UniProt Accession

 CALM_HUMAN; P62158; P02593; P70667; P99014; Q13942; Q53S29; Q61379; Q61380; Q96HK3 

Genbank Protein ID

 J04046; M19311; M27319; X52606; X52607; X52608; U12022; U11886; D45887; U94728; U94725; U94726; BT006818; BT006855; BT009916; CR541990; CR542021; AC006536; AC073283; BC000454; BC003354; BC005137; BC006464; BC008437; BC008597; BC011834; BC017385; BC018677; BC026065; BC047523 

Genbank Nucleotide ID

 AAA51918.1; AAA35641.1; AAA35635.1; CAA36839.1; CAA36839.1; CAA36839.1; AAB60644.1; AAB60644.1; BAA08302.1; AAC83174.1; AAC83174.1; AAC83174.1; AAP35464.1; AAP35501.1; AAP88918.1; CAG46787.1; CAG46818.1; AAD45181.1; AAY24085.1; AAH00454.1; AAH03354.1; AAH05137.1; AAH06464.1; AAH08437.1; AAH08597.1; AAH11834.1; AAH17385.1; AAH18677.1; AAH26065.1 

Protein Name

 Calmodulin 

Protein Synonyms/Alias

 CaM 

Gene Name

 CALM1; CALM2; CALM3 

Gene Synonyms/Alias

 CALM; CAM; CAM1; CAM2; CAMB; CALML2; CAM3; CAMC; CAMIII 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
14	EEQIAEFKEAFSLFD	acetylation	[1, 2]
14	EEQIAEFKEAFSLFD	methylation	[3]
14	EEQIAEFKEAFSLFD	ubiquitination	[4]
22	EAFSLFDKDGDGTIT	acetylation	[1, 2, 5]
22	EAFSLFDKDGDGTIT	ubiquitination	[4, 6, 7, 8]
31	GDGTITTKELGTVMR	acetylation	[1]
31	GDGTITTKELGTVMR	ubiquitination	[4, 6, 7, 8, 9, 10]
76	FLTMMARKMKDTDSE	acetylation	[1, 5]
76	FLTMMARKMKDTDSE	ubiquitination	[7]
78	TMMARKMKDTDSEEE	acetylation	[1]
78	TMMARKMKDTDSEEE	methylation	[11]
78	TMMARKMKDTDSEEE	ubiquitination	[7, 8]
95	EAFRVFDKDGNGYIS	acetylation	[1, 2]
95	EAFRVFDKDGNGYIS	methylation	[3, 12]
95	EAFRVFDKDGNGYIS	ubiquitination	[4, 7, 8, 9]
116	VMTNLGEKLTDEEVD	acetylation	[13]
116	VMTNLGEKLTDEEVD	methylation	[3, 11, 14, 15]
149	FVQMMTAK*******	acetylation	[1, 5]
149	FVQMMTAK*******	methylation	[3]
149	FVQMMTAK*******	ubiquitination	[7]

Reference

 [1] Effects of the binding of myosin light chain kinase on the reactivities of calmodulin lysines.
 Jackson AE, Carraway KL 3rd, Puett D, Brew K.
 J Biol Chem. 1986 Sep 15;261(26):12226-32. [PMID: 3091599]
 [2] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [3] Update on activities at the Universal Protein Resource (UniProt) in 2013.
 e="String">UniProt Consortium.
 Nucleic Acids Res. 2013 Jan;41(Database issue):D43-7. [PMID: 23161681]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] A mass spectrometry method for mapping the interface topography of interacting proteins, illustrated by the melittin-calmodulin system.
 Steiner RF, Albaugh S, Fenselau C, Murphy C, Vestling M.
 Anal Biochem. 1991 Jul;196(1):120-5. [PMID: 1888025]
 [6] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [7] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [8] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [9] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [10] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [11] Method for identification and quantitative analysis of protein lysine methylation using matrix-assisted laser desorption/ionization--time-of-flight mass spectrometry and amino acid analysis.
 Yan JX, Sanchez JC, Binz PA, Williams KL, Hochstrasser DF.
 Electrophoresis. 1999 Apr-May;20(4-5):749-54. [PMID: 10344244]
 [12] Novel eye-specific calmodulin methylation characterized by protein mapping in Drosophila melanogaster.
 Takemori N, Komori N, Thompson JN Jr, Yamamoto MT, Matsumoto H.
 Proteomics. 2007 Aug;7(15):2651-8. [PMID: 17610210]
 [13] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [14] Structural requirements for N-trimethylation of lysine 115 of calmodulin.
 Cobb JA, Roberts DM.
 J Biol Chem. 2000 Jun 23;275(25):18969-75. [PMID: 10766755]
 [15] Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin.
 Magnani R, Dirk LM, Trievel RC, Houtz RL.
 Nat Commun. 2010 Jul 27;1:43. [PMID: 20975703] 

