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Ca+2/calmodulin-dependent protein kinase 4 (CaM kinase 4, CAM kinase-GR, CAMK4)

Function: - Ca+2/calmodulin-dependent protein kinase - role in Ca+2-triggered signaling cascade - may be involved in transcriptional regulation - may be involved in regulation of microtubule dynamics - in vitro, phosphorylates CREB1, CREBBP, PRM2, MEF2A, MEF2D & STMN1/OP18 - may be involved in spermatogenesis - may play a role in the consolidation/retention of hippocampus-dependent long-term memory (putative) - activated by Ca+2/calmodulin - binding of calmodulin may releave intrasteric autoinhibition - must be phosphorylated to be maximally active - phosphorylated by CAMKK1 or CAMKK2 - autophosphorylation of the N-terminus is required for full activation - in part, activity is independent on Ca+2/calmodulin & autophosphorylation of Ser-336 allows to switch to a Ca+2/calmodulin-independent state (putative) - probably inactivated protein phosphatase 2A - dephosphorylated by protein phosphatase 2A, probably on Thr-200 - autophosphorylated & phosphorylated by CAMKK1 & CAMKK2 (putative) Structure: - monomer (putative) - interacts with serine/threonine protein phosphatase 2A catalytic subunit, PPP2CA or PPP2CB - interaction with PP2CA or PP2CB is mutually exclusive with binding to Ca+2/calmodulin - belongs to the protein kinase superfamily, CAMK Ser/Thr protein kinase family. CaMK subfamily - contains 1 protein kinase domain Compartment: - cytoplasm, nucleus - substantial localization in certain neuronal nuclei - in spermatids associated with chromatin & nuclear matrix Expression: restricted to brain in rat; appears after birth Pathology: expressed in epithelial ovarian cancer tissue

General

Ca+2/calmodulin-dependent protein kinase (CaM kinase)

Properties

SIZE: entity length = 473 aa MW = 52 kD COMPARTMENT: cytoplasm cell nucleus STATE: active state MOTIF: Ser phosphorylation site {S12} Ser phosphorylation site {S13} kinase domain SITE: 46-300 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 52-60 ATP-binding site NAME: ATP-binding site SITE: 75-75 aspartate residue {D164} Thr phosphorylation site {T200} Autoinhibitory {301-340} binding site SITE: 322-341 FOR-BINDING-OF: calmodulin MOTIF: Ser phosphorylation site {S336} Ser phosphorylation site {S341} Ser phosphorylation site {S360}

Database Correlations

OMIM 114080 UniProt Q16566 Pfam PF00069 Entrez Gene 814 Kegg hsa:814 ENZYME 2.7.11.17

References

  1. OMIM :accession 114080
  2. UniProt :accession Q16566