The Case of EC 3.5.3.13 in Histidine Degradation

Ross Overbeek, Fellowship for Interpretation of Genomes


I recently constructed a subsystem for histidine degradation as an exercise. KEGG shows the pathway as containing three initial steps:

  1. Histidine ammonia-lyase (EC 4.3.1.3)
  2. Urocanate hydratase (EC 4.2.1.49)
  3. Imidazolonepropionase (EC 3.5.2.7)
These are followed by three alternatives: That is, the pathway will be complete if you have (1,2,3) and any one of these last three alternatives. What I discovered is that there is no sequence in entrez (or KEGG) with the function EC 3.5.3.13. There are numerous (over 20) beautiful clusters with an obvious candidate for 3.5.3.13. For example, in Caulobacter crescentus CB15 the gene with RefSeq id: NP_419777.1 and UniProt id: uni|Q9A9L9 is, I assert, a gene playing the functional role Formiminoglutamic iminohydrolase (EC 3.5.3.13).
The functional roles in the diagram are as follows:

Functional Roles
Column Abbrev Functional Role
1 HutH Histidine ammonia-lyase (EC 4.3.1.3)
2 HutU Urocanate hydratase (EC 4.2.1.49)
3 HutI Imidazolonepropionase (EC 3.5.2.7)
4 GluF Glutamate formiminotransferase (EC 2.1.2.5)
5 HutG Formiminoglutamase (EC 3.5.3.8)
6 NfoD N-formylglutamate deformylase (EC 3.5.1.68)
7 ForI Formiminoglutamic iminohydrolase (EC 3.5.3.13)


The following spreadsheet shows instances of gene clusters implementing the three alternative versions of the pathway. The protein IDs in each row are given the same color to show that they are produced by genes that are physically clustered on the chromosome. In each case, the genes are all a single contiguous cluster.
Basic Spreadsheet
Organism HutH HutU HutI GluF HutG NfoD ForI
Caulobacter crescentus P58082 Q9A9M1 P58079 Q9A9M0 Q9A9L9
Pseudomonas putida Q88CZ7 Q88CZ6 Q88CZ9 Q88D00 Q88CZ3
Xanthomonas campestris Q8PAA7 P58988 Q8PAA6 Q8PAA8 Q8PAA5
Halobacterium sp. Q9HQD5 Q9HQD8 Q9HQD6 Q9HQD7
Deinococcus radiodurans Q9RZ06 Q9RZ02 Q9RZ05 Q9RZ04
Bacillus subtilis P10944 P25503 P42084 P42068
Bacteroides thetaiotaomicron Q8A4B3 Q8A4A9 Q8A4B1 Q8A4B0
Desulfotalea psychrophila gi|51246205 gi|51246204 gi|51246203 gi|51246202

The following tree includes the subtree that I believe should be assigned EC 3.5.3.13. Note that fig|266835.1.peg.6537 (uni|Q983I2 - Mesorhizobium loti MAFF303099) and fig|227882.1.peg.3497 (uni|Q82HL4 -[Streptomyces avermitilis MA-4680) occur clustered with Imidazolonepropionase (EC 3.5.2.7) and represent diverse subgroups within the tree I have labeled as 3.5.3.13.
