Q16566 (KCC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Calcium/calmodulin-dependent protein kinase type IV
Short name=CaMK IV
EC=2.7.11.17

Alternative name(s):
CaM kinase-GR

Gene names

Name:	CAMK4
Synonyms:	CAMK, CAMK-GR, CAMKIV

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	473 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA, which play pivotal roles in immune response, inflammation, and memory consolidation. In the thymus, regulates the CD4+/CD8+ double positive thymocytes selection threshold during T-cell ontogeny. In CD4 memory T-cells, is required to link T-cell antigen receptor (TCR) signaling to the production of IL2, IFNG and IL4 (through the regulation of CREB and MEF2). Regulates the differentiation and survival phases of osteoclasts and dendritic cells (DCs). Mediates DCs survival by linking TLR4 and the regulation of temporal expression of BCL2. Phosphorylates the transcription activator CREB1 on 'Ser-133' in hippocampal neuron nuclei and contribute to memory consolidation and long term potentiation (LTP) in the hippocampus. Can activate the MAP kinases MAPK1/ERK2, MAPK8/JNK1 and MAPK14/p38 and stimulate transcription through the phosphorylation of ELK1 and ATF2. Can also phosphorylate in vitro CREBBP, PRM2, MEF2A and STMN1/OP18. Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13 Ref.17 Ref.18
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 phosphorylation of Thr-200 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-200 results in a 10-20-fold increase in total activity to generate Ca2+/calmodulin-independent activity. Autophosphorylation of the N-terminus Ser-12 and Ser-13 is required for full activation. Inactivated by protein phosphatase 2A (PPP2CA/PPP2CB) which dephosphorylates Thr-200, thereby terminating autonomous activity and helping to maintain the enzyme in its autoinhibited state. Ref.10 Ref.15 Ref.16
Subunit structure	Monomer By similarity. Interacts with protein phosphatase 2A (PPP2CA/PPP2CB); the interaction is mutually exclusive with binding to Ca2+/calmodulin. Ref.15
Subcellular location	Cytoplasm. Nucleus. Note: Localized in hippocampal neuron nuclei. In spermatids, associated with chromatin and nuclear matrix By similarity. Ref.8 Ref.9
Tissue specificity	Expressed in brain, thymus, CD4 T-cells, testis and epithelial ovarian cancer tissue. Ref.6 Ref.7 Ref.14
Developmental stage	Expressed during differentiation of monocyte-derived dendritic cells (at protein level). Ref.17
Domain	The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate. Ref.7 Ref.16
Post-translational modification	Phosphorylated by CaMKK1 and CaMKK2 on Thr-200. Dephosphorylated by protein phosphatase 2A. Autophosphorylated on Ser-12 and Ser-13. Ref.10 Ref.15 Ref.19 Glycosylation at Ser-189 modulates the phosphorylation of CaMK4 at Thr-200 and negatively regulates its activity toward CREB1 in basal conditions and during early inomycin stimulation.
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 AAH16695.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity Inflammatory response
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Calcium Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of phospholipase C activity Traceable author statement. Source: Reactome epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW long-term memory Inferred from genetic interaction Ref.18. Source: UniProtKB myeloid dendritic cell differentiation Inferred from mutant phenotype Ref.17. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome neuron-neuron synaptic transmission Inferred from electronic annotation. Source: Compara nucleocytoplasmic transport Inferred from electronic annotation. Source: Compara positive regulation of protein export from nucleus Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.11. Source: UniProtKB protein phosphorylation Traceable author statement Ref.1. Source: ProtInc regulation of T cell differentiation in thymus Traceable author statement Ref.22. Source: UniProtKB regulation of osteoclast differentiation Traceable author statement Ref.22. Source: UniProtKB synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleolus Inferred from direct assay. Source: HPA nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ATP 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

