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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: -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)DescriptionActionsGraphical viewLength
Binding sitei43ATPPROSITE-ProRule annotation1
Active sitei136Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi20 – 28ATPPROSITE-ProRule annotation9

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

  • cell differentiation Source: GO_Central
  • chemical synaptic transmission Source: FlyBase
  • courtship behavior Source: FlyBase
  • intracellular signal transduction Source: GO_Central
  • learning or memory Source: FlyBase
  • long-term memory Source: FlyBase
  • male courtship behavior Source: FlyBase
  • neuromuscular junction development Source: FlyBase
  • peptidyl-serine phosphorylation Source: GO_Central
  • peptidyl-threonine phosphorylation Source: GO_Central
  • protein phosphorylation Source: FlyBase
  • regulation of filopodium assembly Source: FlyBase
  • regulation of ovulation Source: FlyBase
  • regulation of synaptic growth at neuromuscular junction Source: FlyBase

Keywordsi

Molecular functionCalmodulin-binding, Kinase, Serine/threonine-protein kinase, Transferase
LigandATP-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-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-DME-5578775 Ion homeostasis
R-DME-5673001 RAF/MAP kinase cascade
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 lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraHolometabolaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 4

Organism-specific databases

FlyBaseiFBgn0264607 CaMKII

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi306T → A: Fails to interact with CASK, catalytically active but fails to autophosphorylate, when associated with A-307. 1 Publication1
Mutagenesisi306T → D: Fails to interact with CASK, kinase inactive, when associated with D-307. 1 Publication1
Mutagenesisi306T → S: Fails to interact with CASK, catalytically active and can autophosphorylate, when associated with S-307. 1 Publication1
Mutagenesisi307T → A: Fails to interact with CASK, catalytically active but fails to autophosphorylate, when associated with A-306. 1 Publication1
Mutagenesisi307T → D: Fails to interact with CASK, kinase inactive, when associated with D-306. 1 Publication1
Mutagenesisi307T → S: Fails to interact with CASK, catalytically active and can autophosphorylate, when associated with S-306. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860951 – 530Calcium/calmodulin-dependent protein kinase type II alpha chainAdd BLAST530

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei287Phosphothreonine; by autocatalysis2 Publications1
Modified residuei306Phosphothreonine; by autocatalysis1 Publication1
Modified residuei307Phosphothreonine; by autocatalysis1 Publication1
Modified residuei327Phosphoserine1 Publication1

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 baseline and 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, 24 interactors
IntActiQ00168, 5 interactors
MINTiQ00168
STRINGi7227.FBpp0289608

Structurei

Secondary structure

1530
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 13Combined sources5
Beta strandi14 – 23Combined sources10
Beta strandi26 – 33Combined sources8
Turni34 – 36Combined sources3
Beta strandi39 – 46Combined sources8
Helixi52 – 67Combined sources16
Beta strandi76 – 81Combined sources6
Beta strandi83 – 91Combined sources9
Helixi98 – 105Combined sources8
Helixi110 – 128Combined sources19
Turni129 – 131Combined sources3
Helixi139 – 141Combined sources3
Beta strandi142 – 145Combined sources4
Beta strandi153 – 155Combined sources3
Beta strandi174 – 176Combined sources3
Helixi178 – 180Combined sources3
Helixi183 – 186Combined sources4
Helixi194 – 209Combined sources16
Helixi219 – 228Combined sources10
Turni235 – 240Combined sources6
Helixi243 – 252Combined sources10
Turni257 – 259Combined sources3
Helixi263 – 266Combined sources4
Helixi270 – 273Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5FG8X-ray1.96A1-283[»]
5H9BX-ray2.25A1-283[»]
5HU3X-ray1.89A1-283[»]
ProteinModelPortaliQ00168
SMRiQ00168
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 272Protein kinasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni291 – 301Calmodulin-bindingAdd BLAST11

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0033 Eukaryota
ENOG410XNRX LUCA
GeneTreeiENSGT00760000118944
InParanoidiQ00168
KOiK04515
OrthoDBiEOG091G0SCS
PhylomeDBiQ00168

Family and domain databases

InterProiView protein in InterPro
IPR013543 Ca/CaM-dep_prot_kinase-assoc
IPR011009 Kinase-like_dom_sf
IPR032710 NTF2-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF08332 CaMKII_AD, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF54427 SSF54427, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti388A → S in AAB28246 (PubMed:1910789).Curated1
Sequence conflicti388A → S in AAB28248 (PubMed:1910789).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_050261347 – 386Missing in isoform 4. 2 PublicationsAdd BLAST40
Alternative sequenceiVSP_050262366 – 387DIRIL…SQCSS → VNLFTNKA in isoform 2. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_050263366 – 387DIRIL…SQCSS → A in isoform 3. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_050264387S → A in isoform 4. 2 Publications1

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

EnsemblMetazoaiFBtr0089217; FBpp0088281; FBgn0264607 [Q00168-4]
FBtr0089218; FBpp0088282; FBgn0264607 [Q00168-4]
FBtr0089219; FBpp0088283; FBgn0264607 [Q00168-3]
FBtr0100146; FBpp0099496; FBgn0264607 [Q00168-1]
FBtr0100147; FBpp0099497; FBgn0264607 [Q00168-3]
FBtr0100148; FBpp0099498; FBgn0264607 [Q00168-2]
FBtr0300377; FBpp0289606; FBgn0264607 [Q00168-4]
FBtr0300378; FBpp0289607; FBgn0264607 [Q00168-1]
GeneIDi43828
KEGGidme:Dmel_CG18069

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKCC2A_DROME
AccessioniPrimary (citable) accession number: Q00168
Secondary accession number(s): Q59DP1, Q59DP2, Q9V495
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: November 1, 1996
Last modified: May 23, 2018
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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