Difference between revisions of "Protein Domain GRAM"

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(List of profiles)
 
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[[Protein_Domain_PH|PH]]: [[Protein_Domain_GRAM|GRAM]]
 
[[Protein_Domain_PH|PH]]: [[Protein_Domain_GRAM|GRAM]]
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=== List of Profiles ===
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* Pfam GRAM
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* SMART GRAM
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* Custom GRAM
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** GRAM-MTMR_1: MTMR1, MTMR5, MTMR6, MTMR9 and MTMR10 subfamilies
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** GRAM-MTMR3: MTMR3 subfamily
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** GRAM-MTMR14: MTMR14 subfamily
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** GRAM-MTMR: myotubularin family
  
 
=== Evolution ===
 
=== Evolution ===
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=== Technical notes ===
 
=== Technical notes ===
==== Profile ====
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==== Why build in-house profile for GRAM? ====
The GRAM domain in MTMR2 is from 74 to 185 as shown in crystal structure <cite>Begley03</cite>. However, its profiles in Pfam and SMART database are incomplete: Pfam gives 78-138 (envelope 68-139); SMART gives 71-139. The region covers beta sheets 1-5, but not beta sheet 6, 7 and alpha helix 1.  
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The GRAM domain in MTMR2 is from 74 to 185 as shown in crystal structure <cite>Begley03</cite>. However, its profiles in Pfam and SMART database are incomplete: Pfam gives 78-138 (envelope 68-139); SMART gives 71-139. The region covers beta sheets 1-5, but not beta sheet 6, 7 and alpha helix 1. We therefore built a profile to capture the full GRAM domain. Below are the sequence of GRAM domain of human MTMR2 determined by structure with 5 flanking residues at both N- and C-terminal (69-190):
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KLAEMEEPPLLPGENIKDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLETVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVSNNL
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Note: We tried to align the full sequences of myotubularins in phosphatome.net database. The region of GRAM domain defined by MTMR2 GRAM (74-185) does not seem well aligned. Instead, we PSI-BLASTed the GRAM domain sequences of individual subfamilies.
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==== GRAM-MTMR_1 profile for MTMR1, MTMR5, MTMR6, MTMR9 and MTMR10 subfamilies ====
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When we PSI-BLASTed the GRAM domain sequence of MTMR10 defined by CDD profile PH-GRAM_MTMR10 (see below) against SWISS-PROT dataset, we found the hits of MTMR1, MTMR5, MTMR6, MTMR9 and MTMR10 subfamilies and converged at 7th round. We selected the sequences with coverage higher than 80% of the query sequence (see below). We then downloaded the aligned sequences, performed multiple sequence alignment using Clustal Omega and built HMM profile using HMM3b.
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TDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICSNFKISFITDDPMPLQKFHYKNLLLGEHDVPLTCIEQIVTVNDHKRKQKVLGPNQKLKFNPTELIIYCKDFRVVRFRFDESGPESAKKVCLAIAHYSQPTDLQLLFAFEYVGKKYHNSVSSINGM
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==== GRAM-MTMR14 profile specific for MTMR14 subfamily ====
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We PSI-BLASTed the GRAM domain sequence of MTMR14 defined by CDD profile PH-GRAM_MTMR14 against SWISS-PROT dataset (see below). There was few hit, so we searched against RefSeq dataset, instead. The search converged at 3rd round and the hits were only from MTMR14. We selected the sequences with coverage higher than 80% of the query sequence (see below). We then downloaded the aligned sequences, remove redundant sequences (by CD-HIT, threshold 0.9) and performed multiple sequence alignment using Clustal Omega and built HMM profile using HMM3b.
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RFPFPVIYFHNKNLCRSSTLSKKIEYMFQSGVNSMKKQFstapttnqspnpnpnnnttivnIQPQAEETEIGdQNMENLRnNDINAIKHLSVKYICDLMVEnKKKKFGFYvcSSEKADMHDRYTKQFV
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==== GRAM-MTMR3 profile specific for MTMR3 subfamily ====
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We PSI-BLASTed the GRAM domain sequence of MTMR3 defined by CDD profile PH-GRAM_MTMR3 against SWISS-PROT dataset (see below). There was few hit, so we searched against RefSeq dataset, instead. The search converged at 2nd round and the hits were only from MTMR3. We selected the sequences with coverage higher than 80% of the query sequence (see below). We then downloaded the aligned sequences, remove redundant sequences (by CD-HIT, threshold 0.9) and performed multiple sequence alignment using Clustal Omega and built HMM profile using HMM3b.
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MDEETRHSLECIQANQIFPRKQLIREDENLQVPFLELHGESTEFVGRAEDAIIALSNYRLHIKFKESLVNVPLQLIESVECRDIFQLHLTCKDCKVIRCQFSTFEQCQEWLKRLNNAIRPPAKIEDLFSFAYHAWCMEVYASEKEQHG
  
