PROSITE documentation PDOC00528
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{PDOC00528}
{PS00371; PTS_EIIA_TYPE_1_HIS}
{PS00372; PTS_EIIA_TYPE_2_HIS}
{PS51093; PTS_EIIA_TYPE_1}
{PS51094; PTS_EIIA_TYPE_2}
{PS51095; PTS_EIIA_TYPE_3}
{PS51096; PTS_EIIA_TYPE_4}
{PS51097; PTS_EIIA_TYPE_5}
{BEGIN}
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* PTS EIIA domain profiles and phosphorylation site signatures *
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The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) [1,2]
is a major carbohydrate transport system in bacteria. The PTS catalyzes the
phosphorylation of incoming sugar substrates concomitant with their
translocation across the cell membrane. The general mechanism of the PTS is
the following: a phosphoryl group from phosphoenolpyruvate (PEP) is
transferred to enzyme I (EI) of PTS which in turn transfers it to a phosphoryl
carrier protein (HPr) (see <PDOC00318>). Phospho-HPr then transfers the
phosphoryl group to a sugar-specific permease which consists of at least three
structurally distinct domains (IIA, IIB, and IIC), [3] which can either be
fused together in a single polypeptide chain or exist as two or three
interactive chains, formerly called enzymes II (EII) and III (EIII).
The first domain (IIA) , carries the first permease-specific phosphorylation
site, an histidine which is phosphorylated by phospho-HPr. The second domain
(IIB) (see <PDOC00795>) is phosphorylated by phospho-IIA on a cysteinyl or
histidyl residue, depending on the sugar transported. Finally, the phosphoryl
group is transferred from the IIB domain to the sugar substrate concomitantly
with the sugar uptake processed by the IIC domain (see <PDOC51103>). The IIC
domain forms the translocation channel and at the specific substrate-binding
site. An additional transmembrane domain IID (see <PDOC51108>), homologous to
IIC, can be found in some PTSs, e.g. for mannose [1,3,4,5,6].
According to structural and sequence analyses, the PTS EIIA domain
(EC 2.7.1.-) can be divided in five groups [7,8,9,10].
- The PTS EIIA type 1 domain, which is found in the Glucose class of PTS, has
an average length of about 100 amino acids. It forms an antiparallel
beta-barrel structure that incorporates 'Greek key' and 'jellyroll'
topological motifs (see <PDB:1GPR>). The phosphorylation site (His) is
located in the middle of the domain, at the C-terminus of a beta-strand
[7].
- The PTS EIIA type 2 domain, which is found in the Mannitol class of PTS,
has an average length of about 142 amino acids. It consists of an
alternating beta/alpha arrangement of five-stranded beta-sheet and five
alpha-helices, where the two last alpha helices forms an helical hairpin
(see <PDB:1PDO>). The phosphorylation site (His) is located at the
N-terminus of the domain, at the topological switch-point of the structure,
close to the subunit interface [8].
- The PTS EIIA type 3 domain, which is found in the Lactose class of PTS, has
an average length of about 100 amino acids. It is composed of three
alpha-helices (see <PDB:1E2A>). The phosphorylation site (His) is located
at the C-terminus of the domain in the third alpha helix [9].
- The PTS EIIA type 4 domain, which is found in the Mannose class of PTS, has
an average length of about 130 amino acids. It consists of a single
five-stranded mixed beta sheet, flanked by helices on both sides (see
<PDB:1A3A>). The phosphorylation site (His) is located at the end of the
third beta strand, in a shallow crevice lined with hydrophobic residues
[10].
- The PTS EIIA type 5 domain, which is found in the Sorbitol class of PTS,
has an average length of about 110 amino acids. The phosphorylation site
(His) is located at the N-terminus of the domain.
EIIA-like domains similar to type 1 to 4 can be found in other kind of
proteins, which are mainly transcriptional regulators [5]. In these cases, the
EIIA-like domain is found in association with other domains like the Sigma-54
interaction domain (see <PDOC00579>), the DeoR-type HTH domain
(see <PDOC00696>), or the PTS regulation domain (transcriptional
antiterminator). It may possess a regulatory function, through its
phosphorylation activity, or act as a simple phosphoryl donor. Some proteins
known to contains a EIIA-like domain are listed below:
- Bacterial transcriptional regulatory proteins levR, nrtC, bglG.
- Bacterial lactose permease lacS, a non-PTS transport system.
- Bacterial PTS-dependent dihydroxyacetone kinase, phosphotransferase subunit
dhaM.
