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Q13557

- KCC2D_HUMAN

UniProt

Q13557 - KCC2D_HUMAN

Protein

Calcium/calmodulin-dependent protein kinase type II subunit delta

Gene

CAMK2D

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 156 (01 Oct 2014)
      Sequence version 3 (17 Oct 2006)
      Previous versions | rss
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    Functioni

    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.2 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    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.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

    1. ATP binding Source: UniProtKB-KW
    2. calmodulin-dependent protein kinase activity Source: BHF-UCL
    3. ion channel binding Source: BHF-UCL
    4. protein serine/threonine kinase activity Source: BHF-UCL
    5. sodium channel inhibitor activity Source: BHF-UCL
    6. titin binding Source: BHF-UCL

    GO - Biological processi

    1. calcium ion transport Source: Ensembl
    2. cardiac muscle cell contraction Source: BHF-UCL
    3. cellular response to calcium ion Source: BHF-UCL
    4. cytokine-mediated signaling pathway Source: Reactome
    5. G1/S transition of mitotic cell cycle Source: Ensembl
    6. interferon-gamma-mediated signaling pathway Source: Reactome
    7. negative regulation of sodium ion transmembrane transport Source: BHF-UCL
    8. negative regulation of sodium ion transmembrane transporter activity Source: BHF-UCL
    9. peptidyl-serine phosphorylation Source: BHF-UCL
    10. peptidyl-threonine phosphorylation Source: BHF-UCL
    11. positive regulation of cardiac muscle hypertrophy Source: UniProtKB
    12. protein autophosphorylation Source: BHF-UCL
    13. protein phosphorylation Source: UniProtKB
    14. regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: UniProtKB
    15. regulation of cell growth Source: UniProtKB
    16. regulation of cellular localization Source: UniProtKB
    17. regulation of heart contraction Source: UniProtKB
    18. regulation of heart rate by cardiac conduction Source: BHF-UCL
    19. regulation of histone deacetylase activity Source: BHF-UCL
    20. regulation of membrane depolarization Source: BHF-UCL
    21. regulation of relaxation of cardiac muscle Source: BHF-UCL
    22. regulation of ryanodine-sensitive calcium-release channel activity Source: UniProtKB
    23. regulation of the force of heart contraction Source: BHF-UCL
    24. regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    25. relaxation of cardiac muscle Source: BHF-UCL
    26. synaptic transmission Source: Reactome

    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. 2681.
    ReactomeiREACT_18307. Trafficking of AMPA receptors.
    REACT_200775. HSF1-dependent transactivation.
    REACT_20546. Ras activation uopn Ca2+ infux through NMDA receptor.
    REACT_20568. CREB phosphorylation through the activation of Ras.
    REACT_20594. Unblocking of NMDA receptor, glutamate binding and activation.
    REACT_20642. CREB phosphorylation through the activation of CaMKII.
    REACT_25078. Interferon gamma signaling.
    SignaLinkiQ13557.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Calcium/calmodulin-dependent protein kinase type II subunit delta (EC:2.7.11.17)
    Short name:
    CaM kinase II subunit delta
    Short name:
    CaMK-II subunit delta
    Gene namesi
    Name:CAMK2D
    Synonyms:CAMKD
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:1462. CAMK2D.

    Subcellular locationi

    GO - Cellular componenti

    1. axon initial segment Source: Ensembl
    2. calcium- and calmodulin-dependent protein kinase complex Source: UniProtKB
    3. calcium channel complex Source: Ensembl
    4. cytoplasm Source: BHF-UCL
    5. cytosol Source: Reactome
    6. endocytic vesicle membrane Source: Reactome
    7. intercalated disc Source: Ensembl
    8. membrane Source: UniProtKB
    9. neuromuscular junction Source: Ensembl
    10. neuronal cell body Source: Ensembl
    11. nucleoplasm Source: Reactome
    12. nucleus Source: BHF-UCL
    13. plasma membrane Source: Reactome
    14. sarcoplasmic reticulum membrane Source: UniProtKB-SubCell
    15. T-tubule Source: Ensembl

    Keywords - Cellular componenti

    Cell membrane, Membrane, Sarcoplasmic reticulum

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA92.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 499498Calcium/calmodulin-dependent protein kinase type II subunit deltaPRO_0000086099Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication
    Modified residuei287 – 2871Phosphothreonine; by autocatalysis1 Publication
    Modified residuei306 – 3061Phosphothreonine; by autocatalysisCurated
    Modified residuei307 – 3071Phosphothreonine; by autocatalysisCurated
    Modified residuei318 – 3181N6-acetyllysineBy similarity
    Modified residuei319 – 3191Phosphoserine1 Publication
    Modified residuei330 – 3301PhosphoserineBy similarity
    Modified residuei337 – 3371PhosphothreonineBy similarity
    Modified residuei404 – 4041Phosphoserine1 Publication
    Modified residuei490 – 4901Phosphoserine1 Publication

    Post-translational modificationi

    Autophosphorylation of Thr-287 following activation by Ca2+/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state.2 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ13557.
    PaxDbiQ13557.
    PRIDEiQ13557.

