ID   RXFP2_HUMAN             Reviewed;         754 AA.
AC   Q8WXD0; B1ALE9; Q3KU23;
DT   06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   27-MAR-2024, entry version 193.
DE   RecName: Full=Relaxin receptor 2;
DE   AltName: Full=G-protein coupled receptor 106;
DE   AltName: Full=G-protein coupled receptor affecting testicular descent;
DE   AltName: Full=Leucine-rich repeat-containing G-protein coupled receptor 8;
DE   AltName: Full=Relaxin family peptide receptor 2;
GN   Name=RXFP2; Synonyms=GPR106, GREAT, LGR8;
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 MUTAGENESIS OF ASP-647.
RX   PubMed=11809971; DOI=10.1126/science.1065654;
RA   Hsu S.Y., Nakabayashi K., Nishi S., Kumagai J., Kudo M., Sherwood O.D.,
RA   Hsueh A.J.W.;
RT   "Activation of orphan receptors by the hormone relaxin.";
RL   Science 295:671-674(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT CRYPTO PRO-222, AND VARIANT
RP   VAL-604.
RX   PubMed=12217959; DOI=10.1093/hmg/11.19.2309;
RA   Gorlov I.P., Kamat A., Bogatcheva N.V., Jones E., Lamb D.J., Truong A.,
RA   Bishop C.E., McElreavey K., Agoulnik A.I.;
RT   "Mutations of the GREAT gene cause cryptorchidism.";
RL   Hum. Mol. Genet. 11:2309-2318(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX   PubMed=16051677; DOI=10.1093/molehr/gah205;
RA   Muda M., He C., Martini P.G.V., Ferraro T., Layfield S., Taylor D.,
RA   Chevrier C., Schweickhardt R., Kelton C., Ryan P.L., Bathgate R.A.D.;
RT   "Splice variants of the relaxin and INSL3 receptors reveal unanticipated
RT   molecular complexity.";
RL   Mol. Hum. Reprod. 11:591-600(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15057823; DOI=10.1038/nature02379;
RA   Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA   Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA   Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA   Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA   Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA   Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA   Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA   Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA   Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA   Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA   Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA   Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA   Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA   Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA   Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA   Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA   Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA   Rogers J., Ross M.T.;
RT   "The DNA sequence and analysis of human chromosome 13.";
RL   Nature 428:522-528(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Receptor for relaxin. The activity of this receptor is
CC       mediated by G proteins leading to stimulation of adenylate cyclase and
CC       an increase of cAMP. May also be a receptor for Leydig insulin-like
CC       peptide (INSL3).
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8WXD0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8WXD0-2; Sequence=VSP_042831;
CC   -!- TISSUE SPECIFICITY: Expressed mainly in the brain, kidney, muscle,
CC       testis, thyroid, uterus, peripheral blood cells and bone marrow.
CC   -!- DISEASE: Cryptorchidism (CRYPTO) [MIM:219050]: One of the most frequent
CC       congenital abnormalities in humans, involving 2-5% of male births.
CC       Cryptorchidism is associated with increased risk of infertility and
CC       testicular cancer. {ECO:0000269|PubMed:12217959}. Note=The disease is
CC       caused by variants affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-18 is the initiator.
CC       {ECO:0000305}.
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DR   EMBL; AF403384; AAL69324.2; -; mRNA.
DR   EMBL; AF453828; AAL73946.1; -; mRNA.
DR   EMBL; AY899851; AAX85199.1; -; mRNA.
DR   EMBL; AL138708; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL159161; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471075; EAX08484.1; -; Genomic_DNA.
DR   CCDS; CCDS53862.1; -. [Q8WXD0-2]
DR   CCDS; CCDS9342.1; -. [Q8WXD0-1]
DR   RefSeq; NP_001159530.1; NM_001166058.1. [Q8WXD0-2]
DR   RefSeq; NP_570718.1; NM_130806.4. [Q8WXD0-1]
DR   PDB; 2M96; NMR; -; A=38-81.
DR   PDBsum; 2M96; -.
DR   AlphaFoldDB; Q8WXD0; -.
DR   BMRB; Q8WXD0; -.
DR   SASBDB; Q8WXD0; -.
DR   SMR; Q8WXD0; -.
DR   BioGRID; 125757; 4.
DR   IntAct; Q8WXD0; 2.
DR   STRING; 9606.ENSP00000298386; -.
DR   ChEMBL; CHEMBL1628482; -.
DR   GuidetoPHARMACOLOGY; 352; -.
DR   GlyCosmos; Q8WXD0; 5 sites, No reported glycans.
DR   GlyGen; Q8WXD0; 5 sites.
DR   iPTMnet; Q8WXD0; -.
DR   PhosphoSitePlus; Q8WXD0; -.
DR   BioMuta; RXFP2; -.
DR   DMDM; 21362625; -.
DR   EPD; Q8WXD0; -.
DR   MassIVE; Q8WXD0; -.
DR   PaxDb; 9606-ENSP00000298386; -.
DR   PeptideAtlas; Q8WXD0; -.
DR   Antibodypedia; 22835; 351 antibodies from 30 providers.
DR   DNASU; 122042; -.
DR   Ensembl; ENST00000298386.7; ENSP00000298386.2; ENSG00000133105.8. [Q8WXD0-1]
DR   Ensembl; ENST00000380314.2; ENSP00000369670.1; ENSG00000133105.8. [Q8WXD0-2]
DR   GeneID; 122042; -.
DR   KEGG; hsa:122042; -.
DR   MANE-Select; ENST00000298386.7; ENSP00000298386.2; NM_130806.5; NP_570718.1.
DR   UCSC; uc001utt.4; human. [Q8WXD0-1]
DR   AGR; HGNC:17318; -.
DR   DisGeNET; 122042; -.
DR   GeneCards; RXFP2; -.
DR   HGNC; HGNC:17318; RXFP2.
DR   HPA; ENSG00000133105; Not detected.
DR   MalaCards; RXFP2; -.
DR   MIM; 219050; phenotype.
DR   MIM; 606655; gene.
DR   neXtProt; NX_Q8WXD0; -.
DR   OpenTargets; ENSG00000133105; -.
DR   PharmGKB; PA134918556; -.
DR   VEuPathDB; HostDB:ENSG00000133105; -.
DR   eggNOG; KOG0619; Eukaryota.
DR   eggNOG; KOG2087; Eukaryota.
DR   GeneTree; ENSGT00940000158948; -.
DR   HOGENOM; CLU_006130_2_1_1; -.
DR   InParanoid; Q8WXD0; -.
DR   OMA; MYLSMVN; -.
DR   OrthoDB; 2913881at2759; -.
DR   PhylomeDB; Q8WXD0; -.
DR   TreeFam; TF326185; -.
DR   PathwayCommons; Q8WXD0; -.
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   Reactome; R-HSA-444821; Relaxin receptors.
DR   SignaLink; Q8WXD0; -.
DR   SIGNOR; Q8WXD0; -.
DR   BioGRID-ORCS; 122042; 5 hits in 1135 CRISPR screens.
DR   ChiTaRS; RXFP2; human.
DR   GeneWiki; Relaxin/insulin-like_family_peptide_receptor_2; -.
DR   GenomeRNAi; 122042; -.
DR   Pharos; Q8WXD0; Tbio.
DR   PRO; PR:Q8WXD0; -.
DR   Proteomes; UP000005640; Chromosome 13.
DR   RNAct; Q8WXD0; Protein.
DR   Bgee; ENSG00000133105; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 42 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:0017046; F:peptide hormone binding; IEA:Ensembl.
DR   GO; GO:0016500; F:protein-hormone receptor activity; IEA:Ensembl.
DR   GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR   GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR   GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR   GO; GO:0001556; P:oocyte maturation; IEA:Ensembl.
DR   GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IEA:Ensembl.
DR   CDD; cd15966; 7tmA_RXFP2_LGR8; 1.
DR   CDD; cd00112; LDLa; 1.
DR   Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 2.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR036055; LDL_receptor-like_sf.
DR   InterPro; IPR023415; LDLR_class-A_CS.
DR   InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   InterPro; IPR008112; Relaxin_rcpt.
DR   PANTHER; PTHR24372; GLYCOPROTEIN HORMONE RECEPTOR; 1.
DR   PANTHER; PTHR24372:SF72; RELAXIN RECEPTOR 2; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   Pfam; PF00057; Ldl_recept_a; 1.
DR   Pfam; PF13855; LRR_8; 3.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01739; RELAXINR.
DR   SMART; SM00192; LDLa; 1.
DR   SMART; SM00369; LRR_TYP; 10.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   SUPFAM; SSF57424; LDL receptor-like module; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   PROSITE; PS01209; LDLRA_1; 1.
DR   PROSITE; PS50068; LDLRA_2; 1.
DR   PROSITE; PS51450; LRR; 9.
DR   Genevisible; Q8WXD0; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane; Disease variant;
KW   Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW   Leucine-rich repeat; Membrane; Receptor; Reference proteome; Repeat;
KW   Transducer; Transmembrane; Transmembrane helix.
FT   CHAIN           1..754
FT                   /note="Relaxin receptor 2"
FT                   /id="PRO_0000069702"
FT   TOPO_DOM        1..416
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        417..437
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        438..455
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        456..476
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        477..495
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        496..518
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        519..537
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        538..558
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        559..592
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        593..613
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        614..639
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        640..660
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        661..670
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        671..691
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        692..754
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          44..81
FT                   /note="LDL-receptor class A"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT   REPEAT          138..159
FT                   /note="LRR 1"
FT   REPEAT          162..183
FT                   /note="LRR 2"
FT   REPEAT          186..207
FT                   /note="LRR 3"
FT   REPEAT          210..231
FT                   /note="LRR 4"
FT   REPEAT          234..255
FT                   /note="LRR 5"
FT   REPEAT          258..279
FT                   /note="LRR 6"
FT   REPEAT          282..303
FT                   /note="LRR 7"
FT   REPEAT          306..327
FT                   /note="LRR 8"
FT   REPEAT          330..351
FT                   /note="LRR 9"
FT   REPEAT          354..375
FT                   /note="LRR 10"
FT   CARBOHYD        54
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        138
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        335
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        378
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        45..58
FT                   /evidence="ECO:0000250"
FT   DISULFID        52..71
FT                   /evidence="ECO:0000250"
FT   DISULFID        65..80
FT                   /evidence="ECO:0000250"
FT   DISULFID        495..573
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         286..309
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16051677"
FT                   /id="VSP_042831"
FT   VARIANT         222
FT                   /note="T -> P (in CRYPTO; functionally inactive;
FT                   dbSNP:rs121918303)"
FT                   /evidence="ECO:0000269|PubMed:12217959"
FT                   /id="VAR_015386"
FT   VARIANT         604
FT                   /note="I -> V (in dbSNP:rs17076657)"
FT                   /evidence="ECO:0000269|PubMed:12217959"
FT                   /id="VAR_015387"
FT   MUTAGEN         647
FT                   /note="D->Y: Leads to constitutive increase of basal cAMP."
FT                   /evidence="ECO:0000269|PubMed:11809971"
FT   HELIX           61..63
FT                   /evidence="ECO:0007829|PDB:2M96"
FT   STRAND          70..75
FT                   /evidence="ECO:0007829|PDB:2M96"
SQ   SEQUENCE   754 AA;  86453 MW;  2088ECD204C6A6C5 CRC64;
     MIVFLVFKHL FSLRLITMFF LLHFIVLINV KDFALTQGSM ITPSCQKGYF PCGNLTKCLP
     RAFHCDGKDD CGNGADEENC GDTSGWATIF GTVHGNANSV ALTQECFLKQ YPQCCDCKET
     ELECVNGDLK SVPMISNNVT LLSLKKNKIH SLPDKVFIKY TKLKKIFLQH NCIRHISRKA
     FFGLCNLQIL YLNHNCITTL RPGIFKDLHQ LTWLILDDNP ITRISQRLFT GLNSLFFLSM
     VNNYLEALPK QMCAQMPQLN WVDLEGNRIK YLTNSTFLSC DSLTVLFLPR NQIGFVPEKT
     FSSLKNLGEL DLSSNTITEL SPHLFKDLKL LQKLNLSSNP LMYLHKNQFE SLKQLQSLDL
     ERIEIPNINT RMFQPMKNLS HIYFKNFRYC SYAPHVRICM PLTDGISSFE DLLANNILRI
     FVWVIAFITC FGNLFVIGMR SFIKAENTTH AMSIKILCCA DCLMGVYLFF VGIFDIKYRG
     QYQKYALLWM ESVQCRLMGF LAMLSTEVSV LLLTYLTLEK FLVIVFPFSN IRPGKRQTSV
     ILICIWMAGF LIAVIPFWNK DYFGNFYGKN GVCFPLYYDQ TEDIGSKGYS LGIFLGVNLL
     AFLIIVFSYI TMFCSIQKTA LQTTEVRNCF GREVAVANRF FFIVFSDAIC WIPVFVVKIL
     SLFRVEIPDT MTSWIVIFFL PVNSALNPIL YTLTTNFFKD KLKQLLHKHQ RKSIFKIKKK
     SLSTSIVWIE DSSSLKLGVL NKITLGDSIM KPVS
//