CALM2

CALM2

Identifiers

CALM2, CAMII, PHKD, PHKD2, LQT15, caM, calmodulin 2 (phosphorylase kinase, delta), calmodulin 2, CAMC, CAM1, CAMIII, CAM3, CALM, CALML2

External IDs

OMIM: 114182 HomoloGene: 134804 GeneCards: CALM2

Gene location (Human)

Chr.	Chromosome 2 (human)^[1]

Band	2p21	Start	47,160,084 bp^[1]
Band	2p21	End	47,176,921 bp^[1]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

middle temporal gyrus

Brodmann area 23

orbitofrontal cortex

visceral pleura

pons

occipital lobe

germinal epithelium

parietal pleura

prefrontal cortex

entorhinal cortex

n/a

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	calcium ion binding protein binding adenylate cyclase binding adenylate cyclase activator activity calcium channel inhibitor activity protein kinase binding protein domain specific binding titin binding N-terminal myristoylation domain binding protein serine/threonine kinase activator activity transmembrane transporter binding metal ion binding protein phosphatase activator activity disordered domain specific binding nitric-oxide synthase regulator activity type 3 metabotropic glutamate receptor binding phosphatidylinositol 3-kinase binding protein N-terminus binding calcium-dependent protein binding nitric-oxide synthase binding
Cellular component	spindle pole nucleus cytoplasm centrosome microtubule organizing center spindle cytoskeleton spindle microtubule plasma membrane voltage-gated potassium channel complex sarcomere vesicle protein-containing complex calcium channel complex myelin sheath catalytic complex growth cone synaptic vesicle membrane mitochondrial membrane neuron projection
Biological process	G2/M transition of mitotic cell cycle regulation of heart rate detection of calcium ion G protein-coupled receptor signaling pathway positive regulation of peptidyl-threonine phosphorylation negative regulation of peptidyl-threonine phosphorylation regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion calcium-mediated signaling substantia nigra development positive regulation of protein autophosphorylation regulation of cytokinesis positive regulation of phosphoprotein phosphatase activity positive regulation of protein dephosphorylation positive regulation of DNA binding positive regulation of cyclic-nucleotide phosphodiesterase activity response to calcium ion regulation of cardiac muscle contraction negative regulation of ryanodine-sensitive calcium-release channel activity positive regulation of ryanodine-sensitive calcium-release channel activity positive regulation of protein serine/threonine kinase activity regulation of cell communication by electrical coupling involved in cardiac conduction response to amphetamine activation of adenylate cyclase activity positive regulation of nitric-oxide synthase activity response to corticosterone regulation of ryanodine-sensitive calcium-release channel activity establishment of protein localization to membrane establishment of protein localization to mitochondrial membrane regulation of synaptic vesicle endocytosis regulation of high voltage-gated calcium channel activity regulation of synaptic vesicle exocytosis
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


805


n/a

Ensembl


ENSG00000143933


n/a

UniProt


P0DP31 P0DP24


n/a

RefSeq (mRNA)


NM_001305624 NM_001305625 NM_001305626 NM_001743


n/a

RefSeq (protein)

NP_059022 NP_001350598 NP_001350599 NP_008819 NP_001292553
NP_001292554 NP_001292555 NP_001734 NP_001316850 NP_001316851 NP_001316852 NP_001316853 NP_001316854 NP_001316855 NP_005175


n/a

Location (UCSC)

Chr 2: 47.16 – 47.18 Mb

n/a

PubMed search

^[2]

n/a

Wikidata

View/Edit Human

Calmodulin 2 is a protein that in humans is encoded by the CALM2 gene.^[3]^[4] A member of the calmodulin family of signaling molecules, it is an intermediary between calcium ions, which act as a second messenger, and many intracellular processes, such as the contraction of cardiac muscle.^[5]

Clinical significance

Mutations in CALM2 are associated with cardiac arrhythmias.^[6] In particular, several single-nucleotide polymorphisms of CALM2 have been reported as potential causes of sudden infant death syndrome. Due to their heritability, CALM2 mutations can affect multiple children in a family,^[7] and the discovery of the deadly consequences of these mutations has led to challenges against the murder convictions of mothers of multiple deceased infants, as in the case of Kathleen Folbigg, acquitted after more than 20 years imprisonment, in Australia.^[8]

