A39045.
DR PIR; A44302; A44302.
DR PIR; S68092; S68092.
DR RefSeq; NP_004604.2; NM_004613.2.
DR RefSeq; NP_945189.1; NM_198951.1.
DR RefSeq; XP_005260595.1; XM_005260538.1.
DR UniGene; Hs.517033; -.
DR PDB; 1FAU; Model; -; A=1-687.
DR PDB; 1KV3; X-ray; 2.80 A; A/B/C/D/E/F=1-687.
DR PDB; 2Q3Z; X-ray; 2.00 A; A=1-687.
DR PDB; 3LY6; X-ray; 3.14 A; A/B/C=1-687.
DR PDB; 3S3J; X-ray; 2.25 A; A=2-687.
DR PDB; 3S3P; X-ray; 2.50 A; A=2-687.
DR PDB; 3S3S; X-ray; 2.30 A; A=2-687.
DR PDBsum; 1FAU; -.
DR PDBsum; 1KV3; -.
DR PDBsum; 2Q3Z; -.
DR PDBsum; 3LY6; -.
DR PDBsum; 3S3J; -.
DR PDBsum; 3S3P; -.
DR PDBsum; 3S3S; -.
DR ProteinModelPortal; P21980; -.
DR SMR; P21980; 4-687.
DR DIP; DIP-33557N; -.
DR IntAct; P21980; 40.
DR MINT; MINT-88880; -.
DR STRING; 9606.ENSP00000355330; -.
DR BindingDB; P21980; -.
DR ChEMBL; CHEMBL2730; -.
DR DrugBank; DB00130; L-Glutamine.
DR PhosphoSite; P21980; -.
DR DMDM; 20141877; -.
DR PaxDb; P21980; -.
DR PeptideAtlas; P21980; -.
DR PRIDE; P21980; -.
DR Ensembl; ENST00000361475; ENSP00000355330; ENSG00000198959.
DR GeneID; 7052; -.
DR KEGG; hsa:7052; -.
DR UCSC; uc002xhr.3; human.
DR CTD; 7052; -.
DR GeneCards; GC20M036756; -.
DR HGNC; HGNC:11778; TGM2.
DR HPA; CAB002598; -.
DR HPA; HPA021019; -.
DR HPA; HPA029518; -.
DR MIM; 190196; gene.
DR neXtProt; NX_P21980; -.
DR PharmGKB; PA36491; -.
DR eggNOG; NOG80379; -.
DR HOGENOM; HOG000231695; -.
DR HOVERGEN; HBG004342; -.
DR InParanoid; P21980; -.
DR KO; K05625; -.
DR OMA; ANGRDHH; -.
DR OrthoDB; EOG7WT40M; -.
DR PhylomeDB; P21980; -.
DR SignaLink; P21980; -.
DR ChiTaRS; TGM2; human.
DR EvolutionaryTrace; P21980; -.
DR GeneWiki; Tissue_transglutaminase; -.
DR GenomeRNAi; 7052; -.
DR NextBio; 27573; -.
DR PMAP-CutDB; P21980; -.
DR PRO; PR:P21980; -.
DR ArrayExpress; P21980; -.
DR Bgee; P21980; -.
DR CleanEx; HS_TGM2; -.
DR Genevestigator; P21980; -.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; ISS:UniProtKB.
DR GO; GO:0043277; P:apoptotic cell clearance; IDA:UniProtKB.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0060445; P:branching involved in salivary gland morphogenesis; IEA:Ensembl.
DR GO; GO:0018153; P:isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine; IEA:Ensembl.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0051260; P:protein homooligomerization; IEA:Ensembl.
DR GO; GO:0060662; P:salivary gland cavitation; IEA:Ensembl.
DR Gene3D; 2.60.40.10; -; 3.
DR Gene3D; 3.90.260.10; -; 1.
DR InterPro; IPR023608; Gln_gamma-glutamylTfrase_euk.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002931; Transglutaminase-like.
DR InterPro; IPR008958; Transglutaminase_C.
DR InterPro; IPR013808; Transglutaminase_CS.
DR InterPro; IPR001102; Transglutaminase_N.
DR PANTHER; PTHR11590; PTHR11590; 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; SSF49309; SSF49309; 2.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS00547; TRANSGLUTAMINASES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Acyltransferase; Alternative splicing;
KW Calcium; Complete proteome; Direct protein sequencing; Metal-binding;
KW Polymorphism; Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 687 Protein-glutamine gamma-
FT glutamyltransferase 2.
FT /FTId=PRO_0000213707.
FT ACT_SITE 277 277 By similarity.
FT ACT_SITE 335 335 By similarity.
FT ACT_SITE 358 358 By similarity.
FT METAL 398 398 Calcium (By similarity).
FT METAL 400 400 Calcium (By similarity).
FT METAL 447 447 Calcium (By similarity).
FT METAL 452 452 Calcium (By similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 287 349 VLRCLGIPTRVVTNYNSAHDQNSNLLIEYFRNEFGEIQGDK
FT SEMIWNFHCWVESWMTRPDLQP -> GELHAGMWVMSPGRG
FT HEEHWSRNQDIPALVLPPATNTLNALCGLEPVTTLSGPLSN
FT SHPSSGC (in isoform 3).
