ID   MSX2_MOUSE              Reviewed;         267 AA.
AC   Q03358; Q63856;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 2.
DT   24-JAN-2024, entry version 193.
DE   RecName: Full=Homeobox protein MSX-2;
DE   AltName: Full=Homeobox protein Hox-8-1;
GN   Name=Msx2; Synonyms=Hox-8.1, Msx-2;
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].
RC   STRAIN=C57BL/6J;
RX   PubMed=1682128; DOI=10.1242/dev.112.4.1053;
RA   Monaghan A.P., Davidson D.R., Sime C., Graham E., Baldock R.,
RA   Bhattacharya S.S., Hill R.E.;
RT   "The Msh-like homeobox genes define domains in the developing vertebrate
RT   eye.";
RL   Development 112:1053-1061(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8098007; DOI=10.1006/geno.1993.1149;
RA   Bell J.R., Noveen A., Liu Y.H., Ma L., Dobias S., Kundu R., Luo W., Xia Y.;
RT   "Genomic structure, chromosomal location, and evolution of the mouse Hox 8
RT   gene.";
RL   Genomics 16:123-131(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 142-202.
RX   PubMed=1673109; DOI=10.1016/0378-1119(91)90182-b;
RA   Holland P.W.H.;
RT   "Cloning and evolutionary analysis of msh-like homeobox genes from mouse,
RT   zebrafish and ascidian.";
RL   Gene 98:253-257(1991).
RN   [4]
RP   FUNCTION.
RX   PubMed=1677742; DOI=10.1038/352429a0;
RA   Davidson D.R., Crawley A., Hill R.E., Tickle C.;
RT   "Position-dependent expression of two related homeobox genes in developing
RT   vertebrate limbs.";
RL   Nature 352:429-431(1991).
RN   [5]
RP   INTERACTION WITH MINT.
RX   PubMed=10451362; DOI=10.1021/bi990967j;
RA   Newberry E.P., Latifi T., Towler D.A.;
RT   "The RRM domain of MINT, a novel msx2 binding protein, recognizes and
RT   regulates the rat osteocalcin promoter.";
RL   Biochemistry 38:10678-10690(1999).
RN   [6]
RP   FUNCTION, INDUCTION, AND DNA-BINDING.
RX   PubMed=15383550; DOI=10.1074/jbc.m404145200;
RA   Kim Y.J., Lee M.H., Wozney J.M., Cho J.Y., Ryoo H.M.;
RT   "Bone morphogenetic protein-2-induced alkaline phosphatase expression is
RT   stimulated by Dlx5 and repressed by Msx2.";
RL   J. Biol. Chem. 279:50773-50780(2004).
CC   -!- FUNCTION: Acts as a transcriptional regulator in bone development.
CC       Represses the ALPL promoter activity and antagonizes the stimulatory
CC       effect of DLX5 on ALPL expression during osteoblast differentiation.
CC       Probable morphogenetic role. May play a role in limb-pattern formation.
CC       In osteoblasts, suppresses transcription driven by the osteocalcin FGF
CC       response element (OCFRE). Binds to the homeodomain-response element of
CC       the ALPL promoter. {ECO:0000269|PubMed:15383550,
CC       ECO:0000269|PubMed:1677742}.
CC   -!- SUBUNIT: Interacts with MINT. Interacts with XRCC6 (Ku70) and XRCC5
CC       (Ku80) (By similarity). {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q03358; Q9QYH6: Maged1; NbExp=5; IntAct=EBI-1801354, EBI-1801274;
CC       Q03358; P25233: Ndn; NbExp=3; IntAct=EBI-1801354, EBI-1801080;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- TISSUE SPECIFICITY: Expressed in mesenchymal tissue in the developing
CC       spinal cord and limbs.
CC   -!- INDUCTION: Up-regulated by BMP2. {ECO:0000269|PubMed:15383550}.
CC   -!- SIMILARITY: Belongs to the Msh homeobox family. {ECO:0000305}.
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DR   EMBL; L11739; AAA03477.1; -; Unassigned_DNA.
