PROSITE documentation PDOC00377

Thyroglobulin type-1 domain signature and profile

Thyroglobulin (Tg) is a large glycoprotein specific to the thyroid gland and it is the precursor of the iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3). The N-terminal section of Tg contains 11 repeats of a domain of about 70 amino acids which is known as the Tg type-1 repeat [1,2,3]. Such a domain has also been found (as a single or repeated sequence) in the proteins listed below:

• In the HLA class II associated invariant chain [3]. In that protein the type-1 repeat is encoded by an exon which is alternatively spliced and is only present in a longer form of the protein.
• In human pancreatic carcinoma marker proteins GA733-1 and GA733-2 (which is also known as epithelial cell surface antigen (EPG) or adenocarcinoma- associated antigen (KSA) or antigen KS 1/4). These proteins may function as growth factor receptors [4].
• In nidogen (entactin), a sulfated glycoprotein which is widely distributed in basement membranes and that is tightly associated with laminin. Nidogen probably has a role in cell-extracellular matrix interactions.
• In the insulin-like growth factor binding proteins (IGFBP) [5] (see <PDOC00194>).
• In saxiphilin, a transferrin-like protein from frog that binds specifically to the neurotoxin saxitoxin [6].
• In equistatin, a thiol-protease inhibitor from sea anemone [7].

The domain contains six cysteines (Tg type-1a) involved in 3 disulfide bonds (see <PDB:1ZT3>) [5], but also exists in a variant that lacks the third and fourth cysteines (Tg type-1b). One Gln residue is strongly conserved. Schematic representations of the two Tg type-1 domains are shown below:

 Tg type-1a:
            +-------------------+          +------+ +--------------------+
            |                   |          |      | |                    |
         xxxCxxxxxxxxxxxxxxxxxxxCxxxxxxxxxQCxxxxxxCxCxxxxxxxxxxxxxxxxxxxxC
                            *******************************
 Tg type-1b:
            +-------------------+                   +--------------------+
            |                   |                   |                    |
         xxxCxxxxxxxxxxxxxxxxxxxCxxxxxxxxxQxxxxxxxxxCxxxxxxxxxxxxxxxxxxxxC
                            *******************************

'C': Conserved cysteine involved in a disulfide bond.
'*': Position of the consensus pattern in the domain.

The central part of the domain is well conserved, we have used this region as a signature pattern for Tg type-1 domains. We also developed a profile which covers the entire Tg type-1 domain.