UniProtKB - Q08188 (TGM3_HUMAN)
Protein-glutamine gamma-glutamyltransferase E
TGM3
Functioni
Catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins, as well as the conjugation of polyamines to proteins. Involved in the formation of the cornified envelope (CE), a specialized component consisting of covalent cross-links of proteins beneath the plasma membrane of terminally differentiated keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and SPRR2) and LOR cross-linking to form small interchain oligomers, which are further cross-linked by TGM1 onto the growing CE scaffold (By similarity).
In hair follicles, involved in cross-linking structural proteins to hardening the inner root sheath.
By similarityCatalytic activityi
- L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L-lysyl-N6-5-L-glutamyl-[protein] + NH4+PROSITE-ProRule annotation3 PublicationsEC:2.3.2.13PROSITE-ProRule annotation3 Publications
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 222 | Calcium 1; via carbonyl oxygen2 Publications | 1 | |
Metal bindingi | 225 | Calcium 12 Publications | 1 | |
Metal bindingi | 227 | Calcium 1; via carbonyl oxygen2 Publications | 1 | |
Metal bindingi | 228 | Calcium 12 Publications | 1 | |
Metal bindingi | 230 | Calcium 1; via carbonyl oxygen2 Publications | 1 | |
Active sitei | 273 | PROSITE-ProRule annotation | 1 | |
Metal bindingi | 302 | Calcium 22 Publications | 1 | |
Metal bindingi | 304 | Calcium 22 Publications | 1 | |
Metal bindingi | 306 | Calcium 22 Publications | 1 | |
Metal bindingi | 308 | Calcium 2; via carbonyl oxygen2 Publications | 1 | |
Metal bindingi | 325 | Calcium 22 Publications | 1 | |
Active sitei | 331 | PROSITE-ProRule annotation | 1 | |
Active sitei | 354 | PROSITE-ProRule annotation | 1 | |
Metal bindingi | 394 | Calcium 32 Publications | 1 | |
Metal bindingi | 416 | Calcium 3; via carbonyl oxygen2 Publications | 1 | |
Metal bindingi | 444 | Calcium 32 Publications | 1 | |
Metal bindingi | 449 | Calcium 32 Publications | 1 |
GO - Molecular functioni
- acyltransferase activity Source: UniProtKB
- calcium ion binding Source: UniProtKB
- catalytic activity Source: UniProtKB
- protein-glutamine gamma-glutamyltransferase activity Source: UniProtKB
- structural molecule activity Source: UniProtKB
GO - Biological processi
- cell envelope organization Source: UniProtKB
- cellular protein modification process Source: UniProtKB
- hair follicle morphogenesis Source: UniProtKB
- keratinization Source: UniProtKB-KW
- keratinocyte differentiation Source: UniProtKB
- peptide cross-linking Source: UniProtKB
Keywordsi
Molecular function | Acyltransferase, Transferase |
Biological process | Keratinization |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
BRENDAi | 2.3.2.13, 2681 |
PathwayCommonsi | Q08188 |
SignaLinki | Q08188 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein-glutamine gamma-glutamyltransferase E (EC:2.3.2.133 Publications)Alternative name(s): Transglutaminase E Short name: TG(E) Short name: TGE Short name: TGase E Transglutaminase-3 Short name: TGase-3 Cleaved into the following 2 chains: |
Gene namesi | Name:TGM3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11779, TGM3 |
MIMi | 600238, gene |
neXtProti | NX_Q08188 |
VEuPathDBi | HostDB:ENSG00000125780 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Plasma Membrane
- extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Involvement in diseasei
Uncombable hair syndrome 2 (UHS2)1 Publication