                                                                              ,- fig|176299.1.peg.3660 [Agrobacterium tumefaciens str. C58] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                                        ,---------------------|
                                                        |                     `- fig|176299.1.peg.9005 [Agrobacterium tumefaciens str. C58] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                                   ,----|
                                                   |    |  ,------------------- fig|266779.1.peg.1515 [Mesorhizobium sp. BNC1] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                                   |    `--|
                                                   |       `------------------- fig|216596.1.peg.5296 [Rhizobium leguminosarum bv. viciae 3841] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                                ,--|
                                                |  |                            ,- fig|235.1.peg.1262 [Brucella abortus] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                                |  |                          ,-|
                                                |  |                          | `- fig|204722.1.peg.3004 [Brucella suis 1330] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                                |  | ,------------------------|
                                                |  | |                        `- fig|224914.1.peg.2429 [uni|Q8YD08] [Brucella melitensis 16M] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                                |  `-|
                                                |    `---------------------- fig|266835.1.peg.6537 [uni|Q983I2] [Mesorhizobium loti MAFF303099] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                             ,--|
                                             |  `-------------------------- fig|224911.1.peg.6244 [uni|Q89GV1] [Bradyrhizobium japonicum USDA 110] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                         ,---|
                                         |   | ,---------------------------- fig|190650.1.peg.957 [uni|Q9A9L9] [Caulobacter crescentus CB15] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                         |   `-|
                                         |     |                 ,------------ fig|190485.1.peg.1557 [uni|Q8PAA5] [Xanthomonas campestris pv. campestris str. ATCC 33913] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                         |     |        ,--------|
                                         |     |        |        `------------ fig|190486.1.peg.1615 [uni|Q8PLZ6] [Xanthomonas axonopodis pv. citri str. 306] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                         |     `--------|
                                         |              `-------------------- fig|40324.1.peg.85 [Stenotrophomonas maltophilia K279a] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                       ,-|
                                       | |  ,--------------------------------- fig|1063.1.peg.3139 [Rhodobacter sphaeroides] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                       | `--|
                                       |    |     ,------------------------- fig|292414.1.peg.1025 [Silicibacter sp. TM1040] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                                       |    `-----|
                                       |          `------------------------- fig|246200.1.peg.2147 [Silicibacter pomeroyi DSS-3] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            ,----------|
                            |          |                ,-------------------- fig|354.1.peg.626 [Azotobacter vinelandii] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |          ,-----|
                            |          |          |     |                   ,- fig|208964.1.peg.5103 [uni|Q9HU77] [Pseudomonas aeruginosa PAO1] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |          |     |     ,-------------|
                            |          |          |     |     |             `- fig|208963.1.peg.5691 [Pseudomonas aeruginosa UCBPP-PA14] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |          |     `-----|
                            |          |          |           |  ,------------ fig|160488.1.peg.4967 [uni|Q88CZ3] [Pseudomonas putida KT2440] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |          |           `--|
                            |          |          |              |         ,---- fig|205918.1.peg.1362 [Pseudomonas syringae pv. syringae B728a] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |          |              |  ,------|
                            |          |          |              |  |      `---- fig|223283.1.peg.5040 [uni|Q87UX1] [Pseudomonas syringae pv. tomato str. DC3000] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |          |              `--|
