Full text data of ISL1
ISL1
[Confidence: low (only semi-automatic identification from reviews)]
Insulin gene enhancer protein ISL-1; Islet-1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Insulin gene enhancer protein ISL-1; Islet-1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P61371
ID ISL1_HUMAN Reviewed; 349 AA.
AC P61371; P20663; P47894;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 24-MAY-2004, sequence version 1.
DT 22-JAN-2014, entry version 102.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7907017; DOI=10.1210/en.134.3.1416;
RA Wang M., Drucker D.J.;
RT "The LIM domain homeobox gene isl-1: conservation of human, hamster,
RT and rat complementary deoxyribonucleic acid sequences and expression
RT in cell 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.,
RA Liu L., Donis-Keller H., Permutt M.A.;
RT "Isolation of the human LIM/homeodomain gene islet-1 and
RT identification of a simple sequence repeat polymorphism.";
RL Diabetes 43:935-941(1994).
RN [3]
RP ERRATUM.
RA Tanizawa Y., Riggs A.C., Dagogo-Jack S., Vaxillaire M., Froguel P.,
RA Liu L., 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
RT project: 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).
CC -!- FUNCTION: Binds and regulates the promoters of the insulin,
CC glucagon and somatostatin genes. Involved in the specificarion of
CC motor neurons in cooperation with LHX3 and LDB1 (By similarity).
CC -!- SUBUNIT: At neuronal promoters, displaces LDB1 from LHX3 LIM
CC domain to form a ternary complex in which ISL1 contacts both LHX3
CC and LDB1 (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus.
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 -!- PTM: Phosphorylated (By similarity).
CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain.
CC -!- SIMILARITY: Contains 2 LIM zinc-binding domains.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; S70721; AAD14064.1; -; mRNA.
DR EMBL; U07559; AAA81946.1; -; mRNA.
DR EMBL; BC031213; AAH31213.1; -; mRNA.
DR PIR; I53277; I53277.
DR RefSeq; NP_002193.2; NM_002202.2.
DR UniGene; Hs.505; -.
DR ProteinModelPortal; P61371; -.
DR SMR; P61371; 13-168, 180-244, 254-288.
DR IntAct; P61371; 5.
DR MINT; MINT-3022667; -.
DR STRING; 9606.ENSP00000230658; -.
DR PhosphoSite; P61371; -.
DR DMDM; 47606423; -.
DR PaxDb; P61371; -.
DR PRIDE; P61371; -.
DR DNASU; 3670; -.
DR Ensembl; ENST00000230658; ENSP00000230658; ENSG00000016082.
DR GeneID; 3670; -.
DR KEGG; hsa:3670; -.
DR UCSC; uc003jor.3; human.
DR CTD; 3670; -.
DR GeneCards; GC05P050714; -.
DR HGNC; HGNC:6132; ISL1.
DR MIM; 600366; gene.
DR neXtProt; NX_P61371; -.
DR PharmGKB; PA29932; -.
DR eggNOG; COG5576; -.
DR HOGENOM; HOG000236304; -.
DR HOVERGEN; HBG004671; -.
DR InParanoid; P61371; -.
DR KO; K09370; -.
DR OMA; TDMGDMG; -.
DR OrthoDB; EOG7JQBPW; -.
DR PhylomeDB; P61371; -.
DR GeneWiki; ISL1; -.
DR GenomeRNAi; 3670; -.
DR NextBio; 14363; -.
DR PRO; PR:P61371; -.
DR ArrayExpress; P61371; -.
DR Bgee; P61371; -.
DR CleanEx; HS_ISL1; -.
DR Genevestigator; P61371; -.
DR GO; GO:0005737; C:cytoplasm; NAS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; NAS:BHF-UCL.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0001158; F:enhancer sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0030331; F:estrogen receptor binding; ISS:BHF-UCL.
DR GO; GO:0016922; F:ligand-dependent nuclear receptor binding; ISS:BHF-UCL.
DR GO; GO:0001105; F:RNA polymerase II transcription coactivator activity; IDA:BHF-UCL.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0060413; P:atrial septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0031103; P:axon regeneration; 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:0071385; P:cellular response to glucocorticoid stimulus; ISS:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
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 receptor signaling pathway; 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:0090074; P:negative regulation of protein homodimerization activity; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; 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: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:0008284; P:positive regulation of cell 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; ISS:BHF-UCL.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISS:BHF-UCL.