DR   EMBL; L11738; AAA03477.1; JOINED; Unassigned_DNA.
DR   EMBL; S60460; AAC60657.2; -; Genomic_DNA.
DR   EMBL; S60698; AAC60657.2; JOINED; Genomic_DNA.
DR   EMBL; X59252; CAA41945.1; -; mRNA.
DR   EMBL; M38576; AAA37824.1; -; Genomic_DNA.
DR   CCDS; CCDS26522.1; -.
DR   PIR; A46122; A46122.
DR   PIR; PS0410; PS0410.
DR   PIR; S18814; S18814.
DR   RefSeq; NP_038629.2; NM_013601.2.
DR   AlphaFoldDB; Q03358; -.
DR   SMR; Q03358; -.
DR   BioGRID; 201537; 8.
DR   IntAct; Q03358; 3.
DR   STRING; 10090.ENSMUSP00000021922; -.
DR   iPTMnet; Q03358; -.
DR   PhosphoSitePlus; Q03358; -.
DR   PaxDb; 10090-ENSMUSP00000021922; -.
DR   ProteomicsDB; 287511; -.
DR   Antibodypedia; 905; 437 antibodies from 31 providers.
DR   DNASU; 17702; -.
DR   Ensembl; ENSMUST00000021922.10; ENSMUSP00000021922.8; ENSMUSG00000021469.10.
DR   GeneID; 17702; -.
DR   KEGG; mmu:17702; -.
DR   UCSC; uc007qnw.1; mouse.
DR   AGR; MGI:97169; -.
DR   CTD; 4488; -.
DR   MGI; MGI:97169; Msx2.
DR   VEuPathDB; HostDB:ENSMUSG00000021469; -.
DR   eggNOG; KOG0492; Eukaryota.
DR   GeneTree; ENSGT00940000159824; -.
DR   HOGENOM; CLU_072675_0_0_1; -.
DR   InParanoid; Q03358; -.
DR   OMA; PVGYNMY; -.
DR   OrthoDB; 4848801at2759; -.
DR   PhylomeDB; Q03358; -.
DR   TreeFam; TF350699; -.
DR   BioGRID-ORCS; 17702; 1 hit in 77 CRISPR screens.
DR   PRO; PR:Q03358; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   RNAct; Q03358; Protein.
DR   Bgee; ENSMUSG00000021469; Expressed in tooth bud and 241 other cell types or tissues.
DR   ExpressionAtlas; Q03358; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005667; C:transcription regulator complex; IPI:MGI.
DR   GO; GO:0003677; F:DNA binding; IDA:MGI.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:MGI.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR   GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IMP:NTNU_SB.
DR   GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR   GO; GO:0090427; P:activation of meiosis; IPI:MGI.
DR   GO; GO:0009952; P:anterior/posterior pattern specification; IGI:MGI.
DR   GO; GO:0030509; P:BMP signaling pathway; IDA:MGI.
DR   GO; GO:0060349; P:bone morphogenesis; IGI:MGI.
DR   GO; GO:0060346; P:bone trabecula formation; IMP:MGI.
DR   GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IMP:MGI.
DR   GO; GO:0051216; P:cartilage development; IMP:MGI.
DR   GO; GO:0061311; P:cell surface receptor signaling pathway involved in heart development; IGI:MGI.
DR   GO; GO:0071392; P:cellular response to estradiol stimulus; IDA:MGI.
DR   GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:MGI.
DR   GO; GO:0002063; P:chondrocyte development; IMP:MGI.
DR   GO; GO:0042733; P:embryonic digit morphogenesis; IGI:MGI.
DR   GO; GO:0035115; P:embryonic forelimb morphogenesis; IGI:MGI.
DR   GO; GO:0035116; P:embryonic hindlimb morphogenesis; IGI:MGI.
DR   GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
DR   GO; GO:0048598; P:embryonic morphogenesis; IBA:GO_Central.
DR   GO; GO:0035880; P:embryonic nail plate morphogenesis; IGI:MGI.