FT /FTId=VSP_006413.
FT VAR_SEQ 350 687 Missing (in isoform 3).
FT /FTId=VSP_006414.
FT VAR_SEQ 539 548 EKSVPLCILY -> GKALCSWSIC (in isoform 2).
FT /FTId=VSP_006411.
FT VAR_SEQ 549 687 Missing (in isoform 2).
FT /FTId=VSP_006412.
FT VARIANT 76 76 R -> H (in dbSNP:rs41274720).
FT /FTId=VAR_052553.
FT VARIANT 214 214 R -> H (in dbSNP:rs45530133).
FT /FTId=VAR_055357.
FT VARIANT 324 324 Q -> R (in dbSNP:rs45567334).
FT /FTId=VAR_055358.
FT VARIANT 330 330 M -> R (in patients with early-onset
FT diabetes type 2; pathological
FT significance unknown).
FT /FTId=VAR_037998.
FT VARIANT 331 331 I -> N (in patients with early-onset
FT diabetes type 2; pathological
FT significance unknown).
FT /FTId=VAR_037999.
FT VARIANT 436 436 R -> W (in dbSNP:rs45629036).
FT /FTId=VAR_055359.
FT VARIANT 536 536 P -> S (in dbSNP:rs45556333).
FT /FTId=VAR_052554.
FT VARIANT 660 660 G -> V (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_036554.
FT CONFLICT 51 51 E -> Q (in Ref. 1; AAA63261).
FT CONFLICT 186 186 E -> Q (in Ref. 1; AAA63261).
FT CONFLICT 224 224 V -> G (in Ref. 1; AAA63261).
FT CONFLICT 533 533 N -> T (in Ref. 1; AAA63261).
FT CONFLICT 655 655 L -> V (in Ref. 1; AAA63261).
FT STRAND 7 11
FT HELIX 14 20
FT HELIX 24 26
FT STRAND 28 30
FT STRAND 32 34
FT STRAND 39 48
FT TURN 52 54
FT STRAND 55 66
FT TURN 69 72
FT STRAND 73 79
FT STRAND 89 95
FT STRAND 97 105
FT STRAND 113 123
FT STRAND 126 138
FT HELIX 153 159
FT STRAND 164 170
FT STRAND 172 181
FT HELIX 189 198
FT HELIX 201 205
FT HELIX 207 213
FT HELIX 217 226
FT TURN 227 229
FT TURN 231 234
FT STRAND 235 239
FT TURN 251 253
FT HELIX 258 266
FT TURN 267 269
FT STRAND 272 275
FT HELIX 277 291
FT STRAND 295 304
FT STRAND 306 309
FT HELIX 311 317
FT STRAND 332 342
FT STRAND 347 350
FT STRAND 353 357
FT STRAND 365 369
FT HELIX 376 380
FT TURN 387 389
FT HELIX 390 397
FT STRAND 400 404
FT STRAND 412 414
FT STRAND 419 429
FT STRAND 433 438
FT HELIX 440 443
FT STRAND 447 449
FT HELIX 450 460
FT TURN 468 471
FT STRAND 473 478
FT STRAND 489 497
FT STRAND 499 501
FT STRAND 503 514
FT STRAND 520 534
FT STRAND 538 546
FT HELIX 548 551
FT TURN 552 554
FT STRAND 560 569
FT TURN 570 573
FT STRAND 574 583
FT STRAND 590 595
FT STRAND 598 601
FT STRAND 603 610
FT STRAND 613 615
FT STRAND 619 625
FT TURN 627 629
FT STRAND 634 638
FT STRAND 647 654
FT STRAND 658 660
FT STRAND 662 669
FT STRAND 671 673
FT STRAND 676 682
SQ SEQUENCE 687 AA; 77329 MW; 7DA33FF335DE7B37 CRC64;
MAEELVLERC DLELETNGRD HHTADLCREK LVVRRGQPFW LTLHFEGRNY EASVDSLTFS
VVTGPAPSQE AGTKARFPLR DAVEEGDWTA TVVDQQDCTL SLQLTTPANA PIGLYRLSLE
ASTGYQGSSF VLGHFILLFN AWCPADAVYL DSEEERQEYV LTQQGFIYQG SAKFIKNIPW
NFGQFEDGIL DICLILLDVN PKFLKNAGRD CSRRSSPVYV GRVVSGMVNC NDDQGVLLGR
WDNNYGDGVS PMSWIGSVDI LRRWKNHGCQ RVKYGQCWVF AAVACTVLRC LGIPTRVVTN
YNSAHDQNSN LLIEYFRNEF GEIQGDKSEM IWNFHCWVES WMTRPDLQPG YEGWQALDPT
PQEKSEGTYC CGPVPVRAIK EGDLSTKYDA PFVFAEVNAD VVDWIQQDDG SVHKSINRSL
IVGLKISTKS VGRDEREDIT HTYKYPEGSS EEREAFTRAN HLNKLAEKEE TGMAMRIRVG
QSMNMGSDFD VFAHITNNTA EEYVCRLLLC ARTVSYNGIL GPECGTKYLL NLNLEPFSEK
SVPLCILYEK YRDCLTESNL IKVRALLVEP VINSYLLAER DLYLENPEIK IRILGEPKQK
RKLVAEVSLQ NPLPVALEGC TFTVEGAGLT EEQKTVEIPD PVEAGEEVKV RMDLLPLHMG
LHKLVVNFES DKLKAVKGFR NVIIGPA
//
MIM
190196
*RECORD*
*FIELD* NO
190196
*FIELD* TI
*190196 TRANSGLUTAMINASE 2; TGM2
;;TRANSGLUTAMINASE, TISSUE;;
TRANSGLUTAMINASE C; TGC;;
read moreGUANINE NUCLEOTIDE-BINDING PROTEIN, H POLYPEPTIDE; GNAH;;
G PROTEIN, ALPHA SUBUNIT, Gh CLASS;;
G-ALPHA-h
*FIELD* TX
DESCRIPTION
Transglutaminases (EC 2.3.2.13) catalyze the crosslinking of proteins by
epsilon-gamma glutamyl lysine isopeptide bonds. The transglutaminases
include factor XIII (plasma transglutaminase; 134570), keratinocyte
transglutaminase (TGM1; 190195), hair follicle transglutaminase,
prostate transglutaminase (TGM4; 600585), and tissue transglutaminase
(TGM2). Although the overall primary structures of these enzymes are
different, they all share a common amino acid sequence at the active
site (YGQCW) and a strict calcium dependence for their activity.
