UNC4_MOUSE
ID UNC4_MOUSE Reviewed; 530 AA.
AC O08934; P70457; Q78DU3;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Homeobox protein unc-4 homolog;
DE AltName: Full=Homeobox protein Uncx4.1;
GN Name=Uncx; Synonyms=Uncx4.1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10804169; DOI=10.1242/dev.127.11.2259;
RA Leitges M., Neidhardt L., Haenig B., Herrmann B.G., Kispert A.;
RT "The paired homeobox gene Uncx4.1 specifies pedicles, transverse processes
RT and proximal ribs of the vertebral column.";
RL Development 127:2259-2267(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spinal cord;
RA Nicholson L.F.B., Ma L., Goulding M.;
RT "Cloning and expression of the mouse homolog of Caenorhabditis elegans unc4
RT gene.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-387, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=C57BL/6J;
RX PubMed=9286595;
RX DOI=10.1002/(sici)1097-0177(199709)210:1<53::aid-aja6>3.0.co;2-0;
RA Mansouri A., Yokota Y., Wehr R., Copeland N.G., Jenkins N.A., Gruss P.;
RT "Paired-related murine homeobox gene expressed in the developing
RT sclerotome, kidney, and nervous system.";
RL Dev. Dyn. 210:53-65(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 109-304.
RX PubMed=8855241; DOI=10.1073/pnas.93.20.10691;
RA Rovescalli A.C., Asoh S., Nirenberg M.W.;
RT "Cloning and characterization of four murine homeobox genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10691-10696(1996).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=10330372; DOI=10.1016/s0960-9822(99)80212-7;
RA del Barco Barrantes I., Elia A.J., Wuensch K., De Angelis M.H., Mak T.W.,
RA Rossant J., Conlon R.A., Gossler A., de la Pompa J.L.;
RT "Interaction between Notch signalling and Lunatic fringe during somite
RT boundary formation in the mouse.";
RL Curr. Biol. 9:470-480(1999).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=10545229; DOI=10.1006/dbio.1999.9463;
RA Horikawa K., Radice G., Takeichi M., Chisaka O.;
RT "Adhesive subdivisions intrinsic to the epithelial somites.";
RL Dev. Biol. 215:182-189(1999).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10804168; DOI=10.1242/dev.127.11.2251;
RA Mansouri A., Voss A.K., Thomas T., Yokota Y., Gruss P.;
RT "Uncx4.1 is required for the formation of the pedicles and proximal ribs
RT and acts upstream of Pax9.";
RL Development 127:2251-2258(2000).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=11747084; DOI=10.1002/dvdy.1211;
RA Schubert F.R., Tremblay P., Mansouri A., Faisst A.M., Kammandel B.,
RA Lumsden A., Gruss P., Dietrich S.;
RT "Early mesodermal phenotypes in splotch suggest a role for Pax3 in the
RT formation of epithelial somites.";
RL Dev. Dyn. 222:506-521(2001).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=11973278; DOI=10.1242/dev.129.10.2473;
RA Nomura-Kitabayashi A., Takahashi Y., Kitajima S., Inoue T., Takeda H.,
RA Saga Y.;
RT "Hypomorphic Mesp allele distinguishes establishment of rostrocaudal
RT polarity and segment border formation in somitogenesis.";
RL Development 129:2473-2481(2002).
RN [11]
RP TISSUE SPECIFICITY.
RX PubMed=16728472; DOI=10.1242/dev.02422;
RA Nakajima Y., Morimoto M., Takahashi Y., Koseki H., Saga Y.;
RT "Identification of Epha4 enhancer required for segmental expression and the
RT regulation by Mesp2.";
RL Development 133:2517-2525(2006).
RN [12]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=16461927; DOI=10.1677/jme.1.01831;
RA Asbreuk C.H.J., van Doorninck J.H., Mansouri A., Smidt M.P.,
RA Burbach J.P.H.;
RT "Neurohypophysial dysmorphogenesis in mice lacking the homeobox gene
RT Uncx4.1.";
RL J. Mol. Endocrinol. 36:65-71(2006).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=17477400; DOI=10.1002/dvdy.21178;
RA Takahashi Y., Takagi A., Hiraoka S., Koseki H., Kanno J., Rawls A.,
RA Saga Y.;
RT "Transcription factors Mesp2 and Paraxis have critical roles in axial
RT musculoskeletal formation.";
RL Dev. Dyn. 236:1484-1494(2007).
RN [14]
RP TISSUE SPECIFICITY.
RX PubMed=17531978; DOI=10.1016/j.febslet.2007.05.017;
RA Chan T., Kondow A., Hosoya A., Hitachi K., Yukita A., Okabayashi K.,
RA Nakamura H., Ozawa H., Kiyonari H., Michiue T., Ito Y., Asashima M.;
RT "Ripply2 is essential for precise somite formation during mouse early
RT development.";
RL FEBS Lett. 581:2691-2696(2007).
CC -!- FUNCTION: Transcription factor involved in somitogenesis and
CC neurogenesis. Required for the maintenance and differentiation of
CC particular elements of the axial skeleton. May act upstream of PAX9.
CC Plays a role in controlling the development of connections of
CC hypothalamic neurons to pituitary elements, allowing central neurons to
CC reach the peripheral blood circulation and to deliver hormones for
CC control of peripheral functions. {ECO:0000269|PubMed:10804168,
CC ECO:0000269|PubMed:10804169, ECO:0000269|PubMed:16461927}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- TISSUE SPECIFICITY: Expressed in the paraxial mesoderm, in the
CC developing kidney and central nervous system. In the somite, it is
CC restricted to the caudal half of the newly formed somite and
CC sclerotome. In the central nervous system, it is detected in the
CC developing spinal cord, hindbrain, mesencephalon and telencephalon.
CC Expressed in adult and embryonic magnocellular neurons of the
CC hypothalamo-neurohypophysial system. {ECO:0000269|PubMed:10330372,
CC ECO:0000269|PubMed:10545229, ECO:0000269|PubMed:11747084,
CC ECO:0000269|PubMed:11973278, ECO:0000269|PubMed:16461927,
CC ECO:0000269|PubMed:16728472, ECO:0000269|PubMed:17477400,
CC ECO:0000269|PubMed:17531978, ECO:0000269|PubMed:9286595}.
CC -!- DISRUPTION PHENOTYPE: Mice die perinatally and exhibit severe
CC malformations of the axial skeleton. Pedicles of the neural arches and
CC proximal ribs are not formed. In addition, dorsal root ganglia are
CC disorganized. In the hypothalamo-neurohypophysial system, neurons are
CC viable and able to express neuropeptides; however, the connectivity of
CC magnocellular neurons with posterior pituitary elements is compromised.
CC {ECO:0000269|PubMed:10804168, ECO:0000269|PubMed:10804169,
CC ECO:0000269|PubMed:16461927}.
CC -!- MISCELLANEOUS: Marker of antero-posterior subdivisions of the somite.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Unc-4 subfamily.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ001116; CAA04542.1; -; mRNA.
DR EMBL; AF247550; AAF71322.1; -; mRNA.
DR EMBL; BC051973; AAH51973.1; -; mRNA.
DR EMBL; Z96107; CAB09537.1; -; mRNA.
DR EMBL; AH006754; AAC52830.1; -; Genomic_DNA.
DR CCDS; CCDS19813.1; -.
DR RefSeq; NP_038730.1; NM_013702.3.
DR AlphaFoldDB; O08934; -.
DR STRING; 10090.ENSMUSP00000031523; -.
DR PhosphoSitePlus; O08934; -.
DR MaxQB; O08934; -.
DR PaxDb; O08934; -.
DR PRIDE; O08934; -.
DR ProteomicsDB; 298199; -.
DR Antibodypedia; 24186; 131 antibodies from 21 providers.
DR DNASU; 22255; -.
DR Ensembl; ENSMUST00000172997; ENSMUSP00000134067; ENSMUSG00000029546.
DR GeneID; 22255; -.
DR KEGG; mmu:22255; -.
DR UCSC; uc009agv.1; mouse.
DR CTD; 340260; -.
DR MGI; MGI:108013; Uncx.
DR VEuPathDB; HostDB:ENSMUSG00000029546; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000161420; -.
DR HOGENOM; CLU_041996_0_0_1; -.
DR InParanoid; O08934; -.
DR OMA; HHNHISN; -.
DR OrthoDB; 1401774at2759; -.
DR PhylomeDB; O08934; -.
DR TreeFam; TF315554; -.
DR BioGRID-ORCS; 22255; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Uncx; mouse.
DR PRO; PR:O08934; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O08934; protein.
DR Bgee; ENSMUSG00000029546; Expressed in olfactory epithelium and 85 other tissues.
DR ExpressionAtlas; O08934; baseline and differential.
DR Genevisible; O08934; MM.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0001502; P:cartilage condensation; IMP:MGI.
DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; IMP:MGI.
DR GO; GO:0021516; P:dorsal spinal cord development; IMP:MGI.
DR GO; GO:0021889; P:olfactory bulb interneuron differentiation; IMP:MGI.
DR GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR GO; GO:0045595; P:regulation of cell differentiation; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR Pfam; PF00046; Homeodomain; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 2: Evidence at transcript level;
KW Developmental protein; Differentiation; DNA-binding; Homeobox;
KW Neurogenesis; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..530
FT /note="Homeobox protein unc-4 homolog"
FT /id="PRO_0000334625"
FT DNA_BIND 109..168
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 90..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..530
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 95..110
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..207
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 223..243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 405..423
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..503
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 260
FT /note="A -> D (in Ref. 5; AAC52830)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 530 AA; 53936 MW; 2E3A4DE98428E381 CRC64;
MMDGRLLEHP HAQFGGSLGG VVGFPYPLGH HHVYELAGHQ LQSAAAAAAA ASVPFSIDGL
LSGSCAAAAA SVVNPTPLLP AACGVAGESQ PFKLADSGDP DKESPGCKRR RTRTNFTGWQ
LEELEKAFNE SHYPDVFMRE ALALRLDLVE SRVQVWFQNR RAKWRKKENT KKGPGRPAHN
SHPTTCSGEP MDPEEIARKE LEKMEKKKRK HEKKLLKSQS RHLHSPGGLS LHSAPSSDSD
SGGGGLSPEP PEPPPPTAAA KGPGAHGSGI AGSAPVPPGE PPAPGTCDPA FYPSQRSGAG
SQPRLGRPAD KDTVPCGPGA AATAGLPKAS PFSVESLLSD SPPRRKATPA NAAATAGLDF
TPGLPCAPRT LIGKGHFLLY PITQPLGFLV PQAALKGGAG PELVPKDAPP APPAPPAPPA
QASFGTFPGP GGAADPAFAR RSPEVVASPG PPAPASFRDL TAAAAESGAG DCADVGTVCP
AASPPPPLET SPGPGPRAPS PPGEPATCGA AEPGAATGPS PPEGEEVDMD
