REL2_HUMAN
ID REL2_HUMAN Reviewed; 185 AA.
AC P04090; A0AVM0; Q99936; Q9UCX3; Q9UQJ2;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1986, sequence version 1.
DT 03-AUG-2022, entry version 206.
DE RecName: Full=Prorelaxin H2;
DE Contains:
DE RecName: Full=Relaxin B chain;
DE Contains:
DE RecName: Full=Relaxin A chain;
DE Flags: Precursor;
GN Name=RLN2;
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 TISSUE SPECIFICITY.
RX PubMed=6548702; DOI=10.1002/j.1460-2075.1984.tb02135.x;
RA Hudson P., John M., Crawford R., Haralambidis J., Scanlon D., Gorman J.,
RA Tregear G., Shine J., Niall H.;
RT "Relaxin gene expression in human ovaries and the predicted structure of a
RT human preprorelaxin by analysis of cDNA clones.";
RL EMBO J. 3:2333-2339(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 71-185 (ISOFORM 2), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Prostate;
RX PubMed=8735594; DOI=10.1016/0303-7207(96)03770-7;
RA Gunnersen J.M., Fu P., Roche P.J., Tregear G.W.;
RT "Expression of human relaxin genes: characterization of a novel
RT alternatively-spliced human relaxin mRNA species.";
RL Mol. Cell. Endocrinol. 118:85-94(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
RX PubMed=10601981; DOI=10.1677/jme.0.0230355;
RA Garibay-Tupas J.L., Csiszar K., Fox M., Povey S., Bryant-Greenwood G.D.;
RT "Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes
RT and their chromosomal localization on chromosome 9p24.1 by radiation hybrid
RT and breakpoint mapping.";
RL J. Mol. Endocrinol. 23:355-365(1999).
RN [6]
RP PROTEIN SEQUENCE OF 25-51.
RC TISSUE=Semen;
RX PubMed=1572287; DOI=10.1210/endo.130.5.1572287;
RA Winslow J.W., Shih A., Bourell J.H., Weiss G., Reed B., Stults J.T.,
RA Goldsmith L.T.;
RT "Human seminal relaxin is a product of the same gene as human luteal
RT relaxin.";
RL Endocrinology 130:2660-2668(1992).
RN [7]
RP PROTEIN SEQUENCE OF 25-53 AND 162-185 (ISOFORM 1), AND PYROGLUTAMATE
RP FORMATION AT GLN-162.
RX PubMed=2076464; DOI=10.1002/bms.1200191105;
RA Winslow J.W., Griffin P.R., Rinderknecht E., Vandlen R.L.;
RT "Structural characterization by mass spectrometry of native and recombinant
RT human relaxin.";
RL Biomed. Environ. Mass Spectrom. 19:655-664(1990).
RN [8]
RP SYNTHESIS.
RX PubMed=2040595; DOI=10.1016/s0021-9258(18)99082-4;
RA Buellesbach E.E., Schwabe C.;
RT "Total synthesis of human relaxin and human relaxin derivatives by solid-
RT phase peptide synthesis and site-directed chain combination.";
RL J. Biol. Chem. 266:10754-10761(1991).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS).
RX PubMed=1656049; DOI=10.1016/0022-2836(91)90796-9;
RA Eigenbrot C., Randal M., Quan C., Burnier J., O'Connell L.,
RA Rinderknecht E., Kossiakoff A.A.;
RT "X-ray structure of human relaxin at 1.5 A. Comparison to insulin and
RT implications for receptor binding determinants.";
RL J. Mol. Biol. 221:15-21(1991).
CC -!- FUNCTION: Relaxin is an ovarian hormone that acts with estrogen to
CC produce dilatation of the birth canal in many mammals. May be involved
CC in remodeling of connective tissues during pregnancy, promoting growth
CC of pubic ligaments and ripening of the cervix.
CC -!- SUBUNIT: Heterodimer of a B chain and an A chain linked by two
CC disulfide bonds.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P04090-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P04090-2; Sequence=VSP_002711, VSP_002712;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in the ovary during
CC pregnancy. Also expressed in placenta, decidua and prostate. Isoform 2
CC is relatively abundant in placenta. It is in much lower abundance in
CC the prostate gland. Not detected in the ovary.
CC {ECO:0000269|PubMed:6548702, ECO:0000269|PubMed:8735594}.
CC -!- SIMILARITY: Belongs to the insulin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RLN2ID44421ch9p24.html";
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DR EMBL; X00948; CAA25460.1; -; mRNA.
DR EMBL; AL135786; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC126415; AAI26416.1; -; mRNA.
DR EMBL; BC126419; AAI26420.1; -; mRNA.
DR EMBL; S83200; AAD14429.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AF104935; AAD21961.1; -; Genomic_DNA.
DR CCDS; CCDS6460.1; -. [P04090-1]
DR PIR; A05092; A60982.
DR RefSeq; NP_005050.2; NM_005059.3. [P04090-2]
DR RefSeq; NP_604390.1; NM_134441.2. [P04090-1]
DR PDB; 2MV1; NMR; -; A=163-185, B=25-53.
DR PDB; 6RLX; X-ray; 1.50 A; A/C=163-185, B/D=26-53.
DR PDBsum; 2MV1; -.
DR PDBsum; 6RLX; -.
DR AlphaFoldDB; P04090; -.
DR SMR; P04090; -.
DR BioGRID; 111951; 11.
DR STRING; 9606.ENSP00000371040; -.
DR BioMuta; RLN2; -.
DR DMDM; 132281; -.
DR MassIVE; P04090; -.
DR PaxDb; P04090; -.
DR PeptideAtlas; P04090; -.
DR PRIDE; P04090; -.
DR Antibodypedia; 9541; 275 antibodies from 29 providers.
DR DNASU; 6019; -.
DR Ensembl; ENST00000381627.4; ENSP00000371040.3; ENSG00000107014.9. [P04090-1]
DR GeneID; 6019; -.
DR KEGG; hsa:6019; -.
DR MANE-Select; ENST00000381627.4; ENSP00000371040.3; NM_134441.3; NP_604390.1.
DR UCSC; uc003zja.3; human. [P04090-1]
DR CTD; 6019; -.
DR DisGeNET; 6019; -.
DR GeneCards; RLN2; -.
DR HGNC; HGNC:10027; RLN2.
DR HPA; ENSG00000107014; Tissue enhanced (fallopian).
DR MIM; 179740; gene.
DR neXtProt; NX_P04090; -.
DR OpenTargets; ENSG00000107014; -.
DR PharmGKB; PA34400; -.
DR VEuPathDB; HostDB:ENSG00000107014; -.
DR eggNOG; ENOG502TH8D; Eukaryota.
DR GeneTree; ENSGT00940000154434; -.
DR HOGENOM; CLU_115657_0_0_1; -.
DR InParanoid; P04090; -.
DR OMA; TINMMSE; -.
DR OrthoDB; 1331287at2759; -.
DR PhylomeDB; P04090; -.
DR TreeFam; TF333404; -.
DR PathwayCommons; P04090; -.
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; P04090; -.
DR SIGNOR; P04090; -.
DR BioGRID-ORCS; 6019; 15 hits in 1032 CRISPR screens.
DR ChiTaRS; RLN2; human.
DR EvolutionaryTrace; P04090; -.
DR GenomeRNAi; 6019; -.
DR Pharos; P04090; Tbio.
DR PRO; PR:P04090; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P04090; protein.
DR Bgee; ENSG00000107014; Expressed in endometrium epithelium and 110 other tissues.
DR ExpressionAtlas; P04090; baseline and differential.
DR Genevisible; P04090; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0007565; P:female pregnancy; TAS:ProtInc.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:CACAO.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:CACAO.
DR GO; GO:0050790; P:regulation of catalytic activity; IDA:CACAO.
DR InterPro; IPR016179; Insulin-like.
DR InterPro; IPR036438; Insulin-like_sf.
DR InterPro; IPR022353; Insulin_CS.
DR InterPro; IPR022352; Insulin_family.
DR InterPro; IPR022421; Relaxin.
DR Pfam; PF00049; Insulin; 1.
DR PRINTS; PR00276; INSULINFAMLY.
DR PRINTS; PR02004; RELAXIN.
DR SMART; SM00078; IlGF; 1.
DR SUPFAM; SSF56994; SSF56994; 1.
DR PROSITE; PS00262; INSULIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Hormone;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:1572287"
FT PEPTIDE 25..53
FT /note="Relaxin B chain"
FT /id="PRO_0000016079"
FT PROPEP 56..157
FT /note="Connecting peptide"
FT /id="PRO_0000016080"
FT PEPTIDE 162..185
FT /note="Relaxin A chain"
FT /id="PRO_0000016081"
FT MOD_RES 162
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:2076464"
FT DISULFID 35..172
FT /note="Interchain (between B and A chains)"
FT DISULFID 47..185
FT /note="Interchain (between B and A chains)"
FT DISULFID 171..176
FT /evidence="ECO:0000269|PubMed:2040595"
FT VAR_SEQ 71..117
FT /note="EIVPSFINKDTETINMMSEFVANLPQELKLTLSEMQPALPQLQQHVP -> G
FT DFIQTVSLGISPDGGKALRTGSCFTREFLGALSKLCHPSSTKIQKP (in isoform
FT 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_002711"
FT VAR_SEQ 118..185
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_002712"
FT VARIANT 12
FT /note="V -> F (in dbSNP:rs2020050)"
FT /id="VAR_050007"
FT VARIANT 28
FT /note="M -> K (in dbSNP:rs618066)"
FT /id="VAR_034444"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:6RLX"
FT HELIX 36..49
FT /evidence="ECO:0007829|PDB:6RLX"
FT HELIX 163..173
FT /evidence="ECO:0007829|PDB:6RLX"
FT HELIX 178..182
FT /evidence="ECO:0007829|PDB:6RLX"
SQ SEQUENCE 185 AA; 21043 MW; AC73DBDE2090091B CRC64;
MPRLFFFHLL GVCLLLNQFS RAVADSWMEE VIKLCGRELV RAQIAICGMS TWSKRSLSQE
DAPQTPRPVA EIVPSFINKD TETINMMSEF VANLPQELKL TLSEMQPALP QLQQHVPVLK
DSSLLFEEFK KLIRNRQSEA ADSSPSELKY LGLDTHSRKK RQLYSALANK CCHVGCTKRS
LARFC
