ISL1

Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene.[5][6]

ISL1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2RGT, 4JCJ
Identifiers
Aliases	ISL1, ISLET1, Isl-1, ISL LIM homeobox 1
External IDs	OMIM: 600366 MGI: 101791 HomoloGene: 1661 GeneCards: ISL1
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q11.1 Start 51,383,448 bp[1] End 51,394,730 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 D2.2 Start 116,298,281 bp[2] End 116,309,689 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • DNA binding • GO:0001105 transcription coactivator activity • sequence-specific DNA binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • chromatin binding • metal ion binding • RNA polymerase II activating transcription factor binding • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • bHLH transcription factor binding • GO:0001948 protein binding • ligand-dependent nuclear receptor binding • GO:0001158 core promoter proximal region sequence-specific DNA binding • estrogen receptor binding • promoter-specific chromatin binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • cytoplasm • nucleoplasm • cell nucleus Biological process • negative regulation of neuron apoptotic process • peripheral nervous system neuron development • positive regulation of interleukin-1 alpha production • pituitary gland development • regulation of transcription, DNA-templated • negative regulation of neuron differentiation • positive regulation of interleukin-12 production • axon regeneration • spinal cord motor neuron cell fate specification • trigeminal nerve development • neuron fate specification • outflow tract morphogenesis • positive regulation of interferon-gamma production • positive regulation of granulocyte colony-stimulating factor production • heart morphogenesis • negative regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • positive regulation of angiogenesis • positive regulation of histone acetylation • outflow tract septum morphogenesis • endocardial cushion morphogenesis • ventricular cardiac muscle tissue morphogenesis • atrial septum morphogenesis • multicellular organism development • cardiac cell fate determination • regulation of secondary heart field cardioblast proliferation • cardiac muscle cell myoblast differentiation • cellular response to glucocorticoid stimulus • visceral motor neuron differentiation • mesenchymal cell differentiation • positive regulation of granulocyte macrophage colony-stimulating factor production • neural crest cell migration • neuron differentiation • positive regulation of cell proliferation • positive regulation of interleukin-1 beta production • positive regulation of interleukin-6 production • positive regulation of tumor necrosis factor production • regulation of gene expression • pancreas development • positive regulation of macrophage colony-stimulating factor production • positive regulation of vascular endothelial growth factor production • negative regulation of protein homodimerization activity • positive regulation of DNA binding • peripheral nervous system neuron axonogenesis • spinal cord motor neuron differentiation • neuron fate commitment • secondary heart field specification • innervation • negative regulation of intracellular estrogen receptor signaling pathway • negative regulation of inflammatory response • cardiac right ventricle morphogenesis • negative regulation of canonical Wnt signaling pathway • positive regulation of insulin secretion • sensory system development • pharyngeal system development • retinal ganglion cell axon guidance • positive regulation of transcription from RNA polymerase II promoter • positive regulation of cell differentiation • transcription, DNA-templated • cell differentiation • positive regulation of tyrosine phosphorylation of STAT protein • positive regulation of epithelial to mesenchymal transition • negative regulation of epithelial cell proliferation • heart development • axonogenesis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3670	16392
Ensembl	ENSG00000016082	ENSMUSG00000042258
UniProt	P61371	P61372
RefSeq (mRNA)	NM_002202	NM_021459
RefSeq (protein)	NP_002193	NP_067434
Location (UCSC)	Chr 5: 51.38 – 51.39 Mb	Chr 13: 116.3 – 116.31 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a transcription factor containing two N-terminal LIM domains and one C-terminal homeodomain. The encoded protein plays an important role in the embryogenesis of pancreatic islets of Langerhans. In mouse embryos, a deficiency of this gene results in failure to undergo neural tube motor neuron differentiation.[6]

Interactions

ISL1 has been shown to interact with Estrogen receptor alpha.[7]

Role in cardiac development

ISL1 is a marker for cardiac progenitors of the secondary heart field (SHF) which includes the right ventricle and the outflow tract. It also has a biological function as shown in Isl1 knockout mice which have a severely deformed heart.[8] More recently it has been defined as a marker for a cardiac progenitor cell lineage that is capable of differentiating into all 3 major cell types of the heart: cardiomyocytes, smooth muscle and endothelial cell lineages.[9][10][11]

The validity of ISL1 as a marker for cardiac progenitor cells has been questioned since some groups have found no evidence that ISL1 cells serve as cardiac progenitors.[12] Furthermore, ISL1 is not restricted to second heart field progenitors in the developing heart, but also labels cardiac neural crest.[13] This paper supports work from the Vilquin group in 2011, which concluded that ISL1 can represent cells from both neural crest and cardiomyocyte lineages.[14] While it has been demonstrated by multiple groups that ISL1-positive cells can indeed differentiate into all 3 major cell types of the heart, their significance in cardiovascular development is still unclear and their clinical relevance has been seriously questioned.

References

1. GRCh38: Ensembl release 89: ENSG00000016082 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000042258 - 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.
5. Tanizawa Y, Riggs AC, Dagogo-Jack S, Vaxillaire M, Froguel P, Liu L, Donis-Keller H, Permutt MA (July 1994). "Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected]". Diabetes. 43 (7): 935–41. doi:10.2337/diabetes.43.7.935. PMID 7912209.
6. "Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)".
7. Gay F, Anglade I, Gong Z, Salbert G (October 2000). "The LIM/homeodomain protein islet-1 modulates estrogen receptor functions". Mol. Endocrinol. 14 (10): 1627–48. doi:10.1210/me.14.10.1627. PMID 11043578.
8. Cai CL, Liang X, Shi Y, Chu PH, Pfaff SL, Chen J, Evans S (December 2003). "Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart". Dev. Cell. 5 (6): 877–89. doi:10.1016/S1534-5807(03)00363-0. PMC 5578462. PMID 14667410.
9. Moretti A, Caron L, Nakano A, Lam JT, Bernshausen A, Chen Y, Qyang Y, Bu L, Sasaki M, Martin-Puig S, Sun Y, Evans SM, Laugwitz KL, Chien KR (December 2006). "Multipotent embryonic isl1+ progenitor cells lead to cardiac, smooth muscle, and endothelial cell diversification". Cell. 127 (6): 1151–65. doi:10.1016/j.cell.2006.10.029. PMID 17123592.
10. Laugwitz KL, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin LZ, Cai CL, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S, Chien KR (February 2005). "Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages". Nature. 433 (7026): 647–53. doi:10.1038/nature03215. PMC 5578466. PMID 15703750.
11. Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, Roberts DJ, Huang PL, Domian IJ, Chien KR (July 2009). "Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages". Nature. 460 (7251): 113–7. doi:10.1038/nature08191. PMID 19571884.
12. Weinberger F, Mehrkens D, Friedrich FW, Stubbendorff M, Hua X, Müller JC, Schrepfer S, Evans SM, Carrier L, Eschenhagen T (May 2012). "Localization of Islet-1-positive cells in the healthy and infarcted adult murine heart". Circ. Res. 110 (10): 1303–10. doi:10.1161/CIRCRESAHA.111.259630. PMC 5559221. PMID 22427341.
13. Engleka KA, Manderfield LJ, Brust RD, Li L, Cohen A, Dymecki SM, Epstein JA (March 2012). "Islet1 derivatives in the heart are of both neural crest and second heart field origin". Circ. Res. 110 (7): 922–6. doi:10.1161/CIRCRESAHA.112.266510. PMC 3355870. PMID 22394517.
14. Khattar P, Friedrich FW, Bonne G, Carrier L, Eschenhagen T, Evans SM, Schwartz K, Fiszman MY, Vilquin JT (June 2011). "Distinction between two populations of islet-1-positive cells in hearts of different murine strains". Stem Cells Dev. 20 (6): 1043–52. doi:10.1089/scd.2010.0374. PMC 5880329. PMID 20942609.