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:0032760; P:positive regulation of tumor necrosis factor production; ISS:BHF-UCL.
DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IEA:Ensembl.
DR GO; GO:0010575; P:positive regulation vascular endothelial growth factor production; ISS:BHF-UCL.
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; IMP:BHF-UCL.
DR GO; GO:0048880; P:sensory system 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: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 Gene3D; 1.10.10.60; -; 1.
DR Gene3D; 2.10.110.10; -; 2.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR009057; Homeodomain-like.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00046; Homeobox; 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 Complete proteome; Developmental protein; DNA-binding; Homeobox;
KW LIM domain; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Zinc.
FT CHAIN 1 349 Insulin gene enhancer protein ISL-1.
FT /FTId=PRO_0000075746.
FT DOMAIN 17 70 LIM zinc-binding 1.
FT DOMAIN 79 133 LIM zinc-binding 2.
FT DNA_BIND 181 240 Homeobox.
FT REGION 262 291 LIM-binding domain (LID) (By similarity).
FT COMPBIAS 241 349 Gln-rich.
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
//
ID ISL1_HUMAN Reviewed; 349 AA.
AC P61371; P20663; P47894;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 24-MAY-2004, sequence version 1.
DT 22-JAN-2014, entry version 102.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7907017; DOI=10.1210/en.134.3.1416;
RA Wang M., Drucker D.J.;
RT "The LIM domain homeobox gene isl-1: conservation of human, hamster,
RT and rat complementary deoxyribonucleic acid sequences and expression
RT in cell 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.,
RA Liu L., Donis-Keller H., Permutt M.A.;
RT "Isolation of the human LIM/homeodomain gene islet-1 and
RT identification of a simple sequence repeat polymorphism.";
RL Diabetes 43:935-941(1994).
RN [3]
RP ERRATUM.
RA Tanizawa Y., Riggs A.C., Dagogo-Jack S., Vaxillaire M., Froguel P.,
RA Liu L., 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
RT project: 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).
CC -!- FUNCTION: Binds and regulates the promoters of the insulin,
CC glucagon and somatostatin genes. Involved in the specificarion of
CC motor neurons in cooperation with LHX3 and LDB1 (By similarity).
CC -!- SUBUNIT: At neuronal promoters, displaces LDB1 from LHX3 LIM
CC domain to form a ternary complex in which ISL1 contacts both LHX3
CC and LDB1 (By similarity).
CC -!- SUBCELLULAR LOCATION: Nucleus.
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 -!- PTM: Phosphorylated (By similarity).
CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain.
CC -!- SIMILARITY: Contains 2 LIM zinc-binding domains.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; S70721; AAD14064.1; -; mRNA.
DR EMBL; U07559; AAA81946.1; -; mRNA.
DR EMBL; BC031213; AAH31213.1; -; mRNA.
DR PIR; I53277; I53277.
DR RefSeq; NP_002193.2; NM_002202.2.
DR UniGene; Hs.505; -.
DR ProteinModelPortal; P61371; -.
DR SMR; P61371; 13-168, 180-244, 254-288.
DR IntAct; P61371; 5.
DR MINT; MINT-3022667; -.
DR STRING; 9606.ENSP00000230658; -.
DR PhosphoSite; P61371; -.
DR DMDM; 47606423; -.
DR PaxDb; P61371; -.
DR PRIDE; P61371; -.
DR DNASU; 3670; -.
DR Ensembl; ENST00000230658; ENSP00000230658; ENSG00000016082.
DR GeneID; 3670; -.
DR KEGG; hsa:3670; -.
DR UCSC; uc003jor.3; human.
DR CTD; 3670; -.
DR GeneCards; GC05P050714; -.
DR HGNC; HGNC:6132; ISL1.
DR MIM; 600366; gene.
DR neXtProt; NX_P61371; -.
DR PharmGKB; PA29932; -.
DR eggNOG; COG5576; -.
DR HOGENOM; HOG000236304; -.
DR HOVERGEN; HBG004671; -.
DR InParanoid; P61371; -.
DR KO; K09370; -.
DR OMA; TDMGDMG; -.
