ISL1_RAT
ID ISL1_RAT Reviewed; 349 AA.
AC P61374; P20663; P47894;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Insulin gene enhancer protein ISL-1;
DE Short=Islet-1;
GN Name=Isl1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Keratinocyte;
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] (ISOFORM 2).
RC STRAIN=Wistar;
RA Liu J., Chen D., Zheng Y., Meng X., Liu Y.;
RT "Variation of insulin gene enhancer binding protein Isl-1.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-316 (ISOFORM 1), DNA-BINDING, AND TISSUE
RP SPECIFICITY.
RX PubMed=1691825; DOI=10.1038/344879a0;
RA Karlsson O., Thor S., Norberg T., Ohlsson H., Edlund T.;
RT "Insulin gene enhancer binding protein Isl-1 is a member of a novel class
RT of proteins containing both a homeo- and a Cys-His domain.";
RL Nature 344:879-882(1990).
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 (By similarity). Binds to insulin gene
CC enhancer sequences (PubMed:1691825). Essential for heart development.
CC Marker of one progenitor cell population that give rise to the outflow
CC tract, right ventricle, a subset of left ventricular cells, and a large
CC number of atrial cells as well, its function is required for these
CC progenitors to contribute to the heart. Controls the expression of FGF
CC and BMP growth factors in this cell population and is required for
CC proliferation and survival of cells within pharyngeal foregut endoderm
CC and adjacent splanchnic mesoderm as well as for migration of cardiac
CC progenitors into the heart (By similarity).
CC {ECO:0000250|UniProtKB:P61372, ECO:0000269|PubMed:1691825}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Isl1-alpha;
CC IsoId=P61374-1; Sequence=Displayed;
CC Name=2; Synonyms=Isl1-beta;
CC IsoId=P61374-2; Sequence=VSP_010339;
CC -!- TISSUE SPECIFICITY: Expressed in islet cells of the pancreas
CC (PubMed:7907017, PubMed:1691825). {ECO:0000269|PubMed:1691825,
CC ECO:0000269|PubMed:7907017}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:P61372}.
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DR EMBL; S69329; AAB30128.1; -; mRNA.
DR EMBL; AY557632; AAS46773.1; -; mRNA.
DR EMBL; X53258; CAA37349.1; -; mRNA.
DR PIR; I67417; I67417.
DR RefSeq; NP_059035.3; NM_017339.3. [P61374-1]
DR AlphaFoldDB; P61374; -.
DR SMR; P61374; -.
DR STRING; 10116.ENSRNOP00000017305; -.
DR PhosphoSitePlus; P61374; -.
DR PaxDb; P61374; -.
DR PRIDE; P61374; -.
DR GeneID; 64444; -.
DR KEGG; rno:64444; -.
DR CTD; 3670; -.
DR RGD; 61957; Isl1.
DR VEuPathDB; HostDB:ENSRNOG00000012556; -.
DR eggNOG; KOG0490; Eukaryota.
DR HOGENOM; CLU_027802_2_0_1; -.
DR InParanoid; P61374; -.
DR OMA; VSQMHGY; -.
DR OrthoDB; 948890at2759; -.
DR PhylomeDB; P61374; -.
DR TreeFam; TF315442; -.
DR PRO; PR:P61374; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000012556; Expressed in stomach and 9 other tissues.
DR Genevisible; P61374; RN.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IDA:BHF-UCL.
DR GO; GO:0016922; F:nuclear receptor binding; IDA: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; IDA:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0060413; P:atrial septum morphogenesis; ISO:RGD.
DR GO; GO:0031103; P:axon regeneration; IEP:RGD.
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; ISO:RGD.
DR GO; GO:0060379; P:cardiac muscle cell myoblast differentiation; ISO:RGD.
DR GO; GO:0003215; P:cardiac right ventricle morphogenesis; ISO:RGD.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEP:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0003007; P:heart morphogenesis; ISO:RGD.
DR GO; GO:0060384; P:innervation; ISO:RGD.
DR GO; GO:0048762; P:mesenchymal cell differentiation; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:RGD.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0001755; P:neural crest cell migration; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR GO; GO:0048663; P:neuron fate commitment; ISO:RGD.
DR GO; GO:0048665; P:neuron fate specification; ISO:RGD.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISO:RGD.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISO:RGD.
DR GO; GO:0031016; P:pancreas development; ISO:RGD.
DR GO; GO:0048936; P:peripheral nervous system neuron axonogenesis; ISO:RGD.
DR GO; GO:0048935; P:peripheral nervous system neuron development; ISO:RGD.
DR GO; GO:0060037; P:pharyngeal system development; ISO:RGD.
DR GO; GO:0021983; P:pituitary gland development; ISO:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISO:RGD.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0071657; P:positive regulation of granulocyte colony-stimulating factor production; ISO:RGD.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:RGD.
DR GO; GO:0035066; P:positive regulation of histone acetylation; ISO:RGD.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:RGD.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO:RGD.
DR GO; GO:0032730; P:positive regulation of interleukin-1 alpha production; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:1901258; P:positive regulation of macrophage colony-stimulating factor production; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISO:RGD.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISO:RGD.
DR GO; GO:0003266; P:regulation of secondary heart field cardioblast proliferation; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:RGD.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; ISO:RGD.
DR GO; GO:0003139; P:secondary heart field specification; ISO:RGD.
DR GO; GO:0048880; P:sensory system development; ISO:RGD.
DR GO; GO:0060931; P:sinoatrial node cell development; ISO:RGD.
DR GO; GO:0021520; P:spinal cord motor neuron cell fate specification; ISO:RGD.
DR GO; GO:0021522; P:spinal cord motor neuron differentiation; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0021559; P:trigeminal nerve development; ISO:RGD.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISO:RGD.
DR GO; GO:0021524; P:visceral motor neuron differentiation; ISO:RGD.
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; Alternative splicing; Developmental protein; Differentiation;
KW DNA-binding; Homeobox; LIM domain; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation; Zinc.
FT CHAIN 1..349
FT /note="Insulin gene enhancer protein ISL-1"
FT /id="PRO_0000075749"
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"
FT VAR_SEQ 256..278
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_010339"
FT CONFLICT 67
FT /note="C -> S (in Ref. 2; AAS46773)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="C -> R (in Ref. 2; AAS46773)"
FT /evidence="ECO:0000305"
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
