cyclin-D-binding Myb-like transcription factor 1 (hDMTF1, cyclin-D-interacting Myb-like protein 1, hDMP1, DMTF1, DMP1)

Function: - transcriptional activator - activates CDKN2A/ARF locus in response to Ras-Raf signaling, thereby promoting TP53/p53-dependent growth arrest (putative) - binds to the consensus sequence 5'-CCCG[GT]ATGT-3' - isoform 1 may cooperate with MYB to activate transcription of the ANPEP gene - isoform 2 may antagonize transcriptional activation by isoform 1 - interacts with the D-type cyclins CCND1, CCND2 & CCND3 (putative) - interaction with D-type cyclins may modulate transcriptional activation by this protein (putative) - phosphorylated by the cyclin-D2/CDK4, cyclin-D3/CDK4 & cyclin-D2/CDK6 complexes & to a lesser extent by the cyclin-D1/CDK4 complex (putative) Structure: - belongs to the DMTF1 family - contains 1 HTH myb-type DNA-binding domain - contains 2 Myb-like domains Compartment: nucleus Alternative splicing: named isoforms=4 Expression: - expressed at relatively low levels in colonic mucosa, ovary, peripheral leukocytes, prostate & small intestine - expressed at higher levels in spleen, testis & thymus - expressed in multiple regions of the brain & CNS including amygdala, caudate, corpus callosum, hippocampus, substantia nigra & subthalmic nucleus - isoform 1 is the predominant isoform in monocytes, macrophages & neutrophils - isoform 2 is most strongly expressed in peripheral blood leukocytes & quiescent CD34 positive cells - isoform 3 is expressed at low levels in all hematopoietic cell types - expression of isoform 2 is down-regulated during myeloid differentiation, while the expression of isoform 1 & isoform 3 remain constant Pathology: - expression is frequently diminished in non-small-cell lung carcinomas (NSCLC) due to hemizygous gene deletion, strongly suggesting that this locus is haplo-insufficient for tumor suppression - loss of this locus frequently occurs in tumors which retain wild-type CDKN2A/ARF & TP53/p53 loci - hemizygous gene deletion has also been observed in leukemic blasts from patients with abnormalities of the long arm of chromosome 7

Properties

SIZE: entity length = 760 aa MW = 84 kD COMPARTMENT: cell nucleus MOTIF: CCND2 interaction {1-237} binding site SITE: 87-458 FOR-BINDING-OF: REQUIRED FOR DNA MOTIF: transcriptional activation {87-170} CCND1/CCND2/CCND3 interaction {176-760} MOTIF: Myb-like 1 {225-263} HTH myb-type {268-333} DNA-binding motif SITE: 306-329 Myb-like 2 {339-388} transcriptional activation {459-760}

Database Correlations

OMIM 608491 UniProt Q9Y222 Pfam PF00249 Kegg hsa:9988

References

UniProt :accession Q9Y222