INSL3

INSL3
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2H8B, 2K6T, 2K6U
Identifiers
Aliases	INSL3 , RLF, RLNL, ley-I-L, insulin like 3
External IDs	OMIM: 146738 MGI: 108427 HomoloGene: 4048 GeneCards: INSL3
Gene location (Human)
Chr.	Chromosome 19 (human)
End	17,821,574 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	72,143,219 bp
RNA expression pattern
	Top expressed in
	blood; ; spleen; ; appendix; ; lymph node; ; body of stomach; ; right coronary artery; ; cerebellar hemisphere; ; bone marrow; ; rectum; ; cingulate gyrus;
	Top expressed in
	testicle; ; spermatocyte; ; spleen; ; islet of Langerhans; ; bone marrow; ; urinary bladder; ; adrenal gland; ; duodenum; ; thymus; ; morula;
	More reference expression data
	n/a
Gene ontology
Molecular function	protease binding ; signaling receptor binding ; insulin receptor binding ; hormone activity ; G protein-coupled receptor binding ;
Cellular component	extracellular region ; extracellular space ;
Biological process	cell-cell signaling ; positive regulation of wound healing ; positive regulation of epithelial cell migration ; spermatogenesis ; regulation of signaling receptor activity ; G protein-coupled receptor signaling pathway ; adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway ;
	Sources:Amigo / QuickGO
Orthologs
	3640
	16336
	ENSG00000248099
	ENSMUSG00000079019
	P51460
	O09107 ; Q5RL10
	NM_005543 ; NM_001265587
	NM_013564
	NP_001252516 ; NP_005534
	NP_038592
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated April 03, 2024

Insulin-like 3 is a protein that in humans is encoded by the INSL3 gene.^[5]^[6]

Function

The protein encoded by this gene is an insulin like hormone produced mainly in gonadal tissues in males and females. Studies of the mouse counterpart suggest that this gene may be involved in the development of urogenital tract and female fertility. INSL-3 initiates meiotic progression in follicle-enclosed oocytes by mediating a reduction in intra-oocyte cAMP concentration by activating leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8).^[7] It may also act as a hormone to regulate growth and differentiation of gubernaculum, and thus mediating intra-abdominal testicular descent. The mutations in this gene may lead to, but not a frequent cause of, cryptorchidism.^[6]

Related Research Articles

The JAK-STAT signaling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death, and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through the process of transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), signal transducer and activator of transcription proteins (STATs), and receptors. Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.

The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR), is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction.

Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the TYK2 gene.

Tyrosine-protein kinase JAK3 is a tyrosine kinase enzyme that in humans is encoded by the JAK3 gene.

Janus kinase 2 is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family, the GM-CSF receptor family, the gp130 receptor family, and the single chain receptors.

JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family, the IL-4 receptor family, the gp130 receptor family. It is also important for transducing a signal by type I (IFN-α/β) and type II (IFN-γ) interferons, and members of the IL-10 family via type II cytokine receptors. Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. Loss of Jak1 is lethal in neonatal mice, possibly due to difficulties suckling. Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body.

T-cell surface glycoprotein CD3 zeta chain also known as T-cell receptor T3 zeta chain or CD247 is a protein that in humans is encoded by the CD247 gene.

Relaxin/insulin-like family peptide receptor 3, also known as RXFP3, is a human G-protein coupled receptor.

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.

Relaxin/insulin-like family peptide receptor 4, also known as RXFP4, is a human G-protein coupled receptor.

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

Eukaryotic translation initiation factor 2 subunit 1 (eIF2α) is a protein that in humans is encoded by the EIF2S1 gene.

Protein kinase C iota type is an enzyme that in humans is encoded by the PRKCI gene.

SH2B adapter protein 2 is a protein that in humans is encoded by the SH2B2 gene.

Selenoprotein N is a protein that in humans is encoded by the SEPN1 gene.

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

A Janus kinase inhibitor, also known as JAK inhibitor or jakinib, is a type of immune modulating medication, which inhibits the activity of one or more of the Janus kinase family of enzymes, thereby interfering with the JAK-STAT signaling pathway in lymphocytes.

JAK3 deficiency is a dysfunction in cytokine receptor signalling and their production of cytokines.