Differences in the primary structures of transglutaminases are probably
responsible for their diverse biologic functions. The unique C terminus
of TGM2, which is not involved in TGase activity, functions as a G
protein (see GNAQ; 600998) in receptor signaling.
CLONING
Gentile et al. (1991) isolated mouse and human cDNAs encoding tissue
transglutaminase. The predicted 687-amino acid human protein is 84% and
81% identical to mouse and guinea pig tissue transglutaminase,
respectively. In vitro translated human tissue transglutaminase has an
apparent molecular mass of 85 kD by SDS-PAGE. The translated product
exhibited calcium-dependent catalytic activity. Northern blot analysis
revealed that tissue transglutaminase is expressed as a 3.6-kb mRNA in
human endothelial cells.
Hwang et al. (1995) cloned TGM2, which they called G-alpha-h, from a
heart cDNA library. Transfected COS-1 cells expressed TGM2 protein at an
apparent molecular mass of about 80 kD.
Lu et al. (1995) cloned the promoter region of TGM2, ligated it to a
reporter construct, and demonstrated its activity in transient
transfection experiments.
By RT-PCR and immunoblot analysis, Vezza et al. (1999) demonstrated that
TGM2 was expressed in platelets, megakaryocytic cell lines, and
endothelial and vascular smooth muscle cells.
Antonyak et al. (2006) described a splice variant of TGM2 that encodes a
548-amino acid protein, which they called TGase-S. TGase-S contains the
GTP-binding domain, transamidation domain, and Ca(2+)-binding domain of
full-length TGase, but it lacks the C-terminal phospholipase C (PLC; see
604114)-binding domain.
GENE FUNCTION
Fesus et al. (1987) observed a significant increase of tissue
transglutaminase activity and enzyme concentration in programmed cell
death of hepatocytes. Immunohistochemical examination showed
transglutaminase within apoptotic hepatocytes, suggesting a role for the
enzyme in apoptosis.
In neonatal rat liver cells stimulated with epidermal growth factor
(EGF; 131530), Piacentini et al. (1991) found that the proliferative
phase was paralleled by a 10-fold increase in tissue transglutaminase
mRNA levels. During the phase of involution, there were sequential
increases in enzyme activity and increased levels of insoluble apoptotic
bodies. Immunostaining localized the TGM2 protein within apoptotic
bodies. The findings suggested that tissue transglutaminase leads to the
formation of a detergent-insoluble cross-linked protein scaffold in
cells undergoing apoptosis. This scaffold could stabilize cell membranes
and prevent nonspecific release of harmful intracellular components,
such as lysosomal enzymes. In human neuroblastoma cells, Melino et al.
(1994) showed that overexpression of tissue transglutaminase resulted in
a large increase in cell death rate with changes characteristic of cells
undergoing apoptosis. Transfection of cells with TGM2 cDNA in antisense
orientation resulted in a pronounced decrease in apoptosis. The authors
concluded that tissue transglutaminase-dependent irreversible
cross-linking of intracellular protein is an important biochemical event
in apoptotic cells.
Nakaoka et al. (1994) demonstrated that membranes of COS-1 cells
cotransfected with the cDNAs for rat liver Tgm2 and hamster Adra1b
(104220) adrenergic receptor showed both TGase activity and
agonist-dependent inositol phosphate accumulation. TGase activity was
blocked by a TGase inhibitor, a nonhydrolyzable GTP analog, and alpha-1
adrenergic receptor activation. The nucleotide exchange activity of rat
liver Tgm2 was comparable to that of G-alpha-q. Nakaoka et al. (1994)
hypothesized that, since receptor activation stimulates the binding of
GTP to TGM2, activation may be a switch that allows TGM2 to act as a
signaling molecule rather than a TGase.
Using C-terminal deletion mutants, Hwang et al. (1995) mapped the region
of TGM2 involved in ADRA1 and PLC binding. Deletion of up to 40
C-terminal amino acids had no effect on GTP binding and TGase activity.
