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DMTF1 (cyclin D binding myb-like transcription factor 1)

Written2008-11Kazushi Inoue
Dept. of Pathology, Wake Forest University Health Sciences, 2102 Gray Building, Medical Center Boulevard, Winston-Salem, NC 27157-0001, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namescyclin D binding myb-like transcription factor 1
Alias_symbol (synonym)DMP1
DMTF
hDMP1
MRUL
Other alias
HGNC (Hugo) DMTF1
LocusID (NCBI) 9988
Atlas_Id 40340
Location 7q21.12  [Link to chromosome band 7q21]
Location_base_pair Starts at 87152361 and ends at 87196332 bp from pter ( according to hg19-Feb_2009)  [Mapping DMTF1.png]
Local_order Centromere--- GRM3 - KIAA1324L - DMTF1 - MGC4175 - CROT - ABCB4 - ABCB1 ---Telomere
Fusion genes
(updated 2016)
BAZ2B (2q24.2) / DMTF1 (7q21.12)DMTF1 (7q21.12) / GRM3 (7q21.11)DMTF1 (7q21.12) / SEMA3D (7q21.11)
YAF2 (12q12) / DMTF1 (7q21.12)

DNA/RNA

Note There are at least three splicing variants for hDMTF1 alpha, beta and gamma.
 
  The human DMTF1 genomic locus. DMTF1 consists of 20 exons and a gene named MGC4175 is localized at its 3' end in a reverse orientation.
Description 20 Exons.
Transcription Major transcript: 3.9kb (human) (and 3.75kb in the mouse).
Pseudogene In mus musculus, the pseudogene of Dmtf1 exists on chromosome XE3.
NT 039716, gi:149272292.

Protein

Note The human DMTF1alpha protein consists of 760 amino acids; DMTF1beta, 272 amino acids; and DMTF1gamma, 285 amino acids. Mouse Dmp1 consists of 761 amino acids.
 
  Proteins generated from splicing variants of the human DMTF1 gene. The hDMTF1 beta and gamma isoforms lack most of the Myb-like repeats and the principal transactivation domains, and thus, they do not bind to DNA.
Description Dmtf1 is a MYB-like transcription factor isolated in a yeast two-hybrid screen of a mouse T lymphocyte library with cyclin D2 bait. It binds to a consensus sequence CCCG(G/T)ATG(T/C) that is also recognized by Ets family proteins. DMTF1 is a novel tumor suppressor that receives signals from oncogenic RAS and activates the ARF - P53 pathway. D-type cyclins antagonize the activity of Dmtf1 when E2F sites are not on the promoter; however, they synergize with Dmtf1 on the Arf promoter. Recent study shows significant involvement of DMTF1 in human non-small-cell lung carcinomas.
Expression Mouse Dmtf1 protein is expressed in the testis, thymus, spleen, brain, lung, and kidney.
Localisation Both human and mouse DMTF1 alpha proteins are localized in the nucleus.
Function Dmtf1-null mice are prone to spontaneous tumor development, which was accelerated when the animals were neonatally treated with ionizing radiation or dimethylbenzanthracene. Lung adenomas/adenocarcinomas were the most common tumors found in Dmtf1-deficient mice. Eµ-Myc-induced lymphomagenesis was significantly accelerated in Dmtf1-deficient mice. The retention and expression of the wild-type Dmtf1 allele in tumors arising in heterozygotes indicated that Dmtf1 is haplo-insufficient for tumor suppression. The low frequency of Arf deletion and p53 mutation in tumors from Dmtf1-knockout mice suggested that Dmtf1 is a physiological regulator of the Arf-p53 pathway in vivo.
The DMTF1 promoter is activated by the oncogenic RAS - RAF - MEK - ERK - JUN pathway, and the induction of ARF by RAS is DMTF1-dependent. Thus, DMTF1 is a critical mediator of p19ARF in response to oncogenic RAS signaling. The importance of dmp1 in P53 regulation was recently demonstrated by crossing Dmtf1-deficient mice with K-rasLA transgenic mice. The Dmtf1 promoter is repressed by overexpression of E2Fs and also by physiological mitogenic signaling. Thus, DMTF1 is a marker of cells that have exited from the cell cycle. The DMTF1 promoter is repressed by genotoxic stimuli mediated by NF-kappa B, and repression of the ARF promoter by genotoxic stimuli is DMP1-dependent. Very little studies have been conducted on the post-translational modifications for DMTF1.
Homology Human DMTF1 vs. mouse Dmtf1: 95% (723/761), positives 97% (739/761) at the amino acids level.
Mouse Dmtf1 vs. mouse TTF-1 (transcription termination factor 1): Identities 29% (90/309), positives 47% (148/309).
Mouse Dmtf1 vs. mouse C-myb: Identities 32% (23/71), positives 54% (39/71).
Mouse Dmtf1 vs. mouse A-myb: Identities 29% (31/106), positives 50% (54/106).
Mouse Dmtf1 vs. mouse B-myb: Identities 27% (22/80), positives 53% (43/80)

