MIXL1_MOUSE
ID MIXL1_MOUSE Reviewed; 231 AA.
AC Q9WUI0; Q9QZ61;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Homeobox protein MIXL1;
DE AltName: Full=Homeodomain protein MIX;
DE Short=mMix;
DE AltName: Full=MIX1 homeobox-like protein 1;
DE AltName: Full=Mix.1 homeobox-like protein;
GN Name=Mixl1; Synonyms=Mix, Mml;
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.
RX PubMed=10495285; DOI=10.1016/s0925-4773(99)00135-5;
RA Pearce J.J.H., Evans M.J.;
RT "Mml, a mouse Mix-like gene expressed in the primitive streak.";
RL Mech. Dev. 87:189-192(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv; TISSUE=Embryo;
RX PubMed=11084649;
RX DOI=10.1002/1097-0177(2000)9999:9999<::aid-dvdy1070>3.0.co;2-o;
RA Robb L., Hartley L., Begley C.G., Brodnicki T.C., Copeland N.G.,
RA Gilbert D.J., Jenkins N.A., Elefanty A.G.;
RT "Cloning, expression analysis, and chromosomal localization of murine and
RT human homologues of a Xenopus mix gene.";
RL Dev. Dyn. 219:497-504(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 13-231,
RP AND DNA-BINDING.
RC STRAIN=129/SvJ;
RX PubMed=12095687; DOI=10.1016/s0378-1119(02)00590-5;
RA Sahr K., Dias D.C., Sanchez R., Chen D., Chen S.W., Gudas L.J., Baron M.H.;
RT "Structure, upstream promoter region, and functional domains of a mouse and
RT human Mix paired-like homeobox gene.";
RL Gene 291:135-147(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12117810; DOI=10.1242/dev.129.15.3597;
RA Hart A.H., Hartley L., Sourris K., Stadler E.S., Li R., Stanley E.G.,
RA Tam P.P.L., Elefanty A.G., Robb L.;
RT "Mixl1 is required for axial mesendoderm morphogenesis and patterning in
RT the murine embryo.";
RL Development 129:3597-3608(2002).
RN [6]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12619131; DOI=10.1002/dvdy.10263;
RA Mohn D., Chen S.W., Dias D.C., Weinstein D.C., Dyer M.A., Sahr K.,
RA Ducker C.E., Zahradka E., Keller G., Zaret K.S., Gudas L.J., Baron M.H.;
RT "Mouse Mix gene is activated early during differentiation of ES and F9 stem
RT cells and induces endoderm in frog embryos.";
RL Dev. Dyn. 226:446-459(2003).
RN [7]
RP INDUCTION.
RX PubMed=15982639; DOI=10.1016/j.bbrc.2005.06.044;
RA Hart A.H., Willson T.A., Wong M., Parker K., Robb L.;
RT "Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and
RT FoxH1.";
RL Biochem. Biophys. Res. Commun. 333:1361-1369(2005).
RN [8]
RP FUNCTION.
RX PubMed=15673572; DOI=10.1242/dev.01657;
RA Ng E.S., Azzola L., Sourris K., Robb L., Stanley E.G., Elefanty A.G.;
RT "The primitive streak gene Mixl1 is required for efficient haematopoiesis
RT and BMP4-induced ventral mesoderm patterning in differentiating ES cells.";
RL Development 132:873-884(2005).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=16433620; DOI=10.1089/scd.2005.14.656;
RA Mossman A.K., Sourris K., Ng E., Stanley E.G., Elefanty A.G.;
RT "Mixl1 and oct4 proteins are transiently co-expressed in differentiating
RT mouse and human embryonic stem cells.";
RL Stem Cells Dev. 14:656-663(2005).
RN [10]
RP FUNCTION.
RX PubMed=16403910; DOI=10.1182/blood-2005-10-4120;
RA Willey S., Ayuso-Sacido A., Zhang H., Fraser S.T., Sahr K.E., Adlam M.J.,
RA Kyba M., Daley G.Q., Keller G., Baron M.H.;
RT "Acceleration of mesoderm development and expansion of hematopoietic
RT progenitors in differentiating ES cells by the mouse Mix-like homeodomain
RT transcription factor.";
RL Blood 107:3122-3130(2006).
RN [11]
RP FUNCTION.
