NeuroPred: a tool to predict cleavage sites in neuropeptide precursors and provide the masses of the resulting peptides

Southey, Bruce R.; Amare, Andinet; Zimmerman, Tyler A.; Rodriguez-Zas, Sandra L.; Sweedler, Jonathan V.

doi:10.1093/nar/gkl161

Cited by 213 publications

(185 citation statements)

References 15 publications

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“…Putative monobasic, dibasic, or tribasic peptide proteolytic consensus cleavage sites (RR, KR, KK) were identified or predicted using NeuroPred (http://stagbeetle. animal.uiuc.edu/cgi-bin/neuropred.py) (Southey et al 2006) to retrieve the mature peptides for further analysis (Supplementary Data 1, see section on supplementary data given at the end of this article).…”

Section: Database Mining and Sequence Retrievalmentioning

confidence: 99%

Corticotropin-releasing hormone family evolution: five ancestral genes remain in some lineages

Cardoso¹,

Bergqvist²,

Félix³

et al. 2016

Journal of Molecular Endocrinology

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The evolution of the peptide family consisting of corticotropin-releasing hormone (CRH) and the three urocortins (UCN1-3) has been puzzling due to uneven evolutionary rates. Distinct gene duplication scenarios have been proposed in relation to the two basal rounds of vertebrate genome doubling (2R) and the teleost fish-specific genome doubling (3R). By analyses of sequences and chromosomal regions, including many neighboring gene families, we show here that the vertebrate progenitor had two peptide genes that served as the founders of separate subfamilies. Then, 2R resulted in a total of five members: one subfamily consists of CRH1, CRH2, and UCN1. The other subfamily contains UCN2 and UCN3. All five peptide genes are present in the slowly evolving genomes of the coelacanth Latimeria chalumnae (a lobe-finned fish), the spotted gar Lepisosteus oculatus (a basal ray-finned fish), and the elephant shark Callorhinchus milii (a cartilaginous fish). The CRH2 gene has been lost independently in placental mammals and in teleost fish, but is present in birds (except chicken), anole lizard, and the nonplacental mammals platypus and opossum. Teleost 3R resulted in an additional surviving duplicate only for crh1 in some teleosts including zebrafish (crh1a and crh1b). We have previously reported that the two vertebrate CRH/UCN receptors arose in 2R and that CRHR1 was duplicated in 3R. Thus, we can now conclude that this peptide-receptor system was quite complex in the ancestor of the jawed vertebrates with five CRH/UCN peptides and two receptors, and that crh and crhr1 were duplicated in the teleost fish tetraploidization.

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Section: Database Mining and Sequence Retrievalmentioning

confidence: 99%

Corticotropin-releasing hormone family evolution: five ancestral genes remain in some lineages

Cardoso¹,

Bergqvist²,

Félix³

et al. 2016

Journal of Molecular Endocrinology

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“…Database Searching-Each .puf file, which typically contained hundreds of experiments from a single nano-LC-MS/MS run, was first searched in absolute mass mode (MS1 and MS2 tolerances of Ϯ10 ppm) against a database of predicted rat neuropeptides (with and without predicted modifications) generated by taking the set of known rat prohormones processed in silico via the NeuroPred algorithm (35)(36)(37). For the searches that did not identify a peptide below an E-value cutoff of 10 Ϫ4 , a search in "neuropeptide" mode was initiated against an intact rat database (UniProt 15.0, 4,318,021 protein forms) with Ϯ100-Da intact mass and Ϯ10-ppm fragment tolerance.…”

Section: Mass Spectral Analysis (Lc-ftms/ms)-mentioning

confidence: 99%

Endogenous Peptide Discovery of the Rat Circadian Clock

Lee

Atkins

Hatcher

et al. 2010

Molecular & Cellular Proteomics

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Understanding how a small brain region, the suprachiasmatic nucleus (SCN), can synchronize the body's circadian rhythms is an ongoing research area. This important time-keeping system requires a complex suite of peptide hormones and transmitters that remain incompletely characterized. Here, capillary liquid chromatography and FTMS have been coupled with tailored software for the analysis of endogenous peptides present in the SCN of the rat brain. After ex vivo processing of brain slices, peptide extraction, identification, and characterization from tandem FTMS data with <5-ppm mass accuracy produced a hyperconfident list of 102 endogenous peptides, including 33 previously unidentified peptides, and 12 peptides that were post-translationally modified with amidation, phosphorylation, pyroglutamylation, or acetylation. This characterization of endogenous peptides from the SCN will aid in understanding the molecular mechanisms that mediate rhythmic behaviors in mammals. Molecular & Cellular Proteomics 9:285-297, 2010.

