Alignments for a candidate for B12-reactivation-domain in Clostridium acetobutylicum ATCC 824

GapMind for Amino acid biosynthesis

Alignments for a candidate for B12-reactivation-domain in Clostridium acetobutylicum ATCC 824

Align candidate NP_347216.1 CA_C0578 (B12-dependent methionine synthase)
to HMM PF02965 (Met_synt_B12)

# hmmsearch :: search profile(s) against a sequence database
# HMMER 3.3.1 (Jul 2020); http://hmmer.org/
# Copyright (C) 2020 Howard Hughes Medical Institute.
# Freely distributed under the BSD open source license.
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
# query HMM file:                  ../tmp/path.aa/PF02965.21.hmm
# target sequence database:        /tmp/gapView.12694.genome.faa
# - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Query:       Met_synt_B12  [M=273]
Accession:   PF02965.21
Description: Vitamin B12 dependent methionine synthase, activation domain
Scores for complete sequences (score includes all domains):
   --- full sequence ---   --- best 1 domain ---    -#dom-
    E-value  score  bias    E-value  score  bias    exp  N  Sequence                              Description
    ------- ------ -----    ------- ------ -----   ---- --  --------                              -----------
   3.9e-116  373.3   0.0   8.4e-116  372.2   0.0    1.6  1  lcl|NCBI__GCF_000008765.1:NP_347216.1  CA_C0578 B12-dependent methionin


Domain annotation for each sequence (and alignments):
>> lcl|NCBI__GCF_000008765.1:NP_347216.1  CA_C0578 B12-dependent methionine synthase
   #    score  bias  c-Evalue  i-Evalue hmmfrom  hmm to    alifrom  ali to    envfrom  env to     acc
 ---   ------ ----- --------- --------- ------- -------    ------- -------    ------- -------    ----
   1 !  372.2   0.0  8.4e-116  8.4e-116       2     272 ..     932    1197 ..     931    1198 .. 0.98

  Alignments for each domain:
  == domain 1  score: 372.2 bits;  conditional E-value: 8.4e-116
                           Met_synt_B12    2 leelveyidWtpffqaWelkgkypkiledekvgeeakklfkdAqamLkkiieekllkakavvglfpAnse 71  
                                             ++el++yidWt+ff++W++ ++ypki++d+k+g+ea+klfkdA++mL+ +++e+l+++++v+g+fpAns+
  lcl|NCBI__GCF_000008765.1:NP_347216.1  932 INELRKYIDWTFFFTSWDMGMNYPKIMKDPKYGAEAQKLFKDANEMLDLLQKENLITCNGVFGIFPANSV 1001
                                             89******************************************************************** PP

                           Met_synt_B12   72 gddievyadesrseelatlhtLrqqaekeegkpnlclaDfvapkesgvkDyiGlFavtaglgieelakef 141 
                                             +ddie+y+d+     ++t++tLrqq+   +++++ +l+D++apk  g+kDyiG+F+vtag+g++e+ +++
  lcl|NCBI__GCF_000008765.1:NP_347216.1 1002 NDDIEIYTDKG----TVTINTLRQQQIL-KDSDYKALSDYIAPKGIGIKDYIGGFIVTAGIGAKEYSDKL 1066
                                             *******7776....689*******765.7889************************************* PP

                           Met_synt_B12  142 eaekddYsailvkaladrLaeAfaellhekvrkelWgyakdeklsneelikekYqgiRpApGYpacpdht 211 
                                             +++ ddY a ++k ++drLaeAf+ellh +vrke+Wgy++de+ls e+l+k +Y+gi+pA+GYp++pdh+
  lcl|NCBI__GCF_000008765.1:NP_347216.1 1067 KKKCDDYGATMLKLICDRLAEAFSELLHLRVRKEYWGYSQDENLSLEKLLKGSYRGIKPAIGYPSIPDHS 1136
                                             ********************************************************************** PP

                           Met_synt_B12  212 ekktlfelldaeekigieLteslamtPaasvsGlyfahpearyFavgkiekdqvedyakrk 272 
                                             ek++lf+ll  +++ig+eLtes++m P++sv+Glyfa+++a+yF+++ki+kdq+edya r 
  lcl|NCBI__GCF_000008765.1:NP_347216.1 1137 EKAKLFDLLLGKTSIGVELTESYMMNPTSSVCGLYFANERAKYFNINKIGKDQLEDYAVRS 1197
                                             **********************************************************996 PP



Internal pipeline statistics summary:
-------------------------------------
Query model(s):                            1  (273 nodes)
Target sequences:                          1  (1212 residues searched)
Passed MSV filter:                         1  (1); expected 0.0 (0.02)
Passed bias filter:                        1  (1); expected 0.0 (0.02)
Passed Vit filter:                         1  (1); expected 0.0 (0.001)
Passed Fwd filter:                         1  (1); expected 0.0 (1e-05)
Initial search space (Z):                  1  [actual number of targets]
Domain search space  (domZ):               1  [number of targets reported over threshold]
# CPU time: 0.01u 0.00s 00:00:00.01 Elapsed: 00:00:00.00
# Mc/sec: 34.86
//
[ok]

This GapMind analysis is from Apr 10 2024. The underlying query database was built on Apr 09 2024.

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About GapMind

Each pathway is defined by a set of rules based on individual steps or genes. Candidates for each step are identified by using ublast (a fast alternative to protein BLAST) against a database of manually-curated proteins (most of which are experimentally characterized) or by using HMMer with enzyme models (usually from TIGRFam). Ublast hits may be split across two different proteins.

A candidate for a step is "high confidence" if either:

ublast finds a hit to a characterized protein at above 40% identity and 80% coverage, and bits >= other bits+10.
- (Hits to curated proteins without experimental data as to their function are never considered high confidence.)
HMMer finds a hit with 80% coverage of the model, and either other identity < 40 or other coverage < 0.75.

where "other" refers to the best ublast hit to a sequence that is not annotated as performing this step (and is not "ignored").

Otherwise, a candidate is "medium confidence" if either:

ublast finds a hit at above 40% identity and 70% coverage (ignoring otherBits).
ublast finds a hit at above 30% identity and 80% coverage, and bits >= other bits.
HMMer finds a hit (regardless of coverage or other bits).

Other blast hits with at least 50% coverage are "low confidence."

Steps with no high- or medium-confidence candidates may be considered "gaps." For the typical bacterium that can make all 20 amino acids, there are 1-2 gaps in amino acid biosynthesis pathways. For diverse bacteria and archaea that can utilize a carbon source, there is a complete high-confidence catabolic pathway (including a transporter) just 38% of the time, and there is a complete medium-confidence pathway 63% of the time. Gaps may be due to:

our ignorance of proteins' functions,
omissions in the gene models,
frame-shift errors in the genome sequence, or
the organism lacks the pathway.

GapMind relies on the predicted proteins in the genome and does not search the six-frame translation. In most cases, you can search the six-frame translation by clicking on links to Curated BLAST for each step definition (in the per-step page).

For more information, see:

the paper from 2019 on GapMind for amino acid biosynthesis
the paper from 2022 on GapMind for carbon sources
the source code
instructions for running GapMind on your computer
changes to Amino acid biosynthesis since the publication.

If you notice any errors or omissions in the step descriptions, or any questionable results, please let us know

by Morgan Price, Arkin group, Lawrence Berkeley National Laboratory

GapMind for Amino acid biosynthesis