The Ca(2+)-stimulated TGase activity was, however, inhibited by excess
GTP, confirming that GTP is a negative regulator of the TGase activity
of TGM2. All mutants, as well as full-length TGM2, elevated basal PLC
activity when cotransfected with ADRA1, but truncation of the final 30
or 40 C-terminal amino acids resulted in loss of agonist-induced PLC
activation. Further mutation analysis determined that an 8-amino acid
region near the C terminus, val665 to lys672, mediated PLC interaction
and stimulation.
Chen et al. (1996) found that mutation of the active site cysteine
(cys277) in TGM2 resulted in the expected loss of TGase activity in
transfected COS-1 cells, but it had no effect on receptor-stimulated
inositol phosphate turnover when TGM2 was cotransfected with ADRA1B.
TGM2 supported receptor-mediated inositol phosphate turnover when it was
cotransfected with ADRA1B or ADRA1D (104219), but not with ADRA1A
(104221).
Dieterich et al. (1997) demonstrated that tissue transglutaminase is the
autoantigen involved in celiac disease (212750).
Vezza et al. (1999) presented evidence that TGM2 interacts with
thromboxane A2 receptor (TBXA2R; 188070). Following cotransfection in
COS-7 cells, 2 splice variants of TBXA2R, designated TP-alpha and
TP-beta, immunoprecipitated with rat Tgm2. Agonist activation of
TP-alpha, but not TP-beta, stimulated PLC-mediated inositol phosphate
production.
Proliferative vitreoretinopathy (193235) is characterized by the
development of epi- and subretinal fibrocellular membranes containing
modified retinal pigment epithelial (RPE) cells among others. Priglinger
et al. (2003) found that tissue transglutaminase was present and
functionally active in proliferative vitreoretinopathy membranes. The
amount and activity of tissue transglutaminase appeared to be related to
the differentiation state of the RPE cells and their stimulation by
transforming growth factor beta-2 (TGFB2; 190220), a growth factor known
to be increased in the vitreous of proliferative vitreoretinopathy.
To elucidate the role of transglutaminase-2 in Huntington disease (HD;
143100), Mastroberardino et al. (2002) generated a transgenic HD mouse
model (R6/1) that was also null for TGM2 (Tgm2 -/-). Comparisons of
transglutaminase activity among different mouse lines showed that Tgm2
is the predominant transglutaminase active in the brain. The deletion of
Tgm2 led to significant ameliorations in generalized and brain weight
loss in the HD mice. Tgm2 ablation led to a large reduction in overall
cell death and to an increased number of neuronal intranuclear
inclusions, suggesting that Tgm2 crosslinking is not directly involved
in the assembly of inclusions. Moreover, the findings suggested a
protective role for neuronal aggregates. Tgm2 -/- HD mice showed a
significant improvement in motor behavior and survival. The results
suggested that TGM2 plays a role in the regulation of neuronal cell
death in HD.
Antonyak et al. (2006) found that, in contrast to the cytoprotective
effect of full-length human TGase, the TGase-S isoform was cytotoxic
when overexpressed in mammalian cells. Mutation analysis showed that the
apoptotic activity of TGase-S was not dependent on its transamidation
activity. TGase-S formed inappropriate oligomers in cells before cell
death, suggesting a novel mechanism for its apoptotic effects.
MAPPING
By fluorescence in situ hybridization (FISH) with a recombinant
lambda-phage containing the full cDNA coding sequence, Gentile et al.
(1994) showed that the tissue transglutaminase gene is located on
chromosome 20q12. Wang et al. (1994) used PCR amplification of DNAs
isolated from a panel of human/rodent somatic cell hybrids and FISH to
map both the TGM2 and the TGM3 (600238) gene to 20q11.2; FISH showed
overlap of the signal into band 20q12. It appeared that TGM3 may be
distal to TGM2. It is noteworthy that the gene structure and amino acid
sequence of TGM2 and TGM3 are more closely related to each other than to
those of other members of the transglutaminase family.
ANIMAL MODEL
To clarify the role of TGase2 in apoptosis, De Laurenzi and Melino
(2001) generated TGase2 -/- mice by homologous recombination. Although
RT-PCR and Western blot analysis demonstrated complete absence of
TGase2, minimal residual TGase activity was measured in liver and thymus
extracts. PCR analysis of mRNA extracted from the same tissues
demonstrated expression of TGase1. The TGase2 -/- mice showed no major
developmental abnormalities, and histologic examination of the major
organs appeared normal. Induction of apoptosis ex vivo and in vitro
showed no significant differences. De Laurenzi and Melino (2001)
concluded that TGase2 is not a crucial component of the main pathway of
the apoptotic program, and that residual enzymatic activity, due to
TGase1 or other as yet unidentified TGases, may compensate for the lack
of TGase2.
Because the TGase2 -/- mice generated by De Laurenzi and Melino (2001)
did not show an overt apoptosis-related phenotype during fetal life,
Szondy et al. (2003) investigated the role of TGase2 in the in vivo
apoptosis program in distinct biologic context by using the thymus and
liver as models for study. They presented data indicating that the lack
of TGase2 affects both the killing and the clearance of dying cells. The
disturbance of these events results from a deficiency in TGF-beta
activation and is associated with the development of splenomegaly,
autoantibodies, and glomerulonephritis in TGase2 -/- mice.
