HMX3_MOUSE
ID HMX3_MOUSE Reviewed; 356 AA.
AC P42581; B9EIJ0; O88699;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Homeobox protein HMX3;
DE AltName: Full=Homeobox protein H6 family member 3;
DE AltName: Full=Homeobox protein Nkx-5.1;
GN Name=Hmx3; Synonyms=Nkx-5.1, Nkx5-1;
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], AND DEVELOPMENTAL STAGE.
RC STRAIN=ICR X Swiss Webster; TISSUE=Embryo;
RX PubMed=7510254; DOI=10.1006/dbio.1994.1086;
RA Bober E., Baum C., Braun T., Arnold H.-H.;
RT "A novel NK-related mouse homeobox gene: expression in central and
RT peripheral nervous structures during embryonic development.";
RL Dev. Biol. 162:288-303(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10543441; DOI=10.1515/bc.1999.130;
RA Mennerich D., Hoffmann S., Hadrys T., Arnold H.H., Bober E.;
RT "Two highly related homeodomain proteins, Nkx5-1 and Nkx5-2, display
RT different DNA binding specificities.";
RL Biol. Chem. 380:1041-1048(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=8541222; DOI=10.1016/0925-4773(95)00414-v;
RA Rinkwitz-Brandt S., Justus M., Oldenettel I., Arnold H.-H., Bober E.;
RT "Distinct temporal expression of mouse Nkx-5.1 and Nkx-5.2 homeobox genes
RT during brain and ear development.";
RL Mech. Dev. 52:371-381(1995).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=8970821; DOI=10.1016/s0378-5955(96)00093-7;
RA Rinkwitz-Brandt S., Arnold H.H., Bober E.;
RT "Regionalized expression of Nkx5-1, Nkx5-2, Pax2 and sek genes during mouse
RT inner ear development.";
RL Hear. Res. 99:129-138(1996).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=9435283; DOI=10.1242/dev.125.4.621;
RA Wang W., Van De Water T., Lufkin T.;
RT "Inner ear and maternal reproductive defects in mice lacking the Hmx3
RT homeobox gene.";
RL Development 125:621-634(1998).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=9389661; DOI=10.1242/dev.125.1.33;
RA Hadrys T., Braun T., Rinkwitz-Brandt S., Arnold H.-H., Bober E.;
RT "Nkx5-1 controls semicircular canal formation in the mouse inner ear.";
RL Development 125:33-39(1998).
RN [9]
RP DNA-BINDING, AND MUTAGENESIS OF GLN-276.
RX PubMed=10206974; DOI=10.1074/jbc.274.17.11635;
RA Amendt B.A., Sutherland L.B., Russo A.F.;
RT "Transcriptional antagonism between Hmx1 and Nkx2.5 for a shared DNA-
RT binding site.";
RL J. Biol. Chem. 274:11635-11642(1999).
RN [10]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11748138; DOI=10.1242/dev.128.24.5017;
RA Wang W., Chan E.K., Baron S., Van de Water T., Lufkin T.;
RT "Hmx2 homeobox gene control of murine vestibular morphogenesis.";
RL Development 128:5017-5029(2001).
RN [11]
RP INDUCTION.
RX PubMed=11731242; DOI=10.1016/s0925-4773(01)00550-0;
RA Adamska M., Herbrand H., Adamski M., Krueger M., Braun T., Bober E.;
RT "FGFs control the patterning of the inner ear but are not able to induce
RT the full ear program.";
RL Mech. Dev. 109:303-313(2001).
RN [12]
RP INDUCTION.
RX PubMed=12874121; DOI=10.1242/dev.00628;
RA Zheng W., Huang L., Wei Z.B., Silvius D., Tang B., Xu P.-X.;
RT "The role of Six1 in mammalian auditory system development.";
RL Development 130:3989-4000(2003).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15363417; DOI=10.1016/j.devcel.2004.06.016;
RA Wang W., Grimmer J.F., Van De Water T.R., Lufkin T.;
RT "Hmx2 and Hmx3 homeobox genes direct development of the murine inner ear
RT and hypothalamus and can be functionally replaced by Drosophila Hmx.";
RL Dev. Cell 7:439-453(2004).
