Humanin

Humanin is a twenty-four-residue peptide encoded inside the mitochondrial 16S ribosomal RNA gene, MT-RNR2, rather than by nuclear DNA. Hashimoto and colleagues identified it in PNAS in 2001.

The sequence is Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala, carried as the free acid with a free N-terminal amine. There is no acetylation, no amidation and no disulfide, because the single cysteine has no partner.

There is a second molecule sold under a very similar name and it is not this one. The analogue commonly abbreviated HNG carries glycine in place of the serine at position 14, and it is thirty daltons lighter at 2657.2; PubChem registers the two separately, as CID 16131438 and CID 155887372. Only the native peptide has a CAS number and an FDA UNII, so a listing pairing CAS 330936-69-1 with a mass near 2657 is internally contradictory. The figures on this page describe the native serine-14 peptide. Note also that the sequence contains two serines, at positions 7 and 14, and the analogue position is the second one.

The defining structural feature is the run of four consecutive leucines at positions 9 to 12, flanked by Phe6 and Ile16, which gives a strongly hydrophobic core in an otherwise short and charged molecule. Prolines at positions 3 and 19 constrain the backbone at both ends. Serine 14 sits immediately after the leucine block, which is why substituting it is a conformationally meaningful change rather than a neutral one.

The molecule has no tryptophan and no tyrosine, only a single phenylalanine at position 6. Absorbance at 280 nm therefore returns noise rather than a concentration, for this peptide and for its glycine-14 analogue alike; amino-acid analysis, low-ultraviolet absorbance or the certificate's own peptide-content figure is required instead. This is a practical trap because the peptide is long enough that an operator expects an ultraviolet reading to work.

Two receptor systems appear in the primary literature and both are named here because they come from distinct sources. Ying and colleagues reported FPR2, the N-formyl peptide receptor 2 (UniProt P25090), in 2004. Hashimoto and colleagues reported a trimeric cytokine receptor complex of CNTFR, WSX-1 and gp130 (UniProt P26992, Q6UWB1 and P40189) in 2009.