Interactions

CALM2 has been shown to interact with AKAP9.^[9]^[10]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000143933 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: CALM2 Calmodulin 2 (phosphorylase kinase, delta)".
^ SenGupta B, Friedberg F, Detera-Wadleigh SD (December 1987). "Molecular analysis of human and rat calmodulin complementary DNA clones. Evidence for additional active genes in these species". The Journal of Biological Chemistry. 262 (34): 16663–16670. doi:10.1016/S0021-9258(18)49306-4. PMID 2445749.
^ "Entry - *114205 - CALCIUM CHANNEL, VOLTAGE-DEPENDENT, L TYPE, ALPHA-1C SUBUNIT; CACNA1C - OMIM". omim.org. Retrieved 2023-06-01.
^ Makita N, Yagihara N, Crotti L, Johnson CN, Beckmann BM, Roh MS, et al. (August 2014). "Novel calmodulin mutations associated with congenital arrhythmia susceptibility". Circulation: Cardiovascular Genetics. 7 (4): 466–474. doi:10.1161/CIRCGENETICS.113.000459. PMC 4140998. PMID 24917665.
^ Brohus M, Arsov T, Wallace DA, Jensen HH, Nyegaard M, Crotti L, et al. (March 2021). "Infanticide vs. inherited cardiac arrhythmias". Europace. Volume 23, Issue 3. European Heart Rhythm Association (published 17 November 2020). 23 (3): 441–450. doi:10.1093/europace/euaa272. PMC 7947592. PMID 33200177.
^ Schwartz O. "4 Dead Infants, a Convicted Mother, and a Genetic Mystery". Wired. ISSN 1059-1028. Retrieved 2023-06-01.
^ Takahashi M, Yamagiwa A, Nishimura T, Mukai H, Ono Y (September 2002). "Centrosomal proteins CG-NAP and kendrin provide microtubule nucleation sites by anchoring gamma-tubulin ring complex". Molecular Biology of the Cell. 13 (9): 3235–3245. doi:10.1091/mbc.E02-02-0112. PMC 124155. PMID 12221128.
^ Berchtold MW, Egli R, Rhyner JA, Hameister H, Strehler EE (May 1993). "Localization of the human bona fide calmodulin genes CALM1, CALM2, and CALM3 to chromosomes 14q24-q31, 2p21.1-p21.3, and 19q13.2-q13.3". Genomics. 16 (2): 461–465. doi:10.1006/geno.1993.1211. PMID 8314583.

External links

Human CALM2 genome location and CALM2 gene details page in the UCSC Genome Browser.

