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MIXL1 (Mix1 homeobox-like 1 (Xenopus laevis))

Written2010-08Aaron Raymond, Lalitha Nagarajan
Departement of Genetics, Box 1010, MD Anderson cancer Center, 1515 Holcombe Blvd, Houston Tx 77030, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesMix1 homeobox (Xenopus laevis)-like 1
Mix1 homeobox-like 1 (Xenopus laevis)
Alias_symbol (synonym)MILD1
MIXL
Other aliasMGC138179
MIX
HGNC (Hugo) MIXL1
LocusID (NCBI) 83881
Atlas_Id 47624
Location 1q42.12  [Link to chromosome band 1q42]
Location_base_pair Starts at 226411319 and ends at 226414756 bp from pter ( according to hg19-Feb_2009)  [Mapping MIXL1.png]
Local_order MIXL1 is flanked on its 3' end by Lin9. This proximity is evolutionarily conserved.
 
  MIXL1 genomic context on 1q42.12.
Fusion genes
(updated 2016)
PARP1 (1q42.12) / MIXL1 (1q42.12)

DNA/RNA

 
  Genomic organisation of MIXL1.
Description MIXL1 is 2131 bps long and consists of two exons of length 393 bp and 306 bp, and one intron (Guo et al., 2002; Sahr et al., 2002).
Transcription MIXL1 is transcribed to a full-length 699 bp mRNA. There are no known splice variants.
Pseudogene There are no known pseudogenes for MIXL1.

Protein

 
  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.
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.

Implicated in

Note
  
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).
  
  
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).
  
  
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).
  
  
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).
  
  
Entity Chronic myeloid leukemia
Disease MIXL1 is aberrantly expressed in the K562 established cell line (Guo et al., 2002).
  
  
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).
  
  
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).
  

Bibliography

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
 
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
 
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
 
Amino terminal tyrosine phosphorylation of human MIXL1.
Guo W, Nagarajan L.
J Mol Signal. 2006 Dec 5;1:6.
PMID 17224082
 
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
 
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
 
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
 
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
 

Citation

This paper should be referenced as such :
Raymond, A ; Nagarajan, L
MIXL1 (Mix1 homeobox-like 1 (Xenopus laevis))
Atlas Genet Cytogenet Oncol Haematol. 2011;15(5):419-421.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MIXL1ID47624ch1q42.html


