Difference between revisions of "HMM PD00008"

Latest revision as of 18:22, 26 March 2017

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Symbol: CC1_Sac_PD

Name: Sac phosphatase domain

Description

Based upon the crystal structure of the yeast member, SAC1 has two structural domains: SacN and the catalytic phosphatase 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 (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 first crystal structure:

• Pfam database: Syja_N (PF02383), 56-343
• CDD database: 1) Cdd:pfam02383, 55-348, 2) Cdd:COG5329, 3-578
• SMART: no hit

Thus, Pfam profile contains part of SacN domain and part of the phosphatase domain, and it lacks the region of 451-511 is required for the PtdIns4P phosphatase activity of yeast SAC1 [2]. COG profile contains both SacN and the catalytic phosphatase domain, but also the trans-membrane–spanning domains (523-578) (figure 4A in [2]). We therefore built our own profiles for SacN and catalytic 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

1. 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 | PubMed ID:20389282 | HubMed [Manford10]
2. Cai Y, Deng Y, Horenkamp F, Reinisch KM, and Burd CG. Sac1-Vps74 structure reveals a mechanism to terminate phosphoinositide signaling in the Golgi apparatus. J Cell Biol. 2014 Aug 18;206(4):485-91. DOI:10.1083/jcb.201404041 | PubMed ID:25113029 | HubMed [Cai14]

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