Details for: RLN2

Gene ID: 6019

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: RLN2

Ensembl ID: ENSG00000107014

Description: relaxin 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ciliated epithelial cell CL0000067
    CSI 4.69
    rCSI 4.12%
    PRS 99.94

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [RLN2](/details-gene/6019) encodes relaxin 2, a peptide hormone structurally similar to insulin that plays a critical role in female reproduction, particularly during pregnancy. Functionally, it acts as a ligand for G-protein coupled receptors (GPCRs), initiating downstream signaling cascades involved in processes such as angiogenesis and the regulation of gene expression. As an extracellular hormone, its primary role is in cell-to-cell communication. **Overall**, expression data indicates a significant association of [RLN2](/details-gene/6019) with [ciliated epithelial cells](/details-cell/CL0000067), suggesting potential functions beyond its well-established roles in reproductive tissues. Its clinical relevance is noted under OMIM entry [179740](https://omim.org/entry/179740). ## Cellular Roles and Expression Landscape The expression profile of [RLN2](/details-gene/6019) highlights its specific functional contexts. Analysis shows that the gene has a notably high cell significance index (CSI: 4.69) in [ciliated epithelial cells](/details-cell/CL0000067). This suggests that [RLN2](/details-gene/6019) may serve as a key signaling molecule produced by or acting upon these cells, which are critical for mucociliary clearance in the respiratory and reproductive tracts. While classically studied for its expression in the corpus luteum of the ovary during pregnancy and in the prostate gland [Link](https://doi.org/10.1210/endo.130.5.1572287), the high significance in ciliated epithelium points towards a broader role in mucosal biology, potentially involving tissue remodeling or local vasodilation. The lack of significant expression in other cell lineages within the provided data underscores its specialized function. ## Pathways and Molecular Function [RLN2](/details-gene/6019) functions as a hormone, as annotated by its involvement in [hormone activity](/details-cell/GO:0005179). It operates within the [extracellular region](/details-cell/GO:0005576), where it binds to and activates its cognate receptors. The functional annotations strongly link [RLN2](/details-gene/6019) to GPCR signaling pathways. Specifically, it is involved in the [Relaxin receptors](/details-cell/R-HSA-444821) pathway, which is a part of the larger [Class a/1 (rhodopsin-like receptors)](/details-cell/R-HSA-373076) family. Upon receptor binding ([Gpcr ligand binding](/details-cell/R-HSA-500792)), it triggers [Gpcr downstream signalling](/details-cell/R-HSA-388396), often through [G alpha (s) signalling events](/details-cell/R-HSA-418555). Biologically, these signaling events translate into broader processes such as [female pregnancy](/details-cell/GO:0007565) and the [positive regulation of angiogenesis](/details-cell/GO:0045766). Its role in modulating cellular activity is further supported by annotations for the [positive regulation of gene expression](/details-cell/GO:0010628) and the [regulation of catalytic activity](/details-cell/GO:0050790). ## Research Directions The significant expression of [RLN2](/details-gene/6019) in [ciliated epithelial cells](/details-cell/CL0000067) opens up new avenues for research beyond its traditional reproductive and cardiovascular roles. **Proposed Hypotheses:** 1. [RLN2](/details-gene/6019) produced by [ciliated epithelial cells](/details-cell/CL0000067) in the respiratory tract acts as a paracrine factor to modulate airway smooth muscle tone and promote tissue repair following injury, contributing to the maintenance of mucosal homeostasis. 2. The [RLN2](/details-gene/6019)-receptor axis in the female reproductive tract epithelium is involved in regulating ciliary beat frequency and fluid dynamics, thereby facilitating gamete and embryo transport. **Experimental Approach:** To test the first hypothesis, an *in vitro* co-culture system could be established using human primary [ciliated epithelial cells](/details-cell/CL0000067) grown on a permeable support and primary human airway smooth muscle cells in the lower chamber. The epithelial layer could be transfected with siRNA targeting [RLN2](/details-gene/6019). The effect of [RLN2](/details-gene/6019) knockdown on smooth muscle cell contractility could be measured in response to agonists like methacholine. Furthermore, after inducing a mechanical scratch wound to the epithelial layer, the rate of wound healing and expression of extracellular matrix components could be quantified via immunofluorescence and qPCR in both control and [RLN2](/details-gene/6019)-depleted conditions. **Therapeutic Potential:** As a secreted peptide hormone with vasodilatory, anti-inflammatory, and anti-fibrotic properties, [RLN2](/details-gene/6019) (or its recombinant form, serelaxin) holds considerable therapeutic potential. The primary strategy would be **activation** or supplementation, making it a candidate for treating diseases characterized by fibrosis and vasoconstriction, such as scleroderma, pulmonary fibrosis, and acute heart failure. Its specificity is mediated by the expression of its receptors, RXFP1 and RXFP2, which could limit off-target effects. Developing stable, long-acting agonists of these receptors remains a key goal for harnessing the therapeutic benefits of the relaxin signaling system.

Genular Protein ID: 2527825208

Symbol: REL2_HUMAN

Name: Prorelaxin H2

UniProtKB Accession Codes:

P04090 A0AVM0 Q99936 Q9UCX3 Q9UQJ2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 2 RefSeq 2 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 6548702

Title: Relaxin gene expression in human ovaries and the predicted structure of a human preprorelaxin by analysis of cDNA clones.

PubMed ID: 6548702

DOI: 10.1002/j.1460-2075.1984.tb02135.x

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 8735594

Title: Expression of human relaxin genes: characterization of a novel alternatively-spliced human relaxin mRNA species.

PubMed ID: 8735594

DOI: 10.1016/0303-7207(96)03770-7

PubMed ID: 10601981

Title: Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes and their chromosomal localization on chromosome 9p24.1 by radiation hybrid and breakpoint mapping.

PubMed ID: 10601981

DOI: 10.1677/jme.0.0230355

PubMed ID: 1572287

Title: Human seminal relaxin is a product of the same gene as human luteal relaxin.

PubMed ID: 1572287

DOI: 10.1210/endo.130.5.1572287

PubMed ID: 2076464

Title: Structural characterization by mass spectrometry of native and recombinant human relaxin.

PubMed ID: 2076464

DOI: 10.1002/bms.1200191105

PubMed ID: 2040595

Title: Total synthesis of human relaxin and human relaxin derivatives by solid-phase peptide synthesis and site-directed chain combination.

PubMed ID: 2040595

DOI: 10.1016/s0021-9258(18)99082-4

PubMed ID: 1656049

Title: X-ray structure of human relaxin at 1.5 A. Comparison to insulin and implications for receptor binding determinants.

PubMed ID: 1656049

DOI: 10.1016/0022-2836(91)90796-9

Sequence Information:

  • Length: 185
  • Mass: 21043
  • Checksum: AC73DBDE2090091B
  • Sequence:
    • MPRLFFFHLL GVCLLLNQFS RAVADSWMEE VIKLCGRELV RAQIAICGMS TWSKRSLSQE 
DAPQTPRPVA EIVPSFINKD TETINMMSEF VANLPQELKL TLSEMQPALP QLQQHVPVLK 
DSSLLFEEFK KLIRNRQSEA ADSSPSELKY LGLDTHSRKK RQLYSALANK CCHVGCTKRS 
LARFC