CAMK4

Calcium/calmodulin-dependent protein kinase IV

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2W4O

Identifiers

Symbols

CAMK4 ; CaMK IV; CaMK-GR; IV; caMK

External IDs

OMIM: 114080 MGI: 88258 HomoloGene: 100780 IUPHAR: 1955 ChEMBL: 2494 GeneCards: CAMK4 Gene

EC number

2.7.11.17

Gene ontology
Molecular function	• calmodulin-dependent protein kinase activity • calmodulin binding • ATP binding
Cellular component	• nucleus • nucleoplasm • nucleolus • cytosol • extracellular vesicular exosome
Biological process	• myeloid dendritic cell cytokine production • protein phosphorylation • nucleocytoplasmic transport • inflammatory response • signal transduction • epidermal growth factor receptor signaling pathway • activation of phospholipase C activity • synaptic transmission • neuron-neuron synaptic transmission • long-term memory • fibroblast growth factor receptor signaling pathway • regulation of T cell differentiation in thymus • myeloid dendritic cell differentiation • innate immune response • regulation of osteoclast differentiation • positive regulation of transcription, DNA-templated • positive regulation of protein export from nucleus • neurotrophin TRK receptor signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 5:
111.22 – 111.49 Mb

Chr 18:
32.94 – 33.2 Mb

PubMed search

Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.^[1]

The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca²⁺/calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells.^[2]

References

↑ Sikela JM, Law ML, Kao FT, Hartz JA, Wei Q, Hahn WE (Mar 1989). "Chromosomal localization of the human gene for brain Ca²⁺/calmodulin-dependent protein kinase type IV". Genomics 4 (1): 21–7. doi:10.1016/0888-7543(89)90309-1. PMID 2536634.
↑ "Entrez Gene: CAMK4 calcium/calmodulin-dependent protein kinase IV".

