Q13557 (KCC2D_HUMAN) 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
Synonyms:	CAMKD

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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 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 membrane › sarcolemma; 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 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. 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 component	Cell membrane Membrane Sarcoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G1/S transition of mitotic cell cycle Inferred from electronic annotation. Source: Compara calcium ion transport Inferred from electronic annotation. Source: Compara cardiac muscle contraction Inferred from electronic annotation. Source: Compara interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of cardiac muscle hypertrophy Inferred from mutant phenotype Ref.11. Source: UniProtKB protein autophosphorylation Inferred from electronic annotation. Source: Compara 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 ryanodine-sensitive calcium-release channel activity Traceable author statement Ref.15. Source: UniProtKB regulation of sodium ion transport Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	T-tubule Inferred from electronic annotation. Source: Compara axon initial segment Inferred from electronic annotation. Source: Compara calcium- and calmodulin-dependent protein kinase complex Traceable author statement PubMed 11264466. Source: UniProtKB cytosol Traceable author statement. Source: Reactome endocytic vesicle membrane Traceable author statement. Source: Reactome intercalated disc Inferred from electronic annotation. Source: Compara neuromuscular junction Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome sarcoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Non-traceable author statement. Source: UniProtKB calmodulin-dependent protein kinase activity Inferred from electronic annotation. Source: EC
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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.16

Chain

2 – 499

498

Calcium/calmodulin-dependent protein kinase type II subunit delta

PRO_0000086099

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 Ref.16

Modified residue

231

1

Phosphotyrosine By similarity

Modified residue

287

1

Phosphothreonine; by autocatalysis Ref.10

Modified residue

306

1

Phosphothreonine; by autocatalysis Probable

Modified residue

307

1

Phosphothreonine; by autocatalysis Probable

Modified residue

319

1

Phosphoserine Ref.16

Modified residue

330

1

Phosphoserine By similarity

Modified residue

337

1

Phosphothreonine By similarity

Modified residue

404

1

Phosphoserine Ref.16

Modified residue

490

1

Phosphoserine Ref.16

Natural variations

Alternative sequence

328

1

K → KKRKSSSSVQMMEPQTTVIH NPDGNK in isoform Delta 11.

VSP_023095

Alternative sequence

328

1

K → KKRKSSSSVQMM in isoform Delta 3 and isoform Delta 7.

VSP_023096

Alternative sequence

328

1

K → KINNKANVVTSPKENIPTPA L in isoform Delta 4 and isoform Delta 8.

VSP_023097

Alternative sequence

329

1

E → EPQTTVIHNPDGNKE in isoform Delta 9 and isoform Delta 10.

VSP_023098

Alternative sequence

478

1

K → N in isoform Delta 12.

VSP_041820

Alternative sequence

479 – 499

21

Missing in isoform Delta 6, isoform Delta 7, isoform Delta 8, isoform Delta 10 and isoform Delta 12.

VSP_023099

Natural variant

167

1

D → E. Ref.23
Corresponds to variant rs35367671 [ dbSNP | Ensembl ].

VAR_040602

Natural variant

463

1

Q → E.
Corresponds to variant rs1053668 [ dbSNP | Ensembl ].

VAR_028196

Natural variant

493

1

T → I. Ref.23
Corresponds to variant rs35765784 [ dbSNP | Ensembl ].

VAR_040603

Experimental info

Sequence conflict

39

1

E → G in AAD20442. Ref.1

Sequence conflict

272

1

I → T in AAX88806. Ref.4

Secondary structure

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499

Helix Strand Turn

Details...

