RBCC Red Blood Cell Collection

CALM1 (CALML2, CAM3, CAMC, CAMIII) [Confidence: high (present in two of the MS resources)]
Calmodulin; CaM
Note: presumably soluble (membrane word is not in UniProt keywords or features)

hRBCD IPI00075248
IPI00075248 Calmodulin 2 Calmodulin 2 membrane n/a 3 1 n/a n/a n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a n/a n/a 1 1 1 cytoplasmic n/a found at its expected molecular weight found at molecular weight

UniProt P62158
ID CALM_HUMAN Reviewed; 149 AA.
AC P62158; P02593; P70667; P99014; Q13942; Q53S29; Q61379; Q61380;
read moreAC Q96HK3;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Calmodulin;
DE Short=CaM;
GN Name=CALM1; Synonyms=CALM, CAM, CAM1;
GN and
GN Name=CALM2; Synonyms=CAM2, CAMB;
GN and
GN Name=CALM3; Synonyms=CALML2, CAM3, CAMC, CAMIII;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6385987;
RA Wawrzynczak E.J., Perham R.N.;
RT "Isolation and nucleotide sequence of a cDNA encoding human
RT calmodulin.";
RL Biochem. Int. 9:177-185(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2445749;
RA Sengupta B., Friedberg F., Detera-Wadleigh S.D.;
RT "Molecular analysis of human and rat calmodulin complementary DNA
RT clones. Evidence for additional active genes in these species.";
RL J. Biol. Chem. 262:16663-16670(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3182832;
RA Fischer R., Koller M., Flura M., Mathews S., Strehler-Page M.A.,
RA Krebs J., Penniston J.T., Carafoli E., Strehler E.E.;
RT "Multiple divergent mRNAs code for a single human calmodulin.";
RL J. Biol. Chem. 263:17055-17062(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (CALM3).
RC TISSUE=Blood;
RX PubMed=2223880; DOI=10.1016/0167-4781(90)90203-E;
RA Koller M., Schnyder B., Strehler E.E.;
RT "Structural organization of the human CaMIII calmodulin gene.";
RL Biochim. Biophys. Acta 1087:180-189(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (CALM1).
RC TISSUE=Blood;
RX PubMed=7925473; DOI=10.1111/j.1432-1033.1994.00071.x;
RA Rhyner J.A., Ottiger M., Wicki R., Greenwood T.M., Strehler E.E.;
RT "Structure of the human CALM1 calmodulin gene and identification of
RT two CALM1-related pseudogenes CALM1P1 and CALM1P2.";
RL Eur. J. Biochem. 225:71-82(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lymphoma;
RA Kato S.;
RT "Human calmodulin cDNA.";
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (CALM2).
RX PubMed=9681195; DOI=10.1016/S0143-4160(98)90028-8;
RA Toutenhoofd S.L., Foletti D., Wicki R., Rhyner J.A., Garcia F.,
RA Tolon R., Strehler E.E.;
RT "Characterization of the human CALM2 calmodulin gene and comparison of
RT the transcriptional activity of CALM1, CALM2 and CALM3.";
RL Cell Calcium 23:323-338(1998).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (CALM1; CALM2 AND CALM3).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (CALM2).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (CALM1).
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (CALM2).
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (CALM1; CALM2 AND CALM3).
RC TISSUE=Brain, Lung, Lymph, Placenta, and Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [13]
RP PROTEIN SEQUENCE OF 2-149, ACETYLATION AT ALA-2, AND METHYLATION AT
RP LYS-116.
RC TISSUE=Brain;
RX PubMed=7093203; DOI=10.1021/bi00539a041;
RA Sasagawa T., Ericsson L.H., Walsh K.A., Schreiber W.E., Fischer E.H.,
RA Titani K.;
RT "Complete amino acid sequence of human brain calmodulin.";
RL Biochemistry 21:2565-2569(1982).
RN [14]
RP PROTEIN SEQUENCE OF 2-31 AND 92-107, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Bensaad K., Vousden K.H.;
RL Submitted (FEB-2008) to UniProtKB.
RN [15]
RP PROTEIN SEQUENCE OF 15-31; 77-107 AND 128-149, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [16]
RP INTERACTION WITH TTN.
RX PubMed=9804419; DOI=10.1038/27603;
RA Mayans O., van der Ven P.F.M., Wilm M., Mues A., Young P., Furst D.O.,
RA Wilmanns M., Gautel M.;
RT "Structural basis for activation of the titin kinase domain during
RT myofibrillogenesis.";
RL Nature 395:863-869(1998).
RN [17]
RP INTERACTION WITH SRY.