RN [14]
RP INDUCTION.
RX PubMed=14695375; DOI=10.1242/dev.00943;
RA Ozaki H., Nakamura K., Funahashi J., Ikeda K., Yamada G., Tokano H.,
RA Okamura H.O., Kitamura K., Muto S., Kotaki H., Sudo K., Horai R.,
RA Iwakura Y., Kawakami K.;
RT "Six1 controls patterning of the mouse otic vesicle.";
RL Development 131:551-562(2004).
CC -!- FUNCTION: Transcription factor involved in specification of neuronal
CC cell types and which is required for inner ear and hypothalamus
CC development. Binds to the 5'-CAAGTG-3' core sequence. Controls
CC semicircular canal formation in the inner ear. Also required for
CC hypothalamic/pituitary axis of the CNS. {ECO:0000269|PubMed:15363417,
CC ECO:0000269|PubMed:9389661, ECO:0000269|PubMed:9435283}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Expressed in the developing CNS, including a
CC specific expression in vestibular structures throughout inner ear
CC development. {ECO:0000269|PubMed:11748138, ECO:0000269|PubMed:9389661,
CC ECO:0000269|PubMed:9435283}.
CC -!- DEVELOPMENTAL STAGE: Begins at embryonic day 10.5 in the developing
CC ear, hypothalamus, the neural tube and dorsal root ganglia. It
CC continues to be active throughout prenatal life in discrete regions of
CC the brain with an anterior border in the ventral diencephalon at the
CC optic chiasma and expression domains in mesencephalon, metencephalon,
CC and myelencephalon. At midgestation, it is also expressed in mesenchyme
CC of the head and branchial arches, and in some cranial ganglia, as well
CC as in derivatives of neural crest, such as the truncus sympathicus and
CC myenteric ganglia. In inner ear, it is expressed between 13.5 dpc and
CC birth in non-sensory epithelium of the semicircular canals, utricle and
CC saccule. Also expressed in the cochlea, where the expression is
CC restricted to the stria vascularis. {ECO:0000269|PubMed:11748138,
CC ECO:0000269|PubMed:7510254, ECO:0000269|PubMed:8541222,
CC ECO:0000269|PubMed:8970821}.
CC -!- INDUCTION: Regulated by Six1 and FGFs in inner ear.
CC {ECO:0000269|PubMed:11731242, ECO:0000269|PubMed:12874121,
CC ECO:0000269|PubMed:14695375}.
CC -!- DISRUPTION PHENOTYPE: Mice display abnormal circling behavior and
CC severe vestibular defects owing to a depletion of sensory cells in the
CC saccule and utricle, and a complete loss of the horizontal semicircular
CC canal crista, as well as a fusion of the utricle and saccule
CC endolymphatic spaces into a common utriculosaccular cavity. Moreover,
CC most females have a reproductive defect: females can be fertilized and
CC their embryos undergo normal preimplantation development, but the
CC embryos fail to implant successfully in the uterus and subsequently
CC die. Mice lacking both Hmx2 and Hmx3 show a complete loss of balance,
CC postnatal dwarfism, defects in neuroendocrine system, disturbed
CC hypothalamic-pituitary axis and subsequent die. Defects caused in mice
CC lacking both Hmx2 and Hmx3 can be rescued by expressing the Drosophila
CC Hmx protein. {ECO:0000269|PubMed:15363417, ECO:0000269|PubMed:9389661,
CC ECO:0000269|PubMed:9435283}.
CC -!- SIMILARITY: Belongs to the HMX homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA53079.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};
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DR EMBL; X75330; CAA53079.1; ALT_SEQ; mRNA.
DR EMBL; AJ009935; CAA08911.1; -; Genomic_DNA.
DR EMBL; CH466531; EDL17717.1; -; Genomic_DNA.
DR EMBL; BC139482; AAI39483.1; -; mRNA.
DR EMBL; BC139483; AAI39484.1; -; mRNA.
DR CCDS; CCDS21917.1; -.
DR PIR; I48690; I48690.
DR RefSeq; NP_032283.3; NM_008257.3.
DR RefSeq; XP_006507441.1; XM_006507378.3.
DR RefSeq; XP_006507442.1; XM_006507379.3.
DR AlphaFoldDB; P42581; -.
DR SMR; P42581; -.
DR BioGRID; 200349; 1.
DR STRING; 10090.ENSMUSP00000039018; -.
DR PhosphoSitePlus; P42581; -.
DR MaxQB; P42581; -.
DR PaxDb; P42581; -.
DR PRIDE; P42581; -.
DR Antibodypedia; 32340; 91 antibodies from 18 providers.
DR DNASU; 15373; -.
DR Ensembl; ENSMUST00000046093; ENSMUSP00000039018; ENSMUSG00000040148.
DR GeneID; 15373; -.
DR KEGG; mmu:15373; -.
DR UCSC; uc009kbo.2; mouse.
DR CTD; 340784; -.
DR MGI; MGI:107160; Hmx3.
DR VEuPathDB; HostDB:ENSMUSG00000040148; -.
DR eggNOG; KOG0485; Eukaryota.
DR GeneTree; ENSGT00940000158286; -.
DR HOGENOM; CLU_064096_0_0_1; -.
DR InParanoid; P42581; -.
DR OMA; CAPAKDS; -.
DR OrthoDB; 1313583at2759; -.
DR TreeFam; TF320562; -.
DR BioGRID-ORCS; 15373; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Hmx3; mouse.
DR PRO; PR:P42581; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P42581; protein.
DR Bgee; ENSMUSG00000040148; Expressed in parasympathetic nervous system and 54 other tissues.
DR Genevisible; P42581; MM.
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:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0007420; P:brain development; IGI:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0043583; P:ear development; IMP:CACAO.
DR GO; GO:0007566; P:embryo implantation; IMP:MGI.
DR GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IMP:MGI.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IMP:MGI.
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; IPR020479; Homeobox_metazoa.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
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; Differentiation; DNA-binding; Homeobox;
KW Neurogenesis; Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..356
FT /note="Homeobox protein HMX3"
FT /id="PRO_0000048949"
FT DNA_BIND 227..286
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 129..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..28
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..190
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6NHT5"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A6NHT5"
FT MUTAGEN 276
FT /note="Q->K: Abolishes DNA-binding."
FT /evidence="ECO:0000269|PubMed:10206974"
FT CONFLICT 68
FT /note="A -> V (in Ref. 2; CAA08911)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 356 AA; 37859 MW; 5AB4E8D8FCCE296A CRC64;
MPEPGPDASG TASAPPPQPP PQPPAPKESP FSIRNLLNGD HHRPPPKPQP PPRTLFAPAS
AAAAAAAAAA AAAKGALEGA AGFALSQVGD LAFPRFEIPA QRFALPAHYL ERSPAWWYPY
TLTPAGGHLP RPEASEKALL RDSSPASGTD RDSPEPLLKA DPDHKELDSK SPDEIILEES
DSEEGKKEGE AVPGAAGTTV GATTATPGSE DWKAGAESPE KKPACRKKKT RTVFSRSQVF
QLESTFDMKR YLSSSERAGL AASLHLTETQ VKIWFQNRRN KWKRQLAAEL EAANLSHAAA
QRIVRVPILY HENSAAEGAA AAAGAPVPVS QPLLTFPHPV YYSHPVVSSV PLLRPV
