Home | Contact

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.

Molina F.

November 2005 / Text revised; profile added.

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

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

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Domain architecture view of Swiss-Prot proteins matching PS51162 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS51162 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS51162 • Scan Swiss-Prot/TrEMBL entries against PS51162 • view ligand binding statistics

Matching PDB structures: 1ICF 1L3H 1RMJ 1ZT3 ... [ALL]

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

Consensus pattern: [FYWHPVAS]-x(3)-C-x(3,4)-[SG]-x-[FYW]-x(3)-Q-x(5,12)-[FYW]-C-[VA]-x(3,4)-[SG] Sequences known to belong to this class detected by the pattern: ALL, except for 2 IGFBP-1 and -3 from mouse (where the conserved Gln is mutated to an Arg or Glu) and the third and eighth repeats from thyroglobulin because of big insertions Other sequence(s) detected in Swiss-Prot: NONE.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS00484 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS00484 • Scan Swiss-Prot/TrEMBL entries against PS00484 • view ligand binding statistics

Matching PDB structures: 1ICF 1L3H 1RMJ 1ZT3 ... [ALL]

1	Authors	Malthiery Y., Lissitzky S.
	Title	Primary structure of human thyroglobulin deduced from the sequence of its 8448-base complementary DNA.
	Source	Eur. J. Biochem. 165:491-498(1987).
	PubMed ID	3595599

2	Authors	Molina F., Bouanani M., Pau B., Granier C.
	Title	Characterization of the type-1 repeat from thyroglobulin, a cysteine-rich module found in proteins from different families.
	Source	Eur. J. Biochem. 240:125-133(1996).
	PubMed ID	8797845

3	Authors	Guncar G., Pungercic G., Klemencic I., Turk V., Turk D.
	Title	Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S.
	Source	EMBO J. 18:793-803(1999).
	PubMed ID	10022822
	DOI	10.1093/emboj/18.4.793

4	Authors	Szala S., Froehlich M., Scollon M., Kasai Y., Steplewski Z., Koprowski H., Linnenbach A.J.
	Title	Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2.
	Source	Proc. Natl. Acad. Sci. U.S.A. 87:3542-3546(1990).
	PubMed ID	2333300

5	Authors	Sala 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.
	Title	Structure and properties of the C-terminal domain of insulin-like growth factor-binding protein-1 isolated from human amniotic fluid.
	Source	J. Biol. Chem. 280:29812-29819(2005).
	PubMed ID	15972819
	DOI	10.1074/jbc.M504304200

6	Authors	Morabito M.A., Moczydlowski E.
	Title	Molecular cloning of bullfrog saxiphilin: a unique relative of the transferrin family that binds saxitoxin.
	Source	Proc. Natl. Acad. Sci. U.S.A. 91:2478-2482(1994).
	PubMed ID	8146142

7	Authors	Lenarcic B., Ritonja A., Strukelj B., Turk B., Turk V.
	Title	Equistatin, a new inhibitor of cysteine proteinases from Actinia equina, is structurally related to thyroglobulin type-1 domain.
	Source	J. Biol. Chem. 272:13899-13903(1997).
	PubMed ID	9153250

PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to

Prosite License or see: prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)

SIB Swiss Institute of Bioinformatics | Disclaimer