HMM PD00008
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Symbol: CC1_Sac_PD
Name: Sac phosphatase domain
Description
Based upon the crystal structure of yeast SAC1, the yeast SAC1 has two structure domains: SacN and catalytic domain [1] (see the sequences in supplementary materials). The SacN ranges from 1-181; the catalytic phosphatase domain ranges from 182-504. The SacN domain mediates the interaction with VPS74, which is proposed to mediate packaging of medial Golgi glycosyltransferases into coatomer (also called COP1)-coated vesicles, thereby maintaining Golgi residence [2].
When using the HMM/PSSM profiles of public databases to determine the region of phosphatase domain, they gave different regions from the region determined from the crystal structure paper:
- Pfam database: Syja_N (PF02383), 56-343
- CDD database: 1) Cdd:pfam02383, 55-348, 2) Cdd:COG5329, 3-578
- SMART: no hit
In brief, Pfam profile contains part of SacN domain and part of the phosphatase domain; COG profile contains both SacN and the catalytic phosphatase domain. Because the region of 451-511 is required for PtdIns4P phosphatase activity [2], Pfam PF02383 is not a good profile for Sac phosphatase domain.
How the HMM was built
We PSI-BLASTed the full sequence of yeast SAC1 (see supplementary materials) against SwissProt via NCBI BLAST server. The search converged right after 1st round. The query yeast SAC1 hit the SACs from animals and plants. We downloaded the aligned sequences, aligned them with Clustal Omega, manually adjusted the alignment, built the HMM and validated the HMM using the protein phosphatases of the nine genomes.
We found the alignment contains both SacN and the catalytic phosphatase domain. We split them based upon the ranges of the two domains of yeast SAC1 derived from the crystal structure study mentioned above.
References
- Manford A, Xia T, Saxena AK, Stefan C, Hu F, Emr SD, and Mao Y. Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function. EMBO J. 2010 May 5;29(9):1489-98. DOI:10.1038/emboj.2010.57 |
Supplementary materials
The full sequence of yeast SAC1:
>yeast_SAC1 MTGPIVYVQNADGIFFKLAEGKGTNDAVIHLANQDQGVRVLGAEEFPVQGEVVKIASLMGFIKLKLNRYAIIANTVEETGRFNGHVFYRVLQHSIVSTKFNSRIDSEEAEYIKLLELHLKNSTFYFSYTYDLTNSLQRNEKVGPAASWKTADERFFWNHYLTEDLRNFAHQDPRIDSFIQPVIYGYAKTVDAVLNATPIVLGLITRRSIFRAGTRYFRRGVDKDGNVGNFNETEQILLAENPESEKIHVFSFLQTRGSVPIYWAEINNLKYKPNLVLGENSLDATKKHFDQQKELYGDNYLVNLVNQKGHELPVKEGYESVVHALNDPKIHYVYFDFHHECRKMQWHRVKLLIDHLEKLGLSNEDFFHKVIDSNGNTVEIVNEQHSVVRTNCMDCLDRTNVVQSVLAQWVLQKEFESADVVATGSTWEDNAPLLTSYQNLWADNADAVSVAYSGTGALKTDFTRTGKRTRLGAFNDFLNSASRYYQNNWTDGPRQDSYDLFLGGFRPHTASIKSPFPDRRPVYIQLIPMIICAALTVLGATIFFPKDRFTSSKNLLYFAGASIVLALSTKFMFKNGIQFVNWPKLVDVGFLVVHQTHDKEQQFKGLKYAQSPKFSKPDPLKRD
The sequence of SacN domain of SAC1: >yeast_SAC1_SacN MTGPIVYVQNADGIFFKLAEGKGTNDAVIHLANQDQGVRVLGAEEFPVQGEVVKIASLMGFIKLKLNRYAIIANTVEETGRFNGHVFYRVLQHSIVSTKFNSRIDSEEAEYIKLLELHLKNSTFYFSYTYDLTNSLQRNEKVGPAASWKTADERFFWNHYLTEDLRNFAHQDPRIDSFIQP
The sequence of catalytic domain of yeast SAC1: >yeast_SAC1_Catalytic_Domain VIYGYAKTVDAVLNATPIVLGLITRRSIFRAGTRYFRRGVDKDGNVGNFNETEQILLAENPESEKIHVFSFLQTRGSVPIYWAEINNLKYKPNLVLGENSLDATKKHFDQQKELYGDNYLVNLVNQKGHELPVKEGYESVVHALNDPKIHYVYFDFHHECRKMQWHRVKLLIDHLEKLGLSNEDFFHKVIDSNGNTVEIVNEQHSVVRTNCMDCLDRTNVVQSVLAQWVLQKEFESADVVATGSTWEDNAPLLTSYQNLWADNADAVSVAYSGTGALKTDFTRTGKRTRLGAFNDFLNSASRYYQNNWTDGPRQDSYDLFLGG
