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Protein

Neuropeptide FF receptor 2

Gene

NPFFR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.

GO - Molecular functioni

  • G-protein coupled receptor activity Source: ProtInc
  • neuropeptide receptor activity Source: GO_Central
  • peptide binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000056291-MONOMER.
ReactomeiR-HSA-389397. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiQ9Y5X5.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuropeptide FF receptor 2
Alternative name(s):
G-protein coupled receptor 74
G-protein coupled receptor HLWAR77
Neuropeptide G-protein coupled receptor
Gene namesi
Name:NPFFR2
Synonyms:GPR74, NPFF2, NPGPR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:4525. NPFFR2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 147ExtracellularSequence analysisAdd BLAST147
Transmembranei148 – 168Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini169 – 184CytoplasmicSequence analysisAdd BLAST16
Transmembranei185 – 205Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini206 – 221ExtracellularSequence analysisAdd BLAST16
Transmembranei222 – 242Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini243 – 262CytoplasmicSequence analysisAdd BLAST20
Transmembranei263 – 283Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini284 – 319ExtracellularSequence analysisAdd BLAST36
Transmembranei320 – 340Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini341 – 377CytoplasmicSequence analysisAdd BLAST37
Transmembranei378 – 398Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini399 – 413ExtracellularSequence analysisAdd BLAST15
Transmembranei414 – 434Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini435 – 522CytoplasmicSequence analysisAdd BLAST88

GO - Cellular componenti

  • actin cytoskeleton Source: HPA
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi10886.
OpenTargetsiENSG00000056291.
PharmGKBiPA28918.

Chemistry databases

ChEMBLiCHEMBL5952.
GuidetoPHARMACOLOGYi301.

Polymorphism and mutation databases

BioMutaiNPFFR2.
DMDMi13878604.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000699151 – 522Neuropeptide FF receptor 2Add BLAST522

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi110N-linked (GlcNAc...)Sequence analysis1
Glycosylationi122N-linked (GlcNAc...)Sequence analysis1
Glycosylationi133N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi220 ↔ 308PROSITE-ProRule annotation
Glycosylationi300N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9Y5X5.
PaxDbiQ9Y5X5.
PeptideAtlasiQ9Y5X5.
PRIDEiQ9Y5X5.

PTM databases

iPTMnetiQ9Y5X5.
PhosphoSitePlusiQ9Y5X5.

Expressioni

Tissue specificityi

Isoform 1 is abundant in placenta. Relatively highly expressed in thymus, testis, and small intestine. Expressed at low levels in several tissues including spleen, prostate, brain, heart, ovary, colon, kidney, lung, liver and pancreas and not expressed in skeletal muscle and leukocytes. Isoform 2 expression is highest in placenta (but at relatively low level compared to isoform 1). Very low level of expression in numerous tissues including adipose tissue and many brain regions. Isoform 3 is expressed in brain and heart and, at lower levels, in kidney, liver, lung and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000056291.
CleanExiHS_NPFFR2.
ExpressionAtlasiQ9Y5X5. baseline and differential.
GenevisibleiQ9Y5X5. HS.

Organism-specific databases

HPAiCAB004780.
HPA026825.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000307822.

Chemistry databases

BindingDBiQ9Y5X5.

Structurei

3D structure databases

ProteinModelPortaliQ9Y5X5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000041285.
HOVERGENiHBG099624.
InParanoidiQ9Y5X5.
KOiK08375.
OMAiNTMCKIS.
OrthoDBiEOG091G098F.
PhylomeDBiQ9Y5X5.
TreeFamiTF315303.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR005395. NPFF_rcpt.
IPR005397. NPFF_rcpt_2.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01570. NPFFRECEPTOR.
PR01572. NPFFRECEPTR2.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q9Y5X5-1) [UniParc]FASTAAdd to basket
Also known as: long form

