Calcium/calmodulin-dependent protein kinase type 1

Details

Name
Calcium/calmodulin-dependent protein kinase type 1
Synonyms
  • 2.7.11.17
  • CaM kinase I
  • CaM kinase I alpha
  • CaM-KI
  • CaMKI-alpha
Gene Name
CAMK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051712|Calcium/calmodulin-dependent protein kinase type 1
MLGAVEGPRWKQAEDIRDIYDFRDVLGTGAFSEVILAEDKRTQKLVAIKCIAKEALEGKE
GSMENEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVSGGELFDRIVEKGFYTERDASR
LIFQVLDAVKYLHDLGIVHRDLKPENLLYYSLDEDSKIMISDFGLSKMEDPGSVLSTACG
TPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDAKLFEQILKAEYEFDSP
YWDDISDSAKDFIRHLMEKDPEKRFTCEQALQHPWIAGDTALDKNIHQSVSEQIKKNFAK
SKWKQAFNATAVVRHMRKLQLGTSQEGQGQTASHGELLTPVAGGPAAGCCCRDCCVEPGT
ELSPTLPHQL
Number of residues
370
Molecular Weight
41336.705
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / calmodulin binding / calmodulin-dependent protein kinase activity
Processes
cell cycle / intracellular signal transduction / negative regulation of protein binding / nucleocytoplasmic transport / peptidyl-threonine phosphorylation / positive regulation of dendritic spine development / positive regulation of muscle cell differentiation / positive regulation of neuron projection development / positive regulation of peptidyl-serine phosphorylation / positive regulation of protein acetylation / positive regulation of protein export from nucleus / positive regulation of protein serine/threonine kinase activity / positive regulation of synapse structural plasticity / positive regulation of syncytium formation by plasma membrane fusion / positive regulation of transcription by RNA polymerase II / protein phosphorylation / regulation of muscle cell differentiation / regulation of protein binding / regulation of protein localization / signal transduction
Components
cytoplasm / intracellular / nucleus
General Function
Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0051713|Calcium/calmodulin-dependent protein kinase type 1 (CAMK1)
ATGCTGGGGGCAGTGGAAGGCCCCAGGTGGAAGCAGGCGGAGGACATTAGAGACATCTAC
GACTTCCGAGATGTTCTGGGCACGGGGGCCTTCTCGGAGGTGATCCTGGCAGAAGATAAG
AGGACGCAGAAGCTGGTGGCCATCAAATGCATTGCCAAGGAGGCCCTGGAGGGCAAGGAA
GGCAGCATGGAGAATGAGATTGCTGTCCTGCACAAGATCAAGCACCCCAACATTGTAGCC
CTGGATGACATCTATGAGAGTGGGGGCCACCTCTACCTCATCATGCAGCTGGTGTCGGGT
GGGGAGCTCTTTGACCGTATTGTGGAAAAAGGCTTCTACACGGAGCGGGACGCCAGCCGC
CTCATCTTCCAGGTGCTGGATGCTGTGAAATACCTGCATGACCTGGGCATTGTACACCGG
GATCTCAAGCCAGAGAATCTGCTGTACTACAGCCTGGATGAAGACTCCAAAATCATGATC
TCCGACTTTGGCCTCTCCAAGATGGAGGACCCGGGCAGTGTGCTCTCCACCGCCTGTGGA
ACTCCGGGATACGTGGCCCCTGAAGTCCTGGCCCAGAAGCCCTACAGCAAGGCTGTGGAT
TGCTGGTCCATAGGTGTCATCGCCTACATCTTGCTCTGCGGTTACCCTCCCTTCTATGAC
GAGAATGATGCCAAACTCTTTGAACAGATTTTGAAGGCCGAGTACGAGTTTGACTCTCCT
TACTGGGACGACATCTCTGACTCTGCCAAAGATTTCATCCGGCACTTGATGGAGAAGGAC
CCAGAGAAAAGATTCACCTGTGAGCAGGCCTTGCAGCACCCATGGATTGCAGGAGATACA
GCTCTAGATAAGAATATCCACCAGTCGGTGAGTGAGCAGATCAAGAAGAACTTTGCCAAG
AGCAAGTGGAAGCAAGCCTTCAATGCCACGGCTGTGGTGCGGCACATGAGGAAACTGCAG
CTGGGCACCAGCCAGGAGGGGCAGGGGCAGACGGCGAGCCATGGGGAGCTGCTGACACCA
GTGGCTGGGGGGCCGGCAGCTGGCTGTTGCTGTCGAGACTGCTGCGTGGAGCCGGGCACA
GAACTGTCCCCCACACTGCCCCACCAGCTCTAG
Chromosome Location
3
Locus
3p25.3
External Identifiers
ResourceLink
UniProtKB IDQ14012
UniProtKB Entry NameKCC1A_HUMAN
HGNC IDHGNC:1459
General References
  1. Haribabu B, Hook SS, Selbert MA, Goldstein EG, Tomhave ED, Edelman AM, Snyderman R, Means AR: Human calcium-calmodulin dependent protein kinase I: cDNA cloning, domain structure and activation by phosphorylation at threonine-177 by calcium-calmodulin dependent protein kinase I kinase. EMBO J. 1995 Aug 1;14(15):3679-86. [Article]
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  3. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [Article]
  4. Hsu LS, Tsou AP, Chi CW, Lee CH, Chen JY: Cloning, expression and chromosomal localization of human Ca2+/calmodulin-dependent protein kinase kinase. J Biomed Sci. 1998;5(2):141-9. [Article]
  5. McKinsey TA, Zhang CL, Olson EN: Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14400-5. [Article]
  6. Hsu LS, Chen GD, Lee LS, Chi CW, Cheng JF, Chen JY: Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity. J Biol Chem. 2001 Aug 17;276(33):31113-23. Epub 2001 Jun 6. [Article]
  7. Condon JC, Pezzi V, Drummond BM, Yin S, Rainey WE: Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase. Endocrinology. 2002 Sep;143(9):3651-7. [Article]
  8. Qin H, Raught B, Sonenberg N, Goldstein EG, Edelman AM: Phosphorylation screening identifies translational initiation factor 4GII as an intracellular target of Ca(2+)/calmodulin-dependent protein kinase I. J Biol Chem. 2003 Dec 5;278(49):48570-9. Epub 2003 Sep 24. [Article]
  9. Kahl CR, Means AR: Regulation of cyclin D1/Cdk4 complexes by calcium/calmodulin-dependent protein kinase I. J Biol Chem. 2004 Apr 9;279(15):15411-9. Epub 2004 Jan 30. [Article]
  10. Uboha NV, Flajolet M, Nairn AC, Picciotto MR: A calcium- and calmodulin-dependent kinase Ialpha/microtubule affinity regulating kinase 2 signaling cascade mediates calcium-dependent neurite outgrowth. J Neurosci. 2007 Apr 18;27(16):4413-23. [Article]
  11. Kamata A, Sakagami H, Tokumitsu H, Owada Y, Fukunaga K, Kondo H: Spatiotemporal expression of four isoforms of Ca2+/calmodulin-dependent protein kinase I in brain and its possible roles in hippocampal dendritic growth. Neurosci Res. 2007 Jan;57(1):86-97. Epub 2006 Oct 23. [Article]
  12. Saneyoshi T, Wayman G, Fortin D, Davare M, Hoshi N, Nozaki N, Natsume T, Soderling TR: Activity-dependent synaptogenesis: regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. Neuron. 2008 Jan 10;57(1):94-107. doi: 10.1016/j.neuron.2007.11.016. [Article]
  13. Neal AP, Molina-Campos E, Marrero-Rosado B, Bradford AB, Fox SM, Kovalova N, Hannon HE: CaMKK-CaMKI signaling pathways differentially control axon and dendrite elongation in cortical neurons. J Neurosci. 2010 Feb 24;30(8):2807-9. doi: 10.1523/JNEUROSCI.5984-09.2010. [Article]
  14. Soderling TR, Stull JT: Structure and regulation of calcium/calmodulin-dependent protein kinases. Chem Rev. 2001 Aug;101(8):2341-52. [Article]
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  17. Skelding KA, Rostas JA, Verrills NM: Controlling the cell cycle: the role of calcium/calmodulin-stimulated protein kinases I and II. Cell Cycle. 2011 Feb 15;10(4):631-9. Epub 2011 Feb 15. [Article]
  18. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
  19. Mallampalli RK, Kaercher L, Snavely C, Pulijala R, Chen BB, Coon T, Zhao J, Agassandian M: Fbxl12 triggers G1 arrest by mediating degradation of calmodulin kinase I. Cell Signal. 2013 Oct;25(10):2047-59. doi: 10.1016/j.cellsig.2013.05.012. Epub 2013 May 23. [Article]
  20. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  21. Zha M, Zhong C, Ou Y, Han L, Wang J, Ding J: Crystal structures of human CaMKIalpha reveal insights into the regulation mechanism of CaMKI. PLoS One. 2012;7(9):e44828. doi: 10.1371/journal.pone.0044828. Epub 2012 Sep 20. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails