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Protein

Homeobox protein MIXL1

Gene

Mixl1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor that play a central role in proper axial mesendoderm morphogenesis and endoderm formation. Required for efficient differentiation of cells from the primitive streak stage to blood, by acting early in the recruitment and/or expansion of mesodermal progenitors to the hemangioblastic and hematopoietic lineages. Also involved in the morphogenesis of the heart and the gut during embryogenesis. Acts as a negative regulator of brachyury expression.6 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi86 – 14560HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • cell migration involved in gastrulation Source: MGI
  • digestive tract development Source: MGI
  • endodermal cell differentiation Source: BHF-UCL
  • endoderm development Source: MGI
  • endoderm formation Source: MGI
  • gastrulation Source: MGI
  • heart development Source: MGI
  • hematopoietic progenitor cell differentiation Source: BHF-UCL
  • hemopoiesis Source: MGI
  • negative regulation of hematopoietic progenitor cell differentiation Source: BHF-UCL
  • positive regulation of mesoderm development Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • transcription from RNA polymerase II promoter Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein MIXL1
Alternative name(s):
Homeodomain protein MIX
Short name:
mMix
MIX1 homeobox-like protein 1
Mix.1 homeobox-like protein
Gene namesi
Name:Mixl1
Synonyms:Mix, Mml
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1351322. Mixl1.

Subcellular locationi

GO - Cellular componenti

  • nuclear chromatin Source: BHF-UCL
  • nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice display defects in mesendoderm morphogenesis and patterning during development. Embryos show a marked thickening of the primitive streak. By the early somite stage, embryonic development is arrested, with the formation of abnormal head folds, foreshortened body axis, absence of heart tube and gut, deficient paraxial mesoderm, and an enlarged midline tissue mass that replaces the notochord. Development of extra-embryonic structures is generally normal except that the allantois is often disproportionately large for the size of the mutant embryo.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 231231Homeobox protein MIXL1PRO_0000311334Add
BLAST

Proteomic databases

PaxDbiQ9WUI0.
PRIDEiQ9WUI0.

PTM databases

PhosphoSiteiQ9WUI0.

Expressioni

Tissue specificityi

Expressed in the primitive streak of the gastrulating embryo, and marks cells destined to form mesoderm and endoderm. Present in differentiating embryonic stem cells (at protein level).2 Publications

Developmental stagei

Initially expressed in visceral endoderm and becomes restricted to primitive streak and nascent mesoderm at gastrulation. This includes the hemangioblast, a precursor of hematopoietic and vascular stem cells. At E5.5, it is expressed symmetrically in the visceral endoderm but by E6.0 this expression is noticeably asymmetric. At E6.5, expression is restricted to the nascent primitive streak and persists in the primitive streak through E7.5-E9.5, marking those cells fated to form extra-embryonic and lateral mesoderm.2 Publications

Inductioni

By TGF-beta. Regulated by Nodal in mesendoderm morphogenesis. Regulated by FOXH1, which acts as a negative regulator by recruiting GSC to promoter during early development.2 Publications

Gene expression databases

BgeeiQ9WUI0.
CleanExiMM_MIXL1.
GenevisibleiQ9WUI0. MM.

Interactioni

GO - Molecular functioni

  • protein homodimerization activity Source: BHF-UCL
  • RNA polymerase II repressing transcription factor binding Source: BHF-UCL
  • RNA polymerase II transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi205138. 10 interactions.
STRINGi10090.ENSMUSP00000027778.

Structurei

3D structure databases

ProteinModelPortaliQ9WUI0.
SMRiQ9WUI0. Positions 86-144.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the paired homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0849. Eukaryota.
ENOG410XS01. LUCA.
GeneTreeiENSGT00820000126963.
HOGENOMiHOG000113594.
HOVERGENiHBG106595.
InParanoidiQ9WUI0.
OMAiVFRRTRY.
OrthoDBiEOG7DRJ3Q.
PhylomeDBiQ9WUI0.
TreeFamiTF334098.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9WUI0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAAGSQQLQ FAEGAAFPIF PAAHPGGQLL PAMRPASGLP AAPHDSRAPA
60 70 80 90 100
ATQCFPNRDS SPTAQTPAGL DPPGPSKGSA APSAPQRRKR TSFSSEQLQL
110 120 130 140 150
LELVFRQTMY PDIHLRERLA ALTLLPESRI QVWFQNRRAK SRRQSGKSFQ
160 170 180 190 200
PLSSRRGVFL HCPAPGTEAR CLKPQLPLEA DVNHVPDPSM TGGGVCTSGS
210 220 230
QSFETYSSLS EDIGSKLDSW EEHIFSALGN F
Length:231
Mass (Da):24,844
Last modified:November 1, 1999 - v1
Checksum:i59DA80A5E7E6EE33
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF135063 mRNA. Translation: AAD25543.1.
AF154573 mRNA. Translation: AAK59867.1.
AF201959 mRNA. Translation: AAF08314.1.
AF447591 Genomic DNA. Translation: AAM77218.1.
BC099876 mRNA. Translation: AAH99876.1.
BC099877 mRNA. Translation: AAH99877.1.
CCDSiCCDS15571.1.
RefSeqiNP_038757.1. NM_013729.3.
XP_006496934.1. XM_006496871.1.
UniGeneiMm.103647.

