MIXL1 (Mix1 homeobox-like 1 (Xenopus laevis))
2010-08-01 Aaron Raymond , Lalitha Nagarajan AffiliationDepartement of Genetics, Box 1010, MD Anderson cancer Center, 1515 Holcombe Blvd, Houston Tx 77030, USA
Identity
HGNC
LOCATION
1q42.12
IMAGE
LEGEND
MIXL1 genomic context on 1q42.12.
LOCUSID
ALIAS
MILD1,MIX,MIXL
FUSION GENES
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.
Proteins
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).
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.
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
Entity name
Disease
MIXL1 is aberrantly expressed in patient samples derived from Hodgkins 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 name
Disease
MIXL1 is aberrantly expressed in patient samples derived from High Grade T-cell non-Hodgkins 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 name
B-cell NHL lymphoma
Disease
MIXL1 is aberrantly expressed in patient samples derived from High Grade B-cell non-Hodgkins 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 name
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).
The following established AML cell lines aberrantly express MIXL1: U937, KG1, and ML3 (Guo et al., 2002).
Entity name
Disease
MIXL1 is aberrantly expressed in the K562 established cell line (Guo et al., 2002).
Entity name
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).
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 name
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).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17303500 | 2007 | Differential expression of the human MIXL1 gene product in non-Hodgkin and Hodgkin lymphomas. | Drakos E et al |
| 17060613 | 2006 | Enforced expression of the homeobox gene Mixl1 impairs hematopoietic differentiation and results in acute myeloid leukemia. | Glaser S et al |
| 12070013 | 2002 | A human Mix-like homeobox gene MIXL shows functional similarity to Xenopus Mix.1. | Guo W et al |
| 17224082 | 2006 | Amino terminal tyrosine phosphorylation of human MIXL1. | Guo W et al |
| 12151601 | 2002 | Identification of oncogenes collaborating with p27Kip1 loss by insertional mutagenesis and high-throughput insertion site analysis. | Hwang HC et al |
| 8684465 | 1996 | BMP-4-responsive regulation of dorsal-ventral patterning by the homeobox protein Mix.1. | Mead PE et al |
| 12095687 | 2002 | Structure, upstream promoter region, and functional domains of a mouse and human Mix paired-like homeobox gene. | Sahr K et al |
| 7901121 | 1993 | Cooperative dimerization of paired class homeo domains on DNA. | Wilson D et al |
Other Information
Locus ID:
NCBI: 83881
MIM: 609852
HGNC: 13363
Ensembl: ENSG00000185155
Variants:
dbSNP: 83881
ClinVar: 83881
TCGA: ENSG00000185155
COSMIC: MIXL1
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000185155 | ENST00000366810 | Q9H2W2 |
| ENSG00000185155 | ENST00000366810 | A0A024R3T7 |
| ENSG00000185155 | ENST00000542034 | Q9H2W2 |
Expression (GTEx)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 25521758 | 2015 | Mixl1 and Flk1 Are Key Players of Wnt/TGF-β Signaling During DMSO-Induced Mesodermal Specification in P19 cells. | 10 |
| 25521758 | 2015 | Mixl1 and Flk1 Are Key Players of Wnt/TGF-β Signaling During DMSO-Induced Mesodermal Specification in P19 cells. | 10 |
| 25544748 | 2014 | A role for BMP-induced homeobox gene MIXL1 in acute myelogenous leukemia and identification of type I BMP receptor as a potential target for therapy. | 13 |
| 25544748 | 2014 | A role for BMP-induced homeobox gene MIXL1 in acute myelogenous leukemia and identification of type I BMP receptor as a potential target for therapy. | 13 |
| 22164283 | 2011 | Brachyury and related Tbx proteins interact with the Mixl1 homeodomain protein and negatively regulate Mixl1 transcriptional activity. | 9 |
| 22164283 | 2011 | Brachyury and related Tbx proteins interact with the Mixl1 homeodomain protein and negatively regulate Mixl1 transcriptional activity. | 9 |
| 18032708 | 2008 | Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak-like cells and enables isolation of primitive hematopoietic precursors. | 90 |
| 18032708 | 2008 | Targeting a GFP reporter gene to the MIXL1 locus of human embryonic stem cells identifies human primitive streak-like cells and enables isolation of primitive hematopoietic precursors. | 90 |
| 17303500 | 2007 | Differential expression of the human MIXL1 gene product in non-Hodgkin and Hodgkin lymphomas. | 3 |
| 17303500 | 2007 | Differential expression of the human MIXL1 gene product in non-Hodgkin and Hodgkin lymphomas. | 3 |
| 15982639 | 2005 | Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and FoxH1. | 12 |
| 15982639 | 2005 | Transcriptional regulation of the homeobox gene Mixl1 by TGF-beta and FoxH1. | 12 |
| 12070013 | 2002 | A human Mix-like homeobox gene MIXL shows functional similarity to Xenopus Mix.1. | 7 |
| 12070013 | 2002 | A human Mix-like homeobox gene MIXL shows functional similarity to Xenopus Mix.1. | 7 |
Citation
Aaron Raymond ; Lalitha Nagarajan
MIXL1 (Mix1 homeobox-like 1 (Xenopus laevis))
Atlas Genet Cytogenet Oncol Haematol. 2010-08-01
Online version: http://atlasgeneticsoncology.org/gene/47624/mixl1
