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Protein

Insulin gene enhancer protein ISL-1

Gene

Isl1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

DNA-binding transcriptional activator (PubMed:14664703, PubMed:24643061, PubMed:25775587, PubMed:22343712). Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes (PubMed:24643061, PubMed:25775587). Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation (PubMed:25775587). Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina (PubMed:24643061, PubMed:25775587). Involved in the specification of motor neurons in cooperation with LHX3 and LDB1 (PubMed:18583962). Binds to insulin gene enhancer sequences (By similarity). Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (PubMed:14667410).By similarity6 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi181 – 240HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

GO - Biological processi

  • atrial septum morphogenesis Source: BHF-UCL
  • axon regeneration Source: Ensembl
  • cardiac cell fate determination Source: MGI
  • cardiac muscle cell myoblast differentiation Source: MGI
  • cardiac right ventricle morphogenesis Source: BHF-UCL
  • cellular response to glucocorticoid stimulus Source: Ensembl
  • endocardial cushion morphogenesis Source: BHF-UCL
  • heart development Source: MGI
  • heart morphogenesis Source: MGI
  • innervation Source: BHF-UCL
  • mesenchymal cell differentiation Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of epithelial cell proliferation Source: Ensembl
  • negative regulation of inflammatory response Source: BHF-UCL
  • negative regulation of intracellular estrogen receptor signaling pathway Source: Ensembl
  • negative regulation of neuron apoptotic process Source: BHF-UCL
  • negative regulation of neuron differentiation Source: MGI
  • negative regulation of protein homodimerization activity Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • neural crest cell migration Source: MGI
  • neuron differentiation Source: MGI
  • neuron fate commitment Source: MGI
  • neuron fate specification Source: BHF-UCL
  • outflow tract morphogenesis Source: BHF-UCL
  • outflow tract septum morphogenesis Source: BHF-UCL
  • pancreas development Source: MGI
  • peripheral nervous system neuron axonogenesis Source: BHF-UCL
  • peripheral nervous system neuron development Source: MGI
  • pharyngeal system development Source: BHF-UCL
  • pituitary gland development Source: MGI
  • positive regulation of angiogenesis Source: BHF-UCL
  • positive regulation of cell differentiation Source: UniProtKB
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of DNA binding Source: MGI
  • positive regulation of epithelial to mesenchymal transition Source: Ensembl
  • positive regulation of granulocyte colony-stimulating factor production Source: BHF-UCL
  • positive regulation of granulocyte macrophage colony-stimulating factor production Source: BHF-UCL
  • positive regulation of histone acetylation Source: CACAO
  • positive regulation of insulin secretion Source: Ensembl
  • positive regulation of interferon-gamma production Source: BHF-UCL
  • positive regulation of interleukin-12 production Source: BHF-UCL
  • positive regulation of interleukin-1 alpha production Source: BHF-UCL
  • positive regulation of interleukin-1 beta production Source: BHF-UCL
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • positive regulation of macrophage colony-stimulating factor production Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of tumor necrosis factor production Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of STAT protein Source: MGI
  • positive regulation of vascular endothelial growth factor production Source: BHF-UCL
  • regulation of gene expression Source: MGI
  • regulation of secondary heart field cardioblast proliferation Source: MGI
  • retinal ganglion cell axon guidance Source: MGI
  • secondary heart field specification Source: MGI
  • sensory system development Source: BHF-UCL
  • spinal cord motor neuron cell fate specification Source: MGI
  • spinal cord motor neuron differentiation Source: MGI
  • trigeminal nerve development Source: BHF-UCL
  • ventricular cardiac muscle tissue morphogenesis Source: BHF-UCL
  • visceral motor neuron differentiation Source: MGI

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processDifferentiation, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin gene enhancer protein ISL-1
Short name:
Islet-1
Gene namesi
Name:Isl1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:101791. Isl1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryonic mutants exhibit growth retardation at approximately E9.5 and die at approximately E10.5. Between E9.0 and E9.5 hearts are severely abnormal, appear misshapen and unlooped. Hearts are completely missing the outflow tract, right ventricle, and much of the atria (PubMed:14667410). Conditional mutants for retina expression show a decrease in several gene expression levels involved in the differentiation of retinal ganglion cells (RGC) (PubMed:24643061).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000757481 – 349Insulin gene enhancer protein ISL-1Add BLAST349

Post-translational modificationi

Isoform 1 is phosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP61372.
PaxDbiP61372.
PRIDEiP61372.

PTM databases

iPTMnetiP61372.
PhosphoSitePlusiP61372.

Expressioni

Developmental stagei

Between E7.5 and E8.5, as the heart tube forms, expressed in splanchnic mesenchyme comprising the mesocardium and adjacent to foregut endoderm as well as in both splanchnic mesoderm and in ventral foregut endoderm. At E10, continues to be expressed in ventral endoderm and splanchnic mesoderm but is not expressed in the myocardium of the heart (PubMed:14667410). At E10.5, expressed in cardiomyocytes located in the outflow tract (PubMed:22343712).2 Publications

Gene expression databases

BgeeiENSMUSG00000042258.
CleanExiMM_ISL1.
ExpressionAtlasiP61372. baseline and differential.
GenevisibleiP61372. MM.