RX PubMed=12871148;
RA Kelly S., Yotis J., Macris M., Harley V.;
RT "Recombinant expression, purification and characterisation of the HMG
RT domain of human SRY.";
RL Protein Pept. Lett. 10:281-286(2003).
RN [18]
RP INTERACTION WITH USP6.
RX PubMed=16127172; DOI=10.1074/jbc.M505220200;
RA Shen C., Ye Y., Robertson S.E., Lau A.W., Mak D.O., Chou M.M.;
RT "Calcium/calmodulin regulates ubiquitination of the ubiquitin-specific
RT protease TRE17/USP6.";
RL J. Biol. Chem. 280:35967-35973(2005).
RN [19]
RP INTERACTION WITH SRY.
RX PubMed=15746192; DOI=10.1210/me.2004-0334;
RA Sim H., Rimmer K., Kelly S., Ludbrook L.M., Clayton A.H., Harley V.R.;
RT "Defective calmodulin-mediated nuclear transport of the sex-
RT determining region of the Y chromosome (SRY) in XY sex reversal.";
RL Mol. Endocrinol. 19:1884-1892(2005).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [21]
RP FUNCTION, INTERACTION WITH CCP110, AND SUBCELLULAR LOCATION.
RX PubMed=16760425; DOI=10.1091/mbc.E06-04-0371;
RA Tsang W.Y., Spektor A., Luciano D.J., Indjeian V.B., Chen Z.,
RA Salisbury J.L., Sanchez I., Dynlacht B.D.;
RT "CP110 cooperates with two calcium-binding proteins to regulate
RT cytokinesis and genome stability.";
RL Mol. Biol. Cell 17:3423-3434(2006).
RN [22]
RP INTERACTION WITH CEP97 AND CCP110.
RX PubMed=17719545; DOI=10.1016/j.cell.2007.06.027;
RA Spektor A., Tsang W.Y., Khoo D., Dynlacht B.D.;
RT "Cep97 and CP110 suppress a cilia assembly program.";
RL Cell 130:678-690(2007).
RN [23]
RP INTERACTION WITH RYR1 AND RYR2.
RX PubMed=18650434; DOI=10.1074/jbc.M804432200;
RA Wright N.T., Prosser B.L., Varney K.M., Zimmer D.B., Schneider M.F.,
RA Weber D.J.;
RT "S100A1 and calmodulin compete for the same binding site on ryanodine
RT receptor.";
RL J. Biol. Chem. 283:26676-26683(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-100, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-100 AND TYR-139, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-22 AND LYS-95, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [28]
RP INTERACTION WITH CDK5RAP2.
RX PubMed=20466722; DOI=10.1074/jbc.M110.105965;
RA Wang Z., Wu T., Shi L., Zhang L., Zheng W., Qu J.Y., Niu R., Qi R.Z.;
RT "Conserved motif of CDK5RAP2 mediates its localization to centrosomes
RT and the Golgi complex.";
RL J. Biol. Chem. 285:22658-22665(2010).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [31]
RP INTERACTION WITH FCHO1.
RX PubMed=22484487; DOI=10.1038/ncb2473;
RA Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B.,
RA Tsang M., Traub L.M.;
RT "Distinct and separable activities of the endocytic clathrin-coat
RT components Fcho1/2 and AP-2 in developmental patterning.";
RL Nat. Cell Biol. 14:488-501(2012).
RN [32]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [33]
RP STRUCTURE BY NMR OF 95-104.
RX PubMed=9927666; DOI=10.1073/pnas.96.3.903;
RA Siedlecka M., Goch G., Ejchart A., Sticht H., Bierzyski A.;
RT "Alpha-helix nucleation by a calcium-binding peptide loop.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:903-908(1999).
RN [34]
RP STRUCTURE BY NMR OF 1-77 AND 83-149.
RX PubMed=11685248; DOI=10.1038/nsb1101-990;
RA Chou J.J., Li S., Klee C.B., Bax A.;
RT "Solution structure of Ca(2+)-calmodulin reveals flexible hand-like
RT properties of its domains.";
RL Nat. Struct. Biol. 8:990-997(2001).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
RX PubMed=1474585; DOI=10.1016/0022-2836(92)90324-D;
RA Chattopadhyaya R., Meador W.E., Means A.R., Quiocho F.A.;
RT "Calmodulin structure refined at 1.7 A resolution.";
RL J. Mol. Biol. 228:1177-1192(1992).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS).
RX PubMed=7803388; DOI=10.1021/bi00255a006;
RA Cook W.J., Walter L.J., Walter M.R.;
RT "Drug binding by calmodulin: crystal structure of a calmodulin-
RT trifluoperazine complex.";
RL Biochemistry 33:15259-15265(1994).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 6-149.