                            |          |          |                 `---------- fig|205922.1.peg.490 [Pseudomonas fluorescens PfO-1] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |      ,---|
                            |          |      |   |                              ,- fig|187410.1.peg.2298 [uni|Q8D0E1] [Yersinia pestis KIM] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |      |   |                            ,-|
                            |          |      |   |                            | |   ,- fig|633.2.peg.2107 [Yersinia pseudotuberculosis (Livermore)] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |      |   |                            | | ,-|
                            |          |      |   |                            | | | `- fig|273123.1.peg.2067 [Yersinia pseudotuberculosis IP 32953] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |      |   |                            | `-|
                            |          |      |   |                            |   | ,- fig|214092.1.peg.2047 [Yersinia pestis CO92] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |      |   |                            |   `-|
                            |          |      |   |                            |     `- fig|229193.1.peg.1765 [Yersinia pestis biovar Medievalis str. 91001] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |      |   |                   ,--------|
                            |          |      |   |                   |        `- fig|633.1.peg.2917 [Yersinia pseudotuberculosis] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |      |   |         ,---------|
                            |          |      |   |         |         `--------- fig|630.2.peg.2383 [Yersinia enterocolitica 8081] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |      |   `---------|
                            |          |      |             `------------------ fig|615.1.peg.234 [Serratia marcescens Db11] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          |   ,--|
                            |          |   |  `------------------------------- fig|266834.1.peg.3993 [uni|Q92MC7] [Sinorhizobium meliloti 1021] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          | ,-|
                            |          | | |                                ,-- fig|216591.1.peg.673 [Burkholderia cepacia J2315] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          | | |                              ,-|
                            |          | | |                              | `--- fig|269483.1.peg.6487 [Burkholderia cepacia R18194] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          | | |                   ,----------|
                            |          | | |                   |          `---- fig|269482.1.peg.2107 [Burkholderia cepacia R1808] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          | | |              ,----|
                            |          | | |              |    `-------------- fig|28450.1.peg.4196 [Burkholderia pseudomallei K96243] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          | | |   ,----------|
                            |          | | |   |          `------------------- fig|134537.1.peg.2488 [Burkholderia fungorum] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          | | `---|
                            |          | |     |             ,----------------- fig|119219.1.peg.2960 [Ralstonia metallidurans] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          | |     `-------------|
                            |          | |                   `---------------- fig|264198.1.peg.6150 [Ralstonia eutropha JMP134] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                            |          `-|
                            |            `----------------------------------- fig|1085.1.peg.3064 [Rhodospirillum rubrum] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                          ,-|
                          | `------------------------------------------ fig|266117.1.peg.2318 [Rubrobacter xylanophilus DSM 9941] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                    ,-----|
                    |     |                                   ,------- fig|100226.1.peg.3033 [uni|Q9KZ77] [Streptomyces coelicolor A3(2)] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                    |     |           ,-----------------------|
                    |     |           |                       `------- fig|227882.1.peg.3497 [uni|Q82HL4] [Streptomyces avermitilis MA-4680] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                    |     |     ,-----|
                    |     |     |     `------------------------------- fig|266940.1.peg.2493 [Kineococcus radiotolerans SRS30216] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
                    |     `-----|
