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Table 1 Representative examples of protein, RNA and DNA motifs

From: Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation

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]

  1. 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