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NPFFR2 neuropeptide FF receptor 2 [ Homo sapiens (human) ]

Gene ID: 10886, updated on 11-Apr-2024

Summary

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Official Symbol
NPFFR2provided by HGNC
Official Full Name
neuropeptide FF receptor 2provided by HGNC
Primary source
HGNC:HGNC:4525
See related
Ensembl:ENSG00000056291 MIM:607449; AllianceGenome:HGNC:4525
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
GPR74; NPFF2; NPGPR; HLWAR77
Summary
This gene encodes a member of a subfamily of G-protein-coupled neuropeptide receptors. This protein is activated by the neuropeptides A-18-amide (NPAF) and F-8-amide (NPFF) and may function in pain modulation and regulation of the opioid system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]
Expression
Biased expression in placenta (RPKM 1.4), thyroid (RPKM 0.2) and 7 other tissues See more
Orthologs
mouse all
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Genomic context

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See NPFFR2 in Genome Data Viewer
Location:
4q13.3
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (72032000..72148305)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (75374029..75490284)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (72897717..73014022)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:72479894-72481093 Neighboring gene uncharacterized LOC105377271 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr4:72519382-72520581 Neighboring gene RNA, 5S ribosomal pseudogene 163 Neighboring gene VISTA enhancer hs2570 Neighboring gene GC vitamin D binding protein Neighboring gene ReSE screen-validated silencer GRCh37_chr4:72836369-72836534 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:72897326-72897928 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:72960191-72960690 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr4:72977919-72979118 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:73019056-73019842 Neighboring gene ADAM metallopeptidase with thrombospondin type 1 motif 3 Neighboring gene Sharpr-MPRA regulatory region 5509 Neighboring gene NANOG hESC enhancer GRCh37_chr4:73529485-73530023 Neighboring gene heterogeneous nuclear ribonucleoprotein A1 pseudogene 67

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. NPFFR2 gene compound heterozygous variants associated with preeclampsia identified by whole-exome sequencing. Jiang H, et al. Gene, 2023 Feb 20. PMID 36535464
  2. Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs. Ovejero-Benito MC, et al. Exp Dermatol, 2020 Dec. PMID 33058233
  3. Identification and functional characterization of the phosphorylation sites of the neuropeptide FF2 receptor. Bray L, et al. J Biol Chem, 2014 Dec 5. PMID 25326382, Free PMC Article
  4. Neuropeptide FF2 receptor distribution in the human brain. An immunohistochemical study. Goncharuk V, et al. Peptides, 2008 Sep. PMID 18565622
  5. A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis. Dahlman I, et al. Am J Hum Genet, 2007 Jun. PMID 17503329, Free PMC Article

See all (27) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NPFFR2 gene compound heterozygous variants associated with preeclampsia identified by whole-exome sequencing.
    Title: NPFFR2 gene compound heterozygous variants associated with preeclampsia identified by whole-exome sequencing.
  2. Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs.
    Title: Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs.
  3. Effects of systematic N-terminus deletions and benzoylations of endogenous RF-amide peptides on NPFF1R, NPFF2R, GPR10, GPR54 and GPR103.
    Title: Effects of systematic N-terminus deletions and benzoylations of endogenous RF-amide peptides on NPFF1R, NPFF2R, GPR10, GPR54 and GPR103.
  4. The NPFF2 neuropeptide FF receptor phosphorylation sites have been mapped and their role identified in receptor regulation.
    Title: Identification and functional characterization of the phosphorylation sites of the neuropeptide FF2 receptor.
  5. These data show that NPFF-induced heterologous desensitization of MOP receptor signaling is mediated by GRK2 and could involve transphosphorylation within the heteromeric receptor complex.
    Title: GRK2 protein-mediated transphosphorylation contributes to loss of function of μ-opioid receptors induced by neuropeptide FF (NPFF2) receptors.
  6. Four genetic loci were strongly and independently associated with obesity, NPY2R, NPFFR2, MC4R, and FTO.
    Title: Polymorphisms in the NPY2R gene show significant associations with BMI that are additive to FTO, MC4R, and NPFFR2 gene effects.
  7. Besides regulation of reproduction, kisspeptins have a potential to mediate physiological effects on autonomic regulation and nociception in humans via the NPFF2R pathways.
    Title: Human kisspeptins activate neuropeptide FF2 receptor.
  8. species-related differences in the binding properties of NPFF(2) receptors
    Title: Pharmacological characterization of the mouse NPFF2 receptor.
  9. we identified hFF2 positive neurons in the forebrain and medulla oblongata of individuals who died suddenly.
    Title: Neuropeptide FF2 receptor distribution in the human brain. An immunohistochemical study.
  10. Observational study of gene-disease association. (HuGE Navigator)
    Title: A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis.
Submit: New GeneRIF Correction See all GeneRIFs (16)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables G protein-coupled receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables G protein-coupled receptor activity TAS
Traceable Author Statement
more info
 PubMed 
enables neuropeptide receptor activity IEA
Inferred from Electronic Annotation
more info
  
