Summary

GTP cyclohydrolase I feedback regulatory protein (GFRP)

Tetrahydrobiopterin, the cofactor required for hydroxylation of aromatic amino acids regulates its own synthesis in via feedback inhibition of GTP cyclohydrolase I. This mechanism is mediated by the regulatory subunit called GTP cyclohydrolase I feedback regulatory protein (GFRP) [1].

Literature references

Bader G, Schiffmann S, Herrmann A, Fischer M, Gutlich M, Auerbach G, Ploom T, Bacher A, Huber R, Lemm T; , J Mol Biol 2001;312:1051-1057.: Crystal structure of rat GTP cyclohydrolase I feedback regulatory protein, GFRP. PUBMED:11580249

InterPro entry IPR009112

GTP cyclohydrolase I feedback regulatory protein (GFRP) in mammals helps regulate the biosynthesis of tetrahydrobiopterin through the feedback inhibition of the rate-limiting enzyme GTP cyclohydrolase I (GTPCHI). Tetrahydrobiopterin is the cofactor required for the hydroxylation of aromatic amino acids. The crystal structure of GFRP reveals that the protein forms a homopentamer PUBMED:11580249. In the presence of phenylalanine, the stimulatory complex consists of a GTPCHI decamer sandwiched by two GFRP pentamers, which is thought to enhance GTPCHI activity by locking the enzyme in the active state PUBMED:11818540. The structure of GFRP consists of two alpha/beta layers arranged beta(2)-alpha-beta(2)-alpha-beta(2), with antiparallel beta-sheets in the order 342165.

Gene Ontology

Molecular function	protein binding (GO:0005515)
Biological process	negative regulation of biosynthetic process (GO:0009890)

External database links

PANDIT:	PF06399
SCOP:	1jg5
SYSTERS:	GFRP

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 (4) Full (25) NCBI (43) Metagenomics
Viewer:

Formatting options

Alignment:	Seed (4) Full (25)
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 (4) Full (25) NCBI (43) Metagenomics
Full length sequences	Full-sequences (25)

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:

Pfam-B_63435 (release 9.0)

Previous IDs:

none

Type:

Domain

Author:

Finn RD

Number in seed:

4

Number in full:

25

Average length of the domain:

81.80 aa

Average identity of full alignment:

66 %

Average coverage of the sequence by the domain:

91.41 %

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	25.0	25.0
Trusted cut-off	35.0	34.8
Noise cut-off	21.1	20.0

Model length:

83

Family (HMM) version:

6

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
save a plain text representation of the tree

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Interactions

There are 2 interactions for this family. More...

GFRP GTP_cyclohydroI

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 GFRP domain has been found.

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Family: GFRP (PF06399)

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