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601  structures 2536  species 4  interactions 26099  sequences 730  architectures

Family: PDZ (PF00595)

Summary: PDZ domain (Also known as DHR or GLGF)

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This is the Wikipedia entry entitled "PDZ domain". More...

PDZ domain Edit Wikipedia article

PDZ domain 2DC2.png
Molecular structure of the PDZ domain included in the human GOPC (Golgi-associated PDZ and coiled-coil motif-containing protein) protein
Identifiers
Symbol PDZ
Pfam PF00595
InterPro IPR001478
SMART PDZ
PROSITE PDOC50106
SCOP 1lcy
SUPERFAMILY 1lcy
CDD cd00136

The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses[1] and animals.[2] PDZ is an acronym combining the first letters of three proteins — post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) — which were first discovered to share the domain.[3] PDZ domains have previously been referred to as DHR (Dlg homologous region)[4] or GLGF (glycine-leucine-glycine-phenylalanine) domains.[5] Proteins with these domains help hold together and organize signaling complexes at cellular membranes.[6]

In general PDZ domains bind to a short region of the C-terminus of other specific proteins. These short regions bind to the PDZ domain by beta sheet augmentation. This means that the beta sheet in the PDZ domain is extended by the addition of a further beta strand from the tail of the binding partner protein.[7]

Proteins containing this domain

Examples of PDZ domain-containing proteins (Figure from Lee et al. 2010).[8] Proteins are indicated by black lines scaled to the length of the primary sequence of the protein.

PDZ domains are found in many thousands of known proteins. PDZ domain proteins are widespread in eukaryotes and eubacteria,[2] whereas there are very few examples of the protein in archaea. PDZ domains are often associated with other protein domains and these combinations allow them to carry out their specific functions. For example the PDZ domains in the PSD-95 protein are found associated with an SH3 domain and a guanylate kinase domain.

Human

There are roughly 260 human PDZ domains. However, several proteins contain multiple PDZ domains, so the number of unique PDZ-containing proteins is closer to 180. Listed below are some of the better studied members of this family:

Below is a complete list:

AAG12; AHNAK; AHNAK2; AIP1; ALP; APBA1; APBA2; APBA3; ARHGAP21; ARHGAP23; ARHGEF11; ARHGEF12; CASK; CLP-36; CNKSR2; CNKSR3; DFNB31; DLG1; DLG2; DLG3; DLG4; DLG5; DVL1; DVL1L1; DVL2; DVL3; ERBB2IP; FRMPD1; FRMPD2; FRMPD2L1; FRMPD3; FRMPD4; GIPC1; GIPC2; GIPC3; GOPC; GRASP; GRIP1; GRIP2; HTRA1; HTRA2; HTRA3; HTRA4; IL16; INADL; KIAA1849; LDB3; LIMK1; LIMK2; LIN7A; LIN7B; LIN7C; LMO7; LNX1; LNX2; LRRC7; MAGI1; MAGI2; MAGI3; MAGIX; MAST1; MAST2; MAST3; MAST4; MCSP; MLLT4; MPDZ; MPP1; MPP2; MPP3; MPP4; MPP5; MPP6; MPP7; MYO18A;  ;NOS1; PARD3; PARD3B; PARD6A; PARD6B; PARD6G; PDLIM1; PDLIM2; PDLIM3; PDLIM4; PDLIM5; PDLIM7; PDZD11; PDZD2; PDZD3; PDZD4; PDZD5A; PDZD7; PDZD8; PDZK1; PDZRN3; PDZRN4; PICK1; PPP1R9A; PPP1R9B; PREX1; PRX; PSCDBP; PTPN13; PTPN3; PTPN4; RAPGEF2; RAPGEF6; RGS12; RGS3; RHPN1; RIL; RIMS1; RIMS2; SCN5A; SCRIB; SDCBP; SDCBP2; SHANK1; SHANK2; SHANK3; SHROOM2; SHROOM3; SHROOM4; SIPA1; SIPA1L1; SIPA1L2; SIPA1L3; SLC9A3R1; SLC9A3R2; SNTA1; SNTB1; SNTB2; SNTG1; SNTG2; SNX27; SPAL2; STXBP4; SYNJ2BP; SYNPO2; SYNPO2L; TAX1BP3; TIAM1; TIAM2; TJP1; TJP2; TJP3; TRPC4; TRPC5; USH1C; WHRN;

Virus

Tax1

References

  1. ^ Boxus M, Twizere JC, Legros S, Dewulf JF, Kettmann R, Willems L (2008). "The HTLV-1 Tax interactome". Retrovirology 5: 76. doi:10.1186/1742-4690-5-76. PMC 2533353. PMID 18702816. 
  2. ^ a b Ponting CP (February 1997). "Evidence for PDZ domains in bacteria, yeast, and plants". Protein Sci. 6 (2): 464–468. doi:10.1002/pro.5560060225. PMC 2143646. PMID 9041651. 
  3. ^ Kennedy MB (September 1995). "Origin of PDZ(DHR,GLGF) domains". Trends Biochem. Sci. 20 (9): 350. doi:10.1016/S0968-0004(00)89074-X. PMID 7482701. 
  4. ^ Ponting CP, Phillips C (March 1995). "DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins". Trends Biochem. Sci. 20 (3): 102–103. doi:10.1016/S0968-0004(00)88973-2. PMID 7535955. 
  5. ^ Cho KO, Hunt CA, Kennedy MB (Nov 1992). "The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein". Neuron 9 (5): 929–42. doi:10.1016/0896-6273(92)90245-9. PMID 1419001. 
  6. ^ Ranganathan R, Ross E (1997). "PDZ domain proteins: scaffolds for signaling complexes". Curr Biol 7 (12): R770–R773. doi:10.1016/S0960-9822(06)00401-5. PMID 9382826. 
  7. ^ Cowburn D (December 1997). "Peptide recognition by PTB and PDZ domains". Curr. Opin. Struct. Biol. 7 (6): 835–838. doi:10.1016/S0959-440X(97)80155-8. PMID 9434904. 
  8. ^ Lee HJ, Zheng JJ (2010). "PDZ domains and their binding partners: structure, specificity, and modification". Cell Commun. Signal 8: 8. doi:10.1186/1478-811X-8-8. PMC 2891790. PMID 20509869. 
  9. ^ Jemth P, Gianni S (July 2007). "PDZ domains: folding and binding". Biochemistry 46 (30): 8701–8708. doi:10.1021/bi7008618. PMID 17620015. 

Further reading

  • Ponting CP, Phillips C, Davies KE, Blake DJ (June 1997). "PDZ domains: targeting signalling molecules to sub-membranous sites". BioEssays 19 (6): 469–479. doi:10.1002/bies.950190606. PMID 9204764. 
  • Doyle DA, Lee A, Lewis J, Kim E, Sheng M, MacKinnon R (June 1996). "Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ". Cell 85 (7): 1067–1076. doi:10.1016/S0092-8674(00)81307-0. PMID 8674113. 

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

PDZ domain (Also known as DHR or GLGF) Provide feedback

PDZ domains are found in diverse signaling proteins.

Literature references

  1. Ponting CP, Phillips C, Davies KE, Blake DJ , Bioessays 1997;19:469-479.: PDZ domains: targeting signalling molecules to sub-membranous sites. PUBMED:9204764 EPMC:9204764

  2. Doyle DA, Lee A, Lewis J, Kim E, Sheng M, MacKinnon R; , Cell. 1996;85:1067-1076.: Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. PUBMED:8674113 EPMC:8674113

  3. Ponting CP; , Protein Sci 1997;6:464-468.: Evidence for PDZ domains in bacteria, yeast, and plants. PUBMED:9041651 EPMC:9041651

  4. Ernst A, Sazinsky SL, Hui S, Currell B, Dharsee M, Seshagiri S, Bader GD, Sidhu SS;, Sci Signal. 2009;2:ra50.: Rapid evolution of functional complexity in a domain family. PUBMED:19738200 EPMC:19738200


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001478

PDZ domains (also known as Discs-large homologous regions (DHR) or GLGF)) are found in diverse signalling proteins in bacteria, yeasts, plants, insects and vertebrates [PUBMED:9041651, PUBMED:9204764]. PDZ domains can occur in one or multiple copies and are nearly always found in cytoplasmic proteins. They bind either the carboxyl-terminal sequences of proteins or internal peptide sequences [PUBMED:9204764]. In most cases, interaction between a PDZ domain and its target is constitutive, with a binding affinity of 1 to 10 microns. However, agonist-dependent activation of cell surface receptors is sometimes required to promote interaction with a PDZ protein. PDZ domain proteins are frequently associated with the plasma membrane, a compartment where high concentrations of phosphatidylinositol 4,5-bisphosphate (PIP2) are found. Direct interaction between PIP2 and a subset of class II PDZ domains (syntenin, CASK, Tiam-1) has been demonstrated.

PDZ domains consist of 80 to 90 amino acids comprising six beta-strands (beta-A to beta-F) and two alpha-helices, A and B, compactly arranged in a globular structure. Peptide binding of the ligand takes place in an elongated surface groove as an anti-parallel beta-strand interacts with the beta-B strand and the B helix. The structure of PDZ domains allows binding to a free carboxylate group at the end of a peptide through a carboxylate-binding loop between the beta-A and beta-B strands.

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...

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Pfam Clan

This family is a member of clan PDZ-like (CL0466), which has the following description:

This superfamily comprises families of PDZ domains, which are peptide binding sites.

The clan contains the following 5 members:

GRASP55_65 PDZ PDZ_1 PDZ_2 Tricorn_PDZ

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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.

  Seed
(58)
Full
(26099)
Representative proteomes NCBI
(33290)
Meta
(6344)
RP15
(2855)
RP35
(4028)
RP55
(7376)
RP75
(11639)
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Format an alignment

  Seed
(58)
Full
(26099)
Representative proteomes NCBI
(33290)
Meta
(6344)
RP15
(2855)
RP35
(4028)
RP55
(7376)
RP75
(11639)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

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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
(58)
Full
(26099)
Representative proteomes NCBI
(33290)
Meta
(6344)
RP15
(2855)
RP35
(4028)
RP55
(7376)
RP75
(11639)
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.

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 HMMER3.

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.

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: [1]
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 58
Number in full: 26099
Average length of the domain: 80.30 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 16.19 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.7 22.7
Trusted cut-off 22.7 22.7
Noise cut-off 22.6 22.6
Model length: 81
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 4 interactions for this family. More...

Trypsin Ras Peptidase_S41 PDZ

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 PDZ domain has been found. There are 601 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 seqence.

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