NPFF2_HUMAN
ID NPFF2_HUMAN Reviewed; 522 AA.
AC Q9Y5X5; Q96RV1; Q9NR49;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Neuropeptide FF receptor 2;
DE AltName: Full=G-protein coupled receptor 74;
DE AltName: Full=G-protein coupled receptor HLWAR77;
DE AltName: Full=Neuropeptide G-protein coupled receptor;
GN Name=NPFFR2; Synonyms=GPR74, NPFF2, NPGPR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Fetus;
RX PubMed=10079187; DOI=10.1006/bbrc.1999.0332;
RA Cikos S., Gregor P., Koppel J.;
RT "Sequence and tissue distribution of a novel G-protein-coupled receptor
RT expressed prominently in human placenta.";
RL Biochem. Biophys. Res. Commun. 256:352-356(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND CHARACTERIZATION.
RC TISSUE=Brain;
RX PubMed=10851242; DOI=10.1074/jbc.m004515200;
RA Elshourbagy N.A., Ames R.S., Fitzgerald L.R., Foley J.J., Chambers J.K.,
RA Szekeres P.G., Evans N.A., Schmidt D.B., Buckley P.T., Dytko G.M.,
RA Murdock P.R., Milligan G., Groarke D.A., Tan K.B., Shabon U.,
RA Nuthulaganti P., Wang D.Y., Wilson S., Bergsma D.J., Sarau H.M.;
RT "Receptor for the pain modulatory neuropeptides FF and AF is an orphan G
RT protein-coupled receptor.";
RL J. Biol. Chem. 275:25965-25971(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND CHARACTERIZATION.
RC TISSUE=Spinal cord;
RX PubMed=11024015; DOI=10.1074/jbc.m004385200;
RA Bonini J.A., Jones K.A., Adham N., Forray C., Artymyshyn R., Durkin M.M.,
RA Smith K.E., Tamm J.A., Boteju L.W., Lakhlani P.P., Raddatz R., Yao W.-J.,
RA Ogozalek K.L., Boyle N., Kouranova E.V., Quan Y., Vaysse P.J., Wetzel J.M.,
RA Branchek T.A., Gerald C., Borowsky B.;
RT "Identification and characterization of two G protein-coupled receptors for
RT neuropeptide FF.";
RL J. Biol. Chem. 275:39324-39331(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=10837915; DOI=10.1016/s0169-328x(00)00052-8;
RA Parker R.M.C., Copeland N.G., Eyre H.J., Liu M., Gilbert D.J., Crawford J.,
RA Couzens M., Sutherland G.R., Jenkins N.A., Herzog H.;
RT "Molecular cloning and characterisation of GPR74 a novel G-protein coupled
RT receptor closest related to the Y-receptor family.";
RL Brain Res. Mol. Brain Res. 77:199-208(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Liu Q., Guan X.-M., McDonald T.P., Jiang Q., Zeng Z., Marlene J.,
RA Williams D.L. Jr., Hong Y., Figueroa D., Clements M.K., Mallee J., Wang R.,
RA Evans J., Gould R., Austin C.P.;
RT "Identification and characterization of two cognate receptors for mammalian
RT FMRFamide-like neuropeptides.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RA Laemmle B.S., Schindler M., Beilmann M., Hamilton B.S., Doods H.N.,
RA Wieland H.A.;
RT "Cloning and characterization of the NPGP receptor and identification of a
RT novel short mRNA isoform in human hypothalamus.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide)
CC neuropeptides, also known as morphine-modulating peptides. Can also be
CC activated by a variety of naturally occurring or synthetic FMRF-amide
CC like ligands. This receptor mediates its action by association with G
CC proteins that activate a phosphatidylinositol-calcium second messenger
CC system.
