Calcium/calmodulin-dependent protein kinase type II alpha chain

Preferred order of sections

Names and origin

Protein names

Recommended name:
Calcium/calmodulin-dependent protein kinase type II alpha chain
Short name=CaM-kinase II alpha chain
EC=2.7.11.17

Gene names

Name:	CaMKII
Synonyms:	CaM
ORF Names:	CG18069

Organism

Drosophila melanogaster (Fruit fly)

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	530 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	A key regulator of plasticity in synaptic physiology and behavior, alterations in its activity produce pleiotrophic effects that involve synaptic transmission and development as well as various aspects of behavior. Directly modulates eag potassium channels. Ref.6 Ref.7
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	CASK plays a role in regulation of CaMKII autophosphorylation. When complexed with CASK and in the presence Ca[2+]/CaM, autophosphorylation of Thr-287 causes constitutive activation of the kinase. In the absence of Ca[2+]/CaM, autophosphorylation of Thr-306 causes inactivation of the kinase. Ref.8
Subunit structure	Interacts with CASK. Ref.7
Tissue specificity	Expressed at a high level in the central nervous system during the late embryonic stage. In adults, expression is more abundant in the head than in the body. Ref.1 Ref.2
Post-translational modification	Autophosphorylation at Thr-287 is independent of autophosphorylation at Thr-306 and Thr-307.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	long-term memory Inferred from mutant phenotype. Source: FlyBase male courtship behavior Inferred from mutant phenotype. Source: FlyBase neuromuscular junction development Non-traceable author statement. Source: FlyBase regulation of filopodium assembly Inferred from mutant phenotype. Source: FlyBase synaptic transmission Inferred from mutant phenotype. Source: FlyBase
Cellular component	axon Inferred from direct assay. Source: FlyBase calcium- and calmodulin-dependent protein kinase complex Traceable author statement. Source: UniProtKB dendrite Inferred from direct assay. Source: FlyBase postsynaptic membrane Inferred from direct assay. Source: FlyBase presynaptic active zone Inferred from direct assay. Source: FlyBase
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin binding Traceable author statement. Source: FlyBase calmodulin-dependent protein kinase activity Inferred from direct assay Ref.2. Source: FlyBase
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CASK	Q24210	5	EBI-124595,EBI-214423

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q00168-1) Also known as: 530aa; D; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q00168-2) Also known as: 516aa; G; The sequence of this isoform differs from the canonical sequence as follows: 366-387: DIRILCPAKTYQQNIGNSQCSS → VNLFTNKA

Isoform 3 (identifier: Q00168-3) Also known as: 509aa; B; E; The sequence of this isoform differs from the canonical sequence as follows: 366-387: DIRILCPAKTYQQNIGNSQCSS → A

Isoform 4 (identifier: Q00168-4) Also known as: 490aa; A; C; The sequence of this isoform differs from the canonical sequence as follows: 347-386: Missing. 387-387: S → A

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 530

530

Calcium/calmodulin-dependent protein kinase type II alpha chain

PRO_0000086095

Regions

Domain

12 – 272

261

Protein kinase

Nucleotide binding

20 – 28

9

ATP By similarity

Region

291 – 301

11

Calmodulin-binding

Sites

Active site

136

1

Proton acceptor By similarity

Binding site

43

1

ATP By similarity

Amino acid modifications

Modified residue

287

1

Phosphothreonine; by autocatalysis Ref.7 Ref.8

Modified residue

306

1

Phosphothreonine; by autocatalysis Ref.7

Modified residue

307

1

Phosphothreonine; by autocatalysis Ref.7

Modified residue

327

1

Phosphoserine Ref.9

Natural variations

Alternative sequence

347 – 386

40

Missing in isoform 4.

VSP_050261

Alternative sequence

366 – 387

22

DIRIL…SQCSS → VNLFTNKA in isoform 2.

VSP_050262

Alternative sequence

366 – 387

22

DIRIL…SQCSS → A in isoform 3.

VSP_050263

Alternative sequence

387

1

S → A in isoform 4.

