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546  structures 1462  species 0  interactions 7814  sequences 113  architectures

Family: 14-3-3 (PF00244)

Summary: 14-3-3 protein

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This is the Wikipedia entry entitled "14-3-3 protein". More...

14-3-3 protein Edit Wikipedia article

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Literature references

  1. Xiao B, Smerdon SJ, Jones DH, Dodson GG, Soneji Y, Aitken A, Gamblin SJ; , Nature 1995;376:188-191.: Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways. PUBMED:7603573 EPMC:7603573

  2. Liu D, Bienkowska J, Petosa C, Collier RJ, Fu H, Liddington R; , Nature 1995;376:191-194.: Crystal structure of the zeta isoform of the 14-3-3 protein. PUBMED:7603574 EPMC:7603574

  3. Muslin AJ, Tanner JW, Allen PM, Shaw AS; , Cell 1996;84:889-897.: Interaction of 14-3-3 with signaling proteins is mediated by the recognition of phosphoserine. PUBMED:8601312 EPMC:8601312

  4. Ichimura T, Ito M, Itagaki C, Takahashi M, Horigome T, Omata S, Ohno S, Isobe T , FEBS Lett 1997;413:273-276.: The 14-3-3 protein binds its target proteins with a common site located towards the C-terminus. PUBMED:9280296 EPMC:9280296

  5. Wang W, Shakes DC , J Mol Evol 1996;43:384-398.: Molecular evolution of the 14-3-3 protein family. PUBMED:8798343 EPMC:8798343

  6. Jin DY, Lyu MS, Kozak CA, Jeang KT , Nature 1996;382:308-308.: Function of 14-3-3 proteins. PUBMED:8684458 EPMC:8684458

  7. Ferl RJ, Manak MS, Reyes MF; , Genome Biol 2002;3:REVIEWS3010.: The 14-3-3s. PUBMED:12184815 EPMC:12184815

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR023410

The 14-3-3 proteins are a large family of approximately 30kDa acidic proteins which exist primarily as homo- and heterodimers within all eukaryotic cells [ PUBMED:1671102 , PUBMED:11911880 ]. There is a high degree of sequence identity and conservation between all the 14-3-3 isotypes, particularly in the regions which form the dimer interface or line the central ligand binding channel of the dimeric molecule. Each 14-3-3 protein sequence can be roughly divided into three sections: a divergent amino terminus, the conserved core region and a divergent carboxyl terminus. The conserved middle core region of the 14-3-3s encodes an amphipathic groove that forms the main functional domain, a cradle for interacting with client proteins. The monomer consists of nine helices organised in an antiparallel manner, forming an L-shaped structure. The interior of the L-structure is composed of four helices: H3 and H5, which contain many charged and polar amino acids, and H7 and H9, which contain hydrophobic amino acids. These four helices form the concave amphipathic groove that interacts with target peptides.

The 14-3-3 proteins mainly bind proteins containing phosphothreonine or phosphoserine motifs, however exceptions to this rule do exist. Extensive investigation of the 14-3-3 binding site of the mammalian serine/threonine kinase Raf-1 has produced a consensus sequence for 14-3-3-binding, RSxpSxP (in the single-letter amino-acid code, where x denotes any amino acid and p indicates that the next residue is phosphorylated). The 14-3-3 proteins appear to effect intracellular signalling in one of three ways - by direct regulation of the catalytic activity of the bound protein, by regulating interactions between the bound protein and other molecules in the cell by sequestration or modification or by controlling the subcellular localisation of the bound ligand. Proteins appear to initially bind to a single dominant site and then subsequently to many, much weaker secondary interaction sites. The 14-3-3 dimer is capable of changing the conformation of its bound ligand whilst itself undergoing minimal structural alteration.

This entry represents the structural domain found in 14-3-3 proteins.

Domain organisation

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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 149
Number in full: 7814
Average length of the domain: 196.40 aa
Average identity of full alignment: 59 %
Average coverage of the sequence by the domain: 79.02 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 33.2 33.2
Trusted cut-off 33.2 33.2
Noise cut-off 33.1 33.1
Model length: 222
Family (HMM) version: 22
Download: download the raw HMM for this family

Species distribution

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Colour assignments

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 14-3-3 domain has been found. There are 546 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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