ISL1

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]
End	51,394,730 bp[1]
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)[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
	3670
	16392
	ENSG00000016082
	ENSMUSG00000042258
	P61371
	P61372
	NM_002202
	NM_021459
	NP_002193
	NP_067434
	Wikidata
View/Edit Human	View/Edit Mouse

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

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

GRCh38: Ensembl release 89: ENSG00000016082 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000042258 - 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.
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.
"Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)".
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.
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.
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. S2CID 31238870.
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. Bibcode:2005Natur.433..647L. doi:10.1038/nature03215. PMC 5578466. PMID 15703750.
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. Bibcode:2009Natur.460..113B. doi:10.1038/nature08191. PMID 19571884. S2CID 801804.
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.
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.
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.

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.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000016082 - Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid7912209-5] 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.

[entrez-6] "Entrez Gene: ISL1 ISL1 transcription factor, LIM/homeodomain, (islet-1)".

[pmid11043578-7] 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.

[pmid14667410-8] 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.

[pmid17123592-9] 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. S2CID 31238870.

[pmid15703750-10] 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. Bibcode:2005Natur.433..647L. doi:10.1038/nature03215. PMC 5578466. PMID 15703750.

[pmid19571884-11] 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. Bibcode:2009Natur.460..113B. doi:10.1038/nature08191. PMID 19571884. S2CID 801804.

[pmid22427341-12] 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.

[pmid22394517-13] 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.

[pmid20942609-14] 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.