DR OrthoDB; EOG7JQBPW; -.
DR PhylomeDB; P61371; -.
DR GeneWiki; ISL1; -.
DR GenomeRNAi; 3670; -.
DR NextBio; 14363; -.
DR PRO; PR:P61371; -.
DR ArrayExpress; P61371; -.
DR Bgee; P61371; -.
DR CleanEx; HS_ISL1; -.
DR Genevestigator; P61371; -.
DR GO; GO:0005737; C:cytoplasm; NAS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; NAS:BHF-UCL.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0001158; F:enhancer sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0030331; F:estrogen receptor binding; ISS:BHF-UCL.
DR GO; GO:0016922; F:ligand-dependent nuclear receptor binding; ISS:BHF-UCL.
DR GO; GO:0001105; F:RNA polymerase II transcription coactivator activity; IDA:BHF-UCL.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0060413; P:atrial septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0031103; P:axon regeneration; 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:0071385; P:cellular response to glucocorticoid stimulus; ISS:BHF-UCL.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:BHF-UCL.
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 receptor signaling pathway; 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:0090074; P:negative regulation of protein homodimerization activity; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; 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: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:0008284; P:positive regulation of cell 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; ISS:BHF-UCL.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISS:BHF-UCL.
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:0032760; P:positive regulation of tumor necrosis factor production; ISS:BHF-UCL.
DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IEA:Ensembl.
DR GO; GO:0010575; P:positive regulation vascular endothelial growth factor production; ISS:BHF-UCL.
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; IMP:BHF-UCL.
DR GO; GO:0048880; P:sensory system 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: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 Gene3D; 1.10.10.60; -; 1.
DR Gene3D; 2.10.110.10; -; 2.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR009057; Homeodomain-like.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00046; Homeobox; 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 Complete proteome; Developmental protein; DNA-binding; Homeobox;
KW LIM domain; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Zinc.
FT CHAIN 1 349 Insulin gene enhancer protein ISL-1.
FT /FTId=PRO_0000075746.
FT DOMAIN 17 70 LIM zinc-binding 1.
FT DOMAIN 79 133 LIM zinc-binding 2.
FT DNA_BIND 181 240 Homeobox.
FT REGION 262 291 LIM-binding domain (LID) (By similarity).
FT COMPBIAS 241 349 Gln-rich.
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
//
MIM
600366
*RECORD*
*FIELD* NO
600366
*FIELD* TI
*600366 ISL LIM HOMEOBOX 1; ISL1
;;ISL1 TRANSCRIPTION FACTOR, LIM/HOMEODOMAIN;;
ISLET 1
read more*FIELD* TX
DESCRIPTION
The ISL1 gene encodes a member of the LIM/homeodomain family of
transcription factors that binds to the enhancer region of the insulin
gene (176730).
CLONING
Because insulin deficiency, either relative or absolute, is a cardinal
feature of noninsulin-dependent diabetes mellitus (NIDDM; 125853),
Tanizawa et al. (1994) investigated the possible involvement of
mutations in genes that regulate insulin production. Rat Isl1 was the
first insulin enhancer-binding protein to be isolated; Tanizawa et al.
(1994) used the rat gene to isolate a partial human ISL1 cDNA and
subsequently to isolate genomic clones. A simple sequence repeat was
found in the ISL1 gene. PCR amplification of this region of genomic DNA
revealed 12 alleles in St. Louis African Americans (heterozygosity =
0.87), 14 alleles in black Nigerians (heterozygosity = 0.89), 8 alleles
in Japanese (heterozygosity = 0.69), and 8 alleles in Caucasians
(heterozygosity = 0.81). Allelic frequencies in the gene did not differ
between patients with NIDDM and nondiabetic control subjects in 2 black
populations.
GENE FUNCTION
Tsuchida et al. (1994) found that the combinatorial expression of 4 LIM
genes, Isl1, Isl2 (609481), Lim1 (LHX1; 601999), and Lim3 (LHX3;
600577), in the developing embryonic chicken defined subclasses of motor
neurons that segregated into columns in the spinal cord and selected
distinct axonal pathways. These genes were expressed prior to the
formation of distinct motor axon pathways and before motor columns
appeared.
