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

    Gene ID: 10886, updated on 2-Nov-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_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (72032000..72148305)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (75374029..75490284)
    RS_2024_09 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 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. Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs. Ovejero-Benito MC, et al. Exp Dermatol, 2020 Dec. PMID 33058233
    2. Sequence and tissue distribution of a novel G-protein-coupled receptor expressed prominently in human placenta. Cikos S, et al. Biochem Biophys Res Commun, 1999 Mar 16. PMID 10079187
    3. Prolactin releasing peptide has high affinity and efficacy at neuropeptide FF2 receptors. Engström M, et al. J Pharmacol Exp Ther, 2003 Jun. PMID 12606605
    4. Functional properties of Pfr(Tic)amide and BIBP3226 at human neuropeptide FF2 receptors. Engström M, et al. Peptides, 2003 Dec. PMID 15127947
    5. Neuropeptide FF (NPFF) analogs functionally antagonize opioid activities in NPFF2 receptor-transfected SH-SY5Y neuroblastoma cells. Mollereau C, et al. Mol Pharmacol, 2005 Mar. PMID 15608144

    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables opioid receptor binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of adenylate cyclase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of cAMP-dependent protein kinase activity 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
    		  
    is_active_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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