Lot certificates published
Plain, secure packaging
Purely Peptides
Research Catalog

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.

Published: 2026-09-16Literature/identifier verification: 2026-09-15
Also known asSHLP-2
Mitochondrial-derived peptides

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 formulaC142H214N36O35S
Molecular mass3017.6 Da
CAS Registry Number1191923-93-9
PubChem CID171716852
One-letter sequenceMGVKFFTLSTRFFPSVQRAVPLWTNS
Terminal groupsFree N-terminus; Free C-terminal carboxyl

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

05

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.

Disagreements and mix-ups

Points where sources disagree about this compound's identity, or where a name or form is easily confused with another, as noted in this record. The discrepancy register quotes the passage for each one.

What the studies reported

Each finding describes one cited study in its stated model. These observations are specific to that study and do not establish effects in other settings.

Cell and tissue studies

  • Purified IAPP seed co-sedimentation assay

    Using a purified IAPP seed co-sedimentation assay, the study found direct binding of SHLP2 to IAPP seeds.

    Reference [2]

  • Spin-labeled monomeric IAPP EPR spectroscopy assay

    Using a spin-labeled monomeric IAPP EPR spectroscopy assay, the study detected no direct binding interaction with SHLP2 under the tested conditions.

    Reference [2]

  • CXCR7-expressing CHO-K1 PathHunter β-Arrestin recruitment assay

    Using a CXCR7-expressing CHO-K1 PathHunter β-Arrestin recruitment assay, the study reported a SHLP2 EC50 of 0.9696 µM.

    Reference [3]

  • HEK293 SHLP2-APEX proximity labeling and isolated mitochondrial protein affinity-column assays

    Using HEK293 SHLP2-APEX proximity labeling and isolated mitochondrial protein affinity-column assays, the study reported that the combined results supported SHLP2 binding to the Pd modules of mitochondrial complex 1.

    Reference [4]

Animal studies

  • Conscious Sprague Dawley rats studied with insulin clamps

    In conscious Sprague Dawley rats studied with insulin clamps (n = 6), the study reported an approximately 50% increase in the glucose infusion rate required to maintain euglycemia with SHLP2.

    Reference [1]

  • C57BL/6 mouse serum biomarker assays

    In C57BL/6 mice (n = 5), the study observed no SHLP2-associated change in serum insulin, interleukin-6 or MCP-1 levels.

    Reference [1]

  • Male C57BL/6J mice with high-fat-diet-induced obesity

    In male C57BL/6J mice with high-fat-diet-induced obesity, the study reported reduced body weight gain and improved glucose tolerance and insulin sensitivity with SHLP2.

    Reference [3]

Computational studies

  • Comparative vertebrate mitochondrial coding-sequence analysis

    Using comparative vertebrate mitochondrial coding-sequence analysis, the study reported no significant synonymous codon bias and poor conservation for SHLP2.

    Reference [5]

06

Verified bibliography

Cited studies by type

The 6 papers this record cites, counted by the kind of work each reports. A count is the size of this record's selection, not of the research that exists, and says nothing about results, safety, effectiveness or approval.

A paper can report more than one kind of work. Each count opens those papers in the bibliography. Compare every record on the Evidence Map.

  1. Reference 1

    Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.

    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

    current
    PMID 27070352PMC4925829DOI 10.18632/aging.100943SHLP2SHLP3SHLP6

  2. Reference 2

    The Mitochondrial-Derived Peptides, HumaninS14G and Small Humanin-like Peptide 2, Exhibit Chaperone-like Activity.

    Okada AK, Teranishi K, Lobo F, Isas JM, Xiao J, Yen K, Cohen P, Langen R

    Scientific reports · 2017-08-10 · Journal Article

    current
    PMID 28798389PMC5552803DOI 10.1038/s41598-017-08372-5HNG ([Gly14]-Humanin)SHLP2Amylin (human IAPP)

  3. Reference 3

    Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.

    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

    current
    PMID 37468558PMC10356901DOI 10.1038/s41467-023-40082-7SHLP2

  4. Reference 4

    A naturally occurring variant of SHLP2 is a protective factor in Parkinson's disease.

    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

    current
    PMID 38167865PMC11116102DOI 10.1038/s41380-023-02344-0SHLP2

  5. Reference 5

    Evidence of natural selection in the mitochondrial-derived peptides humanin and SHLP6.

    Gruschus JM, Morris DL, Tjandra N

    Scientific reports · 2023-08-29 · Journal Article

    current
    PMID 37644144PMC10465549DOI 10.1038/s41598-023-41053-0Humanin (HN)SHLP2SHLP3SHLP6

  6. Reference 6

    The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.

    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

    current
    PMID 25738459PMC4350682DOI 10.1016/j.cmet.2015.02.009MOTS-cHumanin (HN)SHLP2SHLP3SHLP6AMP-activated protein kinase

Study models of these references

What kind of experiment each cited paper reports, taken from its abstract unless marked. Not a summary of results.

ReferenceStudy models
Cobb LJ et al. 2016Study models reported: in vitro; animal (rat, mouse) · from the full text
Okada AK et al. 2017Study models reported: in vitro · from the abstract
Kim SK et al. 2023Study models reported: in vitro; animal (mouse); human participants (observational) · from the full textCorrection published: Nat Commun. 2023 Aug 17;14(1):4995. doi: 10.1038/s41467-023-40832-7.
Kim SJ et al. 2024Study models reported: in vitro; animal (mouse); human participants (observational) · from the full text
Gruschus JM et al. 2023Computational analysis
Lee C et al. 2015Study models reported: in vitro; animal (mouse) · from the full text

Record history

Published 2026-09-16.

No changes to this record's content have been recorded since publication.

Each entry names the parts of this record that changed on that date. Changes to links between records and to catalogue links are not listed. This history covers the tracked record fields; study findings are not listed here.

Cite this record: Purely Peptides Research Library. SHLP2. Published 2026-09-16. https://purelypeptides.org/research/compounds/shlp2/

10

Methodology & citation verification

Reference identity is checked against official PubMed metadata. Local deterministic receipts bind each normalized title and canonical metadata record to its verification date. Scientific values remain absent when an authoritative source has not been verified.

Read the full methodology →