FXD3A_XENLA
ID FXD3A_XENLA Reviewed; 371 AA.
AC Q9DEN4; Q9PS83;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Forkhead box protein D3-A;
DE Short=FoxD3-A;
DE Short=FoxD3a;
DE AltName: Full=Fork head domain-related protein 6;
DE Short=FKH-6;
DE Short=Forkhead protein 6;
DE Short=xFD-6;
DE Short=xFKH6;
GN Name=foxd3-a; Synonyms=fkh6, foxd3a {ECO:0000312|EMBL:CAC12963.1};
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:BAA36334.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Neural crest {ECO:0000312|EMBL:BAA36334.1};
RX PubMed=11493569; DOI=10.1242/dev.128.13.2525;
RA Sasai N., Mizuseki K., Sasai Y.;
RT "Requirement of FoxD3-class signaling for neural crest determination in
RT Xenopus.";
RL Development 128:2525-2536(2001).
RN [2] {ECO:0000305, ECO:0000312|EMBL:CAC12963.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, INDUCTION, AND MUTAGENESIS OF LEU-146.
RC TISSUE=Gastrula {ECO:0000269|PubMed:11335115};
RX PubMed=11335115; DOI=10.1016/s0925-4773(01)00334-3;
RA Pohl B.S., Knoechel W.;
RT "Overexpression of the transcriptional repressor FoxD3 prevents neural
RT crest formation in Xenopus embryos.";
RL Mech. Dev. 103:93-106(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-238, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RA Scheucher M., Dege P., Lef J., Hille S., Knoechel W.;
RT "Transcription patterns of four different fork head/HNF-3 related genes
RT (XFD-4, 6, 9 and 10) in Xenopus laevis embryos.";
RL Roux's Arch. Dev. Biol. 204:203-211(1995).
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 85-195.
RX PubMed=1358174; DOI=10.1016/0925-4773(92)90007-7;
RA Knoechel S., Lef J., Clement J.H., Klocke B., Hille S., Koester M.,
RA Knoechel W.;
RT "Activin A induced expression of a fork head related gene in posterior
RT chordamesoderm (notochord) of Xenopus laevis embryos.";
RL Mech. Dev. 38:157-165(1992).
RN [6] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 94-155, AND TISSUE SPECIFICITY.
RC TISSUE=Embryo {ECO:0000269|PubMed:7586752};
RX PubMed=7586752; DOI=10.1002/dvg.1020170203;
RA Dirksen M.-L., Jamrich M.;
RT "Differential expression of fork head genes during early Xenopus and
RT zebrafish development.";
RL Dev. Genet. 17:107-116(1995).
RN [7] {ECO:0000305}
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=8735935;
RA Lef J., Dege P., Scheucher M., Forsbach-Birk V., Clement J.H., Knoechel W.;
RT "A fork head related multigene family is transcribed in Xenopus laevis
RT embryos.";
RL Int. J. Dev. Biol. 40:245-253(1996).
RN [8] {ECO:0000305}
RP REVIEW.
RX PubMed=15656969; DOI=10.1016/j.gene.2004.09.037;
RA Pohl B.S., Knoechel W.;
RT "Of fox and frogs: fox (fork head/winged helix) transcription factors in
RT Xenopus development.";
RL Gene 344:21-32(2005).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH TLE4, AND MUTAGENESIS OF
RP ASN-140; HIS-144; PHE-297 AND 297-PHE--ILE-302.
RX PubMed=17138566; DOI=10.1074/jbc.m607412200;
RA Yaklichkin S., Steiner A.B., Lu Q., Kessler D.S.;
RT "FoxD3 and Grg4 physically interact to repress transcription and induce
RT mesoderm in Xenopus.";
RL J. Biol. Chem. 282:2548-2557(2007).
CC -!- FUNCTION: Transcriptional repressor that is an essential upstream
CC regulator of neural crest determination and mesoderm induction.
CC Functions by recruiting the transcriptional corepressor tle4. Also acts
CC in a negative auto-regulator loop by inhibiting the transcription of
CC its own gene. {ECO:0000269|PubMed:11335115,
CC ECO:0000269|PubMed:11493569, ECO:0000269|PubMed:17138566}.
CC -!- SUBUNIT: Interacts with tle4. {ECO:0000269|PubMed:17138566}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089,
CC ECO:0000269|PubMed:17138566}.
