Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure

Gough, Julian; Karplus, Kevin; Hughey, Richard; Chothia, Cyrus

doi:10.1006/jmbi.2001.5080

Cited by 1,106 publications

(958 citation statements)

References 27 publications

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“…Hence, identifying the presence of various domains can provide clues to novel functions of RBPs. We annotated the RBP catalogue with existing Pfam [20] and Superfamily [21] definitions (Materials and Methods, Supplementary Table 1). Depending on the type of domain associated with an RBP and definitions provided by Castello et al [1], we categorized these proteins into "classical" and "non-classical".…”

Section: Resultsmentioning

confidence: 99%

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The human RBPome: From genes and proteins to human disease

Neelamraju

Hashemikhabir

Janga

2015

Journal of Proteomics

114

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Section: Resultsmentioning

confidence: 99%

“…The superfamily annotations were obtained from the Superfamily database [21]. Domains in RBPs were categorized as classical and non-classical based on the definitions proposed by Castello et.…”

Section: Annotation Of Domains For Human Proteinsmentioning

confidence: 99%

The human RBPome: From genes and proteins to human disease

Neelamraju

Hashemikhabir

Janga

2015

Journal of Proteomics

114

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“…The T. gondii genome possesses over 50 proteins that contain ab-hydrolase domains. Using Hidden Markov Models (HMM) (Gough et al, 2001), 20 of these can be grouped into families that are potentially relevant for APT activity (Kemp et al, 2013). Three candidates exhibit the most significant homology to TgPPT1 and present across the Apicomplexa phylum and were investigated further.…”

Section: Enzymes Implicated In Protein Depalmitoylationmentioning

confidence: 99%

Emerging roles for protein S-palmitoylation in Toxoplasma biology

Frénal

Kemp

Soldati‐Favre

2014

International Journal for Parasitology

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a b s t r a c tPost-translational modifications are refined, rapidly responsive and powerful ways to modulate protein function. Among post-translational modifications, acylation is now emerging as a widespread modification exploited by eukaryotes, bacteria and viruses to control biological processes. Protein palmitoylation involves the attachment of palmitic acid, also known as hexadecanoic acid, to cysteine residues of integral and peripheral membrane proteins and increases their affinity for membranes. Importantly, similar to phosphorylation, palmitoylation is reversible and is becoming recognised as instrumental for the regulation of protein function by modulating protein interactions, stability, folding, trafficking and signalling. Palmitoylation appears to play a central role in the biology of the Apicomplexa, regulating critical processes such as host cell invasion which is vital for parasite survival and dissemination. The recent identification of over 400 palmitoylated proteins in Plasmodium falciparum erythrocytic stages illustrates the broad spread and impact of this modification on parasite biology. The main enzymes responsible for protein palmitoylation are multi-membrane protein S-acyl transferases harbouring a catalytic Asp-HisHis-Cys (DHHC) motif. A global functional analysis of the repertoire of protein S-acyl transferases in Toxoplasma gondii and Plasmodium berghei has recently been performed. The essential nature of some of these enzymes illustrates the key roles played by this post-translational modification in the corresponding substrates implicated in fundamental processes such as parasite motility and organelle biogenesis. Toward a better understanding of the depalmitoylation event, a protein with palmitoyl protein thioesterase activity has been identified in T. gondii. TgPPT1/TgASH1 is the main target of specific acyl protein thioesterase inhibitors but is dispensable for parasite survival, suggesting the implication of other genes in depalmitoylation. Palmitoylation/depalmitoylation cycles are now emerging as potential novel regulatory networks and T. gondii represents a superb model organism in which to explore their significance.

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“…Using the Superfamily server, a hidden Markov model-based protein fold library, the domain architecture of the vertebrate NAGS protein is predicted to have a carbamate kinase-like fold for amino acids 137-373 and an acyl-CoA N-acyltransferase-like fold for residues 377-472 [20,21]. Carbamate kinase has structural similarities to E. coli N-acetylglutamate kinase, suggesting that the region 137-373 contains the glutamate binding domain, while region 377-472 is part of the acetyl-CoA binding domain.…”

Section: Protein Sequencementioning

confidence: 99%

Mammalian N-acetylglutamate synthase

Morizono

Caldovic

Shi

et al. 2004

Molecular Genetics and Metabolism

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N-Acetylglutamate synthase (NAGS, E.C. 2.3.1.1) is a mitochondrial enzyme that catalyzes the formation of N-acetylglutamate (NAG), an essential allosteric activator of carbamylphosphate synthetase I (CPSI). The mouse and human NAGS genes have been identified based on similarity to regions of NAGS from Neurospora crassa and cloned from liver cDNA libraries. These genes were shown to complement an argA-(NAGS) deficient Escherichia coli strain, and enzymatic activity of the proteins was confirmed by a new stable isotope dilution assay. The deduced amino acid sequence of mammalian NAGS contains a putative mitochondrial-targeting signal at the Nterminus. The mouse NAGS preprotein was overexpressed in insect cells to determine posttranslational modifications and two processed proteins with different N-terminal truncations have been identified. Sequence analysis using a hidden Markov model suggests that the vertebrate NAGS protein contains domains with a carbamate kinase fold and an acyl-CoA N-acyltransferase fold, and protein crystallization experiments are currently underway. Inherited NAGS deficiency results in hyperammonemia, presumably due to the loss of CPSI activity. We, and others, have recently identified mutations in families with neonatal and late-onset NAGS deficiency and the identification of the gene has now made carrier testing and prenatal diagnosis feasible. A structural analog of NAG, carbamylglutamate, has been shown to bind and activate CPSI, and several patients have been reported to respond favorably to this drug (Carbaglu®).

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Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure

Cited by 1,106 publications

References 27 publications

The human RBPome: From genes and proteins to human disease

The human RBPome: From genes and proteins to human disease

Emerging roles for protein S-palmitoylation in Toxoplasma biology

Mammalian N-acetylglutamate synthase

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