View source for CAMK

{{Short description|Enzyme type}}
{{for|the astronomical research centre in Poland|Nicolaus Copernicus Astronomical Center of the Polish Academy of Sciences}}
{{infobox enzyme
| Name       = Ca<sup>2+</sup>/calmodulin-dependent protein kinase
| EC_number  = 2.7.11.17
| CAS_number = 97350-82-8
| GO_code    = 0004683
}}
'''CAMK''', also written as '''CaMK''' or '''CCaMK''', is an abbreviation for the '''Ca<sup>2+</sup>/calmodulin-dependent protein kinase''' class of enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca<sup>2+</sup>) and [[calmodulin]]. When activated, the enzymes transfer phosphates from [[Adenosine triphosphate|ATP]] to defined [[serine]] or [[threonine]] residues in other proteins, so they are [[serine/threonine-specific protein kinase]]s. Activated CAMK is involved in the [[phosphorylation]] of transcription factors and therefore, in the regulation of expression of responding genes. CAMK also works to regulate the cell life cycle (i.e. programmed cell death), rearrangement of the cell's cytoskeletal network, and mechanisms involved in the learning and memory of an organism.<ref name=":0" />

== Types ==
There are 2 common types of CAM Kinase proteins: specialized and multi-functional CAM kinases.

;Substrate-specific CAM Kinases: only have one target that they can phosphorylate, such as myosin light chain kinases.<ref name=":0" /> This group of proteins includes CAMK III. More on [[CAMKIII]] can be found following this link.
;Multi-functional CAM Kinases: have multiple targets they can phosphorylate and are found in processes including the secretion of neurotransmitters, metabolism of glycogen, and the regulation of various transcription factors.<ref name=":0" /> CAMK II is the main protein in this subset. More on [[CAMKII]] can be found following this link.

== Substrate phosphorylation ==
[[File:Psy161ST redrawn.svg|thumb|309x309px|Figure 1: Diagram of how CAMK II becomes active in the presence of calcium or calmodulin.]]
Once calcium concentrations in the cell rise, CAM kinases become saturated and bind the maximum of four calcium molecules.<ref name=":0" /> This calcium saturation activates the kinase and allows it to undergo a conformational change which permits the kinase to bind to its phosphorylation target sites. CAMK removes a phosphate group from ATP, most typically using a Mg<sup>2+</sup> ion, and adds it to the CAM protein, rendering it active.<ref name="pmid11749373">{{cite journal | vauthors = Adams JA | title = Kinetic and catalytic mechanisms of protein kinases | journal = Chemical Reviews | volume = 101 | issue = 8 | pages = 2271–90 | date = August 2001 | pmid = 11749373 | doi = 10.1021/cr000230w }}</ref> The CAM Kinase contains a highly concentrated glycine loop where the gamma phosphate from the donor ATP molecule is easily able to bind to the enzyme which then utilizes the metal ion to facilitate a smooth phosphate transfer to the target protein.<ref name="pmid9202006">{{cite journal | vauthors = Hemmer W, McGlone M, Tsigelny I, Taylor SS | title = Role of the glycine triad in the ATP-binding site of cAMP-dependent protein kinase | journal = The Journal of Biological Chemistry | volume = 272 | issue = 27 | pages = 16946–54 | date = July 1997 | pmid = 9202006 | doi = 10.1074/jbc.272.27.16946 | s2cid = 33795382 | doi-access = free }}</ref> This phosphate transfer then activates the kinase's target and completes the phosphorylation cycle.