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Gusev NB (October 2001). "Some properties of caldesmon and calponin and the participation of these proteins in regulation of smooth muscle contraction and cytoskeleton formation". Biochemistry. Biokhimiia. 66 (10): 1112–1121. doi:10.1023/A:1012480829618. PMID 11736632. S2CID 310781.
Benaim G, Villalobo A (August 2002). "Phosphorylation of calmodulin. Functional implications". European Journal of Biochemistry. 269 (15): 3619–3631. doi:10.1046/j.1432-1033.2002.03038.x. hdl:10261/79981. PMID 12153558.
Koller M, Schnyder B, Strehler EE (October 1990). "Structural organization of the human CaMIII calmodulin gene". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1087 (2): 180–189. doi:10.1016/0167-4781(90)90203-e. PMID 2223880.
Baudier J, Mochly-Rosen D, Newton A, Lee SH, Koshland DE, Cole RD (May 1987). "Comparison of S100b protein with calmodulin: interactions with melittin and microtubule-associated tau proteins and inhibition of phosphorylation of tau proteins by protein kinase C". Biochemistry. 26 (10): 2886–2893. doi:10.1021/bi00384a033. PMID 3111527.
Matoba R, Okubo K, Hori N, Fukushima A, Matsubara K (September 1994). "The addition of 5'-coding information to a 3'-directed cDNA library improves analysis of gene expression". Gene. 146 (2): 199–207. doi:10.1016/0378-1119(94)90293-3. PMID 8076819.
Srinivas SK, Srinivas RV, Anantharamaiah GM, Compans RW, Segrest JP (October 1993). "Cytosolic domain of the human immunodeficiency virus envelope glycoproteins binds to calmodulin and inhibits calmodulin-regulated proteins". The Journal of Biological Chemistry. 268 (30): 22895–22899. doi:10.1016/S0021-9258(18)41610-9. PMID 8226798.
Miller MA, Mietzner TA, Cloyd MW, Robey WG, Montelaro RC (November 1993). "Identification of a calmodulin-binding and inhibitory peptide domain in the HIV-1 transmembrane glycoprotein". AIDS Research and Human Retroviruses. 9 (11): 1057–1066. doi:10.1089/aid.1993.9.1057. PMID 8312049.
Radding W, Pan ZQ, Hunter E, Johnston P, Williams JP, McDonald JM (January 1996). "Expression of HIV-1 envelope glycoprotein alters cellular calmodulin". Biochemical and Biophysical Research Communications. 218 (1): 192–197. doi:10.1006/bbrc.1996.0034. PMID 8573130.
Pan Z, Radding W, Zhou T, Hunter E, Mountz J, McDonald JM (September 1996). "Role of calmodulin in HIV-potentiated Fas-mediated apoptosis". The American Journal of Pathology. 149 (3): 903–910. PMC 1865159. PMID 8780394.
Sasaki M, Uchiyama J, Ishikawa H, Matsushita S, Kimura G, Nomoto K, Koga Y (October 1996). "Induction of apoptosis by calmodulin-dependent intracellular Ca2+ elevation in CD4+ cells expressing gp 160 of HIV". Virology. 224 (1): 18–24. doi:10.1006/viro.1996.0502. PMID 8862395.
Brigino E, Haraguchi S, Koutsonikolis A, Cianciolo GJ, Owens U, Good RA, Day NK (April 1997). "Interleukin 10 is induced by recombinant HIV-1 Nef protein involving the calcium/calmodulin-dependent phosphodiesterase signal transduction pathway". Proceedings of the National Academy of Sciences of the United States of America. 94 (7): 3178–3182. Bibcode:1997PNAS...94.3178B. doi:10.1073/pnas.94.7.3178. PMC 20342. PMID 9096366.
Minakami R, Jinnai N, Sugiyama H (August 1997). "Phosphorylation and calmodulin binding of the metabotropic glutamate receptor subtype 5 (mGluR5) are antagonistic in vitro". The Journal of Biological Chemistry. 272 (32): 20291–20298. doi:10.1074/jbc.272.32.20291. PMID 9242710.
Miyawaki A, Llopis J, Heim R, McCaffery JM, Adams JA, Ikura M, Tsien RY (August 1997). "Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin". Nature. 388 (6645): 882–887. doi:10.1038/42264. PMID 9278050. S2CID 13745050.
Malvoisin E, Wild F (August 1997). "Inhibition of HIV-1, HIV-2 and SIV envelope glycoprotein-mediated cell fusion by calmodulin". Virus Research. 50 (2): 119–127. doi:10.1016/S0168-1702(97)00060-9. PMID 9282777.
Martoglio B, Graf R, Dobberstein B (November 1997). "Signal peptide fragments of preprolactin and HIV-1 p-gp160 interact with calmodulin". The EMBO Journal. 16 (22): 6636–6645. doi:10.1093/emboj/16.22.6636. PMC 1170268. PMID 9362478.
Ishikawa H, Sasaki M, Noda S, Koga Y (August 1998). "Apoptosis induction by the binding of the carboxyl terminus of human immunodeficiency virus type 1 gp160 to calmodulin". Journal of Virology. 72 (8): 6574–6580. doi:10.1128/JVI.72.8.6574-6580.1998. PMC 109834. PMID 9658102.
Toutenhoofd SL, Foletti D, Wicki R, Rhyner JA, Garcia F, Tolon R, Strehler EE (May 1998). "Characterization of the human CALM2 calmodulin gene and comparison of the transcriptional activity of CALM1, CALM2 and CALM3". Cell Calcium. 23 (5): 323–338. doi:10.1016/S0143-4160(98)90028-8. PMID 9681195.

