Q95266 (KCC2D_PIG) Reviewed, UniProtKB/Swiss-Prot

Names 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

Name:

CAMK2D

Organism

Sus scrofa (Pig) [Complete proteome]

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	499 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 By similarity.
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 CACNB2 By similarity.
Subcellular location	Cell membrane › sarcolemma; Peripheral membrane protein; Cytoplasmic side Probable. Sarcoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side Probable.
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

Keywords
Cellular component	Cell membrane Membrane Sarcoplasmic reticulum
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	positive regulation of cardiac muscle hypertrophy Inferred from sequence or structural similarity. Source: UniProtKB regulation of cellular localization Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	sarcoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin-dependent protein kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 499	498	Calcium/calmodulin-dependent protein kinase type II subunit delta		PRO_0000277818
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	330	1	Phosphoserine By similarity
	Modified residue	331	1	Phosphothreonine By similarity
	Modified residue	333	1	Phosphoserine By similarity
	Modified residue	334	1	Phosphoserine By similarity
	Modified residue	336	1	Phosphothreonine By similarity
	Modified residue	337	1	Phosphothreonine By similarity
	Modified residue	404	1	Phosphoserine By similarity
	Modified residue	441	1	Phosphoserine By similarity
	Modified residue	470	1	Phosphoserine By similarity
	Modified residue	472	1	Phosphoserine By similarity
	Modified residue	490	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q95266 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: D6999FB8D41120D3	FASTA	499	56,389
	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 GSPTVPIKPS 490 CIPNGKENFS GSTSLWQNI

References

[1]	"Novel Ca2+/calmodulin-dependent protein kinase II gamma-subunit variants expressed in vascular smooth muscle, brain, and cardiomyocytes." Singer H.A., Benscoter H.A., Schworer C.M. J. Biol. Chem. 272:9393-9400(1997) [PubMed: 9083077] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Aortic smooth muscle.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U73504 mRNA. Translation: AAC48715.1.
RefSeq	NP_999546.1. NM_214381.1.
UniGene	Ssc.14480.
3D structure databases
HSSP	HSSP built from PDB template 2BDW based on UniProtKB Q9NG91.
ProteinModelPortal	Q95266.
SMR	Q95266. Positions 11-309, 336-474.
ModBase	Search...
Protein-protein interaction databases
STRING	Q95266.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSSSCT00000009990; ENSSSCP00000009730; ENSSSCG00000009123.
GeneID	397674.
KEGG	ssc:397674.
Organism-specific databases
CTD	817.
Phylogenomic databases
GeneTree	ENSGT00550000074354.
HOVERGEN	HBG108055.
OMA	INTMSAL.
OrthoDB	EOG42JNR7.
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]
KO	K04515.
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_PIG

Accession

Primary (citable) accession number: Q95266

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 20, 2007
Last sequence update:	February 1, 1997
Last modified:	January 25, 2012
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program