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15  structures 295  species 0  interactions 1253  sequences 10  architectures

Family: PDE4_UCR (PF18100)

Summary: Phosphodiesterase 4 upstream conserved regions (UCR)

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Phosphodiesterase 4 upstream conserved regions (UCR) Provide feedback

This is the upstream conserved region (UCR) found in Phosphodiesterase 4 (PDE4) enzymes. PDE4 is a contributor to intracellular signalling and an important drug target. The four members of this enzyme family (PDE4A to -D) are functional dimers in which each subunit contains two upstream conserved regions (UCR), UCR1 and -2, which precede the C-terminal catalytic domain PF00233 . Due to alternative promoters/start sites and variable mRNA splicing, transcription from the four PDE4 genes results in the expression of more than 25 different isoforms of PDE4. Each isoform has a unique N-terminal region that determines its specific subcellular localization by mediating interactions with scaffolding proteins. The isoforms are further classified into long, short, and supershort forms based on the presence or absence of two upstream conserved regions (UCRs, known as UCR1 and UCR2). Long splice variants contain both UCR1 and UCR2, short variants lack UCR1, and the supershort forms of PDE4 additionally lack part of UCR2. The extent to which UCRs are present determines critical functional differences between the isoforms. Phosphorylation by protein kinase A (PKA) at a conserved site on UCR1 activates all long PDE4 isoforms. Mutation and deletion studies have shown that long forms of PDE4 are dimeric, with key dimerization interactions mediated by UCR1 and UCR2, and that the C-terminal half of UCR2 could play a negative regulatory role [1].

Literature references

  1. Cedervall P, Aulabaugh A, Geoghegan KF, McLellan TJ, Pandit J;, Proc Natl Acad Sci U S A. 2015;112:E1414-E1422.: Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4. PUBMED:25775568 EPMC:25775568


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No InterPro data for this Pfam family.

Domain organisation

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Alignments

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

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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.

  Seed
(33)
Full
(1253)
Representative proteomes UniProt
(2102)
NCBI
(4828)
Meta
(0)
RP15
(169)
RP35
(404)
RP55
(668)
RP75
(823)
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PP/heatmap 1 View               

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

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

Format an alignment

  Seed
(33)
Full
(1253)
Representative proteomes UniProt
(2102)
NCBI
(4828)
Meta
(0)
RP15
(169)
RP35
(404)
RP55
(668)
RP75
(823)
Alignment:
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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.

  Seed
(33)
Full
(1253)
Representative proteomes UniProt
(2102)
NCBI
(4828)
Meta
(0)
RP15
(169)
RP35
(404)
RP55
(668)
RP75
(823)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   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...

Trees

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.

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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.

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This family is new in this Pfam release.

Seed source: ECOD:EUF02958
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: El-Gebali S
Number in seed: 33
Number in full: 1253
Average length of the domain: 94.80 aa
Average identity of full alignment: 59 %
Average coverage of the sequence by the domain: 15.86 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.9 26.9
Trusted cut-off 26.9 26.9
Noise cut-off 26.6 26.6
Model length: 119
Family (HMM) version: 1
Download: download the raw HMM for this family

Species distribution

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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 PDE4_UCR domain has been found. There are 15 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.

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