Beta strand

14 – 23

10

Beta strand

26 – 33

8

Turn

34 – 36

3

Beta strand

39 – 46

8

Helix

47 – 49

3

Helix

52 – 67

16

Beta strand

76 – 82

7

Beta strand

85 – 90

6

Helix

98 – 105

8

Helix

110 – 129

20

Helix

139 – 141

3

Beta strand

142 – 148

7

Beta strand

153 – 155

3

Helix

158 – 160

3

Helix

178 – 180

3

Helix

183 – 186

4

Helix

194 – 209

16

Helix

219 – 228

10

Turn

235 – 240

6

Helix

243 – 252

10

Turn

257 – 259

3

Helix

263 – 266

4

Helix

270 – 273

4

Helix

275 – 278

4

Helix

296 – 310

15

Helix

340 – 363

24

Helix

366 – 372

7

Beta strand

373 – 380

8

Helix

382 – 384

3

Beta strand

389 – 392

4

Helix

393 – 401

9

Beta strand

410 – 421

12

Beta strand

426 – 438

13

Beta strand

444 – 458

15

Beta strand

461 – 470

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform Delta 2 [UniParc]. Last modified October 17, 2006. Version 3. Checksum: 62999FBAB98120CE	FASTA	499	56,369
	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
	Isoform Delta 3 [UniParc]. Checksum: 0F312AC0E5938A07	FASTA	510	57,620
	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 LKKPDGVKKR KSSSSVQMME STESSNTTIE DEDVKARKQE 370 380 390 400 410 420 IIKVTEQLIE AINNGDFEAY TKICDPGLTA FEPEALGNLV EGMDFHRFYF ENALSKSNKP 430 440 450 460 470 480 IHTIILNPHV HLVGDDAACI AYIRLTQYMD GSGMPKTMQS EETRVWHRRD GKWQNVHFHR 490 500 510 SGSPTVPIKP PCIPNGKENF SGGTSLWQNI
	Isoform Delta 4 [UniParc]. Checksum: 184D4250A261D923	FASTA	519	58,472
	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 LKKPDGVKIN NKANVVTSPK ENIPTPALES TESSNTTIED 370 380 390 400 410 420 EDVKARKQEI IKVTEQLIEA INNGDFEAYT KICDPGLTAF EPEALGNLVE GMDFHRFYFE 430 440 450 460 470 480 NALSKSNKPI HTIILNPHVH LVGDDAACIA YIRLTQYMDG SGMPKTMQSE ETRVWHRRDG 490 500 510 KWQNVHFHRS GSPTVPIKPP CIPNGKENFS GGTSLWQNI
	Isoform Delta 6 [UniParc]. Checksum: 571DA27C914E4F7E	FASTA	478	54,128
	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 LVGDDAACIA YIRLTQYMDG SGMPKTMQSE ETRVWHRRDG KWQNVHFHRS GSPTVPIK
	Isoform Delta 7 [UniParc]. Checksum: A45841A7EBFBFA5E	FASTA	489	55,378
	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 LKKPDGVKKR KSSSSVQMME STESSNTTIE DEDVKARKQE 370 380 390 400 410 420 IIKVTEQLIE AINNGDFEAY TKICDPGLTA FEPEALGNLV EGMDFHRFYF ENALSKSNKP 430 440 450 460 470 480 IHTIILNPHV HLVGDDAACI AYIRLTQYMD GSGMPKTMQS EETRVWHRRD GKWQNVHFHR SGSPTVPIK
	Isoform Delta 8 [UniParc]. Checksum: 3EE4353E136343BB	FASTA	498	56,230
	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 LKKPDGVKIN NKANVVTSPK ENIPTPALES TESSNTTIED 370 380 390 400 410 420 EDVKARKQEI IKVTEQLIEA INNGDFEAYT KICDPGLTAF EPEALGNLVE GMDFHRFYFE 430 440 450 460 470 480 NALSKSNKPI HTIILNPHVH LVGDDAACIA YIRLTQYMDG SGMPKTMQSE ETRVWHRRDG 490 KWQNVHFHRS GSPTVPIK
	Isoform Delta 9 [UniParc]. Checksum: 79B81366F7E1C69B	FASTA	513	57,901
	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 LKKPDGVKEP QTTVIHNPDG NKESTESSNT TIEDEDVKAR 370 380 390 400 410 420 KQEIIKVTEQ LIEAINNGDF EAYTKICDPG LTAFEPEALG NLVEGMDFHR FYFENALSKS 430 440 450 460 470 480 NKPIHTIILN PHVHLVGDDA ACIAYIRLTQ YMDGSGMPKT MQSEETRVWH RRDGKWQNVH 490 500 510 FHRSGSPTVP IKPPCIPNGK ENFSGGTSLW QNI
	Isoform Delta 10 [UniParc]. Checksum: E78D0E736590F908	FASTA	492	55,660
	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 LKKPDGVKEP QTTVIHNPDG NKESTESSNT TIEDEDVKAR 370 380 390 400 410 420 KQEIIKVTEQ LIEAINNGDF EAYTKICDPG LTAFEPEALG NLVEGMDFHR FYFENALSKS 430 440 450 460 470 480 NKPIHTIILN PHVHLVGDDA ACIAYIRLTQ YMDGSGMPKT MQSEETRVWH RRDGKWQNVH 490 FHRSGSPTVP IK
	Isoform Delta 11 [UniParc]. Checksum: 3BFC4B5CAF9B3B88	FASTA	524	59,152
	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 LKKPDGVKKR KSSSSVQMME PQTTVIHNPD GNKESTESSN 370 380 390 400 410 420 TTIEDEDVKA RKQEIIKVTE QLIEAINNGD FEAYTKICDP GLTAFEPEAL GNLVEGMDFH 430 440 450 460 470 480 RFYFENALSK SNKPIHTIIL NPHVHLVGDD AACIAYIRLT QYMDGSGMPK TMQSEETRVW 490 500 510 520 HRRDGKWQNV HFHRSGSPTV PIKPPCIPNG KENFSGGTSL WQNI
	Isoform Delta 12 [UniParc]. Checksum: 506DA27C914E4F7E	FASTA	478	54,114
	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 LVGDDAACIA YIRLTQYMDG SGMPKTMQSE ETRVWHRRDG KWQNVHFHRS GSPTVPIN