    PTM databases

    PhosphoSiteiQ13557.

    Expressioni

    Tissue specificityi

    Expressed in cardiac muscle and skeletal muscle. Isoform Delta 3, isoform Delta 2, isoform Delta 8 and isoform Delta 9 are expressed in cardiac muscle. Isoform Delta 11 is expressed in skeletal muscle.2 Publications

    Inductioni

    Activity is induced in skeletal muscle during exercise.1 Publication

    Gene expression databases

    ArrayExpressiQ13557.
    BgeeiQ13557.
    CleanExiHS_CAMK2D.
    GenevestigatoriQ13557.

    Organism-specific databases

    HPAiHPA026281.

    Interactioni

    Subunit structurei

    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.By similarity

    Protein-protein interaction databases

    BioGridi107267. 19 interactions.
    DIPiDIP-33129N.
    IntActiQ13557. 15 interactions.
    MINTiMINT-3028061.
    STRINGi9606.ENSP00000339740.

    Structurei

    Secondary structure

    1
    499
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi14 – 2310
    Beta strandi26 – 338
    Turni34 – 363
    Beta strandi39 – 468
    Helixi47 – 493
    Helixi52 – 6716
    Beta strandi76 – 827
    Beta strandi85 – 906
    Helixi98 – 1058
    Helixi110 – 12920
    Helixi139 – 1413
    Beta strandi142 – 1487
    Beta strandi153 – 1553
    Helixi158 – 1603
    Helixi178 – 1803
    Helixi183 – 1864
    Helixi194 – 20916
    Helixi219 – 22810
    Turni235 – 2406
    Helixi243 – 25210
    Turni257 – 2593
    Helixi263 – 2664
    Helixi270 – 2734
    Helixi275 – 2784
    Helixi296 – 31015
    Helixi340 – 36324
    Helixi366 – 3727
    Beta strandi373 – 3808
    Helixi382 – 3843
    Beta strandi389 – 3924
    Helixi393 – 4019
    Beta strandi410 – 42112
    Beta strandi426 – 43813
    Beta strandi444 – 45815
    Beta strandi461 – 47010

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliQ13557.
    SMRiQ13557. Positions 8-474.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ13557.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini14 – 272259Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni283 – 29210Autoinhibitory domainBy similarity
    Regioni291 – 30111Calmodulin-bindingBy similarityAdd
    BLAST

    Domaini

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

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOVERGENiHBG108055.
    InParanoidiQ13557.
    KOiK04515.
    OrthoDBiEOG7ZD1VM.
    PhylomeDBiQ13557.
    TreeFamiTF315229.

    Family and domain databases

    InterProiIPR020636. 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]
    PANTHERiPTHR24347. PTHR24347. 1 hit.
    PfamiPF08332. CaMKII_AD. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequences (10)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 10 isoformsi produced by alternative splicing. Align

    Isoform Delta 2 (identifier: Q13557-1) [UniParc]FASTAAdd to Basket

    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

    MASTTTCTRF TDEYQLFEEL GKGAFSVVRR CMKIPTGQEY AAKIINTKKL    50
    SARDHQKLER EARICRLLKH PNIVRLHDSI SEEGFHYLVF DLVTGGELFE 100
    DIVAREYYSE ADASHCIQQI LESVNHCHLN GIVHRDLKPE NLLLASKSKG 150
    AAVKLADFGL AIEVQGDQQA WFGFAGTPGY LSPEVLRKDP YGKPVDMWAC 200
    GVILYILLVG YPPFWDEDQH RLYQQIKAGA YDFPSPEWDT VTPEAKDLIN 250
    KMLTINPAKR ITASEALKHP WICQRSTVAS MMHRQETVDC LKKFNARRKL 300
    KGAILTTMLA TRNFSAAKSL LKKPDGVKES TESSNTTIED EDVKARKQEI 350
    IKVTEQLIEA INNGDFEAYT KICDPGLTAF EPEALGNLVE GMDFHRFYFE 400
    NALSKSNKPI HTIILNPHVH LVGDDAACIA YIRLTQYMDG SGMPKTMQSE 450
    ETRVWHRRDG KWQNVHFHRS GSPTVPIKPP CIPNGKENFS GGTSLWQNI 499
    Length:499
    Mass (Da):56,369
    Last modified:October 17, 2006 - v3
    Checksum:i62999FBAB98120CE
    GO
    Isoform Delta 3 (identifier: Q13557-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         328-328: K → KKRKSSSSVQMM

    Show »
    Length:510
    Mass (Da):57,620
    Checksum:i0F312AC0E5938A07
    GO
    Isoform Delta 4 (identifier: Q13557-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         328-328: K → KINNKANVVTSPKENIPTPAL

    Show »
    Length:519
    Mass (Da):58,472
    Checksum:i184D4250A261D923
    GO
    Isoform Delta 6 (identifier: Q13557-8) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         479-499: Missing.

