OPRL1 opioid related nociceptin receptor 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: OPRL1provided by HGNC
Official Full Name: opioid related nociceptin receptor 1provided by HGNC
Primary source: HGNC:HGNC:8155
See related: Ensembl:ENSG00000125510 MIM:602548; AllianceGenome:HGNC:8155
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: NOP; OOR; KOR3; NOPr; OPRL; ORL1; KOR-3; NOCIR; PNOCR
Summary: The protein encoded by this gene is a member of the 7 transmembrane-spanning G protein-coupled receptor family, and functions as a receptor for the endogenous, opioid-related neuropeptide, nociceptin/orphanin FQ. This receptor-ligand system modulates a variety of biological functions and neurobehavior, including stress responses and anxiety behavior, learning and memory, locomotor activity, and inflammatory and immune responses. A promoter region between this gene and the 5'-adjacent RGS19 (regulator of G-protein signaling 19) gene on the opposite strand functions bi-directionally as a core-promoter for both genes, suggesting co-operative transcriptional regulation of these two functionally related genes. Alternatively spliced transcript variants have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]
Expression: Broad expression in brain (RPKM 1.7), testis (RPKM 0.9) and 14 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20q13.33

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (64080082..64100643)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (65900137..65922785)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (62711435..62731996)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Heterodimerization of apelin and opioid receptor-like 1 receptors mediates apelin-13-induced G protein biased signaling.
Title: Heterodimerization of apelin and opioid receptor-like 1 receptors mediates apelin-13-induced G protein biased signaling.
Decreased Nociceptin Receptors Are Related to Resilience and Recovery in College Women Who Have Experienced Sexual Violence. Decreased midbrain and cerebellum nociceptin receptors are associated with less severe PTSD symptoms. Medications that target nociceptin should be explored to prevent and treat PTSD.
Title: Decreased Nociceptin Receptors Are Related to Resilience and Recovery in College Women Who Have Experienced Sexual Violence: Therapeutic Implications for Posttraumatic Stress Disorder.
Low methylation levels in intron 1 of OPRL1 are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by OPRL1 methylation: in individuals with low methylation of OPRL1, frequency of binge drinking is associated with stronger BOLD response in the ventral striatum during reward anticipation.
Title: Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents.
NOP-R is expressed on epidermal keratinocytes in pachyonychia congenita. Robust NOP-R expression was detected in epidermal keratinocytes and in a subset of PGP9.5+ fibers in both epidermis and dermis. NOP-R expression in keratinocytes was reduced in -affected plantar skin vs unaffected skin. Expression occurred in dermal NFH+ myelinated fibers in all groups, and SP+ fibers, but few CGRP+ fibers co-expressed it.
Title: Nociceptin/orphanin FQ opioid peptide-receptor expression in pachyonychia congenita.
Nociceptin receptor ORL1 increases the cell surface expression of reticulon 4 receptor (NgR1) in HEK293T cells.
Title: The nociceptin receptor inhibits axonal regeneration and recovery from spinal cord injury.
the present findings on OPRM1 and OPRL1 methylation together with our previous study on OPRK1 and OPRD1, suggest an epigenetic involvement of the opioid system in AD, and a potential diagnostic value of opioid receptor methylation for AD.
Title: Elevated methylation of OPRM1 and OPRL1 genes in Alzheimer's disease.
The rs2229205 SNP in the OPRL1 gene may be a genetic factor that contributes to individual differences in the vulnerability to smoking in Japanese individuals
Title: Pharmacogenetics of cystic fibrosis treatment.
The results of in vitro Ala scanning analyses revealed that the labeled residues were Cys59 in TM1, Cys215 and Cys231 in TM5, and Cys310 in TM7. The present study has provided a novel method of Cys(Npys)-affinity labeling for identification of the ligand-binding sites in the ORL1 receptor.
Title: Specific affinity-labeling of the nociceptin ORL1 receptor using a thiol-activated Cys(Npys)-containing peptide ligand.
Study presents evidence suggesting that the PNOC and OPRL1 are dysregulated in suicide completers, thereby potentially contributing to impaired emotional and behavioral control and, ultimately, to the suicidal crisis
Title: Decreased expression of nociceptin/orphanin FQ in the dorsal anterior cingulate cortex of suicides.
Data suggest that nociceptin/nociceptin receptor signaling in neurons of the hippocampus modulate learning and memory. [REVIEW]
Title: Nociceptin/orphanin-FQ modulation of learning and memory.

