Insulin Superfamily

Author: paola marolo
Date: 06/03/2013



The relaxin-like peptide family belongs in the insulin superfamily and consists of 7 peptides of high structural but low sequence similarity; relaxin-1 (RLN1), 2 (RLN2) and 3 (RLN3), and the insulin-like (INSL) peptides, INSL3, INSL4, INSL5 and INSL6.
Of the three known relaxin genes, Relaxin-2 is the only relaxin known to circulate in the blood.

The length of the precursor peptide is 185 aminoacids with a molecular weight of 21,043 Daltons.
The functional peptide has 21 aminoacids in the A chain and 27 in the B chain, with a molecular weight of 5,989 Daltons. The localisation is the cytoplasm.
There is a specific binding motif (Arg-X-X-X-Arg-X-X-Ile/Val) which is vital for providing the tertiary structure and for binding to the LGR receptor.
These receptors have a large and very distinctive ectodomain which includes an LDL module at the far end of the N-terminus followed by a LRR domain. It is thought that this links with a unique hinge-like region leading into the transmembrane domain. There are seven transmembrane helices and an intracellular C-terminus.

Identifiers Relaxin 2:
Symbol RLN2
Alternative symbols H2, RLXH2, bA12D24.1.1, bA12D24.1.2

Atlas of genetics and Cytogenetics in oncology and haematology


RLN2 is located on chromosome 9 on the reverse strand. Starts at 5299868 and ends at 5304580. The location is 9p24.1.





Relaxin interacts with the relaxin receptor LGR7 (RXFP1) and LGR8 (RXFP2), which belong to the G protein-coupled receptor superfamily. They contain a heptahelical transmembrane domain and a large glycosylated ectodomain, distantly related to the receptors for the glycoproteohormones, such as the LH-receptor or FSH-receptor.
Relaxin receptors have been found in the heart, smooth muscle, the connective tissue, and central and autonomous nervous system.

Protein Aminoacids Percentage (Width 700 px)



Schematic representation of the transcription of the human RLN2 gene. The gene is located with the RLN1, INSL4 and INSL6 genes on chromosome 9 at 9p24. The RLN2 gene consists of two exons and is transcribed to give preprorelaxin-2 mRNA. Exon I encodes for the signal peptide, the B Chain and part of the C Chain, and Exon II encodes for the remainder of the C Chain and the A chain of H2 relaxin.
RLN2 is a functioning gene of 4,712 bp comprising 2 exons and 1 intron.
The length of the transcript is 588bp.

The degradation is due to the insulin degrading enzyme.


In the female, it is produced by the corpus luteum of the ovary, the breast and, during pregnancy, also by the placenta, chorion and decidua.
In the male, it is produced in the prostate and is present in human semen.

In humans
In females relaxin is produced mainly by the corpus luteum, in both pregnant and nonpregnant females; it rises to a peak within approximately 14 days of ovulation, and then declines in the absence of pregnancy, resulting in menstruation. During the first trimester of pregnancy, levels rise and additional relaxin is produced by the decidua. Relaxin's peak is reached during the 14 weeks of the first trimester and at delivery. However, is known to mediate the hemodynamic changes that occur during pregnancy, such as increased cardiac output, increased renal blood flow, and increased arterial compliance. It also relaxes other pelvic ligaments and softens the pubic symphysis.
In males, relaxin enhances motility of sperm in semen.

In other animals
In animals, relaxin widens the pubic bone and facilitates labor; it also softens the cervix, and relaxes the uterine musculature.
Relaxin affects collagen metabolism, inhibiting collagen synthesis. It also enhances angiogenesis and is a potent renal vasodilator.


It was identified a positive auto-regulatory loop of human relaxin-2 expression which involves GR and relaxin/GR binding to half-GREs in the relaxin-2 promoter.
It was found that porcine relaxin increases the secretion of human relaxin-like immunoreactivity in HeLa and THP-1 cells.
Silencing of GR gene expression completely abolished this effect whereas transfection of wild-type GR into naturally GR-devoid HT-29 cells established relaxin sensitivity.
Relaxin was shown to stimulate CAT expression driven by different deletion constructs of the 5'-flanking region of the relaxin-2 promoter.
In chromatin immunoprecipitation assays, both GR and relaxin were detected binded to the relaxin-2 promoter. Gel shift assays indicated binding of relaxin-activated GR to half-GREs located between 160 and 200 bp upstream of transcription start but not to the GRE at -900 bp. Relaxin bound to human GR and displaced established GR agonists. Immunofluorescence experiments visualized nuclear co-localization of relaxin and GR in response to relaxin.


Relaxin concentration in serum and urine may be used as a marker of pregnancy.


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