ID   ALX1_DANRE              Reviewed;         320 AA.
AC   Q1LVQ7;
DT   27-MAY-2015, integrated into UniProtKB/Swiss-Prot.
DT   20-FEB-2007, sequence version 1.
DT   03-AUG-2022, entry version 121.
DE   RecName: Full=ALX homeobox protein 1 {ECO:0000305};
DE   AltName: Full=Cartilage homeoprotein 1 {ECO:0000250|UniProtKB:Q63087};
DE            Short=CART-1 {ECO:0000250|UniProtKB:Q63087};
GN   Name=alx1 {ECO:0000250|UniProtKB:Q15699};
GN   Synonyms=cart1 {ECO:0000250|UniProtKB:Q15699};
GN   ORFNames=si:ch211-154h20.1 {ECO:0000312|EMBL:BX649507},
GN   si:dkey-66c4.1 {ECO:0000312|EMBL:CAK11128.1};
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;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tuebingen;
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   [2]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX   PubMed=23059813; DOI=10.1093/hmg/dds423;
RA   Dee C.T., Szymoniuk C.R., Mills P.E., Takahashi T.;
RT   "Defective neural crest migration revealed by a Zebrafish model of Alx1-
RT   related frontonasal dysplasia.";
RL   Hum. Mol. Genet. 22:239-251(2013).
CC   -!- FUNCTION: Sequence-specific DNA-binding transcription factor that binds
CC       palindromic sequences within promoters and may activate or repress the
CC       transcription of a subset of genes. Most probably regulates the
CC       expression of genes involved in the development of mesenchyme-derived
CC       craniofacial structures (By similarity). Required for proper neural
CC       crest cell migration into the frontonasal primordia during development
CC       (PubMed:23059813). {ECO:0000250|UniProtKB:Q15699,
CC       ECO:0000269|PubMed:23059813}.
CC   -!- SUBUNIT: Binds DNA as a homodimer; required for transcriptional
CC       activation. {ECO:0000250|UniProtKB:Q63087}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q15699}.
CC   -!- DEVELOPMENTAL STAGE: Expression is initially detected at the tailbud
CC       stage, immediately after gastrulation, in the cephalic mesoderm. It is
CC       maintained in the mesoderm during early stages of development.
CC       Expression is initiated in the neural crest by the 5 somites stage, and
CC       is restricted to a rostral domain of cranial neural crest. Later during
CC       development it is still expressed in specific regions of the neural
CC       crest-derived facial mesenchyme. In 24 hpf stage embryos, expressed
CC       strongly in the periocular mesenchyme. By 48 hpf, expression is
CC       maintained in the periocular mesenchyme towards the anterior of the
CC       head, with weaker expression in the nasal region and the prospective
CC       palate. Also expressed in a discrete region at the distal tip of the
CC       mandible arch and in the pectoral fin bud primordia.
CC       {ECO:0000269|PubMed:23059813}.
CC   -!- DOMAIN: The OAR motif may negatively regulate DNA-binding and therefore
CC       transcriptional activity. It is found in the C-terminal transactivation
CC       domain that stimulates transcription. {ECO:0000250|UniProtKB:Q63087}.
CC   -!- DISRUPTION PHENOTYPE: Morpholino-mediated knockdown causes severe
CC       craniofacial alterations including small, misshapen head,
CC       microphthalmia and loss of the jaw. It is associated with a more or
CC       less severe loss of the cartilaginous facial skeleton. Pericardial
CC       edema is also detected. {ECO:0000269|PubMed:23059813}.
CC   -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
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DR   EMBL; BX000347; CAK11128.1; -; Genomic_DNA.
DR   EMBL; BX649507; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001038539.1; NM_001045074.1.
DR   AlphaFoldDB; Q1LVQ7; -.
DR   SMR; Q1LVQ7; -.
DR   STRING; 7955.ENSDARP00000123391; -.
DR   PaxDb; Q1LVQ7; -.
DR   Ensembl; ENSDART00000142584; ENSDARP00000123391; ENSDARG00000062824.
DR   Ensembl; ENSDART00000184539; ENSDARP00000150329; ENSDARG00000110530.
DR   Ensembl; ENSDART00000184848; ENSDARP00000148539; ENSDARG00000115230.
DR   GeneID; 565176; -.
DR   KEGG; dre:565176; -.
DR   CTD; 8092; -.
DR   ZFIN; ZDB-GENE-050419-191; alx1.
DR   eggNOG; KOG0490; Eukaryota.
DR   GeneTree; ENSGT00940000158251; -.
DR   HOGENOM; CLU_047013_0_1_1; -.
DR   OMA; SSPCGDQ; -.
DR   OrthoDB; 738339at2759; -.
DR   PhylomeDB; Q1LVQ7; -.
DR   PRO; PR:Q1LVQ7; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 18.
DR   Bgee; ENSDARG00000062824; Expressed in camera-type eye and 5 other tissues.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:ZFIN.
DR   GO; GO:0048704; P:embryonic skeletal system morphogenesis; IBA:GO_Central.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IBA:GO_Central.
DR   GO; GO:0001755; P:neural crest cell migration; IMP:ZFIN.
DR   GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   CDD; cd00086; homeodomain; 1.
DR   InterPro; IPR033209; ALX1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR003654; OAR_dom.
DR   PANTHER; PTHR24329:SF359; PTHR24329:SF359; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   Pfam; PF03826; OAR; 1.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; SSF46689; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   PROSITE; PS50803; OAR; 1.
PE   2: Evidence at transcript level;
KW   Activator; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW   Reference proteome; Repressor; Transcription; Transcription regulation.
FT   CHAIN           1..320
FT                   /note="ALX homeobox protein 1"
FT                   /id="PRO_0000433021"
FT   DNA_BIND        120..179
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          180..320
FT                   /note="Transactivation domain"
FT                   /evidence="ECO:0000250|UniProtKB:Q63087"
FT   MOTIF           300..313
FT                   /note="OAR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00138"
SQ   SEQUENCE   320 AA;  36131 MW;  38C1017AAE17BC26 CRC64;
     MEYLSDKFSL KSPAIKGSDY YMDQVMDTLD NVQYYNKASP KCVQAFPMQS NDQHSSMDRS
     SPCDNQSSVT YCAPKSEESS LHAMENCCSL RVSPATSGPD KTDLDELGEK CDSNVSSSKK
     RRHRTTFTSA QLEELEKVFQ KTHYPDVYVR EQLAMRTELT EARVQVWFQN RRAKWRKRER
     YGQIQQAKSH FAATYDISML PRTDSYSQIS NNLWTGPSAG SSVVSSCMIP RGSPPCVTSP
     YPHSPRAAEH GYVGFPNHQQ NQFGVNHVSL NNFFADSLLA SSANSHAAFE TKPEFERRSS
     SIAVLRMKAK EHTANISWAM