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1219  structures 2999  species 0  interactions 167674  sequences 2095  architectures

Family: PDZ (PF00595)

Summary: PDZ domain

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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

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] Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to cytoskeletal components. Proteins with these domains help hold together and organize signaling complexes at cellular membranes. These domains play a key role in the formation and function of signal transduction complexes.[3] PDZ domains also play a highly significant role in the anchoring of cell surface receptors (such as Cftr and FZD7) to the actin cytoskeleton via mediators like NHERF and ezrin.[4]

PDZ is an initialism combining the first letters of the first three proteins discovered to share the domain — post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1).[5] PDZ domains have previously been referred to as DHR (Dlg homologous region)[6] or GLGF (glycine-leucine-glycine-phenylalanine) domains.[7]

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.[8] The C-terminal carboxylate group is bound by a nest (protein structural motif) in the PDZ domain.

Origins of discovery

PDZ is an acronym derived from the names of the first proteins in which the domain was observed. Post-synaptic density protein 95 (PSD-95) is a synaptic protein found only in the brain.[7] Drosophila disc large tumor suppressor (Dlg1) and zona occludens 1 (ZO-1) both play an important role at cell junctions and in cell signaling complexes.[9] Since the discovery of PDZ domains more than 20 years ago, hundreds of additional PDZ domains have been identified. The first published use of the phrase “PDZ domain” was not in a paper, but a letter. In September 1995, Dr. Mary B. Kennedy of the California Institute of Technology wrote a letter of correction to Trends in Biomedical Sciences.[10] Earlier that year, another set of scientists had claimed to discover a new protein domain which they called a DHR domain.[6] Dr. Kennedy refuted that her lab had previously described exactly the same domain as a series of “GLGF repeats”.[7] She continued to explain that in order to “better reflect the origin and distribution of the domain,” the new title of the domain would be changed. Thus, the name “PDZ domain” was introduced to the world.


6 β-strands (blue) and two α-helix (red) are the common motif for PDZ domains.

PDZ domain structure is partially conserved across the various proteins that contain them. They usually have 5-6 β-strands and one short and one long α-helix. Apart from this conserved fold, the secondary structure differs across PDZ domains.[3] This domain tends to be globular with a diameter of about 35 Å.[11]

When studied, PDZ domains are usually isolated as monomers, however some PDZ proteins form dimers. The function of PDZ dimers as compared to monomers is not yet known.[3]

A commonly accepted theory for the binding pocket of the PDZ domain is that it is constituted by several hydrophobic amino acids, apart from the GLGF sequence mentioned earlier, the mainchain atoms of which form a nest (protein structural motif) binding the C-terminal carboxylate of the protein or peptide ligand. Most PDZ domains have such a binding site located between one of the β-strands and the long α-helix.[12]


PDZ domains have two main functions: Localizing cellular elements, and regulating cellular pathways.

An example of a protein (GRIP) with seven PDZ domains.

The first discovered function of the PDZ domains was to anchor receptor proteins in the membrane to cytoskeletal components. PDZ domains also have regulatory functions on different signaling pathways.[13] Any protein may have one or several PDZ domains, which can be identical or unique (see figure to right). This variety allows these proteins to be very versatile in their interactions. Different PDZ domains in the same protein can have different roles, each binding a different part of the target protein or a different protein altogether.[14]


PDZ domains play a vital role in organizing and maintaining complex scaffolding formations.

PDZ domains are found in diverse proteins, but all assist in localization of cellular elements. PDZ domains are primarily involved in anchoring receptor proteins to the cytoskeleton. For cells to function properly it is important for components—proteins and other molecules— to be in the right place at the right time. Proteins with PDZ domains bind different components to ensure correct arrangements.[13] In the neuron, making sense of neurotransmitter activity requires specific receptors to be located in the lipid membrane at the synapse. PDZ domains are crucial to this receptor localization process.[15] Proteins with PDZ domains generally associate with both the C-terminus of the receptor and cytoskeletal elements in order to anchor the receptor to the cytoskeleton and keep it in place.[14][16] Without such an interaction, receptors would diffuse out of the synapse due to the fluid nature of the lipid membrane.