Chain

1 – 473

473

Calcium/calmodulin-dependent protein kinase type IV

PRO_0000086106

Regions

Domain

46 – 300

255

Protein kinase

Nucleotide binding

52 – 60

9

ATP By similarity

Region

305 – 321

17

Autoinhibitory domain

Region

306 – 323

18

PP2A-binding

Region

322 – 341

20

Calmodulin-binding Potential

Sites

Active site

164

1

Proton acceptor By similarity

Binding site

75

1

ATP By similarity

Amino acid modifications

Modified residue

12

1

Phosphoserine; by autocatalysis Ref.10

Modified residue

13

1

Phosphoserine; by autocatalysis Ref.10

Modified residue

200

1

Phosphothreonine; by CaMKK1 and CaMKK2 Ref.10 Ref.15 Ref.19

Modified residue

336

1

Phosphoserine; by autocatalysis

Modified residue

360

1

Phosphoserine Ref.23

Glycosylation

57

1

O-linked (GlcNAc) Ref.19

Glycosylation

58

1

O-linked (GlcNAc) Ref.19

Glycosylation

137

1

O-linked (GlcNAc) Ref.19

Glycosylation

189

1

O-linked (GlcNAc) Ref.19

Glycosylation

344

1

O-linked (GlcNAc) Ref.19

Glycosylation

345

1

O-linked (GlcNAc) Ref.19

Glycosylation

356

1

O-linked (GlcNAc) Ref.19

Natural variations

Natural variant

150

1

E → G in a lung adenocarcinoma sample; somatic mutation. Ref.26

VAR_040604

Natural variant

178

1

D → N. Ref.26
Corresponds to variant rs35548075 [ dbSNP | Ensembl ].

VAR_040605

Natural variant

465

1

Q → R. Ref.26
Corresponds to variant rs56360861 [ dbSNP | Ensembl ].

VAR_040606

Natural variant

469

1

I → M in a lung large cell carcinoma sample; somatic mutation. Ref.26

VAR_040607

Experimental info

Mutagenesis

12

1

S → A: Loss of activity. Ref.10 Ref.15

Mutagenesis

13

1

S → A: Loss of activity. Ref.10 Ref.15

Mutagenesis

57 – 58

2

TS → AA: Loss of phosphorylation of CREB1. Ref.15

Mutagenesis

75

1

K → E: Loss of activity; dominant negative form. Ref.13 Ref.15

Mutagenesis

189

1

S → A: Increases phosphorylation of CREB1 2-fold. Decreases total O-linked glycosylation 2-fold. Increases ATP-binding affinity. Ref.15 Ref.19

Mutagenesis

200

1

T → A: Loss of activation by CaMKK1 or CaMKK2. Ref.11 Ref.15

Mutagenesis

309 – 312

4

HMDT → DEDD: Fully active Ca2+/CaM-independent kinase; when associated with 320-A-A-321. Ref.7 Ref.15

Mutagenesis

320 – 321

2

FN → DD: Fully active Ca2+/CaM-independent kinase; when associated with 309-A--A-312. Loss of interaction with PPP2CA/PPP2CB. Ref.15

Secondary structure

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473

Helix Strand Turn

Details...

