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10  structures 191  species 2  interactions 2274  sequences 161  architectures

Family: Thyroglobulin_1 (PF00086)

Summary: Thyroglobulin type-1 repeat

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Thyroglobulin domain". More...

Thyroglobulin domain Edit Wikipedia article

Thyroglobulin type-1 repeat
Protein CD74 PDB 1icf.png
Thyroglobulin type-1 domain
Identifiers
Symbol Thyroglobulin_1
Pfam PF00086
InterPro IPR000716
PROSITE PDOC00377
SCOP 1icf
SUPERFAMILY 1icf
CDD cd00191

Thyroglobulin type-1 repeat is an evolutionary conserved protein domain. Thyroglobulin type 1 repeats are thought to be involved in the control of proteolytic degradation. The domain usually contains six conserved cysteines. These form three disulphide bridges. Cysteines 1 pairs with 2, 3 with 4 and 5 with 6.

[edit] Human proteins containing this domain

CD74; IGFBP-4; IGFBP1; IGFBP2; IGFBP3; IGFBP4; IGFBP5; IGFBP6; NID1; NID2; SMOC1; SMOC2; SPOCK1; SPOCK2; SPOCK3; TACSTD1; TACSTD2; TG;

[edit] References


This article incorporates text from the public domain Pfam and InterPro IPR000519

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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Thyroglobulin type 1 repeats are thought to be involved in the control of proteolytic degradation [2]. The domain usually contains six conserved cysteines. These form three disulphide bridges. Cysteines 1 pairs with 2, 3 with 4 and 5 with 6.

Literature references

  1. Guncar G, Pungercic G, Klemencic I, Turk V, Turk D; , EMBO J 1999;18:793-803.: 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. PUBMED:10022822 EPMC:10022822

  2. Molina F, Bouanani M, Pau B, Granier C; , Eur J Biochem 1996;240:125-133.: Characterization of the type-1 repeat from thyroglobulin, a cysteine- rich module found in proteins from different families. PUBMED:8797845 EPMC:8797845


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000716

Thyroglobulin (Tg) is a large glycoprotein specific to the thyroid gland and is the precursor of the iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3). The N-terminal section of Tg contains 10 repeats of a domain of about 65 amino acids which is known as the Tg type-1 repeat [PUBMED:3595599, PUBMED:8797845]. Such a domain has also been found as a single or repeated sequence in the HLA class II associated invariant chain [PUBMED:3038530]; human pancreatic carcinoma marker proteins GA733-1 and GA733-2 [PUBMED:2333300]; nidogen (entactin), a sulphated glycoprotein which is widely distributed in basement membranes and that is tightly associated with laminin; insulin-like growth factor binding proteins (IGFBP) [PUBMED:1709161]; saxiphilin, a transferrin-like protein from Rana catesbeiana (Bull frog) that binds specifically to the neurotoxin saxitoxin [PUBMED:8146142]; chum salmon egg cysteine proteinase inhibitor, and equistatin, a thiol-protease inhibitor from Actinia equina (sea anemone) [PUBMED:9153250]. The existence of Thyr-1 domains in such a wide variety of proteins raises questions about their activity and function, and their interactions with neighbouring domains. The Thyr-1 and related domains belong to MEROPS proteinase inhibitor family I31, clan IX.

Equistatin from A. equina is composed of three Thyr-1 domains; as with other proteins that contains Thyr-1 domains, the thyropins, they bind reversibly and tightly to cysteine proteases (inhibitor family C1). In equistatin inhibition of papain is a function of domain-1. Unusually domain-2 inhibits cathepsin D, an aspartic protease (inhibitor family A1) and has no activity against papain. Domain-3, does not inhibit either papain or cathepsin D, and its function or its target peptidase has yet to be determined [PUBMED:9153250, PUBMED:12650938].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(20)
Full
(2274)
Representative proteomes NCBI
(2134)
Meta
(3)
RP15
(270)
RP35
(360)
RP55
(665)
RP75
(1102)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(20)
Full
(2274)
Representative proteomes NCBI
(2134)
Meta
(3)
RP15
(270)
RP35
(360)
RP55
(665)
RP75
(1102)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(20)
Full
(2274)
Representative proteomes NCBI
(2134)
Meta
(3)
RP15
(270)
RP35
(360)
RP55
(665)
RP75
(1102)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Swissprot_feature_table
Previous IDs: thyroglobulin_1;
Type: Domain
Author: Bateman A, Sonnhammer ELL
Number in seed: 20
Number in full: 2274
Average length of the domain: 67.10 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 20.34 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 21.3 20.6
Noise cut-off 20.4 20.5
Model length: 68
Family (HMM) version: 13
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

Insulin IGFBP

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Thyroglobulin_1 domain has been found. There are 10 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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