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Protein

Calcium/calmodulin-dependent protein kinase type II alpha chain

Gene

CaMKII

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei43 – 431ATPPROSITE-ProRule annotation
Active sitei136 – 1361Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi20 – 289ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calmodulin binding Source: FlyBase
  • calmodulin-dependent protein kinase activity Source: FlyBase
  • protein serine/threonine kinase activity Source: FlyBase

GO - Biological processi

  • chemical synaptic transmission Source: FlyBase
  • courtship behavior Source: FlyBase
  • learning or memory Source: FlyBase
  • long-term memory Source: FlyBase
  • male courtship behavior Source: FlyBase
  • neuromuscular junction development Source: FlyBase
  • protein phosphorylation Source: FlyBase
  • regulation of filopodium assembly Source: FlyBase
  • regulation of ovulation Source: FlyBase
  • regulation of synaptic growth at neuromuscular junction Source: FlyBase
  • sensory perception of pain Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Calmodulin-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.17. 1994.
ReactomeiR-DME-3371571. HSF1-dependent transactivation.
R-DME-4086398. Ca2+ pathway.
R-DME-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-DME-442729. CREB phosphorylation through the activation of CaMKII.
R-DME-442742. CREB phosphorylation through the activation of Ras.
R-DME-5578775. Ion homeostasis.
R-DME-936837. Ion transport by P-type ATPases.
SignaLinkiQ00168.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium/calmodulin-dependent protein kinase type II alpha chain (EC:2.7.11.17)
Short name:
CaM-kinase II alpha chain
Gene namesi
Name:CaMKII
Synonyms:CaM
ORF Names:CG18069
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 4

Organism-specific databases

FlyBaseiFBgn0264607. CaMKII.

Subcellular locationi

GO - Cellular componenti

  • axon Source: FlyBase
  • calcium- and calmodulin-dependent protein kinase complex Source: FlyBase
  • cytoplasm Source: FlyBase
  • dendrite Source: FlyBase
  • plasma membrane Source: FlyBase
  • postsynaptic membrane Source: FlyBase
  • presynaptic active zone Source: FlyBase
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi306 – 3061T → A: Fails to interact with CASK, catalytically active but fails to autophosphorylate, when associated with A-307. 1 Publication
Mutagenesisi306 – 3061T → D: Fails to interact with CASK, kinase inactive, when associated with D-307. 1 Publication
Mutagenesisi306 – 3061T → S: Fails to interact with CASK, catalytically active and can autophosphorylate, when associated with S-307. 1 Publication
Mutagenesisi307 – 3071T → A: Fails to interact with CASK, catalytically active but fails to autophosphorylate, when associated with A-306. 1 Publication
Mutagenesisi307 – 3071T → D: Fails to interact with CASK, kinase inactive, when associated with D-306. 1 Publication
Mutagenesisi307 – 3071T → S: Fails to interact with CASK, catalytically active and can autophosphorylate, when associated with S-306. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 530530Calcium/calmodulin-dependent protein kinase type II alpha chainPRO_0000086095Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei287 – 2871Phosphothreonine; by autocatalysis2 Publications
Modified residuei306 – 3061Phosphothreonine; by autocatalysis1 Publication
Modified residuei307 – 3071Phosphothreonine; by autocatalysis1 Publication
Modified residuei327 – 3271Phosphoserine1 Publication

Post-translational modificationi

Autophosphorylation at Thr-287 is independent of autophosphorylation at Thr-306 and Thr-307.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ00168.
PRIDEiQ00168.

PTM databases

iPTMnetiQ00168.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiFBgn0264607.
ExpressionAtlasiQ00168. differential.
GenevisibleiQ00168. DM.

Interactioni

Subunit structurei

Interacts with CASK.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CASKQ242105EBI-124595,EBI-214423

GO - Molecular functioni

  • calmodulin binding Source: FlyBase

Protein-protein interaction databases

BioGridi68654. 7 interactions.
IntActiQ00168. 5 interactions.
MINTiMINT-1561551.
STRINGi7227.FBpp0289608.

Structurei

3D structure databases

ProteinModelPortaliQ00168.
SMRiQ00168. Positions 8-514.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 272261Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni291 – 30111Calmodulin-bindingAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0033. Eukaryota.
ENOG410XNRX. LUCA.
GeneTreeiENSGT00760000118944.
InParanoidiQ00168.
KOiK04515.
OrthoDBiEOG091G0SCS.
PhylomeDBiQ00168.

Family and domain databases

Gene3Di3.10.450.50. 1 hit.
InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR013543. Ca/CaM-dep_prot_kinase-assoc.
IPR011009. Kinase-like_dom.
IPR032710. NTF2-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 2 hits.
PfamiPF08332. CaMKII_AD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54427. SSF54427. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q00168-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MAAPAACTRF SDNYDIKEEL GKGAFSIVKR CVQKSTGFEF AAKIINTKKL
60 70 80 90 100
TARDFQKLER EARICRKLHH PNIVRLHDSI QEENYHYLVF DLVTGGELFE
110 120 130 140 150
DIVAREFYSE ADASHCIQQI LESVNHCHQN GVVHRDLKPE NLLLASKAKG
160 170 180 190 200
AAVKLADFGL AIEVQGDHQA WFGFAGTPGY LSPEVLKKEP YGKSVDIWAC
210 220 230 240 250
GVILYILLVG YPPFWDEDQH RLYSQIKAGA YDYPSPEWDT VTPEAKNLIN
260 270 280 290 300
QMLTVNPNKR ITAAEALKHP WICQRERVAS VVHRQETVDC LKKFNARRKL
310 320 330 340 350
KGAILTTMLA TRNFSSRSMI TKKGEGSQVK ESTDSSSTTL EDDDIKEDKK
360 370 380 390 400
GTVDRSTTVV SKEPEDIRIL CPAKTYQQNI GNSQCSSARR QEIIKITEQL
410 420 430 440 450
IEAINSGDFD GYTKICDPHL TAFEPEALGN LVEGIDFHKF YFENVLGKNC
460 470 480 490 500
KAINTTILNP HVHLLGEEAA CIAYVRLTQY IDKQGHAHTH QSEETRVWHK
510 520 530
RDNKWQNVHF HRSASAKISG ATTFDFIPQK
Length:530
Mass (Da):59,920
Last modified:November 1, 1996 - v1
Checksum:i4F3D83582ABDFCFD
GO
Isoform 2 (identifier: Q00168-2) [UniParc]FASTAAdd to basket
Also known as: 516aa, G

The sequence of this isoform differs from the canonical sequence as follows:
     366-387: DIRILCPAKTYQQNIGNSQCSS → VNLFTNKA

Show »
Length:516
Mass (Da):58,386
Checksum:i16D891160BEC6FF2
GO
Isoform 3 (identifier: Q00168-3) [UniParc]FASTAAdd to basket
Also known as: 509aa, B, E

The sequence of this isoform differs from the canonical sequence as follows:
     366-387: DIRILCPAKTYQQNIGNSQCSS → A

Show »
Length:509
Mass (Da):57,569
Checksum:iE148946CEA1E057F
GO
Isoform 4 (identifier: Q00168-4) [UniParc]FASTAAdd to basket
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

Show »
Length:490
Mass (Da):55,482
Checksum:i17E1972584F9B2C1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti388 – 3881A → S in AAB28246 (PubMed:1910789).Curated
Sequence conflicti388 – 3881A → S in AAB28248 (PubMed:1910789).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei347 – 38640Missing in isoform 4. 2 PublicationsVSP_050261Add
BLAST
Alternative sequencei366 – 38722DIRIL…SQCSS → VNLFTNKA in isoform 2. 1 PublicationVSP_050262Add
BLAST
Alternative sequencei366 – 38722DIRIL…SQCSS → A in isoform 3. 1 PublicationVSP_050263Add
BLAST
Alternative sequencei387 – 3871S → A in isoform 4. 2 PublicationsVSP_050264