Zhang et al. (2003) generated a transgenic mouse model overexpressing
TGM2 in cardiomyocytes and found that the mice had an age-dependent left
ventricular hypertrophy and cardiac decompensation, characterized by
cardiomyocyte apoptosis and fibrosis and a delayed impact on survival.
Expression of COX2 (600262), thromboxane synthase (274180), and the
thromboxane receptor (188070) were increased coincident with the
emergence of the cardiac phenotype. The COX2-dependent increase in
thromboxane A2 augmented cardiac hypertrophy, whereas formation of PGI2
by the same isozyme, as well as administration of COX2 inhibitors,
rescued the cardiac phenotype. Zhang et al. (2003) concluded that TGM2
activation regulates expression of COX2, and that its products may
differentially modulate cell death or survival of cardiomyocytes.
*FIELD* RF
1. Antonyak, M. A.; Jansen, J. M.; Miller, A. M.; Ly, T. K.; Endo,
M.; Cerione, R. A.: Two isoforms of tissue transglutaminase mediate
opposing cellular fates. Proc. Nat. Acad. Sci. 103: 18609-18614,
2006.
2. Chen, S.; Lin, F.; Iismaa, S.; Lee, K. N.; Birckbichler, P. J.;
Graham, R. M.: Alpha-1-adrenergic receptor signaling via Gh is subtype
specific and independent of its transglutaminase activity. J. Biol.
Chem. 271: 32385-32391, 1996.
3. De Laurenzi, V.; Melino, G.: Gene disruption of tissue transglutaminase. Molec.
Cell. Biol. 21: 148-155, 2001.
4. Dieterich, W.; Ehnis, T.; Bauer, M.; Donner, P.; Volta, U.; Riecken,
E. O.; Schuppan, D.: Identification of tissue transglutaminase as
the autoantigen of celiac disease. Nature Med. 3: 797-801, 1997.
5. Fesus, L.; Thomazy, V.; Falus, A.: Induction and activation of
tissue transglutaminase during programmed cell death. FEBS Lett. 224:
104-108, 1987.
6. Gentile, V.; Davies, P. J. A.; Baldini, A.: The human tissue transglutaminase
gene maps on chromosome 20q12 by in situ fluorescence hybridization. Genomics 20:
295-297, 1994.
7. Gentile, V.; Saydak, M.; Chiocca, E. A.; Akande, O.; Birckbichler,
P. J.; Lee, K. N.; Stein, J. P.; Davies, P. J. A.: Isolation and
characterization of cDNA clones to mouse macrophage and human endothelial
cell tissue transglutaminases. J. Biol. Chem. 266: 478-483, 1991.
8. Hwang, K.-C.; Gray, C. D.; Sivasubramanian, N.; Im, M.-J.: Interaction
site of GTP binding Gh (transglutaminase II) with phospholipase C. J.
Biol. Chem. 270: 27058-27062, 1995.
9. Lu, S.; Saydak, M.; Gentile, V.; Stein, J. P.; Davies, P. J. A.
: Isolation and characterization of the human tissue transglutaminase
gene promoter. J. Biol. Chem. 270: 9748-9756, 1995.
10. Mastroberardino, P. G.; Iannicola, C.; Nardacci, R.; Bernassola,
F.; de Laurenzi, V.; Melino, G.; Moreno, S.; Pavone, F.; Oliverio,
S.; Fesus, L.; Piacentini, M.: 'Tissue' transglutaminase ablation
reduces neuronal death and prolongs survival in a mouse model of Huntington's
disease. Cell Death Differ. 9: 873-880, 2002.
11. Melino, G.; Annicchiarico-Petruzzelli, M.; Piredda, L.; Candi,
E.; Gentile, V.; Davies, P. J. A.; Piacentini, M.: Tissue transglutaminase
and apoptosis: sense and antisense transfection studies with human
neuroblastoma cells. Molec. Cell. Biol. 14: 6584-6596, 1994.
12. Nakaoka, H.; Perez, D. M.; Baek, K. J.; Das, T.; Husain, A.; Misono,
K.; Im, M.-J.; Graham, R. M.: Gh: a GTP-binding protein with transglutaminase
activity and receptor signaling function. Science 264: 1593-1596,
1994.
13. Piacentini, M.; Autuori, F.; Dini, L.; Farrace, M. G.; Ghibelli,
L.; Piredda, L.; Fesus, L.: 'Tissue' transglutaminase is specifically
expressed in neonatal rat liver cells undergoing apoptosis upon epidermal
growth factor-stimulation. Cell Tissue Res. 263: 227-235, 1991.
14. Priglinger, S. G.; May, C. A.; Neubauer, A. S.; Alge, C. S.; Schoenfeld,
C.-L.; Kampik, A.; Welge-Lussen, U.: Tissue transglutaminase as a
modifying enzyme of the extracellular matrix in PVR membranes. Invest.
Ophthal. Vis. Sci. 44: 355-364, 2003.
15. Szondy, Z.; Sarang, Z.; Molnar, P.; Nemeth, T.; Piacentini, M.;
Mastroberardino, P. G.; Falasca, L.; Aeschlimann, D.; Kovacs, J.;
Kiss, I.; Szegezdi, E.; Lakos, G.; Rajnavolgyi, E.; Birckbichler,
P. J.; Melino, G.; Fesus, L.: Transglutaminase 2 -/- mice reveal
a phagocytosis-associated crosstalk between macrophages and apoptotic
cells. Proc. Nat. Acad. Sci. 100: 7812-7817, 2003.
16. Vezza, R.; Habib, A.; FitzGerald, G. A.: Differential signaling
by the thromboxane receptor isoforms via the novel GTP-binding protein,
Gh. J. Biol. Chem. 274: 12774-12779, 1999.
17. Wang, M.; Kim, I.-G.; Steinert, P. M.; McBride, O. W.: Assignment
of the human transglutaminase 2 (TGM2) and transglutaminase 3 (TGM3)
genes to chromosome 20q11.2. Genomics 23: 721-722, 1994.
18. Zhang, Z.; Vezza, R.; Plappert, T.; McNamara, P.; Lawson, J. A.;
Austin, S.; Pratico, D.; Sutton, M. S.; FitzGerald, G. A.: COX-2-dependent
cardiac failure in Gh/tTG transgenic mice. Circ. Res. 92: 1153-1161,
2003.
*FIELD* CN
Patricia A. Hartz - updated: 5/1/2007
Marla J. F. O'Neill - updated: 2/18/2004
Patricia A. Hartz - updated: 2/10/2004
Victor A. McKusick - updated: 7/16/2003
Cassandra L. Kniffin - updated: 6/25/2003
Jane Kelly - updated: 3/18/2003
Rebekah S. Rasooly - updated: 5/12/1999
Victor A. McKusick - updated: 9/4/1997
Alan F. Scott - updated: 6/26/1995
*FIELD* CD
Victor A. McKusick: 12/13/1994
*FIELD* ED
carol: 09/17/2013
mgross: 5/1/2007
carol: 2/18/2004
mgross: 2/10/2004
carol: 10/23/2003
cwells: 7/22/2003
terry: 7/16/2003
carol: 6/26/2003
ckniffin: 6/25/2003
cwells: 3/18/2003
alopez: 5/12/1999
terry: 9/10/1997
terry: 9/4/1997
carol: 12/13/1994
*RECORD*
*FIELD* NO
190196
*FIELD* TI
*190196 TRANSGLUTAMINASE 2; TGM2
;;TRANSGLUTAMINASE, TISSUE;;
TRANSGLUTAMINASE C; TGC;;
read moreGUANINE NUCLEOTIDE-BINDING PROTEIN, H POLYPEPTIDE; GNAH;;
G PROTEIN, ALPHA SUBUNIT, Gh CLASS;;
G-ALPHA-h
*FIELD* TX
DESCRIPTION
Transglutaminases (EC 2.3.2.13) catalyze the crosslinking of proteins by
epsilon-gamma glutamyl lysine isopeptide bonds. The transglutaminases
include factor XIII (plasma transglutaminase; 134570), keratinocyte
transglutaminase (TGM1; 190195), hair follicle transglutaminase,
prostate transglutaminase (TGM4; 600585), and tissue transglutaminase
(TGM2). Although the overall primary structures of these enzymes are
different, they all share a common amino acid sequence at the active
site (YGQCW) and a strict calcium dependence for their activity.
Differences in the primary structures of transglutaminases are probably
responsible for their diverse biologic functions. The unique C terminus
of TGM2, which is not involved in TGase activity, functions as a G
protein (see GNAQ; 600998) in receptor signaling.
CLONING
Gentile et al. (1991) isolated mouse and human cDNAs encoding tissue
transglutaminase. The predicted 687-amino acid human protein is 84% and
81% identical to mouse and guinea pig tissue transglutaminase,
respectively. In vitro translated human tissue transglutaminase has an
apparent molecular mass of 85 kD by SDS-PAGE. The translated product
exhibited calcium-dependent catalytic activity. Northern blot analysis
revealed that tissue transglutaminase is expressed as a 3.6-kb mRNA in
human endothelial cells.
Hwang et al. (1995) cloned TGM2, which they called G-alpha-h, from a
heart cDNA library. Transfected COS-1 cells expressed TGM2 protein at an
apparent molecular mass of about 80 kD.
Lu et al. (1995) cloned the promoter region of TGM2, ligated it to a
reporter construct, and demonstrated its activity in transient
transfection experiments.
By RT-PCR and immunoblot analysis, Vezza et al. (1999) demonstrated that
TGM2 was expressed in platelets, megakaryocytic cell lines, and
endothelial and vascular smooth muscle cells.
Antonyak et al. (2006) described a splice variant of TGM2 that encodes a
548-amino acid protein, which they called TGase-S. TGase-S contains the
GTP-binding domain, transamidation domain, and Ca(2+)-binding domain of
full-length TGase, but it lacks the C-terminal phospholipase C (PLC; see
604114)-binding domain.
GENE FUNCTION
Fesus et al. (1987) observed a significant increase of tissue
transglutaminase activity and enzyme concentration in programmed cell
death of hepatocytes. Immunohistochemical examination showed
transglutaminase within apoptotic hepatocytes, suggesting a role for the
enzyme in apoptosis.
