14-3-3 proteins constitute a highly conserved family of homo- and heterodimeric molecules present in high abundance in eukaryotic cells. The proteins of 14-3-3 family mediate signal transduction by binding to phosphoserine-containing proteins. Through interacting with Cdc25C, 14-3-3 regulates entry into the cell cycle . 14-3-3 interacts with BAD preventing apoptosis by releasing Bcl-XL . In addition, 14-3-3 proteins interact with other signaling molecules including members of the protein kinase C family , Cbl , IRS1 , and polyoma middle-T antigen (1).

Reference
1. Yaffe, M.B., Rittinger, K. (1997) The structural basis for 14-3-3:phosphopeptide binding specificity. Cell, 91, 961-71. PMID: 9428519

    Arrestins comprise a family of four known members in mammals: two visual arrestins, 1 and 4, found in the rod and cone cells of the retina, and two nonvisual arrestins, 2 and 3, which are found in most other tissues of the body. The current model of arrestin-mediated interactions with ligand-occupied GPCRs holds that, after ligand occupancy, cytoplasmic regions of the receptor are phosphorylated at serine and threonine residues by a member of the family of G protein-coupled receptor kinases. Upon arrestin binding, these phosphorylated residues disrupt arrestin's polar core, inducing a conformational change within the molecule that allows it to interact further with the receptor. Recent study examined the interactions between members of the arrestin family with the phosphorylated carboxyl-terminal domain of the FPR using a bead-based, cell-free assay (1).

Reference
1. Potter, R.M. (2002) Arrestin variants display differential binding characteristics for the phosphorylated N-formyl peptide receptor carboxyl terminus . Curr Protein Pept Sci, 12, 3-11. PMID: 11777932

    BRCA1 C-terminal (BRCT) domain was originally discovered as a domain conserved in multiple DNA damage-response proteins. Named after one of the founding members, BRCA1, BRCT domains are often found as tandem repeats within a single protein. BRCA1, 53BP1, DNA LIgase IV, and MDC1, for example, contain 2 BRCT domains, while MCPH1 contains 3, Pax-2 interacting protein (PTIP) contains 6, and TopBP1 contains 8. There are approximately thirty BRCT domain-containing proteins in mammalian cells, and essentially all of these appear to have roles in DNA damage signaling and DNA repair. It must be noted, however, that not all BRCT domains function as phosphopeptide binding modules (1).

Reference
1. Mohammad, D.H. (2009) 14-3-3 proteins, FHA domains and BRCT domains in the DNA damage response . DNA Repair, 8, 1009-17. PMID: 19481982

    FF domains were first identified in the murine splicing factor FBP11 (formin-binding protein 11) as a repeated sequence of about 60 amino acids containing two conserved phenylalanine (F) residues that give name to the domain. FF domains are primarily present in only the following three proteins: Prp40, FBP11, and CA150. Most interestingly, Prp40, FBP11, and CA150 have all been shown to recognize phospho-CTD-RNAPII repeats through their FF domains (1).

Reference
1. Gasch, A. (2006) The structure of Prp40 FF1 domain and its interaction with the crn-TPR1 motif of Clf1 gives a new insight into the binding mode of FF domains . J Biol Chem, 281, 356-64. PMID: 16253993

    FHA domains are conserved sequences of 65-100 amino acid residues found principally within eukaryotic nuclear proteins and also exist in certain prokaryotes. Forkhead-associated (FHA) domains were first identified within a subset of forkhead transcriptional factors, located outside of the conserved DNA-binding forkhead domain.They were subsequently found in a number of other proteins by sequence homology analyses. The FHA domain is thought to possess phosphopeptide-binding specificity. The vast majority of FHA-containing proteins in eukaryotes reside within the nucleus, and many of these have been linked to the control of transcription, DNA repair, and/or cell cycle progression (1).