Bredt DS, Ferris CD, Snyder SH (1992). "Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites". J. Biol. Chem. 267 (16): 10976–81. PMID 1375933.
Jensen KF, Ohmstede CA, Fisher RS, Sahyoun N (1991). "Nuclear and axonal localization of Ca²⁺/calmodulin-dependent protein kinase type Gr in rat cerebellar cortex". Proc. Natl. Acad. Sci. U.S.A. 88 (7): 2850–3. doi:10.1073/pnas.88.7.2850. PMC 51337. PMID 2011593.
Selbert MA, Anderson KA, Huang QH et al. (1995). "Phosphorylation and activation of Ca²⁺-calmodulin-dependent protein kinase IV by Ca²⁺-calmodulin-dependent protein kinase Ia kinase. Phosphorylation of threonine 196 is essential for activation". J. Biol. Chem. 270 (29): 17616–21. doi:10.1074/jbc.270.29.17616. PMID 7615569.
Kitani T, Okuno S, Fujisawa H (1994). "cDNA cloning and expression of human calmodulin-dependent protein kinase IV". J. Biochem. 115 (4): 637–40. PMID 8089075.
Mosialos G, Hanissian SH, Jawahar S et al. (1994). "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". J. Virol. 68 (3): 1697–705. PMC 236629. PMID 8107230.
Bland MM, Monroe RS, Ohmstede CA (1994). "The cDNA sequence and characterization of the Ca²⁺/calmodulin-dependent protein kinase-Gr from human brain and thymus". Gene 142 (2): 191–7. doi:10.1016/0378-1119(94)90260-7. PMID 8194751.
Tokumitsu H, Soderling TR (1996). "Requirements for calcium and calmodulin in the calmodulin kinase activation cascade". J. Biol. Chem. 271 (10): 5617–22. doi:10.1074/jbc.271.10.5617. PMID 8621423.
Chatila T, Anderson KA, Ho N, Means AR (1996). "A unique phosphorylation-dependent mechanism for the activation of Ca²⁺/calmodulin-dependent protein kinase type IV/GR". J. Biol. Chem. 271 (35): 21542–8. doi:10.1074/jbc.271.35.21542. PMID 8702940.
Melander Gradin H, Marklund U, Larsson N et al. (1997). "Regulation of microtubule dynamics by Ca²⁺/calmodulin-dependent kinase IV/Gr-dependent phosphorylation of oncoprotein 18". Mol. Cell. Biol. 17 (6): 3459–67. PMC 232199. PMID 9154845.
Matsushita M, Nairn AC (1998). "Characterization of the mechanism of regulation of Ca²⁺/ calmodulin-dependent protein kinase I by calmodulin and by Ca²⁺/calmodulin-dependent protein kinase kinase". J. Biol. Chem. 273 (34): 21473–81. doi:10.1074/jbc.273.34.21473. PMID 9705275.
Anderson KA, Means RL, Huang QH et al. (1998). "Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization and cellular localization of Ca²⁺/calmodulin-dependent protein kinase kinase beta". J. Biol. Chem. 273 (48): 31880–9. doi:10.1074/jbc.273.48.31880. PMID 9822657.
Hayashi Y, Nishio M, Naito Y et al. (1999). "Regulation of neuronal nitric-oxide synthase by calmodulin kinases". J. Biol. Chem. 274 (29): 20597–602. doi:10.1074/jbc.274.29.20597. PMID 10400690.
Blaeser F, Ho N, Prywes R, Chatila TA (2000). "Ca²⁺-dependent gene expression mediated by MEF2 transcription factors". J. Biol. Chem. 275 (1): 197–209. doi:10.1074/jbc.275.1.197. PMID 10617605.
Moreno CS, Park S, Nelson K et al. (2000). "WD40 repeat proteins striatin and S/G(2) nuclear autoantigen are members of a novel family of calmodulin-binding proteins that associate with protein phosphatase 2A". J. Biol. Chem. 275 (8): 5257–63. doi:10.1074/jbc.275.8.5257. PMC 3505218. PMID 10681496.
Komeima K, Hayashi Y, Naito Y, Watanabe Y (2000). "Inhibition of neuronal nitric-oxide synthase by calcium/ calmodulin-dependent protein kinase IIalpha through Ser847 phosphorylation in NG108-15 neuronal cells". J. Biol. Chem. 275 (36): 28139–43. doi:10.1074/jbc.M003198200. PMID 10874031.
Wu JY, Ribar TJ, Cummings DE et al. (2000). "Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ cells lacking Camk4". Nat. Genet. 25 (4): 448–52. doi:10.1038/78153. PMID 10932193.
Jang MK, Goo YH, Sohn YC et al. (2001). "Ca²⁺/calmodulin-dependent protein kinase IV stimulates nuclear factor-kappa B transactivation via phosphorylation of the p65 subunit". J. Biol. Chem. 276 (23): 20005–10. doi:10.1074/jbc.M010211200. PMID 11274168.
Hsu LS, Chen GD, Lee LS et al. (2001). "Human Ca²⁺/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity". J. Biol. Chem. 276 (33): 31113–23. doi:10.1074/jbc.M011720200. PMID 11395482.
Zhao X, Ito A, Kane CD et al. (2001). "The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking". J. Biol. Chem. 276 (37): 35042–8. doi:10.1074/jbc.M105086200. PMID 11470791.
Ainhoa Bilbaoa, Jan Rodriguez Parkitnab, David Engblomb, Stéphanie Perreau-Lenza, Carles Sanchis-Seguraa, Miriam Schneidera, Witold Konopkab, Magdalena Westphalb, Gerome Breenc, Sylvane Desrivieresc, Matthias Klugmannd, Camila Guindalinie, Homero Valladag, Ronaldo Laranjeirae, Fernando Rodriguez de Fonsecah, Gunter Schumannc, Günther Schützb, and Rainer Spanagela (2008). "Loss of the Ca²⁺/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine". Proceedings of the National Academy of Sciences of the United States of America (PNAS) 105 (45): 17549–54. doi:10.1073/pnas.0803959105. PMC 2582267. PMID 19001277.
Feliciano DM and Edelman AM (2009). "Repression of Ca²⁺/calmodulin-dependent protein kinase IV signaling accelerates retinoic acid-induced differentiation of human neuroblastoma cells.". J. Biol. Chem. 284 (39): 26466–81. doi:10.1074/jbc.M109.027680. PMC 2785335. PMID 19633294.

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated Mammalian target of rapamycin EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3

(3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)) (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDC2L5 CRKRS PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

Biochemistry overview
Enzymes overview
By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
  - 2.7.10
  - 11-12
- 8
3.1
- - 3.1.3.48
- 2
- 3
- 4
  - 3.4.21
  - 22
  - 23
  - 24
- 5
- 6
- 7
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

CAMK4

References

Further reading