                    |           `--------------------------------------- fig|267747.1.peg.2109 [Propionibacterium acnes KPA171202] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
       ,------------|
       |            `------------------------------------------------- fig|6239.1.peg.11521 [uni|Q20166] [Caenorhabditis elegans] CyPIn, guanine aminohydrolase homolog (cpi-1) / CyPIn, guanine aminohydrolase homolog (cpi-1)
    ,--|
    |  |                                                     ,----- fig|216595.1.peg.3281 [Pseudomonas fluorescens SBW25] Chlorohydrolase/deaminase family protein
    |  |                                                  ,--|
    |  |                                                  |  `----- fig|205922.1.peg.805 [Pseudomonas fluorescens PfO-1]
    |  |                                      ,-----------|
    |  |                                      |           |    ,-- fig|205918.1.peg.1661 [Pseudomonas syringae pv. syringae B728a] Cytosine deaminase and related metal-dependent hydrolases
    |  |                                      |           `----|
    |  |                                      |                `--- fig|223283.1.peg.750 [uni|Q889I4] [Pseudomonas syringae pv. tomato str. DC3000] hydroxydechloroatrazine ethylaminohydrolase
    |  |                                    ,-|
    |  |                                    | `------------------ fig|188.1.peg.3497 [Magnetospirillum magnetotacticum] Cytosine deaminase and related metal-dependent hydrolases
    |  |                             ,------|
    |  |                             |      `--------------------- fig|62977.1.peg.696 [Acinetobacter sp. ADP1]
    |  |                ,------------|
    |  |                |            `---------------------------- fig|224911.1.peg.6159 [uni|Q89H36] [Bradyrhizobium japonicum USDA 110] bll6159; putative hydroxydechloroatrazine ethylaminohydrolase (EC 3.5.99.3)
    |  |              ,-|
    |  |              | |                    ,------------------ fig|1061.1.peg.1990 [Rhodobacter capsulatus SB1003] Chlorohydrolase/deaminase family protein
    |  |              | |          ,---------|
    |  |              | |          |         `------------------ fig|292414.1.peg.297 [Silicibacter sp. TM1040] Cytosine deaminase and related metal-dependent hydrolases
    |  |              | |    ,-----|
    |  |              | |    |     |              ,--------------- fig|267608.1.peg.2119 [uni|Q8XXJ4] [Ralstonia solanacearum GMI1000] cell processes; protection responses; detoxification
    |  |              | |    |     |         ,----|
    |  |              | |    |     |         |    |       ,---------- fig|119219.1.peg.5603 [Ralstonia metallidurans] Cytosine deaminase and related metal-dependent hydrolases
    |  |              | |    |     |         |    `-------|
    |  |              | |    |     |         |            `------ fig|264198.1.peg.3874 [Ralstonia eutropha JMP134]
    |  |              | |    |     `---------|
    |  |              | |    |               |          ,---------- fig|28450.1.peg.4441 [Burkholderia pseudomallei K96243] Chlorohydrolase/deaminase family protein
    |  |              | |    |               |       ,--|
    |  |              | |    |               |       |  |         ,- fig|269483.1.peg.6035 [Burkholderia cepacia R18194] Cytosine deaminase and related metal-dependent hydrolases
    |  |              | |    |               |       |  |       ,-|
    |  |              | |    |               |       |  |       | `- fig|216591.1.peg.5865 [Burkholderia cepacia J2315] Chlorohydrolase/deaminase family protein
    |  |              | |    |               |       |  `-------|
    |  |              | |    |               |       |          `-- fig|269482.1.peg.5837 [Burkholderia cepacia R1808] Cytosine deaminase and related metal-dependent hydrolases
    |  |              | |    |               |   ,---|
    |  |              | |    |               |   |   `------------- fig|134537.1.peg.2991 [Burkholderia fungorum] Cytosine deaminase and related metal-dependent hydrolases
    |  |              | |    |               | ,-|
    |  |              | |    |               | | `----------------- fig|188.1.peg.5477 [Magnetospirillum magnetotacticum] Cytosine deaminase and related metal-dependent hydrolases
    |  |              | |    |               `-|
    |  |              | |    |                 `----------------- fig|160488.1.peg.2558 [uni|Q88JR5] [Pseudomonas putida KT2440] chlorohydrolase family protein
    |  |              | `----|
    |  |              |      `------------------------------------------ fig|264732.1.peg.2622 [Moorella thermoacetica ATCC 39073]
    |  |           ,--|
    |  |           |  |           ,----------------------------- fig|266940.1.peg.4012 [Kineococcus radiotolerans SRS30216] Chlorohydrolase/deaminase family protein
    |  |           |  |     ,-----|
    |  |           |  |     |     `----------------------------- fig|216594.1.peg.1624 [Mycobacterium marinum M] Chlorohydrolase/deaminase family protein
