4c36: Difference between revisions
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{{STRUCTURE_4c36| PDB=4c36 | SCENE= }} | |||
===PKA-S6K1 Chimera with compound 15e (CCT147581) bound=== | |||
{{ABSTRACT_PUBMED_24072592}} | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/KAPCA_BOVIN KAPCA_BOVIN]] Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). [[http://www.uniprot.org/uniprot/IPKA_BOVIN IPKA_BOVIN]] Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains (By similarity). | |||
==About this Structure== | |||
[[4c36]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4C36 OCA]. | |||
==Reference== | |||
<ref group="xtra">PMID:024072592</ref><references group="xtra"/><references/> | |||
[[Category: Bos taurus]] | |||
[[Category: CAMP-dependent protein kinase]] | |||
[[Category: Aherne, G W.]] | |||
[[Category: Barillari, C.]] | |||
[[Category: Boxall, K.]] | |||
[[Category: Burns, S.]] | |||
[[Category: Cano, C.]] | |||
[[Category: Chow, C L.]] | |||
[[Category: Clarke, P A.]] | |||
[[Category: Couty, S.]] | |||
[[Category: Griffin, R J.]] | |||
[[Category: Jones, K.]] | |||
[[Category: Kalusa, A.]] | |||
[[Category: Linardopoulos, S.]] | |||
[[Category: McAndrew, P C.]] | |||
[[Category: Montfort, R L.M van.]] | |||
[[Category: Pickard, L.]] | |||
[[Category: Raynaud, F I.]] | |||
[[Category: Schmitt, J.]] | |||
[[Category: Travers, J.]] | |||
[[Category: Westwood, I M.]] | |||
[[Category: Workman, P.]] | |||
[[Category: Chimera]] | |||
[[Category: S6k1]] | |||
[[Category: Transferase-inhibitor complex]] |
Revision as of 09:28, 10 October 2013
PKA-S6K1 Chimera with compound 15e (CCT147581) boundPKA-S6K1 Chimera with compound 15e (CCT147581) bound
Template:ABSTRACT PUBMED 24072592
FunctionFunction
[KAPCA_BOVIN] Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, TRPC1 and VASP. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). TRPC1 activation by phosphorylation promotes Ca(2+) influx, essential for the increase in permeability induced by thrombin in confluent endothelial monolayers. PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Regulates negatively tight junction (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis. Isoform 2 phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT) (By similarity). [IPKA_BOVIN] Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains (By similarity).
About this StructureAbout this Structure
4c36 is a 2 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Couty S, Westwood IM, Kalusa A, Cano C, Travers J, Boxall K, Chow CL, Burns S, Schmitt J, Pickard L, Barillari C, McAndrew PC, Clarke PA, Linardopoulos S, Griffin RJ, Aherne GW, Raynaud FI, Workman P, Jones K, van Montfort RL. The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design. Oncotarget. 2013 Aug 25. PMID:24072592
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Bos taurus
- CAMP-dependent protein kinase
- Aherne, G W.
- Barillari, C.
- Boxall, K.
- Burns, S.
- Cano, C.
- Chow, C L.
- Clarke, P A.
- Couty, S.
- Griffin, R J.
- Jones, K.
- Kalusa, A.
- Linardopoulos, S.
- McAndrew, P C.
- Montfort, R L.M van.
- Pickard, L.
- Raynaud, F I.
- Schmitt, J.
- Travers, J.
- Westwood, I M.
- Workman, P.
- Chimera
- S6k1
- Transferase-inhibitor complex