FXA4A_XENLA
ID FXA4A_XENLA Reviewed; 399 AA.
AC P33205; P70042; Q01364; Q641H9;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 3.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Forkhead box protein A4-A;
DE Short=FoxA4-A;
DE Short=FoxA4a;
DE AltName: Full=Fork head domain-related protein 1;
DE Short=xFD-1;
DE AltName: Full=Protein pintallavis;
GN Name=foxa4-a;
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]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Neurula;
RX PubMed=1483397; DOI=10.1242/dev.116.supplement.81;
RA Ruiz i Altaba A., Jessell T.M.;
RT "Pintallavis, a gene expressed in the organizer and midline cells of frog
RT embryos: involvement in the development of the neural axis.";
RL Development 116:81-93(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND INDUCTION.
RC TISSUE=Gastrula;
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 [3]
RP SEQUENCE REVISION TO 245.
RA Kaufmann E., Paul H., Friedle H., Metz A., Scheucher M., Clement J.H.,
RA Knoechel W.;
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION.
RX PubMed=8367492; DOI=10.1073/pnas.90.17.8268;
RA Ruiz i Altaba A., Cox C., Jessell T.M., Klar A.;
RT "Ectopic neural expression of a floor plate marker in frog embryos injected
RT with the midline transcription factor Pintallavis.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:8268-8272(1993).
RN [6]
RP FUNCTION.
RX PubMed=7789266; DOI=10.1242/dev.121.5.1351;
RA O'Reilly M.-A.J., Smith J.C., Cunliffe V.;
RT "Patterning of the mesoderm in Xenopus: dose-dependent and synergistic
RT effects of Brachyury and Pintallavis.";
RL Development 121:1351-1359(1995).
RN [7]
RP TISSUE SPECIFICITY.
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 [8]
RP DNA-BINDING.
RX PubMed=7739038; DOI=10.1016/s0022-2836(95)80047-6;
RA Kaufmann E., Mueller D., Knoechel W.;
RT "DNA recognition site analysis of Xenopus winged helix proteins.";
RL J. Mol. Biol. 248:239-254(1995).
RN [9]
RP INDUCTION.
RX PubMed=8626017; DOI=10.1006/dbio.1996.0061;
RA Gont L.K., Fainsod A., Kim S.-H., De Robertis E.M.;
RT "Overexpression of the homeobox gene Xnot-2 leads to notochord formation in
RT Xenopus.";
RL Dev. Biol. 174:174-178(1996).
RN [10]
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 [11]
RP INDUCTION.
RX PubMed=10068640; DOI=10.1242/dev.126.7.1467;
RA Sun B.I., Bush S.M., Collins-Racie L.A., LaVallie E.R.,
RA DiBlasio-Smith E.A., Wolfman N.M., McCoy J.M., Sive H.L.;
RT "derriere: a TGF-beta family member required for posterior development in
RT Xenopus.";
RL Development 126:1467-1482(1999).
RN [12]
RP FUNCTION.
RX PubMed=15128667; DOI=10.1242/dev.01133;
RA Martynova N., Eroshkin F., Ermakova G., Bayramov A., Gray J., Grainger R.,
RA Zaraisky A.;
RT "Patterning the forebrain: FoxA4a/Pintallavis and Xvent2 determine the
RT posterior limit of Xanf1 expression in the neural plate.";
RL Development 131:2329-2338(2004).
RN [13]
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).
CC -!- FUNCTION: Transcriptional repressor involved in embryonic nervous
CC system development. Plays a role in the induction and patterning of the
CC anterior-posterior neural axis. Involved in the establishment of floor
CC plate differentiation from neural plate cells during gastrulation.
CC Binds the anf1 promoter sequence to restrict expression of anf1 to the
CC anterior of the neural plate, thereby patterning the forebrain. Can
CC bind to the HNF-3-alpha DNA target sequence. Cooperates with t/bra in a
CC dose-dependent manner to specify dorsal mesoderm formation, including
CC notochord. Binds to DNA via the target sequence 5'-[GA]TAAA[TC]A-3',
CC with 5'-GTAAATA-3' being the preferred binding site.
CC {ECO:0000269|PubMed:1358174, ECO:0000269|PubMed:1483397,
CC ECO:0000269|PubMed:15128667, ECO:0000269|PubMed:7789266,
CC ECO:0000269|PubMed:8367492}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: During stages 8.5 to 10, expressed in the part of
CC the dorsal mesoderm invaginating the dorsal blastopore lip (Spemann
CC organizer), as a direct response to dorsal mesodermal induction. At
CC stage 12 (mid-gastrulation), restricted to the dorsal midline in the
CC deeper layers of mesodermal cells. Continuously present in the
CC posterior portion of invaginated mesoderm and expressed within the
CC notochord. Also present in the midline of the neural plate during
CC gastrulation, but absent from the notoplate in exogastrula embryos.
CC Expression in the notochord continues in neurula-stage embryos and at
CC stage 20 in addition to the notochord, expression is seen in the
CC pharyngeal endoderm. {ECO:0000269|PubMed:1358174,
CC ECO:0000269|PubMed:1483397, ECO:0000269|PubMed:7586752,
CC ECO:0000269|PubMed:8735935}.
CC -!- DEVELOPMENTAL STAGE: First expressed at the late blastula stage (stage
CC 9). Most abundant during gastrulation, with levels peaking in mid-
CC gastrula embryos (stage 12) before declining rapidly at the end of
CC neurulation and becoming barely detectable in the late tailbud-early
CC tadpole stage. {ECO:0000269|PubMed:1358174, ECO:0000269|PubMed:1483397,
CC ECO:0000269|PubMed:8735935}.
CC -!- INDUCTION: By activin, derriere and not2. {ECO:0000269|PubMed:10068640,
CC ECO:0000269|PubMed:1358174, ECO:0000269|PubMed:8626017}.
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DR EMBL; X65171; CAA46290.1; -; mRNA.
DR EMBL; U65751; AAD03479.1; -; Genomic_DNA.
DR EMBL; BC082358; AAH82358.1; -; mRNA.
DR PIR; S35719; S35719.
DR RefSeq; NP_001080963.1; NM_001087494.1.
DR AlphaFoldDB; P33205; -.
DR SMR; P33205; -.
DR GeneID; 394304; -.
DR KEGG; xla:394304; -.
DR CTD; 394304; -.
DR Xenbase; XB-GENE-865612; foxa4.L.
DR OrthoDB; 1181467at2759; -.
DR Proteomes; UP000186698; Chromosome 4L.
DR Bgee; 394304; Expressed in gastrula and 2 other tissues.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0009948; P:anterior/posterior axis specification; IMP:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0030900; P:forebrain development; IMP:UniProtKB.
DR GO; GO:0001707; P:mesoderm formation; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0001840; P:neural plate development; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR013638; Fork-head_N.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR018533; Forkhead_box_C.
DR InterPro; IPR018122; TF_fork_head_CS_1.
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 Pfam; PF08430; Forkhead_N; 1.
DR Pfam; PF09354; HNF_C; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00657; FORK_HEAD_1; 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..399
FT /note="Forkhead box protein A4-A"
FT /id="PRO_0000091897"
FT DNA_BIND 119..213
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 219..290
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..235
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 246..290
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 245
FT /note="V -> L (in Ref. 1; CAA46290)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="S -> N (in Ref. 2; AAD03479)"
FT /evidence="ECO:0000305"
FT CONFLICT 382
FT /note="T -> N (in Ref. 4; AAH82358)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 399 AA; 44498 MW; 7DE8114D8D4B9705 CRC64;
MLNRVKLEIK DPMDWNTMYQ ENEMYSGIHN MTNVLPSNSF LPNDVSTVTT SMPYMSNGLP
GPVTSIQGNI GSLGSMPQGM VGSLAPPPST AAYPLGYCQG ESEFQRDPRT YRRNYSHAKP
PYSYISLITM AIQQAPNKMM TLNEIYQWII DLFPYYRQNQ QRWQNSIRHS LSFNDCFVKV
PRSPEKPGKG SYWTLHPESG NMFENGCYLR RQKRFKCERS KSGEGEKKVN KPGEETGGNL
KENPVGYDDC SSSRSPQAAV NDGGRDSTGS SIHQACGSSP VGLSPTSEQA GTASQLMYPL
GLSNDGYLGL VGEDVHLKHD PFSGRHPFSI TQLMSSEQDQ TYANKMEMCP TTDHLVHYSN
YSSDYHNMAS KNGLDMQTSS STDNGYYANM YSRPILSSL
