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Q13557 (KCC2D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Calcium/calmodulin-dependent protein kinase type II subunit delta

Short name=CaM kinase II subunit delta
Short name=CaMK-II subunit delta
EC=2.7.11.17
Gene names
Name:CAMK2D
Synonyms:CAMKD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length499 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca2+ homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca2+ influx into the myocyte, Ca2+ release from the sarcoplasmic reticulum (SR), SR Ca2+ uptake and Na+ and K+ channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca2+ release via direct phosphorylation of RYR2 Ca2+ channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program. Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca2+ influx to myocytes by binding and phosphorylating the L-type Ca2+ channel subunit beta-2 CACNB2. In addition to Ca2+ channels, can target and regulate the cardiac sarcolemmal Na+ channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca2+ uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis. May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca2+ transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. Ref.10 Ref.11

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Activated by Ca2+/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca2+-independent activity. Ref.9

Subunit structure

CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other. Interacts with RRAD and CACNB2 By similarity. Ref.9

Subcellular location

Cell membranesarcolemma; Peripheral membrane protein; Cytoplasmic side Probable. Sarcoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side Probable.

Tissue specificity

Expressed in cardiac muscle and skeletal muscle. Isoform Delta3, isoform Delta2, isoform Delta8 and isoform Delta9 are expressed in cardiac muscle. Isoform Delta11 is expressed in skeletal muscle. Ref.1 Ref.10

Induction

Activity is induced in skeletal muscle during exercise. Ref.9 Ref.10

Domain

The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.

Post-translational modification

Autophosphorylation of Thr-287 following activation by Ca2+/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state.

Miscellaneous

Expression of CAMK2D is significantly increased in patients suffering from dilated cardiomyopathy in Ref.1.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence BAD92525.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Sarcoplasmic reticulum
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Calmodulin-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from electronic annotation. Source: Ensembl

calcium ion transport

Inferred from electronic annotation. Source: Ensembl

cardiac muscle cell contraction

Inferred from sequence or structural similarity PubMed 12676814. Source: BHF-UCL

cellular response to calcium ion

Traceable author statement PubMed 23283722. Source: BHF-UCL

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 23283722. Source: BHF-UCL

peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 23283722. Source: BHF-UCL

positive regulation of cardiac muscle hypertrophy

Inferred from mutant phenotype Ref.11. Source: UniProtKB

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.11. Source: UniProtKB

regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion

Traceable author statement Ref.12. Source: UniProtKB

regulation of cell growth

Non-traceable author statement Ref.8. Source: UniProtKB

regulation of cellular localization

Inferred from mutant phenotype Ref.11. Source: UniProtKB

regulation of heart contraction

Traceable author statement Ref.12. Source: UniProtKB

regulation of histone deacetylase activity

Traceable author statement PubMed 23283722. Source: BHF-UCL

regulation of relaxation of cardiac muscle

Inferred from direct assay PubMed 23283722. Source: BHF-UCL

regulation of ryanodine-sensitive calcium-release channel activity

Traceable author statement Ref.16. Source: UniProtKB

regulation of sodium ion transport

Inferred from electronic annotation. Source: Ensembl

regulation of the force of heart contraction

Traceable author statement PubMed 23283722. Source: BHF-UCL

regulation of transcription from RNA polymerase II promoter

Traceable author statement PubMed 23283722. Source: BHF-UCL

relaxation of cardiac muscle

Inferred from sequence or structural similarity PubMed 12676814. Source: BHF-UCL

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentT-tubule

Inferred from electronic annotation. Source: Ensembl

axon initial segment

Inferred from electronic annotation. Source: Ensembl

calcium channel complex

Inferred from electronic annotation. Source: Ensembl

calcium- and calmodulin-dependent protein kinase complex

Traceable author statement PubMed 11264466. Source: UniProtKB

cytoplasm

Inferred from sequence or structural similarity PubMed 12676814. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

intercalated disc

Inferred from electronic annotation. Source: Ensembl

neuromuscular junction

Inferred from electronic annotation. Source: Ensembl

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from sequence or structural similarity PubMed 12676814. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

sarcoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calmodulin-dependent protein kinase activity

