Q8TDU9 (RL3R2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Relaxin-3 receptor 2
Short name=RLN3 receptor 2

Alternative name(s):
G-protein coupled receptor 100
G-protein coupled receptor GPCR142
Insulin-like peptide INSL5 receptor
Relaxin family peptide receptor 4

Gene names

Name:	RXFP4
Synonyms:	GPR100, RLN3R2

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	374 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	High affinity receptor for INSL5. Also acts as receptor for RLN3/relaxin-3, as well as bradykinin and kallidin. Binding of the ligand inhibit cAMP accumulation. Ref.1 Ref.9
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in a broader range of tissues including brain, kidney, testis, thymus, placenta, prostate, salivary gland, thyroid and colon. Ref.3
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Sequence caution	The sequence BAC05844.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	angiotensin type II receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 374	374	Relaxin-3 receptor 2		PRO_0000070106
Regions
	Topological domain	1 – 43	43	Extracellular Potential
	Transmembrane	44 – 64	21	Helical; Name=1; Potential
	Topological domain	65 – 78	14	Cytoplasmic Potential
	Transmembrane	79 – 99	21	Helical; Name=2; Potential
	Topological domain	100 – 116	17	Extracellular Potential
	Transmembrane	117 – 137	21	Helical; Name=3; Potential
	Topological domain	138 – 154	17	Cytoplasmic Potential
	Transmembrane	155 – 175	21	Helical; Name=4; Potential
	Topological domain	176 – 209	34	Extracellular Potential
	Transmembrane	210 – 230	21	Helical; Name=5; Potential
	Topological domain	231 – 249	19	Cytoplasmic Potential
	Transmembrane	250 – 270	21	Helical; Name=6; Potential
	Topological domain	271 – 281	11	Extracellular Potential
	Transmembrane	282 – 302	21	Helical; Name=7; Potential
	Topological domain	303 – 374	72	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	5	1	N-linked (GlcNAc...) Potential
	Glycosylation	17	1	N-linked (GlcNAc...) Potential
	Disulfide bond	114 ↔ 191		By similarity
Natural variations
	Natural variant	329	1	L → S. Ref.1 Ref.7 Ref.8 Corresponds to variant rs2152051 [ dbSNP | Ensembl ].		VAR_021516

Sequences

	Sequence		Length	Mass (Da)
	Q8TDU9 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 1929EA812C0804DA	FASTA	374	41,141
	10 20 30 40 50 60 MPTLNTSASP PTFFWANASG GSVLSADDAP MPVKFLALRL MVALAYGLVG AIGLLGNLAV 70 80 90 100 110 120 LWVLSNCARR APGPPSDTFV FNLALADLGL ALTLPFWAAE SALDFHWPFG GALCKMVLTA 130 140 150 160 170 180 TVLNVYASIF LITALSVARY WVVAMAAGPG THLSLFWARI ATLAVWAAAA LVTVPTAVFG 190 200 210 220 230 240 VEGEVCGVRL CLLRFPSRYW LGAYQLQRVV LAFMVPLGVI TTSYLLLLAF LQRRQRRRQD 250 260 270 280 290 300 SRVVARSVRI LVASFFLCWF PNHVVTLWGV LVKFDLVPWN STFYTIQTYV FPVTTCLAHS 310 320 330 340 350 360 NSCLNPVLYC LLRREPRQAL AGTFRDLRLR LWPQGGGWVQ QVALKQVGRR WVASNPRESR 370 PSTLLTNLDR GTPG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of relaxin-3/INSL7 as a ligand for GPCR142." Liu C., Chen J., Sutton S., Roland B., Kuei C., Farmer N., Sillard R., Lovenberg T.W. J. Biol. Chem. 278:50765-50770(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-329, FUNCTION AS A RECEPTOR FOR RLN3.
[2]	"Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives." Fredriksson R., Hoeglund P.J., Gloriam D.E.I., Lagerstroem M.C., Schioeth H.B. FEBS Lett. 554:381-388(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Identification and characterisation of GPR100 as a novel human G-protein-coupled bradykinin receptor." Boels K., Schaller H.C. Br. J. Pharmacol. 140:932-938(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH BRADYKININ AND KALLIDIN. Tissue: Pancreatic carcinoma.
[4]	"Genome-wide discovery and analysis of human seven transmembrane helix receptor genes." Suwa M., Sato T., Okouchi I., Arita M., Futami K., Matsumoto S., Tsutsumi S., Aburatani H., Asai K., Akiyama Y. Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Identification of G protein-coupled receptor genes from the human genome sequence." Takeda S., Kadowaki S., Haga T., Takaesu H., Mitaku S. FEBS Lett. 520:97-101(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Kaighin V.A., Martin A.L., Aronstam R.S. Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-329. Tissue: Testis.
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-329. Tissue: Brain.
[9]	"INSL5 is a high affinity specific agonist for GPCR142 (GPR100)." Liu C., Kuei C., Sutton S., Chen J., Bonaventure P., Wu J., Nepomuceno D., Kamme F., Tran D.T., Zhu J., Wilkinson T., Bathgate R., Eriste E., Sillard R., Lovenberg T.W. J. Biol. Chem. 280:292-300(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A RECEPTOR FOR INSL5.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY394502 mRNA. Translation: AAQ92316.1. AY288415 mRNA. Translation: AAP72124.1. AY170824 mRNA. Translation: AAO17676.1. AB065617 Genomic DNA. Translation: BAC05844.1. Sequence problems. AB083593 Genomic DNA. Translation: BAB89306.1. AL355388 Genomic DNA. Translation: CAH72626.1. EU432129 mRNA. Translation: ABY87928.1. BC101507 mRNA. Translation: AAI01508.1. BC101509 mRNA. Translation: AAI01510.1.
IPI	IPI00291503.
RefSeq	NP_871001.1. NM_181885.2.
UniGene	Hs.449914.
3D structure databases
ProteinModelPortal	Q8TDU9.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000357301.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q8TDU9.
Polymorphism databases
DMDM	38258194.
Proteomic databases
PaxDb	Q8TDU9.
PRIDE	Q8TDU9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368318; ENSP00000357301; ENSG00000173080.
GeneID	339403.
KEGG	hsa:339403.
UCSC	uc010pgs.2. human.
Organism-specific databases
CTD	339403.
GeneCards	GC01P155911.
HGNC	HGNC:14666. RXFP4.
MIM	609043. gene.
neXtProt	NX_Q8TDU9.
PharmGKB	PA28848.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG292372.
HOGENOM	HOG000230485.
HOVERGEN	HBG101327.
InParanoid	Q8TDU9.
KO	K08398.
OMA	CLLRFPS.
OrthoDB	EOG4FN4J1.
PhylomeDB	Q8TDU9.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q8TDU9.
CleanEx	HS_RXFP4.
Genevestigator	Q8TDU9.
Family and domain databases
InterPro	IPR000248. ATII_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00241. ANGIOTENSINR. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. False negative. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1628473.
GenomeRNAi	339403.
NextBio	97386.
SOURCE	Search...

Entry information

Entry name

RL3R2_HUMAN

Accession

Primary (citable) accession number: Q8TDU9
Secondary accession number(s): B0M0L4, Q3MJB1, Q8NGZ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 7, 2003
Last sequence update:	June 1, 2002
Last modified:	May 1, 2013
This is version 102 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.