THE ENZYME NOMENCLATURE DATABASE USER MANUAL
                             Release of 03-Aug-2022

   Alan Bridge and Kristian Axelsen
   SIB Swiss Institute of Bioinformatics
   Centre Medical Universitaire (CMU)
   1, rue Michel Servet
   1211 Geneva 4
   Switzerland

   Electronic mail address: enzyme@expasy.org


   ENZYME is available at: http://enzyme.expasy.org/

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   Copyrighted by the SIB Swiss Institute of Bioinformatics and
   distributed under the Creative Commons Attribution (CC BY 4.0) License
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   If you want to refer to ENZYME in a publication you can do so by citing:

      Bairoch A.
      The ENZYME database in 2000.
      Nucleic Acids Res. 28:304-305(2000).

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                              TABLE OF CONTENTS

   1) Introduction
          1.1 Definition of the scope of the database
          1.2 Sources of the data

   2) Conventions used in the database
          2.1 Structure of an entry
          2.2 Two sample entries

   3) The different line types
          3.1 The ID line
          3.2 The DE line
          3.3 The AN line
          3.4 The CA line
          3.5 The CF line
          3.6 The CC line
          3.7 The DI line
          3.8 The DR line
          3.9 The // line

   Appendix 1: Report form of the NC-IUBMB


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                               1) INTRODUCTION


   1.1) Definition of the scope of the database

   The 'ENZYME'  database  contains  the  following data  for each  type of
   characterized enzyme for which an EC number has been provided:

   -  EC number
   -  Recommended name
   -  Alternative names (if any)
   -  Catalytic activity
   -  Cofactors (if any)
   -  Pointers to  the Swiss-Prot  entrie(s) that  correspond to the enzyme
      (if any)

   We believe  that the  ENZYME  database  can be useful to anybody working
   with enzymes  and that  it can be of help in the development of computer
   programs involved with the manipulation of metabolic pathways.


   1.2) Sources of the data

   The main  source for  the  data  in  the  ENZYME   database  comes  from
   recommendations of the Nomenclature Committee of the International Union
   of Biochemistry  and Molecular  Biology (IUBMB) [1]. A minor part of the
   data has been extracted from the literature.

   [1]  Enzyme Nomenclature, NC-IUBMB, Academic Press, New-York, (1992).
        See: http://www.chem.qmul.ac.uk/iubmb/enzyme/

   We do not assign EC numbers for newly characterized enzymes, this is the
   responsibility of  the Nomenclature  Committee of  IUBMB (NC-IUBMB).  To
   contact the committee one should consult the list of members found at:
   http://www.chem.qmul.ac.uk/iupac/jcbn/membr.html

   If you would like to report a new enzyme activity to the NC-IUBMB you
   can use the form found at: http://enzyme-database.org/newform.php.
   We follow the updates and additions to the nomenclature so that they
   can be integrated into the database in a timely manner.

   The database  is  complete  and  up to date. It is regularily updated to
   reflect  updates  and  additions to the nomenclature. We also update the
   Swiss-Prot and PROSITE pointers,  correct  eventual errors, and complete
   the information concerning synonyms and cofactors using the literature.

   We welcome and encourage any type of feedback.



                     2) CONVENTIONS USED IN THE DATABASE


   2.1) Structure of an entry

   The entries  in the database data file (ENZYME.DAT) are structured so as
   to be  usable by  human readers  as well  as by  computer programs. Each
   entry in  the database  is composed  of lines. Different types of lines,
   each with  its own  format, are used to record the various types of data
   which make  up the  entry. The  general  structure  of  a  line  is  the
   following:


   Characters    Content
   ----------    ----------------------------------------------------------
   1 to 2        Two-character line code. Indicates the type of information
                 contained in the line.
   3 to 5        Blank
   6 up to 78    Data


   The currently  used line  types, along with their respective line codes,
   are listed below:

   ID  Identification                         (Begins each entry; 1 per entry)
   DE  Description (official name)            (>=1 per entry)
   AN  Alternate name(s)                      (>=0 per entry)
   CA  Catalytic activity                     (>=1 per entry)
   CF  Cofactor(s)                            (>=0 per entry)
   CC  Comments                               (>=0 per entry)
   PR  Cross-references to PROSITE            (>=0 per entry)
   DR  Cross-references to Swiss-Prot         (>=0 per entry)
   //  Termination line                       (Ends each entry; 1 per entry)

   Line types no longer used:
   DI  Disease(s) associated with the enzyme

   Some entries  do not  contain all of the line types, and some line types
   occur many  times in  a single  entry. Each  entry must  begin  with  an
   identification line (ID) and end with a terminator line (//).

