ID3A_XENLA
ID ID3A_XENLA Reviewed; 118 AA.
AC Q91399; Q91417;
DT 19-JAN-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=DNA-binding protein inhibitor ID-3-A {ECO:0000250|UniProtKB:Q02535};
DE AltName: Full=Inhibitor of DNA binding 3 {ECO:0000303|PubMed:10525185};
DE Short=XId3 {ECO:0000303|PubMed:10525185};
DE Short=XIdI {ECO:0000303|PubMed:7619724};
DE Short=XIdIa {ECO:0000312|EMBL:AAB34946.1};
DE Short=XIdIb {ECO:0000303|PubMed:7619724};
DE Short=XIdx {ECO:0000312|EMBL:AAB34225.1};
DE AltName: Full=Inhibitor of differentiation 3-A;
GN Name=id3-a; Synonyms=id3 {ECO:0000312|EMBL:CAC00501.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAB34225.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, SUBUNIT, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF VAL-59.
RC TISSUE=Neurula {ECO:0000269|PubMed:7734394};
RX PubMed=7734394; DOI=10.1016/0925-4773(94)00319-i;
RA Wilson R., Mohun T.;
RT "XIdx, a dominant negative regulator of bHLH function in early Xenopus
RT embryos.";
RL Mech. Dev. 49:211-222(1995).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAB34946.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Neurula {ECO:0000312|EMBL:AAB34946.1};
RX PubMed=7619724; DOI=10.1016/0925-4773(94)00329-l;
RA Zhang H., Reynaud S., Kloc M., Etkin L.D., Spohr G.;
RT "Id gene activity during Xenopus embryogenesis.";
RL Mech. Dev. 50:119-130(1995).
RN [3] {ECO:0000312|EMBL:CAC00501.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Neurula {ECO:0000312|EMBL:CAC00501.1};
RA Spohr G.B.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:CAC00501.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH44039.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=10646803; DOI=10.1046/j.1440-169x.1999.00477.x;
RA Shimizu-Nishikawa K., Tazawa I., Uchiyama K., Yoshizato K.;
RT "Expression of helix-loop-helix type negative regulators of differentiation
RT during limb regeneration in urodeles and anurans.";
RL Dev. Growth Differ. 41:731-743(1999).
RN [6] {ECO:0000305}
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10525185; DOI=10.1016/s0925-4773(99)00166-5;
RA Afouda A.B., Reynaud-Deonauth S., Mohun T., Spohr G.;
RT "Localized XId3 mRNA activation in Xenopus embryos by cytoplasmic
RT polyadenylation.";
RL Mech. Dev. 88:15-31(1999).
RN [7] {ECO:0000305}
RP INDUCTION.
RX PubMed=11841478; DOI=10.1046/j.1432-0436.2002.690413.x;
RA Reynaud-Deonauth S., Zhang H., Afouda A., Taillefert S., Beatus P.,
RA Kloc M., Etkin L.D., Fischer-Lougheed J., Spohr G.;
RT "Notch signaling is involved in the regulation of Id3 gene transcription
RT during Xenopus embryogenesis.";
RL Differentiation 69:198-208(2002).
RN [8] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=14651922; DOI=10.1016/j.ydbio.2003.08.017;
RA Liu K.J., Harland R.M.;
RT "Cloning and characterization of Xenopus Id4 reveals differing roles for Id
RT genes.";
RL Dev. Biol. 264:339-351(2003).
RN [9] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15772131; DOI=10.1242/dev.01734;
RA Light W., Vernon A.E., Lasorella A., Iavarone A., LaBonne C.;
RT "Xenopus Id3 is required downstream of Myc for the formation of multipotent
RT neural crest progenitor cells.";
RL Development 132:1831-1841(2005).
RN [10] {ECO:0000305}
RP INDUCTION.