Mutations

Note Point mutations for human DMTF1 in human cancer or other human disorders have not been reported.
Promoter hypermethylation for the hDMTF1 promoter is very rare ( around 2%) in human non-small-cell lung carcinomas.
Single nucleotide polymorphisms for hDMTF1 are shown in http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusId=9988.
Germinal N/A.
Somatic N/A.

Implicated in

Note
  
Entity Non-small-cell lung carcinoma
Disease One report shows that loss of heterozygosity (LOH) for the human DMTF1 gene was found in around 35 % of human non-small-cell lung cancers, especially those without deletions or methylation of p14ARF and/or mutations of p53. NSCLC with LOH for hDMTF1 showed significantly weaker nuclear staining for DMTF1 protein than tumors without LOH.
Prognosis The correlation between LOH for hDMTF1 and the prognoses of non-small-cell lung cancer patients has not been reported.
Hybrid/Mutated Gene Not reported.
Abnormal Protein Not reported.
Oncogenesis N/A
  
  
Entity Hematopoietic malignancies involving chromosome del(7q)
Prognosis The prognoses of human leukemias with del(7q) abnormalities are generally poor.
Cytogenetics One allele of the hDMTF1 locus was deleted in 9 of 9 leukemic cells with chromosome 7q abnormalities by FISH analysis, regardless of the detailed karyotype at 7q, suggesting that mono-allelic loss of hDMTF1 could contribute to 7q- leukemias.
Hybrid/Mutated Gene Not reported.
Abnormal Protein Not reported.
Oncogenesis N/A
  

Bibliography

Cloning and chromosomal localization of the gene encoding human cyclin D-binding Myb-like protein (hDMP1).
Bodner SM, Naeve CW, Rakestraw KM, Jones BG, Valentine VA, Valentine MB, Luthardt FW, Willman CL, Raimondi SC, Downing JR, Roussel MF, Sherr CJ, Look AT.
Gene. 1999 Mar 18;229(1-2):223-8.
PMID 10095122
 
Interaction of D-type cyclins with a novel myb-like transcription factor, DMP1.
Hirai H, Sherr CJ.
Mol Cell Biol. 1996 Nov;16(11):6457-67.
PMID 8887674
 
Dmp1 and tumor suppression. (Review).
Inoue K, Mallakin A, Frazier DP.
Oncogene. 2007 Jun 28;26(30):4329-35.
PMID 17237816
 
Induction of ARF tumor suppressor gene expression and cell cycle arrest by transcription factor DMP1.
Inoue K, Roussel MF, Sherr CJ.
Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3993-8.
PMID 10097151
 
Regulation of the CD13/aminopeptidase N gene by DMP1, a transcription factor antagonized by D-type cyclins.
Inoue K, Sherr CJ, Shapiro LH.
J Biol Chem. 1998 Oct 30;273(44):29188-94.
PMID 9786929
 
Emerging roles of DMP1 in lung cancer.
Inoue K, Sugiyama T, Taneja P, Morgan RL, Frazier DP.
Cancer Res. 2008 Jun 15;68(12):4487-90.
PMID 18559489
 
Disruption of the ARF transcriptional activator DMP1 facilitates cell immortalization, Ras transformation, and tumorigenesis.
Inoue K, Wen R, Rehg JE, Adachi M, Cleveland JL, Roussel MF, Sherr CJ.
Genes Dev. 2000 Jul 15;14(14):1797-809.
PMID 10898794
 
Dmp1 is haplo-insufficient for tumor suppression and modifies the frequencies of Arf and p53 mutations in Myc-induced lymphomas.
Inoue K, Zindy F, Randle DH, Rehg JE, Sherr CJ.
Genes Dev. 2001 Nov 15;15(22):2934-9.
PMID 11711428
 
Mutually exclusive inactivation of DMP1 and ARF/p53 in lung cancer.
Mallakin A, Sugiyama T, Taneja P, Matise LA, Frazier DP, Choudhary M, Hawkins GA, D'Agostino RB Jr, Willingham MC, Inoue K.
Cancer Cell. 2007 Oct;12(4):381-94.
PMID 17936562
 
Ras-Raf-Arf signaling critically depends on the Dmp1 transcription factor.
Sreeramaneni R, Chaudhry A, McMahon M, Sherr CJ, Inoue K.
Mol Cell Biol. 2005 Jan;25(1):220-32.
PMID 15601844
 
Oncogenic and non-oncogenic signaling pathways that regulate Dmp1 (Dmtf1).
Sugiyama T, Taneja P, Frazier DP, Kendig R, Morgan RL, Matise LA, Lagedrost SJ, Inoue K.
Clinical Medicine: Oncology. 2008 2, 1-11.
 
Repression of Dmp1 and Arf transcription by anthracyclins: critical roles of the NF-kappaB subunit p65.
Taneja P, Mallakin A, Matise LA, Frazier DP, Choudhary M, Inoue K.
Oncogene. 2007 Nov 22;26(53):7457-66.
PMID 17546045
 
Alternative splicing of the human cyclin D-binding Myb-like protein (hDMP1) yields a truncated protein isoform that alters macrophage differentiation patterns.
Tschan MP, Fischer KM, Fung VS, Pirnia F, Borner MM, Fey MF, Tobler A, Torbett BE.
J Biol Chem. 2003 Oct 31;278(44):42750-60.
PMID 12917399
 
The hDMP1 tumor suppressor is a new WT1 target in myeloid leukemias.
Tschan MP, Gullberg U, Shan D, Torbett BE, Fey MF, Tobler A.
Leukemia. 2008 May;22(5):1087-90.
PMID 17972942
 

Citation

This paper should be referenced as such :
Inoue, K
DMTF1 (cyclin D binding myb-like transcription factor 1)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(10):721-723.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/DMTF1ID40340ch7q21.html


External links

Nomenclature
HGNC (Hugo)DMTF1   14603
Cards
AtlasDMTF1ID40340ch7q21
Entrez_Gene (NCBI)DMTF1  9988  cyclin D binding myb like transcription factor 1
AliasesDMP1; DMTF; MRUL; hDMP1
GeneCards (Weizmann)DMTF1
Ensembl hg19 (Hinxton)ENSG00000135164 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000135164 [Gene_View]  chr7:87152361-87196332 [Contig_View]  DMTF1 [Vega]
ICGC DataPortalENSG00000135164
TCGA cBioPortalDMTF1
AceView (NCBI)DMTF1
Genatlas (Paris)DMTF1
WikiGenes9988
SOURCE (Princeton)DMTF1
Genetics Home Reference (NIH)DMTF1
Genomic and cartography
GoldenPath hg38 (UCSC)DMTF1  -     chr7:87152361-87196332 +  7q21.12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)DMTF1  -     7q21.12   [Description]    (hg19-Feb_2009)
EnsemblDMTF1 - 7q21.12 [CytoView hg19]  DMTF1 - 7q21.12 [CytoView hg38]
Mapping of homologs : NCBIDMTF1 [Mapview hg19]  DMTF1 [Mapview hg38]
OMIM608491   
Gene and transcription
Genbank (Entrez)AA258783 AB209230 AF052102 AF084530 AF202144
RefSeq transcript (Entrez)NM_001142326 NM_001142327 NM_021145
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)DMTF1
Cluster EST : UnigeneHs.196129 [ NCBI ]
CGAP (NCI)Hs.196129
Alternative Splicing GalleryENSG00000135164
Gene ExpressionDMTF1 [ NCBI-GEO ]   DMTF1 [ EBI - ARRAY_EXPRESS ]   DMTF1 [ SEEK ]   DMTF1 [ MEM ]
Gene Expression Viewer (FireBrowse)DMTF1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9988
GTEX Portal (Tissue expression)DMTF1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9Y222   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9Y222  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9Y222
Splice isoforms : SwissVarQ9Y222
PhosPhoSitePlusQ9Y222
Domaine pattern : Prosite (Expaxy)HTH_MYB (PS51294)    MYB_LIKE (PS50090)   
Domains : Interpro (EBI)Homeobox-like    Myb-like_dom    Myb_dom    SANT/Myb   
Domain families : Pfam (Sanger)Myb_DNA-binding (PF00249)   
Domain families : Pfam (NCBI)pfam00249   
Domain families : Smart (EMBL)SANT (SM00717)  
Conserved Domain (NCBI)DMTF1
DMDM Disease mutations9988
Blocks (Seattle)DMTF1
PDB (SRS)2LLK   
PDB (PDBSum)2LLK   
PDB (IMB)2LLK   
PDB (RSDB)2LLK   
Structural Biology KnowledgeBase2LLK   
SCOP (Structural Classification of Proteins)2LLK   
CATH (Classification of proteins structures)2LLK   
SuperfamilyQ9Y222
Human Protein AtlasENSG00000135164
Peptide AtlasQ9Y222
HPRD09770
IPIIPI00028123   IPI00889129   IPI00852885   IPI00887567   IPI01009399   IPI00915375   IPI01021375   IPI00926071   IPI00925365   IPI00926747   IPI00926549   IPI00926340   IPI00927945   IPI00927686   IPI00924886   IPI00927285   IPI00926715   IPI00926030   IPI00925619   IPI00926309   
Protein Interaction databases
DIP (DOE-UCLA)Q9Y222
IntAct (EBI)Q9Y222
FunCoupENSG00000135164
BioGRIDDMTF1
STRING (EMBL)DMTF1
ZODIACDMTF1
Ontologies - Pathways
QuickGOQ9Y222
Ontology : AmiGORNA polymerase II transcription factor activity, sequence-specific DNA binding  transcription factor activity, RNA polymerase II transcription factor recruiting  transcription factor activity, sequence-specific DNA binding  nucleus  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  regulation of transcription from RNA polymerase II promoter  cell cycle  cell differentiation  sequence-specific DNA binding  transcription regulatory region DNA binding  
Ontology : EGO-EBIRNA polymerase II transcription factor activity, sequence-specific DNA binding  transcription factor activity, RNA polymerase II transcription factor recruiting  transcription factor activity, sequence-specific DNA binding  nucleus  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  regulation of transcription from RNA polymerase II promoter  cell cycle  cell differentiation  sequence-specific DNA binding  transcription regulatory region DNA binding  
NDEx NetworkDMTF1
Atlas of Cancer Signalling NetworkDMTF1
Wikipedia pathwaysDMTF1
Orthology - Evolution
OrthoDB9988
GeneTree (enSembl)ENSG00000135164
Phylogenetic Trees/Animal Genes : TreeFamDMTF1
HOVERGENQ9Y222
HOGENOMQ9Y222
Homologs : HomoloGeneDMTF1
Homology/Alignments : Family Browser (UCSC)DMTF1
Gene fusions - Rearrangements
Fusion : MitelmanDMTF1/GRM3 [7q21.12/7q21.11]  
Fusion : MitelmanDMTF1/SEMA3D [7q21.12/7q21.11]  [t(7;7)(q21;q21)]  
Fusion: TCGADMTF1 7q21.12 GRM3 7q21.11 LUSC
Fusion: TCGADMTF1 7q21.12 SEMA3D 7q21.11 LGG
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerDMTF1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)DMTF1
dbVarDMTF1
ClinVarDMTF1
1000_GenomesDMTF1 
Exome Variant ServerDMTF1
ExAC (Exome Aggregation Consortium)DMTF1 (select the gene name)
Genetic variants : HAPMAP9988
Genomic Variants (DGV)DMTF1 [DGVbeta]
DECIPHERDMTF1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisDMTF1 
Mutations
ICGC Data PortalDMTF1 
TCGA Data PortalDMTF1 
Broad Tumor PortalDMTF1
OASIS PortalDMTF1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICDMTF1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDDMTF1
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 DMTF1
DgiDB (Drug Gene Interaction Database)DMTF1
DoCM (Curated mutations)DMTF1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)DMTF1 (select a term)
intoGenDMTF1
NCG5 (London)DMTF1
Cancer3DDMTF1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM608491   
Orphanet
MedgenDMTF1
Genetic Testing Registry DMTF1
NextProtQ9Y222 [Medical]
TSGene9988
GENETestsDMTF1
Target ValidationDMTF1
Huge Navigator DMTF1 [HugePedia]
snp3D : Map Gene to Disease9988
BioCentury BCIQDMTF1
ClinGenDMTF1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9988
Chemical/Pharm GKB GenePA27389
Clinical trialDMTF1
Miscellaneous
canSAR (ICR)DMTF1 (select the gene name)
Probes
Litterature
PubMed29 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineDMTF1
EVEXDMTF1
GoPubMedDMTF1
iHOPDMTF1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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