   A detailed description of each line type is given in the next section of
   this document.



   2.2) Two sample entries

   ID   1.14.17.3
   DE   Peptidylglycine monooxygenase.
   AN   PAM.
   AN   Peptidyl alpha-amidating enzyme.
   AN   Peptidylglycine 2-hydroxylase.
   AN   Peptidylglycine alpha-amidating monooxygenase.
   CA   Peptidylglycine + ascorbate + O(2) = peptidyl(2-hydroxyglycine) +
   CA   dehydroascorbate + H(2)O.
   CF   Copper.
   CC   -!- Peptidylglycines with a neutral amino acid residue in the penultimate
   CC       position are the best substrates for the enzyme.
   CC   -!- The product is unstable and dismutates to glyoxylate and the
   CC       corresponding desglycine peptide amide, a reaction catalyzed by
   CC       EC 4.3.2.5.
   CC   -!- Involved in the final step of biosynthesis of alpha-melanotropin and
   CC       related biologically active peptides.
   PR   PROSITE; PDOC00080;
   DR   P08478, AMD1_XENLA ;  P12890, AMD2_XENLA ;  P83388, AMDL_CAEEL ;
   DR   P10731, AMD_BOVIN  ;  P19021, AMD_HUMAN  ;  P97467, AMD_MOUSE  ;
   DR   P14925, AMD_RAT    ;  Q95XM2, PHM_CAEEL  ;  O01404, PHM_DROME  ;
   //

   ID   2.3.1.43
   DE   Phosphatidylcholine--sterol O-acyltransferase.
   AN   LCAT.
   AN   Lecithin--cholesterol acyltransferase.
   AN   Phospholipid--cholesterol acyltransferase.
   CA   Phosphatidylcholine + a sterol = 1-acylglycerophosphocholine +
   CA   a sterol ester.
   CC   -!- Palmitoyl, oleoyl, and linoleoyl can be transferred; a number of
   CC       sterols, including cholesterol, can act as acceptors.
   CC   -!- The bacterial enzyme also catalyzes the reactions of EC 3.1.1.4 and
   CC       EC 3.1.1.5.
   PR   PROSITE; PDOC00110;
   DR   P10480, GCAT_AERHY ;  P53760, LCAT_CHICK ;  O35573, LCAT_ELIQU ;
   DR   P04180, LCAT_HUMAN ;  O35724, LCAT_MICMN ;  P16301, LCAT_MOUSE ;
   DR   O35502, LCAT_MYOGA ;  Q08758, LCAT_PAPAN ;  P30930, LCAT_PIG   ;
   DR   P53761, LCAT_RABIT ;  P18424, LCAT_RAT   ;  O35840, LCAT_TATKG ;
   //



                         3) THE DIFFERENT LINE TYPES

   This section describes in detail the format of each type of line used in
   the database.


   3.1) The ID line

    The ID  (IDentification) line  is always the first line of an entry. The
    format of the ID line is:

    ID   EC_number
    Examples:

    ID   1.1.1.1
    ID   6.3.2.1
    ID   3.5.1.n3

       Notes

    -  EC numbers  that include  an 'n' as part of the fourth (serial) digit
       are preliminary EC numbers.
    -  Entries  with preliminary  EC numbers  are placed  at the  end of the
       sub-sub-class to which they belong.
    -  Preliminary  EC numbers  are  not  included  in  the  official  IUBMB
       nomenclature,  but   are  created   and  used   only  in  ENZYME  and
       UniProtKB/Swiss-Prot.


   3.2) The DE line

   The DE  (DEscription) line(s) contain the NC-IUB recommended name for an
   enzyme. The format of the DE line is:

   DE   Description.

   Examples:

   DE   Alcohol dehydrogenase.

   DE   UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate--D-
   DE   alanyl-D-alanyl ligase.

