ISL1_HUMAN
ID ISL1_HUMAN Reviewed; 349 AA.
AC P61371; P20663; P47894;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Insulin gene enhancer protein ISL-1;
DE Short=Islet-1;
GN Name=ISL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=7907017; DOI=10.1210/endo.134.3.7907017;
RA Wang M., Drucker D.J.;
RT "The LIM domain homeobox gene isl-1: conservation of human, hamster, and
RT rat complementary deoxyribonucleic acid sequences and expression in cell
RT types of nonneuroendocrine lineage.";
RL Endocrinology 134:1416-1422(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-349.
RC TISSUE=Pancreatic islet;
RX PubMed=7912209; DOI=10.2337/diab.43.7.935;
RA Tanizawa Y., Riggs A.C., Dagogo-Jack S., Vaxillaire M., Froguel P., Liu L.,
RA Donis-Keller H., Permutt M.A.;
RT "Isolation of the human LIM/homeodomain gene islet-1 and identification of
RT a simple sequence repeat polymorphism.";
RL Diabetes 43:935-941(1994).
RN [3]
RP ERRATUM OF PUBMED:7912209.
RA Tanizawa Y., Riggs A.C., Dagogo-Jack S., Vaxillaire M., Froguel P., Liu L.,
RA Donis-Keller H., Permutt M.A.;
RL Diabetes 43:1171-1171(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=21403123; DOI=10.1161/circulationaha.110.980607;
RA Sizarov A., Ya J., de Boer B.A., Lamers W.H., Christoffels V.M.,
RA Moorman A.F.;
RT "Formation of the building plan of the human heart: morphogenesis, growth,
RT and differentiation.";
RL Circulation 123:1125-1135(2011).
CC -!- FUNCTION: DNA-binding transcriptional activator. Recognizes and binds
CC to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of
CC target genes. Plays a fundamental role in the gene regulatory network
CC essential for retinal ganglion cell (RGC) differentiation. Cooperates
CC with the transcription factor POU4F2 to achieve maximal levels of
CC expression of RGC target genes and RGC fate specification in the
CC developing retina. Involved in the specification of motor neurons in
CC cooperation with LHX3 and LDB1. Binds to insulin gene enhancer
CC sequences. Essential for heart development. Marker of one progenitor
CC cell population that give rise to the outflow tract, right ventricle, a
CC subset of left ventricular cells, and a large number of atrial cells as
CC well, its function is required for these progenitors to contribute to
CC the heart. Controls the expression of FGF and BMP growth factors in
CC this cell population and is required for proliferation and survival of
CC cells within pharyngeal foregut endoderm and adjacent splanchnic
CC mesoderm as well as for migration of cardiac progenitors into the heart
CC (By similarity). {ECO:0000250|UniProtKB:P61372,
CC ECO:0000250|UniProtKB:P61374}.
CC -!- SUBUNIT: At neuronal promoters, displaces LDB1 from LHX3 LIM domain to
CC form a ternary complex in which ISL1 contacts both LHX3 and LDB1.
CC Interacts (via C-terminus) with POU4F2 (via C-terminus). Interacts with
CC POU3F2. Interacts with POU4F3. Interacts (via N-terminal domain) with
CC MLIP; the interaction represses ISL1 transactivator activity (By
CC similarity). {ECO:0000250|UniProtKB:P61372}.
CC -!- INTERACTION:
CC P61371; Q86U70-2: LDB1; NbExp=7; IntAct=EBI-3906896, EBI-11979761;
CC P61371; Q969G2: LHX4; NbExp=3; IntAct=EBI-3906896, EBI-2865388;
CC P61371; Q8NB15: ZNF511; NbExp=7; IntAct=EBI-3906896, EBI-10269136;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P61372}.
CC -!- TISSUE SPECIFICITY: Expressed in subsets of neurons of the adrenal
CC medulla and dorsal root ganglion, inner nuclear and ganglion cell
CC layers in the retina, the pineal and some regions of the brain.
CC {ECO:0000269|PubMed:7907017}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the forming heart in the stage 9
CC embryo, in the myocardial trough, and then at stages 10 to 11, in the
CC nondifferentiated mesodermal cells at the venous and arterial poles, as
CC well as cells of the dorsal coelomic wall and ruptured mesocardium (at
CC protein level). {ECO:0000269|PubMed:21403123}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:P61372}.
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DR EMBL; S70721; AAD14064.1; -; mRNA.
DR EMBL; U07559; AAA81946.1; -; mRNA.
DR EMBL; BC031213; AAH31213.1; -; mRNA.
DR CCDS; CCDS43314.1; -.
DR PIR; I53277; I53277.
DR RefSeq; NP_002193.2; NM_002202.2.
DR AlphaFoldDB; P61371; -.
DR SMR; P61371; -.
DR BioGRID; 109877; 35.
DR IntAct; P61371; 20.
DR MINT; P61371; -.
DR STRING; 9606.ENSP00000230658; -.
DR iPTMnet; P61371; -.
DR PhosphoSitePlus; P61371; -.
DR BioMuta; ISL1; -.
DR DMDM; 47606423; -.
DR jPOST; P61371; -.
DR MassIVE; P61371; -.
DR MaxQB; P61371; -.
DR PaxDb; P61371; -.
DR PeptideAtlas; P61371; -.
DR PRIDE; P61371; -.
DR ProteomicsDB; 57299; -.
DR Antibodypedia; 23291; 596 antibodies from 37 providers.
DR DNASU; 3670; -.
DR Ensembl; ENST00000230658.12; ENSP00000230658.7; ENSG00000016082.15.
DR GeneID; 3670; -.
DR KEGG; hsa:3670; -.
DR MANE-Select; ENST00000230658.12; ENSP00000230658.7; NM_002202.3; NP_002193.2.