RX PubMed=11807546; DOI=10.1038/415396a;
RA Drum C.L., Yan S.-Z., Bard J., Shen Y.-Q., Lu D., Soelaiman S.,
RA Grabarek Z., Bohm A., Tang W.-J.;
RT "Structural basis for the activation of anthrax adenylyl cyclase
RT exotoxin by calmodulin.";
RL Nature 415:396-402(2002).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 1-149 IN COMPLEX WITH ANTHRAX
RP EDEMA FACTOR CYA.
RX PubMed=12485993; DOI=10.1093/emboj/cdf681;
RA Shen Y., Lee Y.-S., Soelaiman S., Bergson P., Lu D., Chen A.,
RA Beckingham K., Grabarek Z., Mrksich M., Tang W.-J.;
RT "Physiological calcium concentrations regulate calmodulin binding and
RT catalysis of adenylyl cyclase exotoxins.";
RL EMBO J. 21:6721-6732(2002).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH MARCKS.
RX PubMed=12577052; DOI=10.1038/nsb900;
RA Yamauchi E., Nakatsu T., Matsubara M., Kato H., Taniguchi H.;
RT "Crystal structure of a MARCKS peptide containing the calmodulin-
RT binding domain in complex with Ca2+-calmodulin.";
RL Nat. Struct. Biol. 10:226-231(2003).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-150 IN COMPLEX WITH
RP CACNA1C.
RX PubMed=16299511; DOI=10.1038/nsmb1027;
RA Van Petegem F., Chatelain F.C., Minor D.L. Jr.;
RT "Insights into voltage-gated calcium channel regulation from the
RT structure of the CaV1.2 IQ domain-Ca2+/calmodulin complex.";
RL Nat. Struct. Mol. Biol. 12:1108-1115(2005).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH ANTHRAX EDEMA
RP FACTOR CYA.
RX PubMed=15719022; DOI=10.1038/sj.emboj.7600574;
RA Shen Y., Zhukovskaya N.L., Guo Q., Florian J., Tang W.-J.;
RT "Calcium-independent calmodulin binding and two-metal-ion catalytic
RT mechanism of anthrax edema factor.";
RL EMBO J. 24:929-941(2005).
RN [42]
RP STRUCTURE BY NMR IN COMPLEX WITH SCN5A.
RX PubMed=21167176; DOI=10.1016/j.jmb.2010.11.046;
RA Chagot B., Chazin W.J.;
RT "Solution NMR structure of Apo-calmodulin in complex with the IQ motif
RT of human cardiac sodium channel NaV1.5.";
RL J. Mol. Biol. 406:106-119(2011).
RN [43]
RP STRUCTURE BY ELECTRON MICROSCOPY (25 ANGSTROMS) IN COMPLEX WITH MIP,
RP FUNCTION, AND INTERACTION WITH MIP.
RX PubMed=23893133; DOI=10.1038/nsmb.2630;
RA Reichow S.L., Clemens D.M., Freites J.A., Nemeth-Cahalan K.L.,
RA Heyden M., Tobias D.J., Hall J.E., Gonen T.;
RT "Allosteric mechanism of water-channel gating by Ca(2+)-calmodulin.";
RL Nat. Struct. Mol. Biol. 20:1085-1092(2013).
RN [44]
RP VARIANTS CPVT4 ILE-54 AND SER-98, AND CHARACTERIZATION OF VARIANTS
RP CPVT4 ILE-54 AND SER-98.
RX PubMed=23040497; DOI=10.1016/j.ajhg.2012.08.015;
RA Nyegaard M., Overgaard M.T., Sondergaard M.T., Vranas M., Behr E.R.,
RA Hildebrandt L.L., Lund J., Hedley P.L., Camm A.J., Wettrell G.,
RA Fosdal I., Christiansen M., Borglum A.D.;
RT "Mutations in calmodulin cause ventricular tachycardia and sudden
RT cardiac death.";
RL Am. J. Hum. Genet. 91:703-712(2012).
CC -!- FUNCTION: Calmodulin mediates the control of a large number of
CC enzymes, ion channels, aquaporins and other proteins by Ca(2+).
CC Among the enzymes to be stimulated by the calmodulin-Ca(2+)
CC complex are a number of protein kinases and phosphatases. Together
CC with CCP110 and centrin, is involved in a genetic pathway that
CC regulates the centrosome cycle and progression through
CC cytokinesis.
CC -!- SUBUNIT: Interacts with MYO1C and RRAD. Interacts with MYO10 (By
CC similarity). Interacts with CEP97, CCP110, TTN/titin and SRY.
