RXFP2_HUMAN
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 03-AUG-2022, entry version 184.
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 GlyGen; Q8WXD0; 5 sites.
DR iPTMnet; Q8WXD0; -.
DR PhosphoSitePlus; Q8WXD0; -.
DR BioMuta; RXFP2; -.
DR DMDM; 21362625; -.
DR EPD; Q8WXD0; -.
DR PaxDb; Q8WXD0; -.
DR PeptideAtlas; Q8WXD0; -.
DR PRIDE; Q8WXD0; -.
DR Antibodypedia; 22835; 326 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 CTD; 122042; -.
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; DNIGWAD; -.
DR OrthoDB; 559381at2759; -.
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 Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; Q8WXD0; -.
DR SIGNOR; Q8WXD0; -.
DR BioGRID-ORCS; 122042; 4 hits in 1057 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 monocyte and 40 other tissues.
DR Genevisible; Q8WXD0; HS.
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:0016500; F:protein-hormone receptor activity; IEA:Ensembl.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0009755; P:hormone-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR CDD; cd00112; LDLa; 1.
DR Gene3D; 3.80.10.10; -; 2.
DR Gene3D; 4.10.400.10; -; 1.
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 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; SSF57424; SSF57424; 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.
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
