TGM3

Transglutaminases are enzymes that catalyze the crosslinking of proteins by epsilon-gamma glutamyl lysine isopeptide bonds. While the primary structure of transglutaminases is not conserved, they all have the same amino acid sequence at their active sites and their activity is calcium-dependent. TGM3 consists of two polypeptide chains activated from a single precursor protein by proteolysis. TGM3 is involved the later stages of cell envelope formation in the epidermis and hair follicle.

Full Name

Transglutaminase 3

Function

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.

Biological Process

Biological Process cell envelope organizationSource:UniProtKB1 Publication
Biological Process hair follicle morphogenesisSource:UniProtKB1 Publication
Biological Process keratinizationSource:UniProtKB-KW
Biological Process keratinocyte differentiationSource:UniProtKB1 Publication
Biological Process peptide cross-linkingSource:UniProtKB2 Publications
Biological Process protein modification processSource:UniProtKB1 Publication

Cellular Location

Cytoplasm

Involvement in disease

Uncombable hair syndrome 2 (UHS2):
A form of uncombable hair syndrome, a condition characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair. Most individuals are affected early in childhood and the hair takes on a spun-glass appearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. The hair growth rate can range from slow to normal, and the condition improves with age.

PTM

Activated by proteolytic processing. In vitro activation is commonly achieved by cleavage with dispase, a neutral bacterial protease. Dispase cleavage site was proposed to lie between Ser-470 and Ser-471 (PubMed:8099584) or between Pro-465 and Phe-466 (PubMed:16565075).
Physiological activation may be catalyzed by CTSL and, to a lesser extent, by CTSS, but not by CTSB, CTSD nor CTSV (PubMed:16565075).