CaM kinase 2 selections

calcium/calmodulin dependent protein kinase 2

Function: 1) prominent kinase in the central nervous system 2) the major protein of post-synaptic densities 3) may function in long-term potentiation (LTP) & neurotransmitter release 4) member of the NMDA receptor (NMDAR) signaling complex in excitatory synapses 5) may regulate NMDAR-dependent potentiation of the AMPAR & synaptic plasticity (putative) CaM kinase II substrates include 14-3-3 beta Ser60, Ser65 AMPA receptors Adenylyl Cyclase olfactory AC3 Ser1076 Calpain II RGS*TAGGCR Calponin Ser175 cAMP phosphodiesterase CDC25C Choline Acetyl Transferase CPI 17 Ser 130, Thr 38 Chromogranin A (bovine) CREB Ser142 Dihydropteridine reductase Dystrophin eNOS Ser1117 ErbB2 Thr1172 FLIP GABA A receptor, beta 1 Ser384, Ser409 GABA A receptor, gamma 2 Ser348, Ser350 GluR1 AMPA receptor subunit Ser831, Ser845 Histamine H1 receptor Heat Shock Factor 1 Ser230 Homer 1b Insulin receptor substrate 58kDA Internexin alpha Kv1.4 channel MAP-2 Myogenic factor SRF Ser103, Thr160 D-Myo-inositol 1,4,5 3P3 kinase Thr311 Myosin non muscle form Thr1940 NBP60 Neurofilament L Ser57 NMDA receptor subunit NR2B Ser1303 nNOS Ser847 PSD95/SAP90 PSD95 associated protein PEA-15 Ser116 Phosducin Ser54, Ser73 Phospholamban Thr17 Phospholipase C beta 3 Ser537 Rabphilin 3A Ser34, Thr205,Thr209 Raf-1 RAP (receptor assoc. protein) RF-C replication factor C large subunit Ribosomal protein S18 Ryanodine Receptor (cardiac) Ser2809 & others SAP97 Sepiapterin reductase Stat1 Ser727 Stathmin Ser16 Synapsin 1 Tau Ser262, Ser365 Tiam1 TNF-receptor associated protein TOAD-64 Troponin T Ser190 (bovine) tubulin alpha tubulin beta Tyrosine Hydroxylase Ser19 VAMP/synaptobrevin (SYB) Vanilloid receptor 1 Ser502, Thr 704 Structure: 1) multiple (28) isoforms encoded by four genes: alpha, beta, delta, gamma 2) different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits 3) basic structure of each isoform consists of a) catalytic domain b) autoinhibitory or regulatory domain c) variable segment d) self-association domain Compartment: - cell junction, synapse - presynaptic cell membrane (putative) - postsynaptic lipid rafts (putative) Expression: - highly expressed in brain, constituting 1-2% of total protein; alpha & beta subunits are predominant

Interactions

molecular events

General

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

Properties

SIZE: MW = 600 kD STATE: active state SUBUNITS: CaM kinase 2-alpha (SEVERAL) STATE: active state MOTIF: kinase domain SITE: 13-271 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 19-27 Tyr phosphorylation site {Y13} Ser phosphorylation site {S25} ATP-binding site NAME: ATP-binding site SITE: 42-42 aspartate residue {D135} Ser phosphorylation site {S275} Thr phosphorylation site {T286} binding site SITE: 290-300 FOR-BINDING-OF: calmodulin BAALC interaction {310-320} Ser phosphorylation site {S333} Thr phosphorylation site {T334} Thr phosphorylation site {T337} CaM kinase 2-beta (SEVERAL) STATE: active state MOTIF: kinase domain SITE: 14-272 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 20-28 Tyr phosphorylation site {Y17} ATP-binding site NAME: ATP-binding site SITE: 43-43 aspartate residue {D136} Thr phosphorylation site {T287} binding site SITE: 291-301 FOR-BINDING-OF: calmodulin Ser phosphorylation site {S315} Ser phosphorylation site {S367} Ser phosphorylation site {S397} MISC-INFO: DISTRIBUTION :REGIONAL BROAD :SUBCELLULAR PARTICULATE cytoplasm SUBSTRATE-SPECIFICITY :RANGE BROAD RECOGNITION-MOTIF :SEQUENCE XRXX[S*]X :REF " - Kemp BE, Pearson RB. Protein kinase recognition sequence motifs. Trends Biochem Sci. 1990 Sep;15(9):342-6. Review. PMID: 2238044"

References

Nestler & Greengard Basic Neurochemistry ch 19 1989
Lisman et al. Nature Reviews Neuroscience 3:175-190, 2002
http://www.kinasource.co.uk/Database/C%20substrates/CaMKII%20substrates.html

Component-of

molecular complex

Components

calcium/calmodulin-dependent protein kinase II alpha (CAMK2A, CAMKA, KIAA0968) calcium/calmodulin-dependent protein kinase II beta (CAMK2B, CAMKB)

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