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4  structures 324  species 0  interactions 2746  sequences 308  architectures

Family: ZZ (PF00569)

Summary: Zinc finger, ZZ type

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This is the Wikipedia entry entitled "ZZ zinc finger". More...

ZZ zinc finger Edit Wikipedia article

ZZ
Identifiers
Symbol ZZ
Pfam PF00569
Pfam clan CL0006
InterPro IPR000433
CDD cd02249

In molecular biology the ZZ-type zinc finger domain is a type of protein domain that was named because of its ability to bind two zinc ions.[1] These domains contain 4-6 Cys residues that participate in zinc binding (plus additional Ser/His residues), including a Cys-X2-Cys motif found in other zinc finger domains. These zinc fingers are thought to be involved in protein-protein interactions. The structure of the ZZ domain shows that it belongs to the family of cross-brace zinc finger motifs that include the PHD, RING, and FYVE domains.[2] ZZ-type zinc finger domains are found in:

Single copies of the ZZ zinc finger occur in the transcriptional adaptor/coactivator proteins P300, in cAMP response element-binding protein (CREB)-binding protein (CBP) and ADA2. CBP provides several binding sites for transcriptional coactivators. The site of interaction with the tumour suppressor protein p53 and the oncoprotein E1A with CBP/P300 is a Cys-rich region that incorporates two zinc-binding motifs: ZZ-type and TAZ2-type. The ZZ-type zinc finger of CBP contains two twisted anti-parallel beta-sheets and a short alpha-helix, and binds two zinc ions.[2] One zinc ion is coordinated by four cysteine residues via 2 Cys-X2-Cys motifs, and the third zinc ion via a third Cys-X-Cys motif and a His-X-His motif. The first zinc cluster is strictly conserved, whereas the second zinc cluster displays variability in the position of the two His residues.

In Arabidopsis thaliana (Mouse-ear cress), the hypersensitive to red and blue 1 (Hrb1) protein, which regulating both red and blue light responses, contains a ZZ-type zinc finger domain.[3]

ZZ-type zinc finger domains have also been identified in the testis-specific E3 ubiquitin ligase MEX that promotes death receptor-induced apoptosis.[4] MEX has four putative zinc finger domains: one ZZ-type, one SWIM-type and two RING-type. The region containing the ZZ-type and RING-type zinc fingers is required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination.

In addition, the Cys-rich domains of dystrophin, utrophin and an 87kDa post-synaptic protein contain a ZZ-type zinc finger with high sequence identity to P300/CBP ZZ-type zinc fingers. In dystrophin and utrophin, the ZZ-type zinc finger lies between a WW domain (flanked by and EF hand) and the C-terminal coiled-coil domain. Dystrophin is thought to act as a link between the actin cytoskeleton and the extracellular matrix, and perturbations of the dystrophin-associated complex, for example, between dystrophin and the transmembrane glycoprotein beta-dystroglycan, may lead to muscular dystrophy. Dystrophin and its autosomal homologue utrophin interact with beta-dystroglycan via their C-terminal regions, which are composed of a WW domain, an EF hand domain, and a ZZ-type zinc finger domain.[5] The WW domain is the primary site of interaction between dystrophin or utrophin and dystroglycan, while the EF hand and ZZ-type zinc finger domains stabilise and strengthen this interaction.

References[edit]

  1. ^ Ponting CP, Blake DJ, Davies KE, Kendrick-Jones J, Winder SJ (January 1996). "ZZ and TAZ: new putative zinc fingers in dystrophin and other proteins". Trends Biochem. Sci. 21 (1): 11–13. PMID 8848831. 
  2. ^ a b Legge GB, Martinez-Yamout MA, Hambly DM, Trinh T, Lee BM, Dyson HJ, Wright PE (October 2004). "ZZ domain of CBP: an unusual zinc finger fold in a protein interaction module". J. Mol. Biol. 343 (4): 1081–93. doi:10.1016/j.jmb.2004.08.087. PMID 15476823. 
  3. ^ Kang X, Chong J, Ni M (March 2005). "HYPERSENSITIVE TO RED AND BLUE 1, a ZZ-type zinc finger protein, regulates phytochrome B-mediated red and cryptochrome-mediated blue light responses". Plant Cell 17 (3): 822–35. doi:10.1105/tpc.104.029165. PMC 1069701. PMID 15705950. 
  4. ^ Nishito Y, Hasegawa M, Inohara N, Núñez G (June 2006). "MEX is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis". Biochem. J. 396 (3): 411–7. doi:10.1042/BJ20051814. PMC 1482824. PMID 16522193. 
  5. ^ Hnia K, Zouiten D, Cantel S, Chazalette D, Hugon G, Fehrentz JA, Masmoudi A, Diment A, Bramham J, Mornet D, Winder SJ (February 2007). "ZZ domain of dystrophin and utrophin: topology and mapping of a beta-dystroglycan interaction site". Biochem. J. 401 (3): 667–77. doi:10.1042/BJ20061051. PMC 1770854. PMID 17009962. 

This article incorporates text from the public domain Pfam and InterPro IPR000433

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.

Zinc finger, ZZ type Provide feedback

Zinc finger present in dystrophin, CBP/p300. ZZ in dystrophin binds calmodulin. Putative zinc finger; binding not yet shown. Four to six cysteine residues in its sequence are responsible for coordinating zinc ions, to reinforce the structure [2].

Literature references

  1. Ponting CP, Blake DJ, Davies KE, Kendrick-Jones J, Winder SJ; , Trends Biochem Sci 1996;21:11-13.: ZZ and TAZ: new putative zinc fingers in dystrophin and other proteins. PUBMED:8848831 EPMC:8848831

  2. Roberts RG; , Genome Biol 2001;2:REVIEWS3006.: Dystrophins and dystrobrevins. PUBMED:11305946 EPMC:11305946


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000433

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [PUBMED:10529348, PUBMED:15963892, PUBMED:15718139, PUBMED:17210253, PUBMED:12665246]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [PUBMED:11179890]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

This entry represents ZZ-type zinc finger domains, named because of their ability to bind two zinc ions [PUBMED:8848831]. These domains contain 4-6 Cys residues that participate in zinc binding (plus additional Ser/His residues), including a Cys-X2-Cys motif found in other zinc finger domains. These zinc fingers are thought to be involved in protein-protein interactions. The structure of the ZZ domain shows that it belongs to the family of cross-brace zinc finger motifs that include the PHD, RING, and FYVE domains [PUBMED:15476823]. ZZ-type zinc finger domains are found in:

  • Transcription factors P300 and CBP.
  • Plant proteins involved in light responses, such as Hrb1.
  • E3 ubiquitin ligases MEX and MIB2 (EC).
  • Dystrophin and its homologues.

Single copies of the ZZ zinc finger occur in the transcriptional adaptor/coactivator proteins P300, in cAMP response element-binding protein (CREB)-binding protein (CBP) and ADA2. CBP provides several binding sites for transcriptional coactivators. The site of interaction with the tumour suppressor protein p53 and the oncoprotein E1A with CBP/P300 is a Cys-rich region that incorporates two zinc-binding motifs: ZZ-type and TAZ2-type. The ZZ-type zinc finger of CBP contains two twisted anti-parallel beta-sheets and a short alpha-helix, and binds two zinc ions [PUBMED:15476823]. One zinc ion is coordinated by four cysteine residues via 2 Cys-X2-Cys motifs, and the third zinc ion via a third Cys-X-Cys motif and a His-X-His motif. The first zinc cluster is strictly conserved, whereas the second zinc cluster displays variability in the position of the two His residues.

In Arabidopsis thaliana (Mouse-ear cress), the hypersensitive to red and blue 1 (Hrb1) protein, which regulating both red and blue light responses, contains a ZZ-type zinc finger domain [PUBMED:15705950].

ZZ-type zinc finger domains have also been identified in the testis-specific E3 ubiquitin ligase MEX that promotes death receptor-induced apoptosis [PUBMED:16522193]. MEX has four putative zinc finger domains: one ZZ-type, one SWIM-type and two RING-type. The region containing the ZZ-type and RING-type zinc fingers is required for interaction with UbcH5a and MEX self-association, whereas the SWIM domain was critical for MEX ubiquitination.

In addition, the Cys-rich domains of dystrophin, utrophin and an 87kDa post-synaptic protein contain a ZZ-type zinc finger with high sequence identity to P300/CBP ZZ-type zinc fingers. In dystrophin and utrophin, the ZZ-type zinc finger lies between a WW domain (flanked by and EF hand) and the C-terminal coiled-coil domain. Dystrophin is thought to act as a link between the actin cytoskeleton and the extracellular matrix, and perturbations of the dystrophin-associated complex, for example, between dystrophin and the transmembrane glycoprotein beta-dystroglycan, may lead to muscular dystrophy. Dystrophin and its autosomal homologue utrophin interact with beta-dystroglycan via their C-terminal regions, which are comprised of a WW domain, an EF hand domain and a ZZ-type zinc finger domain [PUBMED:17009962]. The WW domain is the primary site of interaction between dystrophin or utrophin and dystroglycan, while the EF hand and ZZ-type zinc finger domains stabilise and strengthen this interaction.

More information about these proteins can be found at Protein of the Month: Zinc Fingers [PUBMED:].

Gene Ontology

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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 C1 (CL0006), which contains the following 5 members:

C1_1 C1_2 C1_3 C1_4 ZZ

Alignments

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(10)
Full
(2746)
Representative proteomes NCBI
(2687)
Meta
(25)
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(562)
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(809)
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(1281)
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(1705)
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  Seed
(10)
Full
(2746)
Representative proteomes NCBI
(2687)
Meta
(25)
RP15
(562)
RP35
(809)
RP55
(1281)
RP75
(1705)
Alignment:
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  Seed
(10)
Full
(2746)
Representative proteomes NCBI
(2687)
Meta
(25)
RP15
(562)
RP35
(809)
RP55
(1281)
RP75
(1705)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Pfam alignments:

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Trees

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Curation and family details

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Curation View help on the curation process

Seed source: Alignment kindly provided by SMART
Previous IDs: none
Type: Domain
Author: SMART
Number in seed: 10
Number in full: 2746
Average length of the domain: 44.50 aa
Average identity of full alignment: 31 %
Average coverage of the sequence by the domain: 4.44 %

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 21.2 21.2
Trusted cut-off 21.2 21.2
Noise cut-off 21.1 21.1
Model length: 46
Family (HMM) version: 12
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 ZZ domain has been found. There are 4 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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