Inferred from direct assay PubMed 23283722. Source: BHF-UCL

ion channel binding

Inferred from sequence or structural similarity PubMed 12676814. Source: BHF-UCL

titin binding

Inferred from physical interaction PubMed 23283722. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 10 isoforms produced by alternative splicing. [Align] [Select]
Isoform Delta 2 (identifier: Q13557-1)

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 Delta 3 (identifier: Q13557-3)

The sequence of this isoform differs from the canonical sequence as follows:
     328-328: K → KKRKSSSSVQMM
Isoform Delta 4 (identifier: Q13557-4)

The sequence of this isoform differs from the canonical sequence as follows:
     328-328: K → KINNKANVVTSPKENIPTPAL
Isoform Delta 6 (identifier: Q13557-8)

The sequence of this isoform differs from the canonical sequence as follows:
     479-499: Missing.
Isoform Delta 7 (identifier: Q13557-9)

The sequence of this isoform differs from the canonical sequence as follows:
     328-328: K → KKRKSSSSVQMM
     479-499: Missing.
Isoform Delta 8 (identifier: Q13557-5)

The sequence of this isoform differs from the canonical sequence as follows:
     328-328: K → KINNKANVVTSPKENIPTPAL
     479-499: Missing.
Isoform Delta 9 (identifier: Q13557-6)

The sequence of this isoform differs from the canonical sequence as follows:
     329-329: E → EPQTTVIHNPDGNKE
Isoform Delta 10 (identifier: Q13557-10)

The sequence of this isoform differs from the canonical sequence as follows:
     329-329: E → EPQTTVIHNPDGNKE
     479-499: Missing.
Isoform Delta 11 (identifier: Q13557-11)

The sequence of this isoform differs from the canonical sequence as follows:
     328-328: K → KKRKSSSSVQMMEPQTTVIHNPDGNK
Isoform Delta 12 (identifier: Q13557-12)

The sequence of this isoform differs from the canonical sequence as follows:
     478-478: K → N
     479-499: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.17
Chain2 – 499498Calcium/calmodulin-dependent protein kinase type II subunit delta
PRO_0000086099

Regions

Domain14 – 272259Protein kinase
Nucleotide binding20 – 289ATP By similarity
Region283 – 29210Autoinhibitory domain By similarity
Region291 – 30111Calmodulin-binding By similarity

Sites

Active site1361Proton acceptor By similarity
Binding site431ATP By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.17
Modified residue2871Phosphothreonine; by autocatalysis Ref.10
Modified residue3061Phosphothreonine; by autocatalysis Probable
Modified residue3071Phosphothreonine; by autocatalysis Probable
Modified residue3181N6-acetyllysine By similarity
Modified residue3191Phosphoserine Ref.17
Modified residue3301Phosphoserine By similarity
Modified residue3371Phosphothreonine By similarity
Modified residue4041Phosphoserine Ref.17
Modified residue4901Phosphoserine Ref.17

Natural variations

Alternative sequence3281K → KKRKSSSSVQMMEPQTTVIH NPDGNK in isoform Delta 11.
VSP_023095
Alternative sequence3281K → KKRKSSSSVQMM in isoform Delta 3 and isoform Delta 7.
VSP_023096
Alternative sequence3281K → KINNKANVVTSPKENIPTPA L in isoform Delta 4 and isoform Delta 8.
VSP_023097
Alternative sequence3291E → EPQTTVIHNPDGNKE in isoform Delta 9 and isoform Delta 10.
VSP_023098
Alternative sequence4781K → N in isoform Delta 12.
VSP_041820
Alternative sequence479 – 49921Missing in isoform Delta 6, isoform Delta 7, isoform Delta 8, isoform Delta 10 and isoform Delta 12.
VSP_023099
Natural variant1671D → E. Ref.24
Corresponds to variant rs35367671 [ dbSNP | Ensembl ].
VAR_040602
Natural variant4631Q → E.
Corresponds to variant rs1053668 [ dbSNP | Ensembl ].
VAR_028196
Natural variant4931T → I. Ref.24
Corresponds to variant rs35765784 [ dbSNP | Ensembl ].
VAR_040603