The NR4A1 gene is a transcription factor important in the development of cells that secrete the hormone insulin-like 3 (INSL3). In general, the NR4A gene family regulates cell growth and differentiation.

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 2 3 GRCh38: Ensembl release 89: ENSG00000248099 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000079019 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Burkhardt E, Adham IM, Brosig B, Gastmann A, Mattei MG, Engel W (March 1994). "Structural organization of the porcine and human genes coding for a Leydig cell-specific insulin-like peptide (LEY I-L) and chromosomal localization of the human gene (INSL3)". Genomics. 20 (1): 13–9. doi:10.1006/geno.1994.1121. PMID 8020942.
1 2 "Entrez Gene: INSL3 insulin-like 3 (Leydig cell)".
↑ Richard FJ (March 2007). "Regulation of meiotic maturation". Journal of Animal Science. 85 (13 Suppl): E4-6. doi:10.2527/jas.2006-475. PMID 17040950.

Lai KS, Jin Y, Graham DK, Witthuhn BA, Ihle JN, Liu ET (October 1995). "A kinase-deficient splice variant of the human JAK3 is expressed in hematopoietic and epithelial cancer cells". The Journal of Biological Chemistry. 270 (42): 25028–36. doi: 10.1074/jbc.270.42.25028 . PMID 7559633.
Macchi P, Villa A, Giliani S, Sacco MG, Frattini A, Porta F, Ugazio AG, Johnston JA, Candotti F, O'Shea JJ (September 1995). "Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)". Nature. 377 (6544): 65–8. Bibcode:1995Natur.377...65M. doi:10.1038/377065a0. PMID 7659163. S2CID 4329874.
Tashima LS, Hieber AD, Greenwood FC, Bryant-Greenwood GD (February 1995). "The human Leydig insulin-like (hLEY I-L) gene is expressed in the corpus luteum and trophoblast". The Journal of Clinical Endocrinology and Metabolism. 80 (2): 707–10. doi:10.1210/jcem.80.2.7852540. PMID 7852540.
Witthuhn BA, Silvennoinen O, Miura O, Lai KS, Cwik C, Liu ET, Ihle JN (July 1994). "Involvement of the Jak-3 Janus kinase in signalling by interleukins 2 and 4 in lymphoid and myeloid cells". Nature. 370 (6485): 153–7. Bibcode:1994Natur.370..153W. doi:10.1038/370153a0. PMID 8022486. S2CID 11711979.
Kawamura M, McVicar DW, Johnston JA, Blake TB, Chen YQ, Lal BK, Lloyd AR, Kelvin DJ, Staples JE, Ortaldo JR (July 1994). "Molecular cloning of L-JAK, a Janus family protein-tyrosine kinase expressed in natural killer cells and activated leukocytes". Proceedings of the National Academy of Sciences of the United States of America. 91 (14): 6374–8. Bibcode:1994PNAS...91.6374K. doi: 10.1073/pnas.91.14.6374 . PMC 44204 . PMID 8022790.
Burkhardt E, Adham IM, Hobohm U, Murphy D, Sander C, Engel W (July 1994). "A human cDNA coding for the Leydig insulin-like peptide (Ley I-L)". Human Genetics. 94 (1): 91–4. doi:10.1007/BF02272850. PMID 8034302. S2CID 11255499.
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.
Verbsky JW, Bach EA, Fang YF, Yang L, Randolph DA, Fields LE (June 1996). "Expression of Janus kinase 3 in human endothelial and other non-lymphoid and non-myeloid cells". The Journal of Biological Chemistry. 271 (24): 13976–80. doi: 10.1074/jbc.271.24.13976 . PMID 8662778.
Candotti F, Oakes SA, Johnston JA, Giliani S, Schumacher RF, Mella P, Fiorini M, Ugazio AG, Badolato R, Notarangelo LD, Bozzi F, Macchi P, Strina D, Vezzoni P, Blaese RM, O'Shea JJ, Villa A (November 1997). "Structural and functional basis for JAK3-deficient severe combined immunodeficiency". Blood. 90 (10): 3996–4003. doi: 10.1182/blood.V90.10.3996 . PMID 9354668.
Bozzi F, Lefranc G, Villa A, Badolato R, Schumacher RF, Khalil G, Loiselet J, Bresciani S, O'Shea JJ, Vezzoni P, Notarangelo LD, Candotti F (September 1998). "Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment". British Journal of Haematology. 102 (5): 1363–6. doi: 10.1111/j.1365-2141.1998.tb08990.x . PMID 9753072. S2CID 31606560.
Nef S, Parada LF (July 1999). "Cryptorchidism in mice mutant for Insl3". Nature Genetics. 22 (3): 295–9. doi:10.1038/10364. PMID 10391220. S2CID 1394181.
Büllesbach EE, Rhodes R, Rembiesa B, Schwabe C (April 1999). "The relaxin-like factor is a hormone". Endocrine. 10 (2): 167–9. doi:10.1385/ENDO:10:2:167. PMID 10451226. S2CID 27433286.
Krausz C, Quintana-Murci L, Fellous M, Siffroi JP, McElreavey K (April 2000). "Absence of mutations involving the INSL3 gene in human idiopathic cryptorchidism". Molecular Human Reproduction. 6 (4): 298–302. doi:10.1093/molehr/6.4.298. PMID 10729310.
Koskimies P, Virtanen H, Lindström M, Kaleva M, Poutanen M, Huhtaniemi I, Toppari J (April 2000). "A common polymorphism in the human relaxin-like factor (RLF) gene: no relationship with cryptorchidism". Pediatric Research. 47 (4 Pt 1): 538–41. doi: 10.1203/00006450-200004000-00020 . PMID 10759163.
Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K (July 2000). "STAM2, a new member of the STAM family, binding to the Janus kinases". FEBS Letters. 477 (1–2): 55–61. doi:10.1016/S0014-5793(00)01760-9. PMID 10899310. S2CID 31811757.
Schumacher RF, Mella P, Badolato R, Fiorini M, Savoldi G, Giliani S, Villa A, Candotti F, Tampalini A, O'Shea JJ, Notarangelo LD (January 2000). "Complete genomic organization of the human JAK3 gene and mutation analysis in severe combined immunodeficiency by single-strand conformation polymorphism". Human Genetics. 106 (1): 73–9. doi:10.1007/s004390051012 (inactive 2024-04-02). PMID 10982185.{{cite journal}}: CS1 maint: DOI inactive as of April 2024 (link)
Tomboc M, Lee PA, Mitwally MF, Schneck FX, Bellinger M, Witchel SF (November 2000). "Insulin-like 3/relaxin-like factor gene mutations are associated with cryptorchidism". The Journal of Clinical Endocrinology and Metabolism. 85 (11): 4013–8. doi: 10.1210/jcem.85.11.6935 . PMID 11095425.
Hombach-Klonisch S, Buchmann J, Sarun S, Fischer B, Klonisch T (December 2000). "Relaxin-like factor (RLF) is differentially expressed in the normal and neoplastic human mammary gland". Cancer. 89 (11): 2161–8. doi: 10.1002/1097-0142(20001201)89:11<2161::AID-CNCR3>3.0.CO;2-K . PMID 11147585.
Lim HN, Raipert-de Meyts E, Skakkebaek NE, Hawkins JR, Hughes IA (February 2001). "Genetic analysis of the INSL3 gene in patients with maldescent of the testis". European Journal of Endocrinology. 144 (2): 129–37. doi: 10.1530/eje.0.1440129 . PMID 11182749.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000248099 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000079019 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8020942-5] Burkhardt E, Adham IM, Brosig B, Gastmann A, Mattei MG, Engel W (March 1994). "Structural organization of the porcine and human genes coding for a Leydig cell-specific insulin-like peptide (LEY I-L) and chromosomal localization of the human gene (INSL3)". Genomics. 20 (1): 13–9. doi:10.1006/geno.1994.1121. PMID 8020942.

[entrez-6] 1 2 "Entrez Gene: INSL3 insulin-like 3 (Leydig cell)".

[pmid17040950-7] Richard FJ (March 2007). "Regulation of meiotic maturation". Journal of Animal Science. 85 (13 Suppl): E4-6. doi:10.2527/jas.2006-475. PMID 17040950.

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INSL3

Contents

Function

Related Research Articles

References

Further reading