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Homeobox protein HMX3 (Homeobox protein H6 family member 3) (Homeobox protein Nkx-5.1)

 HMX3_MOUSE              Reviewed;         356 AA.
P42581; B9EIJ0; O88699;
01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
27-JUL-2011, sequence version 3.
28-MAR-2018, entry version 136.
RecName: Full=Homeobox protein HMX3;
AltName: Full=Homeobox protein H6 family member 3;
AltName: Full=Homeobox protein Nkx-5.1;
Name=Hmx3; Synonyms=Nkx-5.1, Nkx5-1;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
STRAIN=ICR X Swiss Webster; TISSUE=Embryo;
PubMed=7510254; DOI=10.1006/dbio.1994.1086;
Bober E., Baum C., Braun T., Arnold H.-H.;
"A novel NK-related mouse homeobox gene: expression in central and
peripheral nervous structures during embryonic development.";
Dev. Biol. 162:288-303(1994).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=10543441; DOI=10.1515/BC.1999.130;
Mennerich D., Hoffmann S., Hadrys T., Arnold H.H., Bober E.;
"Two highly related homeodomain proteins, Nkx5-1 and Nkx5-2, display
different DNA binding specificities.";
Biol. Chem. 380:1041-1048(1999).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
DEVELOPMENTAL STAGE.
PubMed=8541222; DOI=10.1016/0925-4773(95)00414-V;
Rinkwitz-Brandt S., Justus M., Oldenettel I., Arnold H.-H., Bober E.;
"Distinct temporal expression of mouse Nkx-5.1 and Nkx-5.2 homeobox
genes during brain and ear development.";
Mech. Dev. 52:371-381(1995).
[6]
DEVELOPMENTAL STAGE.
PubMed=8970821; DOI=10.1016/S0378-5955(96)00093-7;
Rinkwitz-Brandt S., Arnold H.H., Bober E.;
"Regionalized expression of Nkx5-1, Nkx5-2, Pax2 and sek genes during
mouse inner ear development.";
Hear. Res. 99:129-138(1996).
[7]
FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
PubMed=9435283;
Wang W., Van De Water T., Lufkin T.;
"Inner ear and maternal reproductive defects in mice lacking the Hmx3
homeobox gene.";
Development 125:621-634(1998).
[8]
FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
PubMed=9389661;
Hadrys T., Braun T., Rinkwitz-Brandt S., Arnold H.-H., Bober E.;
"Nkx5-1 controls semicircular canal formation in the mouse inner
ear.";
Development 125:33-39(1998).
[9]
DNA-BINDING, AND MUTAGENESIS OF GLN-276.
PubMed=10206974; DOI=10.1074/jbc.274.17.11635;
Amendt B.A., Sutherland L.B., Russo A.F.;
"Transcriptional antagonism between Hmx1 and Nkx2.5 for a shared DNA-
binding site.";
J. Biol. Chem. 274:11635-11642(1999).
[10]
TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
PubMed=11748138;
Wang W., Chan E.K., Baron S., Van de Water T., Lufkin T.;
"Hmx2 homeobox gene control of murine vestibular morphogenesis.";
Development 128:5017-5029(2001).
[11]
INDUCTION.
PubMed=11731242; DOI=10.1016/S0925-4773(01)00550-0;
Adamska M., Herbrand H., Adamski M., Krueger M., Braun T., Bober E.;
"FGFs control the patterning of the inner ear but are not able to
induce the full ear program.";
Mech. Dev. 109:303-313(2001).
[12]
INDUCTION.
PubMed=12874121; DOI=10.1242/dev.00628;
Zheng W., Huang L., Wei Z.B., Silvius D., Tang B., Xu P.-X.;
"The role of Six1 in mammalian auditory system development.";
Development 130:3989-4000(2003).
[13]
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=15363417; DOI=10.1016/j.devcel.2004.06.016;
Wang W., Grimmer J.F., Van De Water T.R., Lufkin T.;
"Hmx2 and Hmx3 homeobox genes direct development of the murine inner
ear and hypothalamus and can be functionally replaced by Drosophila
Hmx.";
Dev. Cell 7:439-453(2004).
[14]
INDUCTION.
PubMed=14695375; DOI=10.1242/dev.00943;
Ozaki H., Nakamura K., Funahashi J., Ikeda K., Yamada G., Tokano H.,
Okamura H.O., Kitamura K., Muto S., Kotaki H., Sudo K., Horai R.,
Iwakura Y., Kawakami K.;
"Six1 controls patterning of the mouse otic vesicle.";
Development 131:551-562(2004).
-!- FUNCTION: Transcription factor involved in specification of
neuronal cell types and which is required for inner ear and
hypothalamus development. Binds to the 5'-CAAGTG-3' core sequence.
Controls semicircular canal formation in the inner ear. Also
required for hypothalamic/pituitary axis of the CNS.
{ECO:0000269|PubMed:15363417, ECO:0000269|PubMed:9389661,
ECO:0000269|PubMed:9435283}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
-!- TISSUE SPECIFICITY: Expressed in the developing CNS, including a
specific expression in vestibular structures throughout inner ear
development. {ECO:0000269|PubMed:11748138,
ECO:0000269|PubMed:9389661, ECO:0000269|PubMed:9435283}.
-!- DEVELOPMENTAL STAGE: Begins at embryonic day 10.5 in the
developing ear, hypothalamus, the neural tube and dorsal root
ganglia. It continues to be active throughout prenatal life in
discrete regions of the brain with an anterior border in the
ventral diencephalon at the optic chiasma and expression domains
in mesencephalon, metencephalon, and myelencephalon. At
midgestation, it is also expressed in mesenchyme of the head and
branchial arches, and in some cranial ganglia, as well as in
derivatives of neural crest, such as the truncus sympathicus and
myenteric ganglia. In inner ear, it is expressed between E13.5 and
birth in non-sensory epithelium of the semicircular canals,
utricle and saccule. Also expressed in the cochlea, where the
expression is restricted to the stria vascularis.
{ECO:0000269|PubMed:11748138, ECO:0000269|PubMed:7510254,
ECO:0000269|PubMed:8541222, ECO:0000269|PubMed:8970821}.
-!- INDUCTION: Regulated by Six1 and FGFs in inner ear.
{ECO:0000269|PubMed:11731242, ECO:0000269|PubMed:12874121,
ECO:0000269|PubMed:14695375}.
-!- DISRUPTION PHENOTYPE: Mice display abnormal circling behavior and
severe vestibular defects owing to a depletion of sensory cells in
the saccule and utricle, and a complete loss of the horizontal
semicircular canal crista, as well as a fusion of the utricle and
saccule endolymphatic spaces into a common utriculosaccular
cavity. Moreover, most females have a reproductive defect: females
can be fertilized and their embryos undergo normal preimplantation
development, but the embryos fail to implant successfully in the
uterus and subsequently die. Mice lacking both Hmx2 and Hmx3 show
a complete loss of balance, postnatal dwarfism, defects in
neuroendocrine system, disturbed hypothalamic-pituitary axis and
subsequent die. Defects caused in mice lacking both Hmx2 and Hmx3
can be rescued by expressing the Drosophila Hmx protein.
{ECO:0000269|PubMed:15363417, ECO:0000269|PubMed:9389661,
ECO:0000269|PubMed:9435283}.
-!- SIMILARITY: Belongs to the HMX homeobox family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=CAA53079.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305};
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EMBL; X75330; CAA53079.1; ALT_SEQ; mRNA.
EMBL; AJ009935; CAA08911.1; -; Genomic_DNA.
EMBL; CH466531; EDL17717.1; -; Genomic_DNA.
EMBL; BC139482; AAI39483.1; -; mRNA.
EMBL; BC139483; AAI39484.1; -; mRNA.
CCDS; CCDS21917.1; -.
PIR; I48690; I48690.
RefSeq; NP_032283.3; NM_008257.3.
RefSeq; XP_006507441.1; XM_006507378.3.
RefSeq; XP_006507442.1; XM_006507379.3.
UniGene; Mm.323562; -.
ProteinModelPortal; P42581; -.
SMR; P42581; -.
STRING; 10090.ENSMUSP00000039018; -.
PhosphoSitePlus; P42581; -.
MaxQB; P42581; -.
PaxDb; P42581; -.
PRIDE; P42581; -.
Ensembl; ENSMUST00000046093; ENSMUSP00000039018; ENSMUSG00000040148.
GeneID; 15373; -.
KEGG; mmu:15373; -.
UCSC; uc009kbo.2; mouse.
CTD; 340784; -.
MGI; MGI:107160; Hmx3.
eggNOG; KOG0485; Eukaryota.
eggNOG; ENOG4111R8D; LUCA.
GeneTree; ENSGT00910000144003; -.
HOGENOM; HOG000231923; -.
HOVERGEN; HBG098273; -.
InParanoid; P42581; -.
KO; K09349; -.
OMA; VYYSHPI; -.
OrthoDB; EOG091G0RNV; -.
TreeFam; TF320562; -.
ChiTaRS; Hmx3; mouse.
PRO; PR:P42581; -.
Proteomes; UP000000589; Chromosome 7.
Bgee; ENSMUSG00000040148; -.
CleanEx; MM_HMX3; -.
Genevisible; P42581; MM.
GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0007420; P:brain development; IGI:MGI.
GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
GO; GO:0043583; P:ear development; IMP:CACAO.
GO; GO:0007566; P:embryo implantation; IMP:MGI.
GO; GO:0042472; P:inner ear morphogenesis; IMP:MGI.
GO; GO:0060135; P:maternal process involved in female pregnancy; IMP:MGI.
GO; GO:0050885; P:neuromuscular process controlling balance; IMP:MGI.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR020479; Homeobox_metazoa.
Pfam; PF00046; Homeobox; 1.
PRINTS; PR00024; HOMEOBOX.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
Complete proteome; Developmental protein; Differentiation;
DNA-binding; Homeobox; Neurogenesis; Nucleus; Phosphoprotein;
Reference proteome; Transcription; Transcription regulation.
CHAIN 1 356 Homeobox protein HMX3.
/FTId=PRO_0000048949.
DNA_BIND 227 286 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
COMPBIAS 2 52 Pro-rich.
COMPBIAS 57 84 Ala-rich.
COMPBIAS 319 325 Poly-Ala.
MOD_RES 153 153 Phosphoserine.
{ECO:0000250|UniProtKB:A6NHT5}.
MOD_RES 180 180 Phosphoserine.
{ECO:0000250|UniProtKB:A6NHT5}.
MUTAGEN 276 276 Q->K: Abolishes DNA-binding.
{ECO:0000269|PubMed:10206974}.
CONFLICT 68 68 A -> V (in Ref. 2; CAA08911).
{ECO:0000305}.
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


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