Interactioni

Subunit structurei

At neuronal promoters, displaces LDB1 from LHX3 LIM domain to form a ternary complex in which ISL1 contacts both LHX3 and LDB1 (PubMed:18583962). Interacts (via C-terminus) with POU4F2 (via C-terminus) isoform 1 (PubMed:24643061). Interacts with POU3F2 (PubMed:24643061). Interacts with POU4F3 (PubMed:24643061). Interacts (via N-terminal domain) with MLIP; the interaction represses ISL1 transactivator activity (PubMed:22343712).3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200812. 3 interactors.
CORUMiP61372.
IntActiP61372. 2 interactors.
MINTiMINT-4594016.
STRINGi10090.ENSMUSP00000044879.

Structurei

Secondary structure

1349
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi127 – 129Combined sources3
Turni130 – 132Combined sources3
Beta strandi263 – 266Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RGTX-ray2.05A/B262-291[»]
4JCJX-ray3.00A/B/C123-138[»]
ProteinModelPortaliP61372.
SMRiP61372.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61372.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini17 – 70LIM zinc-binding 1PROSITE-ProRule annotationAdd BLAST54
Domaini79 – 133LIM zinc-binding 2PROSITE-ProRule annotationAdd BLAST55

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni262 – 291LIM-binding domain (LID)Add BLAST30

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi241 – 349Gln-richAdd BLAST109

Keywords - Domaini

Homeobox, LIM domain, Repeat

Phylogenomic databases

eggNOGiKOG0490. Eukaryota.
ENOG410YIJ3. LUCA.
GeneTreeiENSGT00760000118921.
HOGENOMiHOG000236304.
HOVERGENiHBG004671.
InParanoidiP61372.
KOiK09370.
OMAiRIHDQWI.
OrthoDBiEOG091G09L9.
PhylomeDBiP61372.
TreeFamiTF315442.

Family and domain databases

CDDicd00086. homeodomain. 1 hit.
InterProiView protein in InterPro
IPR009057. Homeobox-like_sf.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR001781. Znf_LIM.
PfamiView protein in Pfam
PF00046. Homeobox. 1 hit.
PF00412. LIM. 2 hits.
SMARTiView protein in SMART
SM00389. HOX. 1 hit.
SM00132. LIM. 2 hits.
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiView protein in PROSITE
PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P61372-1) [UniParc]FASTAAdd to basket
Also known as: Isl1-alpha1 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGDMGDPPKK KRLISLCVGC GNQIHDQYIL RVSPDLEWHA ACLKCAECNQ
60 70 80 90 100
YLDESCTCFV RDGKTYCKRD YIRLYGIKCA KCSIGFSKND FVMRARSKVY
110 120 130 140 150
HIECFRCVAC SRQLIPGDEF ALREDGLFCR ADHDVVERAS LGAGDPLSPL
160 170 180 190 200
HPARPLQMAA EPISARQPAL RPHVHKQPEK TTRVRTVLNE KQLHTLRTCY
210 220 230 240 250
AANPRPDALM KEQLVEMTGL SPRVIRVWFQ NKRCKDKKRS IMMKQLQQQQ
260 270 280 290 300
PNDKTNIQGM TGTPMVAASP ERHDGGLQAN PVEVQSYQPP WKVLSDFALQ
310 320 330 340
SDIDQPAFQQ LVNFSEGGPG SNSTGSEVAS MSSQLPDTPN SMVASPIEA
Length:349
Mass (Da):39,036
Last modified:May 24, 2004 - v1
Checksum:i4DB82FD09154F404
GO
Isoform 2 (identifier: P61372-2) [UniParc]FASTAAdd to basket
Also known as: Isl1-beta1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     256-278: Missing.

Note: Preferentially expressed in insulinoma cell lines. Expression is much lower than that of isoform 1. Shows relatively higher transcriptional activity than isoform 1.1 Publication
Show »
Length:326
Mass (Da):36,686
Checksum:i226972F6D190C598
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010338256 – 278Missing in isoform 2. 1 PublicationAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB104633 mRNA. Translation: BAC57891.1.
AJ132765 mRNA. Translation: CAB38446.1.
CCDSiCCDS26790.1. [P61372-1]
RefSeqiNP_067434.3. NM_021459.4. [P61372-1]
XP_006517596.1. XM_006517533.2. [P61372-2]
UniGeneiMm.42242.

Genome annotation databases

EnsembliENSMUST00000036060; ENSMUSP00000044879; ENSMUSG00000042258. [P61372-1]
ENSMUST00000176044; ENSMUSP00000135567; ENSMUSG00000042258. [P61372-2]
GeneIDi16392.
KEGGimmu:16392.
UCSCiuc007rye.2. mouse. [P61372-1]
uc007ryf.2. mouse. [P61372-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiISL1_MOUSE
AccessioniPrimary (citable) accession number: P61372
Secondary accession number(s): P20663, P47894, Q812D8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 24, 2004
Last modified: November 22, 2017
This is version 132 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references