 
=== References ===
 
=== References ===

Latest revision as of 00:46, 28 June 2015

PH: GRAM

List of Profiles

  • Pfam GRAM
  • SMART GRAM
  • Custom GRAM
    • GRAM-MTMR_1: MTMR1, MTMR5, MTMR6, MTMR9 and MTMR10 subfamilies
    • GRAM-MTMR3: MTMR3 subfamily
    • GRAM-MTMR14: MTMR14 subfamily
    • GRAM-MTMR: myotubularin family

Evolution

Structure

The GRAM domain in MTMR2 has 7 beta sheets and 1 alpha helix, resembling Pleckstrin (PH) domain [1].

Functions

Technical notes

Why build in-house profile for GRAM?

The GRAM domain in MTMR2 is from 74 to 185 as shown in crystal structure [1]. However, its profiles in Pfam and SMART database are incomplete: Pfam gives 78-138 (envelope 68-139); SMART gives 71-139. The region covers beta sheets 1-5, but not beta sheet 6, 7 and alpha helix 1. We therefore built a profile to capture the full GRAM domain. Below are the sequence of GRAM domain of human MTMR2 determined by structure with 5 flanking residues at both N- and C-terminal (69-190):

KLAEMEEPPLLPGENIKDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLETVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVSNNL

Note: We tried to align the full sequences of myotubularins in phosphatome.net database. The region of GRAM domain defined by MTMR2 GRAM (74-185) does not seem well aligned. Instead, we PSI-BLASTed the GRAM domain sequences of individual subfamilies.

GRAM-MTMR_1 profile for MTMR1, MTMR5, MTMR6, MTMR9 and MTMR10 subfamilies

When we PSI-BLASTed the GRAM domain sequence of MTMR10 defined by CDD profile PH-GRAM_MTMR10 (see below) against SWISS-PROT dataset, we found the hits of MTMR1, MTMR5, MTMR6, MTMR9 and MTMR10 subfamilies and converged at 7th round. We selected the sequences with coverage higher than 80% of the query sequence (see below). We then downloaded the aligned sequences, performed multiple sequence alignment using Clustal Omega and built HMM profile using HMM3b.

TDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICSNFKISFITDDPMPLQKFHYKNLLLGEHDVPLTCIEQIVTVNDHKRKQKVLGPNQKLKFNPTELIIYCKDFRVVRFRFDESGPESAKKVCLAIAHYSQPTDLQLLFAFEYVGKKYHNSVSSINGM

GRAM-MTMR14 profile specific for MTMR14 subfamily

We PSI-BLASTed the GRAM domain sequence of MTMR14 defined by CDD profile PH-GRAM_MTMR14 against SWISS-PROT dataset (see below). There was few hit, so we searched against RefSeq dataset, instead. The search converged at 3rd round and the hits were only from MTMR14. We selected the sequences with coverage higher than 80% of the query sequence (see below). We then downloaded the aligned sequences, remove redundant sequences (by CD-HIT, threshold 0.9) and performed multiple sequence alignment using Clustal Omega and built HMM profile using HMM3b.

RFPFPVIYFHNKNLCRSSTLSKKIEYMFQSGVNSMKKQFstapttnqspnpnpnnnttivnIQPQAEETEIGdQNMENLRnNDINAIKHLSVKYICDLMVEnKKKKFGFYvcSSEKADMHDRYTKQFV

GRAM-MTMR3 profile specific for MTMR3 subfamily

We PSI-BLASTed the GRAM domain sequence of MTMR3 defined by CDD profile PH-GRAM_MTMR3 against SWISS-PROT dataset (see below). There was few hit, so we searched against RefSeq dataset, instead. The search converged at 2nd round and the hits were only from MTMR3. We selected the sequences with coverage higher than 80% of the query sequence (see below). We then downloaded the aligned sequences, remove redundant sequences (by CD-HIT, threshold 0.9) and performed multiple sequence alignment using Clustal Omega and built HMM profile using HMM3b.

MDEETRHSLECIQANQIFPRKQLIREDENLQVPFLELHGESTEFVGRAEDAIIALSNYRLHIKFKESLVNVPLQLIESVECRDIFQLHLTCKDCKVIRCQFSTFEQCQEWLKRLNNAIRPPAKIEDLFSFAYHAWCMEVYASEKEQHG

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]