Submit: New GeneRIF Correction See all GeneRIFs (40)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

OPRL1_1278 (e-PCR)
- UniSTS:277545

RH66077 (e-PCR)
- UniSTS:84573

RH102037 (e-PCR)
- UniSTS:96371

G10715 (e-PCR)
- UniSTS:35215

SHGC-12017 (e-PCR)
- UniSTS:9685

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein-coupled receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables G protein-coupled receptor activity	IPI Inferred from Physical Interaction more info	PubMed
enables neuropeptide binding	IBA Inferred from Biological aspect of Ancestor more info
enables nociceptin receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables nociceptin receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled opioid receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within_positive_effect calcium-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in conditioned place preference	IEA Inferred from Electronic Annotation more info
involved_in eating behavior	IEA Inferred from Electronic Annotation more info
involved_in estrous cycle	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of blood pressure	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cAMP-mediated signaling	IEA Inferred from Electronic Annotation more info
involved_in neuropeptide signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in phospholipase C-activating G protein-coupled receptor signaling pathway	IPI Inferred from Physical Interaction more info	PubMed
involved_in positive regulation of urine volume	IEA Inferred from Electronic Annotation more info
involved_in regulation of locomotor rhythm	IEA Inferred from Electronic Annotation more info
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info
involved_in sensory perception	TAS Traceable Author Statement more info	PubMed
involved_in sensory perception of pain	IBA Inferred from Biological aspect of Ancestor more info
involved_in sensory perception of pain	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor 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	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: nociceptin receptor

Names: kappa-type 3 opioid receptor; kappa3-related opioid receptor; nociceptin/orphanin FQ receptor; opiate receptor-like 1; orphanin FQ 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)

NM_000913.6 → NP_000904.1 nociceptin receptor isoform 1

See identical proteins and their annotated locations for NP_000904.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the 5' non-coding region; therefore, has a shorter 5' UTR compared to variant 1. Variants 1, 2, and 3 encode the same isoform (1).

Source sequence(s)

AF285093, BC038433, CB048300, R17579

Consensus CDS

CCDS13556.1

UniProtKB/Swiss-Prot

P41146, Q8TD34, Q8WYH9, Q9H4K4

UniProtKB/TrEMBL

Q6FGM5

Related

ENSP00000347848.4, ENST00000355631.8

Conserved Domains (1) summary

cd15092
Location:52 → 330

7tmA_NOFQ_opioid_R; nociceptin/orphanin FQ peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001200019.2 → NP_001186948.1 nociceptin receptor isoform 1

See identical proteins and their annotated locations for NP_001186948.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains alternate 5' non-coding exons; therefore, has a different 5' UTR compared to variant 1. Variants 1, 2, and 3 encode the same isoform (1).

Source sequence(s)

AL590548, BC038433, CB048300, R17579

Consensus CDS

CCDS13556.1

UniProtKB/Swiss-Prot

P41146, Q8TD34, Q8WYH9, Q9H4K4

UniProtKB/TrEMBL

Q6FGM5

Related

ENSP00000336764.3, ENST00000349451.3

Conserved Domains (1) summary

cd15092
Location:52 → 330

7tmA_NOFQ_opioid_R; nociceptin/orphanin FQ peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001318853.2 → NP_001305782.1 nociceptin receptor isoform 1x

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes two isoforms, which result from the use of alternative in-frame translation termination codons. The shorter isoform (1) results from translation termination at the upstream UGA stop codon, while the longer isoform (1x) results from UGA stop codon readthrough to the downstream UAG termination codon. This RefSeq represents the longer, C-terminally extended isoform (1x). As the UGA stop codon has been reported to specify several alternative amino acids (tryptophan, cysteine, arginine and serine), the location of the upstream UGA stop codon in the longer isoform is denoted by an 'X'.