   Important note:  enzymes are  sometimes deleted from the EC list, others
   are renumbered;  however the  NC-IUBMB does not allocate the old numbers
   to new  enzymes. Obsolete  EC numbers are indicated in this database  by
   the following DE line syntaxes. For deleted enzymes:

   DE   Deleted entry.

   and for renumbered enzymes:

   DE   Transferred entry: x.x.x.x.

   where x.x.x.x  is the  new, valid,  EC number; as shown in the following
   example:

   DE   Transferred entry: 1.7.99.5.


   3.3) The AN line

   The AN  (Alternate Name)  line(s) are  used to  indicate  the  different
   name(s), other  than the NC-IUBMB recommended name, that are used in the
   literature to describe an enzyme. The format of the AN line is:

   AN   Alternate_Name.

   As an  example we  list here  both the DE and AN lines for the enzyme EC
   2.7.7.31:

   DE   DNA nucleotidylexotransferase.
   AN   Terminal addition enzyme.
   AN   Terminal deoxynucleotidyltransferase.
   AN   Terminal deoxyribonucleotidyltransferase.
   AN   Terminal transferase.


   3.4) The CA line

   The CA (Catalytic Activity) line(s) are used to indicate the reaction(s)
   catalyzed by an enzyme. The format of the CA line is:

   CA   Reaction.

   Where the reaction is indicated following the recommendations of the NC-
   IUBMB. The  majority of  the reactions  are described  using a  standard
   chemical reaction format:

   CA   Substrate_11 + Substrate_12 [+ Substrate_1N...] = Substrate_21 +
   CA   Substrate_22 [+ Substrate_2N].

   As shown in the following examples:

   CA   L-malate + NAD(+) = oxaloacetate + NADH.

   CA   2 ATP + NH(3) + CO(2) + H(2)O = 2 ADP + phosphate + carbamoyl
   CA   phosphate.

   In some  cases free text is used to describe a reaction. As shown in the
   following examples:

   CA   Cyclizes part of a 1,4-alpha-D-glucan chain by formation of a
   CA   1,4-alpha-D-glucosidic bond.

   CA   Cleavage of Leu-|-Xaa bond in angiotensinogen to generate
   CA   angiotensin I.


        Notes

   -  Subscript and superscript are indicated between brackets: for example
      NAD+ and NADP+ are indicated as NAD(+) and NADP(+), H2O as H(2)O, CO2
      as CO(2), etc.
   -  Greek letters are spelled out (i.e. alpha, beta, etc.).


   3.5) The CF line

   The CF  (CoFactor) line(s)  are used  to indicate  which cofactor(s) are
   required by an enzyme. The format of the CF line is:

   CF   Cofactor_1; Cofactor_2 or Cofactor_3[; Cofactor_N...].

   Examples:

   CF   Pyridoxal-phosphate.
   CF   Iron-sulfur; Molybdenum or vanadium.
   CF   Ascorbate; Iron.


   3.6) The CC line

   The CC  lines are  free text  comments on  the entry, and may be used to
   convey any useful information.

   Examples:

   CC   -!- The product spontaneously isomerizes to L-ascorbate.

   CC   -!- Some members of this group oxidize only primary alcohols;
   CC       others act also on secondary alcohols.


   3.7) The DI line

   The DI (DIsease) line(s) are no longer used. Information about specific
   diseases can be found in the relevant UniProtKB/Swiss-Prot entries.


   3.8) The DR line

   The  DR  (Database Reference)  line(s)  are  used  as  pointers  to  the
   UniProtKB/Swiss-Prot  entries  that  corresponds  to  the  enzyme  being
   described. The format of the DR line is:

   DR   AC_Nb, Entry_name;  AC_Nb, Entry_name;  AC_Nb, Entry_name;

   where:

   -  'AC_Nb' is  the Swiss-Prot  primary accession  number of the entry to
      which reference is being made.
   -  'Entry_name' is the Swiss-Prot entry name.

   Example:

   DR   P35497, DHSO1_YEAST;  Q07786, DHSO2_YEAST;  Q9Z9U1, DHSO_BACHD ;
   DR   Q06004, DHSO_BACSU ;  Q02912, DHSO_BOMMO ;  Q00796, DHSO_HUMAN ;


   3.9) The termination line

   The // (terminator) line contains no data or comments. It designates the
   end of an entry.