CAMKK2

Calcium/calmodulin-dependent protein kinase kinase 2 is an enzyme that in humans is encoded by the CAMKK2 gene.[5][6]

CAMKK2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCAMKK2, CAMKK, CAMKKB, calcium/calmodulin-dependent protein kinase kinase 2, calcium/calmodulin dependent protein kinase kinase 2
External IDsOMIM: 615002 MGI: 2444812 HomoloGene: 32756 GeneCards: CAMKK2
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12q24.31Start121,237,675 bp[1]
End121,298,308 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

10645

207565

Ensembl

ENSG00000110931

ENSMUSG00000029471

UniProt

Q96RR4

Q8C078

RefSeq (mRNA)

NM_001199676
NM_145358

RefSeq (protein)

NP_001186605
NP_663333

Location (UCSC)Chr 12: 121.24 – 121.3 MbChr 5: 122.73 – 122.78 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

The product of this gene belongs to the serine/threonine-specific protein kinase family, and to the Ca++/calmodulin-dependent protein kinase subfamily. This protein plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade by phosphorylating the downstream kinases CaMK1 and CaMK4.[6]

CaMKK2 regulates production of the appetite stimulating hormone neuropeptide Y and functions as an AMPK kinase in the hypothalamus.[7] It also has an important role in the development of hyperalgesia and tolerance to opioid analgesic drugs, through reduction in downstream signalling pathways and mu opioid receptor downregulation.[8][9][10] Inhibition of CaMKK2 in mice reduces appetite and promotes weight loss.[7]

Isoforms

Seven transcript variants encoding six distinct isoforms have been identified for this gene. Additional splice variants have been described but their full-length nature has not been determined. The identified isoforms exhibit a distinct ability to undergo autophosphorylation and to phosphorylate the downstream kinases.[6][11]

References

  1. GRCh38: Ensembl release 89: ENSG00000110931 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000029471 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Hsu LS, Tsou AP, Chi CW, Lee CH, Chen JY (Sep 1998). "Cloning, expression and chromosomal localization of human Ca2+/calmodulin-dependent protein kinase kinase". J Biomed Sci. 5 (2): 141–9. doi:10.1159/000025324. PMID 9662074. S2CID 90281764.
  6. "Entrez Gene: CAMKK2 calcium/calmodulin-dependent protein kinase kinase 2, beta".
  7. Anderson KA, Ribar TJ, Lin F, Noeldner PK, Green MF, Muehlbauer MJ, Witters LA, Kemp BE, Means AR (May 2008). "Hypothalamic CaMKK2 contributes to the regulation of energy balance". Cell Metab. 7 (5): 377–88. doi:10.1016/j.cmet.2008.02.011. PMID 18460329.
  8. Sánchez-Blázquez P, Rodríguez-Muñoz M, Montero C, de la Torre-Madrid E, Garzón J (February 2008). "Calcium/calmodulin-dependent protein kinase II supports morphine antinociceptive tolerance by phosphorylation of glycosylated phosducin-like protein". Neuropharmacology. 54 (2): 319–30. doi:10.1016/j.neuropharm.2007.10.002. hdl:10261/63344. PMID 18006024. S2CID 23956064.
  9. Chen Y, Jiang Y, Yue W, Zhou Y, Lu L, Ma L (October 2008). "Chronic, but not acute morphine treatment, up-regulates alpha-Ca2+/calmodulin dependent protein kinase II gene expression in rat brain". Neurochemical Research. 33 (10): 2092–8. doi:10.1007/s11064-008-9690-0. PMID 18408996. S2CID 1686579.
  10. Chen Y, Yang C, Wang ZJ (January 2010). "Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation and maintenance of opioid-induced hyperalgesia". Journal of Neuroscience. 30 (1): 38–46. doi:10.1523/JNEUROSCI.4346-09.2010. PMC 2821163. PMID 20053885.
  11. Hsu LS, Chen GD, Lee LS, Chi CW, Cheng JF, Chen JY (August 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.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.