RX PubMed=15893974; DOI=10.1016/j.ydbio.2005.02.014;
RA von Bubnoff A., Peiffer D.A., Blitz I.L., Hayata T., Ogata S., Zeng Q.,
RA Trunnell M., Cho K.W.;
RT "Phylogenetic footprinting and genome scanning identify vertebrate BMP
RT response elements and new target genes.";
RL Dev. Biol. 281:210-226(2005).
RN [11] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15769946; DOI=10.1101/gad.1257405;
RA Kee Y., Bronner-Fraser M.;
RT "To proliferate or to die: role of Id3 in cell cycle progression and
RT survival of neural crest progenitors.";
RL Genes Dev. 19:744-755(2005).
RN [12] {ECO:0000305}
RP FUNCTION, INTERACTION WITH HES4-B, AND INDUCTION.
RX PubMed=18721802; DOI=10.1016/j.ydbio.2008.08.003;
RA Nichane M., de Croze N., Ren X., Souopgui J., Monsoro-Burq A.H.,
RA Bellefroid E.J.;
RT "Hairy2-Id3 interactions play an essential role in Xenopus neural crest
RT progenitor specification.";
RL Dev. Biol. 322:355-367(2008).
RN [13] {ECO:0000305}
RP FUNCTION, AND INDUCTION.
RX PubMed=18710660; DOI=10.1016/j.ydbio.2008.07.026;
RA Nichane M., Ren X., Souopgui J., Bellefroid E.J.;
RT "Hairy2 functions through both DNA-binding and non DNA-binding mechanisms
RT at the neural plate border in Xenopus.";
RL Dev. Biol. 322:368-380(2008).
RN [14] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH STAT3.
RX PubMed=19851287; DOI=10.1038/emboj.2009.313;
RA Nichane M., Ren X., Bellefroid E.J.;
RT "Self-regulation of Stat3 activity coordinates cell-cycle progression and
RT neural crest specification.";
RL EMBO J. 29:55-67(2010).
CC -!- FUNCTION: Transcriptional regulator (lacking a basic DNA binding
CC domain) which negatively regulates the basic helix-loop-helix (bHLH)
CC transcription factors by forming heterodimers and inhibiting their DNA
CC binding and transcriptional activity. Influences cell fate decisions in
CC the embryo by sequestering and blocking the activity of the bHLH
CC transcription factors that control these decisions. Inhibits the
CC binding of myogenic bHLH-containing complexes to E-box DNA, thereby
CC preventing activation of muscle-specific target genes. Also inhibits
CC the activity of neurogenic factor neurod1/neuroD. Plays a role in cell
CC cycle progression and survival of neural crest progenitors; binding to
CC either hes4-B/hairy2b or stat3 blocks the formation of transcription
CC factor complexes and the repressor function of hes4-B/hairy2B, to allow
CC neural crest progenitors to differentiate. May play a role in the
CC regulation of the circadian rhythm. {ECO:0000269|PubMed:14651922,
CC ECO:0000269|PubMed:15769946, ECO:0000269|PubMed:15772131,
CC ECO:0000269|PubMed:18710660, ECO:0000269|PubMed:18721802,
CC ECO:0000269|PubMed:19851287, ECO:0000269|PubMed:7619724,
CC ECO:0000269|PubMed:7734394}.
CC -!- SUBUNIT: Homodimer (By similarity). Heterodimer with other HLH
CC proteins. Interacts (via HLH domain) with the bHLH protein hes4/hairy2
CC (via Orange domain). Interacts with stat3.
CC {ECO:0000250|UniProtKB:Q02535, ECO:0000269|PubMed:18721802,
CC ECO:0000269|PubMed:19851287, ECO:0000269|PubMed:7734394}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q02535,
CC ECO:0000255|PROSITE-ProRule:PRU00981}.
CC -!- TISSUE SPECIFICITY: At gastrula stage, expressed in all three germ
CC layers, but becomes localized to discrete domains of the developing
CC nervous system during neurulation, including the anterior neural plate,
CC cement gland, eye anlagen, otic placode and both cranial and trunk
CC premigratory and early migratory neural crest cells. Also expressed in
CC the most dorsal and ventral portions of the myotome, the developing
CC heart and anterior blood islets, and in the tail fin mesenchyme.