DR   GO; GO:0070166; P:enamel mineralization; IMP:MGI.
DR   GO; GO:0003416; P:endochondral bone growth; IMP:MGI.
DR   GO; GO:0003198; P:epithelial to mesenchymal transition involved in endocardial cushion formation; IGI:MGI.
DR   GO; GO:0060364; P:frontal suture morphogenesis; IMP:MGI.
DR   GO; GO:0061180; P:mammary gland epithelium development; IGI:MGI.
DR   GO; GO:0097152; P:mesenchymal cell apoptotic process; IGI:MGI.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IGI:MGI.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR   GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:MGI.
DR   GO; GO:0045617; P:negative regulation of keratinocyte differentiation; IMP:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0042476; P:odontogenesis; IMP:MGI.
DR   GO; GO:0001503; P:ossification; IMP:MGI.
DR   GO; GO:0002076; P:osteoblast development; IMP:MGI.
DR   GO; GO:0001649; P:osteoblast differentiation; IDA:UniProtKB.
DR   GO; GO:0003151; P:outflow tract morphogenesis; IGI:MGI.
DR   GO; GO:0003148; P:outflow tract septum morphogenesis; IGI:MGI.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0030513; P:positive regulation of BMP signaling pathway; IGI:MGI.
DR   GO; GO:2001055; P:positive regulation of mesenchymal cell apoptotic process; IGI:MGI.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:MGI.
DR   GO; GO:0051795; P:positive regulation of timing of catagen; IMP:MGI.
DR   GO; GO:0042981; P:regulation of apoptotic process; IDA:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IGI:MGI.
DR   GO; GO:0048863; P:stem cell differentiation; IGI:MGI.
DR   GO; GO:0006366; P:transcription by RNA polymerase II; ISO:MGI.
DR   GO; GO:0042060; P:wound healing; IMP:MGI.
DR   GO; GO:0035313; P:wound healing, spreading of epidermal cells; IMP:MGI.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR009057; Homeobox-like_sf.
DR   InterPro; IPR017970; Homeobox_CS.
DR   InterPro; IPR001356; Homeobox_dom.
DR   InterPro; IPR020479; Homeobox_metazoa.
DR   PANTHER; PTHR24338; HOMEOBOX PROTEIN MSX; 1.
DR   PANTHER; PTHR24338:SF10; HOMEOBOX PROTEIN MSX-2; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00024; HOMEOBOX.
DR   SMART; SM00389; HOX; 1.
DR   SUPFAM; SSF46689; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   Genevisible; Q03358; MM.
PE   1: Evidence at protein level;
KW   Developmental protein; DNA-binding; Homeobox; Nucleus; Osteogenesis;
KW   Reference proteome; Repressor; Transcription; Transcription regulation.
FT   CHAIN           1..267
FT                   /note="Homeobox protein MSX-2"
FT                   /id="PRO_0000049100"
FT   DNA_BIND        142..201
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          1..42
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          104..132
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CONFLICT        11
FT                   /note="F -> FF (in Ref. 1; CAA41945)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        89
FT                   /note="A -> R (in Ref. 2; AAC60657)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        263
FT                   /note="M -> I (in Ref. 1; CAA41945)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        266
FT                   /note="L -> V (in Ref. 1; CAA41945)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   267 AA;  28915 MW;  F2F4528D6E9C951E CRC64;
     MASPTKGGDL FSSDEEGPAV LAGPGPGPGG AEGSAEERRV KVSSLPFSVE ALMSDKKPPK
     ESPAVPPDCA SAGAVLRPLL LPGHGVRDAH SPGPLVKPFE TASVKSENSE DGAPWIQEPG
     RYSPPPRHMS PTTCTLRKHK TNRKPRTPFT TSQLLALERK FRQKQYLSIA ERAEFSSSLN
     LTETQVKIWF QNRRAKAKRL QEAELEKLKM AAKPMLPSGF SLPFPINSPL QAASIYGASY
     PFHRPVLPIP PVGLYATPVG YGMYHLS
//