    |  |           |  `-----|
    |  |           |        `--------------------------------- fig|227882.1.peg.2019 [uni|Q82LJ3] [Streptomyces avermitilis MA-4680] Chlorohydrolase/deaminase family protein
    |  |         ,-|
    |  |         | |                    ,--------------------------- fig|62977.1.peg.1352 [Acinetobacter sp. ADP1]
    |  |         | |           ,--------|
    |  |         | |           |        | ,------------------------- fig|134537.1.peg.6947 [Burkholderia fungorum] Cytosine deaminase and related metal-dependent hydrolases
    |  |         | |           |        `-|
    |  |         | |           |          `------------------------ fig|160488.1.peg.3183 [uni|Q88HZ3] [Pseudomonas putida KT2440] chlorohydrolase, putative
    |  |         | `-----------|
    |  |         |             |           ,--------------------- fig|264198.1.peg.1469 [Ralstonia eutropha JMP134]
    |  |         |             `-----------|
    |  |         |                         `-------------------- fig|216591.1.peg.4278 [Burkholderia cepacia J2315] Chlorohydrolase/deaminase family protein
    |  |     ,---|
    |  |     |   |                                  ,------------- fig|216596.1.peg.6831 [Rhizobium leguminosarum bv. viciae 3841]
    |  |     |   `----------------------------------|
    |  |     |                                      `------------ fig|188.1.peg.5896 [Magnetospirillum magnetotacticum] Cytosine deaminase and related metal-dependent hydrolases
    |  | ,---|
    |  | |   `-------------------------------------------- fig|264732.1.peg.2621 [Moorella thermoacetica ATCC 39073]
    |  `-|
    |    |                                                ,--- fig|103690.1.peg.4056 [uni|Q8YQS0] [Nostoc sp. PCC 7120] probable chlorohydrolase
    |    |                                      ,---------|
    |    |                                      |         `--- fig|240292.1.peg.1959 [Anabaena variabilis ATCC 29413]
    |    `--------------------------------------|
    |                                           `------------ fig|63737.1.peg.1439 [Nostoc punctiforme] Cytosine deaminase and related metal-dependent hydrolases
  ,-|
  | |   ,---------------------------------------------- fig|4896.1.peg.2763 [uni|Q92342] [Schizosaccharomyces pombe] putative chlorohydrolase/deaminase
  | | ,-|
  | | | |                ,------------------------------- fig|207559.1.peg.1707 [Desulfovibrio desulfuricans G20] Cytosine deaminase and related metal-dependent hydrolases
  | | | | ,--------------|
  | | | | |              |    ,-------------------------- fig|1496.1.peg.2285 [Clostridium difficile 630] Chlorohydrolase/deaminase family protein
  | | | | |              `----|
  | | | | |                   `------------------------ fig|1491.1.peg.3096 [Clostridium botulinum ATCC 3502] Chlorohydrolase/deaminase family protein
  | | | `-|
  | | |   |                       ,-------------------- fig|1496.1.peg.2690 [Clostridium difficile 630] Chlorohydrolase/deaminase family protein
  | | |   `-----------------------|
  | | |                           `-------------------- fig|1496.1.peg.2697 [Clostridium difficile 630] Chlorohydrolase/deaminase family protein
  | `-|
  |   |     ,--------------------------------------- fig|64091.1.peg.1114 [uni|Q9HQE0] [Halobacterium sp. NRC-1] conserved hypothetical protein
  |   `-----|
  |         |          ,-------------------------- fig|264732.1.peg.1644 [Moorella thermoacetica ATCC 39073]
  |         `----------|
  |                    `---------------------------- fig|272558.1.peg.746 [uni|Q9KEV3] [Bacillus halodurans C-125] N-ethylammeline chlorohydrolase
 -|
  |                                                      ,- fig|260799.1.peg.1703 [Bacillus anthracis str. Sterne] Chlorohydrolase family protein
  |                                                    ,-|
  |                                                    | |   ,- fig|191218.1.peg.2677 [Bacillus anthracis str. A2012] Adenine_deam, Adenine deaminase
  |                                                    | | ,-|
  |                                                    | | | `- fig|261594.1.peg.2017 [Bacillus anthracis str. 'Ames Ancestor'] chlorohydrolase family protein
  |                                                    | `-|
  |                                                    |   `- fig|198094.1.peg.1710 [Bacillus anthracis str. Ames] Cytosine deaminase, related metal-dependent hydrolases, chlorohydrolase
  |                                                  ,-|
  |                                                  | `- fig|281309.1.peg.1679 [Bacillus thuringiensis serovar konkukian str. 97-27] chlorohydrolase/deaminase family protein
  |                                               ,--|
  |                                               |  | ,- fig|226900.1.peg.1678 [uni|Q81F14] [Bacillus cereus ATCC 14579] Chlorohydrolase/deaminase family protein
  |                                               |  `-|
