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| Representation and comparison of Human MIXL1, Mouse Mixl1, Chicken Mixl1, and Xenopus Mix.1 protein domains. The Mix family of proteins all contain evolutionarily conserved homeodomain and C-terminal acidic domains. Human, mouse and chicken also share a conserved N-terminal proline rich domain. While these three domains are highly conserved, the remainder of protein varies significantly between species. |
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Description | MIXL1 is a paired type homeobox protein which has 232 amino acids, and a molecular weight of 27 kDa. The protein contains three identified domains: a proline-rich domain, a paired-type homeobox, and a c-terminal acidic domain. While MIXL1 does have an expected weight of 27 kDa, it will migrate on a Western Blot at 36 kDa (Guo et al., 2002). MIXL1 is phosphorylated in the amino-terminal region at Tyr20 (Guo et al., 2006). |
Expression | MIXL1 expression is restricted to embryonic mesendoderm precursors and adult hematopoietic stem cells and progenitors. |
Localisation | MIXL1 expression is predominantly nuclear. |
Function | MIXL1 is paired-type homeobox transcription factor, and as such preferentially binds to the DNA sequence TAAT. MIXL1 homologs preferentially bind as dimers to 11 bp palindromic sequences consisting of two TAAT segments and a three nucleotide spacer (Wilson et al., 1993). MIXL1 expression is required for both mesendoderm development and hematopoiesis. The MIXL1 homologs are necessary intermediate factors to the BMP4 (bone morphogenetic protein 4)-mediated mesendoderm formation, as dominant negative mutants block this pathway (Mead et al., 1996). Development into mesoderm and endoderm cell layers is dependant on the expression collaborating factors. MIXL1 expression is required for the early stages of hematopoiesis and is normally expressed in all early hematopoietic precursor types (Guo et al., 2002). |
Homology | MIXL1 is a member of the Mix/Bix family of transcription factors, of which it is the only member identified in humans. It is also a member of the larger grouping of paired type homeoboxes, a family of genes which share sequence similarity in the homeobox domain with paired box family (PAX). MIXL1 shares 41% sequence similarity to its chicken homolog, and 69% to its mouse homolog. Its homeodomain is highly conserved across species, sharing identity of 66% to that of Xenopus Mix.1, 79% to that of chicken Mixl1, and 94% to that of mouse Mixl1. |
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Entity | Hodgkin's lymphoma |
Disease | MIXL1 is aberrantly expressed in patient samples derived from Hodgkin's lymphoma, along with the following Hodgkin cell lines: L-1236, L-428, HD-MyZ, HD-LM2, MDA-E, MDA-V, KM-H2, and Daudi (Drakos et al., 2007). |
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Entity | T-cell NHL lymphoma |
Disease | MIXL1 is aberrantly expressed in patient samples derived from High Grade T-cell non-Hodgkin's lymphoma, along with the following T-cell NHL established lines: Karpas 299, MAC2A, SR-786, and Peer (Drakos et al., 2007; Guo et al., 2002). |
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Entity | B-cell NHL lymphoma |
Disease | MIXL1 is aberrantly expressed in patient samples derived from High Grade B-cell non-Hodgkin's lymphoma, along with the following B-cell NHL established lines: SKI-DLBL, DB, DOHH1, IM-9, Mino, Sp-53, Z-138, and CJ (Drakos et al., 2007; Guo et al., 2002). |
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Entity | Acute myeloid leukemia |
