*******************************************************************************
******                                                                   ******
******                   PROTEIN MUTANT DATA BASE                        ******
******                                                                   ******
******                  National Institute of Genetics                   ******
******                              (NIG)                                ******
******            1111, Yata, Mishima, Shizuoka-ken 411, Japan           ******
******                                                                   ******
******        In collaboration with:                                     ****** 
******                   Protein Engineering Research Institute (PERI)   ******
******                   6-2-3, Furuedai, Suita, Osaka 565, Japan        ****** 
******                         and                                       ******
******                   Protein Research Foundation (PRF)               ******
******                   4-1-2, Ina, Mino, Osaka 562,Japan               ****** 
******                                                                   ******
******       Correspondence:  Dr. Ken Nishikawa                          ******
******                        National Institute of Genetics             ******
******                        1111, Yata, Mishima, Shizuoka 411, Japan   ******
******                                                                   ******
******                        TEL: +81-559-81-6859                       ******
******                        FAX: +81-559-81-6889                       ******
******                        E-Mail: knishika@genes.nig.ac.jp           ******
******                                                                   ******
******      This document has been updated on November 24, 2000.         ******
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       Mutant database of proteins would be valuable as a basis of protein 
   engineering.  Our database is of a type based on literature (not on
   proteins); that is, each entry of the database corresponds to one
   article which describes protein mutations.    

       Each entry of the database is identified with a serial number, and
   distinguished either "variant" or "artificial" depending on the type
   of mutation.  For each entry the following items are to be typed in:

AUTHORS/JOURNAL/TITLE/CROSS-REFERENCE/PROTEIN/SOURCE/N-TERMINAL/EXPRESSION-SYSTEM/
CHANGE/CHIMERA/EXTENSION/INSERTION/REPLACEMENT/DE NOVO/MULTIPLE/ 
/FUNCTION/STRUCTURE/STABILITY/EXPRESSION/TRANSPORT/DISEASE/COMMENT/SEQUENCE,
 and ends with '///'.


    'CROSS-REFERENCE' indicates code names of the protein given in other
   databases such as PIR/SWISS-PROT or PDB.  'N-TERMINAL' shows the N-terminal 
   five amino acids which may help to show the unambiguous numbering of the
   sequence. 'CHANGE', 'REPLACEMENT', 'EXTENSION', 'INSERTION', 'CHIMERA', 
   'DE NOVO' and 'MULTIPLE' indicate the position and kind of mutations (see
   the attached listing for the notation). 
   Any mutant irrespective of the number of amino acids involved is described 
   under a single headline of CHANGE, so that the number of header 'CHANGE', 
   'REPLACEMENT', 'EXTENSION', 'INSERTION', 'CHIMERA', 'DE NOVO' and 'MULTIPLE'
   imply the number of different mutants.  Any functional, structural features
   observed in the mutant are described right after them.
   Relative differences in activity and/or stability in comparison with the 
   wild type is indicated with symbols [- -], [-], [=], [+], or [+ +]. 
   Special comments or important remarks if mentioned in the article are given 
   in 'COMMENT' lines. 'SEQUENCE' shows a amino acid sequence of wild type.  

*******************************************************************************
******                            CONTENTS                              ******
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 ENTRY          *___++++ - ******                     +++++++
                |   |      |                          |
                |   |      |_ Kind of mutations       |_Article number
                |   |                 Artificial              in PRF/LITDB
                |   |                 Variant
                |   |                 Chemical
                |   |                 Chimera
                |   |                 Enzymatic
                |   |                 Synthetic
                |   |                 Signal
                |   |
                |   |_ Number in "MUTANT DATABASE"
                |
                |_ A;article
                   R;review
                   B;preliminaly entry, type 'B', 
                     which contains the "CHANGE" items, but does not contain 
                     results of mutations('FUNCTION','STABILITY'.etc)
                   C;preliminaly entry, type 'C', which does not contain 
                     the "CHANGE" items. 

