Protein-glutamine gamma-glutamyltransferase E (TGM3)
The protein contains 693 amino acids for an estimated molecular weight of 76632 Da.
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. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs214803 | |
| dbSNP:rs6048066 | |
| dbSNP:rs214814 | |
| dbSNP:rs1042617 | |
| dbSNP:rs214830 | |
| dbSNP:rs45581032 |
Biological Process
Cell envelope organization
Cellular protein modification process
Hair follicle morphogenesis
Keratinization
Keratinocyte differentiation
Peptide cross-linking
Protein tetramerization
The reference OMIM entry for this protein is 600238
Transglutaminase 3; tgm3
Transglutaminase e; tge
DESCRIPTION
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 ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for TGM3
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600238 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed