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The cohesin complex: sequence homologies, interaction networks and shared motifs.

Jones S, Sgouros J - Genome Biol. (2001)

Bottom Line: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex.We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs.The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Genome Analysis Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. Susan.Jones@icrf.icnet.uk

ABSTRACT

Background: Cohesin is a macromolecular complex that links sister chromatids together at the metaphase plate during mitosis. The links are formed during DNA replication and destroyed during the metaphase-to-anaphase transition. In budding yeast, the 14S cohesin complex comprises at least two classes of SMC (structural maintenance of chromosomes) proteins - Smc1 and Smc3 - and two SCC (sister-chromatid cohesion) proteins - Scc1 and Scc3. The exact function of these proteins is unknown.

Results: Searches of protein sequence databases have revealed new homologs of cohesin proteins. In mouse, Mmip1 (Mad member interacting protein 1) and Smc3 share 99% sequence identity and are products of the same gene. A phylogenetic tree of SMC homologs reveals five families: Smc1, Smc2, Smc3, Smc4 and an ancestral family that includes the sequences from the Archaea and Eubacteria. This ancestral family also includes sequences from eukaryotes. A cohesion interaction network, comprising 17 proteins, has been constructed using two proteomic databases. Genes encoding six proteins in the cohesion network share a common upstream region that includes the MluI cell-cycle box (MCB) element. Pairs of the proteins in this network share common sequence motifs that could represent common structural features such as binding sites. Scc2 shares a motif with Chk1 (kinase checkpoint protein), that comprises part of the serine/threonine protein kinase motif, including the active-site residue.

Conclusions: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex. We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs. The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

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Sequence alignment of the conserved motif in Scc2, Chk1 and Pkh1, which includes the PROSITE serine/threonine (S/T) protein kinase motif. In the alignment the conserved residues of the motif identified using Teiresias are in red and additional conserved positions are in green. The residues that coincide with the S/T kinase motif are outlined with a box. The number before each motif indicates the position of the first residue within the complete sequence. The PROSITE S/T kinase motif is shown beneath the alignment. The alternative residues are shown in squared brackets; X denotes any residue; the active-site aspartic acid is in blue.
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Figure 4: Sequence alignment of the conserved motif in Scc2, Chk1 and Pkh1, which includes the PROSITE serine/threonine (S/T) protein kinase motif. In the alignment the conserved residues of the motif identified using Teiresias are in red and additional conserved positions are in green. The residues that coincide with the S/T kinase motif are outlined with a box. The number before each motif indicates the position of the first residue within the complete sequence. The PROSITE S/T kinase motif is shown beneath the alignment. The alternative residues are shown in squared brackets; X denotes any residue; the active-site aspartic acid is in blue.

Mentions: One motif shared by two sequences in the network and one additional sequence, is the DXXPENIXLXKN motif shared by the sequences of Scc2, Chk1 and a third S. cerevisiae protein PKH1 (yeast ORF YDR490C) (Figure 4). Both Chk1 and PKH1 are serine/threonine (ST) protein kinases, and the motif they share with Scc2 includes part of the PROSITE ST kinase signature motif ([LIVMFYC]X[HY]XD[LIVMFY]KXXN[LIVMFYCT](3), where X indicates any residue, (3) indicates that the previous residue is repeated three times, and D is the active site residue). The sequence of Scc2 does not match the ST kinase signature motif exactly. Of the 13 residues in the ST kinase motif, Scc2 has four mismatches but, importantly, the active-site aspartic acid is conserved.


The cohesin complex: sequence homologies, interaction networks and shared motifs.

Jones S, Sgouros J - Genome Biol. (2001)

Sequence alignment of the conserved motif in Scc2, Chk1 and Pkh1, which includes the PROSITE serine/threonine (S/T) protein kinase motif. In the alignment the conserved residues of the motif identified using Teiresias are in red and additional conserved positions are in green. The residues that coincide with the S/T kinase motif are outlined with a box. The number before each motif indicates the position of the first residue within the complete sequence. The PROSITE S/T kinase motif is shown beneath the alignment. The alternative residues are shown in squared brackets; X denotes any residue; the active-site aspartic acid is in blue.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC30708&req=5

Figure 4: Sequence alignment of the conserved motif in Scc2, Chk1 and Pkh1, which includes the PROSITE serine/threonine (S/T) protein kinase motif. In the alignment the conserved residues of the motif identified using Teiresias are in red and additional conserved positions are in green. The residues that coincide with the S/T kinase motif are outlined with a box. The number before each motif indicates the position of the first residue within the complete sequence. The PROSITE S/T kinase motif is shown beneath the alignment. The alternative residues are shown in squared brackets; X denotes any residue; the active-site aspartic acid is in blue.
Mentions: One motif shared by two sequences in the network and one additional sequence, is the DXXPENIXLXKN motif shared by the sequences of Scc2, Chk1 and a third S. cerevisiae protein PKH1 (yeast ORF YDR490C) (Figure 4). Both Chk1 and PKH1 are serine/threonine (ST) protein kinases, and the motif they share with Scc2 includes part of the PROSITE ST kinase signature motif ([LIVMFYC]X[HY]XD[LIVMFY]KXXN[LIVMFYCT](3), where X indicates any residue, (3) indicates that the previous residue is repeated three times, and D is the active site residue). The sequence of Scc2 does not match the ST kinase signature motif exactly. Of the 13 residues in the ST kinase motif, Scc2 has four mismatches but, importantly, the active-site aspartic acid is conserved.

Bottom Line: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex.We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs.The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Genome Analysis Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. Susan.Jones@icrf.icnet.uk

ABSTRACT

Background: Cohesin is a macromolecular complex that links sister chromatids together at the metaphase plate during mitosis. The links are formed during DNA replication and destroyed during the metaphase-to-anaphase transition. In budding yeast, the 14S cohesin complex comprises at least two classes of SMC (structural maintenance of chromosomes) proteins - Smc1 and Smc3 - and two SCC (sister-chromatid cohesion) proteins - Scc1 and Scc3. The exact function of these proteins is unknown.

Results: Searches of protein sequence databases have revealed new homologs of cohesin proteins. In mouse, Mmip1 (Mad member interacting protein 1) and Smc3 share 99% sequence identity and are products of the same gene. A phylogenetic tree of SMC homologs reveals five families: Smc1, Smc2, Smc3, Smc4 and an ancestral family that includes the sequences from the Archaea and Eubacteria. This ancestral family also includes sequences from eukaryotes. A cohesion interaction network, comprising 17 proteins, has been constructed using two proteomic databases. Genes encoding six proteins in the cohesion network share a common upstream region that includes the MluI cell-cycle box (MCB) element. Pairs of the proteins in this network share common sequence motifs that could represent common structural features such as binding sites. Scc2 shares a motif with Chk1 (kinase checkpoint protein), that comprises part of the serine/threonine protein kinase motif, including the active-site residue.

Conclusions: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex. We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs. The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

Show MeSH