ID KCC2A_PONAB Reviewed; 478 AA.
AC Q5RCC4;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 27-MAR-2024, entry version 123.
DE RecName: Full=Calcium/calmodulin-dependent protein kinase type II subunit alpha;
DE Short=CaM kinase II subunit alpha;
DE Short=CaMK-II subunit alpha;
DE EC=2.7.11.17 {ECO:0000250|UniProtKB:Q9UQM7};
GN Name=CAMK2A;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Calcium/calmodulin-dependent protein kinase that functions
CC autonomously after Ca(2+)/calmodulin-binding and autophosphorylation,
CC and is involved in various processes, such as synaptic plasticity,
CC neurotransmitter release and long-term potentiation. Member of the
CC NMDAR signaling complex in excitatory synapses, it regulates NMDAR-
CC dependent potentiation of the AMPAR and therefore excitatory synaptic
CC transmission (By similarity). Regulates dendritic spine development.
CC Also regulates the migration of developing neurons. Phosphorylates the
CC transcription factor FOXO3 to activate its transcriptional activity (By
CC similarity). Phosphorylates the transcription factor ETS1 in response
CC to calcium signaling, thereby decreasing ETS1 affinity for DNA (By
CC similarity). In response to interferon-gamma (IFN-gamma) stimulation,
CC catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling
CC pathway (By similarity). In response to interferon-beta (IFN-beta)
CC stimulation, stimulates the JAK-STAT signaling pathway (By similarity).
CC Acts as a negative regulator of 2-arachidonoylglycerol (2-AG)-mediated
CC synaptic signaling via modulation of DAGLA activity (By similarity).
CC {ECO:0000250|UniProtKB:P11275, ECO:0000250|UniProtKB:P11798,
CC ECO:0000250|UniProtKB:Q9UQM7}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.17;
CC Evidence={ECO:0000250|UniProtKB:Q9UQM7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.17; Evidence={ECO:0000250|UniProtKB:Q9UQM7};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9UQM7};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Binding of
CC calmodulin results in conformational change that relieves intrasteric
CC autoinhibition and allows autophosphorylation of Thr-286 which turns
CC the kinase in a constitutively active form and confers to the kinase a
CC Ca(2+)-independent activity. {ECO:0000250|UniProtKB:Q9UQM7}.
CC -!- SUBUNIT: There are 4 genes encoding calcium/calmodulin-dependent
CC protein kinase type II chains: CAMK2A, CAMK2B, CAMK2G and CAMK2D. The
CC corresponding proteins assemble into homo- or heteromultimeric
CC holoenzymes composed of 12 subunits with two hexameric rings stacked
CC one on top of the other (By similarity). Interacts with BAALC.
CC Interacts with MPDZ. Interacts with SYN1. Interacts with CAMK2N2.
CC Interacts with SYNGAP1. Interacts with SYNPO2 (By similarity).
CC Interacts with SHANK3. Interacts with GRIN2B. Interacts with CACNB2.
CC Interacts with LRRC7. Interacts with GRM5 (By similarity). Interacts
CC with DAGLA (via C-terminal); this interaction is enhanced by
CC autophosphorylation of CAMK2A at Thr-286 (By similarity). Interacts
CC with CAMK2N1; this interaction requires CAMK2A activation by Ca(2+) (By
CC similarity). {ECO:0000250|UniProtKB:P11275,
CC ECO:0000250|UniProtKB:P11798, ECO:0000250|UniProtKB:Q9UQM7}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000250|UniProtKB:P11275}.
CC Postsynaptic density {ECO:0000250|UniProtKB:P11275}. Cell projection,
CC dendritic spine {ECO:0000250|UniProtKB:Q9UQM7}. Cell projection,
CC dendrite {ECO:0000250|UniProtKB:Q9UQM7}. Note=Postsynaptic lipid rafts.
CC {ECO:0000250|UniProtKB:P11275}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=Q5RCC4-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q5RCC4-2; Sequence=VSP_014224;
CC -!- PTM: Autophosphorylation of Thr-286 following activation by
CC Ca(2+)/calmodulin. Phosphorylation of Thr-286 locks the kinase into an
CC activated state. {ECO:0000250|UniProtKB:Q9UQM7}.
CC -!- PTM: Palmitoylated. Probably palmitoylated by ZDHHC3 and ZDHHC7.
CC {ECO:0000250|UniProtKB:P11275}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. CaMK subfamily. {ECO:0000305}.