Lee and Pfaff (2003) showed that Neurod4 (611635) and Ngn2 (NEUROG2;
606624) actively participated with Isl1 and Lhx3 to specify motor neuron
subtype in embryonic chicken spinal cord and in P19 mouse stem cells.
Laugwitz et al. (2005) reported the identification of ISL1-positive
cardiac progenitors in postnatal rat, mouse, and human myocardium. A
cardiac mesenchymal feeder layer allows renewal of the isolated
progenitor cells with maintenance of their capability to adopt a fully
differentiated cardiomyocyte phenotype. Tamoxifen-inducible Cre/lox
technology enabled selective marking of this progenitor cell population,
including its progeny, at a defined time, and purification to relative
homogeneity. Coculture studies with neonatal myocytes indicated that
ISL1-positive cells represent authentic, endogenous cardiac progenitors
(cardioblasts) that display highly efficient conversion to a mature
cardiac phenotype with stable expression of myocytic markers (25%) in
the absence of cell fusion, intact calcium cycling, and the generation
of action potentials.
Mitsiadis et al. (2003) studied the expression pattern of Isl1 in
developing mouse teeth and suggested that Isl1 plays a role in
patterning of dentition as an activator of Bmp4 expression in incisor
(distal) areas of the stomatodeal epithelium.
Bu et al. (2009) identified a diverse set of human fetal ISL1-positive
cardiovascular progenitors that give rise to the cardiomyocyte, smooth
muscle, and endothelial cell lineages. Using 2 independent transgenic
and gene targeting approaches in human embryonic stem cell lines, they
showed that purified ISL1-positive primordial progenitors are capable of
self-renewal and expansion before differentiation into the 3 major cell
types in the heart.
Peng et al. (2013) identified a population of multipotent
cardiopulmonary mesoderm progenitors (CPPs) within the posterior pole of
the heart that are marked by the expression of Wnt2 (147870), Gli1
(165220), and Isl1. Peng et al. (2013) showed that CPPs arise from
cardiac progenitors before lung development. Lineage tracing and clonal
analysis demonstrates that CPPs generate the mesoderm lineages within
the cardiac inflow tract and lung, including cardiomyocytes, pulmonary
vascular and airway smooth muscle, proximal vascular endothelium, and
pericyte-like cells. CPPs are regulated by hedgehog (SHH; 600725)
expression from the foregut endoderm, which is required for connection
of the pulmonary vasculature to the heart. Peng et al. (2013) concluded
that taken together, their studies identified a novel population of
multipotent cardiopulmonary progenitors that coordinates heart and lung
codevelopment that is required for adaptation to terrestrial existence.
MAPPING
By genetic linkage analysis, Tanizawa et al. (1994) mapped the ISL1 gene
on 5q, 12.8 cM from D5S395 on one side and 11.6 cM from D5S407 on the
other side. A diagram presented by Tanizawa et al. (1994) indicated that
D5S395 and D5S407 are located in the proximal part of 5q, with D5S395
nearer the centromere. Linkage analyses in 15 nonglucokinase MODY
(125850) pedigrees indicated that linkage could be rejected over a
distance of 15 cM.
MOLECULAR GENETICS
Shimomura et al. (2000) found a nonsense mutation (Q310X) in the ISL1
gene in a Japanese patient with type II diabetes and a strong family
history. The mutation led to decreased activity of the islet-1
transcription factor and thus may have been pathogenic. However, as
indicated by Fajans et al. (2001), additional genetic and clinical
studies were required to determine whether mutations in ISL1 are the
cause of another subtype of MODY.
EVOLUTION
Stolfi et al. (2010) found that heart progenitor cells of the simple
chordate Ciona intestinalis generated precursors of the atrial siphon
muscles. These precursors expressed Islet and Tbx1 (602054)/Tbx10
(604648), evocative of the splanchnic mesoderm that produces the lower
jaw muscles and second heart field of vertebrates. Stolfi et al. (2010)
presented evidence identifying the transcription factor Coe (EBF1;
164343) as a critical determinant of atrial siphon muscle fate. They
proposed that the last common ancestor of tunicates and vertebrates
possessed multipotent cardiopharyngeal muscle precursors, and that their
reallocation might have contributed to the emergence of the second heart
field.