 AUTHORS

 JOURNAL

 TITLE

 CROSS-REFERENCE    Code names of the proteins given in the databases such as
                    SWISS-PROT, PIR.
                 e.g. 1. MYG_HUMAN ( this is for SWISS_PROT) 
                      2. MYHU      ( this is for PIR) 
                      2. /databases other than SWISS-PROT/PIR (if the protein is not found 
                         in SWISS-PROT/PIR) 
                    If the code names of proteins are not identified, they are  
                      shown for the similar structural proteins using the 
                      parenthesis.
                 e.g.  (JKLCN) 
PROTEIN             Names of the protein including EC number and/or length    
                 e.g.  protein names in the article (abbrevation in the 
                       article); entry names of PIR

SEQUENCE           In the cases of "CHIMERA" and "FRAGMENT", the sequence is 
                   shown as follows.
                  e.g. FRAGMENT- SEQUENCE    MDLVVVLGLCSCALHHddd
                 
 SOURCE             The source of the protein

 N-TERMINAL         The N-terminal five amino acids which may help to show the
                      unambiguous numbering of the sequence

 EXPRESSION-SYSTEM  Only for artificial mutants

 CHANGE             The position and the kind of mutations such as amino acid
                      substitution, replacement or deletion (see "Notation of 
                      mutants") 
                    Any mutant irrespective of the number of amino acids
                      involved is described under a single headline of "CHANGE"
                      so that each header CHANGE corresponds to a different
                      mutant.

 REPLACEMENT        The number of replaced amino acids are different from the
                      wild type.
 EXTENSION            
 INSERTION 
 CHIMERA            For chimeric proteins 

 FUNCTION           Any features observed in the mutant; Relative defferences 
 STRUCTURE            in comparison with the wild-type protein is,if possible,
 STABILITY            indicated with symbols [- -],[-],[=],[+],[+ +]. Complete 
 EXPRESSION           loss of activity is indicated as [0].
 TRANSPORT
 MATURATION
 DISEASE            In cases where a given mutation is associated with some 
                      disease, the name of disease is described.       

 COMMENT            Special comments or important remarks if mentioned in the
                      article

 ///                End of entry





*******************************************************************************
******                      NOTATION  OF MUTANTS                     ******
*******************************************************************************
[CHANGE]
 CHANGE-POINT    His 44 Arg 
                 ; His-44 replaced by Arg
 CHANGE-MODIFY   Ala 63 (L-parafluorophenyl)Ala
                 ; Ala-63 replaced by (L-parafluorophenyl)Ala 
 CHANGE-DELETE    Lys 35
                 ; Deletion of Lys-35
 CHANGE-DELETE   Glu--Gln 32-46
                 ; Deletion from Glu-32 to Gln-46
 CHANGE-DELETE   Leu 8
       -DELETE   Glu--Gln 15-26
                 ; Deletion of Leu-8 & deletion from Glu--Gln 15-26
 CHANGE-STOP     Pro 76 (termination)
                 ; Pro 76 codon changed to the termination codon, resulting in
                   the truncated protein 
 CHANGE-INSERT   Phe^Gly 441^442 GALKE
                 ; Gly-Ala-Leu-Lys-Glu inserted between Phe-441 and Gly-442 
 CHANGE-EXTEND   Ala^ 53^ YVACN
                 ; Tyr-Val-Ala-Cys-Asn added to the C-terminus of Ala-53
 CHANGE-REPLACE  Ala--Arg 14-16 Gly-Thr-Phe-Val 
                 ; The region from Ala-14 to Arg-16 replaced by Gly-Thr-Phe-Val
 CHANGE-REPLACE  Val--Ile 64-70 GLIVPHALLSFRTHIIK 
 CHANGE-FRAGMENT Ala--Val 35-187 (fragmented)
                 ; Fragmentated region from Ala--35 to Val-187 
 CHANGE-FRAME    Ala 39 (frameshift)
                 ; Translational frameshift after amino acid 38
 CHANGE-POINT    His 3 Ala
       -POINT    Asp 11 Asn 
       -REPLACE  Ala--Arg 14-16 GTFVAP
                 ; Combination of point mutation and replacement (the region 
                   from Ala-14 to Arg-16 replaced by Gly-Thr-Phe-Val-Ala-Pro)
 CHANGE-REPLACE  Ala--Arg 14-16 GTFVM
       -INSERT   Phe^Gly 441^442 GALKE
                 ; Combination of replacement (the region from Ala-14 to Arg-16 
                   replaced by Gly-Thr-Phe-Val-Met) and insertion (Gly-Ala-Leu-
                   Lys-Glu inserted between Phe-441 and Gly-442) is done 
                   simultaneity.
 [CHIMERA]
 CHANGE-CHIMERA  (Ala--Ala 1-25 of GST1-1) - (Ala--Gly 25-114 of GST2-2)
                 ; The region from Ala-1 to Ala-25 of GST1-1 protein fused to 
                   the region from Ala-25 to Gly-114 of GST2-2 protein 
 CHANGE-CHIMERA  Arg--Val 307-490 of cytochrome P450 2C2 is replaced by the
                   corresponding region of 2Cl. 
                 ; The region from Arg-307 to Val-490 of cytochrome P450 2CS is 
                   replaced by the corresponding region of 2Cl
               * See "EXAMPLES OF CHIMERIC PROTEIN" for practical examples. 
*******************************************************************************
"EXAMPLES OF CHIMERIC PROTEIN"

