Full text data of TGM3
TGM3
[Confidence: low (only semi-automatic identification from reviews)]
Protein-glutamine gamma-glutamyltransferase E; 2.3.2.13 (Transglutaminase E; TG(E); TGE; TGase E; Transglutaminase-3; TGase-3; Protein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chain; Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chain; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Protein-glutamine gamma-glutamyltransferase E; 2.3.2.13 (Transglutaminase E; TG(E); TGE; TGase E; Transglutaminase-3; TGase-3; Protein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chain; Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chain; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q08188
ID TGM3_HUMAN Reviewed; 693 AA.
AC Q08188; A8K5N6; B2RCR6; D3DVX1; O95933; Q32ML9; Q32MM0;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-SEP-2009, sequence version 4.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=Protein-glutamine gamma-glutamyltransferase E;
DE EC=2.3.2.13;
DE AltName: Full=Transglutaminase E;
DE Short=TG(E);
DE Short=TGE;
DE Short=TGase E;
DE AltName: Full=Transglutaminase-3;
DE Short=TGase-3;
DE Contains:
DE RecName: Full=Protein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chain;
DE Contains:
DE RecName: Full=Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chain;
DE Flags: Precursor;
GN Name=TGM3;
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], AND VARIANTS LYS-13; ARG-562 AND ARG-654.
RC TISSUE=Foreskin;
RX PubMed=8099584;
RA Kim I.-G., Gorman J.J., Park S.-C., Chung S.-I., Steinert P.M.;
RT "The deduced sequence of the novel protransglutaminase E (TGase3) of
RT human and mouse.";
RL J. Biol. Chem. 268:12682-12690(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LYS-13 AND
RP ARG-654.
RC TISSUE=Tongue;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-13; LEU-163;
RP ASN-249; ARG-654 AND MET-687.
RG NIEHS SNPs program;
RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS LYS-13 AND
RP ARG-654.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LYS-13 AND
RP ARG-654.
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 [7]
RP PROTEIN SEQUENCE OF 2-13 AND 670-684, VARIANT LYS-13, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Bensaad K., Vousden K.H.;
RL Submitted (FEB-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 468-479, AND PROTEOLYTIC CLEAVAGE BY CTSL.
RX PubMed=16565075; DOI=10.1074/jbc.M600694200;
RA Cheng T., Hitomi K., van Vlijmen-Willems I.M., de Jongh G.J.,
RA Yamamoto K., Nishi K., Watts C., Reinheckel T., Schalkwijk J.,
RA Zeeuwen P.L.;
RT "Cystatin M/E is a high affinity inhibitor of cathepsin V and
RT cathepsin L by a reactive site that is distinct from the legumain-
RT binding site. A novel clue for the role of cystatin M/E in epidermal
RT cornification.";
RL J. Biol. Chem. 281:15893-15899(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-111 AND THR-112, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
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).
CC -!- FUNCTION: Catalyzes the calcium-dependent formation of isopeptide
CC cross-links between glutamine and lysine residues in various
CC proteins, as well as the conjugation of polyamines to proteins.
CC Involved in the formation of the cornified envelope (CE), a
CC specialized component consisting of covalent cross-links of
CC proteins beneath the plasma membrane of terminally differentiated
CC keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and
CC SPRR2) and LOR cross-linking to form small interchain oligomers,
CC which are further cross-linked by TGM1 onto the growing CE
CC scaffold (By similarity). In hair follicles, involved in cross-
CC linking structural proteins to hardening the inner root sheath.
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: Consists of two polypeptide chains, which are synthesized
CC as a precursor form of a single polypeptide.
CC -!- PTM: Activated by proteolytic processing. In vitro activation is
CC commonly achieved by cleavage with dispase, a neutral bacterial
CC protease. Dispase cleavage site was proposed to lie between Ser-
CC 470 and Ser-471 (PubMed:8099584) or between Pro-465 and Phe-466
CC (PubMed:16565075). Physiological activation may be catalyzed by
CC CTSL and, to a lesser extent, by CTSS, but not by CTSB, CTSD nor
CC CTSV (PubMed:16565075).
CC -!- SIMILARITY: Belongs to the transglutaminase superfamily.
CC Transglutaminase family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tgm3/";
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DR EMBL; L10386; AAA61155.1; -; mRNA.
DR EMBL; AK290324; BAF83013.1; -; mRNA.
DR EMBL; AK291351; BAF84040.1; -; mRNA.
DR EMBL; AK315236; BAG37663.1; -; mRNA.
DR EMBL; EF102483; ABK41960.1; -; Genomic_DNA.
DR EMBL; AL031678; CAB37633.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10601.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10602.1; -; Genomic_DNA.
DR EMBL; BC109075; AAI09076.1; -; mRNA.
DR EMBL; BC109076; AAI09077.1; -; mRNA.
