{PDOC00377}
{PS00484; THYROGLOBULIN_1_1}
{PS51162; THYROGLOBULIN_1_2}
{BEGIN}
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* 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 [1-3].
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.

-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.

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

-Expert(s) to contact by email:
           Molina F.; fmolina@cryst.bioc.cam.ac.uk

-Last update: November 2005 / Text revised; profile added.

[ 1] Malthiery Y., Lissitzky S.
     "Primary structure of human thyroglobulin deduced from the sequence of
     its 8448-base complementary DNA."
     Eur. J. Biochem. 165:491-498(1987).
     PubMed=3595599
[ 2] Molina F., Bouanani M., Pau B., Granier C.
     "Characterization of the type-1 repeat from thyroglobulin, a
     cysteine-rich module found in proteins from different families."
     Eur. J. Biochem. 240:125-133(1996).
     PubMed=8797845
[ 3] Guncar G., Pungercic G., Klemencic I., Turk V., Turk D.
     "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."
     EMBO J. 18:793-803(1999).
     PubMed=10022822; DOI=10.1093/emboj/18.4.793
[ 4] Szala S., Froehlich M., Scollon M., Kasai Y., Steplewski Z.,
     Koprowski H., Linnenbach A.J.
     "Molecular cloning of cDNA for the carcinoma-associated antigen
     GA733-2."
     Proc. Natl. Acad. Sci. U.S.A. 87:3542-3546(1990).
     PubMed=2333300
[ 5] 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.
     "Structure and properties of the C-terminal domain of insulin-like
     growth factor-binding protein-1 isolated from human amniotic fluid."
     J. Biol. Chem. 280:29812-29819(2005).
     PubMed=15972819; DOI=10.1074/jbc.M504304200
[ 6] Morabito M.A., Moczydlowski E.
     "Molecular cloning of bullfrog saxiphilin: a unique relative of the
     transferrin family that binds saxitoxin."
     Proc. Natl. Acad. Sci. U.S.A. 91:2478-2482(1994).
     PubMed=8146142
[ 7] Lenarcic B., Ritonja A., Strukelj B., Turk B., Turk V.
     "Equistatin, a new inhibitor of cysteine proteinases from Actinia
     equina, is structurally related to thyroglobulin type-1 domain."
     J. Biol. Chem. 272:13899-13903(1997).
     PubMed=9153250

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