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DR EMBL; CR858350; CAH90583.1; -; mRNA.
DR RefSeq; NP_001125313.1; NM_001131841.1. [Q5RCC4-2]
DR AlphaFoldDB; Q5RCC4; -.
DR SMR; Q5RCC4; -.
DR STRING; 9601.ENSPPYP00000017843; -.
DR Ensembl; ENSPPYT00000041841.1; ENSPPYP00000027902.1; ENSPPYG00000015946.3. [Q5RCC4-1]
DR Ensembl; ENSPPYT00000059583.1; ENSPPYP00000034104.1; ENSPPYG00000015946.3. [Q5RCC4-2]
DR GeneID; 100172212; -.
DR KEGG; pon:100172212; -.
DR CTD; 815; -.
DR eggNOG; KOG0033; Eukaryota.
DR GeneTree; ENSGT00940000155150; -.
DR HOGENOM; CLU_000288_71_0_1; -.
DR InParanoid; Q5RCC4; -.
DR OrthoDB; 1121238at2759; -.
DR Proteomes; UP000001595; Chromosome 5.
DR GO; GO:0005954; C:calcium- and calmodulin-dependent protein kinase complex; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0035458; P:cellular response to interferon-beta; ISS:UniProtKB.
DR GO; GO:0060996; P:dendritic spine development; ISS:UniProtKB.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; ISS:UniProtKB.
DR GO; GO:1990443; P:peptidyl-threonine autophosphorylation; ISS:UniProtKB.
DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; ISS:UniProtKB.
DR GO; GO:2000124; P:regulation of endocannabinoid signaling pathway; ISS:UniProtKB.
DR GO; GO:2001222; P:regulation of neuron migration; ISS:UniProtKB.
DR CDD; cd14086; STKc_CaMKII; 1.
DR Gene3D; 3.10.450.50; -; 1.
DR Gene3D; 6.10.140.620; -; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR013543; Ca/CaM-dep_prot_kinase-assoc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR032710; NTF2-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24347:SF384; CALCIUM_CALMODULIN-DEPENDENT PROTEIN KINASE TYPE II SUBUNIT ALPHA; 1.
DR PANTHER; PTHR24347; SERINE/THREONINE-PROTEIN KINASE; 1.
DR Pfam; PF08332; CaMKII_AD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54427; NTF2-like; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Calmodulin-binding; Cell projection;
KW Kinase; Lipoprotein; Magnesium; Metal-binding; Nucleotide-binding;
KW Palmitate; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Synapse; Transferase.
FT CHAIN 1..478
FT /note="Calcium/calmodulin-dependent protein kinase type II
FT subunit alpha"
FT /id="PRO_0000086093"
FT DOMAIN 13..271
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 290..300
FT /note="Calmodulin-binding"
FT REGION 310..320
FT /note="Interaction with BAALC"
FT /evidence="ECO:0000250"
FT REGION 314..341
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..341
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 135
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 19..27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 13
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11275"
FT MOD_RES 286
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P11275"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 336
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 337
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT MOD_RES 404
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P11798"
FT VAR_SEQ 328
FT /note="K -> KKRKSSSSVQLM (in isoform B)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_014224"
SQ SEQUENCE 478 AA; 54088 MW; 208143A311BA9262 CRC64;
MATITCTRFT EEYQLFEELG KGAFSVVRRC VKVLAGQEYA AKIINTKKLS ARDHQKLERE
ARICRLLKHP NIVRLHDSIS EEGHHYLIFD LVTGGELFED IVAREYYSEA DASHCIQQIL
EAVLHCHQMG VVHRDLKPEN LLLASKLKGA AVKLADFGLA IEVEGEQQAW FGFAGTPGYL
SPEVLRKDPY GKPVDLWACG VILYILLVGY PPFWDEDQHR LYQQIKAGAY DFPSPEWDTV
TPEAKDLINK MLTINPSKRI TAAEALKHPW ISHRSTVASC MHRQETVDCL KKFNARRKLK
GAILTTMLAT RNFSGGKSGG NKKSDGVKES SESTNTTIED EDTKVRKQEI IKVTEQLIEA
ISNGDFESYT KMCDPGMTAF EPEALGNLVE GLDFHRFYFE NLWSRNSKPV HTTILNPHIH
LMGDESACIA YIRITQYLDA GGIPRTAQSE ETRVWHRRDG KWQIVHFHRS GAPSVLPH
//
