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23  structures 14953  species 3  interactions 107603  sequences 139  architectures

Family: PTS_EIIA_2 (PF00359)

Summary: Phosphoenolpyruvate-dependent sugar phosphotransferase system, EIIA 2

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Phosphoenolpyruvate-dependent sugar phosphotransferase system, EIIA 2 Provide feedback

No Pfam abstract.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002178

The phosphoenolpyruvate-dependent sugar phosphotransferase system (PTS) [PUBMED:8246840, PUBMED:2197982] is a major carbohydrate transport system in bacteria. The PTS catalyses 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). 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), [PUBMED:1537788] 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) 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. The IIC domain forms the translocation channel and at the specific substrate-binding site. An additional transmembrane domain IID, homologous to IIC, can be found in some PTSs, e.g. for mannose [PUBMED:7815935, PUBMED:11361063, PUBMED:15667312].

According to structural and sequence analyses, the PTS EIIA domain can be divided in five groups [PUBMED:1911744, PUBMED:8676384, PUBMED:9261069].

  • 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. The phosphorylation site (His) is located in the middle of the domain, at the C terminus of a beta-strand [PUBMED:1911744].
  • 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. 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 [PUBMED:8676384].
  • 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. The phosphorylation site (His) is located at the C terminus of the domain in the third alpha helix [PUBMED:9261069].
  • 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. The phosphorylation site (His) is located at the end of the third beta strand, in a shallow crevice lined with hydrophobic residues.
  • 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 [PUBMED:11361063]. In these cases, the EIIA-like domain is found in association with other domains like the Sigma-54 interaction domain, the DeoR-type HTH domain, 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.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan PTase-anion_tr (CL0340), which has the following description:

The families here are the cytoplasmic regions of anion transporter proteins.

The clan contains the following 2 members:

Band_3_cyto PTS_EIIA_2


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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Family
Author: Finn RD, Griffiths-Jones SR
Number in seed: 104
Number in full: 107603
Average length of the domain: 141.80 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 33.42 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.0 21.0
Trusted cut-off 21.0 21.0
Noise cut-off 20.9 20.9
Model length: 144
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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There are 3 interactions for this family. More...



For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PTS_EIIA_2 domain has been found. There are 23 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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