Compound monograph
SHLP2
SHLP2 is a 26-residue peptide assigned to a small open reading frame within the mitochondrial 16S rRNA region. Its experimental characterization includes receptor screening, protein-interaction assays and targeted peptide detection.
01
Identity & nomenclature
SHLP2 is a 26-residue peptide assigned to a small open reading frame within the mitochondrial 16S rRNA region. Its experimental characterization includes receptor screening, protein-interaction assays and targeted peptide detection.
'Humanin-like' describes the genomic neighbourhood, not the sequence: SHLP2 is not a humanin fragment and shares no substantial sequence with it. K4R-SHLP2 is a distinct variant arising from a mitochondrial single-nucleotide polymorphism and is not an alias for this Lys4 form. The mature endogenous terminal chemistry is UNKNOWN; the free-acid termini recorded here specify the synthetic reference molecule.
Canonical name: Small humanin-like peptide 2.
Declared aliases and development codes: SHLP-2.
02
Molecular properties
| Molecular formula | C142H214N36O35S |
|---|---|
| Molecular mass | 3017.6 Da |
| CAS Registry Number | 1191923-93-9 |
| PubChem CID | 171716852 |
| One-letter sequence | MGVKFFTLSTRFFPSVQRAVPLWTNS |
Twenty-six residues, free at both termini. One methionine, no cysteine. Position 4 is LYSINE in this form; a naturally occurring variant carries arginine there and is a different molecule.
03
Structural characteristics
Structural complementation screening identified CXCR7 binding and activation by SHLP2. Separate experiments detected a tryptic fragment in neuronal cells and supported association with mitochondrial complex I. Biophysical assays also support binding to misfolded IAPP seeds. These experimental findings coexist with weaker evolutionary evidence: the synonymous-codon analysis found no significant bias and poor conservation for SHLP2, unlike humanin and SHLP6. Because the coding sequence lies within an rRNA gene, amino-acid conservation is the expected signature of peptide-level functional constraint. This analysis argues against that constraint for SHLP2; it does not erase the reported experimental observations.
Terminal features: Free N-terminus, Free C-terminal carboxyl.
04
Molecular targets & mechanisms
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Analytical considerations
Targeted proteomics detected the internal tryptic fragment FFPSVQR. It omits position 4 and both termini, so it cannot distinguish Lys4 from the Arg4 variant or establish intact endogenous terminal chemistry. Intact-sequence assignment requires additional coverage. Peptide-affinity capture of partner proteins is a separate experiment from endogenous-peptide identification.
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Verified bibliography
- Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.current
Cobb LJ, Lee C, Xiao J, Yen K, Wong RG, Nakamura HK, Mehta HH, Gao Q, Ashur C, Huffman DM, Wan J, Muzumdar R, Barzilai N, Cohen P
Aging · 2016-04 · Journal Article
- The Mitochondrial-Derived Peptides, HumaninS14G and Small Humanin-like Peptide 2, Exhibit Chaperone-like Activity.current
Okada AK, Teranishi K, Lobo F, Isas JM, Xiao J, Yen K, Cohen P, Langen R
Scientific reports · 2017-08-10 · Journal Article
- Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.current
Kim SK, Tran LT, NamKoong C, Choi HJ, Chun HJ, Lee YH, Cheon M, Chung C, Hwang J, Lim HH, Shin DM, Choi YH, Kim KW
Nature communications · 2023-07-19 · Journal Article
- A naturally occurring variant of SHLP2 is a protective factor in Parkinson's disease.current
Kim SJ, Miller B, Hartel NG, Ramirez R 2nd, Braniff RG, Leelaprachakul N, Huang A, Wang Y, Arpawong TE, Crimmins EM, Wang P, Sun X, Liu C, Levy D, Yen K, Petzinger GM, Graham NA, Jakowec MW, Cohen P
Molecular psychiatry · 2024-01-03 · 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
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Methodology & citation verification
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