Summary

Pirin

This family consists of Pirin proteins from both eukaryotes and prokaryotes. The function of Pirin is unknown but the gene coding for this protein is known to be expressed in all tissues in the human body although it is expressed most strongly in the liver and heart. Pirin is known to be a nuclear protein, exclusively localised within the nucleoplasma and predominantly concentrated within dot-like subnuclear structures [1]. A tomato homologue of human Pirin has been found to be induced during programmed cell death [2]. Human Pirin interacts with Bcl-3 and NFI [3] and hence is probably involved in the regulation of DNA transcription and replication. It appears to be an Fe(II)-containing member of the Cupin superfamily.

Literature references

Wendler WM, Kremmer E, Forster R, Winnacker EL; , J Biol Chem 1997;272:8482-8489.: Identification of pirin, a novel highly conserved nuclear protein. PUBMED:9079676
Orzaez D, de Jong AJ, Woltering EJ; , Plant Mol Biol 2001;46:459-468.: A tomato homologue of the human protein PIRIN is induced during programmed cell death. PUBMED:11485202
Dechend R, Hirano F, Lehmann K, Heissmeyer V, Ansieau S, Wulczyn FG, Scheidereit C, Leutz A; , Oncogene 1999;18:3316-3323.: The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators. PUBMED:10362352
Pang H, Bartlam M, Zeng Q, Miyatake H, Hisano T, Miki K, Wong LL, Gao GF, Rao Z; , J Biol Chem 2004;279:1491-1498.: Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor. PUBMED:14573596

InterPro entry IPR003829

This entry represents N-terminal domain of Pirin proteins from both eukaryotes and prokaryotes.

The function of Pirin is unknown but the gene coding for this protein is known to be expressed in all tissues in the human body although it is expressed most strongly in the liver and heart. Pirin is known to be a nuclear protein, exclusively localised within the nucleoplasma and predominantly concentrated within dot-like subnuclear structures PUBMED:9079676.

Pirin is composed of two structurally similar domains arranged face to face. The N-terminal domain additionally features four beta-strands, and the C-terminal domain also includes four additional -strands and a short alpha-helix. Although the two domains are similar, the C-terminal domain of Pirin differs from the N-terminal domain as it does not contain a metal binding site and its sequence does not contain the conserved metal-coordinating residues PUBMED:1457596.

Pirin is confirmed to be a member of the cupin superfamily on the basis of primary sequence and structural similarity. The presence of a metal binding site in the N-terminal beta-barrel of Pirin, may be significant in its role in regulating NFI DNA replication and NF-kappaB transcription factor activity PUBMED:1457596.

Pirin structure has been found to closely resemble members of the cupin superfamily. Pirin contains the two characteristic sequences of the cupin superfamily, namely PG-(X)5-HXH-(X)4-E-(X)6-G and G-(X)5-PXG-(X)2-H-(X)3-N separated by a variable stretch of 15-50 amino acids. These motifs are best conserved in the N-terminal where the conserved histidine and glutamic acid residues correspond to the metal-coordinating residues. The C-terminal domain motifs lack the metal binding residues normally associated with the cupin fold PUBMED:1457596.

Pirin was identified to be a metal-binding protein PUBMED:14573596, and was found that the metal-binding residues of Pirins are highly conserved across mammals, plants, fungi, and prokaryotic organisms. Pirin acts as a cofactor for the transcription factor NFI, the regulatory mechanism of which is generally believed to require the assistance of a metal ion PUBMED:12426136. Structural data supports the hypothesis that the bound iron of Pirin may participate in this transcriptional regulation by enhancing and stabilising the formation of the p50,Bcl3,DNA complex PUBMED:14573596. Metals have been implicated directly or indirectly in the NF-kappaB family of transcription factors that control expression of a number of early response genes associated with inflammatory responses, cell growth, cell cycle progression, and neoplastic transformation PUBMED:12426136. However, most metal-dependent transcription factors are DNA-binding proteins that bind to specific sequences when the metal binds to the protein. Pirin, on the other hand, appears to function differently and bind to the transcription factor DNA complex PUBMED:14573596.

Clan

This family is a member of clan Cupin (CL0029), which contains the following 35 members:

2OG-FeII_Oxy 3-HAO AraC_binding AraC_N ARD Asp_Arg_Hydrox Auxin_BP CDO_I CsiD Cupin_1 Cupin_2 Cupin_3 Cupin_4 Cupin_5 dTDP_sugar_isom DUF1255 DUF1479 DUF1498 DUF1637 DUF1971 DUF386 Ectoine_synth EutQ FdtA GPI HgmA JmjC KduI MannoseP_isomer Mif2 PhyH Pirin Pirin_C PMI_typeI TauD

External database links

PANDIT:	PF02678
SCOP:	1j1l
SYSTERS:	Pirin

Domain organisation

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

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Alignments

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

View options

Alignment:	Seed (52) Full (2025) NCBI (3404) Metagenomics (1898)
Viewer:

Formatting options

Alignment:	Seed (52) Full (2025)
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

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

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (52) Full (2025) NCBI (3404) Metagenomics (1898)
Full length sequences	Full-sequences (2025)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

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...

Trees

This page displays the phylogenetic tree for this family. 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 or full alignments.

Note: You can also download the data files for the seed, full, NCBI or metagenomics trees.

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

Seed source:

COG1741

Previous IDs:

DUF209;

Type:

Family

Author:

Mian N, Bateman A, Moxon SJ, Yeats C

Number in seed:

52

Number in full:

2025

Average length of the domain:

109.30 aa

Average identity of full alignment:

35 %

Average coverage of the sequence by the domain:

40.08 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 9421015 -E 1000 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.6	20.6
Trusted cut-off	20.6	20.6
Noise cut-off	20.5	20.4

Model length:

107

Family (HMM) version:

9

Download:

download the raw HMM for this family

Species distribution

Tree controls

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

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
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Interactions

There is 1 interaction for this family. More...

Pirin_C

Structures

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 Pirin domain has been found.

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Family: Pirin (PF02678)

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