PDZ domains are also utilized to localize elements other than receptor proteins. In the human brain, nitric oxide often acts in the synapse to modify cGMP levels in response to NMDA receptor activation.[17] In order to ensure a favorable spatial arrangements, neuronal nitric oxide synthase (nNOS) is brought close to NMDA receptors via interactions with PDZ domains on PSD-95, which concurrently binds nNOS and NMDA receptors.[16] With nNOS located closely to NMDA receptors, it will be activated immediately after calcium ions begin entering the cell.


PDZ domains are directly involved in the regulation of different cellular pathways. This mechanism of this regulation varies as PDZ domains are able to interact with a range of cellular components. This regulation is usually a result of the co-localization of multiple signaling molecules such as in the example with nNos and NMDA receptors.[16] Some examples of signaling pathway regulation executed by the PDZ domain include phosphatase enzyme activity, mechanosensory signaling, and the sorting pathway of endocytosed receptor proteins.

The signaling pathway of the human protein tyrosine phosphatase non-receptor type 4 (PTPN4) is regulated by PDZ domains. This protein is involved in regulating cell death. Normally the PDZ domain of this enzyme is unbound. In this unbound state the enzyme is active and prevents cell signaling for apoptosis. Binding the PDZ domain of this phosphatase results in a loss of enzyme activity, which leads to apoptosis. The normal regulation of this enzyme prevents cells from prematurely going through apoptosis. When the regulation of the PTPN4 enzyme is lost, there is increased oncogenic activity as the cells are able to proliferate.[18]

PDZ domains also have a regulatory role in mechanosensory signaling in proprioceptors and vestibular and auditory hair cells. The protein Whirlin (WHRN) localizes in the post-synaptic neurons of hair cells that transform mechanical movement into action potentials that the body can interpret. WHRN proteins contains three PDZ domains. The domains located near the N-terminus bind to receptor proteins and other signaling components. When the one of these PDZ domains is inhibited, the signaling pathways of the neurons are disrupted, resulting in auditory, visual, and vestibular impairment. This regulation is thought to be based on the physical positioning WHRN and the selectivity of its PDZ domain.[19]

Regulation of receptor proteins occurs when the PDZ domain on the EBP50 protein binds to the C-terminus of the beta-2 adrenergic receptor (ß2-AR). EBP50 also associates with a complex that connects to actin, thus serving as a link between the cytoskeleton and ß2-AR. The ß2-AR receptor is eventually endocytosed, where it will either be consigned to a lysosome for degradation or recycled back to the cell membrane. Scientists have demonstrated that when the Ser-411 residue of the ß2-AR PDZ binding domain, which interacts directly with EBP50, is phosphorylated, the receptor is degraded. If Ser-411 is left unmodified, the receptor is recycled.[20] The role played by PDZ domains and their binding sites indicate a regulative relevance beyond simply receptor protein localization.

PDZ domains are being studied further to better understand the role they play in different signaling pathways. Research has increased as these domains have been linked to different diseases including cancer as discussed above.[21]

Regulation of PDZ domain activity

PDZ domain function can be both inhibited and activated by various mechanisms. Two of the most prevalent include allosteric interactions and posttraslational modifications.[3]

Post-translational modifications

The most common post-traslational modification seen on PDZ domains is phosphorylation.[22] This modification is primarily an inhibitor of PDZ domain and ligand activity. In some examples, phosphorylation of amino acid side chains eliminates the ability of the PDZ domain to form hydrogen bonds, disrupting the normal binding patterns. The end result is a loss of PDZ domain function and further signaling.[23] Another way phosphorylation can disrupt regular PDZ domain function is by altering the charge ratio and further affecting binding and signaling.[24] In rare cases researchers have seen post-translational modifications activate PDZ domain activity[25] but these cases are few.

Disulfide bridges inhibit PDZ domain function

Another post-translational modification that can regulate PDZ domains is the formation of disulfide bridges. Many PDZ domains contain cysteines and are susceptible to disulfide bond formation in oxidizing conditions. This modification acts primarily as an inhibitor of PDZ domain function.[26]

Allosteric Interactions

Protein-protein interactions have been observed to alter the effectiveness of PDZ domains binding to ligands. These studies show that allosteric effects of certain proteins can affect the binding affinity for different substrates. Different PDZ domains can even have this allosteric effect on each other. This PDZ-PDZ interaction only acts as an inhibitor.[27] Other experiments have shown that certain enzymes can enhance the binding of PDZ domains. Researchers found that the protein ezrin enhances the binding of the PDZ protein NHERF1.[4]

PDZ proteins

PDZ proteins are a family of proteins that contain the PDZ domain. This sequence of amino-acids is 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. Three of the most well documented PDZ proteins are PSD-95, GRIP, and HOMER.

Basic functioning of PSD-95 in forming a complex between NMDA Receptor and Actin.

PSD-95 is a brain synaptic protein with three PDZ domains, each with unique properties and structures that allow PSD-95 to function in many ways. In general, the first two PDZ domains interact with receptors and the third interacts with cytoskeleton-related proteins. The main receptors associated with PSD-95 are NMDA receptors. The first two PDZ domains of PSD-95 bind to the C-terminus of NMDA receptors and anchor them in the membrane at the point of neurotransmitter release.[28] The first two PDZ domains can also interact in a similar fashion with Shaker-type K+ channels.[28] A PDZ interaction between PSD-95, nNOS and syntrophin is mediated by the second PDZ domain. The third and final PDZ domain links to cysteine-rich PDZ-binding protein (CRIPT), which allows PSD-95 to associate with the cytoskeleton.[28]

Examples of PDZ domain-containing proteins (Figure from Lee et al. 2010).[3] Proteins are indicated by black lines scaled to the length of the primary sequence of the protein. Different shapes refer to different protein domains.

Glutamate receptor interacting protein (GRIP) is a post-synaptic protein that interacts with AMPA receptors in a fashion analogous to PSD-95 interactions with NMDA receptors. When researchers noticed apparent structural homology between the C-termini of AMPA receptors and NMDA receptors, they attempted to determine if a similar PDZ interaction was occurring.[29] A yeast two-hybrid system helped them discover that out of GRIP's seven PDZ domains, two (domains four and five) were essential for binding of GRIP to the AMPA subunit called GluR2.[14] This interaction is vital for proper localization of AMPA receptors, which play a large part in memory storage. Other researchers discovered that domains six and seven of GRIP are responsible for connecting GRIP to a family of receptor tyrosine kinases called ephrin receptors, which are important signaling proteins.[30] A clinical study concluded that Fraser syndrome, an autosomal recessive syndrome that can cause severe deformations, can be caused by a simple mutation in GRIP.[31]

HOMER differs significantly from many known PDZ proteins, including GRIP and PSD-95. Instead of mediating receptors near ion channels, as is the case with GRIP and PSD-95, HOMER is involved in metabotropic glutamate signaling.[32] Another unique aspect of HOMER is that it only contains a single PDZ domain, which mediates interactions between HOMER and type 5 metabotropic glutamate receptor (mGluR5).[15] The single GLGF repeat on HOMER binds amino acids on the C-terminus of mGluR5. HOMER expression is measured at high levels during embryologic stages in rats, suggesting an important developmental function.[15]

Human PDZ proteins

There are roughly 260 PDZ domains in humans. Several proteins contain multiple PDZ domains, so the number of unique PDZ-containing proteins is closer to 180. In the table below are some of the better studied members of this family:

