Humanin
The founding mitochondria-derived peptide, studied in apoptosis-pathway biochemistry, receptor pharmacology, and retrograde mitochondrial signaling models.
Molecular Profile
- Type
- Mitochondria-derived peptide (MDP; 21–24 residues depending on translation context)
- Molecular formula
- C₁₁₉H₂₀₄N₃₄O₃₂S₂
- Molecular weight
- ~2,687 g/mol
- CAS number
- 330936-69-1
- Amino acids
- 24
- Sequence
- MAPRGFSCLLLLTSEIDLPVKRRA
- Modification
- Cytosolic translation yields the 24-residue canonical sequence (MAPRGFSCLLLLTSEIDLPVKRRA; UniProt Q8IVG9); mitochondrial translation yields a 21-residue form (MAPRGFSCLLLLTSEIDLPVK) due to differences in the mitochondrial genetic code. Both forms have been studied. Commonly used research analogs include the S14G substitution (HNG, studied for extended in vivo stability), N-formylated Humanin (fHN, studied for receptor pharmacology), the F6A/HNGF6A substitution (abolishes IGFBP-3 binding — used to dissect interaction specificity), and D-Ser14 forms (structural studies). Cys8 and Leu12 are noted as functionally critical residues in mechanistic work.
Mechanism & Target Class
Humanin has been studied as a peptide with both intracellular and extracellular binding partners. Intracellularly, it has been characterized as a binding partner for Bcl-2-family proteins — including BAX, BID/tBID, and BimEL — and for IGFBP-3; structural studies demonstrate that Humanin can induce conformational changes in BAX and recruit it into higher-order β-sheet fiber assemblies, work that provides structural context for the mitochondrial outer-membrane permeabilization (MOMP) literature. Extracellularly, it has been examined as a ligand at members of the G-protein-coupled receptor (GPCR) family and at a trimeric cytokine-receptor complex; cryo-EM and biophysical studies have resolved receptor-bound forms at atomic resolution, mapping the binding interface and the structural basis for competitive ligand models.
Storage & Handling
- Lyophilized
- -20°C (-80°C long term); lyophilized powder typically stable ~24 months under dry, sealed conditions.
- Handling
- Native Humanin is reported to have a short circulating half-life in vivo that varies by species and analog form; the S14G (HNG) analog has been studied for extended in vivo stability in animal models. Protect from light and moisture; Cys8 is an oxidation-sensitive residue.
Primary Database
References (22)
Reviews
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Yen K, Lee C, Mehta H, Cohen P. (2013). J Mol Endocrinol
Clinical
6Miller B, Kim SJ, Cao K, et al. (2024). Aging Cell
- 7
Yen K, Wan J, Mehta HH, et al. (2018). Sci Rep
Primary research
8Zhu Y, Lin X, Zong X, et al. (2022). Nat Commun
- 9
Yen K, Mehta HH, Kim SJ, et al. (2020). Aging (Albany NY)
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Morris DL, Kastner DW, Johnson S, et al. (2019). J Biol Chem
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Kuliawat R, Klein L, Gong Z, et al. (2013). FASEB J
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Muzumdar RH, Huffman DM, Calvert JW, et al. (2010). Arterioscler Thromb Vasc Biol
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Muzumdar RH, Huffman DM, Atzmon G, et al. (2009). PLoS One
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Hashimoto Y, Kurita M, Aiso S, Nishimoto I, Matsuoka M. (2009). Mol Biol Cell
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Luciano F, Zhai D, Zhu X, et al. (2005). J Biol Chem
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Zhai D, Luciano F, Zhu X, Guo B, Satterthwait AC, Reed JC. (2005). J Biol Chem
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Harada M, Habata Y, Hosoya M, et al. (2004). Biochem Biophys Res Commun
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Ying G, Iribarren P, Zhou Y, et al. (2004). J Immunol
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Guo B, Zhai D, Cabezas E, et al. (2003). Nature
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Ikonen M, Liu B, Hashimoto Y, et al. (2003). Proc Natl Acad Sci USA
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Hashimoto Y, Niikura T, Ito Y, et al. (2001). J Neurosci
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Hashimoto Y, Niikura T, Tajima H, et al. (2001). Proc Natl Acad Sci USA