*Example I

CROSS-REFERENCE O4RBP2                                                            
PROTEIN         Cytochrome P450 2C2                                                 
SOURCE          Rabbit
N-TERMINAL      MDLVV
CROSS-REFERENCE O4RBP1
PROTEIN         Cytochrome P450 2C1
SOURCE          Rabbit
N-TERMINAL      MDPVV
EXPRESSION-SYSTEM  COS-1 cells
CHANGE-CHIMERA   Arg--Val 307-490 of cytochrome P450 2C2 is replaced by the 
                  corresponding region of cytochrome P450 2C1.
      -SEQUENCE  MDLVVVLGLCLSCLLLLSLWKQSHGGGKLPPGPTPFPILGNVLQLDFKDLSKSLTNLSKV
                  YGPVFTVYLGMKPTVVVHGYEAVKEALVDLGHELSGRSRFLVTAKLNKGFGVIFSNGKRW
                  TETRRFSLMTLRNFGMGKRSIEERVQEEAHCLVEELRKTNASPCDPTFILGAAPCNVICS
                  VIFQNRFDYTDQDFLSLMGKFNENFKILNSPWVQFCNCFPILFDYFPGSHRKAVKNIFYV
                  KNYITEQ/IKEHQK ddddd
FUNCTION        Enzyme activity [-] (compared to cytochrome P450 2C2)
///

*Example II

CROSS-REFERENCE SYISC3
PROTEIN         Chalcone synthase (CHS); naringenin-chalcone synthase
SOURCE          Sinapis alba
N-TERMINAL      MVMGT
CROSS-REFERENCE SYNPHS
PROTEIN         Stilbene synthase (STS); trihydroxystilbene synthase
SOURCE          Arachis hypogaea
N-TERMINAL      MVSVS
EXPRESSION-SYSTEM  Escherichia coli
CHANGE-CHIMERA  (Met--Val 1-107 of CHS) - (Pro--Ile 103-389 of STS)
      -POINT    Pro 42 Ala (numbered as in CHS)
      -SEQUENCE   MVMGTPSSLDEIRKAQRADGPAGILAIGTANPANHVIQAEY(A)DYYFRITNSEHMTDLK
                  EKKRMCDKSTIRKRHMHLTEEFLKDNPNMCAYMAPSLDARQDIVVVEV/PRVGKEAATKA
                  IKEWGQPMSKITHLIFCTTSGVALPGVDYELIVLLGLDPSVKRYMMYHQGCFAGGTVLRL
                  AKDLAENNKDARVLIVCSENTAVTFRGPSETDMDSLVGQALFADGAAAIIIGSDPVPEVE
                  NPLFEIVSTDQKLVPNSHGAIGGLLREVGLTFYLNKSVPDIISQNINDALSKAFDPLGIS
                  DYNSIFWIAHPGGPAILDQVEQKVNLKPEKMNATRDVLSNYGNMSSACVFFIMDLMRKKS
                  LEEGLKTTGEGLDWGVLFGFGPGLTIETVVLRSVAI
FUNCTION        CHS activity [0] (compared to CHS): STS activity [0] (compared 
                  to STS) 
///