Introduction ATP Binding Cassette (ABC)
systems constitute one of the most abundant families
of proteins. The most prominent characteristic of these
systems is that they share a highly conserved ATPase
domain, the ATP-binding cassette, which has been demonstrated
to bind and hydrolyze ATP, thereby providing energy
to a large number of biological processes. The amino
acid sequence of this cassette displays three major
conserved motifs, the Walker motifs A and B commonly
found in ATPases and a specific signature motif also
known as the linker peptide (figure 1). The tertiary structure of the ABC domain
is apparently conserved. The structural information
for 2 ABC ATPases is available in the Protein Data Bank
(click here
for a comparison of the structures of HisP and MalK).
We have identified more than 2000 ABC ATPase domains
or proteins in translated nucleic acid sequence databases.
A total of about 6000 proteins was found when the partners
of ATPases were taken in account. The size of this mass
of sequences is therefore similar to the coding capacity
of a bacterial genome. ABC systems are involved
not only in the import or the export of a wide variety
of substances, but also in many cellular processes and
in their regulation. Importers constitute mainly the prokaryotic subfamily
of substrate-binding protein dependent transporters
and their main function is to provide essential nutrients
to bacteria even if the latter are present in submicromolar
concentrations in the environment. Exporters are found in both prokaryotes and eukaryotes
and are involved in the extrusion of noxious substances,
the export of extracellular toxins and the targeting
of membrane components. The third class of ABC systems
is apparently not involved in transport but rather in
cellular
processes such
as DNA repair, translation or regulation of gene expression.
Domain
organization of ABC systems ABC Transporters are composed of four
structural domains: two very hydrophobic membrane spanning
or integral membrane domains (IM) and two hydrophilic
cytoplasmic domains carrying the ATP-binding cassette
(ABC) and peripherally associated to IM on the cytosolic
side of the membrane. Importers have in general the four domains
carried by independent polypeptides and they need for
optimal function an extracellular substrate-binding
protein. This protein, an essential component for transport,
is a periplasmic protein in Gram-negative bacteria and
a surface-anchored lipoprotein in Gram-positive bacteria
and archaea (figure 2).
Exporters have the four domains fused in several ways.
Prokaryote exporters have the IM domain fused to the
ABC domain (IM-ABC) and require additional proteins
for function. In general, they need a cytoplasmic membrane
component belonging to the membrane fusion protein (MFP)
family and in Gram-negative bacteria an outer membrane
protein. Eukaryote exporters are similar to prokaryote
exporters in their design. However, some eukaryote families
of exporters display the four domains on the same polypeptide
chain ((IM-ABC)2) (figure 3). Systems involved in cellular processes other than transport do not
have IM domains and are comprised of duplicated and
fused ABC domains (ABC2) (figure 4)
Presentation
of the database
The ABCISSE database is the result of a phylogenetic
and functional classification of ABC systems found in
living organisms. The central objet of the database
is the system, which is comprised of a set of proteins
(called also partners) known or predicted to function
together in order to accomplish a specific function.
The database is comprised of about 2000 systems and
this number is expected to increase very quickly since
10 to 30 new systems are submitted to sequence databases
every month. Systems whose members display a strong
primary sequence conservation are grouped in families,
which may be divided in subfamilies. The database is
comprised of 34 families. In most cases, systems from
a given family are performing similar functions. Families
are grouped in three phylogenetic classes which fit
fairly well wiht the three fuctional categories which
are Import, Export and Non Transport Cellular processes.
The classification is based primarily on two phylogenetic
analyses of the sequences of the highly conserved ATPase
subunit or domain shared by ABC sytems. The first analysis
was concucted with a set of about 200 sequences (Saurin et
al, 1999). A
second round of analyzes was performed with about 600
sequences from completely sequenced organisms. The results
of the studies were consistent with a very early segregation
of the three functional categories within the common
ancestor of living organisms. Additional classifications
were performed on the partners of transport systems
and it was found that the classifications of ABC ATPases
and those of their partners were generally similar.
This behaviour suggests that ABC systems evolve as a
whole entity with little shuffling of domains and partners
during evolvution.
Navigating in the
database
The "Quick look-up" section :
This section is intended to help retrieving quickly a peculiar ABC system.
A system can be accessed from the name of the organism, from the name of
the family to which it belongs, from the name of the transported substrate,
or from the gene name of one of the partners that constitute the
system.
The "List of species" search :
This is a list of organisms known to carry at least 1 ABC system and its
was broken into several sub-lists for a compact display. The species are
sorted according to the initial of the genus. The list gives the number of
ABC systems described in the organisms and reports if the genome is
completely sequenced. Click on the "Organism" name to display the
list of the ABC systems identified in this organism. Then click of the
"Family" name to display a view of the system (see below for
additional help). Alternatively, click on the "Substrate" name to
display a list of organisms known to contain a system specific for this
substrate.
The "List of families" search : This is a list of families sorted according to the physiological function
of the systems (Export, Cellular processes, Import, or Unknown). The
abbreviated name of the family is explained in the "Definition" column.
Click on the "Family" name or on the "Sub-family" name to
display a list of "Species" (organisms) known to possess at least 1 member
of this family or subfamily. This list provides for each species the name
of the substrate handled by the ABC system and if it is not known, the
biological role played by this system. Click on "details" to display
a brief overview of the properties of the family or sub-family.
Click on the "Species" name to display a view of the system.
Alternatively, click on the "Substrate" name to display a list of
organisms known to contain a system specific for this substrate.
The "List of substrates" search
This is an alphabetical list of substrates known to be transported by an
ABC system. Click on the "Substrate" name to display a list of
organisms known to transport this molecule. Click on the "Family"
name to display all the members of the family comprising this
system.
The "gene name" search :
Enter the name of the gene to search and click on the submit
button
2. The "Advanced search" section: under construction
3. The phylogenetic tree section: under construction
Viewing ABC systems:
The complete description of a system is presented on several pages. The
first page "View of ABC system" provides an overview of the properties of
the system and a list of its constituents (partners). Each partner of a
system is described on the "View of ABC partner" pages which can be
accessed by clicking on the name of the partner.
The "View of ABC system" page provides the following information:
| General information
on the
system |
| Abcisse Accession Number |
Internal reference |
| Entered in ABCISSE in |
Internal reference |
| Last
modification |
Internal reference |
| Fonction
(status *
) |
Biological function of the system, this
could be Import, Export or Cellular processes (e.g. DNA repair)
|
| Family |
A series of systems with clear primary sequence similarity
(details **)
|
| Sub-family |
A series of systems with clear primary sequence and functional similarity
(details **)
|
| Substrate
(status *
) |
Molecule transported by a given system
|
| Role
(status *
) |
Physiological function of ABC systems not
involved in transport (e.g. DNA repair)
OR
Physiological function of a putative transport system whose
substrate is unknown (e.g. fimbriae formation)
|
| Associated
disease(s) |
Human disease(s) determined by a mutation in a system |
| Organism |
Genus and species names of the organism
|
| Taxonomy |
Taxonomic position of the organism |
| References |
| [1] Selected bibliography documenting the
function of the system |
| Comments |
|
Some particular features of the system |
| Structure of
System (gene name) |
This section gives the list and the organization
of the genes that constitute the system. Click on the gene name to display
the properties of the gene
|
| * The "status" field
indicates whether a given function, substrate specificity or role of a
system is predicted or experimentally verified |
** The "details" field gives a brief
overview of the properties of the family or sub-family.
|
The "View of ABC partner" page provides the following information:
| Partner |
| Type |
Domain organization of the partner (see above for the
definition of the symbols) |
| GI |
NCBI unique identifier and link to the GenPept format of the translated
gene |
| Gene name |
|
| Strain |
|
| DNA |
Subcellular location (Chromosome, plasmid, plastid, etc.)
|
| Location absolute |
Coordinates of the gene on the genome |
| Location relative |
Coordinates of the gene on the contig |
| [Comp.] (Join) |
[C-] (J- ) |
| Accession
number |
Database accession number and link to the Genbank format |
| DB name :
ID |
Database name and database unique identifier of the
gene |
| Length |
a.a. |
Molecular
Weight |
|
Seq. Fasta |
| Motif(s) |
Characteristic sequence motifs |
| Comments |
Some particular features of the partner |
| Synonym(s) |
List of (and links to) identical sequences in
different databases |
|
|