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.
32  structures 7474  species 0  interactions 9712  sequences 54  architectures

Family: Porphobil_deam (PF01379)

Summary: Porphobilinogen deaminase, dipyromethane cofactor binding domain

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.

Porphobilinogen deaminase, dipyromethane cofactor binding domain Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR022417

Tetrapyrroles are large macrocyclic compounds derived from a common biosynthetic pathway [ PUBMED:16564539 ]. The end-product, uroporphyrinogen III, is used to synthesise a number of important molecules, including vitamin B12, haem, sirohaem, chlorophyll, coenzyme F430 and phytochromobilin [ PUBMED:17227226 ].

  • The first stage in tetrapyrrole synthesis is the synthesis of 5-aminoaevulinic acid ALA via two possible routes: (1) condensation of succinyl CoA and glycine (C4 pathway) using ALA synthase ( EC ), or (2) decarboxylation of glutamate (C5 pathway) via three different enzymes, glutamyl-tRNA synthetase ( EC ) to charge a tRNA with glutamate, glutamyl-tRNA reductase ( EC ) to reduce glutamyl-tRNA to glutamate-1-semialdehyde (GSA), and GSA aminotransferase ( EC ) to catalyse a transamination reaction to produce ALA.

  • The second stage is to convert ALA to uroporphyrinogen III, the first macrocyclic tetrapyrrolic structure in the pathway. This is achieved by the action of three enzymes in one common pathway: porphobilinogen (PBG) synthase (or ALA dehydratase, EC ) to condense two ALA molecules to generate porphobilinogen; hydroxymethylbilane synthase (or PBG deaminase, EC ) to polymerise four PBG molecules into preuroporphyrinogen (tetrapyrrole structure); and uroporphyrinogen III synthase ( EC ) to link two pyrrole units together (rings A and D) to yield uroporphyrinogen III.

  • Uroporphyrinogen III is the first branch point of the pathway. To synthesise cobalamin (vitamin B12), sirohaem, and coenzyme F430, uroporphyrinogen III needs to be converted into precorrin-2 by the action of uroporphyrinogen III methyltransferase ( EC ). To synthesise haem and chlorophyll, uroporphyrinogen III needs to be decarboxylated into coproporphyrinogen III by the action of uroporphyrinogen III decarboxylase ( EC ) [ PUBMED:11215515 ].

Porphobilinogen deaminase (also known as hydroxymethylbilane synthase, EC ) functions during the second stage of tetrapyrrole biosynthesis. This enzyme catalyses the polymerisation of four PBG molecules into the tetrapyrrole structure, preuroporphyrinogen, with the concomitant release of four molecules of ammonia. This enzyme uses a unique dipyrro-methane cofactor made from two molecules of PBG, which is covalently attached to a cysteine side chain. The tetrapyrrole product is synthesized in an ordered, sequential fashion, by initial attachment of the first pyrrole unit (ring A) to the cofactor, followed by subsequent additions of the remaining pyrrole units (rings B, C, D) to the growing pyrrole chain [ PUBMED:11215515 ]. The link between the pyrrole ring and the cofactor is broken once all the pyrroles have been added. This enzyme is folded into three distinct domains that enclose a single, large active site that makes use of an aspartic acid as its one essential catalytic residue, acting as a general acid/base during catalysis [ PUBMED:12555854 , PUBMED:1522882 ]. A deficiency of hydroxymethylbilane synthase is implicated in the neuropathic disease, Acute Intermittent Porphyria (AIP) [ PUBMED:16935474 ].

This entry represents the N-terminal domains 1 and 2 of porphobilinogen deaminase, an enzyme involved in tetrapyrrole biosynthesis. The structure of this domain consists of a duplication of two similar intertwined domains with three layers of (a/b/a) each. Porphobilinogen deaminase has a three-domain structure. Domains 1 (N-terminal) and 2 are duplications with the same structure, resembling the transferrins and periplasmic binding proteins. The dipyrromethane cofactor is covalently linked to domain 3 (C-terminal), but is bound by extensive salt-bridges and hydrogen-bonds within the cleft between domains 1 and 2, at a position corresponding to the binding sites for small-molecule ligands in the analogous proteins [ PUBMED:1522882 ]. The enzyme has a single catalytic site, and the flexibility between domains is thought to aid elongation of the polypyrrole product in the active-site cleft of the enzyme.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

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 PBP (CL0177), which has the following description:

Periplasmic binding proteins (PBPs) consist of two large lobes that close around the bound ligand. This architecture is reiterated in transcriptional regulators, such as the lac repressors. In the process of evolution, genes encoding the PBPs have fused with genes for integral membrane proteins. Thus, diverse mammalian receptors contain extracellular ligand binding domains that are homologous to the PBPs; these include glutamate/glycine-gated ion channels such as the NMDA receptor, G protein-coupled receptors, including metabotropic glutamate, GABA-B, calcium sensing, and pheromone receptors, and atrial natriuretic peptide-guanylate cyclase receptors [2].

The clan contains the following 27 members:

CypI DctP DUF3834 HisG Lig_chan-Glu_bd Lipoprotein_8 Lipoprotein_9 LysR_substrate NMT1 NMT1_2 NMT1_3 OpuAC PBP_like PBP_like_2 PDT Phosphonate-bd Porphobil_deam SBP_bac_1 SBP_bac_11 SBP_bac_3 SBP_bac_5 SBP_bac_6 SBP_bac_8 TctC Transferrin VitK2_biosynth YhfZ_C


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: SCOP
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Griffiths-Jones SR
Number in seed: 666
Number in full: 9712
Average length of the domain: 204 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 62.02 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.1 22.1
Trusted cut-off 22.8 22.1
Noise cut-off 21.2 22.0
Model length: 208
Family (HMM) version: 23
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 Porphobil_deam domain has been found. There are 32 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...

AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0D2HPM6 View 3D Structure Click here
A0A0H3GKD9 View 3D Structure Click here
A0A0R0HHA1 View 3D Structure Click here
A0A0R4IQ55 View 3D Structure Click here
A0A175W0I6 View 3D Structure Click here
A0A1C1C9W4 View 3D Structure Click here
A0A1D6H1H5 View 3D Structure Click here
A0A1D6QSE2 View 3D Structure Click here
A0LN73 View 3D Structure Click here
A0LRF1 View 3D Structure Click here
A0Q2B1 View 3D Structure Click here
A1AUE7 View 3D Structure Click here
A1AX51 View 3D Structure Click here
A1B853 View 3D Structure Click here
A1BHD6 View 3D Structure Click here
A1T0R0 View 3D Structure Click here
A1T3D3 View 3D Structure Click here
A1WVT9 View 3D Structure Click here
A2BL26 View 3D Structure Click here
A3CL78 View 3D Structure Click here
A3DIF0 View 3D Structure Click here
A3PBM0 View 3D Structure Click here
A4J6H7 View 3D Structure Click here
A4SFJ8 View 3D Structure Click here
A4YD92 View 3D Structure Click here
A5CDH4 View 3D Structure Click here
A5D3L5 View 3D Structure Click here
A5EW83 View 3D Structure Click here
A5GCW2 View 3D Structure Click here
A5GSE0 View 3D Structure Click here
A5I0B2 View 3D Structure Click here
A5UU37 View 3D Structure Click here
A5VM67 View 3D Structure Click here
A6Q3S1 View 3D Structure Click here
A6Q7Y4 View 3D Structure Click here
A6TGI8 View 3D Structure Click here
A6TJD5 View 3D Structure Click here
A6VL87 View 3D Structure Click here
A6WXJ2 View 3D Structure Click here
A7GYU4 View 3D Structure Click here