  |                                               |    | ,- fig|222523.1.peg.1939 [uni|O31352] [Bacillus cereus ATCC 10987] chlorohydrolase family protein
  |                                               |    `-|
  |                                               |      `- fig|269801.1.peg.1219 [Bacillus cereus G9241] Atz/Trz family protein
  |               ,-------------------------------|
  |               |                               `- fig|191218.1.peg.2678 [Bacillus anthracis str. A2012] ATZ_TRZ, Chlorohydrolase
  |          ,----|
  |          |    `-------------------------------------- fig|170187.1.peg.1261 [uni|Q97Q72] [Streptococcus pneumoniae TIGR4] Atz/Trz family protein
  |       ,--|
  |       |  `--------------------------------------- fig|272558.1.peg.1692 [uni|Q9KC82] [Bacillus halodurans C-125] Cytosine deaminase, related metal-dependent hydrolases, chlorohydrolase
  |     ,-|
  |     | |    ,----------------------------------------- fig|212717.1.peg.1993 [uni|Q891Y7] [Clostridium tetani E88] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  |     | | ,--|
  |     | | |  |   ,---------------------------------- fig|203119.1.peg.478 [Clostridium thermocellum ATCC 27405] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  |     | | |  `---|
  |     | | |      `--------------------------------- fig|119072.1.peg.1480 [uni|Q8R9L4] [Thermoanaerobacter tengcongensis] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  |     | `-|
  |     |   |    ,-------------------------------- fig|264732.1.peg.2165 [Moorella thermoacetica ATCC 39073] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  |     |   `----|
  |     |        `----------------------------------- fig|49338.1.peg.1385 [Desulfitobacterium hafniense] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  |   ,-|
  |   | `---------------------------------------------- fig|243274.1.peg.928 [uni|Q9X034] [Thermotoga maritima MSB8] Cytosine deaminase, related metal-dependent hydrolases, chlorohydrolase
  | ,-|
  | | |                           ,------------------- fig|243232.1.peg.1586 [uni|Q58936] [Methanocaldococcus jannaschii DSM 2661] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |         ,-----------------|
  | | |         |                 `---------------------- fig|267377.1.peg.1491 [Methanococcus maripaludis S2] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |       ,-|
  | | |       | |               ,------------------------ fig|259564.1.peg.2458 [Methanococcoides burtonii DSM 6242] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |       | |   ,-----------|
  | | |       | |   |           |            ,------- fig|2208.1.peg.2395 [Methanosarcina barkeri] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |       | |   |           `------------|
  | | |       | |   |                        | ,-------- fig|192952.1.peg.2279 [uni|Q8PUQ3] [Methanosarcina mazei Go1] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |       | |   |                        `-|
  | | |       | |   |                          `------- fig|188937.1.peg.1241 [uni|Q8TRA4] [Methanosarcina acetivorans C2A] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |       | | ,-|
  | | |       | | | `--------------------------------- fig|187420.1.peg.1474 [uni|O27549] [Methanothermobacter thermautotrophicus str. Delta H] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |       | `-|
  | | |       |   `------------------------------------- fig|190192.1.peg.364 [uni|Q8TYD4] [Methanopyrus kandleri AV19] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |     ,-|
  | | |     | |                         ,----------------- fig|70601.1.peg.1484 [uni|O59184] [Pyrococcus horikoshii OT3] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |     | |                  ,------|
  | | |     | |                  |      `----------------- fig|272844.1.peg.676 [uni|Q9V0Y5] [Pyrococcus abyssi GE5] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |     | | ,----------------|
  | | |     | | |                `--------------------- fig|186497.1.peg.1585 [uni|Q8U0P7] [Pyrococcus furiosus DSM 3638] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |     | `-|
  | | |     |   `------------------------------------------ fig|224325.1.peg.989 [uni|O29265] [Archaeoglobus fulgidus DSM 4304] Cytosine deaminase, related metal-dependent hydrolases, chlorohydrolase
  | | |   ,-|
  | | |   | |  ,-------------------------------------- fig|224325.1.peg.545 [uni|O29701] [Archaeoglobus fulgidus DSM 4304] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | |   | `--|
  | | |   |    | ,------------------------------------- fig|242619.1.peg.490 [uni|Q7MWP1] [Porphyromonas gingivalis W83] chlorohydrolase family protein
  | | |   |    `-|
  | | |   |      `---------------------------------------- fig|156889.1.peg.4005 [Magnetococcus sp. MC-1] chlorohydrolase family protein
  | | | ,-|
  | | | | |   ,--------------------------------------------- fig|267377.1.peg.378 [Methanococcus maripaludis S2] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  | | | | | ,-|
