Table 1.
Representative examples of protein, RNA and DNA motifs
| Motif type | Example motif | Consensus sequencea | Function |
|---|---|---|---|
| Protein short linear motifs | |||
| Ligand - promote complex formation | SH3 ligand | PxxPx[KR] | Complex formation with SH3 domains [195] |
| Nuclear receptor box | LxxLL | Complex formation with Nuclear receptors [196] | |
| LD motif | [LV][DE]x[LM][LM]xxL | Complex formation with FAT domains [197] | |
| LxCxE motif | [IL]xCxE | Complex formation with Rb [198] | |
| RGD motif | RGD | Complex formation with Integrin family members [199] | |
| Localisation - recruit targeting and transport pathways to control protein localisation | Nuclear Export Signal (NES) | ΦxxΦxxxΦxxΦxΦ | Translocation from the nucleus to the cytoplasm [200] |
| KDEL ER retrieval signal | [KH]DEL-COOH | Translocation from the Golgi to the endoplasmatic reticulum (ER) [201] | |
| Ciliary targeting signal | RVxP | Transport to the plasma membrane of the cilia [202] | |
| Peroxisomal targeting signal | [KRH]xxΦ$ or [KRH]Φ$ | Import into the peroxisomal lumen [203] | |
| Tyrosine endocytic signal | YxxΦ | Directs endocytosis of membrane proteins [204] | |
| Enzyme recruitment - recruit enzymes to the protein/complex to modify/demodify a site distinct from the bound motif | Cyclin docking motif | [RK]xLx{0,1}[LF] | Recruitment of the Cyclin-Cdk holoenzyme [205] |
| PP1 docking motif | RVxF | Recruitment of the PP1 phosphotase holoenzyme [206] | |
| Tankyrase docking motif | Rxx[PGAV][DEIP]G | Recruitment of the Tankyrase poly-(ADP-ribose) polymerase [207] | |
| USP7 docking motif | PxxS | Recruitment of the USP7 deubiquitylating enzyme [208] | |
| NEDD4 docking motif | PPxY | Recruitment of the NEDD4 ubiquitylating enzyme [209] | |
| Stability - recruit E3 ubiquitin ligases and promote substrate polyubiquitylation to control protein stability | APC/C D box degron | RxxLxxΦ | APC/C E3 ubiquitin ligase [210] |
| PIP degron | Φ[ST]D[FY][FY]xxx[KR] | Recruitment of the Cdt2 CRL4 E3 ubiquitin ligase [211] | |
| Fbw7 degron | pTPxxp[ST] | Recruitment of the Fbw7 SCF E3 ubiquitin ligase [212] | |
| Oxygen dependent VHL degron | [IL]AoPx{6,8}ΦxΦ | Recruitment of von Hippel-Lindau protein (pVHL) containing E3 ubiquitin ligase [213] | |
| MDM2 degron | FxxxWxxΦ | Recruitment of the MDM2 ubiquitin ligase [214] | |
| Modification - act as sites of moiety attachment/removal, isomerisation or cleavage | PIKK phosphorylation site | ([ST])Q | Phosphorylation by PIKK family kinases [215] |
| Pin1 isomerisation site | p[ST](P) | Isomerisation by the Pin1 phosphorylation-dependent prolyl isomerase [216] | |
| N-Glycosylation site | Nx([ST]) | Glycosylation by Oligosaccharyltransferase [217] | |
| Caspase-3 and −7 cleavage motif | [DE]xxD|[AGS] | Cleavage by Caspase family proteases [218] | |
| Myristoylation site | NH2-M(G)xxx[AGSTCN] | Myristoylation by Myristoyl-CoA:protein N-myristoyltransferase [219] | |
| RNA motifs | |||
| Stability | Adenosine and uridine (AU)-rich elements (ARE) | AUUUA | Recruits positive and negative regulators of mRNA stability [13] |
| Splicing | 5′ splice junction | AG/GURAGU | Recruits splice site recognising U1 snRNA component of the spliceosome [14] |
| Modification | Polyadenylation signal | AUUAAA | Recruits cleavage and polyadenylation specificity factor (CPSF) to cleave and polyadenylate 3′-UTRs [15] |
| Localisation | Muscleblind binding motifs | YGCUKY | Targets mRNAs to membranes [16] |
| miRNA recruitment | miR-125b miRNA response element | CUCAGGG | Regulates expression of mutiple proteins [17] |
| DNA regulatory elements | |||
| Basal machinery recruitment | TATA box | TATAAAA | Recruitment of the basal transcription machinery to the core gene promoter required for initiation of transcription [9] |
| Promoters/Enhancers | CCAAT/enhancer binding protein (C/EBP) site | CCAAT | Promotion of gene expression [10] |
| Silencers/Insulators | CCCTC-binding factor (CTCF) binding site | CCGCGNGGNGGCAG | Diverse functions including acting as a transcriptional repressor and insulator [11] |
| Endonucleases | EcoRI restriction site | G|AATTC | Sequence specific cleavage of DNA [12] |
aPatterns are representative and roughly define the specificity of the motif binding partner. Pattern syntax for proteins: letters denote a specific amino acid; “x” denotes any amino acid; square brackets denote a subset of allowed amino acids; curly brackets denote length variability; round brackets indicate a position targeted for post-translational modification after motif recognition; “p” denotes a phosphorylation site required for binding; “o” denotes a hydroxylation site required for binding; “|” denotes a cleavage site; “Φ” (phi) denotes a aliphatic residue; “NH2-” indicates the amino-terminus of the protein; “-COOH” indicates the carboxyl-terminus of the protein. Pattern syntax for DNA and RNA: “/” denotes a splice site. “K” denotes a guanine or a uracil; “Y” denotes an adenine or a cytosine; “R” denotes an adenine or a guanine; “N” denotes any base; “|” denotes a cleavage site