Human relaxin gene 3 (H3) and the equivalent mouse relaxin (M3) gene. Novel members of the relaxin peptide family.
We have identified a novel human relaxin gene, designated H3 relaxin, and an equivalent relaxin gene in the mouse from the Celera Genomics data base. Both genes encode a putative prohormone sequence incorporating the classic two-chain, three cysteine-bonded structure of the relaxin/insulin family and, importantly, contain the RXXXRXX(I/V) motif in the B-chain that is essential for relaxin receptor binding. A peptide derived from the likely proteolytic processing of the H3 relaxin prohormone sequence was synthesized and found to possess relaxin activity in bioassays utilizing the human monocytic cell line, THP-1, that expresses the relaxin receptor. The expression of this novel relaxin gene was studied in mouse tissues using RT-PCR, where transcripts were identified with a pattern of expression distinct from that of the previously characterized mouse relaxin. The highest levels of expression were found in the brain, whereas significant expression was also observed in the spleen, thymus, lung, and ovary. Northern blotting demonstrated an approximately 1.2-kb transcript present in mouse brain poly(A) RNA but not in other tissues. These data, together with the localization of transcripts in the pars ventromedialis of the dorsal tegmental nucleus of C57BLK6J mouse brain by in situ hybridization histochemistry, suggest a new role for relaxin in neuropeptide signaling processes. Together, these studies describe a third member of the human relaxin family and its equivalent in the mouse.
Bathgate
Ross A D
RA
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Victoria 3010, Australia. r.bathgate@hfi.unimelb.edu.au
Samuel
Chrishan S
CS
Burazin
Tanya C D
TC
Layfield
Sharon
S
Claasz
Antonia A
AA
Reytomas
Irna Grace T
IG
Dawson
Nicola F
NF
Zhao
Chongxin
C
Bond
Courtney
C
Summers
Roger J
RJ
Parry
Laura J
LJ
Wade
John D
JD
Tregear
Geoffrey W
GW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D016208:Databases, Factual; D005260:Female; D015870:Gene Expression; D015894:Genome, Human; D006801:Humans; D017403:In Situ Hybridization; D007328:Insulin / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010802:Phylogeny; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D012065:Relaxin / Q000138:chemical synthesis / Q000145:classification / Q000235:genetics* / Q000378:metabolism*
D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors; D012065:Relaxin