  | | | | | | `----------------------------------------------- fig|273057.1.peg.614 [uni|Q9UX68] [Sulfolobus solfataricus P2] N-ethylammeline chlorohydrolase, putative (trzA)
  | | | | `-|
  | | | |   |                          ,---------------------- fig|273075.1.peg.1042 [uni|Q9HJB0] [Thermoplasma acidophilum DSM 1728] Metal-dependent hydrolase
  | | | |   |                 ,--------|
  | | | |   |                 |        `----------------------- fig|273116.1.peg.515 [uni|Q97BE1] [Thermoplasma volcanium GSS1] Metal-dependent hydrolase
  | | | |   `-----------------|
  | | | |                     `------------------------------- fig|97393.1.peg.1296 [Ferroplasma acidarmanus]
  | | `-|
  | |   `------------------------------------------ fig|224324.1.peg.426 [uni|O66851] [Aquifex aeolicus VF5] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  |-|
  | |                         ,---------------------- fig|584.1.peg.2300 [Proteus mirabilis HI4320] Chlorohydrolase/deaminase family protein
  | |         ,---------------|
  | |         |               |                       ,- fig|216895.1.peg.1198 [uni|Q8DCU0] [Vibrio vulnificus CMCP6] Cytosine deaminase, related metal-dependent hydrolases, chlorohydrolase
  | |         |               `-----------------------|
  | |         |                                       `- fig|196600.1.peg.3128 [uni|Q7MH11] [Vibrio vulnificus YJ016] Cytosine deaminase, related metal-dependent hydrolases, chlorohydrolase
  | `---------|
  |           |     ,---------------------------------- fig|226185.1.peg.1135 [uni|Q835Z5] [Enterococcus faecalis V583] chlorohydrolase family protein
  |           `-----|
  |                 `--------------------------------- fig|195102.1.peg.1330 [uni|Q8XKX5] [Clostridium perfringens str. 13] Chlorohydrolase/deaminase family protein
  |               ,---------------------------------- fig|203122.1.peg.1114 [Microbulbifer degradans 2-40]
  |           ,---|
  |           |   |                          ,-------- fig|216595.1.peg.578 [Pseudomonas fluorescens SBW25] Chlorohydrolase/deaminase family protein
  |           |   |                      ,---|
  |           |   |                      |   `------- fig|205922.1.peg.5221 [Pseudomonas fluorescens PfO-1]
  |           |   |                ,-----|
  |           |   |                |     `----------- fig|223283.1.peg.1706 [uni|Q885T8] [Pseudomonas syringae pv. tomato str. DC3000] Cytosine deaminase, related metal-dependent hydrolases, chlorohydrolase
  |           |   `----------------|
  |           |                    |                ,- fig|208963.1.peg.745 [Pseudomonas aeruginosa UCBPP-PA14] Cytosine deaminase and related metal-dependent hydrolases
  |           |                    `----------------|
  |           |                                     `- fig|208964.1.peg.3170 [uni|Q9HZ64] [Pseudomonas aeruginosa PAO1] Chlorohydrolase/deaminase family protein
  |   ,-------|
  |   |       |                              ,----------- fig|160492.1.peg.2457 [uni|Q9PAM4] [Xylella fastidiosa 9a5c] conserved hypothetical protein
  |   |       |                       ,------|
  |   |       |                       |      |        ,- fig|190486.1.peg.2338 [uni|Q8PJZ9] [Xanthomonas axonopodis pv. citri str. 306] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
  |   |       |                       |      | ,------|
  |   |       |                       |      | |      `-- fig|190485.1.peg.2230 [uni|Q8P8H1] [Xanthomonas campestris pv. campestris str. ATCC 33913] Cytosine deaminase and related metal-dependent hydrolases
  |   |       |                       |      `-|
  |   |       |                       |        `--------- fig|40324.1.peg.278 [Stenotrophomonas maltophilia K279a] Formiminoglutamic iminohydrolase (EC 3.5.3.13)
  |   |       |    ,------------------|
  |   |       |    |                  `---------------- fig|49338.1.peg.4631 [Desulfitobacterium hafniense] Cytosine deaminase and related metal-dependent hydrolases
  |   |       | ,--|
  |   |       | |  `-------------------------------- fig|227377.1.peg.497 [uni|Q83E15] [Coxiella burnetii RSA 493] Pyrimidine deaminase archaeal predicted (EC 3.5.4.26)
  |   |       `-|
  |   |         |     ,------------------------------- fig|265072.1.peg.2132 [Methylobacillus flagellatus KT] Cytosine deaminase and related metal-dependent hydrolases
  |   |         `-----|
  |   |               `------------------------------- fig|159087.1.peg.1331 [Dechloromonas aromatica RCB]
  | ,-|
  | | `----------------------------------------- fig|882.1.peg.1818 [Desulfovibrio vulgaris subsp. vulgaris str. Hildenborough] amidohydrolase family protein
  `-|
    |   ,----------------------------------------- fig|227882.1.peg.6654 [uni|Q828L7] [Streptomyces avermitilis MA-4680] putative N-ethylammeline chlorohydrolase
    `---|
        `-------------------------------------------- fig|100226.1.peg.1950 [uni|Q93JH8] [Streptomyces coelicolor A3(2)] putative hydrolase