Insulin/IGF/Relaxin family

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Insulin/IGF/Relaxin family
PBB Protein INS image.jpg
PDB rendering based on 1ai0.
Identifiers
SymbolInsulin
Pfam PF00049
Pfam clan CL0239
InterPro IPR004825
PROSITE PDOC00235
SCOP2 1cph / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1a7f , 1ai0 , 1aiy , 1aph , 1b17 , 1b18 , 1b19 , 1b2a , 1b2b , 1b2c , 1b2d , 1b2e , 1b2f , 1b2g , 1b9e , 1b9g , 1ben , 1bom , 1bon , 1bph , 1bqt , 1cph , 1dei , 1dph , 1efe , 1ev3 , 1ev6 , 1evr , 1g7a , 1guj , 1gzr , 1gzy , 1gzz , 1h02 , 1h59 , 1hiq , 1his , 1hit , 1hls , 1ho0 , 1htv , 1hui , 1igl , 1imx , 1iog , 1ioh , 1iza , 1izb , 1j73 , 1jca , 1jco , 1k3m , 1kmf , 1lkq , 1lph , 1m5a , 1mhi , 1mhj , 1mpj , 1mso , 1os3 , 1os4 , 1pid , 1pmx , 1qiy , 1qiz , 1qj0 , 1sdb , 1sf1 , 1sjt , 1sju , 1t1k , 1t1p , 1t1q , 1tgr , 1trz , 1tyl , 1tym , 1vkt , 1wav , 1wqj , 1xda , 1xgl , 1zeg , 1zeh , 1zei , 1zni , 1znj , 2aiy , 2dsp , 2dsq , 2dsr , 2gf1 , 2hiu , 2ins , 2tci , 3aiy , 3gf1 , 3lri , 3mth , 4aiy , 4ins , 5aiy , 6rlx , 7ins , 9ins

The insulin/IGF/relaxin family is a group of evolutionary related proteins which possess a variety of hormonal activities. [1] Family members in human include two subfamilies:

Contents

1) insulin and insulin-like growth factors [2]

2) relaxin family peptides:

Structure

These proteins are characterized by having three disulfide bonds in a characteristic motif. Some family members have an additional disulfide bond also in a conserved location. All of these proteins have a helical segment (corresponding to B chain in insulin) followed by a variable-length chain, followed by a domain (A chain in insulin) with two helices pinned against each other via a disulfide bond. These two regions are linked by two or three disulfide bonds.

Amongst the different proteins in the family, very little of the sequence is conserved except for the disulfide bonds. The variable-length chains may exhibit large inter-species variation even when the remainder of the sequence is highly conserved; and as is in the case of insulin, sometimes the variable length chain is cleaved out by secretory endoproteases, leaving a two-chain protein held together by disulfide bonds.

See also

Related Research Articles

<span class="mw-page-title-main">Insulin-like growth factor</span> Proteins similar to insulin that stimulate cell proliferation

The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system consists of two cell-surface receptors, two ligands, a family of seven high-affinity IGF-binding proteins, as well as associated IGFBP degrading enzymes, referred to collectively as proteases.

<span class="mw-page-title-main">Post-translational modification</span> Chemical changes in proteins following their translation from mRNA

In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translate mRNA into polypeptide chains, which may then change to form the mature protein product. PTMs are important components in cell signalling, as for example when prohormones are converted to hormones.

<span class="mw-page-title-main">Proinsulin</span> Precursor protein in humans

Proinsulin is the prohormone precursor to insulin made in the beta cells of the Pancreatic Islets, specialized regions of the pancreas. In humans, proinsulin is encoded by the INS gene. The pancreatic islets only secrete between 1% and 3% of proinsulin intact. However, because proinsulin has a longer half life than insulin, it can account for anywhere from 5–30% of the insulin-like structures circulating in the blood. There are higher concentrations of proinsulin after meals and lower levels when a person is fasting. Additionally, while proinsulin and insulin have structural differences, proinsulin does demonstrate some affinity for the insulin receptor. Due to the relative similarities in structure, proinsulin can produce between 5% and 10% of the metabolic activity similarly induced by insulin.

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<span class="mw-page-title-main">Relaxin</span> Protein hormone

Relaxin is a protein hormone of about 6000 Da, first described in 1926 by Frederick Hisaw.

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<span class="mw-page-title-main">Cyclotide</span> Disulfide-rich ring peptides found in plants

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<span class="mw-page-title-main">IGFBP3</span> Protein-coding gene in the species Homo sapiens

Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the IGFBP3 gene. IGFBP-3 is one of six IGF binding proteins that have highly conserved structures and bind the insulin-like growth factors IGF-1 and IGF-2 with high affinity. IGFBP-7, sometimes included in this family, shares neither the conserved structural features nor the high IGF affinity. Instead, IGFBP-7 binds IGF1R, which blocks IGF-1 and IGF-2 binding, resulting in apoptosis.

