What is humanin?
Humanin is a 24-amino-acid peptide encoded in mitochondrial DNA, the first member of what are now called mitochondrial-derived peptides. It was found in 2001 in a screen for genes that blocked neuronal cell death in cell models of Alzheimer's disease, and it has since been studied in many cell and animal models.
Humanin in one table.
| Sequence | MAPRGFSCLLLLTSEIDLPVKRRA |
|---|---|
| Length | 24 amino acids; 21 if translated inside mitochondria |
| Formula | C119H204N34O32S2 |
| Molecular weight | 2687.2 g/mol |
| Encoded in | MT-RNR2, the mitochondrial 16S rRNA gene, with related copies in the nuclear genome |
| First described | 2001 |
| Binding partners | BAX and IGFBP-3; formyl peptide receptors FPRL1 and FPRL2 |
| Best-known analog | HNG (S14G-humanin) |
Sequence from UniProt Q8IVG9. Formula and mass from Helion's peptide molecular weight calculator, matching PubChem.
Found in a screen for cell survival.
In 2001, researchers screening for genes that could block neuronal cell death identified a short open reading frame they named humanin. In cell culture, the encoded peptide abolished the death of neuronal cells caused by several familial Alzheimer's disease genes and by amyloid-beta, but not death caused by unrelated insults such as a polyglutamine repeat or mutant superoxide dismutase-1, and cells released it into the culture medium.
A follow-up structure-activity study found cysteine 8 and serine 14 critical to that activity and mapped the active region to residues 3 to 19. It also tested a variant with glycine in place of serine 14, S14G, now known as HNG.
A gene inside a gene.
Humanin's open reading frame sits inside MT-RNR2, the mitochondrial gene for the 16S ribosomal RNA. Mitochondria read some codons differently from the rest of the cell, so where the peptide is made matters: UniProt notes that translation inside mitochondria would give a shorter peptide missing the last three residues, while translation in the cytoplasm gives the 24-residue form.
The nuclear genome also carries humanin-like copies. A 2009 analysis predicted 13 MT-RNR2-like nuclear loci able to encode 15 full-length humanin-like peptides, at least ten of them expressed in human tissues.
What humanin interacts with.
Inside cells, humanin binds BAX, a protein that triggers apoptosis when it moves to mitochondria. In a 2003 study it kept BAX from translocating and blocked cytochrome c release in vitro, and the mitochondrial version of the peptide bound BAX as well. Humanin also binds IGFBP-3 with high affinity, and a single substitution, F6A, abolishes that binding. Outside cells it acts as a ligand for the formyl peptide receptors FPRL1 and FPRL2, although work in a neuronal cell line suggests another receptor also exists.
Mitochondrial-derived peptides.
| Peptide | Length | Encoded in | First described |
|---|---|---|---|
| Humanin | 24 amino acids | 16S rRNA gene (MT-RNR2) | 2001 |
| MOTS-c | 16 amino acids | 12S rRNA gene (MT-RNR1) | 2015 |
| SHLP1 to SHLP6 | Small peptides | 16S rRNA gene, near humanin | 2016 |
Humanin came first. MOTS-c was found in the 12S rRNA gene, and an in silico search of humanin's region of mitochondrial DNA found six small humanin-like peptides (SHLPs). In the 2016 study, circulating SHLP2 declined with age, as humanin does. The SS-31 vs MOTS-c guide compares MOTS-c with SS-31, a synthetic peptide designed to reach mitochondria rather than one encoded by them.
Specs and storage by compound.
Questions (6)
What is humanin?
A 24-amino-acid peptide encoded in the mitochondrial 16S rRNA gene, MT-RNR2. First described in 2001, it was the first known mitochondrial-derived peptide.
What is the humanin sequence?
MAPRGFSCLLLLTSEIDLPVKRRA (Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala), C119H204N34O32S2, 2687.2 g/mol.
Is humanin a mitochondrial-derived peptide?
Yes, the first one described. MOTS-c and the six small humanin-like peptides (SHLPs) were found later in the same genome.
What is HNG?
S14G-humanin, an analog with glycine in place of serine 14, tested in the 2001 structure-activity work and used in many later studies.
How is humanin different from MOTS-c?
Both are encoded in mitochondrial DNA, but humanin comes from the 16S rRNA gene and has 24 residues, while MOTS-c comes from the 12S rRNA gene and has 16. They are different sequences with separate literatures.
Does Helion sell humanin?
No. Helion supplies MOTS-c and SS-31, for laboratory research use only.
Published studies (10)
- A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta
- Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults
- Humanin peptide suppresses apoptosis by interfering with Bax activation
- Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis
- Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection
- Evidence for potential functionality of nuclearly-encoded humanin isoforms
- Humanins, the neuroprotective and cytoprotective peptides with antiapoptotic and anti-inflammatory properties
- Humanin: a harbinger of mitochondrial-derived peptides?
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
- Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers
Citations from PubMed for reference. They describe the compound in the literature, not any Helion lot, and nothing here is guidance on use.