ANIMAL MODEL
Cai et al. (2003) observed that mice with a homozygous null mutation in
the Isl1 gene exhibited growth retardation at embryonic day 9.5 and died
at about day 10.5. The hearts of Isl1-null mice were severely abnormal,
appearing misshapen and unlooped. Cai et al. (2003) determined that a
progenitor cell population expressing Isl1 gave rise to the right
ventricle, a subset of left ventricular cells, and a large number of
atrial cells. Cells not expressing Isl1 gave rise to most of the left
ventricle as well as atrial cells. The authors concluded that Isl1
expression defines cardiac progenitor cell populations and is required
for normal cardiac development and asymmetry.
*FIELD* RF
1. Bu, L.; Jiang, X.; Martin-Puig, S.; Caron, L.; Zhu, S.; Shao, Y.;
Roberts, D. J.; Huang, P. L.; Domian, I. J.; Chien, K. R.: Human
ISL1 heart progenitors generate diverse multipotent cardiovascular
cell lineages. Nature 460: 113-117, 2009.
2. Cai, C.-L.; Liang, X.; Shi, Y.; Chu, P.-H.; Pfaff, S. L.; Chen,
J.; Evans, S.: Isl1 identifies a cardiac progenitor population that
proliferates prior to differentiation and contributes a majority of
cells to the heart. Dev. Cell 5: 877-889, 2003.
3. Fajans, S. S.; Bell, G. I.; Polonsky, K. S.: Molecular mechanisms
and clinical pathophysiology of maturity-onset diabetes of the young. New
Eng. J. Med. 345: 971-980, 2001.
4. Laugwitz, K.-L.; Moretti, A.; Lam, J.; Gruber, P.; Chen, Y.; Woodard,
S.; Lin, L.-Z.; Cai, C.-L.; Lu, M. M.; Reth, M.; Platoshyn, O.; Yuan,
J. X.-J.; Evans, S.; Chien, K. R.: Postnatal isl1-positive cardioblasts
enter fully differentiated cardiomyocyte lineages. Nature 433: 647-653,
2005. Note: Erratum: Nature 446: 934 only, 2007.
5. Lee, S.-K.; Pfaff, S. L.: Synchronization of neurogenesis and
motor neuron specification by direct coupling of bHLH and homeodomain
transcription factors. Neuron 38: 731-745, 2003.
6. Mitsiadis, T. A.; Angeli, I.; James, C.; Lendahl, U.; Sharpe, P.
T.: Role of islet1 in the patterning of murine dentition. Development 130:
4451-4460, 2003.
7. Peng, T.; Tian, Y.; Boogerd, C. J.; Lu, M. M.; Kadzik, R. S.; Stewart,
K. M.; Evans, S. M.; Morrisey, E. E.: Coordination of heart and lung
co-development by a multipotent cardiopulmonary progenitor. Nature 500:
589-592, 2013.
8. Shimomura, H.; Sanke, T.; Hanabusa, T.; Tsunoda, K.; Furuta, H.;
Nanjo, K.: Nonsense mutation of islet-1 gene (Q310X) found in a type
2 diabetic patient with a strong family history. Diabetes 49: 1597-1600,
2000.
9. Stolfi, A.; Gainous, T. B.; Young, J. J.; Mori, A.; Levine, M.;
Christiaen, L.: Early chordate origins of the vertebrate second heart
field. Science 329: 565-568, 2010.
10. Tanizawa, Y.; Riggs, A. C.; Dagogo-Jack, S.; Vaxillaire, M.; Froguel,
P.; Liu, L.; Donis-Keller, H.; Permutt, M. A.: Isolation of the human
LIM/homeodomain gene islet-1 and identification of a simple sequence
repeat polymorphism. Diabetes 43: 935-941, 1994. Note: Erratum:
Diabetes 43: 1171 only, 1994.
11. Tsuchida, T.; Ensini, M.; Morton, S. B.; Baldassare, M.; Edlund,
T.; Jessell, T. M.; Pfaff, S. L.: Topographic organization of embryonic
motor neurons defined by expression of LIM homeobox genes. Cell 79:
957-970, 1994.