    Show »
    Length:478
    Mass (Da):54,128
    Checksum:i571DA27C914E4F7E
    GO
    Isoform Delta 7 (identifier: Q13557-9) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         328-328: K → KKRKSSSSVQMM
         479-499: Missing.

    Show »
    Length:489
    Mass (Da):55,378
    Checksum:iA45841A7EBFBFA5E
    GO
    Isoform Delta 8 (identifier: Q13557-5) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         328-328: K → KINNKANVVTSPKENIPTPAL
         479-499: Missing.

    Show »
    Length:498
    Mass (Da):56,230
    Checksum:i3EE4353E136343BB
    GO
    Isoform Delta 9 (identifier: Q13557-6) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         329-329: E → EPQTTVIHNPDGNKE

    Show »
    Length:513
    Mass (Da):57,901
    Checksum:i79B81366F7E1C69B
    GO
    Isoform Delta 10 (identifier: Q13557-10) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         329-329: E → EPQTTVIHNPDGNKE
         479-499: Missing.

    Show »
    Length:492
    Mass (Da):55,660
    Checksum:iE78D0E736590F908
    GO
    Isoform Delta 11 (identifier: Q13557-11) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         328-328: K → KKRKSSSSVQMMEPQTTVIHNPDGNK

    Show »
    Length:524
    Mass (Da):59,152
    Checksum:i3BFC4B5CAF9B3B88
    GO
    Isoform Delta 12 (identifier: Q13557-12) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         478-478: K → N
         479-499: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:478
    Mass (Da):54,114
    Checksum:i506DA27C914E4F7E
    GO

    Sequence cautioni

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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti39 – 391E → G in AAD20442. (PubMed:10189359)Curated
    Sequence conflicti272 – 2721I → T in AAX88806. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti167 – 1671D → E.1 Publication
    Corresponds to variant rs35367671 [ dbSNP | Ensembl ].
    VAR_040602
    Natural varianti463 – 4631Q → E.
    Corresponds to variant rs1053668 [ dbSNP | Ensembl ].
    VAR_028196
    Natural varianti493 – 4931T → I.1 Publication
    Corresponds to variant rs35765784 [ dbSNP | Ensembl ].
    VAR_040603

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei328 – 3281K → KKRKSSSSVQMMEPQTTVIH NPDGNK in isoform Delta 11. CuratedVSP_023095
    Alternative sequencei328 – 3281K → KKRKSSSSVQMM in isoform Delta 3 and isoform Delta 7. 1 PublicationVSP_023096
    Alternative sequencei328 – 3281K → KINNKANVVTSPKENIPTPA L in isoform Delta 4 and isoform Delta 8. CuratedVSP_023097
    Alternative sequencei329 – 3291E → EPQTTVIHNPDGNKE in isoform Delta 9 and isoform Delta 10. 1 PublicationVSP_023098
    Alternative sequencei478 – 4781K → N in isoform Delta 12. 1 PublicationVSP_041820
    Alternative sequencei479 – 49921Missing in isoform Delta 6, isoform Delta 7, isoform Delta 8, isoform Delta 10 and isoform Delta 12. 4 PublicationsVSP_023099Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS3703.1. [Q13557-1]
    CCDS3704.1. [Q13557-8]
    CCDS43263.1. [Q13557-12]
    CCDS47127.1. [Q13557-10]
    CCDS54797.1. [Q13557-9]
    RefSeqiNP_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]
    UniGeneiHs.144114.

    Genome annotation databases

    EnsembliENST00000296402; ENSP00000296402; ENSG00000145349. [Q13557-8]
    ENST00000342666; ENSP00000339740; ENSG00000145349. [Q13557-1]
    ENST00000379773; ENSP00000369098; ENSG00000145349. [Q13557-8]
    ENST00000394522; ENSP00000378030; ENSG00000145349. [Q13557-10]
    ENST00000394524; ENSP00000378032; ENSG00000145349. [Q13557-12]
    ENST00000508738; ENSP00000422566; ENSG00000145349. [Q13557-9]
    ENST00000515496; ENSP00000423482; ENSG00000145349. [Q13557-3]
    GeneIDi817.
    KEGGihsa:817.
    UCSCiuc003ibi.3. human. [Q13557-1]
    uc003ibj.3. human. [Q13557-12]
    uc003ibm.2. human. [Q13557-10]
    uc003ibn.2. human. [Q13557-9]

