The transthyretin‐related protein family

Eneqvist, Therese; Lundberg, Erik; Nilsson, Lars Göran; Abagyan, Ruben; Sauer‐Eriksson, A. Elisabeth

doi:10.1046/j.1432-1033.2003.03408.x

Cited by 72 publications

(101 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In lamprey, one TTR was recently cloned from two species, P. marinus and L. appendix (Manzon et al, 2007), and expression correlated with metamorphosis. This suggests a deeper ancestry for TTR than previously thought (Eneqvist et al, 2003). In amphioxus and in Ciona, virtually nothing is known about TH transport.…”

Section: Th and Th Derivative Transport In Chordatesmentioning

confidence: 80%

The history of a developmental stage: Metamorphosis in chordates

Paris

Laudet

2008

Genesis

View full text Add to dashboard Cite

Summary: Metamorphosis displays a striking diversity in chordates, a deuterostome phylum that comprises vertebrates, urochordates (tunicates), and cephalochordates (amphioxus). In anuran amphibians, the tadpole loses its tail, develops limbs, and undergoes profound changes at the behavioral, physiological, biochemical, and ecological levels. In ascidian tunicates, the tail is lost and the head tissues are drastically remodeled into the adult animal, whereas in amphioxus, the highly asymmetric larva transforms into a relatively symmetric adult. This wide diversity has led to the proposal that metamorphosis evolved several times independently in the different chordate lineages during evolution. However, the molecular mechanisms involved in metamorphosis are largely unknown outside amphibians and teleost fishes, in which metamorphosis is regulated by the thyroid hormones (TH) T 3 and T 4 binding to their receptors (thyroid hormone receptors). In this review, we compare metamorphosis in chordates and then propose a unifying definition of the larva-to-adult transition, based on the conservation of the role of THs and some of their derivatives as the main regulators of metamorphosis. According to this definition, all chordates (if not, all deuterostomes) have a homologous metamorphosis stage during their postembryonic development. The intensity and the nature of the morphological remodeling varies extensively among taxa, from drastic remodeling like in some ascidians or amphibians to more subtle events, as in mammals. genesis 46:657-672,

show abstract

Section: Th and Th Derivative Transport In Chordatesmentioning

confidence: 80%

The history of a developmental stage: Metamorphosis in chordates

Paris

Laudet

2008

Genesis

View full text Add to dashboard Cite

show abstract

“…Overall, PucM and TTR share many structural features, but their different chemical identities and the size of the active site resulting from the sequence differences sharply distinguish the functions of these two structural homologs. Previous phylogenetic analysis has suggested that TRPs and TTRs belong to separate branches, and that TRP, an ancestor of TTR, has been conserved whereas TTR has evolved independently in vertebrates (12).…”

Section: Discussionmentioning

confidence: 99%

“…PucM from B. subtilis consists of 121 aa and shows 55% sequence similarity with a functionally unrelated protein, transthyretin (TTR), a thyroid hormone-binding protein in vertebrates (12,13). Because of these sequence similarities, PucM has been classified as a member of the TTR-related protein (TRP) family.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Structural and functional analysis of PucM, a hydrolase in the ureide pathway and a member of the transthyretin-related protein family

Jung

Lee

Park

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The ureide pathway, which produces ureides from uric acid, is an essential purine catabolic process for storing and transporting the nitrogen fixed in leguminous plants and some bacteria. PucM from Bacillus subtilis was recently characterized and found to catalyze the second reaction of the pathway, hydrolyzing 5-hydroxyisourate (HIU), a product of uricase in the first step. PucM has 121 amino acid residues and shows high sequence similarity to the functionally unrelated protein transthyretin (TTR), a thyroid hormone-binding protein. Therefore, PucM belongs to the TTRrelated proteins (TRP) family. The crystal structures of PucM at 2.0 Å and its complexes with the substrate analogs 8-azaxanthine and 5,6-diaminouracil reveal that even with their overall structure similarity, homotetrameric PucM and TTR are completely different, both in their electrostatic potential and in the size of the active sites located at the dimeric interface. Nevertheless, the absolutely conserved residues across the TRP family, including His-14, Arg-49, His-105, and the C-terminal Tyr-118 -Arg-119 -Gly-120 -Ser-121, indeed form the active site of PucM. Based on the results of sitedirected mutagenesis of these residues, we propose a possible mechanism for HIU hydrolysis. The PucM structure determined for the TRP family leads to the conclusion that diverse members of the TRP family would function similarly to PucM as HIU hydrolase.5-hydroxyisourate hydrolase ͉ Bacillus subtilis ͉ purine catabolism T he purine de novo biosynthesis is the universal, central metabolic process in all organisms. The pathway begins with glutamine and phosphoribosylpyrophosphate and proceeds through multiple sequential enzymatic steps to the end product inosine monophosphate, which is subsequently used as the precursor for the biosynthesis of other purine nucleotides (1, 2). Some bacteria use the nitrogen in purine bases as an energy source under nitrogen-limited conditions. Therefore, the catabolic pathway degrading purine nucleotides has been proposed to be an essential metabolic process (reviewed in refs. 3 and 4). Uric acid, a major intermediate of purine catabolism, can be excreted or subjected to further degradation, depending on the presence of unique enzyme systems in different organisms. Sequential enzymatic reactions using uric acid as a substrate result in ureides, including allantoin and allantoate (Scheme 1) (1,3,4). This ureide pathway plays a vital role in transporting and storing the nitrogen fixed in leguminous plants in the form of ureides, which have a relatively high N-to-C ratio of 1.0. Moreover, symbiotic N 2 -fixing bacteria actively supply the available nitrogen, which is in turn assimilated into glutamine, a substrate in the first step of purine biosynthesis. In the ureide pathway, the conversion of uric acid into allantoin was initially thought to involve a single step catalyzed by urate oxidase (E.C. 1.7.3.3; uricase), but recent investigations have revealed that this pathway includes two additional, distinct, chemically labile intermedi...