PDB gallery

1a29: CALMODULIN COMPLEXED WITH TRIFLUOPERAZINE (1:2 COMPLEX)
1ahr: CALMODULIN MUTANT WITH A TWO RESIDUE DELETION IN THE CENTRAL HELIX
1ak8: NMR SOLUTION STRUCTURE OF CERIUM-LOADED CALMODULIN AMINO-TERMINAL DOMAIN (CE2-TR1C), 23 STRUCTURES
1cdl: TARGET ENZYME RECOGNITION BY CALMODULIN: 2.4 ANGSTROMS STRUCTURE OF A CALMODULIN-PEPTIDE COMPLEX
1cdm: MODULATION OF CALMODULIN PLASTICITY IN MOLECULAR RECOGNITION ON THE BASIS OF X-RAY STRUCTURES
1cfc: CALCIUM-FREE CALMODULIN
1cfd: CALCIUM-FREE CALMODULIN
1cff: NMR SOLUTION STRUCTURE OF A COMPLEX OF CALMODULIN WITH A BINDING PEPTIDE OF THE CA2+-PUMP
1ckk: CALMODULIN/RAT CA2+/CALMODULIN DEPENDENT PROTEIN KINASE FRAGMENT
1cll: CALMODULIN STRUCTURE REFINED AT 1.7 ANGSTROMS RESOLUTION
1cm1: MOTIONS OF CALMODULIN-SINGLE-CONFORMER REFINEMENT
1cm4: MOTIONS OF CALMODULIN-FOUR-CONFORMER REFINEMENT
1cmf: NMR SOLUTION STRUCTURE OF APO CALMODULIN CARBOXY-TERMINAL DOMAIN
1cmg: NMR SOLUTION STRUCTURE OF CALCIUM-LOADED CALMODULIN CARBOXY-TERMINAL DOMAIN
1ctr: DRUG BINDING BY CALMODULIN: CRYSTAL STRUCTURE OF A CALMODULIN-TRIFLUOPERAZINE COMPLEX
1deg: THE LINKER OF DES-GLU84 CALMODULIN IS BENT AS SEEN IN THE CRYSTAL STRUCTURE
1dmo: CALMODULIN, NMR, 30 STRUCTURES
1f70: REFINED SOLUTION STRUCTURE OF CALMODULIN N-TERMINAL DOMAIN
1f71: REFINED SOLUTION STRUCTURE OF CALMODULIN C-TERMINAL DOMAIN
1fw4: CRYSTAL STRUCTURE OF E. COLI FRAGMENT TR2C FROM CALMODULIN TO 1.7 A RESOLUTION
1g4y: 1.60 A CRYSTAL STRUCTURE OF THE GATING DOMAIN FROM SMALL CONDUCTANCE POTASSIUM CHANNEL COMPLEXED WITH CALCIUM-CALMODULIN
1iq5: Calmodulin/nematode CA2+/Calmodulin dependent kinase kinase fragment
1iwq: Crystal Structure of MARCKS calmodulin binding domain peptide complexed with Ca2+/Calmodulin
1j7o: Solution structure of Calcium-calmodulin N-terminal domain
1j7p: Solution structure of Calcium calmodulin C-terminal domain
1k90: Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP
1k93: Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin
1l7z: Crystal structure of Ca2+/Calmodulin complexed with myristoylated CAP-23/NAP-22 peptide
1lin: CALMODULIN COMPLEXED WITH TRIFLUOPERAZINE (1:4 COMPLEX)
1lvc: Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin and 2' deoxy, 3' anthraniloyl ATP
1mux: SOLUTION NMR STRUCTURE OF CALMODULIN/W-7 COMPLEX: THE BASIS OF DIVERSITY IN MOLECULAR RECOGNITION, 30 STRUCTURES
1mxe: Structure of the Complex of Calmodulin with the Target Sequence of CaMKI
1niw: Crystal structure of endothelial nitric oxide synthase peptide bound to calmodulin
1nwd: Solution Structure of Ca2+/Calmodulin bound to the C-terminal Domain of Petunia Glutamate Decarboxylase
1ooj: Structural genomics of Caenorhabditis elegans : Calmodulin
1pk0: Crystal Structure of the EF3-CaM complexed with PMEApp
1prw: Crystal structure of bovine brain Ca++ calmodulin in a compact form
1qiv: CALMODULIN COMPLEXED WITH N-(3,3,-DIPHENYLPROPYL)-N'-[1-R-(3,4-BIS-BUTOXYPHENYL)-ETHYL]-PROPYLENEDIAMINE (DPD), 1:2 COMPLEX
1qiw: CALMODULIN COMPLEXED WITH N-(3,3,-DIPHENYLPROPYL)-N'-[1-R-(3,4-BIS-BUTOXYPHENYL)-ETHYL]-PROPYLENEDIAMINE (DPD)
1qs7: The 1.8 angstrom structure of calmodulin rs20 peptide complex
1qtx: THE 1.65 ANGSTROM STRUCTURE OF CALMODULIN RS20 PEPTIDE COMPLEX
1qx5: Crystal structure of apoCalmodulin
1qx7: Crystal structure of apoCaM bound to the gating domain of small conductance Ca2+-activated potassium channel
