In molecular biology the DM domain is a protein domain first discovered in the doublesex proteins of Drosophila melanogaster and is also seen in C. elegans and mammalian proteins.[1] In D. melanogaster the doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides.[2] These proteins are believed to function as transcription factors on downstream sex-determination genes, especially on neuroblast differentiation and yolk protein genes transcription.[3][4]

DM domain
Drosophila melanogaster doublesex (dsx), nmr, 18 structures
Identifiers
SymbolDM
PfamPF00751
InterProIPR001275
SMARTSM00718
SCOP21rvv / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

The DM domain binds DNA as a dimer, allowing the recognition of pseudopalindromic sequences .[2][5][6] The NMR analysis of the DSX DM domain [6] revealed a novel zinc module containing 'intertwined' CCHC and HCCC zinc-binding sites. The recognition of the DNA requires the carboxy-terminal basic tail which contacts the minor groove of the target sequence.

Proteins with this domain

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Proteins with the DM domain are found in many model organisms. Many C. elegans Mab proteins contain this domain, the best-known one being mab-3.[1] Human proteins containing this domain include DMRT1, DMRT2, DMRT3, DMRTA1, DMRTA2, DMRTB1, and DMRTC2; each of these have a mouse homolog.[7]

Dmrt1-specific
Identifiers
SymbolDmrt1
PfamPF12374
InterProIPR022114
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

DMRT1 homologs have an additional common domain C-terminal to the DM domain. This domain is only found in bony vertebrates, and neither its structure nor function is unknown.[8]: species tree  Jpred predicts the human version of the section to be mostly coils; it also suggests a weak similarity to PDB: 6BO4​ by BLAST.[9]

DMRTA motif
Identifiers
SymbolDMA
PfamPF03474
InterProIPR005173
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

DMRTA proteins have an additional motif in their C-termina. This motif, ubiquitous in eukaryotes, has an unknown function. It is similar in sequence to some ubiquitin-associated motifs.[10]

References

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  1. ^ a b Raymond CS, Shamu CE, Shen MM, Seifert KJ, Hirsch B, Hodgkin J, Zarkower D (February 1998). "Evidence for evolutionary conservation of sex-determining genes". Nature. 391 (6668): 691–5. Bibcode:1998Natur.391..691R. doi:10.1038/35618. PMID 9490411. S2CID 11414843.
  2. ^ a b Erdman SE, Chen HJ, Burtis KC (December 1996). "Functional and genetic characterization of the oligomerization and DNA binding properties of the Drosophila doublesex proteins". Genetics. 144 (4): 1639–52. doi:10.1093/genetics/144.4.1639. PMC 1207715. PMID 8978051.
  3. ^ Burtis KC, Coschigano KT, Baker BS, Wensink PC (September 1991). "The doublesex proteins of Drosophila melanogaster bind directly to a sex-specific yolk protein gene enhancer". EMBO J. 10 (9): 2577–82. doi:10.1002/j.1460-2075.1991.tb07798.x. PMC 452955. PMID 1907913.
  4. ^ Shen MM, Hodgkin J (September 1988). "mab-3, a gene required for sex-specific yolk protein expression and a male-specific lineage in C. elegans". Cell. 54 (7): 1019–31. doi:10.1016/0092-8674(88)90117-1. PMID 3046751. S2CID 1386352.
  5. ^ Yi W, Zarkower D (February 1999). "Similarity of DNA binding and transcriptional regulation by Caenorhabditis elegans MAB-3 and Drosophila melanogaster DSX suggests conservation of sex determining mechanisms". Development. 126 (5): 873–81. doi:10.1242/dev.126.5.873. PMID 9927589.
  6. ^ a b Zhu L, Wilken J, Phillips NB, Narendra U, Chan G, Stratton SM, Kent SB, Weiss MA (July 2000). "Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers". Genes Dev. 14 (14): 1750–64. doi:10.1101/gad.14.14.1750. PMC 316782. PMID 10898790.
  7. ^ "Proteins matched: DM DNA-binding domain (IPR001275) filtered by species (Homo sapiens)". InterPro.
  8. ^ "Family: Dmrt1 (PF12374)". Pfam.
  9. ^ "Jpred results (MTECSGTSQPPPASVPTTAASEGRMVIQDIPAVTSRGHVENTPD)". www.compbio.dundee.ac.uk. Archived from the original on 10 April 2019. Retrieved 10 April 2019.
  10. ^ "Species: DMRTA motif (IPR005173)". InterPro. Retrieved 10 April 2019.
This article incorporates text from the public domain Pfam and InterPro: IPR001275