REL3_HUMAN
ID REL3_HUMAN Reviewed; 142 AA.
AC Q8WXF3; Q6UXW5;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Relaxin-3;
DE AltName: Full=Insulin-like peptide INSL7;
DE Short=Insulin-like peptide 7;
DE AltName: Full=Prorelaxin H3;
DE Contains:
DE RecName: Full=Relaxin-3 B chain;
DE Contains:
DE RecName: Full=Relaxin-3 A chain;
DE Flags: Precursor;
GN Name=RLN3; Synonyms=INSL7, RXN3, ZINS4; ORFNames=UNQ6188/PRO20213;
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].
RA Holloway J.L., Lok S., Jaspers S.R.;
RT "Homo sapiens insulin homolog polypeptide.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 26-34 AND 119-127.
RX PubMed=12686464; DOI=10.1016/s0167-0115(02)00304-x;
RA Kizawa H., Nishi K., Ishibashi Y., Harada M., Asano T., Ito Y., Suzuki N.,
RA Hinuma S., Fujisawa Y., Onda H., Nishimura O., Fujino M.;
RT "Production of recombinant human relaxin 3 in AtT20 cells.";
RL Regul. Pept. 113:79-84(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP INTERACTION WITH LGR7.
RX PubMed=12506116; DOI=10.1074/jbc.m212457200;
RA Sudo S., Kumagai J., Nishi S., Layfield S., Ferraro T., Bathgate R.A.D.,
RA Hsueh A.J.W.;
RT "H3 relaxin is a specific ligand for LGR7 and activates the receptor by
RT interacting with both the ectodomain and the exoloop 2.";
RL J. Biol. Chem. 278:7855-7862(2003).
RN [5]
RP INTERACTION WITH RXFP3.
RX PubMed=14522968; DOI=10.1074/jbc.m308995200;
RA Liu C., Eriste E., Sutton S., Chen J., Roland B., Kuei C., Farmer N.,
RA Joernvall H., Sillard R., Lovenberg T.W.;
RT "Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan
RT G-protein coupled receptor GPCR135.";
RL J. Biol. Chem. 278:50754-50764(2003).
RN [6]
RP INTERACTION WITH RXFP4.
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 [7]
RP STRUCTURE BY NMR OF 26-142, AND DISULFIDE BONDS.
RX PubMed=16365033; DOI=10.1074/jbc.m511210200;
RA Rosengren K.J., Lin F., Bathgate R.A., Tregear G.W., Daly N.L., Wade J.D.,
RA Craik D.J.;
RT "Solution structure and novel insights into the determinants of the
RT receptor specificity of human relaxin-3.";
RL J. Biol. Chem. 281:5845-5851(2006).
CC -!- FUNCTION: May play a role in neuropeptide signaling processes. Ligand
CC for LGR7, RXFP3 and RXFP4.
CC -!- SUBUNIT: Heterodimer of a B chain and an A chain linked by two
CC disulfide bonds.
CC -!- INTERACTION:
CC Q8WXF3; Q8TDU9: RXFP4; NbExp=9; IntAct=EBI-9519546, EBI-9519524;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ88548.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF447451; AAL40345.1; -; mRNA.
DR EMBL; AB076563; BAC53758.1; -; mRNA.
DR EMBL; AY358181; AAQ88548.1; ALT_INIT; mRNA.
DR CCDS; CCDS12302.1; -.
DR RefSeq; NP_001298126.1; NM_001311197.1.
DR RefSeq; NP_543140.1; NM_080864.3.
DR PDB; 2FHW; NMR; -; A=119-142, B=26-52.
DR PDB; 2K1V; NMR; -; B=26-52.
DR PDBsum; 2FHW; -.
DR PDBsum; 2K1V; -.
DR AlphaFoldDB; Q8WXF3; -.
DR SMR; Q8WXF3; -.
DR BioGRID; 125590; 3.
DR IntAct; Q8WXF3; 1.
DR MINT; Q8WXF3; -.
DR STRING; 9606.ENSP00000397415; -.
DR iPTMnet; Q8WXF3; -.
DR PhosphoSitePlus; Q8WXF3; -.
DR BioMuta; RLN3; -.
DR DMDM; 37999891; -.
DR PaxDb; Q8WXF3; -.
DR PRIDE; Q8WXF3; -.
DR Antibodypedia; 50312; 149 antibodies from 23 providers.
DR DNASU; 117579; -.
DR Ensembl; ENST00000431365.3; ENSP00000397415.2; ENSG00000171136.7.
DR Ensembl; ENST00000673090.1; ENSP00000500641.1; ENSG00000288474.1.
DR GeneID; 117579; -.
DR KEGG; hsa:117579; -.
DR MANE-Select; ENST00000431365.3; ENSP00000397415.2; NM_080864.4; NP_543140.1.
DR UCSC; uc002mxw.2; human.
DR CTD; 117579; -.
DR DisGeNET; 117579; -.
DR GeneCards; RLN3; -.
DR HGNC; HGNC:17135; RLN3.
DR HPA; ENSG00000171136; Group enriched (parathyroid gland, testis).
DR MIM; 606855; gene.
DR neXtProt; NX_Q8WXF3; -.
DR OpenTargets; ENSG00000171136; -.
DR PharmGKB; PA34401; -.
DR VEuPathDB; HostDB:ENSG00000171136; -.
DR eggNOG; ENOG502S2C4; Eukaryota.
DR GeneTree; ENSGT00940000154396; -.
DR HOGENOM; CLU_120043_0_0_1; -.
DR InParanoid; Q8WXF3; -.
DR OMA; CEWGCSK; -.
DR OrthoDB; 1354498at2759; -.
DR PhylomeDB; Q8WXF3; -.
DR TreeFam; TF333404; -.
DR PathwayCommons; Q8WXF3; -.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-444821; Relaxin receptors.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; Q8WXF3; -.
DR BioGRID-ORCS; 117579; 11 hits in 1059 CRISPR screens.
DR EvolutionaryTrace; Q8WXF3; -.
DR GenomeRNAi; 117579; -.
DR Pharos; Q8WXF3; Tbio.
DR PRO; PR:Q8WXF3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8WXF3; protein.
DR Bgee; ENSG00000171136; Expressed in granulocyte and 55 other tissues.
DR ExpressionAtlas; Q8WXF3; baseline and differential.
DR Genevisible; Q8WXF3; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR InterPro; IPR016179; Insulin-like.
DR InterPro; IPR036438; Insulin-like_sf.
DR InterPro; IPR022353; Insulin_CS.
DR InterPro; IPR022352; Insulin_family.
DR Pfam; PF00049; Insulin; 1.
DR PRINTS; PR00276; INSULINFAMLY.
DR SMART; SM00078; IlGF; 1.
DR SUPFAM; SSF56994; SSF56994; 1.
DR PROSITE; PS00262; INSULIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Hormone; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:12686464"
FT PEPTIDE 26..52
FT /note="Relaxin-3 B chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000016082"
FT PROPEP 55..118
FT /note="Connecting peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000016083"
FT PEPTIDE 119..142
FT /note="Relaxin-3 A chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000016084"
FT DISULFID 35..129
FT /note="Interchain (between B and A chains)"
FT /evidence="ECO:0000269|PubMed:16365033"
FT DISULFID 47..142
FT /note="Interchain (between B and A chains)"
FT /evidence="ECO:0000269|PubMed:16365033"
FT DISULFID 128..133
FT /evidence="ECO:0000269|PubMed:16365033"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:2FHW"
FT HELIX 37..47
FT /evidence="ECO:0007829|PDB:2FHW"
FT HELIX 120..130
FT /evidence="ECO:0007829|PDB:2FHW"
FT HELIX 135..139
FT /evidence="ECO:0007829|PDB:2FHW"
SQ SEQUENCE 142 AA; 15451 MW; 23A3E095034B31E4 CRC64;
MARYMLLLLL AVWVLTGELW PGAEARAAPY GVRLCGREFI RAVIFTCGGS RWRRSDILAH
EAMGDTFPDA DADEDSLAGE LDEAMGSSEW LALTKSPQAF YRGRPSWQGT PGVLRGSRDV
LAGLSSSCCK WGCSKSEISS LC
