Difference between revisions of "HMM PD0138"

Revision as of 04:39, 8 October 2015

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Symbol: CC1_MTM_1_PD

Name: Myotubularin phosphatase domain (group 1)

Why built the HMM?

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, which lacks the C-terminal ~45 aa.

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)
• MTMR14: no hit

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

• CC1_MTM_1_PD of MTMR1, MTMR6, MTMR9 (perhaps MTMR3)
• MTMR5_PD of MTMR5
• MTMR10_PD of MTMR10
• MTMR14_PD of MTMR14

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

How was the HMM built?

We PSI-BLASTed the region against PSI-BLASTed, which converged right after 1st round.

References

1. Begley MJ, Taylor GS, Kim SA, Veine DM, Dixon JE, and Stuckey JA. Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome. Mol Cell. 2003 Dec;12(6):1391-402. DOI:10.1016/s1097-2765(03)00486-6 | PubMed ID:14690594 | HubMed [Begley03]