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Group by :Switch typeMotif classProteinEnzymePathway            Group Index    Colouring Info              Filtered: UNIPROT:P31749 (14 hits) x
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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

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Type: Avidity‑sensing Subtype: Type: Binary Subtype: Physicochemical compatibilityType: Specificity Subtype: Motif hiding


ProteinMotifStartEndSwitch descriptionInformation

Type: Specificity Subtype: Motif hiding
Motif hiding occurs when there is a large difference in intrinsic affinity of overlapping or adjacent motifs for their respective binding partners, or a large difference in the local abundance of these partners. Binding of an effector to one motif sterically masks the overlapping or adjacent motif, thereby precluding it from binding. Binding of the masking molecule can be PTM-dependent or -independent.
CDN1B_HUMANLIG_14-3-3_3154159Phosphorylation 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).
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Type: Avidity‑sensing Subtype:
Multiple low-affinity interactions give rise to high-avidity interactions that have increased binding strength, with more than additive affinity.
RAF1_HUMANLIG_14-3-3_1256261Phosphorylation 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.
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FOXO3_HUMANLIG_14-3-3_3250255Phosphorylation 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).
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FOXO3_HUMANLIG_14-3-3_32934Phosphorylation 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).
details
FOXO4_HUMANLIG_14-3-3_12934Phosphorylation 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.
details
FOXO4_HUMANLIG_14-3-3_2193199Phosphorylation 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.
details
CDN1B_HUMANLIG_14-3-3_3154159Phosphorylation 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.
details
CDN1B_HUMANLIG_14-3-3_3193198Phosphorylation 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.
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Type: Binary Subtype: Physicochemical compatibility
PTM of a residue in a motif or in its flanking regions alters the physicochemical and/or structural compatibility of the motif with its binding partner. This can either induce or enhance an interaction, or result in inhibition or even abrogation of an interaction.
AKT1_HUMANDOC_AGCK_PIF_1469474Phosphorylation of S473 in the PIF motif of RAC-alpha serine/threonine-protein kinase (AKT1) by Serine/threonine-protein kinase mTOR (MTOR) (as part of mTORC2 complex) induces intramolecular interaction with the PIF-binding pocket, resulting in cis-activation of RAC-alpha serine/threonine-protein kinase (AKT1). Dephosphorylation of the PIF motif by PHLPP1/2 (PHLPP1 for Akt2/3 and PHLPP2 for Akt1/3) results in reduced Akt activity, probably by disrupting the interaction with the Akt PIF pocket and thus cis-activation.
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AKT1_HUMANDOC_WW_Pin1_4447452Phosphorylation of T450 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
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AKT1_HUMANDOC_WW_Pin1_48994Phosphorylation of T92 in the Pin1-binding motif of RAC-alpha serine/threonine-protein kinase (AKT1) induces binding to the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) protein.
details
ATX1_HUMANLIG_14-3-3_1772777Phosphorylation 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.
details
FOXO4_HUMANLIG_14-3-3_2193199Phosphorylation 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.
details
CDN1A_HUMANLIG_PCNA_PIPBox_1144153Phosphorylation of T145 in the PCNA-binding motif of Cyclin-dependent kinase inhibitor 1 (CDKN1A) by RAC-alpha serine/threonine-protein kinase (AKT1) inhibits binding to Proliferating cell nuclear antigen (PCNA). As a result, Cyclin-dependent kinase inhibitor 1 (CDKN1A) no longer inhibits Proliferating cell nuclear antigen (PCNA) and blocking of DNA replication is relieved.
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