Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
23  structures 4600  species 0  interactions 13238  sequences 147  architectures

Family: PTS_EIIA_2 (PF00359)

Summary: Phosphoenolpyruvate-dependent sugar phosphotransferase system, EIIA 2

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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...

Loading domain graphics...

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


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

Representative proteomes UniProt
Jalview View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

Representative proteomes UniProt

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

Representative proteomes UniProt
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

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

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD , Griffiths-Jones SR
Number in seed: 85
Number in full: 13238
Average length of the domain: 141.70 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 36.94 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -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: 24
Download: download the raw HMM for this family

Species distribution

Sunburst controls


Weight segments by...

Change the size of the sunburst


Colour assignments

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


Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls


The tree shows the occurrence of this domain across different species. More...


Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.


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 sequence.

Loading structure mapping...