In neonatal rat liver cells stimulated with epidermal growth factor
(EGF; 131530), Piacentini et al. (1991) found that the proliferative
phase was paralleled by a 10-fold increase in tissue transglutaminase
mRNA levels. During the phase of involution, there were sequential
increases in enzyme activity and increased levels of insoluble apoptotic
bodies. Immunostaining localized the TGM2 protein within apoptotic
bodies. The findings suggested that tissue transglutaminase leads to the
formation of a detergent-insoluble cross-linked protein scaffold in
cells undergoing apoptosis. This scaffold could stabilize cell membranes
and prevent nonspecific release of harmful intracellular components,
such as lysosomal enzymes. In human neuroblastoma cells, Melino et al.
(1994) showed that overexpression of tissue transglutaminase resulted in
a large increase in cell death rate with changes characteristic of cells
undergoing apoptosis. Transfection of cells with TGM2 cDNA in antisense
orientation resulted in a pronounced decrease in apoptosis. The authors
concluded that tissue transglutaminase-dependent irreversible
cross-linking of intracellular protein is an important biochemical event
in apoptotic cells.
Nakaoka et al. (1994) demonstrated that membranes of COS-1 cells
cotransfected with the cDNAs for rat liver Tgm2 and hamster Adra1b
(104220) adrenergic receptor showed both TGase activity and
agonist-dependent inositol phosphate accumulation. TGase activity was
blocked by a TGase inhibitor, a nonhydrolyzable GTP analog, and alpha-1
adrenergic receptor activation. The nucleotide exchange activity of rat
liver Tgm2 was comparable to that of G-alpha-q. Nakaoka et al. (1994)
hypothesized that, since receptor activation stimulates the binding of
GTP to TGM2, activation may be a switch that allows TGM2 to act as a
signaling molecule rather than a TGase.
Using C-terminal deletion mutants, Hwang et al. (1995) mapped the region
of TGM2 involved in ADRA1 and PLC binding. Deletion of up to 40
C-terminal amino acids had no effect on GTP binding and TGase activity.
The Ca(2+)-stimulated TGase activity was, however, inhibited by excess
GTP, confirming that GTP is a negative regulator of the TGase activity
of TGM2. All mutants, as well as full-length TGM2, elevated basal PLC
activity when cotransfected with ADRA1, but truncation of the final 30
or 40 C-terminal amino acids resulted in loss of agonist-induced PLC
activation. Further mutation analysis determined that an 8-amino acid
region near the C terminus, val665 to lys672, mediated PLC interaction
and stimulation.
Chen et al. (1996) found that mutation of the active site cysteine
(cys277) in TGM2 resulted in the expected loss of TGase activity in
transfected COS-1 cells, but it had no effect on receptor-stimulated
inositol phosphate turnover when TGM2 was cotransfected with ADRA1B.
TGM2 supported receptor-mediated inositol phosphate turnover when it was
cotransfected with ADRA1B or ADRA1D (104219), but not with ADRA1A
(104221).
Dieterich et al. (1997) demonstrated that tissue transglutaminase is the
autoantigen involved in celiac disease (212750).
Vezza et al. (1999) presented evidence that TGM2 interacts with
thromboxane A2 receptor (TBXA2R; 188070). Following cotransfection in
COS-7 cells, 2 splice variants of TBXA2R, designated TP-alpha and
TP-beta, immunoprecipitated with rat Tgm2. Agonist activation of
TP-alpha, but not TP-beta, stimulated PLC-mediated inositol phosphate
production.
Proliferative vitreoretinopathy (193235) is characterized by the
development of epi- and subretinal fibrocellular membranes containing
modified retinal pigment epithelial (RPE) cells among others. Priglinger
et al. (2003) found that tissue transglutaminase was present and
functionally active in proliferative vitreoretinopathy membranes. The
amount and activity of tissue transglutaminase appeared to be related to
the differentiation state of the RPE cells and their stimulation by
transforming growth factor beta-2 (TGFB2; 190220), a growth factor known
to be increased in the vitreous of proliferative vitreoretinopathy.
To elucidate the role of transglutaminase-2 in Huntington disease (HD;
143100), Mastroberardino et al. (2002) generated a transgenic HD mouse
model (R6/1) that was also null for TGM2 (Tgm2 -/-). Comparisons of
transglutaminase activity among different mouse lines showed that Tgm2
is the predominant transglutaminase active in the brain. The deletion of
Tgm2 led to significant ameliorations in generalized and brain weight
loss in the HD mice. Tgm2 ablation led to a large reduction in overall
cell death and to an increased number of neuronal intranuclear
inclusions, suggesting that Tgm2 crosslinking is not directly involved
in the assembly of inclusions. Moreover, the findings suggested a
protective role for neuronal aggregates. Tgm2 -/- HD mice showed a
significant improvement in motor behavior and survival. The results
suggested that TGM2 plays a role in the regulation of neuronal cell
death in HD.
Antonyak et al. (2006) found that, in contrast to the cytoprotective
effect of full-length human TGase, the TGase-S isoform was cytotoxic
when overexpressed in mammalian cells. Mutation analysis showed that the
apoptotic activity of TGase-S was not dependent on its transamidation
activity. TGase-S formed inappropriate oligomers in cells before cell
death, suggesting a novel mechanism for its apoptotic effects.