Further reading

• Larsson LI (1999). "On the development of the islets of Langerhans". Microsc. Res. Tech. 43 (4): 284–91. doi:10.1002/(SICI)1097-0029(19981115)43:4<284::AID-JEMT2>3.0.CO;2-0. PMID 9849969.
• Dong J, Asa SL, Drucker DJ (1992). "Islet cell and extrapancreatic expression of the LIM domain homeobox gene isl-1". Mol. Endocrinol. 5 (11): 1633–41. doi:10.1210/mend-5-11-1633. PMID 1685766.
• Riggs AC, Tanizawa Y, Aoki M, Wasson J, Ferrer J, Rabin DU, Vaxillaire M, Froguel P, Permutt MA (1995). "Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM". Diabetes. 44 (6): 689–94. doi:10.2337/diabetes.44.6.689. PMID 7789634.
• Wang M, Drucker DJ (1994). "The LIM domain homeobox gene isl-1: conservation of human, hamster, and rat complementary deoxyribonucleic acid sequences and expression in cell types of nonneuroendocrine lineage". Endocrinology. 134 (3): 1416–22. doi:10.1210/en.134.3.1416. PMID 7907017.
• Pfaff SL, Mendelsohn M, Stewart CL, Edlund T, Jessell TM (1996). "Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation". Cell. 84 (2): 309–20. doi:10.1016/S0092-8674(00)80985-X. PMID 8565076.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Ahlgren U, Pfaff SL, Jessell TM, Edlund T, Edlund H (1997). "Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells". Nature. 385 (6613): 257–60. doi:10.1038/385257a0. PMID 9000074.
• Jurata LW, Pfaff SL, Gill GN (1998). "The nuclear LIM domain interactor NLI mediates homo- and heterodimerization of LIM domain transcription factors". J. Biol. Chem. 273 (6): 3152–7. doi:10.1074/jbc.273.6.3152. PMID 9452425.
• Bach I, Rodriguez-Esteban C, Carrière C, Bhushan A, Krones A, Rose DW, Glass CK, Andersen B, Izpisúa Belmonte JC, Rosenfeld MG (1999). "RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex". Nat. Genet. 22 (4): 394–9. doi:10.1038/11970. PMID 10431247.
• Gay F, Anglade I, Gong Z, Salbert G (2001). "The LIM/homeodomain protein islet-1 modulates estrogen receptor functions". Mol. Endocrinol. 14 (10): 1627–48. doi:10.1210/me.14.10.1627. PMID 11043578.
• Ostendorff HP, Peirano RI, Peters MA, Schlüter A, Bossenz M, Scheffner M, Bach I (2002). "Ubiquitination-dependent cofactor exchange on LIM homeodomain transcription factors". Nature. 416 (6876): 99–103. doi:10.1038/416099a. PMID 11882901.
• Holm P, Rydlander B, Luthman H, Kockum I, European Consortium for IDDM Genome Studies (2004). "Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families". Diabetes. 53 (6): 1584–91. doi:10.2337/diabetes.53.6.1584. PMID 15161765.
• Hori Y, Gu X, Xie X, Kim SK (2006). "Differentiation of insulin-producing cells from human neural progenitor cells". PLoS Med. 2 (4): e103. doi:10.1371/journal.pmed.0020103. PMC 1087208. PMID 15839736.
• Takeuchi JK, Mileikovskaia M, Koshiba-Takeuchi K, Heidt AB, Mori AD, Arruda EP, Gertsenstein M, Georges R, Davidson L, Mo R, Hui CC, Henkelman RM, Nemer M, Black BL, Nagy A, Bruneau BG (2005). "Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development". Development. 132 (10): 2463–74. doi:10.1242/dev.01827. PMID 15843409.
• Peng SY, Wang WP, Meng J, Li T, Zhang H, Li YM, Chen P, Ma KT, Zhou CY (2006). "ISL1 physically interacts with BETA2 to promote insulin gene transcriptional synergy in non-beta cells". Biochim. Biophys. Acta. 1731 (3): 154–9. doi:10.1016/j.bbaexp.2005.08.013. PMID 16321656.

External links

• ISL1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.