enables opioid receptor binding IEA
Inferred from Electronic Annotation
more info
  
enables peptide binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in G protein-coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cellular response to hormone stimulus IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in detection of abiotic stimulus TAS
Traceable Author Statement
more info
 PubMed 
involved_in neuropeptide signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in actin cytoskeleton IDA
Inferred from Direct Assay
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
neuropeptide FF receptor 2
Names
G-protein coupled receptor 74
G-protein coupled receptor HLWAR77
neuropeptide FF 2
neuropeptide G-protein coupled receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001144756.2 → NP_001138228.1  neuropeptide FF receptor 2 isoform 3

    See identical proteins and their annotated locations for NP_001138228.1

    Status: REVIEWED

    Source sequence(s)
    AC106051, AC106898, AF119815, AF236083, AK290937, CN285250
    Consensus CDS
    CCDS47072.1
    UniProtKB/Swiss-Prot
    Q96RV1, Q9NR49, Q9Y5X5
    Related
    ENSP00000379321.1, ENST00000395999.5
    Conserved Domains (2) summary
    pfam00001
    Location:65 → 336
    7tm_1; 7 transmembrane receptor (rhodopsin family)
    cl21561
    Location:56 → 178
    7tm_4; Olfactory receptor

  2. NM_004885.3 → NP_004876.3  neuropeptide FF receptor 2 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC106051, AC106898
    Consensus CDS
    CCDS3552.1
    UniProtKB/Swiss-Prot
    Q96RV1, Q9NR49, Q9Y5X5
    UniProtKB/TrEMBL
    A0PJM9
    Related
    ENSP00000307822.7, ENST00000308744.12
    Conserved Domains (1) summary
    cd15980
    Location:46 → 344
    7tmA_NPFFR2; neuropeptide FF receptor 2, member of the class A family of seven-transmembrane G protein-coupled receptors

  3. NM_053036.3 → NP_444264.1  neuropeptide FF receptor 2 isoform 1

    See identical proteins and their annotated locations for NP_444264.1

    Status: REVIEWED

    Source sequence(s)
    AC106051, AC106898, AF119815, AK290937, CN285250
    Consensus CDS
    CCDS3552.1
    UniProtKB/Swiss-Prot
    Q96RV1, Q9NR49, Q9Y5X5
    UniProtKB/TrEMBL
    A0PJM9
    Related
    ENSP00000351599.3, ENST00000358749.3
    Conserved Domains (1) summary
    cd15980
    Location:46 → 344
    7tmA_NPFFR2; neuropeptide FF receptor 2, member of the class A family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    72032000..72148305
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011531554.3 → XP_011529856.2  neuropeptide FF receptor 2 isoform X1

  2. XM_047449545.1 → XP_047305501.1  neuropeptide FF receptor 2 isoform X2

    Related
    ENST00000506359.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    75374029..75490284
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054348802.1 → XP_054204777.1  neuropeptide FF receptor 2 isoform X1

  2. XM_054348803.1 → XP_054204778.1  neuropeptide FF receptor 2 isoform X2

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y5X5.2 GenPept UniProtKB/Swiss-Prot:Q9Y5X5

Gene LinkOut

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