MAPPING
By fluorescence in situ hybridization (FISH) with a recombinant
lambda-phage containing the full cDNA coding sequence, Gentile et al.
(1994) showed that the tissue transglutaminase gene is located on
chromosome 20q12. Wang et al. (1994) used PCR amplification of DNAs
isolated from a panel of human/rodent somatic cell hybrids and FISH to
map both the TGM2 and the TGM3 (600238) gene to 20q11.2; FISH showed
overlap of the signal into band 20q12. It appeared that TGM3 may be
distal to TGM2. It is noteworthy that the gene structure and amino acid
sequence of TGM2 and TGM3 are more closely related to each other than to
those of other members of the transglutaminase family.
ANIMAL MODEL
To clarify the role of TGase2 in apoptosis, De Laurenzi and Melino
(2001) generated TGase2 -/- mice by homologous recombination. Although
RT-PCR and Western blot analysis demonstrated complete absence of
TGase2, minimal residual TGase activity was measured in liver and thymus
extracts. PCR analysis of mRNA extracted from the same tissues
demonstrated expression of TGase1. The TGase2 -/- mice showed no major
developmental abnormalities, and histologic examination of the major
organs appeared normal. Induction of apoptosis ex vivo and in vitro
showed no significant differences. De Laurenzi and Melino (2001)
concluded that TGase2 is not a crucial component of the main pathway of
the apoptotic program, and that residual enzymatic activity, due to
TGase1 or other as yet unidentified TGases, may compensate for the lack
of TGase2.
Because the TGase2 -/- mice generated by De Laurenzi and Melino (2001)
did not show an overt apoptosis-related phenotype during fetal life,
Szondy et al. (2003) investigated the role of TGase2 in the in vivo
apoptosis program in distinct biologic context by using the thymus and
liver as models for study. They presented data indicating that the lack
of TGase2 affects both the killing and the clearance of dying cells. The
disturbance of these events results from a deficiency in TGF-beta
activation and is associated with the development of splenomegaly,
autoantibodies, and glomerulonephritis in TGase2 -/- mice.
Zhang et al. (2003) generated a transgenic mouse model overexpressing
TGM2 in cardiomyocytes and found that the mice had an age-dependent left
ventricular hypertrophy and cardiac decompensation, characterized by
cardiomyocyte apoptosis and fibrosis and a delayed impact on survival.
Expression of COX2 (600262), thromboxane synthase (274180), and the
thromboxane receptor (188070) were increased coincident with the
emergence of the cardiac phenotype. The COX2-dependent increase in
thromboxane A2 augmented cardiac hypertrophy, whereas formation of PGI2
by the same isozyme, as well as administration of COX2 inhibitors,
rescued the cardiac phenotype. Zhang et al. (2003) concluded that TGM2
activation regulates expression of COX2, and that its products may
differentially modulate cell death or survival of cardiomyocytes.
*FIELD* RF
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M.; Cerione, R. A.: Two isoforms of tissue transglutaminase mediate
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2006.
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F.; de Laurenzi, V.; Melino, G.; Moreno, S.; Pavone, F.; Oliverio,
S.; Fesus, L.; Piacentini, M.: 'Tissue' transglutaminase ablation
reduces neuronal death and prolongs survival in a mouse model of Huntington's
disease. Cell Death Differ. 9: 873-880, 2002.
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E.; Gentile, V.; Davies, P. J. A.; Piacentini, M.: Tissue transglutaminase
and apoptosis: sense and antisense transfection studies with human
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12. Nakaoka, H.; Perez, D. M.; Baek, K. J.; Das, T.; Husain, A.; Misono,
K.; Im, M.-J.; Graham, R. M.: Gh: a GTP-binding protein with transglutaminase
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modifying enzyme of the extracellular matrix in PVR membranes. Invest.
Ophthal. Vis. Sci. 44: 355-364, 2003.
15. Szondy, Z.; Sarang, Z.; Molnar, P.; Nemeth, T.; Piacentini, M.;
Mastroberardino, P. G.; Falasca, L.; Aeschlimann, D.; Kovacs, J.;
Kiss, I.; Szegezdi, E.; Lakos, G.; Rajnavolgyi, E.; Birckbichler,
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*FIELD* CN
Patricia A. Hartz - updated: 5/1/2007
Marla J. F. O'Neill - updated: 2/18/2004
Patricia A. Hartz - updated: 2/10/2004
Victor A. McKusick - updated: 7/16/2003
Cassandra L. Kniffin - updated: 6/25/2003
Jane Kelly - updated: 3/18/2003
Rebekah S. Rasooly - updated: 5/12/1999
Victor A. McKusick - updated: 9/4/1997
Alan F. Scott - updated: 6/26/1995
*FIELD* CD
Victor A. McKusick: 12/13/1994
*FIELD* ED
carol: 09/17/2013
mgross: 5/1/2007
carol: 2/18/2004
mgross: 2/10/2004
carol: 10/23/2003
cwells: 7/22/2003
terry: 7/16/2003
carol: 6/26/2003
ckniffin: 6/25/2003
cwells: 3/18/2003
alopez: 5/12/1999
terry: 9/10/1997
terry: 9/4/1997
carol: 12/13/1994