CC Expressed at a low level in limbs, with expression decreasing as limbs
CC develop, but expressed at a high level in blastemas (regenerated
CC limbs), where expression is localized to both the blastermal epidermis
CC and mesenchyme. Widely expressed in adults including the liver and
CC heart. {ECO:0000269|PubMed:10525185, ECO:0000269|PubMed:10646803,
CC ECO:0000269|PubMed:14651922, ECO:0000269|PubMed:15769946,
CC ECO:0000269|PubMed:15772131, ECO:0000269|PubMed:7619724,
CC ECO:0000269|PubMed:7734394}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed at a low level in fertilized eggs and cleaving embryos.
CC Zygotic expression begins after the midblastula transition (MBT) with
CC expression levels rising during gastrulation, and remaining constant
CC throughout neurulation and premetamorphic development. Also expressed
CC in adults. {ECO:0000269|PubMed:10525185, ECO:0000269|PubMed:14651922,
CC ECO:0000269|PubMed:7619724, ECO:0000269|PubMed:7734394}.
CC -!- INDUCTION: By bmp and notch signaling, and in response to signaling
CC events of early neural crest induction. Repressed by hes4/hairy2 in a
CC DNA-binding dependent manner through repression of bmp4 transcription,
CC but up-regulated by hes4/hairy2 acting via delta1 activation. By myc.
CC {ECO:0000269|PubMed:11841478, ECO:0000269|PubMed:14651922,
CC ECO:0000269|PubMed:15772131, ECO:0000269|PubMed:15893974,
CC ECO:0000269|PubMed:18710660, ECO:0000269|PubMed:18721802}.
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DR EMBL; S76880; AAB34225.1; -; Genomic_DNA.
DR EMBL; S79007; AAB34946.1; -; mRNA.
DR EMBL; AJ292558; CAC00501.1; -; mRNA.
DR EMBL; BC044039; AAH44039.1; -; mRNA.
DR PIR; I51278; I51278.
DR PIR; I51316; I51316.
DR RefSeq; NP_001079535.1; NM_001086066.1.
DR RefSeq; XP_018100241.1; XM_018244752.1.
DR AlphaFoldDB; Q91399; -.
DR SMR; Q91399; -.
DR DNASU; 379222; -.
DR GeneID; 379222; -.
DR KEGG; xla:379222; -.
DR CTD; 379222; -.
DR Xenbase; XB-GENE-6256366; id3.L.
DR OMA; EPMGLLY; -.
DR OrthoDB; 1624054at2759; -.
DR Proteomes; UP000186698; Chromosome 2L.
DR Bgee; 379222; Expressed in gastrula and 18 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0043392; P:negative regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0014029; P:neural crest formation; IMP:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR026052; DNA-bd_prot-inh.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR PANTHER; PTHR11723; PTHR11723; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Biological rhythms; Developmental protein; Nucleus; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..118
FT /note="DNA-binding protein inhibitor ID-3-A"
FT /id="PRO_0000390724"
FT DOMAIN 32..84
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT MUTAGEN 59
FT /note="V->N: Disrupts the helix-loop-helix structure.
FT Reduces ability to inhibit bHLH complex formation."
FT /evidence="ECO:0000269|PubMed:7734394"
FT CONFLICT 30
FT /note="G -> A (in Ref. 2; AAB34946 and 3; CAC00501)"
FT /evidence="ECO:0000305"
FT CONFLICT 65
FT /note="G -> A (in Ref. 2; AAB34946 and 3; CAC00501)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 118 AA; 12857 MW; C9381A8BB265F6E4 CRC64;
MKAISPVRSM SSCYQAVCCL SEQSLSIARG SSHKGPGMDE PMGLLYDMNG CYSKLKELVP
GIPQGSKLSQ VEILQHVIDY IFDLQIVLGE DQQQSSILSL QKSDFSELAT QGDTSVCH
