Written | 2009-11 | Jordan M Willcox, Alastair JS Summerlee |
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, N1G 2W1, Canada |
Identity |
Alias (NCBI) | H2 | RLXH2 | bA12D24.1.1 | bA12D24.1.2 | prorelaxin H2 |
HGNC (Hugo) | RLN2 |
HGNC Alias symb | H2 | RLXH2 | bA12D24.1.1 | bA12D24.1.2 |
HGNC Alias name | "relaxin H2 | prorelaxin H2 | relaxin, ovarian, of pregnancy" |
HGNC Previous name | relaxin 2 (H2) |
LocusID (NCBI) | 6019 |
Atlas_Id | 44421 |
Location | 9p24.1 [Link to chromosome band 9p24] |
Location_base_pair | Starts at 5299866 and ends at 5304716 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping RLN2.png] |
Local_order | RLN2 is located on chromosome 9 on the reverse strand. |
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RLN2 is located on chromosome 9 (position shown by yellow arrow). | |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
MSN (Xq12) / RLN2 (9p24.1) | RLN1 (9p24.1) / RLN2 (9p24.1) |
Note | See also, in the Deep Insight section: RLN2 and its role in cancer |
DNA/RNA |
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Schematic representation of the transcription of the human RLN2 gene. Adapted from Bathgate et al., 2006 (with permission). 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. The arrows on the diagrams indicate the orientation of the genes. Although insulin and H2 relaxin are similar, there is no report that the insulin gene possess an intron. | |
Description | RLN2 is a functioning gene of 4,712 bp comprising 2 exons and 1 intron. |
Transcription | The length of the transcript is 588bp. mRNA is expressed in high levels in ovary and placenta, and in lower levels in fibroblasts, a number of tumours, heart and brain. Alternate splicing: 2 isoforms: P04090-1, P04090-2. |
Pseudogene | None but there are a number of similar genes of the same family. These include: RLN1 and RLN2 genes in a tight cluster with INSL4 and INSL6 genes on chromosome 9 at 9p24. The RLN3 gene is located on chromosome 19 at 19p13.3 in close proximity to INSL3 at 19p13.2 and the INSL5 gene is located on chromosome 1 at 1p31.1 |
Protein |
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Modified from Westhuizen et al. 2008. Characteristic two-peptide chain hormone held together by disulphide bonds (shown in yellow) which provide the tertiary form of the molecule. There is a relaxin receptor binding motif (shown in red and green). | |
Description | Protein length of the precursor peptide is 185 amino acids with a molecular weight 21,043 Daltons. The functional peptide has 21 amino acids in the A chain and 27 in the B chain and with a molecular weight 5,989 Daltons. There is a specific binding motif (see diagram above) Arg-X-X-X-Arg-X-X-Ile/Val which are vital for binding and the projection from the tertiary structure is important in binding to the Type C LGR receptor (RXPF1). These receptors have a large and very distinctive ectodomain which includes an LDLa module at the far end of the N-terminus followed by a LRR domain (10 LRR). 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. |
Expression | mRNA and protein found in brain, heart, skin, lungs, liver, kidney, ovary, uterus, testis, prostate and in prostatic and mammary neoplasia. Expression induced by a variety of factors in different tissues. |
Localisation | Cytoplasm. |
Function | Brain
- Mediates stress behaviour - Increased fluid intake - Release of a number of hypothalamic peptides including vasopressin, oxytoxcin, LH, and angiotensin II
- Increased force of atrial contraction - Reduced fibrosis - Differentiation and development - Release of ANP
- Decreased total peripheral resistance - Vasodilation
- Relaxes bronchi - Reduced fibrosis - Reduced degranulation mast cells - Reduced inflammatory leukocytes
- Increased ERPF - Increased Na+ excretion - Reduced fibosis
- Germ cell maturation
- Endometrial thickening
- Possible role in hypertrophy and neoplastic change
- Vasodilation - Reduced fibrosis - Reduced apoptosis |
Homology | Generally 30-60% sequence homology is observed between relaxin 2 among species. |
Mutations |
Note | It is assumed that the members of the relaxin-gene family are predominantly functional mutations of an original relaxin gene (RLN3) located on chromosome 19 at 19p13.3 and translocated at some stage predominantly to chromosome 9. |
Implicated in |
Note | |
Entity | Prostate cancer |
Disease | Prostate cancer is the most common form of carcinoma in men (Lippman et al., 2009). If left untreated, this form of cancer becomes highly metastatic, primarily to the bones and lymphatic system. RLN2 is implicated in the progression, development, and spread of prostate cancer. RLN2 increases extra-cellular matrix turnover, promotes tumor invasiveness, and neo-vascularization (Silvertown et al., 2006). |
Prognosis | Given that circulating relaxin increases in experimental models of prostate cancer, it is possible RLN2 may be employed as an early marker for prostate cancer and act as a screening mechanism in clinical settings. Furthermore, RLN2 exhibits the potential for genetic therapy to target and neutralize this gene as a novel treatment for prostate cancer. |
Oncogenesis | RLN2 has been implicated in the progression of prostate tumors. RLN2 expression is increased in prostate tumors (Silvertown et al., 2006). Antagonism with analogues of RLN2 (Silvertown et al., 2007) demonstrates antagonistic properties and impairs prostate tumor growth and development. |
Entity | Breast cancer |
Disease | Breast cancer is the most common form of carcinoma in women. RLN2 increases the invasiveness of breast cancer cells via the induction of matrix metalloproteinases (MMPs) (Binder et al., 2002). Circulating relaxin also increases in patients with breast cancer (Binder et al., 2004). |
Prognosis | Since serum relaxin concentrations are increased in patients with breast cancer, relaxin may be used as a screening tool for breast cancer. Furthermore, RLN2 may be targeted for genetic therapy as a novel treatment for breast cancer. |
Oncogenesis | RLN2 increases the oncogenic potential of breast cancer cells by stimulating growth, invasiveness, and metastasis. |
Entity | Thyroid cancer |
Disease | There are four types of thyroid cancer: papillary, folliculary, medullary, and anaplastic. While limited research has been conducted with regards to RLN2 and thyroid cancer, it is possible relaxin enhances the course and development of thyroid cancer. |
Oncogenesis | RLN2 acts as an autocrine/paracrine factor to enhance growth and invasiveness of thyroid cancer cells (Hombach-Klonisch et al., 2006). RLN2 may also increase motility of thyroid cancer cells thereby contributing to increased metastatic potential. |
Bibliography |
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Relaxin enhances the oncogenic potential of human thyroid carcinoma cells. |
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Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells. |
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PMID 2076464 |
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PMID 9730618 |
Relaxin family peptide receptors--from orphans to therapeutic targets. |
van der Westhuizen ET, Halls ML, Samuel CS, Bathgate RA, Unemori EN, Sutton SW, Summers RJ. |
Drug Discov Today. 2008 Aug;13(15-16):640-51. Epub 2008 Jun 6. (REVIEW) |
PMID 18675759 |
Citation |
This paper should be referenced as such : |
Willcox, JM ; Summerlee, AJS |
RLN2 (relaxin 2) |
Atlas Genet Cytogenet Oncol Haematol. 2010;14(9):841-845. |
Free journal version : [ pdf ] [ DOI ] |
Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ] |
RLN1/RLN2 (9p24)
t(X;9)(q11;p24) MSN/RLN2 |
External links |
REVIEW articles | automatic search in PubMed |
Last year publications | automatic search in PubMed |
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