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   11-NOV-2015, entry version 125.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Suzuki N., 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.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics 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.,
RA   Bathgate R.A.D., Hsueh A.J.W.;
RT   "H3 relaxin is a specific ligand for LGR7 and activates the receptor
RT   by interacting with both the ectodomain and the exoloop 2.";
RL   J. Biol. Chem. 278:7855-7862(2003).
RN   [5]
RP   INTERACTION WITH GPCR135.
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
RT   orphan G-protein coupled receptor GPCR135.";
RL   J. Biol. Chem. 278:50754-50764(2003).
RN   [6]
RP   INTERACTION WITH GPCR142.
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.,
RA   Wade J.D., 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.
CC       Ligand for LGR7, relaxin-3 receptor-1 (GPCR135) and relaxin-3
CC       receptor-2 (GPCR142).
CC   -!- SUBUNIT: Heterodimer of a B chain and an A chain linked by two
CC       disulfide bonds.
CC   -!- INTERACTION:
CC       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   UniGene; Hs.352155; -.
DR   PDB; 2FHW; NMR; -; A=119-142, B=26-52.
DR   PDB; 2K1V; NMR; -; B=26-52.
DR   PDBsum; 2FHW; -.
DR   PDBsum; 2K1V; -.
DR   ProteinModelPortal; Q8WXF3; -.
DR   SMR; Q8WXF3; 26-52.
DR   BioGrid; 125590; 3.
DR   IntAct; Q8WXF3; 1.
DR   STRING; 9606.ENSP00000397415; -.
DR   PhosphoSite; Q8WXF3; -.
DR   BioMuta; RLN3; -.
DR   DMDM; 37999891; -.
DR   PaxDb; Q8WXF3; -.
DR   PRIDE; Q8WXF3; -.
DR   Ensembl; ENST00000431365; ENSP00000397415; ENSG00000171136.
DR   GeneID; 117579; -.
DR   KEGG; hsa:117579; -.
DR   UCSC; uc002mxw.1; human.
DR   CTD; 117579; -.
DR   GeneCards; RLN3; -.
DR   HGNC; HGNC:17135; RLN3.
DR   HPA; HPA043731; -.
DR   MIM; 606855; gene.
DR   neXtProt; NX_Q8WXF3; -.
DR   PharmGKB; PA34401; -.
DR   eggNOG; ENOG410IZRS; Eukaryota.
DR   eggNOG; ENOG41121Z2; LUCA.
DR   GeneTree; ENSGT00510000048203; -.
DR   HOGENOM; HOG000111888; -.
DR   HOVERGEN; HBG045048; -.
DR   InParanoid; Q8WXF3; -.
DR   KO; K05255; -.
DR   OMA; FMVENFL; -.
DR   OrthoDB; EOG7H1JNG; -.
DR   PhylomeDB; Q8WXF3; -.
DR   TreeFam; TF333404; -.
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   EvolutionaryTrace; Q8WXF3; -.
DR   GenomeRNAi; 117579; -.
DR   NextBio; 80214; -.
DR   PRO; PR:Q8WXF3; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   Bgee; Q8WXF3; -.
DR   CleanEx; HS_RLN3; -.
DR   ExpressionAtlas; Q8WXF3; baseline and differential.
DR   Genevisible; Q8WXF3; HS.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   InterPro; IPR016179; Insulin-like.
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; 2.
DR   PROSITE; PS00262; INSULIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; Hormone;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     25       {ECO:0000269|PubMed:12686464}.
FT   PEPTIDE      26     52       Relaxin-3 B chain. {ECO:0000250}.
FT                                /FTId=PRO_0000016082.
FT   PROPEP       55    118       Connecting peptide. {ECO:0000250}.
FT                                /FTId=PRO_0000016083.
FT   PEPTIDE     119    142       Relaxin-3 A chain. {ECO:0000250}.
FT                                /FTId=PRO_0000016084.
FT   DISULFID     35    129       Interchain (between B and A chains).
FT                                {ECO:0000269|PubMed:16365033}.
FT   DISULFID     47    142       Interchain (between B and A chains).
FT                                {ECO:0000269|PubMed:16365033}.
FT   DISULFID    128    133       {ECO:0000269|PubMed:16365033}.
FT   STRAND       29     32       {ECO:0000244|PDB:2FHW}.
FT   HELIX        37     47       {ECO:0000244|PDB:2FHW}.
FT   HELIX       120    130       {ECO:0000244|PDB:2FHW}.
FT   HELIX       135    139       {ECO:0000244|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
//