CC -!- TISSUE SPECIFICITY: Initially located within the dorsal blastopore lip
CC (Spemann organizer) at the mid-gastrula stage. As expression fades in
CC the neuroectoderm, expression begins in the head mesoderm in two
CC regions at the lateral borders of the presumptive neural plate. These
CC regions correspond to neural crest cells originating from the
CC mesencephalon (anterior) and the rhombencephalon (posterior;
CC rhombomeres 2, 4 and 6). Subsequently expressed within trunk
CC premigratory neural crest cells. Expression disappears when neural
CC crest cells begin to differentiate and migrate, except for those which
CC populate the hyoid arch. {ECO:0000269|PubMed:11335115,
CC ECO:0000269|PubMed:11493569, ECO:0000269|PubMed:7586752,
CC ECO:0000269|PubMed:8735935, ECO:0000269|Ref.4}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Maternal expression decreases until the late blastula/early gastrula
CC stage when zygotic expression begins. Expression is highest in the
CC gastrula stage, after which it shows a gradual decrease, being clearly
CC present until the tadpole stage. {ECO:0000269|PubMed:11335115,
CC ECO:0000269|PubMed:11493569, ECO:0000269|PubMed:8735935,
CC ECO:0000269|Ref.4}.
CC -!- INDUCTION: By dorsal wnt signaling. Inhibited by bmp signaling.
CC {ECO:0000269|PubMed:11335115}.
CC -!- DOMAIN: The C-terminus is required for transcriptional repression and
CC mesoderm induction.
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DR EMBL; AB014611; BAA36334.1; -; mRNA.
DR EMBL; AJ298865; CAC12963.1; -; Genomic_DNA.
DR EMBL; BC123272; AAI23273.1; -; mRNA.
DR PIR; G56556; G56556.
DR RefSeq; NP_001079026.1; NM_001085557.1.
DR AlphaFoldDB; Q9DEN4; -.
DR SMR; Q9DEN4; -.
DR GeneID; 373548; -.
DR KEGG; xla:373548; -.
DR CTD; 373548; -.
DR Xenbase; XB-GENE-865691; foxd3.L.
DR OrthoDB; 1270467at2759; -.
DR Proteomes; UP000186698; Chromosome 4L.
DR Bgee; 373548; Expressed in neurula embryo and 13 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0001707; P:mesoderm formation; IMP:UniProtKB.
DR GO; GO:0050768; P:negative regulation of neurogenesis; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0014034; P:neural crest cell fate commitment; IMP:UniProtKB.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:UniProtKB.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Neurogenesis; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..371
FT /note="Forkhead box protein D3-A"
FT /id="PRO_0000250608"
FT DNA_BIND 94..188
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 297..303
FT /note="tle4-binding"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..56
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 69..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 140
FT /note="N->A: Reduces mesoderm-inducing activity; when
FT associated with A-144."
FT /evidence="ECO:0000269|PubMed:17138566"
FT MUTAGEN 144
FT /note="H->A: Reduces mesoderm-inducing activity; when
FT associated with A-140."
FT /evidence="ECO:0000269|PubMed:17138566"
FT MUTAGEN 146
FT /note="L->F: Abolishes DNA-binding and disrupts function."
FT /evidence="ECO:0000269|PubMed:11335115"
FT MUTAGEN 297..302
FT /note="FSIENI->AAAAAA: Abolishes mesoderm inducing activity
FT and interaction with tle4."
FT /evidence="ECO:0000269|PubMed:17138566"
FT MUTAGEN 297
FT /note="F->E: Abolishes mesoderm inducing activity and
FT interaction with tle4."
FT /evidence="ECO:0000269|PubMed:17138566"
SQ SEQUENCE 371 AA; 40018 MW; 234645747EA1F716 CRC64;
MTLSGSGSAS DMSGQTVLSA DDADIDVVGE GDEALDKDSE CESTAGHTDE VGELGGKEIP
RSPSGSGTEA EGKGESQQQQ QEGIQNKPKN SLVKPPYSYI ALITMSILQS PQKKLTLSGI
CEFISNRFPY YREKFPAWQN SIRHNLSLND CFVKIPREPG NPGKGNYWTL DPQSEDMFDN
GSFLRRRKRF KRQQQDSLRE QTALMMQSFG AYSLASPYGR HYGLHPAAYT HPAALQYPYI
PPVGHMLPPA VPLLPSSELT RKAFSSQLSP SLQLQLSSLS STAASIIKSE PSSRPSFSIE
NIIGVSAASS AAPHTFLRPP VTVQSALMSH QPLALSRSTA AIGPILSVPT NLISGQFLPT
AAAAVAKWPA Q