CC -!- INTERACTION:
CC Q9Y5X5-3; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-18076879, EBI-3918971;
CC Q9Y5X5-3; A2RU14: TMEM218; NbExp=3; IntAct=EBI-18076879, EBI-10173151;
CC Q9Y5X5-3; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-18076879, EBI-11988865;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1; Synonyms=long form;
CC IsoId=Q9Y5X5-1; Sequence=Displayed;
CC Name=2; Synonyms=short form;
CC IsoId=Q9Y5X5-2; Sequence=VSP_001907;
CC Name=3;
CC IsoId=Q9Y5X5-3; Sequence=VSP_001908, VSP_001909;
CC Name=4;
CC IsoId=Q9Y5X5-4; Sequence=VSP_001910, VSP_001911;
CC -!- TISSUE SPECIFICITY: Isoform 1 is abundant in placenta. Relatively
CC highly expressed in thymus, testis, and small intestine. Expressed at
CC low levels in several tissues including spleen, prostate, brain, heart,
CC ovary, colon, kidney, lung, liver and pancreas and not expressed in
CC skeletal muscle and leukocytes. Isoform 2 expression is highest in
CC placenta (but at relatively low level compared to isoform 1). Very low
CC level of expression in numerous tissues including adipose tissue and
CC many brain regions. Isoform 3 is expressed in brain and heart and, at
CC lower levels, in kidney, liver, lung and pancreas.
CC {ECO:0000269|PubMed:10079187}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK58513.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF119815; AAD22047.1; -; mRNA.
DR EMBL; AF257210; AAF87078.1; -; mRNA.
DR EMBL; AF268899; AAG41398.1; -; mRNA.
DR EMBL; AF236083; AAK58513.1; ALT_FRAME; mRNA.
DR EMBL; AF330053; AAK94197.1; -; mRNA.
DR EMBL; AJ311393; CAC85427.1; -; mRNA.
DR CCDS; CCDS3551.1; -. [Q9Y5X5-2]
DR CCDS; CCDS3552.1; -. [Q9Y5X5-2]
DR CCDS; CCDS47072.1; -. [Q9Y5X5-3]
DR RefSeq; NP_001138228.1; NM_001144756.1. [Q9Y5X5-3]
DR RefSeq; NP_004876.2; NM_004885.2. [Q9Y5X5-2]
DR RefSeq; NP_444264.1; NM_053036.2. [Q9Y5X5-2]
DR AlphaFoldDB; Q9Y5X5; -.
DR SMR; Q9Y5X5; -.
DR BioGRID; 116093; 3.
DR IntAct; Q9Y5X5; 3.
DR STRING; 9606.ENSP00000307822; -.
DR BindingDB; Q9Y5X5; -.
DR ChEMBL; CHEMBL5952; -.
DR GuidetoPHARMACOLOGY; 301; -.
DR GlyGen; Q9Y5X5; 4 sites.
DR iPTMnet; Q9Y5X5; -.
DR PhosphoSitePlus; Q9Y5X5; -.
DR BioMuta; NPFFR2; -.
DR DMDM; 13878604; -.
DR EPD; Q9Y5X5; -.
DR MassIVE; Q9Y5X5; -.
DR PaxDb; Q9Y5X5; -.
DR PeptideAtlas; Q9Y5X5; -.
DR PRIDE; Q9Y5X5; -.
DR Antibodypedia; 3469; 228 antibodies from 27 providers.
DR DNASU; 10886; -.
DR Ensembl; ENST00000308744.12; ENSP00000307822.7; ENSG00000056291.19. [Q9Y5X5-2]
DR Ensembl; ENST00000358749.3; ENSP00000351599.3; ENSG00000056291.19. [Q9Y5X5-2]
DR Ensembl; ENST00000395999.5; ENSP00000379321.1; ENSG00000056291.19. [Q9Y5X5-3]
DR GeneID; 10886; -.
DR KEGG; hsa:10886; -.
DR MANE-Select; ENST00000308744.12; ENSP00000307822.7; NM_004885.3; NP_004876.3. [Q9Y5X5-2]
DR UCSC; uc003hgg.3; human. [Q9Y5X5-1]
DR CTD; 10886; -.
DR DisGeNET; 10886; -.
DR GeneCards; NPFFR2; -.
DR HGNC; HGNC:4525; NPFFR2.
DR HPA; ENSG00000056291; Tissue enhanced (lymphoid tissue, seminal vesicle).
DR MIM; 607449; gene.
DR neXtProt; NX_Q9Y5X5; -.
DR OpenTargets; ENSG00000056291; -.
DR PharmGKB; PA28918; -.
DR VEuPathDB; HostDB:ENSG00000056291; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01020000230390; -.
DR HOGENOM; CLU_1916367_0_0_1; -.
DR InParanoid; Q9Y5X5; -.
DR OMA; FKMTVPH; -.
DR OrthoDB; 1308959at2759; -.
DR PhylomeDB; Q9Y5X5; -.
DR TreeFam; TF315303; -.
DR PathwayCommons; Q9Y5X5; -.
DR Reactome; R-HSA-389397; Orexin and neuropeptides FF and QRFP bind to their respective receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; Q9Y5X5; -.
DR SIGNOR; Q9Y5X5; -.
DR BioGRID-ORCS; 10886; 6 hits in 1063 CRISPR screens.
DR ChiTaRS; NPFFR2; human.
DR GenomeRNAi; 10886; -.
DR Pharos; Q9Y5X5; Tchem.
DR PRO; PR:Q9Y5X5; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9Y5X5; protein.
DR Bgee; ENSG00000056291; Expressed in placenta and 82 other tissues.
DR ExpressionAtlas; Q9Y5X5; baseline and differential.
DR Genevisible; Q9Y5X5; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IBA:GO_Central.
DR GO; GO:0008188; F:neuropeptide receptor activity; IEA:InterPro.
DR GO; GO:0031628; F:opioid receptor binding; IEA:InterPro.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0009582; P:detection of abiotic stimulus; TAS:ProtInc.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0045761; P:regulation of adenylate cyclase activity; IEA:InterPro.
DR GO; GO:2000479; P:regulation of cAMP-dependent protein kinase activity; IEA:InterPro.
DR GO; GO:0043408; P:regulation of MAPK cascade; IEA:InterPro.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR005395; NPFF_rcpt.
DR InterPro; IPR005397; NPFF_rcpt_2.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01570; NPFFRECEPTOR.
DR PRINTS; PR01572; NPFFRECEPTR2.
DR SMART; SM01381; 7TM_GPCR_Srsx; 1.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..522
FT /note="Neuropeptide FF receptor 2"
FT /id="PRO_0000069915"
FT TOPO_DOM 1..147
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..184
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..205
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 206..221
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 222..242
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 243..262
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 263..283
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 284..319
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 320..340
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 341..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..398
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 399..413
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 414..434
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 435..522
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 25..49
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 220..308
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 1..102
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10851242,
FT ECO:0000303|PubMed:11024015, ECO:0000303|Ref.5"
FT /id="VSP_001907"
FT VAR_SEQ 1..99
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10837915"
FT /id="VSP_001908"
FT VAR_SEQ 100
FT /note="R -> M (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10837915"
FT /id="VSP_001909"
FT VAR_SEQ 101..132
FT /note="FIMNEKWDTNSSENWHPIWNVNDTKHHLYSDI -> MAIWKHDVQDQWIGPG
FT NICRSFSLYVSCNCCR (in isoform 4)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_001910"
FT VAR_SEQ 133..522
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.6"
FT /id="VSP_001911"
FT CONFLICT 466
FT /note="A -> T (in Ref. 1 and 4)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 522 AA; 60270 MW; 40CB9FCD42F77041 CRC64;
MNSFFGTPAA SWCLLESDVS SAPDKEAGRE RRALSVQQRG GPAWSGSLEW SRQSAGDRRR
LGLSRQTAKS SWSRSRDRTC CCRRAWWILV PAADRARRER FIMNEKWDTN SSENWHPIWN
VNDTKHHLYS DINITYVNYY LHQPQVAAIF IISYFLIFFL CMMGNTVVCF IVMRNKHMHT
VTNLFILNLA ISDLLVGIFC MPITLLDNII AGWPFGNTMC KISGLVQGIS VAASVFTLVA
IAVDRFQCVV YPFKPKLTIK TAFVIIMIIW VLAITIMSPS AVMLHVQEEK YYRVRLNSQN
KTSPVYWCRE DWPNQEMRKI YTTVLFANIY LAPLSLIVIM YGRIGISLFR AAVPHTGRKN
QEQWHVVSRK KQKIIKMLLI VALLFILSWL PLWTLMMLSD YADLSPNELQ IINIYIYPFA
HWLAFGNSSV NPIIYGFFNE NFRRGFQEAF QLQLCQKRAK PMEAYALKAK SHVLINTSNQ
LVQESTFQNP HGETLLYRKS AEKPQQELVM EELKETTNSS EI
