Compound monograph
Humanin (HN)
Humanin is a 24-residue peptide encoded within the mitochondrial 16S ribosomal RNA gene, and the first-described member of the mitochondrial-derived peptide family.
01
Identity & nomenclature
Humanin is a 24-residue peptide encoded within the mitochondrial 16S ribosomal RNA gene, and the first-described member of the mitochondrial-derived peptide family.
The humanin coding sequence lies within MT-RNR2, the mitochondrial 16S rRNA gene. A mitochondrial coding locus does not establish where translation occurs. This record specifies the 24-residue standard-code form; a mitochondrial-code prediction is a distinct sequence. Nuclear humanin-like loci further complicate assigning endogenous origin. HNG carries S14G, and HNGF6A carries F6A and S14G. N-formyl humanin is a distinct chemical form. MTRNR2L gene names denote nuclear loci and are not peptide aliases.
Canonical name: Humanin.
Declared aliases and development codes: HN.
02
Molecular properties
| Molecular formula | C119H204N34O32S2 |
|---|---|
| Molecular mass | 2687.3 Da |
| CAS Registry Number | 330936-69-1 |
| PubChem CID | 16131438 |
| UNII | H975EUX36G |
| One-letter sequence | MAPRGFSCLLLLTSEIDLPVKRRA |
Twenty-four residues with free termini and one cysteine at position 8. This record specifies the standard-code form; it does not identify the mature product of mitochondrial translation.
03
Structural characteristics
Functional expression screening identified humanin cDNA, and the corresponding peptide was detected in culture medium. Humanin binds BAX, an intracellular partner, and limits its association with isolated mitochondria. Cell-binding and reconstituted-protein experiments implicate CNTFR-alpha, WSX-1 and gp130 in a separate cell-surface complex. A comparison of unmodified and N-formyl humanin measured receptor binding and activation; the chemical forms must be distinguished. Analysis of synonymous codon bias reports strong bias and conservation for humanin, consistent with amino-acid sequence constraint within the rRNA gene.
Terminal features: Free N-terminus, Free C-terminal carboxyl.
04
Molecular targets & mechanisms
05
Analytical considerations
Fragments spanning positions 14 and 16 and the C-terminal RRA segment distinguish the recorded sequence from related forms. A short shared fragment or immunoassay signal cannot identify the intact 24-mer or its transcript of origin. One cysteine permits an intermolecular disulfide but no intramolecular disulfide. Routine intact mass does not distinguish leucine from isoleucine or establish stereochemistry.
06
Verified bibliography
- A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta.current
Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I
Proceedings of the National Academy of Sciences of the United States of America · 2001-05-22 · Journal Article
- Humanin peptide suppresses apoptosis by interfering with Bax activation.current
Guo B, Zhai D, Cabezas E, Welsh K, Nouraini S, Satterthwait AC, Reed JC
Nature · 2003-05-04 · Journal Article
- Humanin inhibits neuronal cell death by interacting with a cytokine receptor complex or complexes involving CNTF receptor alpha/WSX-1/gp130.current
Hashimoto Y, Kurita M, Aiso S, Nishimoto I, Matsuoka M
Molecular biology of the cell · 2009-04-22 · Journal Article
- N-Formylated humanin activates both formyl peptide receptor-like 1 and 2.current
Harada M, Habata Y, Hosoya M, Nishi K, Fujii R, Kobayashi M, Hinuma S
Biochemical and biophysical research communications · 2004-11-05 · Journal Article
- Evidence for potential functionality of nuclearly-encoded humanin isoforms.current
Bodzioch M, Lapicka-Bodzioch K, Zapala B, Kamysz W, Kiec-Wilk B, Dembinska-Kiec A
Genomics · 2009-05-27 · Journal Article
- Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6.current
Gruschus JM, Morris DL, Tjandra N
Scientific reports · 2023-08-29 · Journal Article
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.current
Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P
Cell metabolism · 2015-03-03 · Journal Article
10
Methodology & citation verification
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