ID TGM3_MOUSE Reviewed; 693 AA. AC Q08189; A1L343; A2ANC3; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 31-MAY-2011, sequence version 2. DT 24-JAN-2024, entry version 172. DE RecName: Full=Protein-glutamine gamma-glutamyltransferase E; DE EC=2.3.2.13 {ECO:0000250|UniProtKB:Q08188}; 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; Synonyms=Tgase3; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/cJ; TISSUE=Epidermis; RX PubMed=8099584; DOI=10.1016/s0021-9258(18)31442-x; 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 human RT and mouse."; RL J. Biol. Chem. 268:12682-12690(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP TISSUE SPECIFICITY. RX PubMed=11331204; DOI=10.1016/s1357-2725(01)00033-4; RA Hitomi K., Horio Y., Ikura K., Yamanishi K., Maki M.; RT "Analysis of epidermal-type transglutaminase (TGase 3) expression in mouse RT tissues and cell lines."; RL Int. J. Biochem. Cell Biol. 33:491-498(2001). RN [6] RP DEVELOPMENTAL STAGE. RX PubMed=15740639; DOI=10.1038/sj.cr.7290274; RA Zhang J., Zhi H.Y., Ding F., Luo A.P., Liu Z.H.; RT "Transglutaminase 3 expression in C57BL/6J mouse embryo epidermis and the RT correlation with its differentiation."; RL Cell Res. 15:105-110(2005). RN [7] RP TISSUE SPECIFICITY. RX PubMed=20716179; DOI=10.1111/j.1742-4658.2010.07765.x; RA Yamane A., Fukui M., Sugimura Y., Itoh M., Alea M.P., Thomas V., RA El Alaoui S., Akiyama M., Hitomi K.; RT "Identification of a preferred substrate peptide for transglutaminase 3 and RT detection of in situ activity in skin and hair follicles."; RL FEBS J. 277:3564-3574(2010). CC -!- FUNCTION: Catalyzes the calcium-dependent formation of isopeptide CC cross-links between glutamine and lysine residues in various proteins, CC as well as the conjugation of polyamines to proteins. Involved in the CC formation of the cornified envelope (CE), a specialized component CC consisting of covalent cross-links of proteins beneath the plasma CC membrane of terminally differentiated keratinocytes. Catalyzes small CC proline-rich proteins (SPRR1 and SPRR2) and LOR cross-linking to form CC small interchain oligomers, which are further cross-linked by TGM1 onto CC the growing CE scaffold (By similarity). In hair follicles, involved in CC cross-linking structural proteins to hardening the inner root sheath. CC {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L- CC lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:54816, CC Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:14005, CC ChEBI:CHEBI:28938, ChEBI:CHEBI:29969, ChEBI:CHEBI:30011, CC ChEBI:CHEBI:138370; EC=2.3.2.13; CC Evidence={ECO:0000250|UniProtKB:Q08188, ECO:0000255|PROSITE- CC ProRule:PRU10024}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; CC Note=Binds 3 Ca(2+) cations per subunit. Binds 1 Ca(2+) as a zymogen, CC and binds 2 more Ca(2+) cations, or other divalent metal cations, after CC proteolytic processing. {ECO:0000250}; CC -!- SUBUNIT: Consists of two polypeptide chains, which are synthesized as a CC precursor form of a single polypeptide. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q08188}. CC -!- TISSUE SPECIFICITY: Expressed in skin and stomach and, at lower levels, CC in testis, kidney and spleen (at protein level). On the basis of its CC catalytic activity, detected in the epidermis, around the granular and CC spinous layers but not in the outermost cornified layers. In hair CC follicles, mainly located in the medulla and the hair cortex. CC {ECO:0000269|PubMed:11331204, ECO:0000269|PubMed:20716179}. CC -!