Alternative titles; symbols
HGNC Approved Gene Symbol: RLN3
Cytogenetic location: 19p13.12 Genomic coordinates (GRCh38) : 19:14,028,148-14,031,551 (from NCBI)
By database searching for sequences showing homology to relaxins (see RLN1, 179730), Bathgate et al. (2002) identified RLN3, which they designated H3, and assembled a complete coding sequence from multiple genomic fragments. They also identified the mouse Rln3 gene by database analysis through its homology with the human sequence. The human and mouse genes encode deduced proteins of 142 and 141 amino acids, respectively. Both proteins contain a putative prohormone sequence incorporating the classic 2-chain, 3-cysteine-bonded structure of the relaxin/insulin family, and the RXXXRXX(I/V) motif in the B chain essential for relaxin receptor binding. Both have a predicted 27-amino acid B chain, a 66-amino acid C-peptide, and a 24-amino acid A chain. Northern blot analysis of human tissues detected weak signals in spleen, thymus, peripheral blood leukocytes, lymph node, and testis. Northern blot analysis of mouse tissues detected a 1.2-kb transcript only in brain. RT-PCR revealed high expression of relaxin in mouse brain, ovary, and testis, moderate expression in thymus, lung, and spleen, very low expression in heart and liver, and no expression in kidney, skin, and gut. In situ hybridization of mouse brain showed expression localized to the pons/medulla, with highest levels in the pars ventromedialis of the dorsal tegmental nucleus. Rln3 was also expressed at far lower levels in the hippocampus and olfactory regions.
Using RT-PCR, Liu et al. (2003) detected RLN3 expression only in brain and testis. In situ hybridization revealed limited Rln3 expression in rat brain, with highest levels in periaqueductal gray, nucleus incertus, and central gray regions in the brainstem.
Bathgate et al. (2002) found that synthetic RLN3 produced a dose-dependent increase in cAMP production in a relaxin receptor-expressing human monocytic cell line.
Liu et al. (2003) found that endogenous rat or porcine brain Rln3 stimulated GPCR135 (RLN3R1; 609445)-transfected Chinese hamster ovary cell membranes to bind a nonhydrolyzable GTP analog. Using FLAG-tagged human RLN3 secreted from transfected COS-7 cells, they confirmed that RLN3 is a ligand for GPCR135. Radiolabeled RLN3 saturably bound GPCR135 in a monophasic manner with high affinity. Labeled RLN3 was displaced from GPCR135 by unlabeled RLN3 or by the RLN3 beta chain, but not by any other insulin/relaxin family members. RLN3 did not stimulate cAMP accumulation, but it inhibited forskolin-stimulated cAMP accumulation in GPCR135-expressing cells in a dose-dependent manner. Liu et al. (2003) concluded that RLN3 is a ligand for GPCR135.
Bathgate et al. (2002) determined that the RLN3 gene contains 2 exons.
Bathgate et al. (2002) stated that the human RLN3 gene maps to chromosome 19p13.3 and the mouse homolog to chromosome 8C2.
Bathgate, R. A. D., Samuel, C. S., Burazin, T. C. D., Layfield, S., Claasz, A. A., Reytomas, I. G. T., Dawson, N. F., Zhao, C., Bond, C., Summers, R. J., Parry, L. J., Wade, J. D., Tregear, G. W. Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene: novel members of the relaxin peptide family. J. Biol. Chem. 277: 1148-1157, 2002. [PubMed: 11689565] [Full Text: https://doi.org/10.1074/jbc.M107882200]
Liu, C., Eriste, E., Sutton, S., Chen, J., Roland, B., Kuei, C., Farmer, N., Jornvall, H., Sillard, R., Lovenberg, T. W. Identification of relaxin-3/INSL7 as an endogenous ligand for the orphan G-protein-coupled receptor GPCR135. J. Biol. Chem. 278: 50754-50764, 2003. [PubMed: 14522968] [Full Text: https://doi.org/10.1074/jbc.M308995200]