Disease | Retroviral transduction of Mixl1 into mouse bone marrow resulted in transplantable acute myeloid leukemia in all lethally irradiated recipient mice after a latency period (Glaser et al., 2006). The following established AML cell lines aberrantly express MIXL1: U937, KG1, and ML3 (Guo et al., 2002). |
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Entity | Chronic myeloid leukemia |
Disease | MIXL1 is aberrantly expressed in the K562 established cell line (Guo et al., 2002). |
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Entity | T-cell leukemia |
Disease | The Mixl1 promoter in mouse was identified as a site of viral insertion, using the Moloney murine leukemia virus, which collaborates with loss of p27 in induction of lymphomagenesis (Hwang et al., 2002). MIXL1 is aberrantly expressed in the following T-cell leukemia established lines: Jurkat, SKW-3, and CEM (Drakos et al., 2007; Guo et al., 2002). |
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Entity | B-cell leukemia |
Disease | MIXL1 is aberrantly expressed in the following B-cell leukemia established lines: NALM6, REH-1 (Drakos et al., 2007; Guo et al., 2002). |
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Differential expression of the human MIXL1 gene product in non-Hodgkin and Hodgkin lymphomas. |
Drakos E, Rassidakis GZ, Leventaki V, Guo W, Medeiros LJ, Nagarajan L. |
Hum Pathol. 2007 Mar;38(3):500-7. |
PMID 17303500 |
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Enforced expression of the homeobox gene Mixl1 impairs hematopoietic differentiation and results in acute myeloid leukemia. |
Glaser S, Metcalf D, Wu L, Hart AH, DiRago L, Mifsud S, D'Amico A, Dagger S, Campo C, Chan AC, Izon DJ, Robb L. |
Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16460-5. Epub 2006 Oct 23. |
PMID 17060613 |
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A human Mix-like homeobox gene MIXL shows functional similarity to Xenopus Mix.1. |
Guo W, Chan AP, Liang H, Wieder ED, Molldrem JJ, Etkin LD, Nagarajan L. |
Blood. 2002 Jul 1;100(1):89-95. |
PMID 12070013 |
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Amino terminal tyrosine phosphorylation of human MIXL1. |
Guo W, Nagarajan L. |
J Mol Signal. 2006 Dec 5;1:6. |
PMID 17224082 |
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Identification of oncogenes collaborating with p27Kip1 loss by insertional mutagenesis and high-throughput insertion site analysis. |
Hwang HC, Martins CP, Bronkhorst Y, Randel E, Berns A, Fero M, Clurman BE. |
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11293-8. Epub 2002 Jul 31. |
PMID 12151601 |
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BMP-4-responsive regulation of dorsal-ventral patterning by the homeobox protein Mix.1. |
Mead PE, Brivanlou IH, Kelley CM, Zon LI. |
Nature. 1996 Jul 25;382(6589):357-60. |
PMID 8684465 |
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Structure, upstream promoter region, and functional domains of a mouse and human Mix paired-like homeobox gene. |
Sahr K, Dias DC, Sanchez R, Chen D, Chen SW, Gudas LJ, Baron MH. |
Gene. 2002 May 29;291(1-2):135-47. |
PMID 12095687 |
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Cooperative dimerization of paired class homeo domains on DNA. |
Wilson D, Sheng G, Lecuit T, Dostatni N, Desplan C. |
Genes Dev. 1993 Nov;7(11):2120-34. |
PMID 7901121 |
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| Nomenclature |
HGNC (Hugo) | MIXL1 13363 |
| Cards |
Atlas | MIXL1ID47624ch1q42 |
Entrez_Gene (NCBI) | MIXL1 Mix paired-like homeobox |
