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| Domain hiding | Altered binding specificity | Motif hiding | Composite binding site formation |
| Uncategorised | Rheostatic | Allostery | Avidity-sensing |
| Physicochemical compatibility | Pre-translational | Competition |
| Motif | Start | End | Switch Type | Switch Subtype | Switch Description | Information |
Ataxin-1 - ATXN1 - Homo sapiens | |||||||
| LIG_14-3-3_1 | 772 | 777 | Binary | Physicochemical compatibility | Phosphorylation of S775 by RAC-alpha serine/threonine-protein kinase (AKT1) in the 14-3-3-binding motif of Ataxin-1 (ATXN1) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||
| LIG_14-3-3_1 | 772 | 777 | Specificity | Altered binding specificity | Phosphorylation of S775 switches binding specificity of Ataxin-1 (ATXN1) from the splicing factor Splicing factor U2AF 65 kDa subunit (U2AF2) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). While association with the spliceosome protects ATXN1 from self-association, its phosphorylation-dependent recruitment to 14-3-3 proteins (e.g. YWHAZ) might result in aggregation. | ||
Bcl2 antagonist of cell death - Bad - Rattus norvegicus | |||||||
| LIG_14-3-3_1 | 134 | 139 | Binary | Physicochemical compatibility | Phosphorylation of S137 by RAC-alpha serine/threonine-protein kinase (Akt1) in the 14-3-3-binding motif of Bcl2 antagonist of cell death (Bad) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad). | ||
Bcl2 antagonist of cell death - Bad - Mus musculus | |||||||
| LIG_14-3-3_1 | 133 | 138 | Binary | Physicochemical compatibility | Phosphorylation of S136 in Bcl2 antagonist of cell death (Bad) by RAC-alpha serine/threonine-protein kinase (Akt1) in response to survival and growth signals such as Interleukin-3 (Il3) induces binding to 14-3-3 protein theta (Ywhaq). Binding of 14-3-3 protein theta (Ywhaq) results in dissociation of Bcl2 antagonist of cell death (Bad) from Bcl-2-like protein 1 (Bcl2l1), and thereby inhibits the pro-apoptotic activity of Bcl2 antagonist of cell death (Bad) by allowing liberated Bcl-2-like protein 1 (Bcl2l1) to exert its anti-apoptotic effect on pro-apoptotic proteins like Apoptosis regulator BAX (Bax). | ||
Cyclin-dependent kinase inhibitor 1B - CDKN1B - Homo sapiens | |||||||
| LIG_14-3-3_3 | 154 | 159 | Specificity | Motif hiding | Phosphorylation of a 14-3-3-binding motif in the NLS of Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) induces binding of 14-3-3 protein gamma (YWHAG), which hides the NLS and prevents binding to Importin subunit alpha-1 (KPNA1), thereby mediating cytoplasmic retention of Cyclin-dependent kinase inhibitor 1B (CDKN1B). Binding of 14-3-3 dimer involves an additional C-terminal 14-3-3-binding motif (see switch details). | ||
| LIG_14-3-3_3 | 154 | 159 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | |||
| LIG_14-3-3_3 | 193 | 198 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Cyclin-dependent kinase inhibitor 1B (CDKN1B) by RAC-alpha serine/threonine-protein kinase (AKT1) and ribosomal protein S6 kinases (Ribosomal protein S6 kinase alpha-1 (RPS6KA1), Ribosomal protein S6 kinase alpha-3 (RPS6KA3)) induces binding of 14-3-3 dimer. Binding of 14-3-3 results in cytoplasmic localisation of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (see switch details), thereby alleviating Cyclin-dependent kinase inhibitor 1B (CDKN1B)-mediated inhibition of cyclin-dependent kinases and cell cycle progression. | |||
Disintegrin and metalloproteinase domain-containing protein 22 - ADAM22 - Homo sapiens | |||||||
| LIG_14-3-3_3 | 831 854 | 836 859 | Specificity | Motif hiding | Phosphorylation-induced binding of dimeric 14-3-3 protein beta/alpha (YWHAB) to Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) blocks ER retention motifs in Disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) and regulates transport of this protein to the membrane. | ||
Dual specificity testis-specific protein kinase 1 - Tesk1 - Rattus norvegicus | |||||||
| LIG_14-3-3_2 | 435 | 441 | Binary | Physicochemical compatibility | Phosphorylation of S439 in the 14-3-3-binding motif of Dual specificity testis-specific protein kinase 1 (Tesk1) induces binding to the 14-3-3 protein beta/alpha (Ywhab) protein. This interaction inhibits the kinase activity of Dual specificity testis-specific protein kinase 1 (Tesk1). | ||
E3 ubiquitin-protein ligase NEDD4-like - NEDD4L - Homo sapiens | |||||||
| LIG_14-3-3_1 | 465 | 470 | Specificity | Domain hiding | Phosphorylation of Isoform Nedd4-2a of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) by Serine/threonine-protein kinase Sgk1 (SGK1) induces binding to 14-3-3 protein eta (YWHAH). This inhibits (whether allosterically or sterically is not known) interactions of NEDD4L via its WW domains with the PY motif in Amiloride-sensitive sodium channel subunit gamma (SCNN1G) (ENaC). As a result, ENaC does not get degraded and ENaC-mediated Na+ currents increase. | ||
Forkhead box protein O3 - FOXO3 - Homo sapiens | |||||||
| LIG_14-3-3_3 | 250 | 255 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3). | |||
| LIG_14-3-3_3 | 29 | 34 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Forkhead box protein O3 (FOXO3) by RAC-alpha serine/threonine-protein kinase (AKT1) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). This interaction results in cytoplasmic retention and inactivation of Forkhead box protein O3 (FOXO3). | |||
Forkhead box protein O4 - FOXO4 - Homo sapiens | |||||||
| LIG_14-3-3_2 | 193 | 199 | Binary | Physicochemical compatibility | Phosphorylation of S197 by in the 14-3-3-binding motif of Forkhead box protein O4 (FOXO4) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||
| LIG_14-3-3_1 | 29 | 34 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding. | |||
| LIG_14-3-3_2 | 193 | 199 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Foxo4 by PKB induces binding of 14-3-3 dimer. In the nucleus, this blocks binding to DNA, while in the cytoplasm it blocks reimport of Foxo4 into the nucleus by blocking its Nuclear Localisation Signal (NLS). Since binding of 14-3-3 to a single motif occurs with an affinity similar to the affinity of Foxo4 for DNA, multivalent binding of 14-3-3 dimer is required for efficient inhibition of DNA binding. | |||
G-protein coupled receptor 15 - GPR15 - Homo sapiens | |||||||
| LIG_14-3-3_4 | 356 | 360 | Specificity | Motif hiding | Phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB) promotes cell surface expression of G-protein coupled receptor 15 (GPR15) by releasing the receptor from the ER retrieval/retention pathway that is mediated by the interaction of its ER retention motif with Coatomer subunit beta (COPB1). | ||
HLA class II histocompatibility antigen gamma chain - CD74 - Homo sapiens | |||||||
| LIG_14-3-3_3 | 5 | 10 | Specificity | Motif hiding | The basic ER retention motif of HLA class II histocompatibility antigen gamma chain (CD74) is blocked from binding to Coatomer subunit beta (COPB1) by phosphorylation-induced binding of 14-3-3 protein beta/alpha (YWHAB), regulating its release from the ER and trafficking to the plasma membrane. | ||
Histone deacetylase 4 - HDAC4 - Homo sapiens | |||||||