1s26: Structure of Anthrax Edema Factor-Calmodulin-alpha,beta-methyleneadenosine 5'-triphosphate Complex Reveals an Alternative Mode of ATP Binding to the Catalytic Site
1sk6: Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin, 3',5' cyclic AMP (cAMP), and pyrophosphate
1sw8: Solution structure of the N-terminal domain of Human N60D calmodulin refined with paramagnetism based strategy
1sy9: Structure of calmodulin complexed with a fragment of the olfactory CNG channel
1up5: CHICKEN CALMODULIN
1vrk: THE 1.9 ANGSTROM STRUCTURE OF E84K-CALMODULIN RS20 PEPTIDE COMPLEX
1wrz: Calmodulin complexed with a peptide from a human death-associated protein kinase
1x02: Solution structure of stereo array isotope labeled (SAIL) calmodulin
1xa5: Structure of Calmodulin in complex with KAR-2, a bis-indol alkaloid
1xfu: Crystal structure of anthrax edema factor (EF) truncation mutant, EF-delta 64 in complex with calmodulin
1xfv: Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP
1xfw: Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3'5' cyclic AMP (cAMP)
1xfx: Crystal structure of anthrax edema factor (EF) in complex with calmodulin in the presence of 10 millimolar exogenously added calcium chloride
1xfy: Crystal structure of anthrax edema factor (EF) in complex with calmodulin
1xfz: Crystal structure of anthrax edema factor (EF) in complex with calmodulin in the presence of 1 millimolar exogenously added calcium chloride
1y0v: Crystal structure of anthrax edema factor (EF) in complex with calmodulin and pyrophosphate
1y6w: Trapped intermediate of calmodulin
1yr5: 1.7-A structure of calmodulin bound to a peptide from DAP kinase
1yrt: Crystal Structure analysis of the adenylyl cyclaes catalytic domain of adenylyl cyclase toxin of Bordetella pertussis in presence of c-terminal calmodulin
1yru: Crystal Structure analysis of the adenylyl cyclaes catalytic domain of adenylyl cyclase toxin of Bordetella pertussis in presence of c-terminal calmodulin and 1mM calcium chloride
1zot: crystal structure analysis of the CyaA/C-Cam with PMEAPP
1zuz: Calmodulin in complex with a mutant peptide from human DRP-1 kinase
2bbm: SOLUTION STRUCTURE OF A CALMODULIN-TARGET PEPTIDE COMPLEX BY MULTIDIMENSIONAL NMR
2bbn: SOLUTION STRUCTURE OF A CALMODULIN-TARGET PEPTIDE COMPLEX BY MULTIDIMENSIONAL NMR
2bcx: Crystal structure of calmodulin in complex with a ryanodine receptor peptide
2be6: 2.0 A crystal structure of the CaV1.2 IQ domain-Ca/CaM complex
2bkh: MYOSIN VI NUCLEOTIDE-FREE (MDINSERT2) CRYSTAL STRUCTURE
2bki: MYOSIN VI NUCLEOTIDE-FREE (MDINSERT2-IQ) CRYSTAL STRUCTURE
2col: Crystal structure analysis of CyaA/C-Cam with Pyrophosphate
2dfs: 3-D structure of Myosin-V inhibited state
2f2o: Structure of calmodulin bound to a calcineurin peptide: a new way of making an old binding mode
2f2p: Structure of calmodulin bound to a calcineurin peptide: a new way of making an old binding mode
2f3y: Calmodulin/IQ domain complex
2f3z: Calmodulin/IQ-AA domain complex
2fot: Crystal structure of the complex between calmodulin and alphaII-spectrin
2hf5: The structure and function of a novel two-site calcium-binding fragment of calmodulin
2ix7: STRUCTURE OF APO-CALMODULIN BOUND TO UNCONVENTIONAL MYOSIN V
3cln: STRUCTURE OF CALMODULIN REFINED AT 2.2 ANGSTROMS RESOLUTION
4cln: STRUCTURE OF A RECOMBINANT CALMODULIN FROM DROSOPHILA MELANOGASTER REFINED AT 2.2-ANGSTROMS RESOLUTION