PROSITE documentation PDOC00037

Myb-type HTH DNA-binding domain profiles

The myb family can be classified into three groups: the myb-type HTH domain, which binds DNA, the SANT domain, which is a protein-protein interaction module (see <PDOC51293>) and the myb-like domain that can be involved in either of these functions.

The myb-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain of ~55 amino acids, typically occurring in a tandem repeat in eukaryotic transcription factors. The domain is named after the retroviral oncogene v-myb, and its cellular counterpart c-myb, which encode nuclear DNA-binding proteins that specifically recognize the sequence YAAC(G/T)G [1,2]. Myb proteins contain three tandem repeats of 51 to 53 amino acids, termed R1, R2 and R3. This repeat region is involved in DNA-binding and R2 and R3 bind directly to the DNA major groove. The major part of the first repeat is missing in retroviral v-Myb sequences and in plant myb-related (R2R3) proteins [3]. A single myb-type HTH DNA-binding domain occurs in TRF1 and TRF2.

The 3D-structure of the myb-type HTH domain forms three α-helices (see <PDB:1H88; C>) [4]. The second and third helices connected via a turn comprise the helix-turn-helix motif. Helix 3 is termed the recognition helix as it binds the DNA major groove, like in other HTHs.

Some proteins known to contain a myb-type HTH domain:

• Fruit fly myb protein [2].
• Vertebrate myb-like proteins A-myb and B-myb.
• Maize anthocyanin regulatory C1 protein, a trans-acting factor which controls the expression of genes involved in anthocyanin biosynthesis.
• Maize P protein [5], a trans-acting factor which regulates the biosynthetic pathway of a flavonoid-derived pigment in certain floral tissues.
• Arabidopsis thaliana protein GL1/GLABROUS1 [6], required for the initiation of differentiation of leaf hair cells (trichomes).
• Maize and barley myb-related proteins Zm1, Zm38 and Hv1, Hv33 [7].
• Yeast BAS1 [8], a transcriptional activator for the HIS4 gene.
• Yeast REB1 [9], which recognizes sites within both the enhancer and the promoter of rRNA transcription, as well as upstream of many genes transcribed by RNA polymerase II.
• Fission yeast cdc5, a possible transcription factor whose activity is required for cell cycle progression and growth during G2.
• Fission yeast myb1, which regulates telomere length and function.
• Baker's yeast pre-mRNA-splicing factor CEF1.
• Vertebrate telomeric repeat-binding factors 1 and 2 (TRF1/2), which bind to telomeric DNA and are involved in telomere length regulation.

We have developed a profile, which has been manually adapted to specifically detect the DNA-binding myb-type HTH domain. A second general profile was developed for detection of the myb-like domain with a high sensitivity. A third profile was developed for the SANT domain (see <PDOC51293>).