Functional Description

 Calmodulin mediates the control of a large number of enzymes, ion channels and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number of protein kinases and phosphatases. Together with CEP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. 

Sequence Annotation

 DOMAIN 8 43 EF-hand 1.
 DOMAIN 44 79 EF-hand 2.
 DOMAIN 81 116 EF-hand 3.
 DOMAIN 117 149 EF-hand 4.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 22 22 N6-acetyllysine; alternate.
 MOD_RES 45 45 Phosphothreonine; by CaMK4 (By
 MOD_RES 95 95 N6-acetyllysine.
 MOD_RES 100 100 Phosphotyrosine.
 MOD_RES 102 102 Phosphoserine.
 MOD_RES 116 116 N6,N6,N6-trimethyllysine.
 MOD_RES 139 139 Phosphotyrosine.
 CROSSLNK 22 22 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Calcium; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Isopeptide bond; Metal-binding; Methylation; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 149 AA 

Protein Sequence

Gene Ontology

 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005576; C:extracellular region; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005886; C:plasma membrane; TAS:UniProtKB.
 GO:0030017; C:sarcomere; IDA:BHF-UCL.
 GO:0005876; C:spindle microtubule; IDA:UniProtKB.
 GO:0000922; C:spindle pole; IDA:UniProtKB.
 GO:0005509; F:calcium ion binding; IDA:BHF-UCL.
 GO:0072542; F:protein phosphatase activator activity; IDA:BHF-UCL.
 GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
 GO:0016044; P:cellular membrane organization; TAS:Reactome.
 GO:0005513; P:detection of calcium ion; IMP:BHF-UCL.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0007186; P:G-protein coupled receptor signaling pathway; TAS:UniProtKB.
 GO:0006006; P:glucose metabolic process; TAS:Reactome.
 GO:0005980; P:glycogen catabolic process; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
 GO:0006936; P:muscle contraction; TAS:Reactome.
 GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; ISS:BHF-UCL.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0046209; P:nitric oxide metabolic process; TAS:Reactome.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0002576; P:platelet degranulation; TAS:Reactome.
 GO:0030801; P:positive regulation of cyclic nucleotide metabolic process; IDA:BHF-UCL.
 GO:0051343; P:positive regulation of cyclic-nucleotide phosphodiesterase activity; IDA:BHF-UCL.
 GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IDA:BHF-UCL.
 GO:0035307; P:positive regulation of protein dephosphorylation; IDA:BHF-UCL.
 GO:0060316; P:positive regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
 GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IC:BHF-UCL.
 GO:1901844; P:regulation of cell communication by electrical coupling involved in cardiac conduction; IC:BHF-UCL.
 GO:0032465; P:regulation of cytokinesis; IMP:UniProtKB.
 GO:0002027; P:regulation of heart rate; IMP:BHF-UCL.
 GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome.
 GO:0001975; P:response to amphetamine; IEA:Compara.
 GO:0051412; P:response to corticosterone stimulus; IEA:Compara.
 GO:0007268; P:synaptic transmission; TAS:Reactome. 

Interpro

 IPR011992; EF-hand-like_dom.
 IPR018247; EF_Hand_1_Ca_BS.
 IPR002048; EF_hand_dom.
 IPR001125; Recoverin. 

Pfam

 PF13499; EF_hand_5 

SMART

 SM00054; EFh 

PROSITE

 PS00018; EF_HAND_1
 PS50222; EF_HAND_2 

PRINTS

 PR00450; RECOVERIN.