ID MSX1_BOVIN Reviewed; 303 AA.
AC O02786;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 2.
DT 24-JAN-2024, entry version 120.
DE RecName: Full=Homeobox protein MSX-1 {ECO:0000305};
DE AltName: Full=Msh homeobox 1-like protein;
GN Name=MSX1 {ECO:0000250|UniProtKB:P13297};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Tooth;
RX PubMed=7626784; DOI=10.3109/10425179509030972;
RA Iimura T., Oida S., Takeda K., Maruoka Y., Shimokawa H., Ibaraki K.,
RA Sasaki S.;
RT "Molecular cloning and sequence of bovine Msx-1 homeobox-containing gene
RT cDNA from a bovine odontoblast library.";
RL DNA Seq. 5:233-237(1995).
CC -!- FUNCTION: Acts as a transcriptional repressor (By similarity). Capable
CC of transcription autoinactivation (By similarity). Binds to the
CC consensus sequence 5'-C/GTAAT-3' in downstream activin regulatory
CC elements (DARE) in the gene promoter, thereby repressing the
CC transcription of CGA/alpha-GSU and GNRHR (By similarity). Represses
CC transcription of myoblast differentiation factors (By similarity).
CC Binds to core enhancer regions in target gene promoters of myoblast
CC differentiation factors with binding specificity facilitated by
CC interaction with PIAS1 (By similarity). Recruits histone H3
CC methyltransferases such as EHMT2/G9a to gene promoter regions which
CC leads to inhibition of myoblast differentiation via transcriptional
CC repression of differentiation factors (By similarity). Regulates, in a
CC stage-specific manner, a developmental program of gene expression in
CC the fetal tooth bud that controls odontoblast differentiation and
CC proliferation of dental mesenchymal cells (By similarity). At the bud
CC stage, required for mesenchymal molar tooth bud development via
CC facilitating reciprocal signaling between dental epithelial and
CC mesenchymal cells (By similarity). May also regulate expression of Wnt
CC antagonists such as DKK2 and SFPR2 in the developing tooth mesenchyme
CC (By similarity). Required for BMP4 expression in dental mesenchyme
CC cells (By similarity). Also, in response to BMP4, required for BMP4
CC expression in neighboring dental epithelial cells (By similarity).
CC Required for maximal FGF4-induced expression of SDC1 in dental
CC mesenchyme cells (By similarity). Also in response to SDC1, required
CC for SDC1 expression in neighboring dental epithelial cells (By
CC similarity). At the early bell stage, acts to drive proliferation of
CC dental mesenchyme cells, however during the late bell stage acts as an
CC homeostatic regulator of the cell cycle (By similarity). Regulates
CC proliferation and inhibits premature mesenchymal odontogenesis during
CC the bell stage via inhibition of the Wnt signaling component CTNNB1 and
CC subsequent repression of the odontoblast differentiation factors BMP2,
CC BMP4, LEF1, ALPL and BGLAP/OCN (By similarity). Additionally, required
CC for correct development and fusion of the palatal shelves and embryonic
CC mandibular formation (By similarity). Plays a role in embryonic bone
CC formation of the middle ear, skull and nasal bones (By similarity).
CC Required for correct formation and thickness of the nail plate (By
CC similarity). May play a role in limb-pattern formation (By similarity).
CC {ECO:0000250|UniProtKB:P13297, ECO:0000250|UniProtKB:P28360}.
CC -!- SUBUNIT: Interacts with CREBBP/CBP, TBP and SP1; interaction with these
CC transcription activators may inhibit autoinactivation (By similarity).
CC Interacts (via homeobox domain) with EHMT2/G9a (By similarity).
CC Interacts with EHMT1/GLP (By similarity). Interacts (via C-terminus)
CC with PIAS1 (via N-terminus); the interaction is required for the
CC localization of both proteins to the nuclear periphery and specific
CC binding of MSX1 to the core enhancer region in target gene promoters
CC (By similarity). Interacts with H1-5 (By similarity).
CC {ECO:0000250|UniProtKB:P13297}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P13297}.
CC Note=Interaction with EHMT2/G9a is required for localization to the
CC nuclear periphery (By similarity). Interaction with PIAS1 is required
CC for localization to the nuclear periphery (By similarity).
CC {ECO:0000250|UniProtKB:P13297}.
CC -!- PTM: Sumoylated by PIAS1, desumoylated by SENP1 (By similarity).
CC Sumoylation of Lys-15 and Lys-133 not required for interaction with H1-
CC 5, transcriptional repression, inhibition of myoblast differentiation,
CC or binding to gene promoters (By similarity).
CC {ECO:0000250|UniProtKB:P13297}.
CC -!- SIMILARITY: Belongs to the Msh homeobox family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-7 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20367.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; D30750; BAA20367.1; ALT_INIT; mRNA.
DR RefSeq; NP_777223.1; NM_174798.2.
DR AlphaFoldDB; O02786; -.
DR SMR; O02786; -.
DR STRING; 9913.ENSBTAP00000014447; -.
DR PaxDb; 9913-ENSBTAP00000014447; -.
DR GeneID; 286872; -.
DR KEGG; bta:286872; -.
DR CTD; 4487; -.
DR eggNOG; KOG0492; Eukaryota.
DR InParanoid; O02786; -.
DR OrthoDB; 4848801at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0034399; C:nuclear periphery; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0048598; P:embryonic morphogenesis; IBA:GO_Central.
DR GO; GO:0048839; P:inner ear development; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:1901330; P:negative regulation of odontoblast differentiation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0043584; P:nose development; ISS:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0042482; P:positive regulation of odontogenesis; ISS:UniProtKB.
DR GO; GO:0042481; P:regulation of odontogenesis; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060021; P:roof of mouth development; ISS:UniProtKB.
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:SF8; HOMEOBOX PROTEIN MSX-1; 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.
PE 2: Evidence at transcript level;
KW Developmental protein; DNA-binding; Homeobox; Isopeptide bond; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..303
FT /note="Homeobox protein MSX-1"
FT /id="PRO_0000049082"
FT DNA_BIND 172..231
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 74..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..161
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..271
FT /note="Required for interaction with EHMT2"
FT /evidence="ECO:0000250|UniProtKB:P13297"
FT CROSSLNK 15
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P13297"
FT CROSSLNK 133
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P13297"
SQ SEQUENCE 303 AA; 31668 MW; 847FA220365E498F CRC64;
MAPAADMTSL PLGVKVEDPP FGKPAGGGGG QTPSTTAATA AAMGADAEGA KPKVSPSLLP
FSVEALMADH RKPGAKKSVL AASEGAQAAG GSAKPLGARP GSLAAPDAPS SPRPLGHFSV
GGLLKLPEDA LVKAESPEKP ERTPWMQNPR FSPPPSRRLS PPACTLRKHK TNRKPRTPFT
TAQLLALERK FRQKQYLSIA ERAEFSSSLS LTETQVKIWF QNRRAKAKRL QEAELEKLKM
AAKPMLPPAT FGLSFPLGGP AAVAAPAGAS LYGASGPFQR AALPVAPVGL YTAHVGYSMY
HLT
//