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiB44412.
C44412. JU0270.
D44412.
RefSeqiNP_001014696.1. NM_001014696.2. [Q00168-2]
NP_001162831.1. NM_001169360.2. [Q00168-4]
NP_001162832.1. NM_001169361.2. [Q00168-1]
NP_524635.3. NM_079896.4. [Q00168-4]
NP_726633.2. NM_166810.5. [Q00168-4]
NP_726634.1. NM_166811.2. [Q00168-3]
NP_726635.2. NM_166812.3. [Q00168-1]
NP_726636.2. NM_166813.3. [Q00168-3]
UniGeneiDm.1709.

Genome annotation databases

EnsemblMetazoaiFBtr0100146; FBpp0099496; FBgn0264607. [Q00168-1]
FBtr0300378; FBpp0289607; FBgn0264607. [Q00168-1]
GeneIDi43828.
KEGGidme:Dmel_CG18069.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Wikipedia

Calmodulin-dependent kinase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiB44412.
C44412. JU0270.
D44412.
RefSeqiNP_001014696.1. NM_001014696.2. [Q00168-2]
NP_001162831.1. NM_001169360.2. [Q00168-4]
NP_001162832.1. NM_001169361.2. [Q00168-1]
NP_524635.3. NM_079896.4. [Q00168-4]
NP_726633.2. NM_166810.5. [Q00168-4]
NP_726634.1. NM_166811.2. [Q00168-3]
NP_726635.2. NM_166812.3. [Q00168-1]
NP_726636.2. NM_166813.3. [Q00168-3]
UniGeneiDm.1709.

3D structure databases

ProteinModelPortaliQ00168.
SMRiQ00168. Positions 8-514.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi68654. 7 interactions.
IntActiQ00168. 5 interactions.
MINTiMINT-1561551.
STRINGi7227.FBpp0289608.

PTM databases

iPTMnetiQ00168.

Proteomic databases

PaxDbiQ00168.
PRIDEiQ00168.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0100146; FBpp0099496; FBgn0264607. [Q00168-1]
FBtr0300378; FBpp0289607; FBgn0264607. [Q00168-1]
GeneIDi43828.
KEGGidme:Dmel_CG18069.

Organism-specific databases

CTDi43828.
FlyBaseiFBgn0264607. CaMKII.

Phylogenomic databases

eggNOGiKOG0033. Eukaryota.
ENOG410XNRX. LUCA.
GeneTreeiENSGT00760000118944.
InParanoidiQ00168.
KOiK04515.
OrthoDBiEOG091G0SCS.
PhylomeDBiQ00168.

Enzyme and pathway databases

BRENDAi2.7.11.17. 1994.
ReactomeiR-DME-3371571. HSF1-dependent transactivation.
R-DME-4086398. Ca2+ pathway.
R-DME-438066. Unblocking of NMDA receptor, glutamate binding and activation.
R-DME-442729. CREB phosphorylation through the activation of CaMKII.
R-DME-442742. CREB phosphorylation through the activation of Ras.
R-DME-5578775. Ion homeostasis.
R-DME-936837. Ion transport by P-type ATPases.
SignaLinkiQ00168.

Miscellaneous databases

GenomeRNAii43828.
PROiQ00168.

Gene expression databases

BgeeiFBgn0264607.
ExpressionAtlasiQ00168. differential.
GenevisibleiQ00168. DM.

Family and domain databases

Gene3Di3.10.450.50. 1 hit.
InterProiIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR013543. Ca/CaM-dep_prot_kinase-assoc.
IPR011009. Kinase-like_dom.
IPR032710. NTF2-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24347. PTHR24347. 2 hits.
PfamiPF08332. CaMKII_AD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54427. SSF54427. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKCC2A_DROME
AccessioniPrimary (citable) accession number: Q00168
Secondary accession number(s): Q59DP1, Q59DP2, Q9V495
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: November 1, 1996
Last modified: September 7, 2016
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.