Beta strand

36 – 38

3

Helix

42 – 44

3

Beta strand

46 – 54

9

Beta strand

56 – 65

10

Turn

66 – 68

3

Beta strand

71 – 78

8

Helix

91 – 95

5

Beta strand

104 – 109

6

Beta strand

111 – 118

8

Helix

126 – 130

5

Helix

138 – 157

20

Helix

167 – 169

3

Beta strand

170 – 176

7

Beta strand

181 – 183

3

Helix

205 – 207

3

Helix

210 – 213

4

Helix

221 – 236

16

Helix

247 – 255

9

Turn

263 – 268

6

Helix

271 – 278

8

Helix

285 – 287

3

Helix

291 – 296

6

Turn

298 – 301

4

Helix

311 – 335

25

Sequences

	Sequence		Length	Mass (Da)
	Q16566 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: EFEE51E5612326DC	FASTA	473	51,926
	10 20 30 40 50 60 MLKVTVPSCS ASSCSSVTAS AAPGTASLVP DYWIDGSNRD ALSDFFEVES ELGRGATSIV 70 80 90 100 110 120 YRCKQKGTQK PYALKVLKKT VDKKIVRTEI GVLLRLSHPN IIKLKEIFET PTEISLVLEL 130 140 150 160 170 180 VTGGELFDRI VEKGYYSERD AADAVKQILE AVAYLHENGI VHRDLKPENL LYATPAPDAP 190 200 210 220 230 240 LKIADFGLSK IVEHQVLMKT VCGTPGYCAP EILRGCAYGP EVDMWSVGII TYILLCGFEP 250 260 270 280 290 300 FYDERGDQFM FRRILNCEYY FISPWWDEVS LNAKDLVRKL IVLDPKKRLT TFQALQHPWV 310 320 330 340 350 360 TGKAANFVHM DTAQKKLQEF NARRKLKAAV KAVVASSRLG SASSSHGSIQ ESHKASRDPS 370 380 390 400 410 420 PIQDGNEDMK AIPEGEKIQG DGAQAAVKGA QAELMKVQAL EKVKGADINA EEAPKMVPKA 430 440 450 460 470 VEDGIKVADL ELEEGLAEEK LKTVEEAAAP REGQGSSAVG FEVPQQDVIL PEY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and expression of human calmodulin-dependent protein kinase IV." Kitani T., Okuno S., Fujisawa H. J. Biochem. 115:637-640(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The cDNA sequence and characterization of the Ca2+/calmodulin-dependent protein kinase-Gr from human brain and thymus." Bland M.M., Monroe R.S., Ohmstede C.A. Gene 142:191-197(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cerebellum and Thymus.
[3]	"A Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, expressed after transformation of primary human B lymphocytes by Epstein-Barr virus (EBV) is induced by the EBV oncogene LMP1." Mosialos G., Hanissian S.H., Jawahar S., Vara L., Kieff E., Chatila T.A. J. Virol. 68:1697-1705(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Brain and Lung.
[6]	"Expression of a Ca2+/calmodulin-dependent protein kinase, CaM kinase-Gr, in human T lymphocytes. Regulation of kinase activity by T cell receptor signaling." Hanissian S.H., Frangakis M., Bland M.M., Jawahar S., Chatila T.A. J. Biol. Chem. 268:20055-20063(1993) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Activation mechanisms for Ca2+/calmodulin-dependent protein kinase IV. Identification of a brain CaM-kinase IV kinase." Tokumitsu H., Brickey D.A., Glod J., Hidaka H., Sikela J., Soderling T.R. J. Biol. Chem. 269:28640-28647(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DOMAIN AUTOINHIBITORY, MUTAGENESIS OF 309-HIS--THR-312 AND 320-PHE-ASN-321.
[8]	"Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression." Matthews R.P., Guthrie C.R., Wailes L.M., Zhao X., Means A.R., McKnight G.S. Mol. Cell. Biol. 14:6107-6116(1994) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CREB1, SUBCELLULAR LOCATION.
[9]	"CREB phosphorylation and dephosphorylation: a Ca(2+)- and stimulus duration-dependent switch for hippocampal gene expression." Bito H., Deisseroth K., Tsien R.W. Cell 87:1203-1214(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]	"A unique phosphorylation-dependent mechanism for the activation of Ca2+/calmodulin-dependent protein kinase type IV/GR." Chatila T., Anderson K.A., Ho N., Means A.R. J. Biol. Chem. 271:21542-21548(1996) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, PHOSPHORYLATION AT SER-12; SER-13 AND THR-200, MUTAGENESIS OF SER-12 AND SER-13.
[11]	"Regulation of mitogen-activated protein kinases by a calcium/calmodulin-dependent protein kinase cascade." Enslen H., Tokumitsu H., Stork P.J., Davis R.J., Soderling T.R. Proc. Natl. Acad. Sci. U.S.A. 93:10803-10808(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF ELK1; JUN AND ATF2, MUTAGENESIS OF THR-200.
[12]	"Regulation of microtubule dynamics by Ca2+/calmodulin-dependent kinase IV/Gr-dependent phosphorylation of oncoprotein 18." Melander Gradin H., Marklund U., Larsson N., Chatila T.A., Gullberg M. Mol. Cell. Biol. 17:3459-3467(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF STMN1.
[13]	"Ca(2+)-dependent gene expression mediated by MEF2 transcription factors." Blaeser F., Ho N., Prywes R., Chatila T.A. J. Biol. Chem. 275:197-209(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MEF2D, MUTAGENESIS OF LYS-75.
[14]	"Ca(2+)/calmodulin-dependent protein kinase IV expression in epithelial ovarian cancer." Takai N., Miyazaki T., Nishida M., Nasu K., Miyakawa I. Cancer Lett. 183:185-193(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[15]	"Regulation and function of the calcium/calmodulin-dependent protein kinase IV/protein serine/threonine phosphatase 2A signaling complex." Anderson K.A., Noeldner P.K., Reece K., Wadzinski B.E., Means A.R. J. Biol. Chem. 279:31708-31716(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, INTERACTION WITH PROTEIN PHOSPHATASE 2A, PHOSPHORYLATION AT THR-200, MUTAGENESIS OF 320-PHE-ASN-321.
[16]	"The autonomous activity of calcium/calmodulin-dependent protein kinase IV is required for its role in transcription." Chow F.A., Anderson K.A., Noeldner P.K., Means A.R. J. Biol. Chem. 280:20530-20538(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, PROTEIN PHOSPHATASE 2A BINDING DOMAIN.
[17]	"Calmodulin-dependent kinase IV links Toll-like receptor 4 signaling with survival pathway of activated dendritic cells." Illario M., Giardino-Torchia M.L., Sankar U., Ribar T.J., Galgani M., Vitiello L., Masci A.M., Bertani F.R., Ciaglia E., Astone D., Maulucci G., Cavallo A., Vitale M., Cimini V., Pastore L., Means A.R., Rossi G., Racioppi L. Blood 111:723-731(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DENDRITIC CELLS LIFESPAN REGULATION, DEVELOPMENTAL STAGE.
[18]	"Upregulation of calcium/calmodulin-dependent protein kinase IV improves memory formation and rescues memory loss with aging." Fukushima H., Maeda R., Suzuki R., Suzuki A., Nomoto M., Toyoda H., Wu L.J., Xu H., Zhao M.G., Ueda K., Kitamoto A., Mamiya N., Yoshida T., Homma S., Masushige S., Zhuo M., Kida S. J. Neurosci. 28:9910-9919(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[19]	"Regulation of calcium/calmodulin-dependent kinase IV by O-GlcNAc modification." Dias W.B., Cheung W.D., Wang Z., Hart G.W. J. Biol. Chem. 284:21327-21337(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-57 SER-58; SER-137; SER-189; SER-344; SER-345 AND SER-356, PHOSPHORYLATION AT THR-200, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF 57-THR-SER-58 AND SER-189.
[20]	"Calmodulin-dependent protein kinase IV: regulation of function and expression." Krebs J. Biochim. Biophys. Acta 1448:183-189(1998) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION, REVIEW ON ENZYME REGULATION.
[21]	"Calmodulin-kinases: modulators of neuronal development and plasticity." Wayman G.A., Lee Y.S., Tokumitsu H., Silva A.J., Silva A., Soderling T.R. Neuron 59:914-931(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION IN NEURONAL PLASTICITY.
[22]	"Calcium/calmodulin-dependent kinase IV in immune and inflammatory responses: novel routes for an ancient traveller." Racioppi L., Means A.R. Trends Immunol. 29:600-607(2008) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON INVOLVEMENT IN IMMUNE AND INFLAMMATORY RESPONSE.
[23]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-360, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[24]	"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].
[25]	"Crystal structure of human CAMK4 in complex with 4-amino(sulfamoyl-phenylamino)-triazole-carbothioic acid (2,6-difluoro-phenyl)-amide)." Muniz J.R.C., Rellos P., Gileadi O., Fedorov O., Filippakopoulos P., Salah E., Pike A., Phillips C., Niesen F., Shrestha L., Burgess-Brown N., Bullock A., Berridge G., Vondelft F., Edwards A.M., Bountra C., Arrowsmith C.H., Weigelt J., Knapp S. Submitted (NOV-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) OF 15-340 IN COMPLEX WITH INHIBITOR.
[26]	"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] GLY-150; ASN-178; ARG-465 AND MET-469.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D30742 mRNA. Translation: BAA06403.1.
L17000 mRNA. Translation: AAA35639.1.
L24959 mRNA. Translation: AAA18251.1.
CH471086 Genomic DNA. Translation: EAW49033.1.
CH471086 Genomic DNA. Translation: EAW49034.1.
BC016695 mRNA. Translation: AAH16695.2. Different initiation.
BC025687 mRNA. Translation: AAH25687.1.

