568:, among others). ANCHOR identifies stretches of intrinsically disordered regions that cannot form favorable intrachain interactions to fold without additional stabilising energy contributed by a globular interaction partner. α-MoRF-Pred uses the inherent propensity of many SLiM to undergo a disorder to order transition upon binding to discover α-helical forming stretches within disordered regions. MoRFPred and MoRFchibi SYSTEM are SVM based predictors which utilize multiple features including local sequence physicochemical properties, long stretches of disordered regions and conservation in their predictions. SLiMPred is neural network–based method for the de novo discovery of SLiMs from the protein sequence. Information about the structural context of the motif (predicted secondary structure, structural motifs, solvent accessibility, and disorder) are used during the predictive process. Importantly, no previous knowledge about the protein (i.e., no evolutionary or experimental information) is required.
294:
the UEV domain binding PTAP late domain. The short generation times and high mutation rates of viruses, in association with natural selection, has led to multiple examples of mimicry of host SLiMs in every step of the viral life cycle (Src binding motif PxxP in Nef modulates replication, WW domain binding PPxY mediates budding in Ebola virus, A Dynein Light Chain binding motif in Rabies virus is vital for host infection). The extent of human SLiM mimicry is surprising with many viral proteins containing several functional SLiMs, for example, the
Adenovirus protein E1A.
81:"The sequences of many proteins contain short, conserved motifs that are involved in recognition and targeting activities, often separate from other functional properties of the molecule in which they occur. These motifs are linear, in the sense that three-dimensional organization is not required to bring distant segments of the molecule together to make the recognizable unit. The conservation of these motifs varies: some are highly conserved while others, for example, allow substitutions that retain only a certain pattern of charge across the motif."
17:
306:
488:(MnM) represent the two largest motif databases as they attempt to capture all motifs from the available literature. Several more specific and specialised databases also exist, PepCyber and ScanSite focus on smaller subsets of motifs, phosphopeptide binding and important signaling domains respectively. PDZBase focuses solely on PDZ domain ligands.
537:
Enrichment in groupings of similar proteins – Motif often evolve convergently to carry out similar tasks in different proteins such as mediating binding to a specific partner or targeting proteins to a particular subcellular localisation. Often in such cases these grouping the motif occurs more often
501:
SLiMs are short and degenerate and as a result the proteome is littered with stochastically occurring peptides that resemble functional motifs. The biologically relevant cellular partners can easily distinguish functional motifs, however computational tools have yet to reach a level of sophistication
297:
Pathogenic bacteria also mimic host motifs (as well as having their own motifs), however, not to the same extent as the obligate parasite viruses. E. Coli injects a protein, EspF(U), that mimics an autoinhibitory element of N-WASP into the host cell to activate actin-nucleating factors WASP. The KDEL
107:
directly contact the binding partner, has two major consequences. First, only few or even a single mutation can result in the generation of a functional motif, with further mutations of flanking residues allowing tuning affinity and specificity. This results in SLiMs having an increased propensity to
492:
and CutDB curate available proteolytic event data including protease specificity and cleavage sites. There has been a large increase in the number of publications describing motif mediated interactions over past decade and as a result a large amount of the available literature remains to be curated.
563:
More recently computational methods have been developed that can identify new Short Linear Motifs de novo. Interactome-based tools rely on identifying a set of proteins that are likely to share a common function, such as binding the same protein or being cleaved by the same peptidase. Two examples
293:
Viruses often mimic human SLiMs to hijack and disrupt a host's cellular machinery, thereby adding functionality to their compact genomes without necessitating new virally encoded proteins. In fact, many motifs were originally discovered in viruses, such as the
Retinoblastoma binding LxCxE motif and
155:
SLiM functions in almost every pathway due to their critical role in regulatory function, protein-protein interaction and signal transduction. SLiM act as interaction modules that are recognised by additional biomolecules. The majority of known interaction partners of SLiMs are globular protein
106:
and determine most of the affinity and specificity of the interaction. Although most motifs have no positional preference, several of them are required to be localized at the protein termini in order to be functional. The key defining attribute of SLiMs, having a limited number of residues that
505:
Motif discovery tools can be split into two major categories, discovery of novel instance of known functional motifs class and discovery of functional motifs class, however, they all use a limited and overlapping set of attributes to discriminate true and false positives. The main discrimatory
239:– Many classes of ligand SLiMs recruit enzymes to their substrate by binding to sites that are distinct from the enzyme's active site. These site, known as docking motifs, act as additional specificity determinants for these enzymes and decrease the likelihood of off-target modification events.
207:
Ligand binding site SLiMs recruit binding partners to the SLiM containing proteins, often mediating transient interactions, or acting co-operatively to produce more stable complexes. Ligand SLiMs are often central to the formation of dynamic multi-protein complexes, however, they more commonly
475:
in the motif literature with the important residues defined based on a combination of experimental, structural and evolutionary evidence. However, high throughput screening such as phage display has seen a large increase in the available information for many motifs classes allowing them to be
529:
Conservation – the conservation of a motif correlates strongly with functionality and many experimental motifs are seen as islands of strong constraint in regions of weak conservation. Alignment of homologous proteins can be used to calculate conservation metric for a
254:
Disordered protein elements like SLiMs are frequently found in factors that regulate gene expression. As a result, several diseases have been linked to mutations that alter key SLiM-mediated functions. For instance, one cause of
533:
Physicochemical properties – Certain intrinsic properties of residues or stretches of amino acids are strong discriminators of functionality, for example, the propensity of a region of disorder to undergo a disorder to order
156:
domains, though, SLiMs that recognise other intrinsically disordered regions, RNA and lipids have also been characterised. SLiMs can be broadly split into two high level classes, modification sites and ligand binding sites.
119:. Second, SLiMs have relatively low affinity for their interaction partners (generally between 1 and 150 ÎĽM), which makes these interactions transient and reversible, and thus ideal to mediate dynamic processes such as
163:
Modification sites SLiMs encompass sites with intrinsic specificity determinant that are recognised and modified by the active site of a catalytic domain of an enzyme. These SLiMs include many classical
225:– A large number of SLiMs act as zipcodes that are recognized by the cellular transport machinery mediating the relocalisation of the containing protein to the correct sub-cellular compartment (e.g.
1086:
Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, et al. (August 2007). "Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy".
215:– Ligand SLiMs often function as simple interfaces that recruit proteins to multi-protein complexes (e.g. the Retinoblastoma-binding LxCxE motif) or act as aggregators in scaffold proteins (e.g.
1186:
Kalay E, de
Brouwer AP, Caylan R, Nabuurs SB, Wollnik B, Karaguzel A, et al. (December 2005). "A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome".
1557:
Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. (February 2004). "In vivo activation of the p53 pathway by small-molecule antagonists of MDM2".
555:(MnM) both provide servers to search for novel instance of known functional motifs in protein sequences. SLiMSearch allows similar searches on a proteome-wide scale.
102:, with an average of just over 6 residues. However, only few hotspot residues (on average 1 hotspot for each 3 residues in the motif) contribute the majority of the
1608:
Goodman SL, Hölzemann G, Sulyok GA, Kessler H (February 2002). "Nanomolar small molecule inhibitors for alphav(beta)6, alphav(beta)5, and alphav(beta)3 integrins".
564:
of such software are DILIMOT and SLiMFinder. Anchor and α-MoRF-Pred use physicochemical properties to search for motif-like peptides in disordered regions (termed
259:
is a mutation in the protein Raf-1 which abrogates the interaction with 14-3-3 proteins mediated by corresponding short linear motifs and thereby deregulate the
245:– A subset of docking motifs recruit E3 ubiquitin ligase to their substrates. The resulting polyubiquitination targets the substrate for proteosomal destruction.
2625:"MoRFpred, a computational tool for sequence-based prediction and characterization of short disorder-to-order transitioning binding regions in proteins"
2372:
Hugo W, Song F, Aung Z, Ng SK, Sung WK (April 2010). "SLiM on Diet: finding short linear motifs on domain interaction interfaces in
Protein Data Bank".
1696:"Grb2-SH3 ligand inhibits the growth of HER2+ cancer cells and has antitumor effects in human cancer xenografts alone and in combination with docetaxel"
278:
has been implicated with autosomal dominant activating mutations in the WW interaction motif in the β-(SCNNB_HUMA) and γ-(SCNNG_HUMA) subunits of the
2997:
328:
Linear motif mediated protein-protein interactions have shown promise in recent years as novel drug targets. Success stories include the
1645:"Cilengitide induces cellular detachment and apoptosis in endothelial and glioma cells mediated by inhibition of FAK/src/AKT pathway"
519:
400:
790:
Davey NE, Van Roey K, Weatheritt RJ, Toedt G, Uyar B, Altenberg B, et al. (January 2012). "Attributes of short linear motifs".
2876:
493:
Recent work has created the tool MiMosa to expedite the annotation process and encourage semantically robust motif descriptions.
127:
that change the structural and physicochemical properties of the motif. Also, regions of high functional density can mediate
1506:
Wells JA, McClendon CL (December 2007). "Reaching for high-hanging fruit in drug discovery at protein-protein interfaces".
1272:"Liddle's syndrome caused by a novel mutation in the proline-rich PY motif of the epithelial sodium channel beta-subunit"
511:
193:-SLiMs can act as recognition sites of endo-peptidases resulting in the irreversible cleavage of the peptide at the SLiM.
91:
3079:
878:"The conservation pattern of short linear motifs is highly correlated with the function of interacting protein domains"
1459:"Targeting of cholera toxin and Escherichia coli heat labile toxin in polarized epithelia: role of COOH-terminal KDEL"
2990:
2829:
Mooney C, Pollastri G, Shields DC, Haslam NJ (January 2012). "Prediction of short linear protein binding regions".
697:"Short Linear Motifs recognized by SH2, SH3 and Ser/Thr Kinase domains are conserved in disordered protein regions"
1745:"Potential disease targets for drugs that disrupt protein-- protein interactions of Grb2 and Crk family adaptors"
111:, which facilitates their proliferation, as is evidenced by their conservation and increased incidence in higher
67:
184:
165:
124:
1988:"PepCyber:P~PEP: a database of human protein protein interactions mediated by phosphoprotein-binding domains"
226:
208:
mediate regulatory interactions that control the stability, localisation or modification state of a protein.
3089:
2983:
2963:
270:
is the most frequent cause of hereditary deaf-blindness in humans and can be caused by mutations in either
2958:
2953:
2723:"Computational Identification of MoRFs in Protein Sequences Using Hierarchical Application of Bayes Rule"
199:– SLiMs can be recognised by isomerases resulting in the cis-trans isomerisation of the peptide backbone.
2948:
1643:
Oliveira-Ferrer L, Hauschild J, Fiedler W, Bokemeyer C, Nippgen J, Celik I, Schuch G (December 2008).
2918:
2174:
Igarashi Y, Eroshkin A, Gramatikova S, Gramatikoff K, Zhang Y, Smith JW, et al. (January 2007).
660:
Dice JF (August 1990). "Peptide sequences that target cytosolic proteins for lysosomal proteolysis".
287:
279:
63:
2386:
1885:
Gould CM, Diella F, Via A, Puntervoll P, GemĂĽnd C, Chabanis-Davidson S, et al. (January 2010).
