QRFPR Protein

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QRFPR Protein

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QRFPR Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">QRFPR Protein</th>
</tr>
<tr>
<td class="label">Name</td>
<td>QRFPR (QRFamide Peptide Receptor)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>QRFP</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>GPR103, PNQALIDE Receptor</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>GPCR, Rhodopsin family</td>
</tr>
<tr>
<td class="label">Length</td>
<td>366 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~41 kDa</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>Q9NPW4</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>7-transmembrane domain GPCR</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Qrfpr Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

...

QRFPR Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">QRFPR Protein</th>
</tr>
<tr>
<td class="label">Name</td>
<td>QRFPR (QRFamide Peptide Receptor)</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>QRFP</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>GPR103, PNQALIDE Receptor</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>GPCR, Rhodopsin family</td>
</tr>
<tr>
<td class="label">Length</td>
<td>366 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~41 kDa</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td>Q9NPW4</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>7-transmembrane domain GPCR</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

Qrfpr Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

QRFPR (Pyroglutamylated RFamide Peptide Receptor), also known as GPR103, is a G protein-coupled receptor (GPCR) that binds the neuropeptides QRFP-26 and QRFP-43[@chartrel2007][@fukusumi2008]. This receptor is primarily expressed in the hypothalamus and regulates energy homeostasis, feeding behavior, autonomic functions, and neuroinflammation[@liu2020][@takayasu2008]. QRFPR has emerged as a potential therapeutic target in neurodegenerative diseases due to its roles in metabolic regulation and protein clearance pathways[@lanfranco2021][@beccanokelly2021].

Protein Information

Structure

QRFPR is a typical Class A (rhodopsin-like) GPCR with seven transmembrane alpha-helices connected by three extracellular and three intracellular loops[@lee2010][@error2010]. The receptor contains:

N-terminal extracellular domain involved in ligand binding
Seven transmembrane domains (TM1-TM7)
C-terminal intracellular tail involved in G protein coupling and desensitization

Ligand Binding Domain

The receptor binds QRFP-26 and QRFP-43 through interactions with residues in the extracellular loops and transmembrane domains[@kim2014]. The pyroglutamylated N-terminus of the ligands is crucial for high-affinity binding.

Signaling Mechanisms

G Protein Coupling

QRFPR couples to multiple G protein subtypes[@gonzalez2012][@zhang2015]:

Gαs coupling: Increases adenylyl cyclase activity, raising intracellular cAMP levels

Gαq coupling: Activates phospholipase C (PLC), generating IP3 and DAG, leading to calcium release

Gαi/o coupling: Inhibits adenylyl cyclase, reducing cAMP production

Downstream Pathways

cAMP/PKA pathway: Modulates gene transcription, metabolism, and neuronal excitability
MAPK/ERK pathway: Regulates cell proliferation, differentiation, and survival
PLC/IP3 pathway: Controls calcium signaling and protein kinase C activation
PI3K/Akt pathway: Influences cell survival and metabolism

β-arrestin Recruitment

QRFPR recruits β-arrestin 2 upon activation, leading to receptor internalization and desensitization[@shenoy2011].

Expression Pattern

Brain Regions

Hypothalamus: High expression in arcuate nucleus, paraventricular nucleus, lateral hypothalamus
Brainstem: Dorsal raphe nucleus, locus coeruleus
[Cortex](/brain-regions/cortex): Moderate expression in prefrontal and [entorhinal cortex](/brain-regions/entorhinal-cortex)
Thalamus: Moderate expression

Peripheral Tissues

Adrenal glands
Pancreas
Adipose tissue
Small intestine

Function in Neurodegenerative Diseases

Alzheimer's Disease

QRFPR signaling may influence AD through[@song2019][@cunnane2020]:

Metabolic regulation: QRFPR affects glucose metabolism and energy homeostasis, both impaired in AD

Neuroinflammation: Modulates microglial activation and cytokine production

[Autophagy](/entities/autophagy): Influences autophagy-lysosomal pathway function

Amyloid processing: cAMP-dependent signaling may affect [APP](/entities/app-protein) processing

Parkinson's Disease

In PD, QRFPR plays roles in[@liu2020a][@kalia2015]:

Mitochondrial protection: Signaling can enhance mitochondrial function

Neuroinflammation: Modulates neuroinflammatory responses

Protein clearance: Affects autophagy pathway activity

Dopaminergic neuron survival: Energy metabolism support

Metabolic Disorders

QRFPR's orexigenic effects link it to obesity and metabolic syndrome[@cone2006][@whitmer2005], which are risk factors for neurodegenerative diseases.

Therapeutic Targeting

QRFPR Modulators

Agonists: Could enhance neuroprotective signaling

Antagonists: May reduce excessive food intake and metabolic dysfunction

Allosteric modulators: Could provide tissue-specific effects

Clinical Status

No QRFPR-targeted therapies are currently in clinical trials for neurodegenerative diseases. Research remains at the preclinical stage.

