Compound monograph
Spexin
Spexin is an endogenous fourteen-residue amidated neuropeptide identified by computational screening of the human proteome, and a ligand of galanin receptors 2 and 3.
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Identity & nomenclature
Spexin is an endogenous fourteen-residue amidated neuropeptide identified by computational screening of the human proteome, and a ligand of galanin receptors 2 and 3.
Spexin and spadin are unrelated peptides. Mature spexin has fourteen residues, and PE 22-28 is derived from the sortilin propeptide. The former alias Spexin (22-28) incorrectly assigned that fragment to spexin. NPQ is a discovery-era designation that may refer to the precursor; it does not by itself identify the mature amidated peptide.
Declared aliases and development codes: SPX, Spexin-1, NPQ.
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Molecular properties
| Molecular formula | C74H114N20O19S |
|---|---|
| Molecular mass | 1619.9 Da |
| CAS Registry Number | 1370290-58-6 |
| PubChem CID | 122705996 |
| One-letter sequence | NWTPQAMLYLKGAQ |
| Three-letter sequence | Asn–Trp–Thr–Pro–Gln–Ala–Met–Leu–Tyr–Leu–Lys–Gly–Ala–Gln–NH2 |
Fourteen residues with a C-terminal amide, free N-terminus and no disulfide, lactam or lipid conjugation.
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Structural characteristics
A hidden Markov model screen identified the spexin precursor, followed by secretory-granule localization and recovery from cell supernatant. These observations concern precursor expression and secretion; they do not alone identify intact mature spexin. Ligand-receptor experiments found spexin activation of GALR2 and GALR3, with no GALR1 activation in the reported panel and greater potency at GALR3 than the galanin comparator. A cryo-EM study determined a spexin-bound GALR2-Gq complex. Evolutionary analysis supports local duplication of spexin, galanin and kisspeptin genes before two rounds of vertebrate whole-genome duplication.
Terminal features: C-terminal amide.
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Molecular targets & mechanisms
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Analytical considerations
Confirmation needs the fourteen-residue sequence and the terminal amide together; the free acid is 0.98 Da heavier than the amide and deamidation must be localised rather than inferred from intact mass. Include a methionine-oxidation assessment. Precursor-derived intermediates extended at the N-terminus or carrying the amidation-donor glycine should be looked for explicitly, since detecting precursor expression or immunoreactivity does not establish that the mature amidated peptide is present.
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Verified bibliography
- Identification of novel peptide hormones in the human proteome by hidden Markov model screening.current
Mirabeau O, Perlas E, Severini C, Audero E, Gascuel O, Possenti R, Birney E, Rosenthal N, Gross C
Genome research · 2007-02-06 · Journal Article
- Coevolution of the spexin/galanin/kisspeptin family: Spexin activates galanin receptor type II and III.current
Kim DK, Yun S, Son GH, Hwang JI, Park CR, Kim JI, Kim K, Vaudry H, Seong JY
Endocrinology · 2014-02-11 · Journal Article
- Structural insights into galanin receptor signaling.current
Jiang W, Zheng S
Proceedings of the National Academy of Sciences of the United States of America · 2022-05-20 · Journal Article
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Methodology & citation verification
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