iep

 

Function

Calculates the isoelectric point of a protein

Description

This calculates the isoelectric point of a protein from its amino acid composition assuming that no electrostatic interactions change the propensity for ionization.

Adjusting the pH of an aqueous protein solution to the point where the numbers of positive and negative charges on the protein are equal brings the protein to its isoelectric point. This is often the point of lowest solubility, presumably because it is the point at which there are fewest intermolecular repulsions, so that the molecules tend to form aggregates.

The application can make a plot of the ionization curve with respect to pH and can write an output file of the data.

Usage

Here is a sample session with iep


% iep tsw:laci_ecoli 
Calculates the isoelectric point of a protein
Output file [laci_ecoli.iep]: 

Go to the input files for this example
Go to the output files for this example

Example 2


% iep tsw:ifna2_human -disulphide 2 -lysinemodified 2  
Calculates the isoelectric point of a protein
Output file [ifna2_human.iep]: 

Go to the input files for this example
Go to the output files for this example

Command line arguments

   Standard (Mandatory) qualifiers (* if not always prompted):
  [-sequence]          seqall     Protein sequence(s) filename and optional
                                  format, or reference (input USA)
*  -graph              xygraph    [$EMBOSS_GRAPHICS value, or x11] Graph type
                                  (ps, hpgl, hp7470, hp7580, meta, cps, x11,
                                  tekt, tek, none, data, xterm, png, gif)
*  -outfile            outfile    [*.iep] Output file name

   Additional (Optional) qualifiers:
   -amino              integer    [1] Number of N-termini (Integer 0 or more)
   -[no]termini        boolean    [Y] Include charge at N and C terminus
   -lysinemodified     integer    [0] Number of modified lysines (Integer 0 or
                                  more)
   -disulphides        integer    [0] Number of disulphide bridges (Integer 0
                                  or more)

   Advanced (Unprompted) qualifiers:
   -step               float      [.5] Step value for pH (Number from 0.010 to
                                  1.000)
   -plot               toggle     [N] Plot charge vs pH
   -[no]report         toggle     [Y] Write results to a file

   Associated qualifiers:

   "-sequence" associated qualifiers
   -sbegin1            integer    Start of each sequence to be used
   -send1              integer    End of each sequence to be used
   -sreverse1          boolean    Reverse (if DNA)
   -sask1              boolean    Ask for begin/end/reverse
   -snucleotide1       boolean    Sequence is nucleotide
   -sprotein1          boolean    Sequence is protein
   -slower1            boolean    Make lower case
   -supper1            boolean    Make upper case
   -sformat1           string     Input sequence format
   -sdbname1           string     Database name
   -sid1               string     Entryname
   -ufo1               string     UFO features
   -fformat1           string     Features format
   -fopenfile1         string     Features file name

   "-graph" associated qualifiers
   -gprompt            boolean    Graph prompting
   -gdesc              string     Graph description
   -gtitle             string     Graph title
   -gsubtitle          string     Graph subtitle
   -gxtitle            string     Graph x axis title
   -gytitle            string     Graph y axis title
   -goutfile           string     Output file for non interactive displays
   -gdirectory         string     Output directory

   "-outfile" associated qualifiers
   -odirectory         string     Output directory

   General qualifiers:
   -auto               boolean    Turn off prompts
   -stdout             boolean    Write standard output
   -filter             boolean    Read standard input, write standard output
   -options            boolean    Prompt for standard and additional values
   -debug              boolean    Write debug output to program.dbg
   -verbose            boolean    Report some/full command line options
   -help               boolean    Report command line options. More
                                  information on associated and general
                                  qualifiers can be found with -help -verbose
   -warning            boolean    Report warnings
   -error              boolean    Report errors
   -fatal              boolean    Report fatal errors
   -die                boolean    Report dying program messages

Standard (Mandatory) qualifiers Allowed values Default
[-sequence]
(Parameter 1)
Protein sequence(s) filename and optional format, or reference (input USA) Readable sequence(s) Required
-graph Graph type EMBOSS has a list of known devices, including ps, hpgl, hp7470, hp7580, meta, cps, x11, tekt, tek, none, data, xterm, png, gif EMBOSS_GRAPHICS value, or x11
-outfile Output file name Output file <*>.iep
Additional (Optional) qualifiers Allowed values Default
-amino Number of N-termini Integer 0 or more 1
-[no]termini Include charge at N and C terminus Boolean value Yes/No Yes
-lysinemodified Number of modified lysines Integer 0 or more 0
-disulphides Number of disulphide bridges Integer 0 or more 0
Advanced (Unprompted) qualifiers Allowed values Default
-step Step value for pH Number from 0.010 to 1.000 .5
-plot Plot charge vs pH Toggle value Yes/No No
-[no]report Write results to a file Toggle value Yes/No Yes

Input file format

iep

reads in any protein sequence USA.

Input files for usage example

'tsw:laci_ecoli' is a sequence entry in the example protein database 'tsw'

Database entry: tsw:laci_ecoli

ID   LACI_ECOLI              Reviewed;         360 AA.
AC   P03023; O09196; P71309; Q2MC79; Q47338;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2003, sequence version 3.
DT   20-MAR-2007, entry version 87.
DE   Lactose operon repressor.
GN   Name=lacI; OrderedLocusNames=b0345, JW0336;
OS   Escherichia coli.
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacteriales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=562;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=78246991; PubMed=355891; DOI=10.1038/274765a0;
RA   Farabaugh P.J.;
RT   "Sequence of the lacI gene.";
RL   Nature 274:765-769(1978).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Chen J., Matthews K.K.S.M.;
RL   Submitted (MAY-1991) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Marsh S.;
RL   Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RA   Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA   Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA   Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT   "Sequence of minutes 4-25 of Escherichia coli.";
RL   Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   MEDLINE=97426617; PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA   Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA   Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA   Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J.,
RA   Mau B., Shao Y.;
RT   "The complete genome sequence of Escherichia coli K-12.";
RL   Science 277:1453-1474(1997).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=16738553; DOI=10.1038/msb4100049;
RA   Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA   Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT   "Highly accurate genome sequences of Escherichia coli K-12 strains


  [Part of this file has been deleted for brevity]

DR   Pfam; PF00532; Peripla_BP_1; 1.
DR   PRINTS; PR00036; HTHLACI.
DR   SMART; SM00354; HTH_LACI; 1.
DR   PROSITE; PS00356; HTH_LACI_1; 1.
DR   PROSITE; PS50932; HTH_LACI_2; 1.
KW   3D-structure; Complete proteome; Direct protein sequencing;
KW   DNA-binding; Repressor; Transcription; Transcription regulation.
FT   CHAIN         1    360       Lactose operon repressor.
FT                                /FTId=PRO_0000107963.
FT   DOMAIN        1     58       HTH lacI-type.
FT   DNA_BIND      6     25       H-T-H motif.
FT   VARIANT     282    282       Y -> D (in T41 mutant).
FT   MUTAGEN      17     17       Y->H: Broadening of specificity.
FT   MUTAGEN      22     22       R->N: Recognizes an operator variant.
FT   CONFLICT    286    286       L -> S (in Ref. 1, 4 and 7).
FT   STRAND       63     69
FT   HELIX        74     89
FT   STRAND       93     98
FT   STRAND      101    103
FT   HELIX       104    115
FT   TURN        116    118
FT   STRAND      122    126
FT   HELIX       130    139
FT   TURN        140    142
FT   STRAND      145    150
FT   STRAND      154    156
FT   STRAND      158    161
FT   HELIX       163    177
FT   STRAND      181    186
FT   HELIX       192    207
FT   STRAND      213    217
FT   HELIX       222    234
FT   STRAND      240    246
FT   HELIX       247    259
FT   TURN        265    267
FT   STRAND      268    271
FT   HELIX       277    281
FT   STRAND      282    284
FT   STRAND      287    290
FT   HELIX       293    308
FT   STRAND      314    319
FT   STRAND      322    324
FT   HELIX       354    356
SQ   SEQUENCE   360 AA;  38590 MW;  347A8DEE92D736CB CRC64;
     MKPVTLYDVA EYAGVSYQTV SRVVNQASHV SAKTREKVEA AMAELNYIPN RVAQQLAGKQ
     SLLIGVATSS LALHAPSQIV AAIKSRADQL GASVVVSMVE RSGVEACKAA VHNLLAQRVS
     GLIINYPLDD QDAIAVEAAC TNVPALFLDV SDQTPINSII FSHEDGTRLG VEHLVALGHQ
     QIALLAGPLS SVSARLRLAG WHKYLTRNQI QPIAEREGDW SAMSGFQQTM QMLNEGIVPT
     AMLVANDQMA LGAMRAITES GLRVGADISV VGYDDTEDSS CYIPPLTTIK QDFRLLGQTS
     VDRLLQLSQG QAVKGNQLLP VSLVKRKTTL APNTQTASPR ALADSLMQLA RQVSRLESGQ
//