RX PubMed=17060613; DOI=10.1073/pnas.0607776103;
RA Glaser S., Metcalf D., Wu L., Hart A.H., DiRago L., Mifsud S., D'Amico A.,
RA Dagger S., Campo C., Chan A.C., Izon D.J., Robb L.;
RT "Enforced expression of the homeobox gene Mixl1 impairs hematopoietic
RT differentiation and results in acute myeloid leukemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16460-16465(2006).
RN [12]
RP FUNCTION.
RX PubMed=17151016; DOI=10.1242/dev.02724;
RA Tam P.P.L., Khoo P.-L., Lewis S.L., Bildsoe H., Wong N., Tsang T.E.,
RA Gad J.M., Robb L.;
RT "Sequential allocation and global pattern of movement of the definitive
RT endoderm in the mouse embryo during gastrulation.";
RL Development 134:251-260(2007).
RN [13]
RP INDUCTION.
RX PubMed=17568773; DOI=10.1038/sj.emboj.7601753;
RA Izzi L., Silvestri C., von Both I., Labbe E., Zakin L., Wrana J.L.,
RA Attisano L.;
RT "Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early
RT mouse development.";
RL EMBO J. 26:3132-3143(2007).
RN [14]
RP FUNCTION.
RX PubMed=17446562; DOI=10.1634/stemcells.2006-0681;
RA Izumi N., Era T., Akimaru H., Yasunaga M., Nishikawa S.;
RT "Dissecting the molecular hierarchy for mesendoderm differentiation through
RT a combination of embryonic stem cell culture and RNA interference.";
RL Stem Cells 25:1664-1674(2007).
CC -!- FUNCTION: Transcription factor that play a central role in proper axial
CC mesendoderm morphogenesis and endoderm formation. Required for
CC efficient differentiation of cells from the primitive streak stage to
CC blood, by acting early in the recruitment and/or expansion of
CC mesodermal progenitors to the hemangioblastic and hematopoietic
CC lineages. Also involved in the morphogenesis of the heart and the gut
CC during embryogenesis. Acts as a negative regulator of brachyury
CC expression. {ECO:0000269|PubMed:12117810, ECO:0000269|PubMed:15673572,
CC ECO:0000269|PubMed:16403910, ECO:0000269|PubMed:17060613,
CC ECO:0000269|PubMed:17151016, ECO:0000269|PubMed:17446562}.
CC -!- INTERACTION:
CC Q9WUI0; Q9WUI0: Mixl1; NbExp=2; IntAct=EBI-13637214, EBI-13637214;
CC Q9WUI0; P20293: Tbxt; NbExp=7; IntAct=EBI-13637214, EBI-13637160;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:12619131}.
CC -!- TISSUE SPECIFICITY: Expressed in the primitive streak of the
CC gastrulating embryo, and marks cells destined to form mesoderm and
CC endoderm. Present in differentiating embryonic stem cells (at protein
CC level). {ECO:0000269|PubMed:12619131, ECO:0000269|PubMed:16433620}.
CC -!- DEVELOPMENTAL STAGE: Initially expressed in visceral endoderm and
CC becomes restricted to primitive streak and nascent mesoderm at
CC gastrulation. This includes the hemangioblast, a precursor of
CC hematopoietic and vascular stem cells. At 5.5 dpc, it is expressed
CC symmetrically in the visceral endoderm but by 6.0 dpc this expression
CC is noticeably asymmetric. At 6.5 dpc, expression is restricted to the
CC nascent primitive streak and persists in the primitive streak through
CC 7.5-9.5 dpc, marking those cells fated to form extra-embryonic and
CC lateral mesoderm. {ECO:0000269|PubMed:10495285,
CC ECO:0000269|PubMed:12619131}.
CC -!- INDUCTION: By TGF-beta. Regulated by Nodal in mesendoderm
CC morphogenesis. Regulated by FOXH1, which acts as a negative regulator
CC by recruiting GSC to promoter during early development.
CC {ECO:0000269|PubMed:15982639, ECO:0000269|PubMed:17568773}.
CC -!- DISRUPTION PHENOTYPE: Mice display defects in mesendoderm morphogenesis
CC and patterning during development. Embryos show a marked thickening of
CC the primitive streak. By the early somite stage, embryonic development
CC is arrested, with the formation of abnormal head folds, foreshortened
CC body axis, absence of heart tube and gut, deficient paraxial mesoderm,
CC and an enlarged midline tissue mass that replaces the notochord.