DR UCSC; uc003jor.4; human.
DR CTD; 3670; -.
DR DisGeNET; 3670; -.
DR GeneCards; ISL1; -.
DR HGNC; HGNC:6132; ISL1.
DR HPA; ENSG00000016082; Tissue enhanced (retina, seminal vesicle, vagina).
DR MalaCards; ISL1; -.
DR MIM; 600366; gene.
DR neXtProt; NX_P61371; -.
DR OpenTargets; ENSG00000016082; -.
DR Orphanet; 93930; Bladder exstrophy.
DR PharmGKB; PA29932; -.
DR VEuPathDB; HostDB:ENSG00000016082; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000153731; -.
DR InParanoid; P61371; -.
DR OMA; VSQMHGY; -.
DR OrthoDB; 948890at2759; -.
DR PhylomeDB; P61371; -.
DR TreeFam; TF315442; -.
DR PathwayCommons; P61371; -.
DR Reactome; R-HSA-400511; Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP).
DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs.
DR SignaLink; P61371; -.
DR SIGNOR; P61371; -.
DR BioGRID-ORCS; 3670; 28 hits in 1094 CRISPR screens.
DR ChiTaRS; ISL1; human.
DR GeneWiki; ISL1; -.
DR GenomeRNAi; 3670; -.
DR Pharos; P61371; Tbio.
DR PRO; PR:P61371; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P61371; protein.
DR Bgee; ENSG00000016082; Expressed in secondary oocyte and 97 other tissues.
DR ExpressionAtlas; P61371; baseline and differential.
DR Genevisible; P61371; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; NAS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISS:BHF-UCL.
DR GO; GO:0016922; F:nuclear receptor binding; ISS:BHF-UCL.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0060413; P:atrial septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0031103; P:axon regeneration; IEA:Ensembl.
DR GO; GO:0007409; P:axonogenesis; IBA:GO_Central.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0060913; P:cardiac cell fate determination; IDA:BHF-UCL.
DR GO; GO:0060379; P:cardiac muscle cell myoblast differentiation; IEA:Ensembl.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; ISS:BHF-UCL.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; ISS:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0060384; P:innervation; ISS:BHF-UCL.
DR GO; GO:0048762; P:mesenchymal cell differentiation; ISS:BHF-UCL.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:BHF-UCL.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:BHF-UCL.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl.
DR GO; GO:0048665; P:neuron fate specification; ISS:BHF-UCL.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0031016; P:pancreas development; ISS:BHF-UCL.
DR GO; GO:0048936; P:peripheral nervous system neuron axonogenesis; ISS:BHF-UCL.
DR GO; GO:0060037; P:pharyngeal system development; ISS:BHF-UCL.
DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:BHF-UCL.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0043388; P:positive regulation of DNA binding; IEA:Ensembl.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IEA:Ensembl.
DR GO; GO:0071657; P:positive regulation of granulocyte colony-stimulating factor production; ISS:BHF-UCL.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISS:BHF-UCL.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IEA:Ensembl.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IC:BHF-UCL.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:BHF-UCL.
DR GO; GO:0032730; P:positive regulation of interleukin-1 alpha production; ISS:BHF-UCL.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:BHF-UCL.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:BHF-UCL.
DR GO; GO:1901258; P:positive regulation of macrophage colony-stimulating factor production; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:ParkinsonsUK-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:BHF-UCL.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IEA:Ensembl.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISS:BHF-UCL.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISS:BHF-UCL.
DR GO; GO:0003266; P:regulation of secondary heart field cardioblast proliferation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; IEA:Ensembl.
DR GO; GO:0003139; P:secondary heart field specification; IMP:BHF-UCL.
DR GO; GO:0048880; P:sensory system development; ISS:BHF-UCL.
DR GO; GO:0060931; P:sinoatrial node cell development; ISS:BHF-UCL.
DR GO; GO:0021520; P:spinal cord motor neuron cell fate specification; IEA:Ensembl.
DR GO; GO:0021522; P:spinal cord motor neuron differentiation; ISS:BHF-UCL.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0021559; P:trigeminal nerve development; ISS:BHF-UCL.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR GO; GO:0021524; P:visceral motor neuron differentiation; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF00412; LIM; 2.
DR SMART; SM00389; HOX; 1.
DR SMART; SM00132; LIM; 2.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR PROSITE; PS50023; LIM_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW Activator; Developmental protein; Differentiation; DNA-binding; Homeobox;
KW LIM domain; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Zinc.
FT CHAIN 1..349
FT /note="Insulin gene enhancer protein ISL-1"
FT /id="PRO_0000075746"
FT DOMAIN 17..70
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 79..133
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DNA_BIND 181..240
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 262..291
FT /note="LIM-binding domain (LID)"
FT /evidence="ECO:0000250"
FT REGION 312..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 312..341
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 349 AA; 39036 MW; 4DB82FD09154F404 CRC64;
MGDMGDPPKK KRLISLCVGC GNQIHDQYIL RVSPDLEWHA ACLKCAECNQ YLDESCTCFV
RDGKTYCKRD YIRLYGIKCA KCSIGFSKND FVMRARSKVY HIECFRCVAC SRQLIPGDEF
ALREDGLFCR ADHDVVERAS LGAGDPLSPL HPARPLQMAA EPISARQPAL RPHVHKQPEK
TTRVRTVLNE KQLHTLRTCY AANPRPDALM KEQLVEMTGL SPRVIRVWFQ NKRCKDKKRS
IMMKQLQQQQ PNDKTNIQGM TGTPMVAASP ERHDGGLQAN PVEVQSYQPP WKVLSDFALQ
SDIDQPAFQQ LVNFSEGGPG SNSTGSEVAS MSSQLPDTPN SMVASPIEA