Input files for usage example 2

Database entry: tsw:ifna2_human

ID   IFNA2_HUMAN             Reviewed;         188 AA.
AC   P01563; P01564; Q14606; Q96KI6;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   20-FEB-2007, entry version 79.
DE   Interferon alpha-2 precursor (Interferon alpha-A) (LeIF A).
GN   Name=IFNA2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   MEDLINE=81052322; PubMed=6159538; DOI=10.1038/287411a0;
RA   Goeddel D.V., Yelverton E., Ullrich A., Heyneker H.L., Miozzari G.,
RA   Holmes W., Seeburg P.H., Dull T.J., May L., Stebbing N., Crea R.,
RA   Maeda S., McCandliss R., Sloma A., Tabor J.M., Gross M.,
RA   Familletti P.C., Pestka S.;
RT   "Human leukocyte interferon produced by E. coli is biologically
RT   active.";
RL   Nature 287:411-416(1980).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   MEDLINE=81148795; PubMed=6163083; DOI=10.1038/290020a0;
RA   Goeddel D.V., Leung D.W., Dull T.J., Gross M., Lawn R.M.,
RA   McCandliss R., Seeburg P.H., Ullrich A., Yelverton E., Gray P.W.;
RT   "The structure of eight distinct cloned human leukocyte interferon
RT   cDNAs.";
RL   Nature 290:20-26(1981).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   MEDLINE=82060261; PubMed=6170983;
RA   Lawn R.M., Gross M., Houck C.M., Franke A.E., Gray P.V., Goeddel D.V.;
RT   "DNA sequence of a major human leukocyte interferon gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 78:5435-5439(1981).
RN   [4]
RP   NUCLEOTIDE SEQUENCE.
RC   TISSUE=Bone marrow tumor;
RX   MEDLINE=86069501; PubMed=3906813;
RA   Oliver G., Balbas P., Valle F., Soberon X., Bolivar F.;
RT   "Cloning of human leukocyte interferon cDNA and a strategy for its
RT   production in E. coli.";
RL   Rev. Latinoam. Microbiol. 27:141-150(1985).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Placenta;
RX   MEDLINE=98357449; PubMed=9694076;
RA   Austruy E., Bagnis C., Carbuccia N., Maroc C., Birg F., Dubreuil P.,
RA   Mannoni P., Chabannon C.;


  [Part of this file has been deleted for brevity]

DR   LinkHub; P01563; -.
DR   ArrayExpress; P01563; -.
DR   GermOnline; ENSG00000188379; Homo sapiens.
DR   RZPD-ProtExp; A0813; -.
DR   RZPD-ProtExp; IOH35221; -.
DR   RZPD-ProtExp; RZPDo834E0933; -.
DR   GO; GO:0005132; F:interferon-alpha/beta receptor binding; TAS:ProtInc.
DR   GO; GO:0007166; P:cell surface receptor linked signal transdu...; TAS:ProtInc.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0006917; P:induction of apoptosis; TAS:ProtInc.
DR   GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR   InterPro; IPR009079; 4_helix_cytokine.
DR   InterPro; IPR000471; Interferon_abd.
DR   Gene3D; G3DSA:1.20.120.210; Interferon_abd; 1.
DR   PANTHER; PTHR11691; Interferon_abd; 1.
DR   Pfam; PF00143; Interferon; 1.
DR   PRINTS; PR00266; INTERFERONAB.
DR   ProDom; PD000550; Interferon_abd; 1.
DR   SMART; SM00076; IFabd; 1.
DR   PROSITE; PS00252; INTERFERON_A_B_D; 1.
KW   3D-structure; Antiviral defense; Cytokine; Direct protein sequencing;
KW   Glycoprotein; Pharmaceutical; Polymorphism; Signal.
FT   SIGNAL        1     23
FT   CHAIN        24    188       Interferon alpha-2.
FT                                /FTId=PRO_0000016360.
FT   CARBOHYD    129    129       O-linked (GalNAc...).
FT                                /FTId=CAR_000049.
FT   DISULFID     24    121
FT   DISULFID     52    161
FT   VARIANT      46     46       K -> R (in alpha-2B and alpha-2C).
FT                                /FTId=VAR_004012.
FT   VARIANT      57     57       H -> R (in alpha-2C).
FT                                /FTId=VAR_013001.
FT   HELIX        33     44
FT   TURN         49     54
FT   HELIX        63     66
FT   HELIX        76     91
FT   HELIX        93     98
FT   HELIX       101    123
FT   TURN        126    127
FT   TURN        133    133
FT   HELIX       134    155
FT   TURN        156    157
FT   HELIX       160    178
FT   TURN        179    182
SQ   SEQUENCE   188 AA;  21550 MW;  101DD21D394CBF97 CRC64;
     MALTFALLVA LLVLSCKSSC SVGCDLPQTH SLGSRRTLML LAQMRKISLF SCLKDRHDFG
     FPQEEFGNQF QKAETIPVLH EMIQQIFNLF STKDSSAAWD ETLLDKFYTE LYQQLNDLEA
     CVIQGVGVTE TPLMKEDSIL AVRKYFQRIT LYLKEKKYSP CAWEVVRAEI MRSFSLSTNL
     QESLRSKE
//

Output file format

Output files for usage example

File: laci_ecoli.iep

IEP of LACI_ECOLI from 1 to 360
Isoelectric Point = 6.8820

   pH     Bound    Charge
  1.00    81.96    37.96
  1.50    81.89    37.89
  2.00    81.65    37.65
  2.50    80.91    36.91
  3.00    78.79    34.79
  3.50    73.70    29.70
  4.00    65.15    21.15
  4.50    56.73    12.73
  5.00    51.75     7.75
  5.50    49.36     5.36
  6.00    47.63     3.63
  6.50    45.56     1.56
  7.00    43.59    -0.41
  7.50    42.27    -1.73
  8.00    41.22    -2.78
  8.50    39.87    -4.13
  9.00    38.26    -5.74
  9.50    36.24    -7.76
 10.00    33.03   -10.97
 10.50    28.46   -15.54
 11.00    23.58   -20.42
 11.50    19.41   -24.59
 12.00    15.19   -28.81
 12.50     9.75   -34.25
 13.00     4.64   -39.36
 13.50     1.75   -42.25
 14.00     0.59   -43.41

Output files for usage example 2

File: ifna2_human.iep

IEP of IFNA2_HUMAN from 1 to 188
Isoelectric Point = 5.7322

   pH     Bound    Charge
  1.00    52.98    22.98
  1.50    52.93    22.93
  2.00    52.77    22.77
  2.50    52.28    22.28
  3.00    50.87    20.87
  3.50    47.47    17.47
  4.00    41.62    11.62
  4.50    35.67     5.67
  5.00    32.10     2.10
  5.50    30.47     0.47
  6.00    29.51    -0.49
  6.50    28.55    -1.45
  7.00    27.65    -2.35
  7.50    27.01    -2.99
  8.00    26.36    -3.64
  8.50    25.41    -4.59
  9.00    24.25    -5.75
  9.50    22.81    -7.19
 10.00    20.49    -9.51
 10.50    17.03   -12.97
 11.00    13.16   -16.84
 11.50    10.04   -19.96
 12.00     7.49   -22.51
 12.50     4.72   -25.28
 13.00     2.23   -27.77
 13.50     0.84   -29.16
 14.00     0.28   -29.72

For each pH point it gives the number of bound electrons and the charge.

Data files

iep reads in local data file Epk.dat which contains amino acid pK values used to calculate the isoelectric point of the whole protein

EMBOSS data files are distributed with the application and stored in the standard EMBOSS data directory, which is defined by the EMBOSS environment variable EMBOSS_DATA.

To see the available EMBOSS data files, run:

% embossdata -showall

To fetch one of the data files (for example 'Exxx.dat') into your current directory for you to inspect or modify, run:


% embossdata -fetch -file Exxx.dat

Users can provide their own data files in their own directories. Project specific files can be put in the current directory, or for tidier directory listings in a subdirectory called ".embossdata". Files for all EMBOSS runs can be put in the user's home directory, or again in a subdirectory called ".embossdata".

The directories are searched in the following order:

Here is the default Epk.dat file:

# pK values for amino acids
# O=Ornithine J=Hydroxyproline
#
# Amino acid	pK
Amino		8.6
Carboxyl	3.6

C		8.5
D		3.9
E		4.1
H		6.5
K		10.8
R		12.5
Y		10.1

Notes

None.

References

None.

Warnings

None.

Diagnostic Error Messages

None.

Exit status

0 if successful.

Known bugs

None.

See also

Program nameDescription
backtranambig Back translate a protein sequence to ambiguous codons
backtranseq Back translate a protein sequence
charge Protein charge plot
checktrans Reports STOP codons and ORF statistics of a protein
compseq Count composition of dimer/trimer/etc words in a sequence
emowse Protein identification by mass spectrometry
freak Residue/base frequency table or plot
mwcontam Shows molwts that match across a set of files
mwfilter Filter noisy molwts from mass spec output
octanol Displays protein hydropathy
pepinfo Plots simple amino acid properties in parallel
pepstats Protein statistics
pepwindow Displays protein hydropathy
pepwindowall Displays protein hydropathy of a set of sequences

Author(s)

Alan Bleasby (ajb © ebi.ac.uk)
European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK

History

Completed 1st August 1999.

Target users

This program is intended to be used by everyone and everything, from naive users to embedded scripts.

Comments

None