    Polymorphism databases

    DMDMi116242602.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS3703.1. [Q13557-1 ]
    CCDS3704.1. [Q13557-8 ]
    CCDS43263.1. [Q13557-12 ]
    CCDS47127.1. [Q13557-10 ]
    CCDS54797.1. [Q13557-9 ]
    RefSeqi NP_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 ]
    UniGenei Hs.144114.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2VN9 X-ray 2.30 A/B 11-309 [» ]
    2W2C X-ray 2.70 A/B/C/D/E/F/G/H/I/J/K/L/M/N 334-475 [» ]
    2WEL X-ray 1.90 A 11-335 [» ]
    3GP2 X-ray 1.46 B 294-311 [» ]
    ProteinModelPortali Q13557.
    SMRi Q13557. Positions 8-474.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107267. 19 interactions.
    DIPi DIP-33129N.
    IntActi Q13557. 15 interactions.
    MINTi MINT-3028061.
    STRINGi 9606.ENSP00000339740.

    Chemistry

    BindingDBi Q13557.
    ChEMBLi CHEMBL2801.
    GuidetoPHARMACOLOGYi 1558.

    PTM databases

    PhosphoSitei Q13557.

    Polymorphism databases

    DMDMi 116242602.

    Proteomic databases

    MaxQBi Q13557.
    PaxDbi Q13557.
    PRIDEi Q13557.

    Protocols and materials databases

    DNASUi 817.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000296402 ; ENSP00000296402 ; ENSG00000145349 . [Q13557-8 ]
    ENST00000342666 ; ENSP00000339740 ; ENSG00000145349 . [Q13557-1 ]
    ENST00000379773 ; ENSP00000369098 ; ENSG00000145349 . [Q13557-8 ]
    ENST00000394522 ; ENSP00000378030 ; ENSG00000145349 . [Q13557-10 ]
    ENST00000394524 ; ENSP00000378032 ; ENSG00000145349 . [Q13557-12 ]
    ENST00000508738 ; ENSP00000422566 ; ENSG00000145349 . [Q13557-9 ]
    ENST00000515496 ; ENSP00000423482 ; ENSG00000145349 . [Q13557-3 ]
    GeneIDi 817.
    KEGGi hsa:817.
    UCSCi uc003ibi.3. human. [Q13557-1 ]
    uc003ibj.3. human. [Q13557-12 ]
    uc003ibm.2. human. [Q13557-10 ]
    uc003ibn.2. human. [Q13557-9 ]

    Organism-specific databases

    CTDi 817.
    GeneCardsi GC04M114372.
    HGNCi HGNC:1462. CAMK2D.
    HPAi HPA026281.
    MIMi 607708. gene.
    neXtProti NX_Q13557.
    PharmGKBi PA92.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOVERGENi HBG108055.
    InParanoidi Q13557.
    KOi K04515.
    OrthoDBi EOG7ZD1VM.
    PhylomeDBi Q13557.
    TreeFami TF315229.

    Enzyme and pathway databases

    BRENDAi 2.7.11.17. 2681.
    Reactomei REACT_18307. Trafficking of AMPA receptors.
    REACT_200775. HSF1-dependent transactivation.
    REACT_20546. Ras activation uopn Ca2+ infux through NMDA receptor.
    REACT_20568. CREB phosphorylation through the activation of Ras.
    REACT_20594. Unblocking of NMDA receptor, glutamate binding and activation.
    REACT_20642. CREB phosphorylation through the activation of CaMKII.
    REACT_25078. Interferon gamma signaling.
    SignaLinki Q13557.

    Miscellaneous databases

    ChiTaRSi CAMK2D. human.
    EvolutionaryTracei Q13557.
    GeneWikii CAMK2D.
    GenomeRNAii 817.
    NextBioi 3330.
    PROi Q13557.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q13557.
    Bgeei Q13557.
    CleanExi HS_CAMK2D.
    Genevestigatori Q13557.

    Family and domain databases

    InterProi IPR020636. 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 ]
    PANTHERi PTHR24347. PTHR24347. 1 hit.
    Pfami PF08332. CaMKII_AD. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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.
      , 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. 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. 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.
      , 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.

    Entry informationi

    Entry nameiKCC2D_HUMAN
    AccessioniPrimary (citable) accession number: Q13557
    Secondary accession number(s): A8MVS8
    , Q52PK4, Q59G21, Q8N553, Q9UGH6, Q9UQE9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: October 17, 2006
    Last modified: October 1, 2014
    This is version 156 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Miscellaneous

    Expression of CAMK2D is significantly increased in patients suffering from dilated cardiomyopathy in PubMed:10189359.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3