VSP_050264

Experimental info

Mutagenesis

306

1

T → A: Fails to interact with CASK, catalytically active but fails to autophosphorylate, when associated with A-307. Ref.7

Mutagenesis

306

1

T → D: Fails to interact with CASK, kinase inactive, when associated with D-307. Ref.7

Mutagenesis

306

1

T → S: Fails to interact with CASK, catalytically active and can autophosphorylate, when associated with S-307. Ref.7

Mutagenesis

307

1

T → A: Fails to interact with CASK, catalytically active but fails to autophosphorylate, when associated with A-306. Ref.7

Mutagenesis

307

1

T → D: Fails to interact with CASK, kinase inactive, when associated with D-306. Ref.7

Mutagenesis

307

1

T → S: Fails to interact with CASK, catalytically active and can autophosphorylate, when associated with S-306. Ref.7

Sequence conflict

388

1

A → S in AAB28246. Ref.2

Sequence conflict

388

1

A → S in AAB28248. Ref.2

Sequences

Sequence		Length	Mass (Da)
Isoform 1 (530aa) (D) [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 4F3D83582ABDFCFD Show »	FASTA	530	59,920
10 20 30 40 50 60 MAAPAACTRF SDNYDIKEEL GKGAFSIVKR CVQKSTGFEF AAKIINTKKL TARDFQKLER 70 80 90 100 110 120 EARICRKLHH PNIVRLHDSI QEENYHYLVF DLVTGGELFE DIVAREFYSE ADASHCIQQI 130 140 150 160 170 180 LESVNHCHQN GVVHRDLKPE NLLLASKAKG AAVKLADFGL AIEVQGDHQA WFGFAGTPGY 190 200 210 220 230 240 LSPEVLKKEP YGKSVDIWAC GVILYILLVG YPPFWDEDQH RLYSQIKAGA YDYPSPEWDT 250 260 270 280 290 300 VTPEAKNLIN QMLTVNPNKR ITAAEALKHP WICQRERVAS VVHRQETVDC LKKFNARRKL 310 320 330 340 350 360 KGAILTTMLA TRNFSSRSMI TKKGEGSQVK ESTDSSSTTL EDDDIKEDKK GTVDRSTTVV 370 380 390 400 410 420 SKEPEDIRIL CPAKTYQQNI GNSQCSSARR QEIIKITEQL IEAINSGDFD GYTKICDPHL 430 440 450 460 470 480 TAFEPEALGN LVEGIDFHKF YFENVLGKNC KAINTTILNP HVHLLGEEAA CIAYVRLTQY 490 500 510 520 530 IDKQGHAHTH QSEETRVWHK RDNKWQNVHF HRSASAKISG ATTFDFIPQK « Hide
Isoform 2 (516aa) (G) [UniParc]. Checksum: 16D891160BEC6FF2 Show »	FASTA	516	58,386
10 20 30 40 50 60 MAAPAACTRF SDNYDIKEEL GKGAFSIVKR CVQKSTGFEF AAKIINTKKL TARDFQKLER 70 80 90 100 110 120 EARICRKLHH PNIVRLHDSI QEENYHYLVF DLVTGGELFE DIVAREFYSE ADASHCIQQI 130 140 150 160 170 180 LESVNHCHQN GVVHRDLKPE NLLLASKAKG AAVKLADFGL AIEVQGDHQA WFGFAGTPGY 190 200 210 220 230 240 LSPEVLKKEP YGKSVDIWAC GVILYILLVG YPPFWDEDQH RLYSQIKAGA YDYPSPEWDT 250 260 270 280 290 300 VTPEAKNLIN QMLTVNPNKR ITAAEALKHP WICQRERVAS VVHRQETVDC LKKFNARRKL 310 320 330 340 350 360 KGAILTTMLA TRNFSSRSMI TKKGEGSQVK ESTDSSSTTL EDDDIKEDKK GTVDRSTTVV 370 380 390 400 410 420 SKEPEVNLFT NKAARRQEII KITEQLIEAI NSGDFDGYTK ICDPHLTAFE PEALGNLVEG 430 440 450 460 470 480 IDFHKFYFEN VLGKNCKAIN TTILNPHVHL LGEEAACIAY VRLTQYIDKQ GHAHTHQSEE 490 500 510 TRVWHKRDNK WQNVHFHRSA SAKISGATTF DFIPQK « Hide
Isoform 3 (509aa) (B) (E) [UniParc]. Checksum: E148946CEA1E057F Show »	FASTA	509	57,569
10 20 30 40 50 60 MAAPAACTRF SDNYDIKEEL GKGAFSIVKR CVQKSTGFEF AAKIINTKKL TARDFQKLER 70 80 90 100 110 120 EARICRKLHH PNIVRLHDSI QEENYHYLVF DLVTGGELFE DIVAREFYSE ADASHCIQQI 130 140 150 160 170 180 LESVNHCHQN GVVHRDLKPE NLLLASKAKG AAVKLADFGL AIEVQGDHQA WFGFAGTPGY 190 200 210 220 230 240 LSPEVLKKEP YGKSVDIWAC GVILYILLVG YPPFWDEDQH RLYSQIKAGA YDYPSPEWDT 250 260 270 280 290 300 VTPEAKNLIN QMLTVNPNKR ITAAEALKHP WICQRERVAS VVHRQETVDC LKKFNARRKL 310 320 330 340 350 360 KGAILTTMLA TRNFSSRSMI TKKGEGSQVK ESTDSSSTTL EDDDIKEDKK GTVDRSTTVV 370 380 390 400 410 420 SKEPEAARRQ EIIKITEQLI EAINSGDFDG YTKICDPHLT AFEPEALGNL VEGIDFHKFY 430 440 450 460 470 480 FENVLGKNCK AINTTILNPH VHLLGEEAAC IAYVRLTQYI DKQGHAHTHQ SEETRVWHKR 490 500 DNKWQNVHFH RSASAKISGA TTFDFIPQK « Hide