- DEVELOPMENTAL STAGE: Expression starts at 11.5 dpc in the early two- CC layered epidermis. From 12.5 dpc, mainly expressed in the periderm CC cells and weakly in the epidermal basal cells. After epidermis CC keratinization, at 15.5 to 17.5 dpc, detected in the granular, CC cornified layers and in the hair follicle. Also expressed in heart, CC lung, bone, muscle, testis and blood vessels at 12.5, 13.5, 14.5 and CC 16.5 dpc, respectively. {ECO:0000269|PubMed:15740639}. CC -!- PTM: Activated by proteolytic processing. In vitro activation is CC commonly achieved by cleavage with dispase, a neutral bacterial CC protease. Physiological activation may be catalyzed by CTSL and, to a CC lesser extent, by CTSS (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the transglutaminase superfamily. CC Transglutaminase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA40421.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L10385; AAA40421.1; ALT_FRAME; mRNA. DR EMBL; AL808127; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH466519; EDL28248.1; -; Genomic_DNA. DR EMBL; BC129890; AAI29891.1; -; mRNA. DR EMBL; BC129891; AAI29892.1; -; mRNA. DR CCDS; CCDS38240.1; -. DR PIR; B45991; B45991. DR RefSeq; NP_033400.2; NM_009374.3. DR AlphaFoldDB; Q08189; -. DR SMR; Q08189; -. DR BioGRID; 204169; 11. DR IntAct; Q08189; 3. DR STRING; 10090.ENSMUSP00000105928; -. DR GlyGen; Q08189; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q08189; -. DR PhosphoSitePlus; Q08189; -. DR MaxQB; Q08189; -. DR PaxDb; 10090-ENSMUSP00000105928; -. DR PeptideAtlas; Q08189; -. DR ProteomicsDB; 263169; -. DR Pumba; Q08189; -. DR DNASU; 21818; -. DR Ensembl; ENSMUST00000110299.3; ENSMUSP00000105928.3; ENSMUSG00000027401.10. DR GeneID; 21818; -. DR KEGG; mmu:21818; -. DR UCSC; uc008mig.2; mouse. DR AGR; MGI:98732; -. DR CTD; 7053; -. DR MGI; MGI:98732; Tgm3. DR VEuPathDB; HostDB:ENSMUSG00000027401; -. DR eggNOG; ENOG502QUPB; Eukaryota. DR GeneTree; ENSGT01050000244866; -. DR HOGENOM; CLU_013435_1_0_1; -. DR InParanoid; Q08189; -. DR OMA; SMVGWNF; -. DR OrthoDB; 5344745at2759; -. DR PhylomeDB; Q08189; -. DR TreeFam; TF324278; -. DR BioGRID-ORCS; 21818; 3 hits in 78 CRISPR screens. DR ChiTaRS; Tgm3; mouse. DR PRO; PR:Q08189; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q08189; Protein. DR Bgee; ENSMUSG00000027401; Expressed in esophagus and 47 other cell types or tissues. DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL. DR GO; GO:0001533; C:cornified envelope; TAS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0003824; F:catalytic activity; ISS:UniProtKB. DR GO; GO:0003810; F:protein-glutamine gamma-glutamyltransferase activity; ISS:UniProtKB. DR GO; GO:0005198; F:structural molecule activity; ISS:UniProtKB. DR GO; GO:0008544; P:epidermis development; TAS:UniProtKB. DR GO; GO:0035315; P:hair cell differentiation; TAS:UniProtKB. DR GO; GO:0031424; P:keratinization; IEA:UniProtKB-KW. DR GO; GO:0030216; P:keratinocyte differentiation; ISS:UniProtKB. DR GO; GO:0018149; P:peptide cross-linking; ISS:UniProtKB. DR GO; GO:0043588; P:skin development; TAS:UniProtKB. DR Gene3D; 2.60.40.10; Immunoglobulins; 3. DR Gene3D; 3.90.260.10; Transglutaminase-like; 1. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR002931; Transglutaminase-like. DR InterPro; IPR036985; Transglutaminase-like_sf. DR InterPro; IPR023608; Transglutaminase_animal. DR InterPro; IPR013808; Transglutaminase_AS. DR InterPro; IPR008958; Transglutaminase_C. DR InterPro; IPR036238; Transglutaminase_C_sf. DR InterPro; IPR001102; Transglutaminase_N. DR PANTHER; PTHR11590; PROTEIN-GLUTAMINE GAMMA-GLUTAMYLTRANSFERASE; 1. DR PANTHER; PTHR11590:SF36; PROTEIN-GLUTAMINE GAMMA-GLUTAMYLTRANSFERASE E; 1. DR Pfam; PF00927; Transglut_C; 2. DR Pfam; PF01841; Transglut_core; 1. DR Pfam; PF00868; Transglut_N; 1. DR PIRSF; PIRSF000459; TGM_EBP42; 1. DR SMART; SM00460; TGc; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF81296; E set domains; 1. DR SUPFAM; SSF49309; Transglutaminase, two C-terminal domains; 2. DR PROSITE; PS00547; TRANSGLUTAMINASES; 1. DR Genevisible; Q08189; MM. PE 1: Evidence at protein level; KW Acyltransferase; Calcium; Cytoplasm; Keratinization; Metal-binding; KW Phosphoprotein; Reference proteome; Transferase; Zymogen. FT CHAIN 1..467 FT /note="Protein-glutamine gamma-glutamyltransferase E 50 kDa FT catalytic chain" FT /id="PRO_0000033654" FT CHAIN 468..693 FT /note="Protein-glutamine gamma-glutamyltransferase E 27 kDa FT non-catalytic chain" FT /id="PRO_0000033655" FT REGION 457..483 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 273 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024" FT ACT_SITE 331 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024" FT ACT_SITE 354 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10024" FT BINDING 222 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 225 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 227 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 228 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 230 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 302 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 304 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 306 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 308 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 325 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 394 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 416 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT BINDING 444 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 449 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT SITE 467..468 FT /note="Cleavage; by CTSL" FT /evidence="ECO:0000250" FT MOD_RES 111 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q08188" FT MOD_RES 112 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q08188" FT CONFLICT 290 FT /note="P -> R (in Ref. 1; AAA40421)" FT /evidence="ECO:0000305" FT CONFLICT 409 FT /note="Q -> P (in Ref. 4; AAI29892/AAI29891)" FT /evidence="ECO:0000305" FT CONFLICT 573 FT /note="T -> S (in Ref. 1; AAA40421)" FT /evidence="ECO:0000305" FT CONFLICT 588 FT /note="R -> W (in Ref. 1; AAA40421)" FT /evidence="ECO:0000305" FT CONFLICT 616 FT /note="L -> I (in Ref. 1; AAA40421)" FT /evidence="ECO:0000305" FT CONFLICT 639 FT /note="R -> G (in Ref. 1; AAA40421)" FT /evidence="ECO:0000305" FT CONFLICT 682 FT /note="A -> T (in Ref. 1; AAA40421)" FT /evidence="ECO:0000305" SQ SEQUENCE 693 AA; 77309 MW; 834D86CD87AE0E9C CRC64; MSALQIQNVN WQVPMNRRAH HTDKFSSQDS IVRRGQPWEI ILVCNRSLES GEDLNFIVST GPQPSESART KAVFSISGRS TGGWNAALKA NSGNNLAIAI ASPVSAPIGL YTLSVEISSR GRASSLKLGT FIMLFNPWLQ ADDVFMSNHA ERQEYVEEDS GIIYVGSTNR IGMVGWNFGQ FEEDILNISL SILDRSLNFR RDPVTDVARR NDPKYVCRVL SAMINGNDDN GVISGNWSGN YTGGVDPRTW NGSVEILKNW KKSGFRPVQF GQCWVFAGTL NTVLRCLGVP SRVITNFNSA HDTDRNLSVD VYYDAMGNPL EKGSDSVWNF HVWNEGWFVR TDLGPTYNGW QVLDATPQER SQGVFQCGPA SVNAIKAGDV DRNFDMIFIF AEVNADRITW IYNNRNNTQK QNSVDTHSIG KYISTKAVGS NSRMDVTDKY KYPEGSSEER QVHQKALDKL KPNASFGATS SRNPEGEDKE PSISGKFKVT GILAVGKEVS LSLMLKNMTN DRKTVTMNMT AWTIVYNGTL VHEVWKDSAT ISLDPEEEIQ YPVKIAYSQY ERYLKADNMI RITAVCKVPD EAEVVVERDV ILDNPALTLE VLEQAHVRKP VNVQMLFSNP LDQPVNNCVL LVEGSGLLRG SLKIDVPSLR PKEKSRIRFE IFPTRSGTKQ LLADFSCNKF PAIKAMLPID VSE //