RGD Reference Report - Identification of novel peptide hormones in the human proteome by hidden Markov model screening. - Rat Genome Database

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Identification of novel peptide hormones in the human proteome by hidden Markov model screening.

Authors: Mirabeau, Olivier  Perlas, Emerald  Severini, Cinzia  Audero, Enrica  Gascuel, Olivier  Possenti, Roberta  Birney, Ewan  Rosenthal, Nadia  Gross, Cornelius 
Citation: Mirabeau O, etal., Genome Res. 2007 Mar;17(3):320-7. Epub 2007 Feb 6.
RGD ID: 12907558
Pubmed: PMID:17284679   (View Abstract at PubMed)
PMCID: PMC1800923   (View Article at PubMed Central)
DOI: DOI:10.1101/gr.5755407   (Journal Full-text)

Peptide hormones are small, processed, and secreted peptides that signal via membrane receptors and play critical roles in normal and pathological physiology. The search for novel peptide hormones has been hampered by their small size, low or restricted expression, and lack of sequence similarity. To overcome these difficulties, we developed a bioinformatics search tool based on the hidden Markov model formalism that uses several peptide hormone sequence features to estimate the likelihood that a protein contains a processed and secreted peptide of this class. Application of this tool to an alignment of mammalian proteomes ranked 90% of known peptide hormones among the top 300 proteins. An analysis of the top scoring hypothetical and poorly annotated human proteins identified two novel candidate peptide hormones. Biochemical analysis of the two candidates, which we called spexin and augurin, showed that both were localized to secretory granules in a transfected pancreatic cell line and were recovered from the cell supernatant. Spexin was expressed in the submucosal layer of the mouse esophagus and stomach, and a predicted peptide from the spexin precursor induced muscle contraction in a rat stomach explant assay. Augurin was specifically expressed in mouse endocrine tissues, including pituitary and adrenal gland, choroid plexus, and the atrio-ventricular node of the heart. Our findings demonstrate the utility of a bioinformatics approach to identify novel biologically active peptides. Peptide hormones and their receptors are important diagnostic and therapeutic targets, and our results suggest that spexin and augurin are novel peptide hormones likely to be involved in physiological homeostasis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of gastro-intestinal system smooth muscle contraction involved_inISSUniProtKB:Q9BT5612907558PMID:17284679UniProt 

Cellular Component

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neuropeptide hormone activity enablesISSUniProtKB:Q9BT5612907558PMID:17284679UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Ecrg4  (ECRG4 augurin precursor)
Spx  (spexin hormone)


Additional Information