*FIELD* CN
Ada Hamosh - updated: 10/01/2013
Ada Hamosh - updated: 8/24/2010
Ada Hamosh - updated: 8/25/2009
Patricia A. Hartz - updated: 11/28/2007
Gregory S. Antonarakis - updated: 9/26/2005
Patricia A. Hartz - updated: 7/19/2005
Ada Hamosh - updated: 4/15/2005
Patricia A. Hartz - updated: 5/14/2004
Victor A. McKusick - updated: 10/8/2001
*FIELD* CD
Victor A. McKusick: 2/2/1995
*FIELD* ED
alopez: 10/01/2013
alopez: 10/1/2013
carol: 8/21/2012
mgross: 8/24/2010
terry: 8/24/2010
alopez: 8/27/2009
terry: 8/25/2009
carol: 2/21/2008
mgross: 11/28/2007
alopez: 6/14/2007
terry: 5/29/2007
terry: 11/16/2006
mgross: 2/16/2006
terry: 2/14/2006
carol: 9/26/2005
mgross: 7/19/2005
terry: 4/15/2005
terry: 4/4/2005
terry: 3/17/2005
mgross: 5/17/2004
terry: 5/14/2004
mcapotos: 12/28/2001
carol: 10/8/2001
terry: 8/5/1998
joanna: 5/13/1997
carol: 2/2/1995
*RECORD*
*FIELD* NO
600366
*FIELD* TI
*600366 ISL LIM HOMEOBOX 1; ISL1
;;ISL1 TRANSCRIPTION FACTOR, LIM/HOMEODOMAIN;;
ISLET 1
read more*FIELD* TX
DESCRIPTION
The ISL1 gene encodes a member of the LIM/homeodomain family of
transcription factors that binds to the enhancer region of the insulin
gene (176730).
CLONING
Because insulin deficiency, either relative or absolute, is a cardinal
feature of noninsulin-dependent diabetes mellitus (NIDDM; 125853),
Tanizawa et al. (1994) investigated the possible involvement of
mutations in genes that regulate insulin production. Rat Isl1 was the
first insulin enhancer-binding protein to be isolated; Tanizawa et al.
(1994) used the rat gene to isolate a partial human ISL1 cDNA and
subsequently to isolate genomic clones. A simple sequence repeat was
found in the ISL1 gene. PCR amplification of this region of genomic DNA
revealed 12 alleles in St. Louis African Americans (heterozygosity =
0.87), 14 alleles in black Nigerians (heterozygosity = 0.89), 8 alleles
in Japanese (heterozygosity = 0.69), and 8 alleles in Caucasians
(heterozygosity = 0.81). Allelic frequencies in the gene did not differ
between patients with NIDDM and nondiabetic control subjects in 2 black
populations.
GENE FUNCTION
Tsuchida et al. (1994) found that the combinatorial expression of 4 LIM
genes, Isl1, Isl2 (609481), Lim1 (LHX1; 601999), and Lim3 (LHX3;
600577), in the developing embryonic chicken defined subclasses of motor
neurons that segregated into columns in the spinal cord and selected
distinct axonal pathways. These genes were expressed prior to the
formation of distinct motor axon pathways and before motor columns
appeared.
Lee and Pfaff (2003) showed that Neurod4 (611635) and Ngn2 (NEUROG2;
606624) actively participated with Isl1 and Lhx3 to specify motor neuron
subtype in embryonic chicken spinal cord and in P19 mouse stem cells.
Laugwitz et al. (2005) reported the identification of ISL1-positive
cardiac progenitors in postnatal rat, mouse, and human myocardium. A
cardiac mesenchymal feeder layer allows renewal of the isolated
progenitor cells with maintenance of their capability to adopt a fully
differentiated cardiomyocyte phenotype. Tamoxifen-inducible Cre/lox
technology enabled selective marking of this progenitor cell population,
including its progeny, at a defined time, and purification to relative
homogeneity. Coculture studies with neonatal myocytes indicated that
ISL1-positive cells represent authentic, endogenous cardiac progenitors
(cardioblasts) that display highly efficient conversion to a mature
cardiac phenotype with stable expression of myocytic markers (25%) in
the absence of cell fusion, intact calcium cycling, and the generation
of action potentials.
Mitsiadis et al. (2003) studied the expression pattern of Isl1 in
developing mouse teeth and suggested that Isl1 plays a role in
patterning of dentition as an activator of Bmp4 expression in incisor
(distal) areas of the stomatodeal epithelium.