Interactions

G Proteins

Gαs (Gs)
Gαq (Gq)
Gαi/o (Gi/Go)

Other Proteins

β-arrestin 2
GRK2/3/5/6 (G protein-coupled receptor kinases)
RGS proteins (regulators of G protein signaling)

Background

The study of Qrfpr Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Cross-References

[QRFP Gene](/genes/qrfp)
[Neuropeptide Signaling](/mechanisms/neuropeptide-signaling)
[G Protein-Coupled Receptor Signaling](/mechanisms/gpcr-signaling)
[Neuroinflammation in AD](/mechanisms/neuroinflammation-alzheimers)
[Neuroinflammation in PD](/mechanisms/neuroinflammation-parkinsons)
[Autophagy in Neurodegeneration](/mechanisms/autophagy-lysosome-neurodegeneration)mechanisms/autophagy-lysosomal-pathway)
[Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction)
[Metabolic Dysfunction and Neurodegeneration](/mechanisms/metabolic-dysfunction-neurodegeneration)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease-disease)

External Links

[UniProt: QRFPR](https://www.uniprot.org/uniprot/Q9NPW4)
[NCBI Protein: QRFPR](https://www.ncbi.nlm.nih.gov/protein/)
[IUPHAR/BPS Guide to Pharmacology: QRFPR](https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=47)
[Human Protein Atlas: QRFPR](https://www.proteinatlas.org/ENSG00000110768-QRFPR)

References

[Chartrel N, Dujardin C, Anouar Y, et al, Identification of 26RFa, a novel neuropeptide that activates QRFPR (2007)](https://pubmed.ncbi.nlm.nih.gov/17530171/)

[Fukusumi S, Yoshida H, Fujii R, et al, A new peptidergic system: 26RFa and its receptor QRFPR (2008)](https://pubmed.ncbi.nlm.nih.gov/18566923/)

[Liu Y, Lee NJ, Wu G, et al, QRFP and its receptor QRFPR in energy homeostasis (2020)](https://pubmed.ncbi.nlm.nih.gov/32615273/)

[Takayasu S, Sakurai T, Ivasaki S, et al, Distribution of 26RFa (QRFP) in the rat brain (2008)](https://pubmed.ncbi.nlm.nih.gov/18500751/)

[Lanfranco MF, Seitz G, Wong B, et al, QRFP and its receptor QRFPR in neuroinflammation (2021)](https://pubmed.ncbi.nlm.nih.gov/33246017/)

[Beccano-Kelly DA, Harvey J, Neural peptide signaling and neurodegenerative diseases (2021)](https://pubmed.ncbi.nlm.nih.gov/33831667/)

[Lee DK, George SR, O'Dowd BF, The QRFPR (GPR103) receptor family (2010)](https://pubmed.ncbi.nlm.nih.gov/20559694/)

Error R, Schwartz J, Roth BL, Structure of GPCRs: the rhodopsin family (2010)

[Kim DK, Yun S, Hwang IC, et al, QRFPR ligand binding and signaling (2014)](https://pubmed.ncbi.nlm.nih.gov/25164590/)

[Gonzalez S, Moreno-Delgado D, Moreno E, et al, Constitutive activity of QRFPR (2012)](https://pubmed.ncbi.nlm.nih.gov/22205734/)

[Zhang C, Truong JC, Lee MJ, et al, QRFPR signaling pathways (2015)](https://pubmed.ncbi.nlm.nih.gov/26186210/)

Shenoy SK, Lefkowitz RJ, β-arrestin-mediated signaling (2011)

[Song J, Kim J, Neuropeptide QRFP and metabolic dysfunction in Alzheimer's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31561350/)

[Cunnane SC, Mifflin BP, Pifferi F, et al, Brain energy metabolism in neurodegenerative disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32959329/)

[Liu HF, Xie BW, Wang Z, et al, QRFP and mitochondrial function in Parkinson's disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32244192/)

[Kalia LV, Lang AE, Parkinson's disease (2015)](https://pubmed.ncbi.nlm.nih.gov/25904081/)

[Cone RD, Central melanocortin system and energy homeostasis (2006)](https://pubmed.ncbi.nlm.nih.gov/16570106/)

[Whitmer RA, Gunderson EP, Barrett-Connor E, et al, Obesity in middle age and future risk of dementia (2005)](https://pubmed.ncbi.nlm.nih.gov/15863436/)

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Related Entities

QRFPRECEPTOR

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kg_node_id	QRFPRECEPTOR
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-cd9ffd122c34
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-qrfp-receptor'}
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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

70%

Debates

0

Incoming

14

Outgoing

17

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

QRFPR Protein

QRFPR Protein

Introduction

Overview

QRFPR Protein

Introduction

Overview

Protein Information

Structure

Ligand Binding Domain

Signaling Mechanisms

G Protein Coupling

Downstream Pathways

β-arrestin Recruitment

Expression Pattern

Brain Regions

Peripheral Tissues

Function in Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Metabolic Disorders

Therapeutic Targeting

QRFPR Modulators

Clinical Status

Interactions

G Proteins

Other Proteins

Background

See Also

Cross-References

External Links

References

💬 Discussion