HMM PD0003
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Symbol: CC1_MTM_PD
Name: Myotubularin phosphatase domain
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. The C-terminal 45 aa consists of helix 15 and a disordered region in crystal structure.
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)
- MTMR14: no hit
We just built the HMM followed the general guidance. By using the protein phosphatases of the nine genomes, we found the HMM profile can detect the phosphatase domains of all subfamilies with good boundaries except MTMR14. The HMM has a length of 391 aa, all subfamilies except MTMR14 has the domains of > 380 aa long. Because the HMM does not capture MTMR14, we archive the HMM in a separate page CC1_MTM_1_PD.
See MTMR14, conserved regions (MTMR14_CR) and MTMR14, phosphatase domain (MTMR14_PD) for MTMR14 conserved regions and phosphatase domain.
Note:
- In addition to PSI-BLAST, we tried to obtain an alignment from HHPRED, but the quality is pretty bad.
- The profile overlaps with 3-PAP of Pfam database.