Bu et al. (2009) identified a diverse set of human fetal ISL1-positive
cardiovascular progenitors that give rise to the cardiomyocyte, smooth
muscle, and endothelial cell lineages. Using 2 independent transgenic
and gene targeting approaches in human embryonic stem cell lines, they
showed that purified ISL1-positive primordial progenitors are capable of
self-renewal and expansion before differentiation into the 3 major cell
types in the heart.
Peng et al. (2013) identified a population of multipotent
cardiopulmonary mesoderm progenitors (CPPs) within the posterior pole of
the heart that are marked by the expression of Wnt2 (147870), Gli1
(165220), and Isl1. Peng et al. (2013) showed that CPPs arise from
cardiac progenitors before lung development. Lineage tracing and clonal
analysis demonstrates that CPPs generate the mesoderm lineages within
the cardiac inflow tract and lung, including cardiomyocytes, pulmonary
vascular and airway smooth muscle, proximal vascular endothelium, and
pericyte-like cells. CPPs are regulated by hedgehog (SHH; 600725)
expression from the foregut endoderm, which is required for connection
of the pulmonary vasculature to the heart. Peng et al. (2013) concluded
that taken together, their studies identified a novel population of
multipotent cardiopulmonary progenitors that coordinates heart and lung
codevelopment that is required for adaptation to terrestrial existence.
MAPPING
By genetic linkage analysis, Tanizawa et al. (1994) mapped the ISL1 gene
on 5q, 12.8 cM from D5S395 on one side and 11.6 cM from D5S407 on the
other side. A diagram presented by Tanizawa et al. (1994) indicated that
D5S395 and D5S407 are located in the proximal part of 5q, with D5S395
nearer the centromere. Linkage analyses in 15 nonglucokinase MODY
(125850) pedigrees indicated that linkage could be rejected over a
distance of 15 cM.
MOLECULAR GENETICS
Shimomura et al. (2000) found a nonsense mutation (Q310X) in the ISL1
gene in a Japanese patient with type II diabetes and a strong family
history. The mutation led to decreased activity of the islet-1
transcription factor and thus may have been pathogenic. However, as
indicated by Fajans et al. (2001), additional genetic and clinical
studies were required to determine whether mutations in ISL1 are the
cause of another subtype of MODY.
EVOLUTION
Stolfi et al. (2010) found that heart progenitor cells of the simple
chordate Ciona intestinalis generated precursors of the atrial siphon
muscles. These precursors expressed Islet and Tbx1 (602054)/Tbx10
(604648), evocative of the splanchnic mesoderm that produces the lower
jaw muscles and second heart field of vertebrates. Stolfi et al. (2010)
presented evidence identifying the transcription factor Coe (EBF1;
164343) as a critical determinant of atrial siphon muscle fate. They
proposed that the last common ancestor of tunicates and vertebrates
possessed multipotent cardiopharyngeal muscle precursors, and that their
reallocation might have contributed to the emergence of the second heart
field.
ANIMAL MODEL
Cai et al. (2003) observed that mice with a homozygous null mutation in
the Isl1 gene exhibited growth retardation at embryonic day 9.5 and died
at about day 10.5. The hearts of Isl1-null mice were severely abnormal,
appearing misshapen and unlooped. Cai et al. (2003) determined that a
progenitor cell population expressing Isl1 gave rise to the right
ventricle, a subset of left ventricular cells, and a large number of
atrial cells. Cells not expressing Isl1 gave rise to most of the left
ventricle as well as atrial cells. The authors concluded that Isl1
expression defines cardiac progenitor cell populations and is required
for normal cardiac development and asymmetry.
*FIELD* RF
1. Bu, L.; Jiang, X.; Martin-Puig, S.; Caron, L.; Zhu, S.; Shao, Y.;
Roberts, D. J.; Huang, P. L.; Domian, I. J.; Chien, K. R.: Human
ISL1 heart progenitors generate diverse multipotent cardiovascular
cell lineages. Nature 460: 113-117, 2009.
2. Cai, C.-L.; Liang, X.; Shi, Y.; Chu, P.-H.; Pfaff, S. L.; Chen,
J.; Evans, S.: Isl1 identifies a cardiac progenitor population that
proliferates prior to differentiation and contributes a majority of
cells to the heart. Dev. Cell 5: 877-889, 2003.