We have developed two signature patterns for the phosphorylation site of the
IIA domains. We also developed five profiles that cover the entire PTS EIIA
domains. These profiles are directed respectively against the Glucose class of
PTS, the Mannitol class of PTS, the Lactose class of PTS, the Mannose class of
PTS, and the Sorbitol class of PTS.
-Consensus pattern: G-x(2)-[LIVMFA]-[LIVMF](2)-H-[LIVMF]-G-[LIVMF]-x-T-[LIVA]
[H is phosphorylated]
-Sequences known to belong to this class detected by the pattern: B. subtilis,
E. coli, and S. typhimurium IIA(Glc), E. coli IIA(Nag), E. coli and E.
chrysanthemi IIA(Bgl), E. coli IIA(Scr), Streptococcal lactose permeases
(gene lacS) and raffinose permease (gene rafP) which contain a C-terminal
PTS-like IIA domain.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Consensus pattern: [DENQ]-x(6)-[LIVMF]-[GA]-x(2)-[LIVM]-A-[LIVM]-P-H-[GAC]
[H is phosphorylated]
-Sequences known to belong to this class detected by the pattern: E. coli, E.
faecalis, S. Aureus and S. carnosus IIA(Mtl), E. coli and S.typhimurium
IIA(Fru), E. coli IIA(C)(Mtl), E. coli frvA, and ptsN.
-Other sequence(s) detected in Swiss-Prot: 1.
-Sequences known to belong to this class detected by the first profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Sequences known to belong to this class detected by the second profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Sequences known to belong to this class detected by the third profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Sequences known to belong to this class detected by the fourth profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Sequences known to belong to this class detected by the fifth profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2005 / Profiles added and text revised.
[ 1] Postma P.W., Lengeler J.W., Jacobson G.R.
"Phosphoenolpyruvate:carbohydrate phosphotransferase systems of
bacteria."
Microbiol. Rev. 57:543-594(1993).
PubMed=8246840
[ 2] Meadow N.D., Fox D.K., Roseman S.
"The bacterial phosphoenolpyruvate: glycose phosphotransferase
system."
Annu. Rev. Biochem. 59:497-542(1990).
PubMed=2197982; DOI=10.1146/annurev.bi.59.070190.002433
[ 3] Saier M.H. Jr., Reizer J.
"Proposed uniform nomenclature for the proteins and protein domains of
the bacterial phosphoenolpyruvate: sugar phosphotransferase system."
J. Bacteriol. 174:1433-1438(1992).
PubMed=1537788
[ 4] Saier M.H. Jr., Reizer J.
"The bacterial phosphotransferase system: new frontiers 30 years
later."
Mol. Microbiol. 13:755-764(1994).
PubMed=7815935
[ 5] Tchieu J.H., Norris V., Edwards J.S., Saier M.H. Jr.
"The complete phosphotranferase system in Escherichia coli."
J. Mol. Microbiol. Biotechnol. 3:329-346(2001).
PubMed=11361063
[ 6] Saier M.H., Hvorup R.N., Barabote R.D.
"Evolution of the bacterial phosphotransferase system: from carriers
and enzymes to group translocators."
Biochem. Soc. Trans. 33:220-224(2005).
PubMed=15667312; DOI=10.1042/BST0330220
[ 7] Liao D.-I., Kapadia G., Reddy P., Saier M.H. Jr., Reizer J.,
Herzberg O.
"Structure of the IIA domain of the glucose permease of Bacillus
subtilis at 2.2-A resolution."
Biochemistry 30:9583-9594(1991).
PubMed=1911744
[ 8] Nunn R.S., Markovic-Housley Z., Genovesio-Taverne J.-C., Flukiger K.,
Rizkallah P.J., Jansonius J.N., Schirmer T., Erni B.
"Structure of the IIA domain of the mannose transporter from
Escherichia coli at 1.7 angstroms resolution."
J. Mol. Biol. 259:502-511(1996).
PubMed=8676384
[ 9] Sliz P., Engelmann R., Hengstenberg W., Pai E.F.
"The structure of enzyme IIAlactose from Lactococcus lactis reveals a
new fold and points to possible interactions of a multicomponent
system."
Structure 5:775-788(1997).
PubMed=9261069
[10] van Montfort R.L.M., Pijning T., Kalk K.H., Hangyi I., Kouwijzer M.L.C.E.,
Robillard G.T., Dijkstra B.W.
Structure 6:377-388(1998).
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