Organism-specific databases
DisGeNETi | 7053 |
MalaCardsi | TGM3 |
MIMi | 617251, phenotype |
OpenTargetsi | ENSG00000125780 |
Orphaneti | 1410, Uncombable hair syndrome |
PharmGKBi | PA36492 |
Miscellaneous databases
Pharosi | Q08188, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3363 |
DrugBanki | DB01864, 5'-Guanosine-Diphosphate-Monothiophosphate DB03152, B-2-Octylglucoside DB04315, Guanosine-5'-Diphosphate DB01972, Guanosine-5'-Monophosphate DB00130, L-Glutamine |
Genetic variation databases
BioMutai | TGM3 |
DMDMi | 257051080 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | Removed1 Publication | |||
ChainiPRO_0000033652 | 2 – 467 | Protein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chainAdd BLAST | 466 | |
ChainiPRO_0000033653 | 468 – 693 | Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chainAdd BLAST | 226 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanine1 Publication | 1 | |
Modified residuei | 111 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 112 | PhosphothreonineCombined sources | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 467 – 468 | Cleavage; by CTSL | 2 |
Keywords - PTMi
Acetylation, Phosphoprotein, ZymogenProteomic databases
EPDi | Q08188 |
jPOSTi | Q08188 |
MassIVEi | Q08188 |
MaxQBi | Q08188 |
PaxDbi | Q08188 |
PeptideAtlasi | Q08188 |
PRIDEi | Q08188 |
ProteomicsDBi | 58578 |
TopDownProteomicsi | Q08188 |
PTM databases
GlyGeni | Q08188, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q08188 |
PhosphoSitePlusi | Q08188 |
Expressioni
Gene expression databases
Bgeei | ENSG00000125780, Expressed in lower esophagus mucosa and 126 other tissues |
Genevisiblei | Q08188, HS |
Organism-specific databases
HPAi | ENSG00000125780, Tissue enriched (esophagus) |
Interactioni
Subunit structurei
Consists of two polypeptide chains, which are synthesized as a precursor form of a single polypeptide.
2 PublicationsProtein-protein interaction databases
BioGRIDi | 112911, 123 interactors |
IntActi | Q08188, 26 interactors |
MINTi | Q08188 |
STRINGi | 9606.ENSP00000370867 |
Chemistry databases
BindingDBi | Q08188 |
Miscellaneous databases
RNActi | Q08188, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q08188 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q08188 |
Family & Domainsi
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502QUPB, Eukaryota |
GeneTreei | ENSGT01040000240478 |
HOGENOMi | CLU_013435_1_0_1 |
InParanoidi | Q08188 |
OMAi | SMVGWNF |
OrthoDBi | 297055at2759 |
PhylomeDBi | Q08188 |
TreeFami | TF324278 |
Family and domain databases
Gene3Di | 2.60.40.10, 3 hits 3.90.260.10, 1 hit |
InterProi | View protein in InterPro IPR013783, Ig-like_fold IPR014756, Ig_E-set IPR038765, Papain-like_cys_pep_sf IPR002931, Transglutaminase-like IPR036985, Transglutaminase-like_sf IPR023608, Transglutaminase_animal IPR013808, Transglutaminase_AS IPR008958, Transglutaminase_C IPR036238, Transglutaminase_C_sf IPR001102, Transglutaminase_N |
Pfami | View protein in Pfam PF00927, Transglut_C, 2 hits PF01841, Transglut_core, 1 hit PF00868, Transglut_N, 1 hit |
PIRSFi | PIRSF000459, TGM_EBP42, 1 hit |
SMARTi | View protein in SMART SM00460, TGc, 1 hit |
SUPFAMi | SSF49309, SSF49309, 2 hits SSF54001, SSF54001, 1 hit SSF81296, SSF81296, 1 hit |
PROSITEi | View protein in PROSITE PS00547, TRANSGLUTAMINASES, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MAALGVQSIN WQTAFNRQAH HTDKFSSQEL ILRRGQNFQV LMIMNKGLGS
60 70 80 90 100
NERLEFIVST GPYPSESAMT KAVFPLSNGS SGGWSAVLQA SNGNTLTISI