Figure 1 shows how the presence of calcium or calmodulin allows for the activation of CAM kinases (CAMK II).[[File:CAMK I structure.png|thumb|Figure 2: Graphic illustration of the crude domains of Calcium/calmodulin-dependent protein kinase 1<ref name=":0">{{cite journal | vauthors = Swulius MT, Waxham MN | title = Ca(2+)/calmodulin-dependent protein kinases | journal = Cellular and Molecular Life Sciences | volume = 65 | issue = 17 | pages = 2637–57 | date = September 2008 | pmid = 18463790 | pmc = 3617042 | doi = 10.1007/s00018-008-8086-2 }}</ref>|186x186px]]

== Structure ==
All kinases have a common structure of a catalytic core including an ATP binding site along with a larger substrate binding site.<ref>{{cite journal | vauthors = Hanks SK | title = Genomic analysis of the eukaryotic protein kinase superfamily: a perspective | journal = Genome Biology | volume = 4 | issue = 5 | pages = 111 | date = 2003 | pmid = 12734000 | pmc = 156577 | doi = 10.1186/gb-2003-4-5-111 | doi-access = free }}</ref> The catalytic core is typically composed of β-strands with the substrate binding site composed of α-helices.<ref>{{cite journal | vauthors = Taylor SS, Yang J, Wu J, Haste NM, Radzio-Andzelm E, Anand G | title = PKA: a portrait of protein kinase dynamics | journal = Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics | volume = 1697 | issue = 1–2 | pages = 259–69 | date = March 2004 | pmid = 15023366 | doi = 10.1016/j.bbapap.2003.11.029 }}</ref> Most all CAM kinases includes a variety of domains, including: a catalytic domain, a regulatory domain, an association domain, and a calcium/calmodulin binding domain.<ref>{{cite journal | vauthors = Hudmon A, Schulman H | title = Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and autoregulation in cellular function | journal = Annual Review of Biochemistry | volume = 71 | issue = 1 | pages = 473–510 | date = 2002-06-01 | pmid = 12045104 | doi = 10.1146/annurev.biochem.71.110601.135410 }}</ref>

;CAMK I: as shown in Figure 2, has a double-lobed structure, consisting of a catalytic, substrate-binding domain and an autoinhibitory domain.<ref name=":0" /> For the autoinhibitory domain to become functional, it must cause the protein to conform in such a way that this domain completely blocks the substrate domain from taking in new targets. Figure 2 goes into detail showing the structure and domains of CAMK I.

;CAMK II: has a variety of different forms, with CAMK 2A being the most common, as shown in Figure 3. CAMK 2A has a ring-like crystalline structure, composed of smaller functional groups. These groups allow for the CaM-dependent phosphorylation of targets, but also allows the structure to autophosphorylate itself and become CaM-independent,<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=815|title=CAMK2A calcium/calmodulin dependent protein kinase II alpha [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2020-03-20}}</ref> as seen in Figure 1. This means once the CAMK 2A protein is initially activated by calcium or calmodulin, it can, in turn, further activate itself, so it doesn't become inactive even when it is without calcium or calmodulin. [[File:PDB 1hkx EBI.jpg|thumb|Figure 3: Image of CAMK 2A which is a form of Calcium/calmodulin-dependent kinase in its crystalline form. |185x185px]]

== Family members ==
Members of the CAMK enzyme class include, but are not limited to:

* [[CAMKI]]
** CAMKIα ([[CAMK1]])
** CAMKIβ (PNCK)
** [[CAMKIδ]]
** CAMKIγ ([[CAMK1G (gene)|CAMK1G]])
* [[CAMKII]]
** [[CAMKIIα]]
** [[CAMKIIβ]]
** [[CAMKIIδ]]
** [[CAMKIIγ]]
* [[CAMKIII]]
* [[CAMKIV]]
* CAMKV CaM kinase like vesicle associated
* SCAMK
* Ca2+/calmodulin-dependent protein kinase kinase
** [[CAMKK1]]
** [[CAMKK2]]

== Pseudokinases ==
[[Pseudokinase]]s are [[pseudoenzyme]]s, proteins that resemble enzymes structurally, but lack catalytic activity.

Some of these pseudokinases that are related to the CAMK family include: 
* Tribbles subfamily
** [[TRIB1]]
** [[TRIB2]]
** [[TRIB3]]

== References ==
{{reflist}}

{{Intracellular signaling peptides and proteins}}
{{Serine/threonine-specific protein kinases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}

[[Category:EC 2.7.11]]