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RLN3 Gene

protein-coding   GIFtS: 50
GCID: GC19P014137

Relaxin 3

(Previous name: relaxin 3 (H3))
  See RLN3-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Relaxin 31 2     H32 5
Prorelaxin H31 2 3     Relaxin 3 (H3)1
RXN32 3 5     insl72
Insulin-Like Peptide 72 3     Insulin-Like 72
Insulin-Like Peptide INSL72 3     relaxin-32
ZINS42 3     INSL73

External Ids:    HGNC: 171351   Entrez Gene: 1175792   Ensembl: ENSG000001711367   OMIM: 6068555   UniProtKB: Q8WXF33   

Export aliases for RLN3 gene to outside databases

Previous GC identifers: GC19P014494 GC19P013984 GC19P014000 GC19P013711


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for RLN3 Gene:
Relaxins are known endocrine and autocrine/paracrine hormones, belonging to the insulin gene superfamily. In the
human there are three non-allelic relaxin genes, RLN1, RLN2 and RLN3. RLN1 and RLN2 share high sequence homology.
Relaxin is produced by the ovary, and targets the mammalian reproductive system to ripen the cervix, elongate the
pubic symphysis and inhibit uterine contraction. It may have additional roles in enhancing sperm motility,
regulating blood pressure, controlling heart rate and releasing oxytocin and vasopressin. The protein encoded by
this gene is a member of the relaxin family. The active form of the encoded protein consists of an A chain and a
B chain but their cleavage sites are not definitely described yet. It may play a role in neuropeptide signaling
processes. (provided by RefSeq, Jul 2008)

GeneCards Summary for RLN3 Gene:
RLN3 (relaxin 3) is a protein-coding gene. Diseases associated with RLN3 include tick infestation. GO annotations related to this gene include hormone activity and G-protein coupled receptor binding.

UniProtKB/Swiss-Prot: REL3_HUMAN, Q8WXF3
Function: May play a role in neuropeptide signaling processes. Ligand for LGR7, relaxin-3 receptor-1 (GPCR135) and
relaxin-3 receptor-2 (GPCR142)




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000019.9  NC_018930.2  NT_011295.12  
Regulatory elements:
   Regulatory transcription factor binding sites in the RLN3 gene promoter:
         TBP   NF-1   NF-1/L   E47   GATA-1   AREB6   PPAR-gamma1   GATA-6   STAT3   PPAR-gamma2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidRLN3 promoter sequence
   Search Chromatin IP Primers for RLN3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat RLN3


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19p13.2   Ensembl cytogenetic band:  19p13.12   HGNC cytogenetic band: 19p13.2

RLN3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RLN3 gene location

GeneLoc information about chromosome 19         GeneLoc Exon Structure

GeneLoc location for GC19P014137:  view genomic region     (about GC identifiers)

Start:
14,138,960 bp from pter      End:
14,141,854 bp from pter
Size:
2,895 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: REL3_HUMAN, Q8WXF3 (See protein sequence)
Recommended Name: Relaxin-3 precursor  
Size: 142 amino acids; 15451 Da
Subunit: Heterodimer of a B chain and an A chain linked by two disulfide bonds
Sequence caution: Sequence=AAQ88548.1; Type=Erroneous initiation;
2 PDB 3D structures from and Proteopedia for RLN3:
2FHW (3D)        2K1V (3D)    
Secondary accessions: Q6UXW5

Explore the universe of human proteins at neXtProt for RLN3: NX_Q8WXF3

Explore proteomics data for RLN3 at MOPED

Post-translational modifications: 

  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See RLN3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_543140.1  
    ENSEMBL proteins: 
     ENSP00000397415   ENSP00000467130  
    Reactome Protein details: Q8WXF3

    RLN3 Human Recombinant Protein Products:

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    ENDOLIG: Endogenous ligands

    3 InterPro protein domains:
     IPR016179 Insulin-like
     IPR022352 Insulin_family
     IPR022353 Insulin_CS

    Graphical View of Domain Structure for InterPro Entry Q8WXF3

    ProtoNet protein and cluster: Q8WXF3

    1 Blocks protein domain: IPB004825 Insulin/IGF/relaxin

    UniProtKB/Swiss-Prot: REL3_HUMAN, Q8WXF3
    Similarity: Belongs to the insulin family


    Find genes that share domains with RLN3           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: REL3_HUMAN, Q8WXF3
    Function: May play a role in neuropeptide signaling processes. Ligand for LGR7, relaxin-3 receptor-1 (GPCR135) and
    relaxin-3 receptor-2 (GPCR142)