Reference
1. Durocher, D. (1999) The FHA domain is a modular phosphopeptide recognition motif. Mol Cell, 4, 387-94. PMID: 10518219

    Membrane-associated guanylate kinases (MAGUKs) are a kind of scaffold proteins that play essential roles in tissue developments, cell–cell communications, cell polarity control, and cellular signal transductions. Despite extensive studies over the past two decades, the functions of the signature guanylate kinase domain (GK) of MAGUKs are poorly understood. However, recent study shows that the GK domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein LGN in a phosphorylation-dependent manner (1).

Reference
1. Zhu, J. (2011) Guanylate kinase domains of the MAGUK family scaffold proteins as specific phospho-protein-bindingmodules. EMBO J, 30, 4986-97. PMID: 22117215

    CREB Ser133 phosphorylation promotes binding with the KIX domain of CBP. The KIX domain of CBP also binds to transactivation domains of other nuclear factors including Myb and Jun (1).

Reference
1. http://pfam.xfam.org/family/PF02172/

    LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions. Grr1 LRR is critical for the recognition of phosphorylated targets of SCF (1).

Reference
1. Hsiung YG, Chang HC, Pellequer JL, La Valle R, Lanker S, Wittenberg C. (2001) F-box protein Grr1 interacts with phosphorylated targets via the cationic surface of its leucine-rich repeat. Mol Cell Biol, 21(7), 2506-20. PMID: 11259599

    The MAD Homology 2 domain found in SMADs binds phosphorylated SxxS motifs both in TGFb receptors and in each other. It is structurally related to the FHA domain (1)

Reference
1. http://kinase.com/wiki/index.php/Phospho-Serine/Threonine_binding_domains/

    C-terminal Polo-box domains (PBDs) of Plks, acting as pS/pT-binding modules, are crucial for orchestrating the proper sub-cellular localizations and kinase activities of Plks during multiple stages of mitosis. Moreover, Plk-mediated phosphoregulation can regulate a variety of biological and cellular processes beyond mitosis, such as DNA damage, centriole duplication, transcription regulation and stress-activated MAPK cascade (1).

Reference
1. Liu, Z. (2013) Systematic analysis of the Plk-mediated phosphoregulation in eukaryotes . Brief Bioinform, 14, 344-60. PMID: 22851512

    The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals. 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. The PDZ domain of RGS3 were found to bind to the Tyr304 phosphopeptide of ephrin B2 in recent study (1).

Reference
1. Su, Z. (2011) Single phosphorylation of Tyr304 in the cytoplasmic tail of ephrin B2 confers high-affinity and bifunctional binding to both the SH2 domain of Grb4 and the PDZ domain of the PDZ-RGS3 protein. Eur J Biochem, 271, 1725-36. PMID: 15096211

    WD-40 repeats (also known as WD or beta-transducin repeats) are short ~40 amino acid motifs, often terminating in a Trp-Asp (W-D) dipeptide. WD40 repeats usually assume a 7-8 bladed beta-propeller fold, but proteins have been found with 4 to 16 repeated units, which also form a circularised beta-propeller structure. WD-repeat proteins are a large family found in all eukaryotes and are implicated in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control and apoptosis. Repeated WD40 motifs act as a site for protein-protein interaction, and proteins containing WD40 repeats are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins. A widespread protein-interaction domain, of which some members (bTRCP and CDC4) bind specifically to pSer or pThr motifs. Many or most are probably not phospho-specific (1).

Reference
1. http://www.ebi.ac.uk/interpro/entry/IPR001680

    WW domains are signaling modules of approximately 40 amino acids that fold into three anti-parallel β strands and bind short proline-rich sequences, predominantly composed of PPXY, PPLP or PPR motifs. It is frequently associated with other domains typical for proteins in signal transduction processes. The proline isomerase Pin1 and the ubiquitin ligase Nedd4, however, contain WW domains that specifically recognize pSer–Pro and pThr–Pro motifs (1).

Reference
1. Yaffe, M.B. (2001) Phosphoserine/threonine-binding domains . Curr Opin Cell Biol, 13, 131-8. PMID: 11248545