HMM PD00008

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Symbol: CC1_Sac_PD

Name: Sac phosphatase domain

Description

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 [1] 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 [1]). The Pfam profile Myotub-related (PF06602) predicted the range from 192-529.

How the HMM was built

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 [1]:

>Hsap_MTMR2:205-586 id=HsapP048_AA CC1:CC1:Myotubularin:MTMR1 [Homo sapiens] GWKLYDPLLEYRRQGIPNESWRITKINERYELCDTYPALLVVPANIPDEELKRVASFRSRGRIPVLSWIHPESQATITRCSQPMVGVSGKRSKEDEKYLQAIMDSNAQSHKIFIFDARPSVNAVANKAKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKLKEIVYPNIEETHWLSNLESTHWLEHIKLILAGALRIADKVESGKTSVVVHSSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGDKNHADADRSPVFLQFIDCVWQMTRQFPTAFEFNEYFLITILDHLYSCLFGTFLCNSEQQRGKENLPKRTVSLWSYINSQLEDFTNPLYGSYSNHVLYPVASMRHLELWVGYYIRWNPR

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:

  • MTM1, MTMR1, MTMR2: ~190-600, 100%
  • MTMR3: ~214-595 (human, rat, mouse); MTMR4: ~225-588 (human, mouse), ~213-598 (xenopus)
  • MTMR5: ~317-535 (human), ~317-579 (mouse); MTMR13 (not in swissprot?)
  • MTMR6: ~195-595 (human, mouse); MTMR7: 192-592 (human), 203-593 (mouse); 192-593 (human, chicken)
  • MTMR9: 192-588 (human, mouse), 204-592 (cow)
  • 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),
  • MTMR13 (MTMRD): 223-581 (human), 345-581 (xenopus)

The result shows we can build four individual HMMs for the subfamilies:

  • MTMR1, MTMR6, MTMR9 (perhaps MTMR3)
  • MTMR10
  • MTMR13
  • MTMR14

Note: In addition to PSI-BLAST, we tried to obtain an alignment from HHPRED, but the quality is pretty bad.

References

  1. []
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