Experimental info

Sequence conflict391E → G in AAD20442. Ref.1
Sequence conflict2721I → T in AAX88806. Ref.4

Secondary structure

.................................................................. 499
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Delta 2 [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: 62999FBAB98120CE

FASTA49956,369
        10         20         30         40         50         60 
MASTTTCTRF TDEYQLFEEL GKGAFSVVRR CMKIPTGQEY AAKIINTKKL SARDHQKLER 

        70         80         90        100        110        120 
EARICRLLKH PNIVRLHDSI SEEGFHYLVF DLVTGGELFE DIVAREYYSE ADASHCIQQI 

       130        140        150        160        170        180 
LESVNHCHLN GIVHRDLKPE NLLLASKSKG AAVKLADFGL AIEVQGDQQA WFGFAGTPGY 

       190        200        210        220        230        240 
LSPEVLRKDP YGKPVDMWAC GVILYILLVG YPPFWDEDQH RLYQQIKAGA YDFPSPEWDT 

       250        260        270        280        290        300 
VTPEAKDLIN KMLTINPAKR ITASEALKHP WICQRSTVAS MMHRQETVDC LKKFNARRKL 

       310        320        330        340        350        360 
KGAILTTMLA TRNFSAAKSL LKKPDGVKES TESSNTTIED EDVKARKQEI IKVTEQLIEA 

       370        380        390        400        410        420 
INNGDFEAYT KICDPGLTAF EPEALGNLVE GMDFHRFYFE NALSKSNKPI HTIILNPHVH 

       430        440        450        460        470        480 
LVGDDAACIA YIRLTQYMDG SGMPKTMQSE ETRVWHRRDG KWQNVHFHRS GSPTVPIKPP 

       490 
CIPNGKENFS GGTSLWQNI 

« Hide

Isoform Delta 3 [UniParc].

Checksum: 0F312AC0E5938A07
Show »

FASTA51057,620
Isoform Delta 4 [UniParc].

Checksum: 184D4250A261D923
Show »

FASTA51958,472
Isoform Delta 6 [UniParc].

Checksum: 571DA27C914E4F7E
Show »

FASTA47854,128
Isoform Delta 7 [UniParc].

Checksum: A45841A7EBFBFA5E
Show »

FASTA48955,378
Isoform Delta 8 [UniParc].

Checksum: 3EE4353E136343BB
Show »

FASTA49856,230
Isoform Delta 9 [UniParc].

Checksum: 79B81366F7E1C69B
Show »

FASTA51357,901
Isoform Delta 10 [UniParc].

Checksum: E78D0E736590F908
Show »

FASTA49255,660
Isoform Delta 11 [UniParc].

Checksum: 3BFC4B5CAF9B3B88
Show »

FASTA52459,152
Isoform Delta 12 [UniParc].

Checksum: 506DA27C914E4F7E
Show »

