Summary: HIUase/Transthyretin family
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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 . HIUases are distinguished in the alignment from the conserved C-terminal YRGS sequence.
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
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
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
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
Internal database links
|Similarity to PfamA using HHSearch:||TTR-52 MG1 CarboxypepD_reg SdrD_B|
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].
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This clan unifies several SCOP superfamilies that all share a 7 stranded beta sandwich fold.
The clan contains the following 19 members:CarbopepD_reg_2 CarboxypepD_reg Cna_B Dioxygenase_C DUF1416 DUF2012 DUF2606 DUF3823 DUF3869 FctA fn3_3 GramPos_pilinBB GramPos_pilinD3 MetallophosN PEGA phage_tail_N SdrD_B Transthyretin TTR-52
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Curation and family details
|Seed source:||Bateman A|
|Author:||Bateman A, Percudani R|
|Number in seed:||386|
|Number in full:||1955|
|Average length of the domain:||112.90 aa|
|Average identity of full alignment:||38 %|
|Average coverage of the sequence by the domain:||77.65 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||20|
|Download:||download the raw HMM for this family|
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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 735 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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