show abstract

“…HIU hydrolase is a member of the transthyretin-related protein (TRP) family, which displays high sequence conservation throughout evolution (9). Current evidence suggests that TRP family members act as HIU hydrolases in bacteria and that the product of the Urah gene performs this biochemical function in mice (1,10,11), catalyzing the second of three steps in the conversion of uric acid to allantoin (Fig.…”

Section: Platelet 2 An Enu-induced Mutation Causing Thrombocytosis Andmentioning

confidence: 99%

Deficiency of 5-hydroxyisourate hydrolase causes hepatomegaly and hepatocellular carcinoma in mice

Stevenson

Hyland²,

Zhang³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

With the notable exception of humans, uric acid is degraded to (S)-allantoin in a biochemical pathway catalyzed by urate oxidase, 5-hydroxyisourate (HIU) hydrolase, and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase in most vertebrate species. A point mutation in the gene encoding mouse HIU hydrolase, Urah, that perturbed uric acid metabolism within the liver was discovered during a mutagenesis screen in mice. The predicted substitution of cysteine for tyrosine in a conserved helical region of the mutantencoded HIU hydrolase resulted in undetectable protein expression. Mice homozygous for this mutation developed elevated platelet counts secondary to excess thrombopoietin production and hepatomegaly. The majority of homozygous mutant mice also developed hepatocellular carcinoma, and tumor development was accelerated by exposure to radiation. The development of hepatomegaly and liver tumors in mice lacking Urah suggests that uric acid metabolites may be toxic and that urate oxidase activity without HIU hydrolase function may affect liver growth and transformation. The absence of HIU hydrolase in humans predicts slowed metabolism of HIU after clinical administration of exogenous urate oxidase in conditions of uric acid-related pathology. The data suggest that prolonged urate oxidase therapy should be combined with careful assessment of toxicity associated with extrahepatic production of uric acid metabolites.N-ethyl-N-nitrosourea mutagenesis | uric acid | 5-hydroxyisourate hydrolase | hepatocellular carcinoma | thrombopoietin U ric acid is the product of purine metabolism. In most mammals, uric acid, or urate, the form that predominates in vivo, is further metabolized to (S)-allantoin (1, 2). In humans and some higher primates, the urate oxidase gene is dysfunctional because of the introduction of premature stop codons during recent evolution (3). A nonfunctional urate oxidase enzyme causes a relative excess of uric acid in humans compared with most other vertebrate species. Because uric acid is relatively insoluble, humans are susceptible to diseases resulting from precipitation of uric acid such as gout and kidney stones as well as urate nephropathy associated with the tumor lysis syndrome. Chronic hyperuricemia in humans has also been linked to the development of cardiovascular disease and hypertension (4, 5).It is unclear why humans have evolved this block in uric acid metabolism during evolution, but suggested theoretical advantages of increased levels of circulating uric acid include its role as a potent antioxidant offering protection from cancer and aging (6) and its potential function in maintenance of adequate blood pressure during periods of low salt intake (7).The components of the full metabolic pathway that converts urate to allantoin in lower mammals have only recently been identified (1). Although it was originally thought that urate oxidase was the sole enzymatic component of this pathway, recent studies have established that conversion of uric acid to allantoin occurs by sequential ch...

show abstract

The transthyretin‐related protein family

Cited by 72 publications

References 59 publications

The history of a developmental stage: Metamorphosis in chordates

The history of a developmental stage: Metamorphosis in chordates

Structural and functional analysis of PucM, a hydrolase in the ureide pathway and a member of the transthyretin-related protein family

Deficiency of 5-hydroxyisourate hydrolase causes hepatomegaly and hepatocellular carcinoma in mice

Contact Info

Product

Resources

About