         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001664G-protein coupled receptor binding IEA--
    GO:0005179hormone activity IEA--
         
    Find genes that share ontologies with RLN3           About GenesLikeMe


    Phenotypes:
         6 MGI mutant phenotypes (inferred from 2 alleles(MGI details for Rln3):
     adipose tissue  behavior/neurological  growth/size/body  homeostasis/metabolism  integument 
     nervous system 

    Find genes that share phenotypes with RLN3           About GenesLikeMe

    Animal Models:
       genOway: Develop your customized and physiologically relevant rodent model for RLN3

    miRNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    REL3_HUMAN, Q8WXF3: Secreted
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    extracellular5
    nucleus2

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005576extracellular region TAS--

    Find genes that share ontologies with RLN3           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for RLN3 About    
    See pathways by source

    SuperPathContained pathways About
    1Peptide ligand-binding receptors
    Class A/1 (Rhodopsin-like receptors)0.71
    G alpha (i) signalling events0.44
    GPCR ligand binding0.71
    Relaxin receptors0.00
    Peptide ligand-binding receptors0.60
    2Signaling by GPCR
    Signaling by GPCR0.90
    Signal Transduction0.58
    GPCR downstream signaling0.90
    3CREB Pathway
    Activation of PKC through GPCR0.63
    4G-Beta Gamma Signaling
    Relaxin Pathway0.37
    5G alpha (s) signalling events
    G alpha (s) signalling events


    Find genes that share SuperPaths with RLN3           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for RLN3
        Relaxin Pathway
    Activation of PKC through GPCR


    3 Reactome Pathways for RLN3
        Relaxin receptors
    G alpha (i) signalling events
    G alpha (s) signalling events


        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for RLN3
    Interactions:

        GeneGlobe Interaction Network for RLN3

    2 Interacting proteins for RLN3 (Q8WXF33) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    RXFP4Q8TDU93I2D: score=2 
    RXFP1Q9HBX93I2D: score=1 
    About this table

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for RLN3 (REL3)

    1 Novoseek inferred chemical compound relationship for RLN3 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    adenylate 17.5 1 14522967 (1)



    Find genes that share compounds with RLN3           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for RLN3 gene: 
    NM_080864.2  

    Unigene Cluster for RLN3:

    Relaxin 3
    Hs.352155  [show with all ESTs]
    Unigene Representative Sequence: AY358181
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000431365(uc002mxw.1 uc010dzj.1) ENST00000585987
    miRNA
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    Additional mRNA sequence: 

    AB076563.1 AF447451.1 AY358181.1 BC110069.1 BC140935.1 

    2 DOTS entries:

    DT.108308  DT.121504421 

    Selected AceView cDNA sequences (see all 81):

    CA426655 BM804052 BP337994 AB076563 BC028003 BM760781 BF829683 NM_080864 
    AI347487 BM764289 AF106912 AW575269 NM_004843 BM761233 BM762764 AF447451 
    BU632122 AI769137 BQ919454 BM761623 AW295066 BF829689 AW298502 BF827655 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    RLN3 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: ACCCTGGCCC
    RLN3 Expression
    About this image

    RLN3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    RLN3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.352155
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    In Situ
    Assay Products:
     

     
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for RLN3 gene from Selected species (see all 7)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Rln31 , 5 relaxin 31, 5 76.77(n)1
    79.55(a)1
      8 (40.26 cM)5
    2121081  NM_173184.11  NP_775276.11 
     840429295 
    lizard
    (Anolis carolinensis)
    Reptilia RLN36
    relaxin 3
    54(a)
    1 ↔ 1
    2(76840180-76846815)
    zebrafish
    (Danio rerio)
    Actinopterygii BI476734.12   -- 78.25(n)    BI476734.1 


    ENSEMBL Gene Tree for RLN3 (if available)
    TreeFam Gene Tree for RLN3 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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      --