FASTA47854,114

References

« Hide 'large scale' references
[1]"Identification and expression of delta-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human myocardium."
Hoch B., Meyer R., Hetzer R., Krause E.-G., Karczewski P.
Circ. Res. 84:713-721(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM DELTA 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
Tissue: Myocardium.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA 12).
[3]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA 10).
Tissue: Brain.
[4]Zhou G., Nong W., Li H., Ke R., Li M., Zheng Z., Zhong G., Shen C., Liang M., Lin L., Yang S.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA 7).
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTA 6).
[7]"Cloning and quantitative determination of the human Ca2+/calmodulin-dependent protein kinase II (CaMK II) isoforms in human beta cells."
Rochlitz H., Voigt A., Lankat-Buttgereit B., Goeke B., Heimberg H., Nauck M.A., Schiemann U., Schatz H., Pfeiffer A.F.
Diabetologia 43:465-473(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-243, ALTERNATIVE SPLICING.
Tissue: Insulinoma.
[8]"Identification of novel human tumor cell-specific CaMK-II variants."
Tombes R.M., Krystal G.W.
Biochim. Biophys. Acta 1355:281-292(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 302-417, ALTERNATIVE SPLICING.
[9]"Comparative analyses of the three-dimensional structures and enzymatic properties of alpha, beta, gamma and delta isoforms of Ca2+-calmodulin-dependent protein kinase II."
Gaertner T.R., Kolodziej S.J., Wang D., Kobayashi R., Koomen J.M., Stoops J.K., Waxham M.N.
J. Biol. Chem. 279:12484-12494(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, SUBUNIT, AUTOPHOSPHORYLATION.
[10]"Ca2+-calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise."
Rose A.J., Kiens B., Richter E.A.
J. Physiol. (Lond.) 574:889-903(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SKELETAL MUSCLE, PHOSPHORYLATION AT THR-287, FUNCTION IN PHOSPHORYLATION OF PLN, TISSUE SPECIFICITY, INDUCTION.
[11]"Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells."
Little G.H., Bai Y., Williams T., Poizat C.
J. Biol. Chem. 282:7219-7231(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC4.
[12]"Role of Ca2+/calmodulin-dependent protein kinase (CaMK) in excitation-contraction coupling in the heart."
Maier L.S., Bers D.M.
Cardiovasc. Res. 73:631-640(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON INVOLVEMENT IN EXCITATION-CONTRACTION COUPLING IN HEART.
[13]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[14]"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography."
Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J.
Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[15]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Cardiac ryanodine receptor phosphorylation by CaM Kinase II: keeping the balance right."
Currie S.
Front. Biosci. 14:5134-5156(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON PHOSPHORYLATION OF RYR2.
[17]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-319; SER-404 AND SER-490, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[18]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[19]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Role of CaMKII in cardiovascular health, disease, and arrhythmia."
Mohler P.J., Hund T.J.
Heart Rhythm 8:142-144(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[21]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"Structure of the CaMKIIdelta/calmodulin complex reveals the molecular mechanism of CaMKII kinase activation."
Rellos P., Pike A.C., Niesen F.H., Salah E., Lee W.H., von Delft F., Knapp S.
PLoS Biol. 8:E1000426-E1000426(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 11-335 IN COMPLEX AND INHIBITORS.
[23]"Calmodulin bound to peptide from calmodulin kinase II (CaMKII)."
Ng H.L., Alber T.A., Wand A.J.
Submitted (MAR-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 294-311 IN COMPLEX WITH CALMODULIN.
[24]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] GLU-167 AND ILE-493.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF071569 mRNA. Translation: AAD20442.1.
AK055642 mRNA. Translation: BAG51545.1.
AB209288 mRNA. Translation: BAD92525.1. Different initiation.
AY987011 mRNA. Translation: AAX88806.1.
AC004056 Genomic DNA. No translation available.
AC004168 Genomic DNA. No translation available.
AC093900 Genomic DNA. No translation available.
AC107386 Genomic DNA. No translation available.
BC032784 mRNA. Translation: AAH32784.1.
AJ252239 mRNA. Translation: CAB65123.1.
U50361 mRNA. Translation: AAB16866.1.
CCDSCCDS3703.1. [Q13557-1]
CCDS3704.1. [Q13557-8]
CCDS43263.1. [Q13557-12]
CCDS47127.1. [Q13557-10]
CCDS54797.1. [Q13557-9]
RefSeqNP_001212.2. NM_001221.3. [Q13557-1]
NP_742112.1. NM_172114.1. [Q13557-10]
NP_742113.1. NM_172115.2. [Q13557-8]
NP_742125.1. NM_172127.2. [Q13557-8]
NP_742126.1. NM_172128.2. [Q13557-12]
NP_742127.1. NM_172129.1. [Q13557-9]
XP_005263312.1. XM_005263255.2. [Q13557-6]
XP_006714392.1. XM_006714329.1. [Q13557-10]
UniGeneHs.144114.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2VN9X-ray2.30A/B11-309[»]
2W2CX-ray2.70A/B/C/D/E/F/G/H/I/J/K/L/M/N334-475[»]
2WELX-ray1.90A11-335[»]
3GP2X-ray1.46B294-311[»]
ProteinModelPortalQ13557.
SMRQ13557. Positions 8-474.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107267. 17 interactions.
DIPDIP-33129N.
IntActQ13557. 15 interactions.
MINTMINT-3028061.
STRING9606.ENSP00000339740.

