Domain hiding |   Altered binding specificity |   Motif hiding |   Composite binding site formation |
  Uncategorised |   Rheostatic |   Allostery |   Avidity-sensing |
  Physicochemical compatibility |   Pre-translational |   Competition |
Protein | Start | End | Switch Type | Switch Subtype | Switch Description | Information |
LIG_14-3-3_1 - Mode 1 interacting phospho-motif for 14-3-3 proteins with key conservation RxxSxP. | |||||||
BAD_RAT | 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). | ||
MT_POVM3 | 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. | ||
ATX1_HUMAN | 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. | ||
M3K5_HUMAN | 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). | ||
RAF1_HUMAN | 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). | ||
YAP1_MOUSE | 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. | ||
ATX1_HUMAN | 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. | ||
NED4L_HUMAN | 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. | ||
MEI2_SCHPO | 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 | ||
RAF1_HUMAN | 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. | |||
RAF1_HUMAN | 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. | |||
MEI2_SCHPO | 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. | |||
WWTR1_HUMAN | 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. | ||
MDM4_HUMAN | 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. | |||
FOXO4_HUMAN | 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. | |||
BAD_MOUSE | 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). | ||
LIG_14-3-3_2 - Longer mode 2 interacting phospho-motif for 14-3-3 proteins with key conservation RxxxS#p. | |||||||
MEI2_SCHPO | 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 |