PROSITE documentation PDOC00377 [for PROSITE entry PS51162]

Thyroglobulin type-1 domain signature and profile




Description

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.

Expert(s) to contact by email:

Molina F.

Last update:

November 2005 / Text revised; profile added.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

THYROGLOBULIN_1_2, PS51162; Thyroglobulin type-1 domain profile  (MATRIX)

THYROGLOBULIN_1_1, PS00484; Thyroglobulin type-1 repeat signature  (PATTERN)


References

1AuthorsMalthiery Y., Lissitzky S.
TitlePrimary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA.
SourceEur. J. Biochem. 165:491-498(1987).
PubMed ID3595599

2AuthorsMolina F., Bouanani M., Pau B., Granier C.
TitleCharacterization of the type-1 repeat from thyroglobulin, a cysteine-rich module found in proteins from different families.
SourceEur. J. Biochem. 240:125-133(1996).
PubMed ID8797845

3AuthorsGuncar G., Pungercic G., Klemencic I., Turk V., Turk D.
TitleCrystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S.
SourceEMBO J. 18:793-803(1999).
PubMed ID10022822
DOI10.1093/emboj/18.4.793

4AuthorsSzala S., Froehlich M., Scollon M., Kasai Y., Steplewski Z., Koprowski H., Linnenbach A.J.
TitleMolecular cloning of cDNA for the carcinoma-associated antigen GA733-2.
SourceProc. Natl. Acad. Sci. U.S.A. 87:3542-3546(1990).
PubMed ID2333300

5AuthorsSala A., Capaldi S., Campagnoli M., Faggion B., Labo S., Perduca M., Romano A., Carrizo M.E., Valli M., Visai L., Minchiotti L., Galliano M., Monaco H.L.
TitleStructure and properties of the C-terminal domain of insulin-like growth factor-binding protein-1 isolated from human amniotic fluid.
SourceJ. Biol. Chem. 280:29812-29819(2005).
PubMed ID15972819
DOI10.1074/jbc.M504304200

6AuthorsMorabito M.A., Moczydlowski E.
TitleMolecular cloning of bullfrog saxiphilin: a unique relative of the transferrin family that binds saxitoxin.
SourceProc. Natl. Acad. Sci. U.S.A. 91:2478-2482(1994).
PubMed ID8146142

7AuthorsLenarcic B., Ritonja A., Strukelj B., Turk B., Turk V.
TitleEquistatin, a new inhibitor of cysteine proteinases from Actinia equina, is structurally related to thyroglobulin type-1 domain.
SourceJ. Biol. Chem. 272:13899-13903(1997).
PubMed ID9153250



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