CC Development of extra-embryonic structures is generally normal except
CC that the allantois is often disproportionately large for the size of
CC the mutant embryo. {ECO:0000269|PubMed:12117810}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. {ECO:0000305}.
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DR EMBL; AF135063; AAD25543.1; -; mRNA.
DR EMBL; AF154573; AAK59867.1; -; mRNA.
DR EMBL; AF201959; AAF08314.1; -; mRNA.
DR EMBL; AF447591; AAM77218.1; -; Genomic_DNA.
DR EMBL; BC099876; AAH99876.1; -; mRNA.
DR EMBL; BC099877; AAH99877.1; -; mRNA.
DR CCDS; CCDS15571.1; -.
DR RefSeq; NP_038757.1; NM_013729.3.
DR RefSeq; XP_006496934.1; XM_006496871.1.
DR AlphaFoldDB; Q9WUI0; -.
DR SMR; Q9WUI0; -.
DR BioGRID; 205138; 10.
DR IntAct; Q9WUI0; 16.
DR STRING; 10090.ENSMUSP00000027778; -.
DR PhosphoSitePlus; Q9WUI0; -.
DR PaxDb; Q9WUI0; -.
DR PeptideAtlas; Q9WUI0; -.
DR PRIDE; Q9WUI0; -.
DR Antibodypedia; 20764; 152 antibodies from 31 providers.
DR DNASU; 27217; -.
DR Ensembl; ENSMUST00000027778; ENSMUSP00000027778; ENSMUSG00000026497.
DR GeneID; 27217; -.
DR KEGG; mmu:27217; -.
DR UCSC; uc007dwp.1; mouse.
DR CTD; 83881; -.
DR MGI; MGI:1351322; Mixl1.
DR VEuPathDB; HostDB:ENSMUSG00000026497; -.
DR eggNOG; KOG0849; Eukaryota.
DR GeneTree; ENSGT00940000162190; -.
DR HOGENOM; CLU_104890_0_0_1; -.
DR InParanoid; Q9WUI0; -.
DR OMA; HHSACET; -.
DR OrthoDB; 1270742at2759; -.
DR PhylomeDB; Q9WUI0; -.
DR TreeFam; TF334098; -.
DR BioGRID-ORCS; 27217; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Mixl1; mouse.
DR PRO; PR:Q9WUI0; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9WUI0; protein.
DR Bgee; ENSMUSG00000026497; Expressed in embryonic post-anal tail and 22 other tissues.
DR Genevisible; Q9WUI0; MM.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0042074; P:cell migration involved in gastrulation; IMP:MGI.
DR GO; GO:0048565; P:digestive tract development; IMP:MGI.
DR GO; GO:0007492; P:endoderm development; IMP:MGI.
DR GO; GO:0001706; P:endoderm formation; IMP:MGI.
DR GO; GO:0035987; P:endodermal cell differentiation; IDA:BHF-UCL.
DR GO; GO:0007369; P:gastrulation; IMP:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IDA:BHF-UCL.
DR GO; GO:0030097; P:hemopoiesis; IDA:MGI.
DR GO; GO:1901533; P:negative regulation of hematopoietic progenitor cell differentiation; IDA:BHF-UCL.
DR GO; GO:2000382; P:positive regulation of mesoderm development; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
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; IPR042917; MIXL1.
DR PANTHER; PTHR47656; PTHR47656; 1.
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 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Homeobox; Nucleus;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..231
FT /note="Homeobox protein MIXL1"
FT /id="PRO_0000311334"
FT DNA_BIND 86..145
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 23..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 53..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 231 AA; 24844 MW; 59DA80A5E7E6EE33 CRC64;
MAAAGSQQLQ FAEGAAFPIF PAAHPGGQLL PAMRPASGLP AAPHDSRAPA ATQCFPNRDS
SPTAQTPAGL DPPGPSKGSA APSAPQRRKR TSFSSEQLQL LELVFRQTMY PDIHLRERLA
ALTLLPESRI QVWFQNRRAK SRRQSGKSFQ PLSSRRGVFL HCPAPGTEAR CLKPQLPLEA
DVNHVPDPSM TGGGVCTSGS QSFETYSSLS EDIGSKLDSW EEHIFSALGN F
