Reviewed, UniProtKB/Swiss-Prot Q00168 (KCC2A_DROME)

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) [Complete proteome]

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.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Autophosphorylation of CaM-kinase II plays an important role in the regulation of the kinase activity.
Developmental stage	Transcripts of CaM kinase II are expressed in great quantities in the central nervous system in the late embryonic stage of development and are more abundant in the head than in the body of the adult fly.
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
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 protein amino acid phosphorylation 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 Ref.2 Inferred from direct assay. Source: FlyBase
Complete GO annotation...

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 By similarity
	Modified residue	327	1	Phosphoserine Ref.6
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

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (530aa) (D) [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 4F3D83582ABDFCFD	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
	Isoform 2 (516aa) (G). Checksum: 16D891160BEC6FF2	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
	Isoform 3 (509aa) (B) (E). Checksum: E148946CEA1E057F	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
	Isoform 4 (490aa) (A) (C). Checksum: 17E1972584F9B2C1	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

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).
[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).
[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. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., 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. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
[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]	"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. Sequence problems. S65719 mRNA. Translation: AAB28247.1. S65724 mRNA. Translation: AAB28248.2. Sequence problems.
PIR	B44412. JU0270. C44412. D44412.
RefSeq	NP_001014696.1. NP_001162831.1. NP_001162832.1. NP_524635.3. NP_726633.2. NP_726634.1. NP_726635.2. NP_726636.2.
UniGene	Dm.1709
3D structure databases
SMR	Q00168. Positions 8-316, 389-515.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q00168. 13 interactions.
STRING	Q00168.
Proteomic databases
PRIDE	Q00168.
Genome annotation databases
Ensembl	FBtr0089217; FBpp0088281; FBgn0004624; Drosophila melanogaster. [Genome view] FBtr0089218; FBpp0088282; FBgn0004624; Drosophila melanogaster. [Genome view] FBtr0089219; FBpp0088283; FBgn0004624; Drosophila melanogaster. [Genome view] FBtr0100146; FBpp0099496; FBgn0004624; Drosophila melanogaster. [Genome view] FBtr0100147; FBpp0099497; FBgn0004624; Drosophila melanogaster. [Genome view] FBtr0100148; FBpp0099498; FBgn0004624; Drosophila melanogaster. [Genome view] FBtr0300377; FBpp0289606; FBgn0004624; Drosophila melanogaster. [Genome view] FBtr0300378; FBpp0289607; FBgn0004624; Drosophila melanogaster. [Genome view] FBtr0300379; FBpp0289608; FBgn0004624; Drosophila melanogaster. [Genome view]
GeneID	43828.
KEGG	dme:Dmel_CG18069.
Organism-specific databases
CTD	43828.
FlyBase	FBgn0004624. CaMKII.
Phylogenomic databases
eggNOG	inNOG08218.
InParanoid	Q00168.
OMA	NHCHQNG.
PhylomeDB	Q00168.
Enzyme and pathway databases
BRENDA	2.7.11.17. 48.
Gene expression databases
GermOnline	CG18069. Drosophila melanogaster.
Family and domain databases
InterPro	IPR020636. Ca/CaM-dep_prot_kinase-like. IPR015742. Ca/CaM-dep_prot_kinase_2. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view]
PANTHER	PTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit. PTHR22982:SF64. CaMKII. 1 hit.
Pfam	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 Resources
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:	March 2, 2010
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project