110 120 130 140 150
SSPASAPIGR YTMALQIFSQ GGISSVKLGT FILLFNPWLN VDSVFMGNHA
160 170 180 190 200
EREEYVQEDA GIIFVGSTNR IGMIGWNFGQ FEEDILSICL SILDRSLNFR
210 220 230 240 250
RDAATDVASR NDPKYVGRVL SAMINSNDDN GVLAGNWSGT YTGGRDPRSW
260 270 280 290 300
NGSVEILKNW KKSGFSPVRY GQCWVFAGTL NTALRSLGIP SRVITNFNSA
310 320 330 340 350
HDTDRNLSVD VYYDPMGNPL DKGSDSVWNF HVWNEGWFVR SDLGPSYGGW
360 370 380 390 400
QVLDATPQER SQGVFQCGPA SVIGVREGDV QLNFDMPFIF AEVNADRITW
410 420 430 440 450
LYDNTTGKQW KNSVNSHTIG RYISTKAVGS NARMDVTDKY KYPEGSDQER
460 470 480 490 500
QVFQKALGKL KPNTPFAATS SMGLETEEQE PSIIGKLKVA GMLAVGKEVN
510 520 530 540 550
LVLLLKNLSR DTKTVTVNMT AWTIIYNGTL VHEVWKDSAT MSLDPEEEAE
560 570 580 590 600
HPIKISYAQY EKYLKSDNMI RITAVCKVPD ESEVVVERDI ILDNPTLTLE
610 620 630 640 650
VLNEARVRKP VNVQMLFSNP LDEPVRDCVL MVEGSGLLLG NLKIDVPTLG
660 670 680 690
PKEGSRVRFD ILPSRSGTKQ LLADFSCNKF PAIKAMLSID VAE
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 58 – 59 | VS → DT in AAA61155 (PubMed:8099584).Curated | 2 | |
Sequence conflicti | 251 | N → G in AAA61155 (PubMed:8099584).Curated | 1 | |
Sequence conflicti | 324 | S → G in BAF84040 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 346 | S → P in AAA61155 (PubMed:8099584).Curated | 1 | |
Sequence conflicti | 674 | D → G in BAF84040 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040067 | 13 | T → K6 PublicationsCorresponds to variant dbSNP:rs214803Ensembl. | 1 | |
Natural variantiVAR_040068 | 163 | I → L1 PublicationCorresponds to variant dbSNP:rs6048066Ensembl. | 1 | |
Natural variantiVAR_040069 | 249 | S → N1 PublicationCorresponds to variant dbSNP:rs214814Ensembl. | 1 | |
Natural variantiVAR_040070 | 562 | K → R1 PublicationCorresponds to variant dbSNP:rs1042617Ensembl. | 1 | |
Natural variantiVAR_040071 | 654 | G → R5 PublicationsCorresponds to variant dbSNP:rs214830Ensembl. | 1 | |
Natural variantiVAR_055360 | 687 | L → M1 PublicationCorresponds to variant dbSNP:rs45581032Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L10386 mRNA Translation: AAA61155.1 AK290324 mRNA Translation: BAF83013.1 AK291351 mRNA Translation: BAF84040.1 AK315236 mRNA Translation: BAG37663.1 EF102483 Genomic DNA Translation: ABK41960.1 AL031678 Genomic DNA No translation available. CH471133 Genomic DNA Translation: EAX10601.1 CH471133 Genomic DNA Translation: EAX10602.1 BC109075 mRNA Translation: AAI09076.1 BC109076 mRNA Translation: AAI09077.1 |
CCDSi | CCDS33435.1 |
PIRi | A45991 |
RefSeqi | NP_003236.3, NM_003245.3 |
Genome annotation databases
Ensembli | ENST00000381458; ENSP00000370867; ENSG00000125780 |
GeneIDi | 7053 |
KEGGi | hsa:7053 |
MANE-Selecti | ENST00000381458.6; ENSP00000370867.5; NM_003245.4; NP_003236.3 |
UCSCi | uc002wfx.5, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L10386 mRNA Translation: AAA61155.1 AK290324 mRNA Translation: BAF83013.1 AK291351 mRNA Translation: BAF84040.1 AK315236 mRNA Translation: BAG37663.1 EF102483 Genomic DNA Translation: ABK41960.1 AL031678 Genomic DNA No translation available. CH471133 Genomic DNA Translation: EAX10601.1 CH471133 Genomic DNA Translation: EAX10602.1 BC109075 mRNA Translation: AAI09076.1 BC109076 mRNA Translation: AAI09077.1 |
CCDSi | CCDS33435.1 |
PIRi | A45991 |
RefSeqi | NP_003236.3, NM_003245.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1L9M | X-ray | 2.10 | A/B | 2-693 | [»] | |
1L9N | X-ray | 2.10 | A/B | 2-693 | [»] | |
1NUD | X-ray | 2.70 | A/B | 2-693 | [»] | |
1NUF | X-ray | 2.70 | A | 2-693 | [»] | |
1NUG | X-ray | 2.40 | A/B | 2-693 | [»] | |
SMRi | Q08188 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112911, 123 interactors |
IntActi | Q08188, 26 interactors |
MINTi | Q08188 |
STRINGi | 9606.ENSP00000370867 |
Chemistry databases
BindingDBi | Q08188 |
ChEMBLi | CHEMBL3363 |
DrugBanki | DB01864, 5'-Guanosine-Diphosphate-Monothiophosphate DB03152, B-2-Octylglucoside DB04315, Guanosine-5'-Diphosphate DB01972, Guanosine-5'-Monophosphate DB00130, L-Glutamine |
PTM databases
GlyGeni | Q08188, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q08188 |
PhosphoSitePlusi | Q08188 |
Genetic variation databases
BioMutai | TGM3 |
DMDMi | 257051080 |
Proteomic databases
EPDi | Q08188 |
jPOSTi | Q08188 |
MassIVEi | Q08188 |
MaxQBi | Q08188 |
PaxDbi | Q08188 |
PeptideAtlasi | Q08188 |
PRIDEi | Q08188 |
ProteomicsDBi | 58578 |
TopDownProteomicsi | Q08188 |
Protocols and materials databases
Antibodypediai | 1375, 311 antibodies from 30 providers |
DNASUi | 7053 |
Genome annotation databases
Ensembli | ENST00000381458; ENSP00000370867; ENSG00000125780 |
GeneIDi | 7053 |
KEGGi | hsa:7053 |
MANE-Selecti | ENST00000381458.6; ENSP00000370867.5; NM_003245.4; NP_003236.3 |
UCSCi | uc002wfx.5, human |
Organism-specific databases
CTDi | 7053 |
DisGeNETi | 7053 |
GeneCardsi | TGM3 |
HGNCi | HGNC:11779, TGM3 |
HPAi | ENSG00000125780, Tissue enriched (esophagus) |
MalaCardsi | TGM3 |
MIMi | 600238, gene 617251, phenotype |
neXtProti | NX_Q08188 |
OpenTargetsi | ENSG00000125780 |
Orphaneti | 1410, Uncombable hair syndrome |
PharmGKBi | PA36492 |
VEuPathDBi | HostDB:ENSG00000125780 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QUPB, Eukaryota |
GeneTreei | ENSGT01040000240478 |
HOGENOMi | CLU_013435_1_0_1 |
InParanoidi | Q08188 |
OMAi | SMVGWNF |
OrthoDBi | 297055at2759 |
PhylomeDBi | Q08188 |
TreeFami | TF324278 |
Enzyme and pathway databases
BRENDAi | 2.3.2.13, 2681 |
PathwayCommonsi | Q08188 |
SignaLinki | Q08188 |
Miscellaneous databases
BioGRID-ORCSi | 7053, 3 hits in 1035 CRISPR screens |
ChiTaRSi | TGM3, human |
EvolutionaryTracei | Q08188 |
GeneWikii | TGM3 |
GenomeRNAii | 7053 |
Pharosi | Q08188, Tchem |
PROi | PR:Q08188 |
RNActi | Q08188, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000125780, Expressed in lower esophagus mucosa and 126 other tissues |
Genevisiblei | Q08188, HS |
Family and domain databases
Gene3Di | 2.60.40.10, 3 hits 3.90.260.10, 1 hit |
InterProi | View protein in InterPro IPR013783, Ig-like_fold IPR014756, Ig_E-set IPR038765, Papain-like_cys_pep_sf IPR002931, Transglutaminase-like IPR036985, Transglutaminase-like_sf IPR023608, Transglutaminase_animal IPR013808, Transglutaminase_AS IPR008958, Transglutaminase_C IPR036238, Transglutaminase_C_sf IPR001102, Transglutaminase_N |
Pfami | View protein in Pfam PF00927, Transglut_C, 2 hits PF01841, Transglut_core, 1 hit PF00868, Transglut_N, 1 hit |
PIRSFi | PIRSF000459, TGM_EBP42, 1 hit |
SMARTi | View protein in SMART SM00460, TGc, 1 hit |
SUPFAMi | SSF49309, SSF49309, 2 hits SSF54001, SSF54001, 1 hit SSF81296, SSF81296, 1 hit |
PROSITEi | View protein in PROSITE PS00547, TRANSGLUTAMINASES, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TGM3_HUMAN | |
Accessioni | Q08188Primary (citable) accession number: Q08188 Secondary accession number(s): A8K5N6 Q32MM0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | September 1, 2009 | |
Last modified: | February 23, 2022 | |
This is version 203 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families