External links

Nomenclature
HGNC (Hugo)MIXL1   13363
Cards
AtlasMIXL1ID47624ch1q42
Entrez_Gene (NCBI)MIXL1  83881  Mix paired-like homeobox
AliasesMILD1; MIX; MIXL
GeneCards (Weizmann)MIXL1
Ensembl hg19 (Hinxton)ENSG00000185155 [Gene_View]  chr1:226411319-226414756 [Contig_View]  MIXL1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000185155 [Gene_View]  chr1:226411319-226414756 [Contig_View]  MIXL1 [Vega]
ICGC DataPortalENSG00000185155
TCGA cBioPortalMIXL1
AceView (NCBI)MIXL1
Genatlas (Paris)MIXL1
WikiGenes83881
SOURCE (Princeton)MIXL1
Genetics Home Reference (NIH)MIXL1
Genomic and cartography
GoldenPath hg19 (UCSC)MIXL1  -     chr1:226411319-226414756 +  1q42.12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MIXL1  -     1q42.12   [Description]    (hg38-Dec_2013)
EnsemblMIXL1 - 1q42.12 [CytoView hg19]  MIXL1 - 1q42.12 [CytoView hg38]
Mapping of homologs : NCBIMIXL1 [Mapview hg19]  MIXL1 [Mapview hg38]
OMIM609852   
Gene and transcription
Genbank (Entrez)AF211891 BC111974 BC113441 BC143784 CX165667
RefSeq transcript (Entrez)NM_001282402 NM_031944
RefSeq genomic (Entrez)NC_000001 NC_018912 NT_167186 NW_004929294
Consensus coding sequences : CCDS (NCBI)MIXL1
Cluster EST : UnigeneHs.282079 [ NCBI ]
CGAP (NCI)Hs.282079
Alternative Splicing GalleryENSG00000185155
Gene ExpressionMIXL1 [ NCBI-GEO ]   MIXL1 [ EBI - ARRAY_EXPRESS ]   MIXL1 [ SEEK ]   MIXL1 [ MEM ]
Gene Expression Viewer (FireBrowse)MIXL1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)83881
GTEX Portal (Tissue expression)MIXL1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9H2W2   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9H2W2  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9H2W2
Splice isoforms : SwissVarQ9H2W2
PhosPhoSitePlusQ9H2W2
Domaine pattern : Prosite (Expaxy)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)   
Domains : Interpro (EBI)Homeobox_CS    Homeobox_dom    Homeodomain-like   
Domain families : Pfam (Sanger)Homeobox (PF00046)   
Domain families : Pfam (NCBI)pfam00046   
Domain families : Smart (EMBL)HOX (SM00389)  
Conserved Domain (NCBI)MIXL1
DMDM Disease mutations83881
Blocks (Seattle)MIXL1
SuperfamilyQ9H2W2
Human Protein AtlasENSG00000185155
Peptide AtlasQ9H2W2
HPRD10086
IPIIPI01012275   IPI00011187   
Protein Interaction databases
DIP (DOE-UCLA)Q9H2W2
IntAct (EBI)Q9H2W2
FunCoupENSG00000185155
BioGRIDMIXL1
STRING (EMBL)MIXL1
ZODIACMIXL1
Ontologies - Pathways
QuickGOQ9H2W2
Ontology : AmiGOnuclear chromatin  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II distal enhancer sequence-specific DNA binding  core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  RNA polymerase II transcription factor binding  RNA polymerase II repressing transcription factor binding  transcriptional activator activity, RNA polymerase II transcription factor binding  transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding  hematopoietic progenitor cell differentiation  transcription from RNA polymerase II promoter  gastrulation  endoderm development  heart development  endodermal cell differentiation  cell migration involved in gastrulation  protein homodimerization activity  positive regulation of transcription from RNA polymerase II promoter  digestive tract development  negative regulation of hematopoietic progenitor cell differentiation  positive regulation of mesoderm development  
Ontology : EGO-EBInuclear chromatin  RNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II distal enhancer sequence-specific DNA binding  core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  RNA polymerase II transcription factor binding  RNA polymerase II repressing transcription factor binding  transcriptional activator activity, RNA polymerase II transcription factor binding  transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding  hematopoietic progenitor cell differentiation  transcription from RNA polymerase II promoter  gastrulation  endoderm development  heart development  endodermal cell differentiation  cell migration involved in gastrulation  protein homodimerization activity  positive regulation of transcription from RNA polymerase II promoter  digestive tract development  negative regulation of hematopoietic progenitor cell differentiation  positive regulation of mesoderm development  
NDEx NetworkMIXL1
Atlas of Cancer Signalling NetworkMIXL1
Wikipedia pathwaysMIXL1
Orthology - Evolution
OrthoDB83881
GeneTree (enSembl)ENSG00000185155
Phylogenetic Trees/Animal Genes : TreeFamMIXL1
HOVERGENQ9H2W2
HOGENOMQ9H2W2
Homologs : HomoloGeneMIXL1
Homology/Alignments : Family Browser (UCSC)MIXL1
Gene fusions - Rearrangements
Fusion : MitelmanPARP1/MIXL1 [1q42.12/1q42.12]  [t(1;1)(q42;q42)]  
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMIXL1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MIXL1
dbVarMIXL1
ClinVarMIXL1
1000_GenomesMIXL1 
Exome Variant ServerMIXL1
ExAC (Exome Aggregation Consortium)MIXL1 (select the gene name)
Genetic variants : HAPMAP83881
Genomic Variants (DGV)MIXL1 [DGVbeta]
DECIPHER (Syndromes)1:226411319-226414756  ENSG00000185155
CONAN: Copy Number AnalysisMIXL1 
Mutations
ICGC Data PortalMIXL1 
TCGA Data PortalMIXL1 
Broad Tumor PortalMIXL1
OASIS PortalMIXL1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMIXL1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMIXL1
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
BioMutasearch 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)
intoGenMIXL1
NCG5 (London)MIXL1
Cancer3DMIXL1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM609852   
Orphanet
MedgenMIXL1
Genetic Testing Registry MIXL1
NextProtQ9H2W2 [Medical]
TSGene83881
GENETestsMIXL1
Huge Navigator MIXL1 [HugePedia]
snp3D : Map Gene to Disease83881
BioCentury BCIQMIXL1
ClinGenMIXL1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD83881
Chemical/Pharm GKB GenePA134976348
Clinical trialMIXL1
Miscellaneous
canSAR (ICR)MIXL1 (select the gene name)
Probes
Litterature
PubMed11 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMIXL1
EVEXMIXL1
GoPubMedMIXL1
iHOPMIXL1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:35:29 CEST 2017

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