O77708 (KCC2D_RABIT) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 74.
History...
Clusters with 
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended 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 |
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| Organism | Oryctolagus cuniculus (Rabbit) [Complete proteome] | ||
| Taxonomic identifier | 9986 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus |
Protein attributes
| Sequence length | 533 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at transcript 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 By similarity. |
| 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. |
| 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. |
| Subcellular location | Cell membrane › sarcolemma; Peripheral membrane protein; Cytoplasmic side Probable. Sarcoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side Probable. |
| Tissue specificity | Expressed in liver. Ref.1 |
| 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 By similarity. |
| Sequence similarities | Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily. Contains 1 protein kinase domain. |
Ontologies
Alternative products
| This entry describes 6 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: O77708-1) Also known as: Delta 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 2 (identifier: O77708-2) Also known as: Delta 2; The sequence of this isoform differs from the canonical sequence as follows: 329-362: Missing. | ||||||
| Isoform 3 (identifier: O77708-3) Also known as: Delta 3; The sequence of this isoform differs from the canonical sequence as follows: 328-328: K → KKRKSSSSVQMM 329-362: Missing. | ||||||
| Isoform 4 (identifier: O77708-4) Also known as: Delta 6; The sequence of this isoform differs from the canonical sequence as follows: 329-362: Missing. 512-512: K → N 513-533: Missing. | ||||||
| Isoform 5 (identifier: O77708-5) Also known as: Delta 11; The sequence of this isoform differs from the canonical sequence as follows: 316-316: Missing. | ||||||
| Isoform 6 (identifier: O77708-6) Also known as: Delta 12; The sequence of this isoform differs from the canonical sequence as follows: 316-316: Missing. 512-512: K → N 513-533: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed By similarity | ||||||
| Chain | 2 – 533 | 532 | Calcium/calmodulin-dependent protein kinase type II subunit delta | PRO_0000277819 | |||||
Regions | |||||||||
| Domain | 14 – 272 | 259 | Protein kinase | ||||||
| Nucleotide binding | 20 – 28 | 9 | ATP By similarity | ||||||
| Region | 283 – 292 | 10 | Autoinhibitory domain By similarity | ||||||
| Region | 291 – 301 | 11 | Calmodulin-binding By similarity | ||||||
Sites | |||||||||
| Active site | 136 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 43 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 2 | 1 | N-acetylalanine By similarity | ||||||
| Modified residue | 3 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 231 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 287 | 1 | Phosphothreonine; by autocatalysis By similarity | ||||||
| Modified residue | 306 | 1 | Phosphothreonine; by autocatalysis By similarity | ||||||
| Modified residue | 307 | 1 | Phosphothreonine; by autocatalysis By similarity | ||||||
| Modified residue | 315 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 319 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 337 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 364 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 365 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 367 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 368 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 370 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 438 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 475 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 504 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 506 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 524 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 316 | 1 | Missing in isoform 5 and isoform 6. | VSP_023104 | |||||
| Alternative sequence | 328 | 1 | K → KKRKSSSSVQMM in isoform 3. | VSP_023105 | |||||
| Alternative sequence | 329 – 362 | 34 | Missing in isoform 2, isoform 3 and isoform 4. | VSP_023106 | |||||
| Alternative sequence | 512 | 1 | K → N in isoform 4 and isoform 6. | VSP_023107 | |||||
| Alternative sequence | 513 – 533 | 21 | Missing in isoform 4 and isoform 6. | VSP_023108 | |||||
Sequences
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References
| [1] | "New alternatively spliced variants of calmodulin-dependent protein kinase II from rabbit liver." Takeuchi M., Fujisawa H. Gene 221:107-115(1998) [PubMed: 9852955] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY. Tissue: Liver. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | D14906 mRNA. Translation: BAA28870.1. |
| RefSeq | NP_001093424.1. NM_001099954.1. |
| UniGene | Ocu.2311. |
3D structure databases | |
| HSSP | HSSP built from PDB template 2BDW based on UniProtKB Q9NG91. |
| ProteinModelPortal | O77708. |
| SMR | O77708. Positions 11-309, 373-506. |
| ModBase | Search... |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| GeneID | 100101557. |
Phylogenomic databases | |
| GeneTree | ENSGT00550000074354. |
| HOVERGEN | HBG108055. |
Family and domain databases | |
| InterPro | IPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase. IPR013543. Ca/CaM-dep_prot_kinase-assoc. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view] |
| PANTHER | PTHR24347. PTHR24347. 1 hit. |
| Pfam | PF08332. CaMKII_AD. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view] |
| SMART | SM00220. S_TKc. 1 hit. [Graphical view] |
| SUPFAM | SSF56112. Kinase_like. 1 hit. |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Entry information
| Entry name | KCC2D_RABIT | ||||||||
| Accession | Primary (citable) accession number: O77708 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
Relevant documents
| SIMILARITY comments Index of protein domains and families |