Source sequence(s)

AF285093, BC038433, CB048300, R17579

Consensus CDS

CCDS93075.1

UniProtKB/TrEMBL

A0A5F9ZI64, Q6FGM5

Related

ENSP00000500894.2, ENST00000672146.3

Conserved Domains (2) summary

pfam00001
Location:68 → 319

7tm_1; 7 transmembrane receptor (rhodopsin family)

cl21561
Location:66 → 188

7tm_4; Olfactory receptor
NM_001318854.1 → NP_001305783.1 nociceptin receptor isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate, in-frame acceptor splice site in the 5' coding region compared to variant 1. The resulting isoform (2, also known as KOR-3D) is shorter, missing a 5 aa protein segment compared to isoform 1.

Source sequence(s)

AF126470, AL121581, BC038433, CB048300, R17579

UniProtKB/TrEMBL

Q6FGM5

Conserved Domains (2) summary

pfam00001
Location:68 → 314

7tm_1; 7 transmembrane receptor (rhodopsin family)

cl21561
Location:66 → 183

7tm_4; Olfactory receptor
NM_001318855.1 → NP_001305784.1 nociceptin receptor isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate acceptor splice site in the 5' coding region, which results in translation initiation from an alternate, downstream start codon compared to variant 1. The encoded isoform (3, also known as KOR-3A) is shorter, with a distinct N-terminus compared to isoform 1.

Source sequence(s)

AF115266, AL121581, BC038433, CB048300, R17579

UniProtKB/TrEMBL

A0A0G2JQE4, Q8IXB0

Conserved Domains (2) summary

pfam00001
Location:48 → 290

7tm_1; 7 transmembrane receptor (rhodopsin family)

cl21561
Location:112 → 159

7tm_4; Olfactory receptor
NM_182647.4 → NP_872588.1 nociceptin receptor isoform 1

See identical proteins and their annotated locations for NP_872588.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes two isoforms, which result from the use of alternative in-frame translation termination codons. The shorter isoform (1) results from translation termination at the upstream UGA stop codon, while the longer isoform (1x) results from UGA stop codon readthrough to the downstream UAG termination codon. This RefSeq represents the shorter isoform (1). Variants 1, 2, and 3 encode the same isoform (1).

Source sequence(s)

AF285093, BC038433, CB048300, R17579

Consensus CDS

CCDS13556.1

UniProtKB/Swiss-Prot

P41146, Q8TD34, Q8WYH9, Q9H4K4

UniProtKB/TrEMBL

Q6FGM5

Related

ENSP00000336843.2, ENST00000336866.7

Conserved Domains (1) summary

cd15092
Location:52 → 330

7tmA_NOFQ_opioid_R; nociceptin/orphanin FQ peptide receptor, 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

NC_000020.11 Reference GRCh38.p14 Primary Assembly

Range

64080082..64100643

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047440155.1 → XP_047296111.1 nociceptin receptor isoform X3
XM_047440156.1 → XP_047296112.1 nociceptin receptor isoform X3
XM_047440157.1 → XP_047296113.1 nociceptin receptor isoform X4
XM_047440154.1 → XP_047296110.1 nociceptin receptor isoform X2

UniProtKB/Swiss-Prot

P41146, Q8TD34, Q8WYH9, Q9H4K4
XM_011528828.4 → XP_011527130.1 nociceptin receptor isoform X1

UniProtKB/TrEMBL

Q6FGM5

Conserved Domains (2) summary

pfam00001
Location:86 → 337

7tm_1; 7 transmembrane receptor (rhodopsin family)

cl21561
Location:84 → 206

7tm_4; Olfactory receptor
XM_011528830.4 → XP_011527132.1 nociceptin receptor isoform X4

See identical proteins and their annotated locations for XP_011527132.1

UniProtKB/TrEMBL

A0A0G2JQE4

Conserved Domains (2) summary

pfam00001
Location:1 → 238

7tm_1; 7 transmembrane receptor (rhodopsin family)

cl21561
Location:60 → 107

7tm_4; Olfactory receptor
XM_047440153.1 → XP_047296109.1 nociceptin receptor isoform X1