HMM PD00008 - Revision history

Gerard: /* Description */

2017-03-26T18:22:11Z

‎Description

Mark: /* References */

2015-10-28T20:18:41Z

‎References

Mark: /* Description */

2015-10-20T18:41:02Z

‎Description

Mark: /* Description */

2015-10-20T18:35:26Z

‎Description

Mark: Mark moved page HMM PD0008 to HMM PD00008

2015-10-20T18:25:57Z

Mark moved page HMM PD0008 to HMM PD00008

Mark: /* Description */

2015-10-20T18:20:50Z

‎Description

Mark: /* How the HMM was built */

2015-10-07T21:31:23Z

‎How the HMM was built

Mark: /* How the HMM was built */

2015-10-07T21:30:24Z

‎How the HMM was built

Mark at 19:24, 7 October 2015

2015-10-07T19:24:58Z

Mark: 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 ..."

2015-10-07T16:48:39Z

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 ..."

New page

Back to '''[[HMM|List of HMMs]]'''

'''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 <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.

=== 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 <cite>Begley03</cite>:

>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 ===
<biblio>
</biblio>

@@ Line 6: / Line 6: @@
 === Description ===
-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. The SacN domain mediates the interaction with VPS74, which is proposed to mediate packaging of medial Golgi glycosyltransferases into coatomer (also called COP1)-coated vesicles, thereby maintaining Golgi residence <cite>Cai14</cite>.
+Based upon the crystal structure of the yeast member, SAC1 has two structural domains: SacN and the catalytic phosphatase domain <cite>Manford10</cite> (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 <cite>Cai14</cite>.
 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:

@@ Line 8: / Line 8: @@
 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. The SacN domain mediates the interaction with VPS74, which is proposed to mediate packaging of medial Golgi glycosyltransferases into coatomer (also called COP1)-coated vesicles, thereby maintaining Golgi residence <cite>Cai14</cite>.
-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:
+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
-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. Because the region of 451-511 is required for PtdIns4P phosphatase activity <cite>Cai14</cite>, Pfam PF02383 is not a good description for Sac phosphatase domain.
+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 <cite>Cai14</cite>. COG profile contains both SacN and the catalytic phosphatase domain, but also the trans-membrane–spanning domains (523-578) (figure 4A in <cite>Cai14</cite>). We therefore built our own profiles for SacN and catalytic phosphatase domain.
 === How the HMM was built ===

@@ Line 13: / Line 13: @@
 * 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. Because the region of 451-511 is required for PtdIns4P phosphatase activity <cite>Cai14</cite>, Pfam PF02383 is not a good profile for Sac phosphatase domain.
+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. Because the region of 451-511 is required for PtdIns4P phosphatase activity <cite>Cai14</cite>, Pfam PF02383 is not a good description for Sac phosphatase domain.
 === How the HMM was built ===

@@ Line 6: / Line 6: @@
 === Description ===
-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.
+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. The SacN domain mediates the interaction with VPS74, which is proposed to mediate packaging of medial Golgi glycosyltransferases into coatomer (also called COP1)-coated vesicles, thereby maintaining Golgi residence <cite>Cai14</cite>.
 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:
@@ Line 13: / Line 13: @@
 * 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.
+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. Because the region of 451-511 is required for PtdIns4P phosphatase activity <cite>Cai14</cite>, Pfam PF02383 is not a good profile for Sac phosphatase domain.
 === How the HMM was built ===

@@ Line 18: / Line 18: @@
 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. The profile of SacN is available at [[HMM_PD0139|here]].
+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 ===

@@ Line 22: / Line 22: @@
 === References ===
 <biblio>
 #Manford10 pmid=20389282
 </biblio>

← Older revision	Revision as of 18:25, 20 October 2015
(No difference)

← Older revision		Revision as of 21:30, 7 October 2015
Line 16:		Line 16:

	=== How the HMM was built ===		=== 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. The profile of SacN is available at [[HMM_PD0139\|here]].

	=== References ===		=== References ===

@@ Line 6: / Line 6: @@
 === 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 <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.
+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.
-=== How the HMM was built ===
+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:
-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>:
+* Pfam database: Syja_N (PF02383), 56-343
->Hsap_MTMR2:205-586 id=HsapP048_AA CC1:CC1:Myotubularin:MTMR1 [Homo sapiens]
+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.
-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:
+=== How the HMM was built ===
-* 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)
 === References ===
 <biblio>
 </biblio>