3. Fajans, S. S.; Bell, G. I.; Polonsky, K. S.: Molecular mechanisms
and clinical pathophysiology of maturity-onset diabetes of the young. New
Eng. J. Med. 345: 971-980, 2001.
4. Laugwitz, K.-L.; Moretti, A.; Lam, J.; Gruber, P.; Chen, Y.; Woodard,
S.; Lin, L.-Z.; Cai, C.-L.; Lu, M. M.; Reth, M.; Platoshyn, O.; Yuan,
J. X.-J.; Evans, S.; Chien, K. R.: Postnatal isl1-positive cardioblasts
enter fully differentiated cardiomyocyte lineages. Nature 433: 647-653,
2005. Note: Erratum: Nature 446: 934 only, 2007.
5. Lee, S.-K.; Pfaff, S. L.: Synchronization of neurogenesis and
motor neuron specification by direct coupling of bHLH and homeodomain
transcription factors. Neuron 38: 731-745, 2003.
6. Mitsiadis, T. A.; Angeli, I.; James, C.; Lendahl, U.; Sharpe, P.
T.: Role of islet1 in the patterning of murine dentition. Development 130:
4451-4460, 2003.
7. Peng, T.; Tian, Y.; Boogerd, C. J.; Lu, M. M.; Kadzik, R. S.; Stewart,
K. M.; Evans, S. M.; Morrisey, E. E.: Coordination of heart and lung
co-development by a multipotent cardiopulmonary progenitor. Nature 500:
589-592, 2013.
8. Shimomura, H.; Sanke, T.; Hanabusa, T.; Tsunoda, K.; Furuta, H.;
Nanjo, K.: Nonsense mutation of islet-1 gene (Q310X) found in a type
2 diabetic patient with a strong family history. Diabetes 49: 1597-1600,
2000.
9. Stolfi, A.; Gainous, T. B.; Young, J. J.; Mori, A.; Levine, M.;
Christiaen, L.: Early chordate origins of the vertebrate second heart
field. Science 329: 565-568, 2010.
10. Tanizawa, Y.; Riggs, A. C.; Dagogo-Jack, S.; Vaxillaire, M.; Froguel,
P.; Liu, L.; Donis-Keller, H.; Permutt, M. A.: Isolation of the human
LIM/homeodomain gene islet-1 and identification of a simple sequence
repeat polymorphism. Diabetes 43: 935-941, 1994. Note: Erratum:
Diabetes 43: 1171 only, 1994.
11. Tsuchida, T.; Ensini, M.; Morton, S. B.; Baldassare, M.; Edlund,
T.; Jessell, T. M.; Pfaff, S. L.: Topographic organization of embryonic
motor neurons defined by expression of LIM homeobox genes. Cell 79:
957-970, 1994.
*FIELD* CN
Ada Hamosh - updated: 10/01/2013
Ada Hamosh - updated: 8/24/2010
Ada Hamosh - updated: 8/25/2009
Patricia A. Hartz - updated: 11/28/2007
Gregory S. Antonarakis - updated: 9/26/2005
Patricia A. Hartz - updated: 7/19/2005
Ada Hamosh - updated: 4/15/2005
Patricia A. Hartz - updated: 5/14/2004
Victor A. McKusick - updated: 10/8/2001
*FIELD* CD
Victor A. McKusick: 2/2/1995
*FIELD* ED
alopez: 10/01/2013
alopez: 10/1/2013
carol: 8/21/2012
mgross: 8/24/2010
terry: 8/24/2010
alopez: 8/27/2009
terry: 8/25/2009
carol: 2/21/2008
mgross: 11/28/2007
alopez: 6/14/2007
terry: 5/29/2007
terry: 11/16/2006
mgross: 2/16/2006
terry: 2/14/2006
carol: 9/26/2005
mgross: 7/19/2005
terry: 4/15/2005
terry: 4/4/2005
terry: 3/17/2005
mgross: 5/17/2004
terry: 5/14/2004
mcapotos: 12/28/2001
carol: 10/8/2001
terry: 8/5/1998
joanna: 5/13/1997
carol: 2/2/1995