ID   ISL1_MESAU              Reviewed;         349 AA.
AC   P61373; P20663; P47894;
DT   24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   24-MAY-2004, sequence version 1.
DT   03-AUG-2022, entry version 105.
DE   RecName: Full=Insulin gene enhancer protein ISL-1;
DE            Short=Islet-1;
GN   Name=ISL1;
OS   Mesocricetus auratus (Golden hamster).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Mesocricetus.
OX   NCBI_TaxID=10036;
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).
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   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P61372}.
CC   -!- TISSUE SPECIFICITY: Expressed in fibroblast.
CC       {ECO:0000269|PubMed:7907017}.
CC   -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:P61372}.
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DR   EMBL; S70720; AAP20776.1; -; mRNA.
DR   RefSeq; XP_005082833.1; XM_005082776.2.
DR   AlphaFoldDB; P61373; -.
DR   SMR; P61373; -.
DR   STRING; 10036.XP_005082833.1; -.
DR   GeneID; 101836649; -.
DR   CTD; 3670; -.
DR   eggNOG; KOG0490; Eukaryota.
DR   OrthoDB; 948890at2759; -.
DR   Proteomes; UP000189706; Unplaced.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0043425; F:bHLH transcription factor binding; IEA:Ensembl.
DR   GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IEA:Ensembl.
DR   GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR   GO; GO:0060413; P:atrial septum morphogenesis; IEA:Ensembl.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR   GO; GO:0060913; P:cardiac cell fate determination; IEA:Ensembl.
DR   GO; GO:0060379; P:cardiac muscle cell myoblast differentiation; IEA:Ensembl.
DR   GO; GO:0003215; P:cardiac right ventricle morphogenesis; IEA:Ensembl.
DR   GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR   GO; GO:0003203; P:endocardial cushion morphogenesis; IEA:Ensembl.
DR   GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR   GO; GO:0060384; P:innervation; IEA:Ensembl.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; IEA:Ensembl.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR   GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0001755; P:neural crest cell migration; IEA:Ensembl.
DR   GO; GO:0003148; P:outflow tract septum morphogenesis; IEA:Ensembl.
DR   GO; GO:0031016; P:pancreas development; IEA:Ensembl.
DR   GO; GO:0048936; P:peripheral nervous system neuron axonogenesis; IEA:Ensembl.
DR   GO; GO:0060037; P:pharyngeal system development; IEA:Ensembl.
DR   GO; GO:0021983; P:pituitary gland development; IEA:Ensembl.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
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:0071657; P:positive regulation of granulocyte colony-stimulating factor production; IEA:Ensembl.
DR   GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IEA:Ensembl.
DR   GO; GO:0035066; P:positive regulation of histone acetylation; IEA:Ensembl.
DR   GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl.
DR   GO; GO:0032730; P:positive regulation of interleukin-1 alpha production; IEA:Ensembl.
DR   GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl.
DR   GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
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; IEA:Ensembl.
DR   GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IEA:Ensembl.
DR   GO; GO:0003266; P:regulation of secondary heart field cardioblast proliferation; IEA:Ensembl.
DR   GO; GO:0031290; P:retinal ganglion cell axon guidance; IEA:Ensembl.
DR   GO; GO:0003139; P:secondary heart field specification; IEA:Ensembl.
DR   GO; GO:0048880; P:sensory system development; IEA:Ensembl.
DR   GO; GO:0060931; P:sinoatrial node cell development; IEA:Ensembl.
DR   GO; GO:0021520; P:spinal cord motor neuron cell fate specification; IEA:Ensembl.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0021559; P:trigeminal nerve development; IEA:Ensembl.
DR   GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IEA:Ensembl.
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   2: Evidence at transcript 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_0000075747"
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