Genome annotation databases

EnsembliENSMUST00000027778; ENSMUSP00000027778; ENSMUSG00000026497.
GeneIDi27217.
KEGGimmu:27217.
UCSCiuc007dwp.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF135063 mRNA. Translation: AAD25543.1.
AF154573 mRNA. Translation: AAK59867.1.
AF201959 mRNA. Translation: AAF08314.1.
AF447591 Genomic DNA. Translation: AAM77218.1.
BC099876 mRNA. Translation: AAH99876.1.
BC099877 mRNA. Translation: AAH99877.1.
CCDSiCCDS15571.1.
RefSeqiNP_038757.1. NM_013729.3.
XP_006496934.1. XM_006496871.1.
UniGeneiMm.103647.

3D structure databases

ProteinModelPortaliQ9WUI0.
SMRiQ9WUI0. Positions 86-144.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205138. 10 interactions.
STRINGi10090.ENSMUSP00000027778.

PTM databases

PhosphoSiteiQ9WUI0.

Proteomic databases

PaxDbiQ9WUI0.
PRIDEiQ9WUI0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000027778; ENSMUSP00000027778; ENSMUSG00000026497.
GeneIDi27217.
KEGGimmu:27217.
UCSCiuc007dwp.1. mouse.

Organism-specific databases

CTDi83881.
MGIiMGI:1351322. Mixl1.

Phylogenomic databases

eggNOGiKOG0849. Eukaryota.
ENOG410XS01. LUCA.
GeneTreeiENSGT00820000126963.
HOGENOMiHOG000113594.
HOVERGENiHBG106595.
InParanoidiQ9WUI0.
OMAiVFRRTRY.
OrthoDBiEOG7DRJ3Q.
PhylomeDBiQ9WUI0.
TreeFamiTF334098.

Miscellaneous databases

NextBioi305112.
PROiQ9WUI0.
SOURCEiSearch...

Gene expression databases

BgeeiQ9WUI0.
CleanExiMM_MIXL1.
GenevisibleiQ9WUI0. MM.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mml, a mouse Mix-like gene expressed in the primitive streak."
    Pearce J.J.H., Evans M.J.
    Mech. Dev. 87:189-192(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
  2. "Cloning, expression analysis, and chromosomal localization of murine and human homologues of a Xenopus mix gene."
    Robb L., Hartley L., Begley C.G., Brodnicki T.C., Copeland N.G., Gilbert D.J., Jenkins N.A., Elefanty A.G.
    Dev. Dyn. 219:497-504(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: 129/Sv.
    Tissue: Embryo.
  3. "Structure, upstream promoter region, and functional domains of a mouse and human Mix paired-like homeobox gene."
    Sahr K., Dias D.C., Sanchez R., Chen D., Chen S.W., Gudas L.J., Baron M.H.
    Gene 291:135-147(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] OF 13-231, DNA-BINDING.
    Strain: 129/SvJ.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  5. "Mixl1 is required for axial mesendoderm morphogenesis and patterning in the murine embryo."
    Hart A.H., Hartley L., Sourris K., Stadler E.S., Li R., Stanley E.G., Tam P.P.L., Elefanty A.G., Robb L.
    Development 129:3597-3608(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  6. "Mouse Mix gene is activated early during differentiation of ES and F9 stem cells and induces endoderm in frog embryos."
    Mohn D., Chen S.W., Dias D.C., Weinstein D.C., Dyer M.A., Sahr K., Ducker C.E., Zahradka E., Keller G., Zaret K.S., Gudas L.J., Baron M.H.
    Dev. Dyn. 226:446-459(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  7. "Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and FoxH1."
    Hart A.H., Willson T.A., Wong M., Parker K., Robb L.
    Biochem. Biophys. Res. Commun. 333:1361-1369(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  8. "The primitive streak gene Mixl1 is required for efficient haematopoiesis and BMP4-induced ventral mesoderm patterning in differentiating ES cells."
    Ng E.S., Azzola L., Sourris K., Robb L., Stanley E.G., Elefanty A.G.
    Development 132:873-884(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Mixl1 and oct4 proteins are transiently co-expressed in differentiating mouse and human embryonic stem cells."
    Mossman A.K., Sourris K., Ng E., Stanley E.G., Elefanty A.G.
    Stem Cells Dev. 14:656-663(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  10. "Acceleration of mesoderm development and expansion of hematopoietic progenitors in differentiating ES cells by the mouse Mix-like homeodomain transcription factor."
    Willey S., Ayuso-Sacido A., Zhang H., Fraser S.T., Sahr K.E., Adlam M.J., Kyba M., Daley G.Q., Keller G., Baron M.H.
    Blood 107:3122-3130(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Enforced expression of the homeobox gene Mixl1 impairs hematopoietic differentiation and results in acute myeloid leukemia."
    Glaser S., Metcalf D., Wu L., Hart A.H., DiRago L., Mifsud S., D'Amico A., Dagger S., Campo C., Chan A.C., Izon D.J., Robb L.
    Proc. Natl. Acad. Sci. U.S.A. 103:16460-16465(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "Sequential allocation and global pattern of movement of the definitive endoderm in the mouse embryo during gastrulation."
    Tam P.P.L., Khoo P.-L., Lewis S.L., Bildsoe H., Wong N., Tsang T.E., Gad J.M., Robb L.
    Development 134:251-260(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. "Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early mouse development."
    Izzi L., Silvestri C., von Both I., Labbe E., Zakin L., Wrana J.L., Attisano L.
    EMBO J. 26:3132-3143(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  14. "Dissecting the molecular hierarchy for mesendoderm differentiation through a combination of embryonic stem cell culture and RNA interference."
    Izumi N., Era T., Akimaru H., Yasunaga M., Nishikawa S.
    Stem Cells 25:1664-1674(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiMIXL1_MOUSE
AccessioniPrimary (citable) accession number: Q9WUI0
Secondary accession number(s): Q9QZ61
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 1, 1999
Last modified: December 9, 2015
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.