Difference between revisions of "HMM PD00008"

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(Created page with "Back to '''List of HMMs''' '''Symbol''': CC1_Sac_PD '''Name''': Sac phosphatase domain === Description === We built the profile because the boundary of phosphatase ...")
 
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=== Description ===
 
=== Description ===
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We built the profile because the boundary of phosphatase domain defined by Pfam profile is not the same as the one reported in crystal structure study <cite>Begley03</cite> and SMART does not have the profile for the myotubularin phosphatase domain. The crystal structure shows the phosphatase domain ranges from 205-586 in human MTMR2 (Figure 6A in <cite>Begley03</cite>). The Pfam profile [http://pfam.xfam.org/family/PF06602.10 Myotub-related (PF06602)] predicted the range from 192-529.
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Based upon the crystal structure of yeast SAC1, the yeast SAC1 has two structure domains: SacN and catalytic domain <cite>Manford10</cite> (see the sequences in supplementary materials). The SacN ranges from 1-181; the catalytic phosphatase domain ranges from 182-504.
  
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=== How the HMM was built ===
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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:
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We PSI-BLASTed the region from 190 to 600 of human MTMR2. The region is the phosphatase domain determined in crystal structure study with flanking regions <cite>Begley03</cite>:
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* Pfam database: Syja_N (PF02383), 56-343
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* CDD database: 1) Cdd:pfam02383, 55-348, 2) Cdd:COG5329, 3-578
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* SMART: no hit
  
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>Hsap_MTMR2:205-586 id=HsapP048_AA CC1:CC1:Myotubularin:MTMR1 [Homo sapiens]
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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.
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GWKLYDPLLEYRRQGIPNESWRITKINERYELCDTYPALLVVPANIPDEELKRVASFRSRGRIPVLSWIHPESQATITRCSQPMVGVSGKRSKEDEKYLQAIMDSNAQSHKIFIFDARPSVNAVANKAKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKLKEIVYPNIEETHWLSNLESTHWLEHIKLILAGALRIADKVESGKTSVVVHSSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGDKNHADADRSPVFLQFIDCVWQMTRQFPTAFEFNEYFLITILDHLYSCLFGTFLCNSEQQRGKENLPKRTVSLWSYINSQLEDFTNPLYGSYSNHVLYPVASMRHLELWVGYYIRWNPR
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We first PSI-BLASTed the region against RefSeq database via NCBI BLAST server. We found 5000+ hits in 1st round, which is difficult to look into. We then  PSI-BLASTed the region against RefSeq database via NCBI BLAST server. The coverage of human myotubularins:
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=== How the HMM was built ===
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* MTM1, MTMR1, MTMR2: ~190-600, 100%
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* MTMR3: ~214-595 (human, rat, mouse); MTMR4: ~225-588 (human, mouse), ~213-598 (xenopus)
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* MTMR5: ~317-535 (human), ~317-579 (mouse); MTMR13 (not in swissprot?)
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* MTMR6: ~195-595 (human, mouse); MTMR7: 192-592 (human), 203-593 (mouse); 192-593 (human, chicken)
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* MTMR9: 192-588 (human, mouse), 204-592 (cow)
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* MTMR10 (MTMRA): 214-532 (human, mouse, xenopus, zebra fish); MTMR11 (MTMRB): 214-561 (human, mouse); MTMR12 (MTMRC): 202-556 (human), 225-556 (mouse, rat, zebra fish),
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* MTMR13 (MTMRD): 223-581 (human), 345-581 (xenopus)
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The result shows we can build four individual HMMs for the subfamilies:
 
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* MTMR1, MTMR6, MTMR9 (perhaps MTMR3)
 
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* MTMR10
 
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* MTMR13
 
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* MTMR14
 
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Note: In addition to PSI-BLAST, we tried to obtain an alignment from HHPRED, but the quality is pretty bad.
 
  
 
=== References ===
 
=== References ===
 
<biblio>
 
<biblio>
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#Manford10 pmid=20389282
 
</biblio>
 
</biblio>
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=== Supplementary materials ===
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The full sequence of yeast SAC1:
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>yeast_SAC1
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MTGPIVYVQNADGIFFKLAEGKGTNDAVIHLANQDQGVRVLGAEEFPVQGEVVKIASLMGFIKLKLNRYAIIANTVEETGRFNGHVFYRVLQHSIVSTKFNSRIDSEEAEYIKLLELHLKNSTFYFSYTYDLTNSLQRNEKVGPAASWKTADERFFWNHYLTEDLRNFAHQDPRIDSFIQPVIYGYAKTVDAVLNATPIVLGLITRRSIFRAGTRYFRRGVDKDGNVGNFNETEQILLAENPESEKIHVFSFLQTRGSVPIYWAEINNLKYKPNLVLGENSLDATKKHFDQQKELYGDNYLVNLVNQKGHELPVKEGYESVVHALNDPKIHYVYFDFHHECRKMQWHRVKLLIDHLEKLGLSNEDFFHKVIDSNGNTVEIVNEQHSVVRTNCMDCLDRTNVVQSVLAQWVLQKEFESADVVATGSTWEDNAPLLTSYQNLWADNADAVSVAYSGTGALKTDFTRTGKRTRLGAFNDFLNSASRYYQNNWTDGPRQDSYDLFLGGFRPHTASIKSPFPDRRPVYIQLIPMIICAALTVLGATIFFPKDRFTSSKNLLYFAGASIVLALSTKFMFKNGIQFVNWPKLVDVGFLVVHQTHDKEQQFKGLKYAQSPKFSKPDPLKRD
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The sequence of SacN domain of SAC1:
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>yeast_SAC1_SacN
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MTGPIVYVQNADGIFFKLAEGKGTNDAVIHLANQDQGVRVLGAEEFPVQGEVVKIASLMGFIKLKLNRYAIIANTVEETGRFNGHVFYRVLQHSIVSTKFNSRIDSEEAEYIKLLELHLKNSTFYFSYTYDLTNSLQRNEKVGPAASWKTADERFFWNHYLTEDLRNFAHQDPRIDSFIQP
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The sequence of catalytic domain of yeast SAC1:
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>yeast_SAC1_Catalytic_Domain
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VIYGYAKTVDAVLNATPIVLGLITRRSIFRAGTRYFRRGVDKDGNVGNFNETEQILLAENPESEKIHVFSFLQTRGSVPIYWAEINNLKYKPNLVLGENSLDATKKHFDQQKELYGDNYLVNLVNQKGHELPVKEGYESVVHALNDPKIHYVYFDFHHECRKMQWHRVKLLIDHLEKLGLSNEDFFHKVIDSNGNTVEIVNEQHSVVRTNCMDCLDRTNVVQSVLAQWVLQKEFESADVVATGSTWEDNAPLLTSYQNLWADNADAVSVAYSGTGALKTDFTRTGKRTRLGAFNDFLNSASRYYQNNWTDGPRQDSYDLFLGG

Revision as of 19:24, 7 October 2015

Back to List of HMMs

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.

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.

How the HMM was built

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]

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

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