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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

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

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 147147ExtracellularSequence analysisAdd
BLAST
Transmembranei148 – 16821Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini169 – 18416CytoplasmicSequence analysisAdd
BLAST
Transmembranei185 – 20521Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini206 – 22116ExtracellularSequence analysisAdd
BLAST
Transmembranei222 – 24221Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini243 – 26220CytoplasmicSequence analysisAdd
BLAST
Transmembranei263 – 28321Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini284 – 31936ExtracellularSequence analysisAdd
BLAST
Transmembranei320 – 34021Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini341 – 37737CytoplasmicSequence analysisAdd
BLAST
Transmembranei378 – 39821Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini399 – 41315ExtracellularSequence analysisAdd
BLAST
Transmembranei414 – 43421Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini435 – 52288CytoplasmicSequence analysisAdd
BLAST

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

PharmGKBiPA28918.

Chemistry

ChEMBLiCHEMBL5952.
GuidetoPHARMACOLOGYi301.

Polymorphism and mutation databases

BioMutaiNPFFR2.
DMDMi13878604.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 522522Neuropeptide FF receptor 2PRO_0000069915Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi110 – 1101N-linked (GlcNAc...)Sequence analysis
Glycosylationi122 – 1221N-linked (GlcNAc...)Sequence analysis
Glycosylationi133 – 1331N-linked (GlcNAc...)Sequence analysis
Disulfide bondi220 ↔ 308PROSITE-ProRule annotation
Glycosylationi300 – 3001N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9Y5X5.
PaxDbiQ9Y5X5.
PRIDEiQ9Y5X5.

PTM databases

PhosphoSiteiQ9Y5X5.

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

BgeeiQ9Y5X5.
CleanExiHS_NPFFR2.
ExpressionAtlasiQ9Y5X5. baseline and differential.
GenevisibleiQ9Y5X5. HS.

Organism-specific databases

HPAiCAB004780.
HPA026825.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000307822.

Chemistry

BindingDBiQ9Y5X5.

Structurei

3D structure databases

ProteinModelPortaliQ9Y5X5.
SMRiQ9Y5X5. Positions 149-450.
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.
OrthoDBiEOG7GBFXN.
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 AAK58513.1 differs from that shown. Reason: Frameshift at position 503. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti466 – 4661A → T (PubMed:10079187).Curated
Sequence conflicti466 – 4661A → T (PubMed:10837915).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 102102Missing in isoform 2. 3 PublicationsVSP_001907Add
BLAST
Alternative sequencei1 – 9999Missing in isoform 3. 1 PublicationVSP_001908Add
BLAST
Alternative sequencei100 – 1001R → M in isoform 3. 1 PublicationVSP_001909
Alternative sequencei101 – 13232FIMNE…LYSDI → MAIWKHDVQDQWIGPGNICR SFSLYVSCNCCR in isoform 4. 1 PublicationVSP_001910Add
BLAST
Alternative sequencei133 – 522390Missing in isoform 4. 1 PublicationVSP_001911Add
BLAST

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.
SMRiQ9Y5X5. Positions 149-450.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000307822.

Chemistry

BindingDBiQ9Y5X5.
ChEMBLiCHEMBL5952.
GuidetoPHARMACOLOGYi301.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ9Y5X5.

Polymorphism and mutation databases

BioMutaiNPFFR2.
DMDMi13878604.

Proteomic databases

EPDiQ9Y5X5.
PaxDbiQ9Y5X5.
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.
GeneCardsiNPFFR2.
HGNCiHGNC:4525. NPFFR2.
HPAiCAB004780.
HPA026825.
MIMi607449. gene.
neXtProtiNX_Q9Y5X5.
PharmGKBiPA28918.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118781.
HOGENOMiHOG000041285.
HOVERGENiHBG099624.
InParanoidiQ9Y5X5.
KOiK08375.
OMAiNTMCKIS.
OrthoDBiEOG7GBFXN.
PhylomeDBiQ9Y5X5.
TreeFamiTF315303.

Enzyme and pathway databases

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

Miscellaneous databases

GenomeRNAii10886.
NextBioi41335.
PROiQ9Y5X5.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y5X5.
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...

Publicationsi

  1. "Sequence and tissue distribution of a novel G-protein-coupled receptor expressed prominently in human placenta."
    Cikos S., Gregor P., Koppel J.
    Biochem. Biophys. Res. Commun. 256:352-356(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Fetus.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHARACTERIZATION.
    Tissue: Brain.
  3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHARACTERIZATION.
    Tissue: Spinal cord.
  4. "Molecular cloning and characterisation of GPR74 a novel G-protein coupled receptor closest related to the Y-receptor family."
    Parker R.M.C., Copeland N.G., Eyre H.J., Liu M., Gilbert D.J., Crawford J., Couzens M., Sutherland G.R., Jenkins N.A., Herzog H.
    Brain Res. Mol. Brain Res. 77:199-208(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
  5. "Identification and characterization of two cognate receptors for mammalian FMRFamide-like neuropeptides."
    Liu Q., Guan X.-M., McDonald T.P., Jiang Q., Zeng Z., Marlene J., Williams D.L. Jr., Hong Y., Figueroa D., Clements M.K., Mallee J., Wang R., Evans J., Gould R., Austin C.P.
    Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  6. "Cloning and characterization of the NPGP receptor and identification of a novel short mRNA isoform in human hypothalamus."
    Laemmle B.S., Schindler M., Beilmann M., Hamilton B.S., Doods H.N., Wieland H.A.
    Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).

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: May 11, 2016
This is version 141 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.