Q8WXD0 (RXFP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Relaxin receptor 2

Alternative name(s):
G-protein coupled receptor 106
G-protein coupled receptor affecting testicular descent
Leucine-rich repeat-containing G-protein coupled receptor 8
Relaxin family peptide receptor 2

Gene names

Name:	RXFP2
Synonyms:	GPR106, GREAT, LGR8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	754 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for relaxin. The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP. May also be a receptor for Leydig insulin-like peptide (INSL3).
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed mainly in the brain, kidney, muscle, testis, thyroid, uterus, peripheral blood cells and bone marrow.
Involvement in disease	Cryptorchidism (CRYPTO) [MIM:219050]: One of the most frequent congenital abnormalities in humans, involving 2-5% of male births. Cryptorchidism is associated with increased risk of infertility and testicular cancer. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2
Sequence similarities	Belongs to the G-protein coupled receptor 1 family. Contains 1 LDL-receptor class A domain. Contains 10 LRR (leucine-rich) repeats.
Caution	It is uncertain whether Met-1 or Met-18 is the initiator.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Leucine-rich repeat Repeat Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-activating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara male gonad development Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara oocyte maturation Inferred from electronic annotation. Source: Compara positive regulation of cAMP biosynthetic process Inferred from electronic annotation. Source: Compara
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	peptide hormone binding Inferred from electronic annotation. Source: Compara protein-hormone receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8WXD0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8WXD0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     286-309: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 754	754	Relaxin receptor 2		PRO_0000069702
Regions
	Topological domain	1 – 416	416	Extracellular Potential
	Transmembrane	417 – 437	21	Helical; Name=1; Potential
	Topological domain	438 – 455	18	Cytoplasmic Potential
	Transmembrane	456 – 476	21	Helical; Name=2; Potential
	Topological domain	477 – 495	19	Extracellular Potential
	Transmembrane	496 – 518	23	Helical; Name=3; Potential
	Topological domain	519 – 537	19	Cytoplasmic Potential
	Transmembrane	538 – 558	21	Helical; Name=4; Potential
	Topological domain	559 – 592	34	Extracellular Potential
	Transmembrane	593 – 613	21	Helical; Name=5; Potential
	Topological domain	614 – 639	26	Cytoplasmic Potential
	Transmembrane	640 – 660	21	Helical; Name=6; Potential
	Topological domain	661 – 670	10	Extracellular Potential
	Transmembrane	671 – 691	21	Helical; Name=7; Potential
	Topological domain	692 – 754	63	Cytoplasmic Potential
	Domain	44 – 81	38	LDL-receptor class A
	Repeat	138 – 159	22	LRR 1
	Repeat	162 – 183	22	LRR 2
	Repeat	186 – 207	22	LRR 3
	Repeat	210 – 231	22	LRR 4
	Repeat	234 – 255	22	LRR 5
	Repeat	258 – 279	22	LRR 6
	Repeat	282 – 303	22	LRR 7
	Repeat	306 – 327	22	LRR 8
	Repeat	330 – 351	22	LRR 9
	Repeat	354 – 375	22	LRR 10
Amino acid modifications
	Glycosylation	54	1	N-linked (GlcNAc...) Potential
	Glycosylation	138	1	N-linked (GlcNAc...) Potential
	Glycosylation	274	1	N-linked (GlcNAc...) Potential
	Glycosylation	335	1	N-linked (GlcNAc...) Potential
	Glycosylation	378	1	N-linked (GlcNAc...) Potential
	Disulfide bond	45 ↔ 58		By similarity
	Disulfide bond	52 ↔ 71		By similarity
	Disulfide bond	65 ↔ 80		By similarity
	Disulfide bond	495 ↔ 573		By similarity
Natural variations
	Alternative sequence	286 – 309	24	Missing in isoform 2.		VSP_042831
	Natural variant	222	1	T → P in CRYPTO; functionally inactive. Ref.2 Corresponds to variant rs28939382 [ dbSNP | Ensembl ].		VAR_015386
	Natural variant	604	1	I → V. Ref.2 Corresponds to variant rs17076657 [ dbSNP | Ensembl ].		VAR_015387
Experimental info
	Mutagenesis	647	1	D → Y: Leads to constitutive increase of basal cAMP. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 2088ECD204C6A6C5	FASTA	754	86,453
	10 20 30 40 50 60 MIVFLVFKHL FSLRLITMFF LLHFIVLINV KDFALTQGSM ITPSCQKGYF PCGNLTKCLP 70 80 90 100 110 120 RAFHCDGKDD CGNGADEENC GDTSGWATIF GTVHGNANSV ALTQECFLKQ YPQCCDCKET 130 140 150 160 170 180 ELECVNGDLK SVPMISNNVT LLSLKKNKIH SLPDKVFIKY TKLKKIFLQH NCIRHISRKA 190 200 210 220 230 240 FFGLCNLQIL YLNHNCITTL RPGIFKDLHQ LTWLILDDNP ITRISQRLFT GLNSLFFLSM 250 260 270 280 290 300 VNNYLEALPK QMCAQMPQLN WVDLEGNRIK YLTNSTFLSC DSLTVLFLPR NQIGFVPEKT 310 320 330 340 350 360 FSSLKNLGEL DLSSNTITEL SPHLFKDLKL LQKLNLSSNP LMYLHKNQFE SLKQLQSLDL 370 380 390 400 410 420 ERIEIPNINT RMFQPMKNLS HIYFKNFRYC SYAPHVRICM PLTDGISSFE DLLANNILRI 430 440 450 460 470 480 FVWVIAFITC FGNLFVIGMR SFIKAENTTH AMSIKILCCA DCLMGVYLFF VGIFDIKYRG 490 500 510 520 530 540 QYQKYALLWM ESVQCRLMGF LAMLSTEVSV LLLTYLTLEK FLVIVFPFSN IRPGKRQTSV 550 560 570 580 590 600 ILICIWMAGF LIAVIPFWNK DYFGNFYGKN GVCFPLYYDQ TEDIGSKGYS LGIFLGVNLL 610 620 630 640 650 660 AFLIIVFSYI TMFCSIQKTA LQTTEVRNCF GREVAVANRF FFIVFSDAIC WIPVFVVKIL 670 680 690 700 710 720 SLFRVEIPDT MTSWIVIFFL PVNSALNPIL YTLTTNFFKD KLKQLLHKHQ RKSIFKIKKK 730 740 750 SLSTSIVWIE DSSSLKLGVL NKITLGDSIM KPVS
	Isoform 2 [UniParc]. Checksum: 36274984AF9314E9	FASTA	730	83,736
	10 20 30 40 50 60 MIVFLVFKHL FSLRLITMFF LLHFIVLINV KDFALTQGSM ITPSCQKGYF PCGNLTKCLP 70 80 90 100 110 120 RAFHCDGKDD CGNGADEENC GDTSGWATIF GTVHGNANSV ALTQECFLKQ YPQCCDCKET 130 140 150 160 170 180 ELECVNGDLK SVPMISNNVT LLSLKKNKIH SLPDKVFIKY TKLKKIFLQH NCIRHISRKA 190 200 210 220 230 240 FFGLCNLQIL YLNHNCITTL RPGIFKDLHQ LTWLILDDNP ITRISQRLFT GLNSLFFLSM 250 260 270 280 290 300 VNNYLEALPK QMCAQMPQLN WVDLEGNRIK YLTNSTFLSC DSLTVLDLSS NTITELSPHL 310 320 330 340 350 360 FKDLKLLQKL NLSSNPLMYL HKNQFESLKQ LQSLDLERIE IPNINTRMFQ PMKNLSHIYF 370 380 390 400 410 420 KNFRYCSYAP HVRICMPLTD GISSFEDLLA NNILRIFVWV IAFITCFGNL FVIGMRSFIK 430 440 450 460 470 480 AENTTHAMSI KILCCADCLM GVYLFFVGIF DIKYRGQYQK YALLWMESVQ CRLMGFLAML 490 500 510 520 530 540 STEVSVLLLT YLTLEKFLVI VFPFSNIRPG KRQTSVILIC IWMAGFLIAV IPFWNKDYFG 550 560 570 580 590 600 NFYGKNGVCF PLYYDQTEDI GSKGYSLGIF LGVNLLAFLI IVFSYITMFC SIQKTALQTT 610 620 630 640 650 660 EVRNCFGREV AVANRFFFIV FSDAICWIPV FVVKILSLFR VEIPDTMTSW IVIFFLPVNS 670 680 690 700 710 720 ALNPILYTLT TNFFKDKLKQ LLHKHQRKSI FKIKKKSLST SIVWIEDSSS LKLGVLNKIT 730 LGDSIMKPVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation of orphan receptors by the hormone relaxin." Hsu S.Y., Nakabayashi K., Nishi S., Kumagai J., Kudo M., Sherwood O.D., Hsueh A.J.W. Science 295:671-674(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF ASP-647.
[2]	"Mutations of the GREAT gene cause cryptorchidism." Gorlov I.P., Kamat A., Bogatcheva N.V., Jones E., Lamb D.J., Truong A., Bishop C.E., McElreavey K., Agoulnik A.I. Hum. Mol. Genet. 11:2309-2318(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT CRYPTO PRO-222, VARIANT VAL-604.
[3]	"Splice variants of the relaxin and INSL3 receptors reveal unanticipated molecular complexity." Muda M., He C., Martini P.G.V., Ferraro T., Layfield S., Taylor D., Chevrier C., Schweickhardt R., Kelton C., Ryan P.L., Bathgate R.A.D. Mol. Hum. Reprod. 11:591-600(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF403384 mRNA. Translation: AAL69324.2. AF453828 mRNA. Translation: AAL73946.1. AY899851 mRNA. Translation: AAX85199.1. AL138708, AL159161 Genomic DNA. Translation: CAH73785.1. AL159161, AL138708 Genomic DNA. Translation: CAI17102.1. CH471075 Genomic DNA. Translation: EAX08484.1.
IPI	IPI00103510. IPI00654597.
RefSeq	NP_001159530.1. NM_001166058.1. NP_570718.1. NM_130806.3.
UniGene	Hs.680763.
3D structure databases
ProteinModelPortal	Q8WXD0.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000298386.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q8WXD0.
Polymorphism databases
DMDM	21362625.
Proteomic databases
PaxDb	Q8WXD0.
PRIDE	Q8WXD0.
Protocols and materials databases
DNASU	122042.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000298386; ENSP00000298386; ENSG00000133105. ENST00000380314; ENSP00000369670; ENSG00000133105.
GeneID	122042.
KEGG	hsa:122042.
UCSC	uc001utt.3. human.
Organism-specific databases
CTD	122042.
GeneCards	GC13P032313.
HGNC	HGNC:17318. RXFP2.
MIM	219050. phenotype. 606655. gene.
neXtProt	NX_Q8WXD0.
PharmGKB	PA134918556.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG4886.
HOGENOM	HOG000049056.
HOVERGEN	HBG026354.
InParanoid	Q8WXD0.
KO	K04307.
OMA	KILCCAD.
OrthoDB	EOG47M1XF.
PhylomeDB	Q8WXD0.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q8WXD0.
CleanEx	HS_RXFP2.
Genevestigator	Q8WXD0.
GermOnline	ENSG00000133105. Homo sapiens.
Family and domain databases
Gene3D	4.10.400.10. 1 hit.
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR023415. LDLR_class-A_CS. IPR002172. LDrepeatLR_classA_rpt. IPR001611. Leu-rich_rpt. IPR003591. Leu-rich_rpt_typical-subtyp. IPR000372. LRR-contain_N. IPR008112. Relaxin_rcpt. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. PF00057. Ldl_recept_a. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR01739. RELAXINR.
SMART	SM00192. LDLa. 1 hit. SM00369. LRR_TYP. 2 hits. SM00013. LRRNT. 1 hit. [Graphical view]
SUPFAM	SSF57424. LDL_rcpt_classA_cys-rich. 1 hit.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. False negative. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. PS01209. LDLRA_1. 1 hit. PS50068. LDLRA_2. 1 hit. PS51450. LRR. 9 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1628482.
GenomeRNAi	122042.
NextBio	80847.
SOURCE	Search...

Entry information

Entry name

RXFP2_HUMAN

Accession

Primary (citable) accession number: Q8WXD0
Secondary accession number(s): B1ALE9, Q3KU23

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 6, 2002
Last sequence update:	March 1, 2002
Last modified:	May 1, 2013
This is version 117 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.