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNSFFGTPAA SWCLLESDVS SAPDKEAGRE RRALSVQQRG GPAWSGSLEW
60 70 80 90 100
SRQSAGDRRR LGLSRQTAKS SWSRSRDRTC CCRRAWWILV PAADRARRER
110 120 130 140 150
FIMNEKWDTN SSENWHPIWN VNDTKHHLYS DINITYVNYY LHQPQVAAIF
160 170 180 190 200
IISYFLIFFL CMMGNTVVCF IVMRNKHMHT VTNLFILNLA ISDLLVGIFC
210 220 230 240 250
MPITLLDNII AGWPFGNTMC KISGLVQGIS VAASVFTLVA IAVDRFQCVV
260 270 280 290 300
YPFKPKLTIK TAFVIIMIIW VLAITIMSPS AVMLHVQEEK YYRVRLNSQN
310 320 330 340 350
KTSPVYWCRE DWPNQEMRKI YTTVLFANIY LAPLSLIVIM YGRIGISLFR
360 370 380 390 400
AAVPHTGRKN QEQWHVVSRK KQKIIKMLLI VALLFILSWL PLWTLMMLSD
410 420 430 440 450
YADLSPNELQ IINIYIYPFA HWLAFGNSSV NPIIYGFFNE NFRRGFQEAF
460 470 480 490 500
QLQLCQKRAK PMEAYALKAK SHVLINTSNQ LVQESTFQNP HGETLLYRKS
510 520
AEKPQQELVM EELKETTNSS EI
Length:522
Mass (Da):60,270
Last modified:April 27, 2001 - v2
Checksum:i40CB9FCD42F77041
GO
Isoform 2 (identifier: Q9Y5X5-2) [UniParc]FASTAAdd to basket
Also known as: short form

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: Missing.

Show »
Length:420
Mass (Da):48,686
Checksum:i7A47C4CEEC1DBE07
GO
Isoform 3 (identifier: Q9Y5X5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-99: Missing.
     100-100: R → M

Show »
Length:423
Mass (Da):49,078
Checksum:i767946C4564A84F4
GO
Isoform 4 (identifier: Q9Y5X5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     101-132: FIMNEKWDTNSSENWHPIWNVNDTKHHLYSDI → MAIWKHDVQDQWIGPGNICRSFSLYVSCNCCR
     133-522: Missing.

Show »
Length:132
Mass (Da):15,055
Checksum:i0C561F6F086FC888
GO

Sequence cautioni

The sequence AAK58513 differs from that shown. Reason: Frameshift at position 503.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti466A → T (PubMed:10079187).Curated1
Sequence conflicti466A → T (PubMed:10837915).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0019071 – 102Missing in isoform 2. 3 PublicationsAdd BLAST102
Alternative sequenceiVSP_0019081 – 99Missing in isoform 3. 1 PublicationAdd BLAST99
Alternative sequenceiVSP_001909100R → M in isoform 3. 1 Publication1
Alternative sequenceiVSP_001910101 – 132FIMNE…LYSDI → MAIWKHDVQDQWIGPGNICR SFSLYVSCNCCR in isoform 4. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_001911133 – 522Missing in isoform 4. 1 PublicationAdd BLAST390

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF119815 mRNA. Translation: AAD22047.1.
AF257210 mRNA. Translation: AAF87078.1.
AF268899 mRNA. Translation: AAG41398.1.
AF236083 mRNA. Translation: AAK58513.1. Frameshift.
AF330053 mRNA. Translation: AAK94197.1.
AJ311393 mRNA. Translation: CAC85427.1.
CCDSiCCDS3551.1. [Q9Y5X5-1]
CCDS3552.1. [Q9Y5X5-2]
CCDS47072.1. [Q9Y5X5-3]
RefSeqiNP_001138228.1. NM_001144756.1. [Q9Y5X5-3]
NP_004876.2. NM_004885.2. [Q9Y5X5-1]
NP_444264.1. NM_053036.2. [Q9Y5X5-2]
UniGeneiHs.99231.

Genome annotation databases

EnsembliENST00000308744; ENSP00000307822; ENSG00000056291. [Q9Y5X5-1]
ENST00000344413; ENSP00000340789; ENSG00000056291. [Q9Y5X5-4]
ENST00000358749; ENSP00000351599; ENSG00000056291. [Q9Y5X5-2]
ENST00000395999; ENSP00000379321; ENSG00000056291. [Q9Y5X5-3]
GeneIDi10886.
KEGGihsa:10886.
UCSCiuc003hgg.3. human. [Q9Y5X5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF119815 mRNA. Translation: AAD22047.1.
AF257210 mRNA. Translation: AAF87078.1.
AF268899 mRNA. Translation: AAG41398.1.
AF236083 mRNA. Translation: AAK58513.1. Frameshift.
AF330053 mRNA. Translation: AAK94197.1.
AJ311393 mRNA. Translation: CAC85427.1.
CCDSiCCDS3551.1. [Q9Y5X5-1]
CCDS3552.1. [Q9Y5X5-2]
CCDS47072.1. [Q9Y5X5-3]
RefSeqiNP_001138228.1. NM_001144756.1. [Q9Y5X5-3]
NP_004876.2. NM_004885.2. [Q9Y5X5-1]
NP_444264.1. NM_053036.2. [Q9Y5X5-2]
UniGeneiHs.99231.

3D structure databases

ProteinModelPortaliQ9Y5X5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000307822.

Chemistry databases

BindingDBiQ9Y5X5.
ChEMBLiCHEMBL5952.
GuidetoPHARMACOLOGYi301.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ9Y5X5.
PhosphoSitePlusiQ9Y5X5.

Polymorphism and mutation databases

BioMutaiNPFFR2.
DMDMi13878604.

Proteomic databases

EPDiQ9Y5X5.
PaxDbiQ9Y5X5.
PeptideAtlasiQ9Y5X5.
PRIDEiQ9Y5X5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000308744; ENSP00000307822; ENSG00000056291. [Q9Y5X5-1]
ENST00000344413; ENSP00000340789; ENSG00000056291. [Q9Y5X5-4]
ENST00000358749; ENSP00000351599; ENSG00000056291. [Q9Y5X5-2]
ENST00000395999; ENSP00000379321; ENSG00000056291. [Q9Y5X5-3]
GeneIDi10886.
KEGGihsa:10886.
UCSCiuc003hgg.3. human. [Q9Y5X5-1]

Organism-specific databases

CTDi10886.
DisGeNETi10886.
GeneCardsiNPFFR2.
HGNCiHGNC:4525. NPFFR2.
HPAiCAB004780.
HPA026825.
MIMi607449. gene.
neXtProtiNX_Q9Y5X5.
OpenTargetsiENSG00000056291.
PharmGKBiPA28918.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000041285.
HOVERGENiHBG099624.
InParanoidiQ9Y5X5.
KOiK08375.
OMAiNTMCKIS.
OrthoDBiEOG091G098F.
PhylomeDBiQ9Y5X5.
TreeFamiTF315303.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000056291-MONOMER.
ReactomeiR-HSA-389397. Orexin and neuropeptides FF and QRFP bind to their respective receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiQ9Y5X5.

Miscellaneous databases

GenomeRNAii10886.
PROiQ9Y5X5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000056291.
CleanExiHS_NPFFR2.
ExpressionAtlasiQ9Y5X5. baseline and differential.
GenevisibleiQ9Y5X5. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR005395. NPFF_rcpt.
IPR005397. NPFF_rcpt_2.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR01570. NPFFRECEPTOR.
PR01572. NPFFRECEPTR2.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNPFF2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5X5
Secondary accession number(s): Q96RV1, Q9NR49
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: April 27, 2001
Last modified: November 2, 2016
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.