DR PIR; A45991; A45991.
DR RefSeq; NP_003236.3; NM_003245.3.
DR UniGene; Hs.2022; -.
DR PDB; 1L9M; X-ray; 2.10 A; A/B=2-693.
DR PDB; 1L9N; X-ray; 2.10 A; A/B=2-693.
DR PDB; 1NUD; X-ray; 2.70 A; A/B=2-693.
DR PDB; 1NUF; X-ray; 2.70 A; A=2-693.
DR PDB; 1NUG; X-ray; 2.40 A; A/B=2-693.
DR PDB; 1RLE; X-ray; 2.10 A; A/B=2-693.
DR PDB; 1SGX; X-ray; 2.00 A; A/B=2-693.
DR PDB; 1VJJ; X-ray; 1.90 A; A/B=2-693.
DR PDBsum; 1L9M; -.
DR PDBsum; 1L9N; -.
DR PDBsum; 1NUD; -.
DR PDBsum; 1NUF; -.
DR PDBsum; 1NUG; -.
DR PDBsum; 1RLE; -.
DR PDBsum; 1SGX; -.
DR PDBsum; 1VJJ; -.
DR ProteinModelPortal; Q08188; -.
DR SMR; Q08188; 2-693.
DR IntAct; Q08188; 6.
DR MINT; MINT-7950929; -.
DR STRING; 9606.ENSP00000370867; -.
DR ChEMBL; CHEMBL3363; -.
DR DrugBank; DB00130; L-Glutamine.
DR PhosphoSite; Q08188; -.
DR DMDM; 257051080; -.
DR PaxDb; Q08188; -.
DR PeptideAtlas; Q08188; -.
DR PRIDE; Q08188; -.
DR Ensembl; ENST00000381458; ENSP00000370867; ENSG00000125780.
DR GeneID; 7053; -.
DR KEGG; hsa:7053; -.
DR UCSC; uc002wfx.4; human.
DR CTD; 7053; -.
DR GeneCards; GC20P002224; -.
DR HGNC; HGNC:11779; TGM3.
DR HPA; HPA004728; -.
DR MIM; 600238; gene.
DR neXtProt; NX_Q08188; -.
DR PharmGKB; PA36492; -.
DR eggNOG; NOG80379; -.
DR HOVERGEN; HBG004342; -.
DR InParanoid; Q08188; -.
DR KO; K05620; -.
DR OMA; EILPTRS; -.
DR OrthoDB; EOG7WT40M; -.
DR PhylomeDB; Q08188; -.
DR EvolutionaryTrace; Q08188; -.
DR GeneWiki; TGM3; -.
DR GenomeRNAi; 7053; -.
DR NextBio; 27579; -.
DR PRO; PR:Q08188; -.
DR Bgee; Q08188; -.
DR CleanEx; HS_TGM3; -.
DR Genevestigator; Q08188; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic to cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; IDA:UniProtKB.
DR GO; GO:0043163; P:cell envelope organization; IDA:UniProtKB.
DR GO; GO:0031069; P:hair follicle morphogenesis; TAS:UniProtKB.
DR GO; GO:0031424; P:keratinization; IEA:UniProtKB-KW.
DR GO; GO:0030216; P:keratinocyte differentiation; IEP:UniProtKB.
DR GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
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; Calcium;
KW Complete proteome; Direct protein sequencing; Keratinization;
KW Metal-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Transferase; Zymogen.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 467 Protein-glutamine gamma-
FT glutamyltransferase E 50 kDa catalytic
FT chain.
FT /FTId=PRO_0000033652.
FT CHAIN 468 693 Protein-glutamine gamma-
FT glutamyltransferase E 27 kDa non-
FT catalytic chain.
FT /FTId=PRO_0000033653.
FT ACT_SITE 273 273 By similarity.
FT ACT_SITE 331 331 By similarity.
FT ACT_SITE 354 354 By similarity.
FT METAL 394 394 Calcium (By similarity).
FT METAL 396 396 Calcium (By similarity).
FT METAL 444 444 Calcium (By similarity).
FT METAL 449 449 Calcium (By similarity).
FT SITE 467 468 Cleavage; by CTSL.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 111 111 Phosphotyrosine.
FT MOD_RES 112 112 Phosphothreonine.
FT VARIANT 13 13 T -> K (in dbSNP:rs214803).
FT /FTId=VAR_040067.
FT VARIANT 163 163 I -> L (in dbSNP:rs6048066).
FT /FTId=VAR_040068.
FT VARIANT 249 249 S -> N (in dbSNP:rs214814).
FT /FTId=VAR_040069.
FT VARIANT 562 562 K -> R (in dbSNP:rs1042617).
FT /FTId=VAR_040070.
FT VARIANT 654 654 G -> R (in dbSNP:rs214830).
FT /FTId=VAR_040071.
FT VARIANT 687 687 L -> M (in dbSNP:rs45581032).
FT /FTId=VAR_055360.
FT CONFLICT 58 59 VS -> DT (in Ref. 1; AAA61155).
FT CONFLICT 251 251 N -> G (in Ref. 1; AAA61155).
FT CONFLICT 324 324 S -> G (in Ref. 2; BAF84040).
FT CONFLICT 346 346 S -> P (in Ref. 1; AAA61155).
FT CONFLICT 674 674 D -> G (in Ref. 2; BAF84040).
FT STRAND 6 10
FT HELIX 13 19
FT STRAND 31 33
FT STRAND 38 46
FT STRAND 53 59
FT STRAND 61 63
FT TURN 66 69
FT STRAND 70 79
FT STRAND 82 92
FT STRAND 95 101
FT STRAND 109 119
FT STRAND 122 134
FT HELIX 149 155
FT STRAND 160 167
FT STRAND 170 177
FT HELIX 185 193
FT HELIX 197 201
FT HELIX 203 208
FT HELIX 209 211
FT HELIX 213 223
FT TURN 227 229
FT STRAND 231 235
FT HELIX 247 249
FT HELIX 253 262
FT STRAND 268 271
FT HELIX 273 287
FT STRAND 291 300
FT STRAND 305 313
FT TURN 322 325
FT STRAND 326 337
FT TURN 341 343
FT HELIX 345 347
FT STRAND 349 353
FT STRAND 356 359
FT HELIX 372 377
FT TURN 383 385
FT HELIX 386 394
FT STRAND 396 403
FT TURN 404 407
FT STRAND 408 426
FT STRAND 433 435
FT HELIX 437 440
FT STRAND 444 446
FT HELIX 447 460
FT STRAND 482 489
FT STRAND 499 507
FT STRAND 509 511
FT STRAND 513 524
FT STRAND 530 543
FT STRAND 548 555
FT HELIX 557 560
FT TURN 561 563
FT STRAND 569 577
FT STRAND 584 591
FT STRAND 597 603
FT STRAND 611 618
FT STRAND 621 623
FT STRAND 627 633
FT TURN 635 637
FT STRAND 638 640
FT STRAND 642 646
FT STRAND 654 661
FT STRAND 667 677
FT STRAND 680 692
SQ SEQUENCE 693 AA; 76632 MW; EAFAC0C9A8AA5FD6 CRC64;
MAALGVQSIN WQTAFNRQAH HTDKFSSQEL ILRRGQNFQV LMIMNKGLGS NERLEFIVST
GPYPSESAMT KAVFPLSNGS SGGWSAVLQA SNGNTLTISI SSPASAPIGR YTMALQIFSQ
GGISSVKLGT FILLFNPWLN VDSVFMGNHA EREEYVQEDA GIIFVGSTNR IGMIGWNFGQ
FEEDILSICL SILDRSLNFR RDAATDVASR NDPKYVGRVL SAMINSNDDN GVLAGNWSGT
YTGGRDPRSW NGSVEILKNW KKSGFSPVRY GQCWVFAGTL NTALRSLGIP SRVITNFNSA
HDTDRNLSVD VYYDPMGNPL DKGSDSVWNF HVWNEGWFVR SDLGPSYGGW QVLDATPQER
SQGVFQCGPA SVIGVREGDV QLNFDMPFIF AEVNADRITW LYDNTTGKQW KNSVNSHTIG
RYISTKAVGS NARMDVTDKY KYPEGSDQER QVFQKALGKL KPNTPFAATS SMGLETEEQE
PSIIGKLKVA GMLAVGKEVN LVLLLKNLSR DTKTVTVNMT AWTIIYNGTL VHEVWKDSAT
MSLDPEEEAE HPIKISYAQY EKYLKSDNMI RITAVCKVPD ESEVVVERDI ILDNPTLTLE
VLNEARVRKP VNVQMLFSNP LDEPVRDCVL MVEGSGLLLG NLKIDVPTLG PKEGSRVRFD
ILPSRSGTKQ LLADFSCNKF PAIKAMLSID VAE
//
ID TGM3_HUMAN Reviewed; 693 AA.
AC Q08188; A8K5N6; B2RCR6; D3DVX1; O95933; Q32ML9; Q32MM0;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-SEP-2009, sequence version 4.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=Protein-glutamine gamma-glutamyltransferase E;
DE EC=2.3.2.13;
DE AltName: Full=Transglutaminase E;
DE Short=TG(E);
DE Short=TGE;
DE Short=TGase E;
DE AltName: Full=Transglutaminase-3;
DE Short=TGase-3;
DE Contains:
DE RecName: Full=Protein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chain;
DE Contains:
DE RecName: Full=Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chain;
DE Flags: Precursor;
GN Name=TGM3;
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], AND VARIANTS LYS-13; ARG-562 AND ARG-654.
RC TISSUE=Foreskin;
RX PubMed=8099584;
RA Kim I.-G., Gorman J.J., Park S.-C., Chung S.-I., Steinert P.M.;
RT "The deduced sequence of the novel protransglutaminase E (TGase3) of
RT human and mouse.";
RL J. Biol. Chem. 268:12682-12690(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LYS-13 AND
RP ARG-654.
RC TISSUE=Tongue;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-13; LEU-163;
RP ASN-249; ARG-654 AND MET-687.
RG NIEHS SNPs program;
RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS LYS-13 AND
RP ARG-654.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LYS-13 AND
RP ARG-654.
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 [7]
RP PROTEIN SEQUENCE OF 2-13 AND 670-684, VARIANT LYS-13, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Bensaad K., Vousden K.H.;
RL Submitted (FEB-2008) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 468-479, AND PROTEOLYTIC CLEAVAGE BY CTSL.
RX PubMed=16565075; DOI=10.1074/jbc.M600694200;
RA Cheng T., Hitomi K., van Vlijmen-Willems I.M., de Jongh G.J.,
RA Yamamoto K., Nishi K., Watts C., Reinheckel T., Schalkwijk J.,
RA Zeeuwen P.L.;
RT "Cystatin M/E is a high affinity inhibitor of cathepsin V and
RT cathepsin L by a reactive site that is distinct from the legumain-
RT binding site. A novel clue for the role of cystatin M/E in epidermal
RT cornification.";
RL J. Biol. Chem. 281:15893-15899(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-111 AND THR-112, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [10]
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).
CC -!- FUNCTION: Catalyzes the calcium-dependent formation of isopeptide
CC cross-links between glutamine and lysine residues in various
CC proteins, as well as the conjugation of polyamines to proteins.
CC Involved in the formation of the cornified envelope (CE), a
CC specialized component consisting of covalent cross-links of
CC proteins beneath the plasma membrane of terminally differentiated
CC keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and
CC SPRR2) and LOR cross-linking to form small interchain oligomers,
CC which are further cross-linked by TGM1 onto the growing CE
CC scaffold (By similarity). In hair follicles, involved in cross-
CC linking structural proteins to hardening the inner root sheath.
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: Consists of two polypeptide chains, which are synthesized
CC as a precursor form of a single polypeptide.
CC -!- PTM: Activated by proteolytic processing. In vitro activation is
CC commonly achieved by cleavage with dispase, a neutral bacterial
CC protease. Dispase cleavage site was proposed to lie between Ser-
CC 470 and Ser-471 (PubMed:8099584) or between Pro-465 and Phe-466
CC (PubMed:16565075). Physiological activation may be catalyzed by
CC CTSL and, to a lesser extent, by CTSS, but not by CTSB, CTSD nor
CC CTSV (PubMed:16565075).
CC -!- SIMILARITY: Belongs to the transglutaminase superfamily.
CC Transglutaminase family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tgm3/";
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DR EMBL; L10386; AAA61155.1; -; mRNA.
DR EMBL; AK290324; BAF83013.1; -; mRNA.
DR EMBL; AK291351; BAF84040.1; -; mRNA.
DR EMBL; AK315236; BAG37663.1; -; mRNA.
DR EMBL; EF102483; ABK41960.1; -; Genomic_DNA.
DR EMBL; AL031678; CAB37633.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10601.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10602.1; -; Genomic_DNA.
DR EMBL; BC109075; AAI09076.1; -; mRNA.
DR EMBL; BC109076; AAI09077.1; -; mRNA.
DR PIR; A45991; A45991.
DR RefSeq; NP_003236.3; NM_003245.3.
DR UniGene; Hs.2022; -.
DR PDB; 1L9M; X-ray; 2.10 A; A/B=2-693.
DR PDB; 1L9N; X-ray; 2.10 A; A/B=2-693.
DR PDB; 1NUD; X-ray; 2.70 A; A/B=2-693.
DR PDB; 1NUF; X-ray; 2.70 A; A=2-693.
DR PDB; 1NUG; X-ray; 2.40 A; A/B=2-693.
DR PDB; 1RLE; X-ray; 2.10 A; A/B=2-693.
DR PDB; 1SGX; X-ray; 2.00 A; A/B=2-693.
DR PDB; 1VJJ; X-ray; 1.90 A; A/B=2-693.
DR PDBsum; 1L9M; -.
DR PDBsum; 1L9N; -.
DR PDBsum; 1NUD; -.
DR PDBsum; 1NUF; -.
DR PDBsum; 1NUG; -.
DR PDBsum; 1RLE; -.
DR PDBsum; 1SGX; -.
DR PDBsum; 1VJJ; -.
DR ProteinModelPortal; Q08188; -.
DR SMR; Q08188; 2-693.
DR IntAct; Q08188; 6.
DR MINT; MINT-7950929; -.
DR STRING; 9606.ENSP00000370867; -.
DR ChEMBL; CHEMBL3363; -.
DR DrugBank; DB00130; L-Glutamine.
DR PhosphoSite; Q08188; -.
DR DMDM; 257051080; -.
DR PaxDb; Q08188; -.
DR PeptideAtlas; Q08188; -.
DR PRIDE; Q08188; -.
DR Ensembl; ENST00000381458; ENSP00000370867; ENSG00000125780.
DR GeneID; 7053; -.
DR KEGG; hsa:7053; -.
DR UCSC; uc002wfx.4; human.
DR CTD; 7053; -.
DR GeneCards; GC20P002224; -.
DR HGNC; HGNC:11779; TGM3.
DR HPA; HPA004728; -.
DR MIM; 600238; gene.
DR neXtProt; NX_Q08188; -.
DR PharmGKB; PA36492; -.
DR eggNOG; NOG80379; -.
DR HOVERGEN; HBG004342; -.
DR InParanoid; Q08188; -.
DR KO; K05620; -.
DR OMA; EILPTRS; -.
DR OrthoDB; EOG7WT40M; -.
DR PhylomeDB; Q08188; -.
DR EvolutionaryTrace; Q08188; -.
DR GeneWiki; TGM3; -.
DR GenomeRNAi; 7053; -.
DR NextBio; 27579; -.
DR PRO; PR:Q08188; -.
DR Bgee; Q08188; -.
DR CleanEx; HS_TGM3; -.
DR Genevestigator; Q08188; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic to cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; IDA:UniProtKB.
DR GO; GO:0043163; P:cell envelope organization; IDA:UniProtKB.
DR GO; GO:0031069; P:hair follicle morphogenesis; TAS:UniProtKB.
DR GO; GO:0031424; P:keratinization; IEA:UniProtKB-KW.
DR GO; GO:0030216; P:keratinocyte differentiation; IEP:UniProtKB.
DR GO; GO:0018149; P:peptide cross-linking; IDA:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
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; Calcium;
KW Complete proteome; Direct protein sequencing; Keratinization;
KW Metal-binding; Phosphoprotein; Polymorphism; Reference proteome;
KW Transferase; Zymogen.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 467 Protein-glutamine gamma-
FT glutamyltransferase E 50 kDa catalytic
FT chain.
FT /FTId=PRO_0000033652.
FT CHAIN 468 693 Protein-glutamine gamma-
FT glutamyltransferase E 27 kDa non-
FT catalytic chain.
FT /FTId=PRO_0000033653.
FT ACT_SITE 273 273 By similarity.
FT ACT_SITE 331 331 By similarity.
FT ACT_SITE 354 354 By similarity.
FT METAL 394 394 Calcium (By similarity).
FT METAL 396 396 Calcium (By similarity).
FT METAL 444 444 Calcium (By similarity).
FT METAL 449 449 Calcium (By similarity).
FT SITE 467 468 Cleavage; by CTSL.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 111 111 Phosphotyrosine.
FT MOD_RES 112 112 Phosphothreonine.
FT VARIANT 13 13 T -> K (in dbSNP:rs214803).
FT /FTId=VAR_040067.
FT VARIANT 163 163 I -> L (in dbSNP:rs6048066).
FT /FTId=VAR_040068.
FT VARIANT 249 249 S -> N (in dbSNP:rs214814).
FT /FTId=VAR_040069.
FT VARIANT 562 562 K -> R (in dbSNP:rs1042617).
FT /FTId=VAR_040070.
FT VARIANT 654 654 G -> R (in dbSNP:rs214830).
FT /FTId=VAR_040071.
FT VARIANT 687 687 L -> M (in dbSNP:rs45581032).
FT /FTId=VAR_055360.
FT CONFLICT 58 59 VS -> DT (in Ref. 1; AAA61155).
FT CONFLICT 251 251 N -> G (in Ref. 1; AAA61155).
FT CONFLICT 324 324 S -> G (in Ref. 2; BAF84040).
FT CONFLICT 346 346 S -> P (in Ref. 1; AAA61155).
FT CONFLICT 674 674 D -> G (in Ref. 2; BAF84040).
FT STRAND 6 10
FT HELIX 13 19
FT STRAND 31 33
FT STRAND 38 46
FT STRAND 53 59
FT STRAND 61 63
FT TURN 66 69
FT STRAND 70 79
FT STRAND 82 92
FT STRAND 95 101
FT STRAND 109 119
FT STRAND 122 134
FT HELIX 149 155
FT STRAND 160 167
FT STRAND 170 177
FT HELIX 185 193
FT HELIX 197 201
FT HELIX 203 208
FT HELIX 209 211
FT HELIX 213 223
FT TURN 227 229
FT STRAND 231 235
FT HELIX 247 249
FT HELIX 253 262
FT STRAND 268 271
FT HELIX 273 287
FT STRAND 291 300
FT STRAND 305 313
FT TURN 322 325
FT STRAND 326 337
FT TURN 341 343
FT HELIX 345 347
FT STRAND 349 353
FT STRAND 356 359
FT HELIX 372 377
FT TURN 383 385
FT HELIX 386 394
FT STRAND 396 403
FT TURN 404 407
FT STRAND 408 426
FT STRAND 433 435
FT HELIX 437 440
FT STRAND 444 446
FT HELIX 447 460
FT STRAND 482 489
FT STRAND 499 507
FT STRAND 509 511
FT STRAND 513 524
FT STRAND 530 543
FT STRAND 548 555
FT HELIX 557 560
FT TURN 561 563
FT STRAND 569 577
FT STRAND 584 591
FT STRAND 597 603
FT STRAND 611 618
FT STRAND 621 623
FT STRAND 627 633
FT TURN 635 637
FT STRAND 638 640
FT STRAND 642 646
FT STRAND 654 661
FT STRAND 667 677
FT STRAND 680 692
SQ SEQUENCE 693 AA; 76632 MW; EAFAC0C9A8AA5FD6 CRC64;
MAALGVQSIN WQTAFNRQAH HTDKFSSQEL ILRRGQNFQV LMIMNKGLGS NERLEFIVST
GPYPSESAMT KAVFPLSNGS SGGWSAVLQA SNGNTLTISI SSPASAPIGR YTMALQIFSQ
GGISSVKLGT FILLFNPWLN VDSVFMGNHA EREEYVQEDA GIIFVGSTNR IGMIGWNFGQ
FEEDILSICL SILDRSLNFR RDAATDVASR NDPKYVGRVL SAMINSNDDN GVLAGNWSGT
YTGGRDPRSW NGSVEILKNW KKSGFSPVRY GQCWVFAGTL NTALRSLGIP SRVITNFNSA
HDTDRNLSVD VYYDPMGNPL DKGSDSVWNF HVWNEGWFVR SDLGPSYGGW QVLDATPQER
SQGVFQCGPA SVIGVREGDV QLNFDMPFIF AEVNADRITW LYDNTTGKQW KNSVNSHTIG
RYISTKAVGS NARMDVTDKY KYPEGSDQER QVFQKALGKL KPNTPFAATS SMGLETEEQE
PSIIGKLKVA GMLAVGKEVN LVLLLKNLSR DTKTVTVNMT AWTIIYNGTL VHEVWKDSAT
MSLDPEEEAE HPIKISYAQY EKYLKSDNMI RITAVCKVPD ESEVVVERDI ILDNPTLTLE
VLNEARVRKP VNVQMLFSNP LDEPVRDCVL MVEGSGLLLG NLKIDVPTLG PKEGSRVRFD
ILPSRSGTKQ LLADFSCNKF PAIKAMLSID VAE
//
MIM
600238
*RECORD*
*FIELD* NO
600238
*FIELD* TI
*600238 TRANSGLUTAMINASE 3; TGM3
;;TRANSGLUTAMINASE E; TGE
*FIELD* TX
DESCRIPTION
read more
Transglutaminases (protein-glutamine:amine gamma-glutamyltransferases;
EC 2.3.2.13) catalyze the formation of lysine isodipeptide crosslinks in
proteins between the gamma-amide of a donor glutamine and the
epsilon-NH2 of an acceptor lysine. The result is a stable, insoluble
macromolecular structure, a process used widely throughout the plant and
animal kingdoms. The human haploid genome contains at least 5 distinct
transglutaminases that are differentially expressed in time-space and
tissue-specific ways. These include the catalytic subunit of factor XIII
(134570); band 4.2 (177070), an inactive enzyme that forms a part of the
subplasma membrane of erythrocytic and other cells; transglutaminase-1
(TGM1; 190195), a membrane-associated enzyme present in many epithelial
as well as some nonepithelial tissues; a ubiquitously expressed tissue
transglutaminase-2 (TGM2; 190196); and a proenzyme activity,
transglutaminase-3, found in terminally differentiating epidermal and
hair keratinocytes. This proenzyme requires activation by proteolysis.
The TGM1 and TGM3 enzymes are thought to be involved in the formation of
the cornified cell envelope (CE) of the epidermis, hair follicle, and
perhaps other stratified squamous epithelia by cross-linking of CE
protein constituents with isodipeptide bonds (Kim et al., (1993)).
CLONING
Using a combination of primer extension and PCR with degenerate
oligonucleotide primers based on the partial protein sequence of guinea
pig TGase3, Kim et al. (1993) isolated partial TGase3 cDNAs from newborn
mouse and human foreskin epidermis. The authors used a combination of
techniques to clone additional cDNAs corresponding to the entire coding
regions of both human and mouse TGase3. The predicted proteins contain
692 amino acids and are 75% identical. Most of the sequence variation
occurs in the vicinity of the proteolytic activation site, which lies at
the most flexible and hydrophilic region of the molecule. Kim et al.
(1993) suggested that cleavage of this exposed flexible hinge region
promotes a conformational change in the protein to a more compact form,
resulting in activation of the enzyme. Northern blot analysis revealed
that the 2.9-kb TGase3 mRNA is expressed in human foreskin and in mouse
epidermis and hair follicles. TGase3 expression in mammalian cells was
regulated by calcium, as with other late epidermal differentiation
products such as loricrin (152445) and profilaggrin (135940), suggesting
to the authors that TGase3 is responsible for the later stages of cell
envelope formation in the epidermis and hair follicle.
GENE FUNCTION
Kim et al. (1993) found that, when expressed in yeast cells, human
TGase3 exhibited significant transglutaminase activity.
Using ELISA, Sardy et al. (2002) found that sera from both celiac
disease (CD; 212750) and dermatitis herpetiformis (DH; 601230) reacted
with TGM2 and TGM3, but the DH antibodies had a markedly higher avidity
for TGM3. Immunofluorescence and confocal microscopy demonstrated that
IgA precipitates in the papillary dermis of DH patients contained TGM3,
but not TGM1 or TGM2. Sardy et al. (2002) concluded that TGM3 is the
dominant autoantigen in DH, explaining why skin symptoms rather than
intestinal symptoms appear in a proportion of patients with
gluten-sensitive disease.
GENE STRUCTURE
Kim et al. (1994) demonstrated that TGM3 is encoded by a gene of 42.8 kb
containing 13 exons. Kim et al. (1994) compared the exon/intron
organization with that of the other transglutaminase genes and suggested
on this basis and on the basis of sequence homologies that TGM2 and TGM3
belong to a branch of a phylogenetic tree distinct from other
transglutaminases.
MAPPING
Using Southern blot hybridization or species-specific PCR amplification
of DNAs isolated from a panel of human/rodent somatic cell hybrids,
followed by fluorescence in situ hybridization, Wang et al. (1994)
mapped the TGM2 and TGM3 genes to chromosome 20q11.2. They stated that
on FISH the signal showed overlap into band 20q12. However, Hartz (2011)
mapped the TGM3 gene to chromosome 20p13 based on an alignment of the
TGM3 sequence (GenBank GENBANK BC109076) with the genomic sequence
(GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 4/20/2011.
2. Kim, I.-G.; Gorman, J. J.; Park, S.-C.; Chung, S.-I.; Steinert,
P. M.: The deduced sequence of the novel protransglutaminase E (TGase3)
of human and mouse. J. Biol. Chem. 268: 12682-12690, 1993.
3. Kim, I.-G.; Lee, S.-C.; Lee, J.-H.; Yang, J.-M.; Chung, S.-I.;
Steinert, P. M.: Structure and organization of the human transglutaminase
3 gene: evolutionary relationship to the transglutaminase family. J.
Invest. Derm. 103: 137-142, 1994.
4. Sardy, M.; Karpati, S.; Merkl, B.; Paulsson, M.; Smyth, N.: Epidermal
transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J.
Exp. Med. 195: 747-757, 2002.
5. 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.
*FIELD* CN
Patricia A. Hartz - updated: 04/20/2011
Paul J. Converse - updated: 1/9/2006
Rebekah S. Rasooly - updated: 5/13/1999
*FIELD* CD
Victor A. McKusick: 12/13/1994
*FIELD* ED
mgross: 04/20/2011
mgross: 1/9/2006
alopez: 5/13/1999
jamie: 1/17/1997
mark: 1/28/1996
carol: 12/30/1994
terry: 12/22/1994
carol: 12/13/1994
*RECORD*
*FIELD* NO
600238
*FIELD* TI
*600238 TRANSGLUTAMINASE 3; TGM3
;;TRANSGLUTAMINASE E; TGE
*FIELD* TX
DESCRIPTION
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Transglutaminases (protein-glutamine:amine gamma-glutamyltransferases;
EC 2.3.2.13) catalyze the formation of lysine isodipeptide crosslinks in
proteins between the gamma-amide of a donor glutamine and the
epsilon-NH2 of an acceptor lysine. The result is a stable, insoluble
macromolecular structure, a process used widely throughout the plant and
animal kingdoms. The human haploid genome contains at least 5 distinct
transglutaminases that are differentially expressed in time-space and
tissue-specific ways. These include the catalytic subunit of factor XIII
(134570); band 4.2 (177070), an inactive enzyme that forms a part of the
subplasma membrane of erythrocytic and other cells; transglutaminase-1
(TGM1; 190195), a membrane-associated enzyme present in many epithelial
as well as some nonepithelial tissues; a ubiquitously expressed tissue
transglutaminase-2 (TGM2; 190196); and a proenzyme activity,
transglutaminase-3, found in terminally differentiating epidermal and
hair keratinocytes. This proenzyme requires activation by proteolysis.
The TGM1 and TGM3 enzymes are thought to be involved in the formation of
the cornified cell envelope (CE) of the epidermis, hair follicle, and
perhaps other stratified squamous epithelia by cross-linking of CE
protein constituents with isodipeptide bonds (Kim et al., (1993)).
CLONING
Using a combination of primer extension and PCR with degenerate
oligonucleotide primers based on the partial protein sequence of guinea
pig TGase3, Kim et al. (1993) isolated partial TGase3 cDNAs from newborn
mouse and human foreskin epidermis. The authors used a combination of
techniques to clone additional cDNAs corresponding to the entire coding
regions of both human and mouse TGase3. The predicted proteins contain
692 amino acids and are 75% identical. Most of the sequence variation
occurs in the vicinity of the proteolytic activation site, which lies at
the most flexible and hydrophilic region of the molecule. Kim et al.
(1993) suggested that cleavage of this exposed flexible hinge region
promotes a conformational change in the protein to a more compact form,
resulting in activation of the enzyme. Northern blot analysis revealed
that the 2.9-kb TGase3 mRNA is expressed in human foreskin and in mouse
epidermis and hair follicles. TGase3 expression in mammalian cells was
regulated by calcium, as with other late epidermal differentiation
products such as loricrin (152445) and profilaggrin (135940), suggesting
to the authors that TGase3 is responsible for the later stages of cell
envelope formation in the epidermis and hair follicle.
GENE FUNCTION
Kim et al. (1993) found that, when expressed in yeast cells, human
TGase3 exhibited significant transglutaminase activity.
Using ELISA, Sardy et al. (2002) found that sera from both celiac
disease (CD; 212750) and dermatitis herpetiformis (DH; 601230) reacted
with TGM2 and TGM3, but the DH antibodies had a markedly higher avidity
for TGM3. Immunofluorescence and confocal microscopy demonstrated that
IgA precipitates in the papillary dermis of DH patients contained TGM3,
but not TGM1 or TGM2. Sardy et al. (2002) concluded that TGM3 is the
dominant autoantigen in DH, explaining why skin symptoms rather than
intestinal symptoms appear in a proportion of patients with
gluten-sensitive disease.
GENE STRUCTURE
Kim et al. (1994) demonstrated that TGM3 is encoded by a gene of 42.8 kb
containing 13 exons. Kim et al. (1994) compared the exon/intron
organization with that of the other transglutaminase genes and suggested
on this basis and on the basis of sequence homologies that TGM2 and TGM3
belong to a branch of a phylogenetic tree distinct from other
transglutaminases.
MAPPING
Using Southern blot hybridization or species-specific PCR amplification
of DNAs isolated from a panel of human/rodent somatic cell hybrids,
followed by fluorescence in situ hybridization, Wang et al. (1994)
mapped the TGM2 and TGM3 genes to chromosome 20q11.2. They stated that
on FISH the signal showed overlap into band 20q12. However, Hartz (2011)
mapped the TGM3 gene to chromosome 20p13 based on an alignment of the
TGM3 sequence (GenBank GENBANK BC109076) with the genomic sequence
(GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 4/20/2011.
2. Kim, I.-G.; Gorman, J. J.; Park, S.-C.; Chung, S.-I.; Steinert,
P. M.: The deduced sequence of the novel protransglutaminase E (TGase3)
of human and mouse. J. Biol. Chem. 268: 12682-12690, 1993.
3. Kim, I.-G.; Lee, S.-C.; Lee, J.-H.; Yang, J.-M.; Chung, S.-I.;
Steinert, P. M.: Structure and organization of the human transglutaminase
3 gene: evolutionary relationship to the transglutaminase family. J.
Invest. Derm. 103: 137-142, 1994.
4. Sardy, M.; Karpati, S.; Merkl, B.; Paulsson, M.; Smyth, N.: Epidermal
transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J.
Exp. Med. 195: 747-757, 2002.
5. 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.
*FIELD* CN
Patricia A. Hartz - updated: 04/20/2011
Paul J. Converse - updated: 1/9/2006
Rebekah S. Rasooly - updated: 5/13/1999
*FIELD* CD
Victor A. McKusick: 12/13/1994
*FIELD* ED
mgross: 04/20/2011
mgross: 1/9/2006
alopez: 5/13/1999
jamie: 1/17/1997
mark: 1/28/1996
carol: 12/30/1994
terry: 12/22/1994
carol: 12/13/1994