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439  structures 1506  species 1  interaction 1803  sequences 7  architectures

Family: Transthyretin (PF00576)

Summary: HIUase/Transthyretin family

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The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

HIUase/Transthyretin family Provide feedback

This family includes transthyretin that is a thyroid hormone-binding protein that transports thyroxine from the bloodstream to the brain. However, most of the sequences listed in this family do not bind thyroid hormones. They are actually enzymes of the purine catabolism that catalyse the conversion of 5-hydroxyisourate (HIU) to OHCU [2,3]. HIU hydrolysis is the original function of the family and is conserved from bacteria to mammals; transthyretins arose by gene duplications in the vertebrate lineage [4]. HIUases are distinguished in the alignment from the conserved C-terminal YRGS sequence.

Literature references

  1. Hamilton JA, Steinrauf LK, Braden BC, Liepnieks J, Benson MD, Holmgren G, Sandgren O, Steen L; , J Biol Chem 1993;268:2416-2424.: The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution. PUBMED:8428915 EPMC:8428915

  2. Ramazzina I, Folli C, Secchi A, Berni R, Percudani R; , Nat Chem Biol. 2006;2:144-148.: Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes. PUBMED:16462750 EPMC:16462750

  3. Lee Y, Lee DH, Kho CW, Lee AY, Jang M, Cho S, Lee CH, Lee JS, Myung PK, Park BC, Park SG; , FEBS Lett. 2005;579:4769-4774.: Transthyretin-related proteins function to facilitate the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction. PUBMED:16098976 EPMC:16098976

  4. Zanotti G, Cendron L, Ramazzina I, Folli C, Percudani R, Berni R; , J Mol Biol. 2006;363:1-9.: Structure of zebra fish HIUase: insights into evolution of an enzyme to a hormone transporter. PUBMED:16952372 EPMC:16952372


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR023416

This family includes transthyretin that is a thyroid hormone-binding protein that transports thyroxine from the bloodstream to the brain. However, most of the sequences listed in this family do not bind thyroid hormones. They are actually enzymes of the purine catabolism that catalyse the conversion of 5-hydroxyisourate (HIU) to OHCU [PUBMED:16098976, PUBMED:16462750]. HIU hydrolysis is the original function of the family and is conserved from bacteria to mammals; transthyretins arose by gene duplications in the vertebrate lineage [PUBMED:16952372, PUBMED:8428915]. HIUases are distinguished in the alignment from the conserved C-terminal YRGS sequence.

Transthyretin (formerly prealbumin) is one of 3 thyroid hormone-binding proteins found in the blood of vertebrates [PUBMED:1833190]. It is produced in the liver and circulates in the bloodstream, where it binds retinol and thyroxine (T4) [PUBMED:4054629]. It differs from the other 2 hormone-binding proteins (T4-binding globulin and albumin) in 3 distinct ways: (1) the gene is expressed at a high rate in the brain choroid plexus; (2) it is enriched in cerebrospinal fluid; and (3) no genetically caused absence has been observed, suggesting an essential role in brain function, distinct from that played in the bloodstream [PUBMED:1833190]. The protein consists of around 130 amino acids, which assemble as a homotetramer that contains an internal channel in which T4 is bound. Within this complex, T4 appears to be transported across the blood-brain barrier, where, in the choroid plexus, the hormone stimulates further synthesis of transthyretin. The protein then diffuses back into the bloodstream, where it binds T4 for transport back to the brain [PUBMED:1833190].

Domain organisation

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

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Pfam Clan

This family is a member of clan Transthyretin (CL0287), which contains the following 13 members:

CarboxypepD_reg Cna_B Dioxygenase_C DUF1416 DUF2012 DUF2606 DUF3823 DUF4480 FctA fn3_3 PEGA phage_tail_N Transthyretin

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...

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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
(26)
Full
(1803)
Representative proteomes NCBI
(1303)
Meta
(706)
RP15
(132)
RP35
(273)
RP55
(418)
RP75
(545)
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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
(26)
Full
(1803)
Representative proteomes NCBI
(1303)
Meta
(706)
RP15
(132)
RP35
(273)
RP55
(418)
RP75
(545)
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
(26)
Full
(1803)
Representative proteomes NCBI
(1303)
Meta
(706)
RP15
(132)
RP35
(273)
RP55
(418)
RP75
(545)
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: Bateman A
Previous IDs: none
Type: Domain
Author: Bateman A, Percudani R
Number in seed: 26
Number in full: 1803
Average length of the domain: 109.50 aa
Average identity of full alignment: 40 %
Average coverage of the sequence by the domain: 82.21 %

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 25.3 25.3
Trusted cut-off 25.3 25.8
Noise cut-off 24.7 25.0
Model length: 112
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

Transthyretin

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 Transthyretin domain has been found. There are 439 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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