| LIG_14-3-3_3 | 629 | 634 | Binary | Physicochemical compatibility | Phosphorylation of S632 in the 14-3-3-binding motif of Histone deacetylase 4 (HDAC4) induces binding to the 14-3-3 protein beta/alpha (YWHAB) protein. This interaction sequesters Histone deacetylase 4 (HDAC4) in the cytoplasm, thereby inhibiting their transcription repression activity. | ||
Huntingtin-associated protein 1 - Hap1 - Rattus norvegicus | |||||||
| LIG_14-3-3_4 | 594 | 598 | Binary | Pre‑translational | Alternative splicing removes the 14-3-3-binding motif of Isoform Short of Huntingtin-associated protein 1 (Hap1), abrogating binding to 14-3-3 protein zeta/delta (Ywhaz). The association of HAP1A (Isoform Short of Huntingtin-associated protein 1 (Hap1)) with 14-3-3 protein zeta/delta (Ywhaz) inhibits binding of the splice variant to members of the kinesin light chain family and diminishes trafficking of Hap1 to neural processes and neurite tips. The result is a decrease in neurite outgrowth. | ||
Insulin receptor substrate 1 - IRS1 - Homo sapiens | |||||||
| LIG_14-3-3_3 | 371 | 376 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE). | |||
| LIG_14-3-3_3 | 638 | 643 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Insulin receptor substrate 1 (IRS1) induces high-avidity binding to dimeric 14-3-3 protein epsilon (YWHAE). | |||
Integrin beta-2 - ITGB2 - Homo sapiens | |||||||
| LIG_14-3-3_3 | 755 | 760 | Specificity | Altered binding specificity | Phosphorylation of T758 in Integrin beta-2 (ITGB2) switches the specificity of ITGB2 from Filamin-A (FLNA) to 14-3-3 proteins (e.g. 14-3-3 protein zeta/delta (YWHAZ)). | ||
Kinase suppressor of Ras 1 - Ksr1 - Mus musculus | |||||||
| LIG_14-3-3_3 | 294 | 299 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors. | |||
| LIG_14-3-3_3 | 389 | 394 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Kinase suppressor of Ras 1 (Ksr1) by Q03141 induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (Ywhab). This interaction prevents Kinase suppressor of Ras 1 (Ksr1) to localise to the membrane where it is involved in activation of MAP kinases by Q99N57 in response to growth factors. | |||
M-phase inducer phosphatase 2 - CDC25B - Homo sapiens | |||||||
| LIG_14-3-3_3 | 320 | 325 | Binary | Physicochemical compatibility | Phosphorylation of S321 in the 14-3-3-binding motif of M-phase inducer phosphatase 2 (CDC25B) by Cyclin-dependent kinase 1 (CDK1) during mitosis abolishes binding of the motif, phosphorylated at S323, to 14-3-3 protein beta/alpha (YWHAB), thereby maintaining active Cdc25B. | ||
M-phase inducer phosphatase 3 - CDC25C - Homo sapiens | |||||||
| LIG_14-3-3_3 | 213 | 218 | Binary | Physicochemical compatibility | Phosphorylation of S216 in a 14-3-3-binding motif of M-phase inducer phosphatase 3 (CDC25C) by Serine/threonine-protein kinase Chk1 (CHEK1) induces binding to 14-3-3 protein beta/alpha (YWHAB), which negatively regulates M-phase inducer phosphatase 3 (CDC25C). | ||
Meiosis protein mei2 - mei2 - Schizosaccharomyces pombe (strain 972 / ATCC 24843) | |||||||
| LIG_14-3-3_1;ELM | 435 523 | 440 529 | Specificity | Domain hiding | Binding of meiRNA meiotic non-coding RNA (meiRNA) to the RRM domains of Meiosis protein mei2 (mei2) is essential for promotion of premeiotic DNA synthesis and meiosis I and is blocked by Pat1-mediated phosphorylation-induced binding of the 14-3-3 protein DNA damage checkpoint protein rad24 (rad24) to 2 14-3-3 binding motifs in mei2 | ||
| LIG_14-3-3_1 | 435 | 440 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Meiosis protein mei2 (mei2) by Negative regulator of sexual conjugation and meiosis (ran1) induces high-avidity binding to dimeric DNA damage checkpoint protein rad24 (rad24), with pT527 being the high-affinity interaction site. | |||
| LIG_14-3-3_2 | 523 | 529 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Meiosis protein mei2 (mei2) by Negative regulator of sexual conjugation and meiosis (ran1) induces high-avidity binding to dimeric DNA damage checkpoint protein rad24 (rad24), with pT527 being the high-affinity interaction site. | |||
Middle T antigen - - Murine polyomavirus (strain 3) | |||||||
| LIG_14-3-3_1 | 254 | 259 | Binary | Physicochemical compatibility | Phosphorylation of S257 in the 14-3-3-binding motif of Middle T antigen induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||
Mitogen-activated protein kinase kinase kinase 5 - MAP3K5 - Homo sapiens | |||||||
| LIG_14-3-3_1 | 963 | 968 | Binary | Physicochemical compatibility | Phosphorylation of S966 in the 14-3-3-binding motif of Mitogen-activated protein kinase kinase kinase 5 (MAP3K5) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. This interaction inhibits the pro-apoptotic activity of Mitogen-activated protein kinase kinase kinase 5 (MAP3K5). | ||
Protein Mdm4 - MDM4 - Homo sapiens | |||||||
| LIG_14-3-3_1 | 364 | 369 | Avidity‑sensing | Optimal binding of 14-3-3 dimer to Hdmx in response to DNA damage requires phosphorylation of two 14-3-3-binding motifs by Chk2 kinase. Binding of 14-3-3 dimer is involved in inactivation of Hdmx, a negative regulator of p53, in response to DNA damage. | |||
| LIG_14-3-3_3 | 339 | 344 | Avidity‑sensing | Optimal binding of 14-3-3 dimer to Hdmx in response to DNA damage requires phosphorylation of two 14-3-3-binding motifs by Chk2 kinase. Binding of 14-3-3 dimer is involved in inactivation of Hdmx, a negative regulator of p53, in response to DNA damage. | |||
Protein kinase C epsilon type - PRKCE - Homo sapiens | |||||||
| LIG_14-3-3_3 | 343 | 348 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Protein kinase C epsilon type (PRKCE) induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ). | |||
| LIG_14-3-3_3 | 365 | 370 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Protein kinase C epsilon type (PRKCE) induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ). | |||
RAF proto-oncogene serine/threonine-protein kinase - RAF1 - Homo sapiens | |||||||
| LIG_14-3-3_1 | 256 | 261 | Binary | Physicochemical compatibility | Phosphorylation of S257 in the 14-3-3-binding motif of RAF proto-oncogene serine/threonine-protein kinase (RAF1) abolishes binding of the motif, phosphorylated at S259, to 14-3-3 protein zeta/delta (YWHAZ). | ||
| LIG_14-3-3_1 | 256 | 261 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation. | |||
| LIG_14-3-3_1 | 618 | 623 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in RAF proto-oncogene serine/threonine-protein kinase (RAF1) in response to growth factors induces high-avidity binding to dimeric 14-3-3 protein zeta/delta (YWHAZ), with pS621 being the high-affinity interaction site. This interaction locks RAF proto-oncogene serine/threonine-protein kinase (RAF1) in an inhibited conformation. | |||
Serine/threonine-protein kinase RIM15 - RIM15 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) | |||||||
| LIG_14-3-3_3 | 1072 | 1077 | Binary | Physicochemical compatibility | Phosphorylation of T1075 in the 14-3-3-binding motif of Serine/threonine-protein kinase RIM15 (RIM15) induces binding to the Protein BMH2 (BMH2) protein. This interaction sequesters Serine/threonine-protein kinase RIM15 (RIM15) in the cytoplasm, thereby inhibiting its function. | ||
Slowpoke-binding protein - Slob - Drosophila melanogaster | |||||||
| LIG_14-3-3_3 | 51 | 56 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Slowpoke-binding protein (Slob) by Calcium/calmodulin-dependent protein kinase type II alpha chain (CaMKII) induces high-avidity binding to dimeric 14-3-3 protein zeta (14-3-3zeta). This interaction recruits 14-3-3 protein zeta (14-3-3zeta) to Calcium-activated potassium channel slowpoke (slo) in the presynapse of neuromuscular junctions. | |||
| LIG_14-3-3_3 | 76 | 81 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Slowpoke-binding protein (Slob) by Calcium/calmodulin-dependent protein kinase type II alpha chain (CaMKII) induces high-avidity binding to dimeric 14-3-3 protein zeta (14-3-3zeta). This interaction recruits 14-3-3 protein zeta (14-3-3zeta) to Calcium-activated potassium channel slowpoke (slo) in the presynapse of neuromuscular junctions. | |||
| LIG_14-3-3_3 | 76 | 81 | Binary | Pre‑translational | Alternative splicing removes the 14-3-3-binding motif of Slowpoke-binding protein (Slob), abrogating binding to 14-3-3 family. Another 14-3-3 motif exists in this protein (50-RSNS-54) that is not altered by Alternative splicing. The removal of this motif therefore decreases the avidity of the interaction with 14-3-3 proteins. | ||
Sodium/calcium exchanger 1 - SLC8A1 - Homo sapiens | |||||||
| LIG_14-3-3_2 | 388 | 394 | Binary | Physicochemical compatibility | Phosphorylation of S392 in the 14-3-3-binding motif of Sodium/calcium exchanger 1 (SLC8A1) induces binding to the 14-3-3 protein epsilon (YWHAE) protein. This interaction inhibits the activity of Sodium/calcium exchanger 1 (SLC8A1). | ||
Transcription factor p65 - RELA - Homo sapiens | |||||||
| LIG_14-3-3_2 | 41 | 47 | Binary | Physicochemical compatibility | Phosphorylation of S45 by in the 14-3-3-binding motif of Transcription factor p65 (RELA) induces binding to the 14-3-3 protein eta (YWHAH) protein. | ||
Tyrosine-protein phosphatase non-receptor type 3 - Ptpn3 - Mus musculus | |||||||
| LIG_14-3-3_2 | 355 | 361 | Binary | Physicochemical compatibility | Phosphorylation of S359 in the 14-3-3-binding motif of Tyrosine-protein phosphatase non-receptor type 3 (Ptpn3) induces binding to the 14-3-3 protein beta/alpha (Ywhab) protein. | ||
Tyrosine-protein phosphatase non-receptor type 3 - PTPN3 - Homo sapiens | |||||||
| LIG_14-3-3_3 | 356 | 361 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). | |||
| LIG_14-3-3_3 | 832 | 837 | Avidity‑sensing | Phosphorylation of two 14-3-3-binding motifs in Tyrosine-protein phosphatase non-receptor type 3 (PTPN3) induces high-avidity binding to dimeric 14-3-3 protein beta/alpha (YWHAB). | |||
WW domain-containing transcription regulator protein 1 - WWTR1 - Homo sapiens | |||||||
| LIG_14-3-3_1 | 86 | 91 | Binary | Physicochemical compatibility | Phosphorylation of S89 in the 14-3-3-binding motif of WW domain-containing transcription regulator protein 1 (WWTR1) induces binding to 14-3-3 protein epsilon (YWHAE), retaining phosphorylated WWTR1 in the cytosol, negatively regulating its function. | ||
Yorkie homolog - Yap1 - Mus musculus | |||||||
| LIG_14-3-3_1 | 109 | 114 | Binary | Physicochemical compatibility | Phosphorylation of S112 in the 14-3-3 binding motif of Yorkie homolog (Yap1) induces binding to the 14-3-3 protein epsilon (Ywhae) protein. 14-3-3 retains phosphorylated YAP in the cytosol, negatively regulating its function. | ||
cGMP-inhibited 3',5'-cyclic phosphodiesterase A - PDE3A - Homo sapiens | |||||||
| LIG_14-3-3_2 | 424 | 430 | Binary | Physicochemical compatibility | Phosphorylation of S428 by in the 14-3-3-binding motif of cGMP-inhibited 3',5'-cyclic phosphodiesterase A (PDE3A) induces binding to the 14-3-3 protein zeta/delta (YWHAZ) protein. | ||