IPI

IPI00430411.

PIR

A53036.

RefSeq

NP_001735.1. NM_001744.4.

UniGene

Hs.591269.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2W4O	X-ray	2.17	A	15-340	[»]

ProteinModelPortal

Q16566.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41997N.

IntAct

Q16566. 1 interaction.

STRING

9606.ENSP00000282356.

PTM databases

PhosphoSite

Q16566.

Polymorphism databases

DMDM

2499586.

Proteomic databases

PaxDb

Q16566.

PeptideAtlas

Q16566.

PRIDE

Q16566.

Protocols and materials databases

DNASU

814.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000282356; ENSP00000282356; ENSG00000152495.
ENST00000512453; ENSP00000422634; ENSG00000152495.

GeneID

814.

KEGG

hsa:814.

UCSC

uc003kpf.3. human.

Organism-specific databases

CTD

814.

GeneCards

GC05P110587.

HGNC

HGNC:1464. CAMK4.

HPA

CAB004347.
HPA011753.
HPA017206.

MIM

114080. gene.

neXtProt

NX_Q16566.

PharmGKB

PA26050.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233016.

HOVERGEN

HBG108055.

InParanoid

Q16566.

KO

K05869.

OMA

CEQFGLS.

PhylomeDB

Q16566.

Enzyme and pathway databases

BRENDA

2.7.11.17. 2681.

Pathway_Interaction_DB

nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
hdac_classii_pathway. Signaling events mediated by HDAC Class II.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.

Reactome

REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q16566.

Bgee

Q16566.

CleanEx

HS_CAMK4.

Genevestigator

Q16566.

GermOnline

ENSG00000152495. Homo sapiens.

Family and domain databases

InterPro

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]

Pfam

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

Q16566.

ChEMBL

CHEMBL2494.

ChiTaRS

CAMK4. human.

EvolutionaryTrace

Q16566.

GenomeRNAi

814.

NextBio

3300.

PMAP-CutDB

Q16566.

SOURCE

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Entry information

Entry name

KCC4_HUMAN

Accession

Primary (citable) accession number: Q16566
Secondary accession number(s): D3DSZ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 130 of the entry and version 1 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.