ISL1

ISL LIM homeobox 1
PDB rendering based on 1bw5.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1bw5​
Identifiers
Symbols	ISL1 ; ISLET1; Isl-1
External IDs	OMIM: 600366 MGI: 101791 HomoloGene: 1661 GeneCards: ISL1 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • RNA polymerase II activating transcription factor binding • RNA polymerase II transcription coactivator activity • enhancer sequence-specific DNA binding • chromatin binding • protein binding • zinc ion binding • ligand-dependent nuclear receptor binding • estrogen receptor binding • bHLH transcription factor binding Cellular component • nucleus • nucleoplasm • cytoplasm • mitochondrion Biological process • negative regulation of transcription from RNA polymerase II promoter • neural crest cell migration • secondary heart field specification • outflow tract septum morphogenesis • outflow tract morphogenesis • endocardial cushion morphogenesis • cardiac right ventricle morphogenesis • regulation of secondary heart field cardioblast proliferation • transcription from RNA polymerase II promoter • positive regulation of cell proliferation • positive regulation of vascular endothelial growth factor production • spinal cord motor neuron cell fate specification • spinal cord motor neuron differentiation • visceral motor neuron differentiation • trigeminal nerve development • pituitary gland development • pancreas development • axon regeneration • retinal ganglion cell axon guidance • positive regulation of insulin secretion • positive regulation of granulocyte macrophage colony-stimulating factor production • positive regulation of interferon-gamma production • positive regulation of interleukin-1 alpha production • positive regulation of interleukin-1 beta production • positive regulation of interleukin-12 production • positive regulation of interleukin-6 production • positive regulation of tumor necrosis factor production • negative regulation of intracellular estrogen receptor signaling pathway • positive regulation of histone acetylation • positive regulation of tyrosine phosphorylation of Stat3 protein • positive regulation of DNA binding • negative regulation of neuron apoptotic process • negative regulation of neuron differentiation • positive regulation of angiogenesis • positive regulation of transcription from RNA polymerase II promoter • neuron fate specification • mesenchymal cell differentiation • sensory system development • peripheral nervous system neuron axonogenesis • negative regulation of inflammatory response • ventricular cardiac muscle tissue morphogenesis • pharyngeal system development • cardiac muscle cell myoblast differentiation • innervation • atrial septum morphogenesis • cardiac cell fate determination • cellular response to glucocorticoid stimulus • positive regulation of granulocyte colony-stimulating factor production • negative regulation of protein homodimerization activity • negative regulation of canonical Wnt signaling pathway • positive regulation of macrophage colony-stimulating factor production Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
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

Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene.^[1][2]

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 fail to undergo neural tube motor neuron differentiation.^[2]

Interactions

ISL1 has been shown to interact with Estrogen receptor alpha.^[3]

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.^[4] 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.^[5][6][7]

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.^[8] Furthermore, ISL1 is not restricted to second heart field progenitors in the developing heart, but also labels cardiac neural crest.^[9] This paper supports work from the Vilquin group in 2011, which concluded that ISL1 can represent cells from both neural crest and cardiomyocyte lineages.^[10] 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. 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.
2. "Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)".
3. 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.
4. 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. PMID 14667410.
5. 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.
6. 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. PMID 15703750.
7. 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.
8. 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. PMID 22427341.
9. 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. PMID 22394517.
10. 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. 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.