<span class="mw-page-title-main">PDGFA</span> Mammalian protein found in Homo sapiens

Platelet-derived growth factor subunit A is a protein that in humans is encoded by the PDGFA gene.

<span class="mw-page-title-main">Relaxin/insulin-like family peptide receptor 1</span> Protein-coding gene in the species Homo sapiens

Relaxin/insulin-like family peptide receptor 1, also known as RXFP1, is a human G protein coupled receptor that is one of the relaxin receptors. It is a rhodopsin-like GPCR which is unusual in this class as it contains a large extracellular binding and signalling domain. Some reports suggest that RXFP1 forms homodimers, however the most recent evidence indicates that relaxin binds a non-homodimer of RXFP1.

<span class="mw-page-title-main">Relaxin/insulin-like family peptide receptor 2</span> Protein-coding gene in the species Homo sapiens

Relaxin/insulin-like family peptide receptor 2, also known as RXFP2, is a human G-protein coupled receptor.

<span class="mw-page-title-main">INSL3</span> Protein-coding gene in the species Homo sapiens

Insulin-like 3 is a protein that in humans is encoded by the INSL3 gene.

<span class="mw-page-title-main">CRHBP</span> Protein-coding gene in the species Homo sapiens

Corticotropin-releasing factor-binding protein is a protein that in humans is encoded by the CRHBP gene. It belongs to corticotropin-releasing hormone binding protein family.

<span class="mw-page-title-main">INSL4</span> Protein-coding gene in the species Homo sapiens

Early placenta insulin-like peptide is a protein that in humans is encoded by the INSL4 gene.

<span class="mw-page-title-main">Cystine knot</span> Protein structural motif

A cystine knot is a protein structural motif containing three disulfide bridges. The sections of polypeptide that occur between two of them form a loop through which a third disulfide bond passes, forming a rotaxane substructure. The cystine knot motif stabilizes protein structure and is conserved in proteins across various species. There are three types of cystine knot, which differ in the topology of the disulfide bonds:

<span class="mw-page-title-main">Relaxin-3</span>

Relaxin-3 is a neuropeptide that was discovered in 2001, and which is highly conserved in species ranging from flies, fish, rodents and humans. Relaxin-3 is a member and ancestral gene of the relaxin family of peptides, which includes the namesake hormone relaxin which mediates peripheral actions during pregnancy and which was found to relax the pelvic ligament in guinea pigs almost a century ago. The cognate receptor for relaxin-3 is the G-protein coupled receptor RXFP3, however relaxin-3 is pharmacologically able to also cross react with RXFP1 and RXFP3.

<span class="mw-page-title-main">Relaxin family peptide hormones</span> Protein family

Relaxin family peptide hormones in humans are represented by seven members: three relaxin-like (RLN) and four insulin-like (INSL) peptides: RLN1, RLN2, RNL3, INSL3, INSL4, INSL5, INSL6. This subdivision into two classes is based primarily on early findings, and does not reflect the evolutionary origins or physiological differences between peptides. For example, it is known that the genes coding for RLN3 and INSL5 arose from one ancestral gene, and INSL3 shares origin with RLN2 and its multiple duplicates: RLN1, INSL4, INSL6.

<span class="mw-page-title-main">Neohormone</span> Group of hormones associated with the success of mammalian development

Neohormones are a group of recently evolved hormones primarily associated to the success of mammalian development. These hormones are specific to mammals and are not found in other vertebrates—this is because neohormones are evolved to enhance specific mammalian functions. In males, neohormones play important roles in regulating testicular descent and preparing the sperm for internal fertilisation. In females, neohormones are essential for regulating early pregnancy, mammary gland development lactation, and viviparity. Neohormones superimpose their actions on the hypothalamic-pituitary-gonadal axis and are not associated with other core bodily functions.

References

  1. Blundell TL, Humbel RE (October 1980). "Hormone families: pancreatic hormones and homologous growth factors". Nature. 287 (5785): 781–7. Bibcode:1980Natur.287..781B. doi:10.1038/287781a0. PMID   6107857. S2CID   4325746.
  2. Humbel RE (July 1990). "Insulin-like growth factors I and II". European Journal of Biochemistry. 190 (3): 445–62. doi:10.1111/j.1432-1033.1990.tb15595.x. PMID   2197088.
  3. Adham IM, Burkhardt E, Benahmed M, Engel W (December 1993). "Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells". The Journal of Biological Chemistry. 268 (35): 26668–72. doi: 10.1016/S0021-9258(19)74364-6 . PMID   8253799. Archived from the original on 2003-11-15. Retrieved 2008-11-08.
  4. Chassin D, Laurent A, Janneau JL, Berger R, Bellet D (September 1995). "Cloning of a new member of the insulin gene superfamily (INSL4) expressed in human placenta". Genomics. 29 (2): 465–70. doi:10.1006/geno.1995.9980. PMID   8666396.