3084:
2037:"Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs"
625:
Neduva V, Russell RB (October 2006). "Peptides mediating interaction networks: new leads at last".
404:
2576:"Mining alpha-helix-forming molecular recognition features with cross species sequence alignments"
2274:
Praefcke GJ, Ford MG, Schmid EM, Olesen LE, Gallop JL, Peak-Chew SY, et al. (November 2004).
548:
481:
480:. Several diverse repositories currently curate the available motif data. In terms of scope, the
399:
domain. This tactic has shown promise in the treatments of various forms of cancer. For example,
443:
converting enzymes inhibitors. Other drugs that target post-translational modifications include
2381:
290:, ultimately resulting in increased Na reabsorption, plasma volume extension and hypertension.
168:(PTMs), proteolytic cleavage sites recognised by proteases and bonds recognised by isomerases.
2468:"SLiMFinder: a web server to find novel, significantly over-represented, short protein motifs"
1937:
Rajasekaran S, Balla S, Gradie P, Gryk MR, Kadaveru K, Kundeti V, et al. (January 2009).
230:
21:
2223:
Vyas J, Nowling RJ, Meusburger T, Sargeant D, Kadaveru K, Gryk MR, et al. (June 2010).
115:. It has been hypothesized that this might increase and restructure the connectivity of the
2734:
2528:
2276:"Evolving nature of the AP2 alpha-appendage hub during clathrin-coated vesicle endocytosis"
1566:
1515:
1457:
Lencer WI, Constable C, Moe S, Jobling MG, Webb HM, Ruston S, et al. (November 1995).
1413:
1270:
Furuhashi M, Kitamura K, Adachi M, Miyoshi T, Wakida N, Ura N, et al. (January 2005).
940:
275:
108:
1402:"The pathogen protein EspF(U) hijacks actin polymerization using mimicry and multivalency"
1400:
Sallee NA, Rivera GM, Dueber JE, Vasilescu D, Mullins RD, Mayer BJ, Lim WA (August 2008).
8:
2623:
Disfani FM, Hsu WL, Mizianty MJ, Oldfield CJ, Xue B, Dunker AK, et al. (June 2012).
95:
2738:
2532:
1570:
1519:
1417:
1155:
1130:
1063:
1028:
944:
586:"Understanding eukaryotic linear motifs and their role in cell signaling and regulation"
94:
regions (over 80% of known SLiMs), however, upon interaction with a structured partner
2806:
2782:"MoRFchibi SYSTEM: software tools for the identification of MoRFs in protein sequences"
2781:
2757:
2722:
2698:
2673:
2649:
2624:
2600:
2575:
2551:
2516:
2492:
2467:
2443:
2418:
2349:
2324:
2251:
2224:
2200:
2175:
2151:
2126:
2012:
1987:
1963:
1938:
1911:
1886:
1859:
1832:
1808:
1783:
1720:
1695:
1671:
1644:
1590:
1539:
1483:
1458:
1434:
1401:
1377:
1352:
1211:
1168:
1111:
966:
904:
877:
853:
826:
723:
696:
472:
2300:
2275:
2061:
2036:
274:
in
Harmonin or the corresponding PDZ interaction motifs in the SANS protein. Finally,
140:
2856:
2811:
2762:
2703:
2654:
2605:
2556:
2497:
2448:
2399:
2354:
2305:
2256:
2205:
2156:
2107:
2066:
2017:
1968:
1916:
1864:
1813:
1764:
1725:
1676:
1625:
1582:
1543:
1531:
1488:
1439:
1382:
1328:
1293:
1252:
1247:
1230:
1203:
1160:
1103:
1068:
1050:
1004:
958:
909:
858:
807:
769:
728:
677:
673:
642:
607:
523:
311:
34:
2689:
2640:
2395:
2102:
2085:
1594:
1215:
1115:
970:
2846:
2838:
2801:
2793:
2752:
2742:
2693:
2685:
2644:
2636:
2595:
2587:
2546:
2536:
2487:
2479:
2438:
2430:
2391:
2344:
2336:
2295:
2287:
2246:
2236:
2195:
2187:
2146:
2138:
2097:
2056:
2048:
2007:
1999:
1958:
1950:
1906:
1898:
1854:
1844:
1803:
1795:
1756:
1715:
1707:
1666:
1656:
1617:
1574:
1523:
1478:
1470:
1429:
1421:
1372:
1364:
1320:
1283:
1242:
1195:
1172:
1150:
1142:
1095:
1058:
1040:
996:
948:
899:
889:
848:
838:
799:
759:
718:
708:
669:
634:
597:
128:
953:
928:
584:
Diella F, Haslam N, Chica C, Budd A, Michael S, Brown NP, et al. (May 2008).
2937:
2922:
2893:
2747:
2541:
1311:
Davey NE, Travé G, Gibson TJ (March 2011). "How viruses hijack cell regulation".
638:
552:
485:
392:
256:
176:
2975:
538:
than is expected by chance and can be detected by searching for enriched motifs.
98:
is often induced. The majority of annotated SLiMs consist of 3 to 11 contiguous
16:
3007:
2574:
Cheng Y, Oldfield CJ, Meng J, Romero P, Uversky VN, Dunker AK (November 2007).
1799:
1760:
1324:
1045:
1000:
713:
448:
415:® is a broad-based tyrosine kinase inhibitor whose targets include Bcr-Abl and
267:
120:
103:
29:
2842:
1199:
987:(October 2009). "Cell regulation: determined to signal discrete cooperation".
843:
764:
747:
3073:
2291:
2241:
1849:
1054:
477:
175:– SLiMs are often targeted for the addition of a small chemical groups (e.g.
123:. In addition, this means that these interactions can be easily modulated by
1661:
1578:
894:
2860:
2815:
2766:
2707:
2658:
2609:
2560:
2501:
2452:
2403:
2358:
2309:
2260:
2209:
2160:
2111:
2070:
2021:
1972:
1920:
1868:
1817:
1768:
1729:
1680:
1629:
1586:
1535:
1443:
1386:
1332:
1297:
1207:
1164:
1107:
1072:
1008:
962:
913:
862:
811:
773:
732:
646:
611:
361:
1986:
Gong W, Zhou D, Ren Y, Wang Y, Zuo Z, Shen Y, et al. (January 2008).
1902:
1492:
1474:
1256:
1146:
681:
3053:
3028:
3018:
2898:
2797:
2483:
2434:
2340:
2191:
2142:
2052:
2003:
1954:
1939:"Minimotif miner 2nd release: a database and web system for motif search"
1288:
1271:
984:
514:
prediction tools (such as IUPred or GlobPlot), domain databases (such as
440:
369:
353:
341:
286:, thereby inhibiting channel degradation and prolonging the half-life of
180:
144:
116:
2325:"SLiMSearch 2.0: biological context for short linear motifs in proteins"
1642:
1527:
1425:
3048:
3043:
3038:
3033:
2084:
Beuming T, Skrabanek L, Niv MY, Mukherjee P, Weinstein H (March 2005).
803:
452:
416:
385:
381:
305:
271:
216:
99:
2851:
2591:
2173:
1711:
1621:
745:
526:) can be used to check the accessibility of predicted motif instances.
510:
Accessibility – the motif must be accessible for the binding partner.
315:
38:
3058:
3023:
1694:
Gril B, Vidal M, Assayag F, Poupon MF, Liu WQ, Garbay C (July 2007).
420:
419:. Cleavage is another process directed by motif recognition with the
365:
112:
695:
Ren S, Uversky VN, Chen Z, Dunker AK, Obradovic Z (September 2008).
1231:"Liddle syndrome: an autosomal dominant form of human hypertension"
1099:
1029:"Interaction modules that impart specificity to disordered protein"
522:) and experimentally derived structural data (from sources such as
502:
where motif discovery can be accomplished with high success rates.
436:
432:
357:
345:
337:
333:
299:
132:
74:
25:
746:
London N, Movshovitz-Attias D, Schueler-Furman O (February 2010).
2927:
2086:"PDZBase: a protein-protein interaction database for PDZ-domains"
1368:
827:"Short linear motifs - ex nihilo evolution of protein regulation"
602:
585:
444:
428:
424:
412:
408:
136:
391:
There are at present no drugs on the market specially targeting
302:
encoded cholera toxin mediates cell entry of the cholera toxin.
489:
396:
373:
309:
MDM2 SWIB domain-binding motif mimic drug Nutlin bound to MDM2(
282:. These mutations abrogate the binding to the ubiquitin ligase
263:
2517:"Prediction of protein binding regions in disordered proteins"
2515:
Mészáros B, Simon I, Dosztányi Z (May 2009). Casadio R (ed.).
1887:"ELM: the status of the 2010 eukaryotic linear motif resource"
1784:"Intrinsically disordered proteins are potential drug targets"
1269:
352:
thus stabilising p53 and inducing senescence in cancer cells.
2222:
1607:
1353:"Viral infection and human disease--insights from minimotifs"
565:
451:
inhibitor and
Farnysyl Transferase inhibitors that block the
283:
260:
131:
by means of overlapping motifs (e.g. the C-terminal tails of
2828:
2674:"Computational identification of MoRFs in protein sequences"
2083:
1185:
1085:
789:
748:"The structural basis of peptide-protein binding strategies"
139:
interactions by multiple low affinity motifs (e.g. multiple
2970:
2903:
1744:
1399:
515:
423:
responsible for cleavage a good drug target. For example,
377:
329:
2915:
2721:
Malhis N, Wong ET, Nassar R, Gsponer J (30 October 2015).
2622:
1936:
876:
Ren S, Yang G, He Y, Wang Y, Li Y, Chen Z (October 2008).
2942:
2466:
Davey NE, Haslam NJ, Shields DC, Edwards RJ (July 2010).
2465:
2323:
Davey NE, Haslam NJ, Shields DC, Edwards RJ (July 2011).
2322:
1456:
349:
2273:
1884:
1556:
2720:
2573:
1027:
Cermakova, Katerina; Hodges, H. Courtney (2023-02-06).
348:
antagonises the interaction of MDM2's SWIB domain with
2514:
2124:
1693:
1649:
407:(RTK) inhibitor for treating gastrointestinal cancer,
2932:
2888:
2779:
583:
323:
2034:
1833:"Profile-based short linear protein motif discovery"
1350:
1276:
The
Journal of Clinical Endocrinology and Metabolism
694:
542:
2125:Rawlings ND, Barrett AJ, Bateman A (January 2010).
929:"Linear motifs: evolutionary interaction switches"
3005:
2419:"DILIMOT: discovery of linear motifs in proteins"
1122:
360:-dependent signaling, causing the disassembly of
28:mimic of the LxCxE motif (red) bound to the host
3071:
2822:
2567:
2508:
2216:
2167:
2118:
2077:
2028:
1979:
1824:
1775:
1736:
1687:
1636:
1601:
1550:
1499:
1393:
1339:
1310:
1263:
1179:
1079:
977:
558:
461:
2035:Obenauer JC, Cantley LC, Yaffe MB (July 2003).
1985:
1932:
1930:
1880:
1878:
1450:
1346:
1344:
1342:
1222:
1026:
920:
869:
824:
818:
780:
739:
688:
2371:
1742:
1505:
825:Davey NE, Cyert MS, Moses AM (November 2015).
785:
783:
388:adaptor domains are also under investigation.
2991:
2877:Pawsons Lab Resource on motif-binding domains
2780:Malhis N, Jacobson M, Gsponer J (July 2016).
2671:
2416:
1830:
926:
875:
624:
395:sites, however, a number of drugs target the
2459:
2410:
2365:
2267:
1927:
1875:
1351:Kadaveru K, Vyas J, Schiller MR (May 2008).
1304:
2225:"MimoSA: a system for minimotif annotation"
376:cells. In addition, peptides targeting the
364:, cellular detachment and the induction of
2998:
2984:
2316:
1128:
2850:
2805:
2756:
2746:
2697:
2648:
2599:
2550:
2540:
2491:
2442:
2385:
2348:
2299:
2250:
2240:
2199:
2150:
2101:
2060:
2011:
1962:
1910:
1858:
1848:
1807:
1719:
1670:
1660:
1482:
1433:
1376:
1287:
1246:
1154:
1062:
1044:
952:
903:
893:
852:
842:
763:
722:
712:
601:
506:attributes used in motif discovery are:
304:
15:
2909:
2773:
1781:
1228:
135:beta subunits), or they can allow high
3072:
1131:"Molecular genetics of Usher syndrome"
983:
2979:
2176:"CutDB: a proteolytic event database"
1022:
1020:
1018:
166:post translational modification sites
1135:Cellular and Molecular Life Sciences
659:
1788:Current Opinion in Chemical Biology
13:
2417:Neduva V, Russell RB (July 2006).
1831:Haslam NJ, Shields DC (May 2012).
1129:Eudy JD, Sumegi J (October 1999).
1015:
927:Neduva V, Russell RB (June 2005).
496:
455:modification to a CAAX-box motif.
324:Potential as leads for drug design
249:
185:post translational moiety addition
73:The first definition was given by
14:
3101:
2882:
2870:
2672:Malhis N, Gsponer J (June 2015).
543:Novel functional motifs instances
219:-binding proline-rich sequences).
2933:Eukaryotic Linear Motif Database
2889:Eukaryotic Linear Motif Database
2127:"MEROPS: the peptidase database"
1248:10.1046/j.1523-1755.1998.00728.x
831:Cell Communication and Signaling
627:Current Opinion in Biotechnology
411:® specially targets bcr-abl and
125:post-translational modifications
90:SLiMs are generally situated in
2714:
2665:
2616:
1700:International Journal of Cancer
471:SLiMs are usually described by
1743:Feller SM, Lewitzky M (2006).
1610:Journal of Medicinal Chemistry
1313:Trends in Biochemical Sciences
1033:Trends in Biochemical Sciences
989:Trends in Biochemical Sciences
662:Trends in Biochemical Sciences
653:
618:
577:
280:Epithelial sodium channel ENaC
1:
2690:10.1093/bioinformatics/btv060
2641:10.1093/bioinformatics/bts209
2396:10.1093/bioinformatics/btq065
2103:10.1093/bioinformatics/bti098
1749:Current Pharmaceutical Design
1188:Journal of Molecular Medicine
954:10.1016/j.febslet.2005.04.005
571:
559:Novel functional motifs class
462:Computational motif resources
458:Recommended further reading:
85:
2831:Journal of Molecular Biology
2748:10.1371/journal.pone.0141603
2542:10.1371/journal.pcbi.1000376
2478:(Web Server issue): W534-9.
2429:(Web Server issue): W350-5.
2335:(Web Server issue): W56-60.
1039:(5): S0968–0004(23)00008–7.
674:10.1016/0968-0004(90)90019-8
639:10.1016/j.copbio.2006.08.002
466:
227:Nuclear localisation signals
7:
2137:(Database issue): D227-33.
1998:(Database issue): D679-83.
1949:(Database issue): D185-90.
1897:(Database issue): D167-80.
1463:The Journal of Cell Biology
1229:Warnock DG (January 1998).
150:
68:protein–protein interaction
10:
3106:
2521:PLOS Computational Biology
2186:(Database issue): D546-9.
1800:10.1016/j.cbpa.2010.06.169
1782:Metallo SJ (August 2010).
1761:10.2174/138161206775474369
1325:10.1016/j.tibs.2010.10.002
1046:10.1016/j.tibs.2023.01.004
1001:10.1016/j.tibs.2009.06.007
714:10.1186/1471-2164-9-S2-S26
183:) or other moieties (e.g.
3080:Protein structural motifs
3014:
2843:10.1016/j.jmb.2011.10.025
1200:10.1007/s00109-005-0719-4
844:10.1186/s12964-015-0120-z
765:10.1016/j.str.2009.11.012
2292:10.1038/sj.emboj.7600445
2242:10.1186/1471-2105-11-328
1850:10.1186/1471-2105-13-104
439:® are substrate mimetic
405:receptor tyrosine kinase
197:Structural modifications
92:intrinsically disordered
1662:10.1186/1756-9966-27-86
1579:10.1126/science.1092472
1357:Frontiers in Bioscience
895:10.1186/1471-2164-9-452
590:Frontiers in Bioscience
549:Eukaryotic Linear Motif
482:Eukaryotic Linear Motif
62:are short stretches of
2786:Nucleic Acids Research
2472:Nucleic Acids Research
2423:Nucleic Acids Research
2329:Nucleic Acids Research
2180:Nucleic Acids Research
2131:Nucleic Acids Research
2041:Nucleic Acids Research
1992:Nucleic Acids Research
1943:Nucleic Acids Research
1891:Nucleic Acids Research
340:targeting RGD-mimetic
320:
231:Nuclear export signals
104:free energy of binding
83:
43:
1475:10.1083/jcb.131.4.951
1147:10.1007/s000180050427
308:
79:
46:In molecular biology
32:protein (dark grey) (
22:human papilloma virus
19:
2910:SLiM discovery tools
1289:10.1210/jc.2004-1027
1235:Kidney International
792:Molecular BioSystems
204:Ligand binding sites
191:Proteolytic cleavage
3090:Short linear motifs
2739:2015PLoSO..1041603M
2533:2009PLSCB...5E0376M
1903:10.1093/nar/gkp1016
1571:2004Sci...303..844V
1528:10.1038/nature06526
1520:2007Natur.450.1001W
1426:10.1038/nature07170
1418:2008Natur.454.1005S
945:2005FEBSL.579.3342N
551:resource (ELM) and
484:resource (ELM) and
473:regular expressions
129:molecular switching
109:evolve convergently
96:secondary structure
48:short linear motifs
2921:2009-10-23 at the
2798:10.1093/nar/gkw409
2484:10.1093/nar/gkq440
2435:10.1093/nar/gkl159
2341:10.1093/nar/gkr402
2229:BMC Bioinformatics
2192:10.1093/nar/gkl813
2143:10.1093/nar/gkp971
2053:10.1093/nar/gkg584
2004:10.1093/nar/gkm854
1955:10.1093/nar/gkn865
1837:BMC Bioinformatics
804:10.1039/c1mb05231d
512:Intrinsic disorder
321:
237:Modification state
179:), proteins (e.g.
160:Modification sites
141:AP2-binding motifs
44:
3067:
3066:
2592:10.1021/bi7012273
1712:10.1002/ijc.22674
1622:10.1021/jm0102598
276:Liddle's Syndrome
213:Complex formation
3097:
3000:
2993:
2986:
2977:
2976:
2865:
2864:
2854:
2826:
2820:
2819:
2809:
2777:
2771:
2770:
2760:
2750:
2733:(10): e0141603.
2718:
2712:
2711:
2701:
2669:
2663:
2662:
2652:
2620:
2614:
2613:
2603:
2586:(47): 13468–77.
2571:
2565:
2564:
2554:
2544:
2512:
2506:
2505:
2495:
2463:
2457:
2456:
2446:
2414:
2408:
2407:
2389:
2369:
2363:
2362:
2352:
2320:
2314:
2313:
2303:
2280:The EMBO Journal
2271:
2265:
2264:
2254:
2244:
2220:
2214:
2213:
2203:
2171:
2165:
2164:
2154:
2122:
2116:
2115:
2105:
2081:
2075:
2074:
2064:
2032:
2026:
2025:
2015:
1983:
1977:
1976:
1966:
1934:
1925:
1924:
1914:
1882:
1873:
1872:
1862:
1852:
1828:
1822:
1821:
1811:
1779:
1773:
1772:
1740:
1734:
1733:
1723:
1691:
1685:
1684:
1674:
1664:
1640:
1634:
1633:
1605:
1599:
1598:
1554:
1548:
1547:
1514:(7172): 1001–9.
1503:
1497:
1496:
1486:
1454:
1448:
1447:
1437:
1412:(7207): 1005–8.
1397:
1391:
1390:
1380:
1348:
1337:
1336:
1308:
1302:
1301:
1291:
1267:
1261:
1260:
1250:
1226:
1220:
1219:
1183:
1177:
1176:
1158:
1126:
1120:
1119:
1083:
1077:
1076:
1066:
1048:
1024:
1013:
1012:
981:
975:
974:
956:
924:
918:
917:
907:
897:
873:
867:
866:
856:
846:
822:
816:
815:
787:
778:
777:
767:
743:
737:
736:
726:
716:
707:(Suppl 2): S26.
692:
686:
685:
657:
651:
650:
622:
616:
615:
605:
596:(13): 6580–603.
581:
447:®, an antiviral
318:
268:Usher's Syndrome
64:protein sequence
41:
3105:
3104:
3100:
3099:
3098:
3096:
3095:
3094:
3085:Protein domains
3070:
3069:
3068:
3063:
3010:
3008:protein domains
3004:
2938:MiniMotif Miner
2923:Wayback Machine
2912:
2894:MiniMotif Miner
2885:
2873:
2868:
2827:
2823:
2792:(W1): W488-93.
2778:
2774:
2719:
2715:
2684:(11): 1738–44.
2670:
2666:
2621:
2617:
2572:
2568:
2527:(5): e1000376.
2513:
2509:
2464:
2460:
2415:
2411:
2387:10.1.1.720.9626
2370:
2366:
2321:
2317:
2286:(22): 4371–83.
2272:
2268:
2221:
2217:
2172:
2168:
2123:
2119:
2082:
2078:
2047:(13): 3635–41.
2033:
2029:
1984:
1980:
1935:
1928:
1883:
1876:
1829:
1825:
1780:
1776:
1741:
1737:
1692:
1688:
1641:
1637:
1606:
1602:
1565:(5659): 844–8.
1555:
1551:
1504:
1500:
1455:
1451:
1398:
1394:
1363:(13): 6455–71.
1349:
1340:
1309:
1305:
1268:
1264:
1227:
1223:
1194:(12): 1025–32.
1184:
1180:
1141:(3–4): 258–67.
1127:
1123:
1088:Nature Genetics
1084:
1080:
1025:
1016:
982:
978:
925:
921:
874:
870:
823:
819:
788:
781:
744:
740:
693:
689:
658:
654:
623:
619:
582:
578:
574:
561:
553:MiniMotif Miner
545:
499:
497:Discovery tools
486:MiniMotif Miner
476:described with
469:
464:
393:phosphorylation
326:
310:
257:Noonan Syndrome
252:
250:Role in disease
206:
177:Phosphorylation
173:Moiety addition
162:
153:
88:
33:
12:
11:
5:
3103:
3093:
3092:
3087:
3082:
3065:
3064:
3062:
3061:
3056:
3051:
3046:
3041:
3036:
3031:
3026:
3021:
3015:
3012:
3011:
3006:Motif binding
3003:
3002:
2995:
2988:
2980:
2974:
2973:
2968:
2967:
2966:
2961:
2956:
2951:
2940:
2935:
2930:
2925:
2911:
2908:
2907:
2906:
2901:
2896:
2891:
2884:
2883:SLiM databases
2881:
2880:
2879:
2872:
2871:External links
2869:
2867:
2866:
2837:(1): 193–204.
2821:
2772:
2713:
2678:Bioinformatics
2664:
2635:(12): i75-83.
2629:Bioinformatics
2615:
2566:
2507:
2458:
2409:
2380:(8): 1036–42.
2374:Bioinformatics
2364:
2315:
2266:
2215:
2166:
2117:
2090:Bioinformatics
2076:
2027:
1978:
1926:
1874:
1823:
1774:
1735:
1686:
1635:
1616:(5): 1045–51.
1600:
1549:
1498:
1449:
1392:
1338:
1303:
1262:
1221:
1178:
1121:
1100:10.1038/ng2073
1094:(8): 1007–12.
1078:
1014:
995:(10): 471–82.
976:
939:(15): 3342–5.
919:
868:
817:
779:
738:
687:
652:
617:
575:
573:
570:
560:
557:
544:
541:
540:
539:
535:
531:
527:
498:
495:
478:sequence logos
468:
465:
463:
460:
449:myristoylation
325:
322:
251:
248:
247:
246:
240:
234:
220:
201:
200:
194:
188:
152:
149:
121:cell signaling
87:
84:
30:retinoblastoma
9:
6:
4:
3:
2:
3102:
3091:
3088:
3086:
3083:
3081:
3078:
3077:
3075:
3060:
3057:
3055:
3052:
3050:
3047:
3045:
3042:
3040:
3037:
3035:
3032:
3030:
3027:
3025:
3022:
3020:
3017:
3016:
3013:
3009:
3001:
2996:
2994:
2989:
2987:
2982:
2981:
2978:
2972:
2969:
2965:
2962:
2960:
2957:
2955:
2952:
2950:
2947:
2946:
2944:
2941:
2939:
2936:
2934:
2931:
2929:
2926:
2924:
2920:
2917:
2914:
2913:
2905:
2902:
2900:
2897:
2895:
2892:
2890:
2887:
2886:
2878:
2875:
2874:
2862:
2858:
2853:
2848:
2844:
2840:
2836:
2832:
2825:
2817:
2813:
2808:
2803:
2799:
2795:
2791:
2787:
2783:
2776:
2768:
2764:
2759:
2754:
2749:
2744:
2740:
2736:
2732:
2728:
2724:
2717:
2709:
2705:
2700:
2695:
2691:
2687:
2683:
2679:
2675:
2668:
2660:
2656:
2651:
2646:
2642:
2638:
2634:
2630:
2626:
2619:
2611:
2607:
2602:
2597:
2593:
2589:
2585:
2581:
2577:
2570:
2562:
2558:
2553:
2548:
2543:
2538:
2534:
2530:
2526:
2522:
2518:
2511:
2503:
2499:
2494:
2489:
2485:
2481:
2477:
2473:
2469:
2462:
2454:
2450:
2445:
2440:
2436:
2432:
2428:
2424:
2420:
2413:
2405:
2401:
2397:
2393:
2388:
2383:
2379:
2375:
2368:
2360:
2356:
2351:
2346:
2342:
2338:
2334:
2330:
2326:
2319:
2311:
2307:
2302:
2297:
2293:
2289:
2285:
2281:
2277:
2270:
2262:
2258:
2253:
2248:
2243:
2238:
2234:
2230:
2226:
2219:
2211:
2207:
2202:
2197:
2193:
2189:
2185:
2181:
2177:
2170:
2162:
2158:
2153:
2148:
2144:
2140:
2136:
2132:
2128:
2121:
2113:
2109:
2104:
2099:
2095:
2091:
2087:
2080:
2072:
2068:
2063:
2058:
2054:
2050:
2046:
2042:
2038:
2031:
2023:
2019:
2014:
2009:
2005:
2001:
1997:
1993:
1989:
1982:
1974:
1970:
1965:
1960:
1956:
1952:
1948:
1944:
1940:
1933:
1931:
1922:
1918:
1913:
1908:
1904:
1900:
1896:
1892:
1888:
1881:
1879:
1870:
1866:
1861:
1856:
1851:
1846:
1842:
1838:
1834:
1827:
1819:
1815:
1810:
1805:
1801:
1797:
1793:
1789:
1785:
1778:
1770:
1766:
1762:
1758:
1755:(5): 529–48.
1754:
1750:
1746:
1739:
1731:
1727:
1722:
1717:
1713:
1709:
1706:(2): 407–15.
1705:
1701:
1697:
1690:
1682:
1678:
1673:
1668:
1663:
1658:
1654:
1650:
1646:
1639:
1631:
1627:
1623:
1619:
1615:
1611:
1604:
1596:
1592:
1588:
1584:
1580:
1576:
1572:
1568:
1564:
1560:
1553:
1545:
1541:
1537:
1533:
1529:
1525:
1521:
1517:
1513:
1509:
1502:
1494:
1490:
1485:
1480:
1476:
1472:
1469:(4): 951–62.
1468:
1464:
1460:
1453:
1445:
1441:
1436:
1431:
1427:
1423:
1419:
1415:
1411:
1407:
1403:
1396:
1388:
1384:
1379:
1374:
1370:
1366:
1362:
1358:
1354:
1347:
1345:
1343:
1334:
1330:
1326:
1322:
1319:(3): 159–69.
1318:
1314:
1307:
1299:
1295:
1290:
1285:
1281:
1277:
1273:
1266:
1258:
1254:
1249:
1244:
1240:
1236:
1232:
1225:
1217:
1213:
1209:
1205:
1201:
1197:
1193:
1189:
1182:
1174:
1170:
1166:
1162:
1157:
1152:
1148:
1144:
1140:
1136:
1132:
1125:
1117:
1113:
1109:
1105:
1101:
1097:
1093:
1089:
1082:
1074:
1070:
1065:
1060:
1056:
1052:
1047:
1042:
1038:
1034:
1030:
1023:
1021:
1019:
1010:
1006:
1002:
998:
994:
990:
986:
980:
972:
968:
964:
960:
955:
950:
946:
942:
938:
934:
930:
923:
915:
911:
906:
901:
896:
891:
887:
883:
879:
872:
864:
860:
855:
850:
845:
840:
836:
832:
828:
821:
813:
809:
805:
801:
798:(1): 268–81.
797:
793:
786:
784:
775:
771:
766:
761:
758:(2): 188–99.
757:
753:
749:
742:
734:
730:
725:
720:
715:
710:
706:
702:
698:
691:
683:
679:
675:
671:
667:
663:
656:
648:
644:
640:
636:
633:(5): 465–71.
632:
628:
621:
613:
609:
604:
599:
595:
591:
587:
580:
576:
569:
567:
556:
554:
550:
536:
532:
528:
525:
521:
517:
513:
509:
508:
507:
503:
494:
491:
487:
483:
479:
474:
459:
456:
454:
450:
446:
442:
438:
434:
430:
426:
422:
418:
414:
410:
406:
402:
398:
394:
389:
387:
383:
379:
375:
371:
367:
363:
359:
355:
351:
347:
343:
339:
335:
332:motif analog
331:
317:
313:
307:
303:
301:
298:motif of the
295:
291:
289:
285:
281:
277:
273:
269:
265:
262:
258:
244:
241:
238:
235:
232:
228:
224:
221:
218:
214:
211:
210:
209:
205:
198:
195:
192:
189:
186:
182:
178:
174:
171:
170:
169:
167:
161:
157:
148:
146:
142:
138:
134:
130:
126:
122:
118:
114:
110:
105:
101:
97:
93:
82:
78:
76:
71:
69:
66:that mediate
65:
61:
57:
56:linear motifs
53:
49:
40:
36:
31:
27:
23:
18:
2964:Comparimotif
2834:
2830:
2824:
2789:
2785:
2775:
2730:
2726:
2716:
2681:
2677:
2667:
2632:
2628:
2618:
2583:
2580:Biochemistry
2579:
2569:
2524:
2520:
2510:
2475:
2471:
2461:
2426:
2422:
2412:
2377:
2373:
2367:
2332:
2328:
2318:
2283:
2279:
2269:
2232:
2228:
2218:
2183:
2179:
2169:
2134:
2130:
2120:
2096:(6): 827–8.
2093:
2089:
2079:
2044:
2040:
2030:
1995:
1991:
1981:
1946:
1942:
1894:
1890:
1840:
1836:
1826:
1794:(4): 481–8.
1791:
1787:
1777:
1752:
1748:
1738:
1703:
1699:
1689:
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1648:
1638:
1613:
1609:
1603:
1562:
1558:
1552:
1511:
1507:
1501:
1466:
1462:
1452:
1409:
1405:
1395:
1369:10.2741/3166
1360:
1356:
1316:
1312:
1306:
1282:(1): 340–4.
1279:
1275:
1265:
1241:(1): 18–24.
1238:
1234:
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1191:
1187:
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1134:
1124:
1091:
1087:
1081:
1036:
1032:
992:
988:
979:
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933:FEBS Letters
932:
922:
885:
882:BMC Genomics
881:
871:
834:
830:
820:
795:
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741:
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700:
690:
668:(8): 305–9.
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630:
626:
620:
603:10.2741/3175
593:
589:
579:
562:
546:
504:
500:
470:
457:
390:
362:cytoskeleton
327:
296:
292:
253:
242:
236:
223:Localisation
222:
212:
203:
202:
196:
190:
172:
159:
158:
154:
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80:
72:
59:
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534:transition.
441:Angiotensin
370:endothelial
354:Cilengitide
342:Cilengitide
272:PDZ domains
229:(NLSs) and
181:SUMOylation
117:interactome
100:amino acids
26:oncoprotein
3074:Categories
2959:SLiMSearch
2954:SLiMFinder
2852:10197/3395
572:References
453:lipidation
266:activity.
217:SH3 domain
113:Eukaryotes
86:Attributes
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1055:0968-0004
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752:Structure
467:Databases
421:proteases
366:apoptosis
356:inhibits
243:Stability
2971:ScanSite
2949:SLiMPred
2945: :
2919:Archived
2904:ScanSite
2899:PepCyber
2861:22079048
2816:27174932
2767:26517836
2727:PLOS ONE
2708:25637562
2659:22689782
2610:17973494
2561:19412530
2502:20497999
2453:16845024
2404:20167627
2359:21622654
2310:15496985
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2161:19892822
2112:15513994
2071:12824383
2022:18160410
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1869:22607209
1818:20598937
1769:16472145
1730:17372910
1681:19114005
1630:11855984
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1108:17603483
1073:36754681
1064:10106370
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863:26589632
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612:18508681
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433:Accupril
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358:integrin
346:Nutlin-3
338:integrin
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300:bacteria
151:Function
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137:avidity
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264:kinase
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1540:S2CID
1212:S2CID
1169:S2CID
1112:S2CID
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566:MoRFs
520:SMART
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3019:BRCT
2857:PMID
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