Studied PDZ Proteins
Erbin GRIP Htra1 Htra2
Htra3 PSD-95 SAP97 CARD10

The table below contains all known PDZ proteins in humans (alphabetical):

PDZ Proteins in Humans

There is currently one known virus containing PDZ domains:



  1. ^ Boxus M, Twizere JC, Legros S, Dewulf JF, Kettmann R, Willems L (August 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 Science. 6 (2): 464–8. doi:10.1002/pro.5560060225. PMC 2143646. PMID 9041651.
  3. ^ a b c d e Lee HJ, Zheng JJ (May 2010). "PDZ domains and their binding partners: structure, specificity, and modification". Cell Communication and Signaling. 8: 8. doi:10.1186/1478-811X-8-8. PMC 2891790. PMID 20509869.
  4. ^ a b Li J, Callaway DJ, Bu Z (September 2009). "Ezrin induces long-range interdomain allostery in the scaffolding protein NHERF1". Journal of Molecular Biology. 392 (1): 166–80. doi:10.1016/j.jmb.2009.07.005. PMC 2756645. PMID 19591839.
  5. ^ Kennedy MB (September 1995). "Origin of PDZ (DHR, GLGF) domains". Trends in Biochemical Sciences. 20 (9): 350. doi:10.1016/S0968-0004(00)89074-X. PMID 7482701.
  6. ^ a b Ponting CP, Phillips C (March 1995). "DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins". Trends in Biochemical Sciences. 20 (3): 102–3. doi:10.1016/S0968-0004(00)88973-2. PMID 7535955.
  7. ^ a b c Cho KO, Hunt CA, Kennedy MB (November 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. S2CID 28528759.
  8. ^ Cowburn D (December 1997). "Peptide recognition by PTB and PDZ domains". Current Opinion in Structural Biology. 7 (6): 835–8. doi:10.1016/S0959-440X(97)80155-8. PMID 9434904.
  9. ^ Liu J, Li J, Ren Y, Liu P (2014-01-01). "DLG5 in cell polarity maintenance and cancer development". International Journal of Biological Sciences. 10 (5): 543–9. doi:10.7150/ijbs.8888. PMC 4046881. PMID 24910533.
  10. ^ Kennedy MB (September 1995). "Origin of PDZ (DHR, GLGF) domains". Trends in Biochemical Sciences. 20 (9): 350. doi:10.1016/s0968-0004(00)89074-x. PMID 7482701.
  11. ^ Erlendsson S, Madsen KL (October 2015). "Membrane Binding and Modulation of the PDZ Domain of PICK1". Membranes. 5 (4): 597–615. doi:10.3390/membranes5040597. PMC 4704001. PMID 26501328.
  12. ^ Morais Cabral JH, Petosa C, Sutcliffe MJ, Raza S, Byron O, Poy F, et al. (August 1996). "Crystal structure of a PDZ domain". Nature. 382 (6592): 649–52. Bibcode:1996Natur.382..649C. doi:10.1038/382649a0. PMID 8757139. S2CID 4344406.
  13. ^ a b Harris BZ, Lim WA (September 2001). "Mechanism and role of PDZ domains in signaling complex assembly". Journal of Cell Science. 114 (Pt 18): 3219–31. PMID 11591811.
  14. ^ a b c Bristol, University of. "Bristol University | Centre for Synaptic Plasticity | AMPAR interactors". Retrieved 2015-12-03.
  15. ^ a b c Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL, Worley PF (March 1997). "Homer: a protein that selectively binds metabotropic glutamate receptors". Nature. 386 (6622): 284–8. Bibcode:1997Natur.386..284B. doi:10.1038/386284a0. PMID 9069287. S2CID 4346579.
  16. ^ a b c 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): 1067–76. doi:10.1016/S0092-8674(00)81307-0. PMID 8674113. S2CID 9739481.
  17. ^ Hopper R, Lancaster B, Garthwaite J (April 2004). "On the regulation of NMDA receptors by nitric oxide". The European Journal of Neuroscience. 19 (7): 1675–82. doi:10.1111/j.1460-9568.2004.03306.x. PMID 15078541.
  18. ^ Maisonneuve P, Caillet-Saguy C, Raynal B, Gilquin B, Chaffotte A, Pérez J, et al. (November 2014). "Regulation of the catalytic activity of the human phosphatase PTPN4 by its PDZ domain". The FEBS Journal. 281 (21): 4852–65. doi:10.1111/febs.13024. PMID 25158884.
  19. ^ de Nooij JC, Simon CM, Simon A, Doobar S, Steel KP, Banks RW, et al. (February 2015). "The PDZ-domain protein Whirlin facilitates mechanosensory signaling in mammalian proprioceptors". The Journal of Neuroscience. 35 (7): 3073–84. doi:10.1523/JNEUROSCI.3699-14.2015. PMC 4331628. PMID 25698744.
  20. ^ Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M (September 1999). "A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor". Nature. 401 (6750): 286–90. Bibcode:1999Natur.401..286C. doi:10.1038/45816. PMID 10499588. S2CID 4386883.
  21. ^ Wang NX, Lee HJ, Zheng JJ (April 2008). "Therapeutic use of PDZ protein-protein interaction antagonism". Drug News & Perspectives. 21 (3): 137–41. PMC 4055467. PMID 18560611.
  22. ^ Chung HJ, Huang YH, Lau LF, Huganir RL (November 2004). "Regulation of the NMDA receptor complex and trafficking by activity-dependent phosphorylation of the NR2B subunit PDZ ligand". The Journal of Neuroscience. 24 (45): 10248–59. doi:10.1523/JNEUROSCI.0546-04.2004. PMC 6730169. PMID 15537897.
  23. ^ Jeleń F, Oleksy A, Smietana K, Otlewski J (2003-01-01). "PDZ domains - common players in the cell signaling". Acta Biochimica Polonica. 50 (4): 985–1017. doi:10.18388/abp.2003_3628. PMID 14739991.
  24. ^ Chen J, Pan L, Wei Z, Zhao Y, Zhang M (August 2008). "Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory connexin43-binding sites". The EMBO Journal. 27 (15): 2113–23. doi:10.1038/emboj.2008.138. PMC 2516886. PMID 18636092.
  25. ^ Chen BS, Braud S, Badger JD, Isaac JT, Roche KW (June 2006). "Regulation of NR1/NR2C N-methyl-D-aspartate (NMDA) receptors by phosphorylation". The Journal of Biological Chemistry. 281 (24): 16583–90. doi:10.1074/jbc.M513029200. PMID 16606616.
  26. ^ Mishra P, Socolich M, Wall MA, Graves J, Wang Z, Ranganathan R (October 2007). "Dynamic scaffolding in a G protein-coupled signaling system". Cell. 131 (1): 80–92. doi:10.1016/j.cell.2007.07.037. PMID 17923089. S2CID 14008319.
  27. ^ van den Berk LC, Landi E, Walma T, Vuister GW, Dente L, Hendriks WJ (November 2007). "An allosteric intramolecular PDZ-PDZ interaction modulates PTP-BL PDZ2 binding specificity". Biochemistry. 46 (47): 13629–37. doi:10.1021/bi700954e. PMID 17979300.
  28. ^ a b c Niethammer M, Valtschanoff JG, Kapoor TM, Allison DW, Weinberg RJ, Craig AM, Sheng M (April 1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90". Neuron. 20 (4): 693–707. doi:10.1016/s0896-6273(00)81009-0. PMID 9581762. S2CID 16068361.
  29. ^ Dong H, O'Brien RJ, Fung ET, Lanahan AA, Worley PF, Huganir RL (March 1997). "GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors". Nature. 386 (6622): 279–84. Bibcode:1997Natur.386..279D. doi:10.1038/386279a0. PMID 9069286. S2CID 4361791.
  30. ^ Torres R, Firestein BL, Dong H, Staudinger J, Olson EN, Huganir RL, et al. (December 1998). "PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands". Neuron. 21 (6): 1453–63. doi:10.1016/S0896-6273(00)80663-7. PMID 9883737. S2CID 15441813.
  31. ^ Vogel MJ, van Zon P, Brueton L, Gijzen M, van Tuil MC, Cox P, et al. (May 2012). "Mutations in GRIP1 cause Fraser syndrome". Journal of Medical Genetics. 49 (5): 303–6. doi:10.1136/jmedgenet-2011-100590. PMID 22510445. S2CID 7211700.
  32. ^ Ranganathan R, Ross EM (December 1997). "PDZ domain proteins: scaffolds for signaling complexes". Current Biology. 7 (12): R770-3. doi:10.1016/S0960-9822(06)00401-5. PMID 9382826. S2CID 13636955.
  33. ^ Jemth P, Gianni S (July 2007). "PDZ domains: folding and binding". Biochemistry. 46 (30): 8701–8. doi:10.1021/bi7008618. PMID 17620015.

Further reading

External links

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PDZ domain 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 [ PUBMED:20509869 ].

Gene Ontology

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Domain organisation

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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 11 members:

DUF6288 EBP50_C GRASP55_65 PDZ PDZ_1 PDZ_2 PDZ_3 PDZ_4 PDZ_5 PDZ_6 Tricorn_PDZ


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Curation and family details

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Seed source: [1]
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 44
Number in full: 167674
Average length of the domain: 81.10 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 15.82 %

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 23.2 23.2
Trusted cut-off 23.2 23.2
Noise cut-off 23.1 23.1
Model length: 82
Family (HMM) version: 27
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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 1219 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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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
A0A087WP46 View 3D Structure Click here
A0A0B4K6Y7 View 3D Structure Click here
A0A0B4LIC4 View 3D Structure Click here
A0A0G2JXI5 View 3D Structure Click here
A0A0G2JYM0 View 3D Structure Click here
A0A0G2K2P5 View 3D Structure Click here
A0A0G2K4N7 View 3D Structure Click here
A0A0G2K8R3 View 3D Structure Click here
A0A0G2KD61 View 3D Structure Click here
A0A0G2KJA6 View 3D Structure Click here
A0A0G2KQM9 View 3D Structure Click here
A0A0G2KQU1 View 3D Structure Click here
A0A0G2KY42 View 3D Structure Click here
A0A0H2UKQ5 View 3D Structure Click here
A0A0H2UKX0 View 3D Structure Click here
A0A0K3AUI8 View 3D Structure Click here
A0A0R0HVP0 View 3D Structure Click here
A0A0R4IDU6 View 3D Structure Click here
A0A0R4IEP0 View 3D Structure Click here
A0A0R4IFC6 View 3D Structure Click here
A0A0R4IFD5 View 3D Structure Click here
A0A0R4IGJ6 View 3D Structure Click here
A0A0R4IGT8 View 3D Structure Click here
A0A0R4IN44 View 3D Structure Click here
A0A0R4IPR0 View 3D Structure Click here
A0A0R4IQG7 View 3D Structure Click here
A0A0R4IRY4 View 3D Structure Click here
A0A0R4IS11 View 3D Structure Click here
A0A0R4IVS6 View 3D Structure Click here
A0A0R4IZD4 View 3D Structure Click here
A0A0R4IZU1 View 3D Structure Click here
A0A0R4J7R2 View 3D Structure Click here
A0A140LI67 View 3D Structure Click here
A0A140LIW3 View 3D Structure Click here
A0A1D5NS70 View 3D Structure Click here
A0A1D5NS76 View 3D Structure Click here
A0A286Y8D1 View 3D Structure Click here
A0A286Y9N6 View 3D Structure Click here
A0A286Y9S9 View 3D Structure Click here
A0A286YAT1 View 3D Structure Click here