Isoform 4 (490aa) (A) (C) [UniParc]. Checksum: 17E1972584F9B2C1 Show »	FASTA	490	55,482
10 20 30 40 50 60 MAAPAACTRF SDNYDIKEEL GKGAFSIVKR CVQKSTGFEF AAKIINTKKL TARDFQKLER 70 80 90 100 110 120 EARICRKLHH PNIVRLHDSI QEENYHYLVF DLVTGGELFE DIVAREFYSE ADASHCIQQI 130 140 150 160 170 180 LESVNHCHQN GVVHRDLKPE NLLLASKAKG AAVKLADFGL AIEVQGDHQA WFGFAGTPGY 190 200 210 220 230 240 LSPEVLKKEP YGKSVDIWAC GVILYILLVG YPPFWDEDQH RLYSQIKAGA YDYPSPEWDT 250 260 270 280 290 300 VTPEAKNLIN QMLTVNPNKR ITAAEALKHP WICQRERVAS VVHRQETVDC LKKFNARRKL 310 320 330 340 350 360 KGAILTTMLA TRNFSSRSMI TKKGEGSQVK ESTDSSSTTL EDDDIKAARR QEIIKITEQL 370 380 390 400 410 420 IEAINSGDFD GYTKICDPHL TAFEPEALGN LVEGIDFHKF YFENVLGKNC KAINTTILNP 430 440 450 460 470 480 HVHLLGEEAA CIAYVRLTQY IDKQGHAHTH QSEETRVWHK RDNKWQNVHF HRSASAKISG 490 ATTFDFIPQK « Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization and expression of the Drosophila Ca2+/calmodulin-dependent protein kinase II gene. Identification of four forms of the enzyme generated from a single gene by alternative splicing." Ohsako S., Nishida Y., Ryo H., Yamauchi T. J. Biol. Chem. 268:2052-2062(1993) [PubMed: 8380587] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), TISSUE SPECIFICITY. Tissue: Head.
[2]	"The alpha subunit of type II Ca2+/calmodulin-dependent protein kinase is highly conserved in Drosophila." Cho K.O., Wall J.B., Pugh P.C., Ito M., Mueller S.A., Kennedy M.B. Neuron 7:439-450(1991) [PubMed: 1910789] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY. Tissue: Head.
[3]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[4]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING. Strain: Berkeley.
[5]	"The diversity of calcium/calmodulin-dependent protein kinase II isoforms in Drosophila is generated by alternative splicing of a single gene." Griffith L.C., Greenspan R.J. J. Neurochem. 61:1534-1537(1993) [PubMed: 8397298] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 347-388.
[6]	"Calcium/calmodulin-dependent protein kinase II phosphorylates and regulates the Drosophila eag potassium channel." Wang Z., Wilson G.F., Griffith L.C. J. Biol. Chem. 277:24022-24029(2002) [PubMed: 11980904] [Abstract] Cited for: FUNCTION.
[7]	"Regulation of the Ca2+/CaM-responsive pool of CaMKII by scaffold-dependent autophosphorylation." Lu C.S., Hodge J.J., Mehren J., Sun X.X., Griffith L.C. Neuron 40:1185-1197(2003) [PubMed: 14687552] [Abstract] Cited for: FUNCTION, INTERACTION WITH CASK, AUTOPHOSPHORYLATION AT THR-287; THR-306 AND THR-307, MUTAGENESIS OF THR-306 AND THR-307.
[8]	"Activity-dependent gating of CaMKII autonomous activity by Drosophila CASK." Hodge J.J., Mullasseril P., Griffith L.C. Neuron 51:327-337(2006) [PubMed: 16880127] [Abstract] Cited for: AUTOPHOSPHORYLATION AT THR-287, ENZYME REGULATION.
[9]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-327, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Web resources

