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   27-MAR-2024, entry version 176.
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 a 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   PDB; 7YJ4; EM; 3.19 A; R=1-374.
DR   PDB; 7YK6; EM; 3.03 A; R=1-374.
DR   PDB; 7YK7; EM; 2.75 A; R=1-374.
DR   PDBsum; 7YJ4; -.
DR   PDBsum; 7YK6; -.
DR   PDBsum; 7YK7; -.
DR   AlphaFoldDB; Q8TDU9; -.
DR   EMDB; EMD-33871; -.
DR   EMDB; EMD-33888; -.
DR   EMDB; EMD-33889; -.
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   GlyCosmos; Q8TDU9; 2 sites, No reported glycans.
DR   GlyGen; Q8TDU9; 2 sites.
DR   iPTMnet; Q8TDU9; -.
DR   PhosphoSitePlus; Q8TDU9; -.
DR   BioMuta; RXFP4; -.
DR   DMDM; 38258194; -.
DR   PaxDb; 9606-ENSP00000357301; -.
DR   ProteomicsDB; 74341; -.
DR   Antibodypedia; 20424; 207 antibodies from 25 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   AGR; HGNC:14666; -.
DR   CTD; 339403; -.
DR   DisGeNET; 339403; -.
DR   GeneCards; RXFP4; -.
DR   HGNC; HGNC:14666; RXFP4.
DR   HPA; ENSG00000173080; Tissue enhanced (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; VWGVRLC; -.
DR   OrthoDB; 5350890at2759; -.
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; 25 hits in 1143 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 cell types or tissues.
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   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000248; ATII_rcpt.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   PANTHER; PTHR10489; CELL ADHESION MOLECULE; 1.
DR   PANTHER; PTHR10489:SF935; RELAXIN-3 RECEPTOR 1-RELATED; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00241; ANGIOTENSINR.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW   Glycoprotein; Membrane; Receptor; Reference proteome; Transducer;
KW   Transmembrane; 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
//