Aliases | MILD1; MIX; MIXL |
GeneCards (Weizmann) | MIXL1 |
Ensembl hg19 (Hinxton) | ENSG00000185155 [Gene_View] |
Ensembl hg38 (Hinxton) | ENSG00000185155 [Gene_View]  ENSG00000185155 [Sequence] chr1:226223664-226227060 [Contig_View] MIXL1 [Vega] |
ICGC DataPortal | ENSG00000185155 |
TCGA cBioPortal | MIXL1 |
AceView (NCBI) | MIXL1 |
Genatlas (Paris) | MIXL1 |
SOURCE (Princeton) | MIXL1 |
Genetics Home Reference (NIH) | MIXL1 |
| Genomic and cartography |
GoldenPath hg38 (UCSC) | MIXL1 - chr1:226223664-226227060 + 1q42.12 [Description] (hg38-Dec_2013) |
GoldenPath hg19 (UCSC) | MIXL1 - 1q42.12 [Description] (hg19-Feb_2009) |
GoldenPath | MIXL1 - 1q42.12 [CytoView hg19] MIXL1 - 1q42.12 [CytoView hg38] |
ImmunoBase | ENSG00000185155 |
genome Data Viewer NCBI | MIXL1 [Mapview hg19] |
OMIM | 609852 |
| Gene and transcription |
Genbank (Entrez) | AF211891 BC111974 BC113441 BC143784 CX165667 |
RefSeq transcript (Entrez) | NM_001282402 NM_031944 |
RefSeq genomic (Entrez) | |
Consensus coding sequences : CCDS (NCBI) | MIXL1 |
Alternative Splicing Gallery | ENSG00000185155 |
Gene Expression | MIXL1 [ NCBI-GEO ] MIXL1 [ EBI - ARRAY_EXPRESS ]
MIXL1 [ SEEK ] MIXL1 [ MEM ] |
Gene Expression Viewer (FireBrowse) | MIXL1 [ Firebrowse - Broad ] |
Genevisible | Expression of MIXL1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]   |
BioGPS (Tissue expression) | 83881 |
GTEX Portal (Tissue expression) | MIXL1 |
Human Protein Atlas | ENSG00000185155-MIXL1 [pathology] [cell] [tissue] |
| Protein : pattern, domain, 3D structure |
UniProt/SwissProt | Q9H2W2 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction] |
NextProt | Q9H2W2 [Sequence] [Exons] [Medical] [Publications] |
With graphics : InterPro | Q9H2W2 |
Splice isoforms : SwissVar | Q9H2W2 |
PhosPhoSitePlus | Q9H2W2 |
Domaine pattern : Prosite (Expaxy) | HOMEOBOX_1 (PS00027) HOMEOBOX_2 (PS50071) |
Domains : Interpro (EBI) | Homeobox-like_sf Homeobox_CS Homeobox_dom MIXL1 |
Domain families : Pfam (Sanger) | Homeodomain (PF00046) |
Domain families : Pfam (NCBI) | pfam00046 |
Domain families : Smart (EMBL) | HOX (SM00389) |
Conserved Domain (NCBI) | MIXL1 |
Blocks (Seattle) | MIXL1 |
Superfamily | Q9H2W2 |
Human Protein Atlas [tissue] | ENSG00000185155-MIXL1 [tissue] |
Peptide Atlas | Q9H2W2 |
HPRD | 10086 |
IPI | IPI01012275 IPI00011187 |
| Protein Interaction databases |
DIP (DOE-UCLA) | Q9H2W2 |
IntAct (EBI) | Q9H2W2 |
BioGRID | MIXL1 |
STRING (EMBL) | MIXL1 |
ZODIAC | MIXL1 |
| Ontologies - Pathways |
QuickGO | Q9H2W2 |
Ontology : AmiGO | "nuclear chromatin nuclear chromatin RNA polymerase II proximal promoter sequence-specific DNA binding RNA polymerase II proximal promoter sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific proximal promoter sequence-specific DNA binding RNA polymerase II transcription factor binding RNA polymerase II transcription factor binding RNA polymerase II repressing transcription factor binding DNA-binding transcription activator activity, RNA polymerase II-specific hematopoietic progenitor cell differentiation nucleus nucleoplasm gastrulation endoderm development heart development endodermal cell differentiation cell migration involved in gastrulation protein homodimerization activity positive regulation of transcription by RNA polymerase II digestive tract development negative regulation of hematopoietic progenitor cell differentiation positive regulation of mesoderm development" |
Ontology : EGO-EBI | "nuclear chromatin nuclear chromatin RNA polymerase II proximal promoter sequence-specific DNA binding RNA polymerase II proximal promoter sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific proximal promoter sequence-specific DNA binding RNA polymerase II transcription factor binding RNA polymerase II transcription factor binding RNA polymerase II repressing transcription factor binding DNA-binding transcription activator activity, RNA polymerase II-specific hematopoietic progenitor cell differentiation nucleus nucleoplasm gastrulation endoderm development heart development endodermal cell differentiation cell migration involved in gastrulation protein homodimerization activity positive regulation of transcription by RNA polymerase II digestive tract development negative regulation of hematopoietic progenitor cell differentiation positive regulation of mesoderm development" |
NDEx Network | MIXL1 |
Atlas of Cancer Signalling Network | MIXL1 |
Wikipedia pathways | MIXL1 |
| Orthology - Evolution |
OrthoDB | 83881 |
GeneTree (enSembl) | ENSG00000185155 |
Phylogenetic Trees/Animal Genes : TreeFam | MIXL1 |
HOGENOM | Q9H2W2 |
Homologs : HomoloGene | MIXL1 |
Homology/Alignments : Family Browser (UCSC) | MIXL1 |
| Gene fusions - Rearrangements |
Fusion : Mitelman | PARP1/MIXL1 [1q42.12/1q42.12]   |
Fusion : Fusion_Hub | C1ORF21--MIXL1 MIXL1--PARP1 |
Fusion : Quiver | MIXL1 |
| Polymorphisms : SNP and Copy number variants |
NCBI Variation Viewer | MIXL1 [hg38] |
dbVar | MIXL1 |
ClinVar | MIXL1 |
Monarch | MIXL1 |
1000_Genomes | MIXL1 |
Exome Variant Server | MIXL1 |
GNOMAD Browser | ENSG00000185155 |
Varsome Browser | MIXL1 |
Genomic Variants (DGV) | MIXL1 [DGVbeta] |
DECIPHER | MIXL1 [patients] [syndromes] [variants] [genes] |
CONAN: Copy Number Analysis | MIXL1 |
| Mutations |
ICGC Data Portal | MIXL1 |
TCGA Data Portal | MIXL1 |
Broad Tumor Portal | MIXL1 |
OASIS Portal | MIXL1 [ Somatic mutations - Copy number] |
Somatic Mutations in Cancer : COSMIC | MIXL1 [overview] [genome browser] [tissue] [distribution] |
Somatic Mutations in Cancer : COSMIC3D | MIXL1 |
Mutations and Diseases : HGMD | MIXL1 |
LOVD (Leiden Open Variation Database) | Whole genome datasets |
LOVD (Leiden Open Variation Database) | LOVD - Leiden Open Variation Database |
LOVD (Leiden Open Variation Database) | LOVD 3.0 shared installation |
BioMuta | search MIXL1 |
DgiDB (Drug Gene Interaction Database) | MIXL1 |
DoCM (Curated mutations) | MIXL1 (select the gene name) |
CIViC (Clinical Interpretations of Variants in Cancer) | MIXL1 (select a term) |
intoGen | MIXL1 |
NCG6 (London) | select MIXL1 |
Cancer3D | MIXL1(select the gene name) |
Impact of mutations | [PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser] |
| Diseases |
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OMIM | 609852 |
Orphanet | |
DisGeNET | MIXL1 |
Medgen | MIXL1 |
Genetic Testing Registry | MIXL1
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NextProt | Q9H2W2 [Medical] |
GENETests | MIXL1 |
Target Validation | MIXL1 |
Huge Navigator |
MIXL1 [HugePedia] |
ClinGen | MIXL1 |
| Clinical trials, drugs, therapy |
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MyCancerGenome | MIXL1 |
Protein Interactions : CTD | |
Pharm GKB Gene | PA134976348 |
Pharos | Q9H2W2 |
Clinical trial | MIXL1 |
| Miscellaneous |
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canSAR (ICR) | MIXL1 (select the gene name) |
Harmonizome | MIXL1 |
DataMed Index | MIXL1 |
| Probes |
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| Litterature |
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PubMed | 13 Pubmed reference(s) in Entrez |
GeneRIFs | Gene References Into Functions (Entrez) |
EVEX | MIXL1 |