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for RLN3 (see all 75)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 19 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1132919051,2
    C--13709168(+) GGTGAC/TACAGC 1 -- us2k11Minor allele frequency- T:0.50CSA 2
    rs1127039261,2
    C--13709315(+) ATCTGC/TTGCCT 1 -- us2k14Minor allele frequency- T:0.06CSA WA NA EA 360
    rs1139263701,2
    C--13709367(+) GAGAAT/CTATCT 1 -- us2k14Minor allele frequency- C:0.07CSA WA NA EA 360
    rs1459344311,2
    --13709436(+) CTCACA/GCCTGT 1 -- us2k10--------
    rs1114292321,2
    C--14137160(+) AAAAAG/TAAAGA 1 -- us2k14Minor allele frequency- T:0.41WA CSA EA 125
    rs1999071621,2
    --14137160(+) AAAAA-/GAAAGA 1 -- us2k10--------
    rs1848485731,2
    --14137253(+) TCCTGA/GGTTCA 1 -- us2k10--------
    rs284750221,2
    C--14137340(+) TTTTAG/ATAGAG 1 -- us2k11Minor allele frequency- A:0.00WA 2
    rs1170777731,2
    C,F--14137460(+) AGCCAA/GTCCCA 1 -- us2k11Minor allele frequency- G:0.09EA 120
    rs1159913121,2
    C,F--14137794(+) GCAGAT/ATCTTA 1 -- us2k12Minor allele frequency- A:0.05WA NA 238

    HapMap Linkage Disequilibrium report for RLN3 (14138960 - 14141854 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for RLN3:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv911102CNV Loss21882294
    dgv3741n71CNV Loss21882294
    nsv833761CNV Loss17160897
    dgv3739n71CNV Loss21882294

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing RLN3
    DNA2.0 Custom Variant and Variant Library Synthesis for RLN3

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 606855    OMIM disorders: --

    1 disease for RLN3:    
    About MalaCards
    tick infestation

    1 disease from the University of Copenhagen DISEASES database for RLN3:
    Tick infestation

    Find genes that share disorders with RLN3           About GenesLikeMe

    Genetic Association Database (GAD): RLN3
    Human Genome Epidemiology (HuGE) Navigator: RLN3 (1 document)

    Export disorders for RLN3 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for RLN3 gene, integrated from 10 sources (see all 79):
    (articles sorted by number of sources associating them with RLN3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Production of recombinant human relaxin 3 in AtT20 cells. (PubMed id 12686464)1, 2, 9 Kizawa H.... Fujino M. (Regul. Pept. 2003)
    2. Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein coupled receptor GPCR135. (PubMed id 14522968)1, 2, 9 Liu C.... Lovenberg T.W. (J. Biol. Chem. 2003)
    3. Solution structure and novel insights into the determinants of the receptor specificity of human relaxin-3. (PubMed id 16365033)1, 2, 9 Rosengren K.J.... Craik D.J. (J. Biol. Chem. 2006)
    4. Identification of relaxin-3/INSL7 as a ligand for GPCR142. (PubMed id 14522967)1, 2, 9 Liu C....Lovenberg T.W. (J. Biol. Chem. 2003)
    5. Polymorphisms in the promoter region of relaxin-2 and preterm birth: involvement of relaxin in the etiology of preterm birth. (PubMed id 20023247)1, 4, 9 Vogel I....Grove J. (In Vivo 2009)
    6. H3 relaxin is a specific ligand for LGR7 and activates the receptor by interacting with both the ectodomain and the exoloop 2. (PubMed id 12506116)1, 2, 9 Sudo S.... Hsueh A.J.W. (J. Biol. Chem. 2003)
    7. Central relaxin-3 administration causes hyperphagia in male Wistar rats. (PubMed id 15845619)1, 9 McGowan B.M....Bloom S.R. (Endocrinology 2005)
    8. The chemistry and biology of human relaxin-3. (PubMed id 15956686)1, 9 Tregear G.W....Wade J.D. (Ann. N. Y. Acad. Sci. 2005)
    9. Relaxin-3 and receptors in the human and rhesus brain and reproductive tissues. (PubMed id 19778557)1, 9 Silvertown J.D....Medin J.A. (Regul. Pept. 2010)
    10. Relaxin-3/insulin-like peptide 5 chimeric peptide, a selective ligand for G protein-coupled receptor (GPCR)135 and GPCR142 over leucine-rich repeat-containing G protein-coupled receptor 7. (PubMed id 15465925)1, 9 Liu C....Lovenberg T.W. (Mol. Pharmacol. 2005)

    (in PubMed, OMIM, and NCBI Bookshelf)
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      Query String
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 117579 HGNC: 17135 AceView: IL27RAandRLN3 Ensembl:ENSG00000171136 euGenes: HUgn117579
    ECgene: RLN3 H-InvDB: RLN3

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for RLN3 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for RLN3 gene:
    Search GeneIP for patents involving RLN3

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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