References

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[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]	"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.
[16]	"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, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE.
[17]	"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.
[18]	"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].
[19]	"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.
[20]	"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].
[21]	"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.
[22]	"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.
[23]	"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.
+	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.

IPI

IPI00172636.
IPI00430291.
IPI00654569.
IPI00827573.
IPI00827606.
IPI00827625.
IPI00827717.
IPI00828139.
IPI00828178.
IPI00876923.

RefSeq

NP_001212.2. NM_001221.3.
NP_742112.1. NM_172114.1.
NP_742113.1. NM_172115.2.
NP_742125.1. NM_172127.2.
NP_742126.1. NM_172128.2.
NP_742127.1. NM_172129.1.

UniGene

Hs.144114.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q13557.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33129N.

IntAct

Q13557. 12 interactions.

MINT

MINT-3028061.

STRING

9606.ENSP00000339740.

PTM databases

PhosphoSite

Q13557.

Polymorphism databases

DMDM

116242602.

Proteomic databases

PaxDb

Q13557.

PRIDE

Q13557.

Protocols and materials databases

DNASU

817.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000296402; ENSP00000296402; ENSG00000145349.
ENST00000342666; ENSP00000339740; ENSG00000145349.
ENST00000379773; ENSP00000369098; ENSG00000145349.
ENST00000394522; ENSP00000378030; ENSG00000145349.
ENST00000394524; ENSP00000378032; ENSG00000145349.
ENST00000394526; ENSP00000378034; ENSG00000145349.
ENST00000418639; ENSP00000406131; ENSG00000145349.
ENST00000429180; ENSP00000415707; ENSG00000145349.
ENST00000454265; ENSP00000415248; ENSG00000145349.
ENST00000508738; ENSP00000422566; ENSG00000145349.
ENST00000515496; ENSP00000423482; ENSG00000145349.

GeneID

817.

KEGG

hsa:817.

UCSC

uc003ibi.3. human.
uc003ibj.3. human.
uc003ibm.2. human.
uc003ibn.2. human.

Organism-specific databases

CTD

817.

GeneCards

GC04M114372.

HGNC

HGNC:1462. CAMK2D.

HPA

HPA026281.

MIM

607708. gene.

neXtProt

NX_Q13557.

PharmGKB

PA92.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG108055.

InParanoid

Q13557.

KO

K04515.

OrthoDB

EOG42JNR7.

PhylomeDB

Q13557.

Enzyme and pathway databases

BRENDA

2.7.11.17. 2681.

Pathway_Interaction_DB

ifngpathway. IFN-gamma pathway.

Reactome

REACT_13685. Neuronal System.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q13557.

Bgee

Q13557.

CleanEx

HS_CAMK2D.

Genevestigator

Q13557.

GermOnline

ENSG00000145349. Homo sapiens.

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.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[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...

Other

BindingDB

Q13557.

ChEMBL

CHEMBL2801.

ChiTaRS

CAMK2D. human.

EvolutionaryTrace

Q13557.

GenomeRNAi

817.

NextBio

3330.

SOURCE

Search...

Entry information

Entry name

KCC2D_HUMAN

Accession

Primary (citable) accession number: Q13557
Secondary accession number(s): A8MVS8 , Q52PK4, Q59G21, Q8N553, Q9UGH6, Q9UQE9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 140 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.