Wikipedia

Calmodulin-dependent kinase entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	D13330 mRNA. Translation: BAA02593.1. D13331 mRNA. Translation: BAA02594.1. D13332 mRNA. Translation: BAA02595.1. D13333 mRNA. Translation: BAA02596.1. M74583 mRNA. Translation: AAA51459.1. AE014135 Genomic DNA. Translation: AAF59388.3. AE014135 Genomic DNA. Translation: AAF59390.2. AE014135 Genomic DNA. Translation: AAN06568.2. AE014135 Genomic DNA. Translation: AAX53595.1. S65712 mRNA. Translation: AAB28244.1. S65716 mRNA. Translation: AAB28245.1. S65717 mRNA. Translation: AAB28246.2. S65719 mRNA. Translation: AAB28247.1. S65724 mRNA. Translation: AAB28248.2.
PIR	B44412. JU0270. C44412. D44412.
RefSeq	NP_001014696.1. NM_001014696.1. NP_001162831.1. NM_001169360.1. NP_001162832.1. NM_001169361.1. NP_524635.3. NM_079896.3. NP_726633.2. NM_166810.4. NP_726634.1. NM_166811.1. NP_726635.2. NM_166812.2. NP_726636.2. NM_166813.2.
UniGene	Dm.1709.
3D structure databases
ProteinModelPortal	Q00168.
SMR	Q00168. Positions 8-517.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q00168. 1 interaction.
MINT	MINT-1561551.
STRING	Q00168.
Proteomic databases
PRIDE	Q00168.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0100146; FBpp0099496; FBgn0004624. FBtr0300378; FBpp0289607; FBgn0004624.
GeneID	43828.
KEGG	dme:Dmel_CG18069.
Organism-specific databases
CTD	43828.
FlyBase	FBgn0004624. CaMKII.
Phylogenomic databases
eggNOG	inNOG08218.
InParanoid	Q00168.
OMA	GAFSIVK.
OrthoDB	EOG4NK99P.
PhylomeDB	Q00168.
Enzyme and pathway databases
BRENDA	2.7.11.17. 1994.
Gene expression databases
Bgee	Q00168.
GermOnline	CG18069. Drosophila melanogaster.
Family and domain databases
InterPro	IPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase. IPR013543. Ca/CaM-dep_prot_kinase-assoc. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K04515.
PANTHER	PTHR24347. PTHR24347. 1 hit.
Pfam	PF08332. CaMKII_AD. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	836100.

Entry information

Entry name

KCC2A_DROME

Accession

Primary (citable) accession number: Q00168
Secondary accession number(s): Q59DP1, Q59DP2, Q9V495

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project

Relevant documents

Drosophila

Drosophila: entries, gene names and cross-references to FlyBase

SIMILARITY comments

Index of protein domains and families

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents