LBX2_DANRE
ID LBX2_DANRE Reviewed; 257 AA.
AC Q804R0;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Transcription factor LBX2 {ECO:0000303|PubMed:19216761};
DE AltName: Full=Ladybird homeobox 2 {ECO:0000250|UniProtKB:Q6XYB7};
DE AltName: Full=Ladybird homeobox protein homolog 2;
GN Name=lbx2 {ECO:0000312|ZFIN:ZDB-GENE-001206-2};
GN Synonyms=Lbx2h {ECO:0000250|UniProtKB:Q9WUN8};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|Proteomes:UP000000437};
RN [1] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=19216761; DOI=10.1186/1471-213x-9-13;
RA Ochi H., Westerfield M.;
RT "Lbx2 regulates formation of myofibrils.";
RL BMC Dev. Biol. 9:13-13(2009).
RN [4] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=22216300; DOI=10.1371/journal.pone.0029515;
RA Chen X., Lou Q., He J., Yin Z.;
RT "Role of zebrafish lbx2 in embryonic lateral line development.";
RL PLoS ONE 6:e29515-e29515(2011).
RN [5] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=22406073; DOI=10.1016/j.bbamcr.2012.02.013;
RA Lou Q., He J., Hu L., Yin Z.;
RT "Role of lbx2 in the noncanonical Wnt signaling pathway for convergence and
RT extension movements and hypaxial myogenesis in zebrafish.";
RL Biochim. Biophys. Acta 1823:1024-1032(2012).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH TLE3A, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP 42-PHE--LEU-48.
RX PubMed=25371059; DOI=10.1038/ncomms6368;
RA Lu F.I., Sun Y.H., Wei C.Y., Thisse C., Thisse B.;
RT "Tissue-specific derepression of TCF/LEF controls the activity of the
RT Wnt/beta-catenin pathway.";
RL Nat. Commun. 5:5368-5368(2014).
CC -!- FUNCTION: Transcription factor required in several developmental
CC processes (PubMed:19216761, PubMed:22216300, PubMed:25371059). Involved
CC in axis formation during embryonic development by inhibiting tle3a/gro2
CC from binding to tcf7l1a, thereby facilitating ctnnb1-mediated
CC transcription of canonical Wnt/CTNNB1 signaling target genes
CC (PubMed:25371059). Regulates convergent extension movements and
CC hypaxial myogenesis during gastrulation by activating non-canonical Wnt
CC signaling via wnt5b (PubMed:19216761, PubMed:22406073). Required for
CC the formation of myofibrils and fusion of fast muscle precursor cells,
CC potentially via transcriptional regulation of genes specific to thick
CC and thin myofilaments (PubMed:19216761). Regulates the migration of the
CC posterior lateral line primordium during embryonic development,
CC possibly via regulation of cxcl12a/sdf1a expression in the posterior
CC lateral mesoderm, thereby modulating the deposition of neuromasts at
CC correct intervals (PubMed:22216300). {ECO:0000269|PubMed:19216761,
CC ECO:0000269|PubMed:22216300, ECO:0000269|PubMed:22406073,
CC ECO:0000269|PubMed:25371059}.
CC -!- SUBUNIT: Interacts (via N-terminus) with tle3a/gro2 (via C-terminus).
CC {ECO:0000269|PubMed:25371059}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the germ ring at the blastoderm
CC margin during the shield stage and when embryo reaches 80% epiboly
CC stage of gastrulation, expression is higher dorsally than ventrally
CC (PubMed:19216761, PubMed:22406073). Expressed in the paraxial mesoderm,
CC posterior lateral mesoderm and adaxial cells at the end of the bud
CC stage (PubMed:19216761, PubMed:22216300). Expressed in the segmental
CC plate and ventral mesoderm during early gastrulation and early
CC somitogenesis (PubMed:25371059). Expressed at the posterior dorsal
CC midline at the three-somite stage and extends to the anterior region
CC along the notochord, and to the trunk somites and cells lateral to them
CC in the 24 hours post-fertilization (hpf) (PubMed:22406073). Expressed
CC in both dorsal and ventral fast muscle cells in the late stages of
CC segmentation (PubMed:19216761). Expressed in the hindbrain, a
CC subpopulation of spinal cord interneurons, hypaxial muscles and in
CC migrating muscle cells giving rise to the hyoid muscles and pectoral
CC fin muscles at 24 hpf (PubMed:25371059). Expressed in the neural tube
CC and hindbrain at 36 and 48 hpf with additional expression in the
CC pectoral fin bud and fin muscles at 48 hpf (PubMed:19216761,
CC PubMed:22406073). Expression is lost from the trunk at 48 hpf
CC (PubMed:19216761). {ECO:0000269|PubMed:19216761,
CC ECO:0000269|PubMed:22216300, ECO:0000269|PubMed:22406073,
CC ECO:0000269|PubMed:25371059}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown results in circling swimming
CC behavior at the larval stage (PubMed:22216300). Reduced fin bud
CC formation and loss of myod1 expression in embryo hyoid muscles
CC (PubMed:19216761, PubMed:22216300, PubMed:22406073). Disruption of
CC cuboidal morphology of adaxial cell pseudo-epithelium, and failure of
CC myod1-expressing cells to incorporate into the adaxial cell layer
CC (PubMed:19216761). Slow muscle fibers are abnormally shaped at 24 hpf
CC and 48 hpf and fast muscle cells form shorter myofibrils at 24 hpf and
CC 48 hpf, in addition unfused fast muscles cells are present at 48 hpf
CC (PubMed:19216761). Reduced expression of thin filament genes in
CC skeletal muscles and thick filament genes in embryos (PubMed:19216761).
CC Weak and discontinuous pattern of cxcl12a/sdf1a expression just before
CC the posterior lateral line (PLL) begins to migrate in the posterior
CC lateral mesoderm at the tail bud stage, and in adaxial cells at the 10-
CC somite stage (PubMed:22216300). Disruption of myoseptum distribution as
CC a result of abnormal differentiation of cxcl12a/sdf1a-expressing cells
CC in the horizontal myoseptum at 24 hpf (PubMed:22216300). Increase in
CC cell death rate in the PLL primordium and deposited neuromasts at 36
CC hpf (PubMed:22216300). Decrease in the number of PLL neuromasts with
CC 15% of morphants showing complete loss of neuromasts at 48 hpf
CC (PubMed:22216300). The speed of PLL primordium migration is reduced and
CC neuromasts are deposited at inappropriate locations along the length of
CC the posteriorly extending primordium (PubMed:22216300). Disruption of
CC the discrete dorsoventral domains resulting in narrowing of the
CC mediolateral region and slower extension of the expression domains
CC towards the dorsal region at the shield stage (PubMed:22406073).
CC Abnormal anterior-posterior axis, reduced dorsalward movement speed of
CC lateral marginal cells and reduced wnt5b expression at the end of
CC gastrulation. Embryos have a broader neural plate in the neuroectoderm
CC with shorter and broader notochords, and reduced cell elongation
CC (PubMed:22406073). {ECO:0000269|PubMed:19216761,
CC ECO:0000269|PubMed:22216300, ECO:0000269|PubMed:22406073}.
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DR EMBL; AL831789; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC075912; AAH75912.1; -; mRNA.
DR RefSeq; NP_001007135.1; NM_001007134.1.
DR AlphaFoldDB; Q804R0; -.
DR SMR; Q804R0; -.
DR STRING; 7955.ENSDARP00000029690; -.
DR PaxDb; Q804R0; -.
DR Ensembl; ENSDART00000031508; ENSDARP00000029690; ENSDARG00000025131.
DR Ensembl; ENSDART00000187825; ENSDARP00000153066; ENSDARG00000025131.
DR GeneID; 64276; -.
DR KEGG; dre:64276; -.
DR CTD; 85474; -.
DR ZFIN; ZDB-GENE-001206-2; lbx2.
DR eggNOG; KOG0488; Eukaryota.
DR GeneTree; ENSGT00940000166497; -.
DR HOGENOM; CLU_086390_0_0_1; -.
DR InParanoid; Q804R0; -.
DR OMA; ANICPPR; -.
DR OrthoDB; 1472248at2759; -.
DR PhylomeDB; Q804R0; -.
DR TreeFam; TF325047; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 14.
DR Bgee; ENSDARG00000025131; Expressed in presumptive paraxial mesoderm and 37 other tissues.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0000578; P:embryonic axis specification; IMP:UniProtKB.
DR GO; GO:0055001; P:muscle cell development; IMP:ZFIN.
DR GO; GO:0042692; P:muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:1904105; P:positive regulation of convergent extension involved in gastrulation; IMP:UniProtKB.
DR GO; GO:2000052; P:positive regulation of non-canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0048922; P:posterior lateral line neuromast deposition; IMP:UniProtKB.
DR GO; GO:0048920; P:posterior lateral line neuromast primordium migration; IMP:UniProtKB.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; IMP:ZFIN.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR000047; HTH_motif.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00031; HTHREPRESSR.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Developmental protein; DNA-binding; Homeobox; Nucleus; Reference proteome.
FT CHAIN 1..257
FT /note="Transcription factor LBX2"
FT /id="PRO_0000451740"
FT DNA_BIND 126..185
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..46
FT /note="Required for convergent extension movement and
FT hypaxial myogenesis during gastrulation. Required for the
FT formation of thick and thin myofilaments. Required for
FT myod1 expression in the pectoral fin bud. Required for
FT continuous expression of cxcl12a in the posterior lateral
FT mesoderm at the tail bud stage and in adaxial cells at the
FT 10-somite stage"
FT /evidence="ECO:0000269|PubMed:19216761,
FT ECO:0000269|PubMed:22216300, ECO:0000269|PubMed:22406073"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 206..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 226..242
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 42..48
FT /note="FSIEDIL->ICLQEFI: Abolishes maternal ctnnb1
FT signaling resulting in a loss of chd expression."
FT /evidence="ECO:0000269|PubMed:25371059"
SQ SEQUENCE 257 AA; 28367 MW; 18BDBBCD2B9A04C9 CRC64;
MTSSSKDMKA GSVLQSSGEE RRRGPLDQLP PPANSNKPLT PFSIEDILNK PSVKKSVGSL
CPPRVLEKVT GSSASRNGIS APSSPLCALE ELASKTFKGL EVSVIQAAEG REHINAFGQR
QASKKRRKSR TAFTNHQIYE LEKRFLYQKY LSPADRDQIA QQLGLTNAQV ITWFQNRRAK
LKRDLEEMKA DVESLKKIPP QALQKLVSME DMEDAHGGSG PISPSLSPRA FPQSPSSSRG
QTTDEFSEED EEIEVDD