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“…The NeuroPred processing prediction web tool (http://neuroproteomics.scs.uiuc.edu/neuropred.html) (Southey et al, 2006a) was used to predict cleavage sites at basic amino acid locations, average masses and post-translational modifications to selected abalone larval EST precursor sequences (Jackson and Degnan, 2006). Signal sequence predictions were performed by SignalP 3.0 server (http://www.cbs.dtu.dk/services/SignalP) (Bendtsen et al, 2004) and cellular pathway prediction determined by PSORTII (http://psort.ims.utokyo.ac.jp/form2.html) (Nakai and Horton, 1999).…”

Section: Prediction Of Larval Precursor Processingmentioning

confidence: 99%

Expression of prohormone convertase 2 and the generation of neuropeptides in the developing nervous system of the gastropod Haliotis

Cummins¹,

York²,

Hanna³

et al. 2009

Int. J. Dev. Biol.

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Prohormone convertase 2 (PC2) belongs to a family of enzymes involved in the proteolytic maturation of neuropeptide precursors into mature peptides that act as neurotransmitters, neuromodulators or neurohormones. Here we show that a gene encoding a PC2-like enzyme (HasPC2) is expressed during larval development and in the adult ganglia of the vetigastropod Haliotis asinina. HasPC2 exhibits high sequence identity to other gastropod PC2s and thus is likely to function in peptide processing. Analysis of HasPC2 expression indicates that it is activated early in nervous system development. During trochophore and early veliger larval stages, HasPC2 is expressed in the vicinity of the forming ganglia of the central nervous system and parts of the putative peripheral nervous system. Later in larval development, at the time the veliger becomes competent to interact with the external environment and initiate metamorphosis, HasPC2 expression largely restricts to cells of the major ganglia and their commissures. Profiling of veliger larvae by bioinformatic approaches suggests the expression of a variety of peptides. Direct MALDI-MS-based peptide profiling of juvenile Haliotis cerebral ganglia (brain) reveals an abundance of neuropeptides, including FMRFamide-related peptides and APGWamide, compatible with PC2 functioning in neuropeptide processing in these regions. These results are consistent with PC2 regulating neuropeptide generation in the earliest functioning of the gastropod nervous system. KEY WORDS: prohormone convertase, abalone, neuropeptide, developmentNeuropeptides are widespread in the animal kingdom and are often involved in the control of critical functions throughout the life cycle. The regulation of development by peptidergic hormones is a common feature of multicellular animals and has been studied in great detail in arthropods and vertebrates. Strikingly, investigations reveal that insects are as well or even better supplied with neuropeptides than mammals. In insects, neuropeptides regulate not only the functioning of endocrine glands, but also a wide range of physiological and developmental processes (Reumer et al., 2008). Although a complete developmental peptidome analysis has not been established for other major invertebrate groups, such as the molluscs, numerous immunolocalization studies suggest that neuropeptides are equally important for their development. For instance, in gastropods FMRFamide and related peptides are amongst the earliest neurotransmitters expressed Int. J. Dev. Biol. 53: 1081-1088 (2009) Abbreviations used in this paper: DIG, digoxigenin; MALDI-MS, matrix-assisted laser desorption/ionization MS; PBS, phosphate-buffered solution; PC, prohormone convertase; RACE, rapid amplification of cDNA ends; WMISH, whole-mount in situ hybridization.within the larval nervous system (Croll and Voronezhskaya, 1996;Dickinson et al., 1999; Dickinson et al., 2000;Haszprunar et al., 2002;Dickinson and Croll, 2003; Croll, 2006). In the adult stages of these same animals, neuropeptides pl...

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NeuroPred: a tool to predict cleavage sites in neuropeptide precursors and provide the masses of the resulting peptides

Cited by 213 publications

References 15 publications

Corticotropin-releasing hormone family evolution: five ancestral genes remain in some lineages

Corticotropin-releasing hormone family evolution: five ancestral genes remain in some lineages

Endogenous Peptide Discovery of the Rat Circadian Clock

Expression of prohormone convertase 2 and the generation of neuropeptides in the developing nervous system of the gastropod Haliotis

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