Chemistry

BindingDBQ13557.
ChEMBLCHEMBL2801.
GuidetoPHARMACOLOGY1558.

PTM databases

PhosphoSiteQ13557.

Polymorphism databases

DMDM116242602.

Proteomic databases

MaxQBQ13557.
PaxDbQ13557.
PRIDEQ13557.

Protocols and materials databases

DNASU817.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296402; ENSP00000296402; ENSG00000145349. [Q13557-8]
ENST00000342666; ENSP00000339740; ENSG00000145349. [Q13557-1]
ENST00000379773; ENSP00000369098; ENSG00000145349. [Q13557-8]
ENST00000394522; ENSP00000378030; ENSG00000145349. [Q13557-10]
ENST00000394524; ENSP00000378032; ENSG00000145349. [Q13557-12]
ENST00000394526; ENSP00000378034; ENSG00000145349. [Q13557-3]
ENST00000418639; ENSP00000406131; ENSG00000145349. [Q13557-6]
ENST00000429180; ENSP00000415707; ENSG00000145349. [Q13557-4]
ENST00000454265; ENSP00000415248; ENSG00000145349. [Q13557-11]
ENST00000508738; ENSP00000422566; ENSG00000145349. [Q13557-9]
ENST00000515496; ENSP00000423482; ENSG00000145349. [Q13557-3]
GeneID817.
KEGGhsa:817.
UCSCuc003ibi.3. human. [Q13557-1]
uc003ibj.3. human. [Q13557-12]
uc003ibm.2. human. [Q13557-10]
uc003ibn.2. human. [Q13557-9]

Organism-specific databases

CTD817.
GeneCardsGC04M114372.
HGNCHGNC:1462. CAMK2D.
HPAHPA026281.
MIM607708. gene.
neXtProtNX_Q13557.
PharmGKBPA92.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG108055.
InParanoidQ13557.
KOK04515.
OrthoDBEOG7ZD1VM.
PhylomeDBQ13557.
TreeFamTF315229.

Enzyme and pathway databases

BRENDA2.7.11.17. 2681.
ReactomeREACT_120956. Cellular responses to stress.
REACT_13685. Neuronal System.
REACT_6900. Immune System.
SignaLinkQ13557.

Gene expression databases

ArrayExpressQ13557.
BgeeQ13557.
CleanExHS_CAMK2D.
GenevestigatorQ13557.

Family and domain databases

InterProIPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR013543. Ca/CaM-dep_prot_kinase-assoc.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24347. PTHR24347. 1 hit.
PfamPF08332. CaMKII_AD. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCAMK2D. human.
EvolutionaryTraceQ13557.
GeneWikiCAMK2D.
GenomeRNAi817.
NextBio3330.
PROQ13557.
SOURCESearch...

Entry information

Entry nameKCC2D_HUMAN
AccessionPrimary (citable) accession number: Q13557
Secondary accession number(s): A8MVS8 expand/collapse secondary AC list , Q52PK4, Q59G21, Q8N553, Q9UGH6, Q9UQE9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 154 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM