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1  structure 79  species 0  interactions 146  sequences 1  architecture

Family: GCM (PF03615)

Summary: GCM motif protein

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This is the Wikipedia entry entitled "GCM transcription factors". More...

GCM transcription factors Edit Wikipedia article

GCM
PDB 1odh EBI.jpg
structure of the gcm domain bound to dna
Identifiers
Symbol GCM
Pfam PF03615
Pfam clan CL0274
InterPro IPR003902
SCOP 1odh
SUPERFAMILY 1odh

In molecular biology, the GCM transcription factors are a family of proteins which contain a GCM motif. The GCM motif is a domain that has been identified in proteins belonging to a family of transcriptional regulators involved in fundamental developmental processes which comprise Drosophila melanogaster GCM and its mammalian homologues.[1][2][3][4] In GCM transcription factors the N-terminal moiety contains a DNA-binding domain of 150 amino acids. Sequence conservation is highest in this GCM domain. In contrast, the C-terminal moiety contains one or two transactivating regions and is only poorly conserved.

The GCM motif has been shown to be a DNA binding domain that recognises preferentially the nonpalindromic octamer 5'-ATGCGGGT-3'.[1][2][3] The GCM motif contains many conserved basic amino acid residues, seven cysteine residues, and four histidine residues.[1] The conserved cysteines are involved in shaping the overall conformation of the domain, in the process of DNA binding and in the redox regulation of DNA binding.[3] The GCM domain as a new class of Zn-containing DNA-binding domain with no similarity to any other DNA-binding domain.[5] The GCM domain consists of a large and a small domain tethered together by one of the two Zn ions present in the structure. The large and the small domains comprise five- and three-stranded beta-sheets, respectively, with three small helical segments packed against the same side of the two beta-sheets. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded beta-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of the beta-pleated sheet and the following loop and strand contact the bases and backbone of both DNA strands, providing specificity for its DNA target site.

References

  1. ^ a b c Akiyama Y, Hosoya T, Poole AM, Hotta Y (December 1996). "The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14912–6. doi:10.1073/pnas.93.25.14912. PMC 26236. PMID 8962155. 
  2. ^ a b Schreiber J, Sock E, Wegner M (April 1997). "The regulator of early gliogenesis glial cells missing is a transcription factor with a novel type of DNA-binding domain". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4739–44. doi:10.1073/pnas.94.9.4739. PMC 20794. PMID 9114061. 
  3. ^ a b c Schreiber J, Enderich J, Wegner M (May 1998). "Structural requirements for DNA binding of GCM proteins". Nucleic Acids Res. 26 (10): 2337–43. doi:10.1093/nar/26.10.2337. PMC 147556. PMID 9580683. 
  4. ^ Tuerk EE, Schreiber J, Wegner M (February 2000). "Protein stability and domain topology determine the transcriptional activity of the mammalian glial cells missing homolog, GCMb". J. Biol. Chem. 275 (7): 4774–82. doi:10.1074/jbc.275.7.4774. PMID 10671510. 
  5. ^ Cohen SX, Moulin M, Hashemolhosseini S, Kilian K, Wegner M, Muller CW (April 2003). "Structure of the GCM domain-DNA complex: a DNA-binding domain with a novel fold and mode of target site recognition". EMBO J. 22 (8): 1835–45. doi:10.1093/emboj/cdg182. PMC 154474. PMID 12682016. 

This article incorporates text from the public domain Pfam and InterPro IPR003902

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003902

GCM transcription factors are a family of proteins which contain a GCM motif. The GCM motif is a domain that has been identified in proteins belonging to a family of transcriptional regulators involved in fundamental developmental processes which comprise Drosophila melanogaster GCM and its mammalian homologs [PUBMED:8962155, PUBMED:9114061, PUBMED:9580683, PUBMED:10671510]. IN GCM transcription factors the N-terminal moiety contains a DNA-binding domain of 150 residues. Sequence conservation is highest in this GCM domain. In contrast, the C-terminal moiety contains one or two transactivating regions and is only poorly conserved.

The GCM motif has been shown to be a DNA binding domain that recognises preferentially the nonpalindromic octamer 5'-ATGCGGGT-3' [PUBMED:8962155, PUBMED:9114061, PUBMED:9580683]. The GCM motif contains many conserved basic amino acid residues, seven cysteine residues, and four histidine residues [PUBMED:8962155]. The conserved cysteines are involved in shaping the overall conformation of the domain, in the process of DNA binding and in the redox regulation of DNA binding [PUBMED:9580683]. The GCM domain as a new class of Zn-containing DNA-binding domain with no similarity to any other DNA-binding domain [PUBMED:12682016]. The GCM domain consists of a large and a small domain tethered together by one of the two Zn ions present in the structure. The large and the small domains comprise five- and three-stranded beta-sheets, respectively, with three small helical segments packed against the same side of the two beta-sheets. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded beta-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of the beta-pleated sheet and the following loop and strand contact the bases and backbone of both DNA strands, providing specificity for its DNA target site.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan WRKY-GCM1 (CL0274), which has the following description:

WRKY and GCM1 are metal chelating DNA-binding domains (DBD) which share a four stranded fold [1]. We present evidence that they share a stabilising core, which suggests a possible origin from a BED finger-like intermediate that was in turn ultimately derived from a C2H2 Zn-finger domain [1].

The clan contains the following 6 members:

AFT DBD_Tnp_Mut FAR1 FLYWCH GCM WRKY

Alignments

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(6)
Full
(146)
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(148)
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(21)
RP35
(27)
RP55
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RP75
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  Seed
(6)
Full
(146)
Representative proteomes NCBI
(148)
Meta
(0)
RP15
(21)
RP35
(27)
RP55
(55)
RP75
(94)
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  Seed
(6)
Full
(146)
Representative proteomes NCBI
(148)
Meta
(0)
RP15
(21)
RP35
(27)
RP55
(55)
RP75
(94)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: PROSITE
Previous IDs: none
Type: Family
Author: Griffiths-Jones SR
Number in seed: 6
Number in full: 146
Average length of the domain: 139.50 aa
Average identity of full alignment: 68 %
Average coverage of the sequence by the domain: 28.86 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.0 25.0
Trusted cut-off 31.8 34.4
Noise cut-off 22.3 21.6
Model length: 143
Family (HMM) version: 10
Download: download the raw HMM for this family

Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the GCM domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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