RL3R2_HUMAN
ID RL3R2_HUMAN Reviewed; 374 AA.
AC Q8TDU9; B0M0L4; Q3MJB1; Q8NGZ8;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Relaxin-3 receptor 2;
DE Short=RLN3 receptor 2;
DE AltName: Full=G-protein coupled receptor 100;
DE AltName: Full=G-protein coupled receptor GPCR142;
DE AltName: Full=Insulin-like peptide INSL5 receptor;
DE AltName: Full=Relaxin family peptide receptor 4;
GN Name=RXFP4; Synonyms=GPCR142, GPR100, RLN3R2;
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], VARIANT SER-329, AND FUNCTION AS A RECEPTOR FOR
RP RLN3.
RX PubMed=14522967; DOI=10.1074/jbc.m308996200;
RA Liu C., Chen J., Sutton S., Roland B., Kuei C., Farmer N., Sillard R.,
RA Lovenberg T.W.;
RT "Identification of relaxin-3/INSL7 as a ligand for GPCR142.";
RL J. Biol. Chem. 278:50765-50770(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=14623098; DOI=10.1016/s0014-5793(03)01196-7;
RA Fredriksson R., Hoeglund P.J., Gloriam D.E.I., Lagerstroem M.C.,
RA Schioeth H.B.;
RT "Seven evolutionarily conserved human rhodopsin G protein-coupled receptors
RT lacking close relatives.";
RL FEBS Lett. 554:381-388(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INTERACTION WITH
RP BRADYKININ AND KALLIDIN.
RC TISSUE=Pancreatic carcinoma;
RX PubMed=14530218; DOI=10.1038/sj.bjp.0705521;
RA Boels K., Schaller H.C.;
RT "Identification and characterisation of GPR100 as a novel human G-protein-
RT coupled bradykinin receptor.";
RL Br. J. Pharmacol. 140:932-938(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S.,
RA Tsutsumi S., Aburatani H., Asai K., Akiyama Y.;
RT "Genome-wide discovery and analysis of human seven transmembrane helix
RT receptor genes.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12044878; DOI=10.1016/s0014-5793(02)02775-8;
RA Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S.;
RT "Identification of G protein-coupled receptor genes from the human genome
RT sequence.";
RL FEBS Lett. 520:97-101(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-329.
RC TISSUE=Testis;
RA Kaighin V.A., Martin A.L., Aronstam R.S.;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-329.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION AS A RECEPTOR FOR INSL5.
RX PubMed=15525639; DOI=10.1074/jbc.m409916200;
RA Liu C., Kuei C., Sutton S., Chen J., Bonaventure P., Wu J., Nepomuceno D.,
RA Kamme F., Tran D.T., Zhu J., Wilkinson T., Bathgate R., Eriste E.,
RA Sillard R., Lovenberg T.W.;
RT "INSL5 is a high affinity specific agonist for GPCR142 (GPR100).";
RL J. Biol. Chem. 280:292-300(2005).
CC -!- FUNCTION: High affinity receptor for INSL5. Also acts as receptor for
CC RLN3/relaxin-3, as well as bradykinin and kallidin. Binding of the
CC ligand inhibit cAMP accumulation. {ECO:0000269|PubMed:14522967,
CC ECO:0000269|PubMed:15525639}.
CC -!- INTERACTION:
CC Q8TDU9; P48165: GJA8; NbExp=3; IntAct=EBI-9519524, EBI-17458373;
CC Q8TDU9; Q8WXF3: RLN3; NbExp=9; IntAct=EBI-9519524, EBI-9519546;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in a broader range of tissues including
CC brain, kidney, testis, thymus, placenta, prostate, salivary gland,
CC thyroid and colon. {ECO:0000269|PubMed:14530218}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC05844.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AY394502; AAQ92316.1; -; mRNA.
DR EMBL; AY288415; AAP72124.1; -; mRNA.
DR EMBL; AY170824; AAO17676.1; -; mRNA.
DR EMBL; AB065617; BAC05844.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB083593; BAB89306.1; -; Genomic_DNA.
DR EMBL; AL355388; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; EU432129; ABY87928.1; -; mRNA.
DR EMBL; BC101507; AAI01508.1; -; mRNA.
DR EMBL; BC101509; AAI01510.1; -; mRNA.
DR CCDS; CCDS1124.1; -.
DR RefSeq; NP_871001.1; NM_181885.2.
DR AlphaFoldDB; Q8TDU9; -.
DR SMR; Q8TDU9; -.
DR BioGRID; 130880; 59.
DR IntAct; Q8TDU9; 11.
DR MINT; Q8TDU9; -.
DR STRING; 9606.ENSP00000357301; -.
DR BindingDB; Q8TDU9; -.
DR ChEMBL; CHEMBL1628473; -.
DR GuidetoPHARMACOLOGY; 354; -.
DR GlyGen; Q8TDU9; 2 sites.
DR iPTMnet; Q8TDU9; -.
DR PhosphoSitePlus; Q8TDU9; -.
DR BioMuta; RXFP4; -.
DR DMDM; 38258194; -.
DR PaxDb; Q8TDU9; -.
DR PeptideAtlas; Q8TDU9; -.
DR PRIDE; Q8TDU9; -.
DR ProteomicsDB; 74341; -.
DR Antibodypedia; 20424; 170 antibodies from 24 providers.
DR DNASU; 339403; -.
DR Ensembl; ENST00000368318.5; ENSP00000357301.4; ENSG00000173080.6.
DR GeneID; 339403; -.
DR KEGG; hsa:339403; -.
DR MANE-Select; ENST00000368318.5; ENSP00000357301.4; NM_181885.3; NP_871001.1.
DR UCSC; uc010pgs.3; human.
DR CTD; 339403; -.
DR DisGeNET; 339403; -.
DR GeneCards; RXFP4; -.
DR HGNC; HGNC:14666; RXFP4.
DR HPA; ENSG00000173080; Tissue enhanced (brain, intestine).
DR MIM; 609043; gene.
DR neXtProt; NX_Q8TDU9; -.
DR OpenTargets; ENSG00000173080; -.
DR PharmGKB; PA28848; -.
DR VEuPathDB; HostDB:ENSG00000173080; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01030000234534; -.
DR HOGENOM; CLU_009579_8_1_1; -.
DR InParanoid; Q8TDU9; -.
DR OMA; LWVLGNC; -.
DR OrthoDB; 880755at2759; -.
DR PhylomeDB; Q8TDU9; -.
DR TreeFam; TF330024; -.
DR PathwayCommons; Q8TDU9; -.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-444821; Relaxin receptors.
DR SignaLink; Q8TDU9; -.
DR BioGRID-ORCS; 339403; 15 hits in 1064 CRISPR screens.
DR GeneWiki; Relaxin/insulin-like_family_peptide_receptor_4; -.
DR GenomeRNAi; 339403; -.
DR Pharos; Q8TDU9; Tchem.
DR PRO; PR:Q8TDU9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8TDU9; protein.
DR Bgee; ENSG00000173080; Expressed in mucosa of transverse colon and 33 other tissues.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; IBA:GO_Central.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR GO; GO:2000253; P:positive regulation of feeding behavior; IEA:Ensembl.
DR InterPro; IPR000248; ATII_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00241; ANGIOTENSINR.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Membrane; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..374
FT /note="Relaxin-3 receptor 2"
FT /id="PRO_0000070106"
FT TOPO_DOM 1..43
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 44..64
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 65..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..99
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..116
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..209
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 210..230
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 231..249
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 271..281
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 282..302
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 303..374
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 17
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 114..191
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 329
FT /note="L -> S (in dbSNP:rs2152051)"
FT /evidence="ECO:0000269|PubMed:14522967,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.7"
FT /id="VAR_021516"
SQ SEQUENCE 374 AA; 41141 MW; 1929EA812C0804DA CRC64;
MPTLNTSASP PTFFWANASG GSVLSADDAP MPVKFLALRL MVALAYGLVG AIGLLGNLAV
LWVLSNCARR APGPPSDTFV FNLALADLGL ALTLPFWAAE SALDFHWPFG GALCKMVLTA
TVLNVYASIF LITALSVARY WVVAMAAGPG THLSLFWARI ATLAVWAAAA LVTVPTAVFG
VEGEVCGVRL CLLRFPSRYW LGAYQLQRVV LAFMVPLGVI TTSYLLLLAF LQRRQRRRQD
SRVVARSVRI LVASFFLCWF PNHVVTLWGV LVKFDLVPWN STFYTIQTYV FPVTTCLAHS
NSCLNPVLYC LLRREPRQAL AGTFRDLRLR LWPQGGGWVQ QVALKQVGRR WVASNPRESR
PSTLLTNLDR GTPG