CC Interacts with USP6; the interaction is calcium dependent.
CC Interacts with CDK5RAP2. Interacts with SCN5A. Interacts with RYR1
CC and RYR2. Interacts with FCHO1. Interacts with MIP in a 1:2
CC stoichiometry; the interaction with the cytoplasmic domains from
CC two MIP subunits promotes MIP water channel closure.
CC -!- INTERACTION:
CC P29274:ADORA2A; NbExp=3; IntAct=EBI-397435, EBI-2902702;
CC P49407:ARRB1; NbExp=3; IntAct=EBI-397435, EBI-743313;
CC P32121:ARRB2; NbExp=3; IntAct=EBI-397435, EBI-714559;
CC Q13936:CACNA1C; NbExp=12; IntAct=EBI-397435, EBI-1038838;
CC O43303:CCP110; NbExp=9; IntAct=EBI-397435, EBI-1566217;
CC P40136:cya (xeno); NbExp=8; IntAct=EBI-397435, EBI-457011;
CC P00533:EGFR; NbExp=3; IntAct=EBI-397435, EBI-297353;
CC P25445:FAS; NbExp=4; IntAct=EBI-397435, EBI-494743;
CC O95259:KCNH1; NbExp=4; IntAct=EBI-397435, EBI-2909270;
CC P26645:Marcks (xeno); NbExp=2; IntAct=EBI-397435, EBI-911805;
CC Q9HD67:MYO10; NbExp=2; IntAct=EBI-397435, EBI-307061;
CC Q96PM5:RCHY1; NbExp=2; IntAct=EBI-397435, EBI-947779;
CC Q14524:SCN5A; NbExp=2; IntAct=EBI-397435, EBI-726858;
CC Q8WZ42:TTN; NbExp=2; IntAct=EBI-397435, EBI-681210;
CC P63104:YWHAZ; NbExp=2; IntAct=EBI-397435, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle. Cytoplasm,
CC cytoskeleton, spindle pole. Note=Distributed throughout the cell
CC during interphase, but during mitosis becomes dramatically
CC localized to the spindle poles and the spindle microtubules.
CC -!- PTM: Ubiquitination results in a strongly decreased activity (By
CC similarity).
CC -!- PTM: Phosphorylation results in a decreased activity (By
CC similarity).
CC -!- DISEASE: Ventricular tachycardia, catecholaminergic polymorphic, 4
CC (CPVT4) [MIM:614916]: An arrhythmogenic disorder characterized by
CC stress-induced, bidirectional ventricular tachycardia that may
CC degenerate into cardiac arrest and cause sudden death. Patients
CC present with recurrent syncope, seizures, or sudden death after
CC physical activity or emotional stress. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: This protein has four functional calcium-binding
CC sites.
CC -!- SIMILARITY: Belongs to the calmodulin family.
CC -!- SIMILARITY: Contains 4 EF-hand domains.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA36839.1; Type=Erroneous gene model prediction;
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A question of length -
CC Issue 105 of May 2009;
CC URL="http://web.expasy.org/spotlight/back_issues/sptlt105.shtml";
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DR EMBL; J04046; AAA51918.1; -; mRNA.
DR EMBL; M19311; AAA35641.1; -; mRNA.
DR EMBL; M27319; AAA35635.1; -; mRNA.
DR EMBL; X52606; CAA36839.1; ALT_SEQ; Genomic_DNA.
DR EMBL; X52607; CAA36839.1; JOINED; Genomic_DNA.
DR EMBL; X52608; CAA36839.1; JOINED; Genomic_DNA.
DR EMBL; U12022; AAB60644.1; -; Genomic_DNA.
DR EMBL; U11886; AAB60644.1; JOINED; Genomic_DNA.
DR EMBL; D45887; BAA08302.1; -; mRNA.
DR EMBL; U94728; AAC83174.1; -; Genomic_DNA.
DR EMBL; U94725; AAC83174.1; JOINED; Genomic_DNA.
DR EMBL; U94726; AAC83174.1; JOINED; Genomic_DNA.
DR EMBL; BT006818; AAP35464.1; -; mRNA.
DR EMBL; BT006855; AAP35501.1; -; mRNA.
DR EMBL; BT009916; AAP88918.1; -; mRNA.
DR EMBL; CR541990; CAG46787.1; -; mRNA.
DR EMBL; CR542021; CAG46818.1; -; mRNA.
DR EMBL; AC006536; AAD45181.1; -; Genomic_DNA.
DR EMBL; AC073283; AAY24085.1; -; Genomic_DNA.
DR EMBL; BC000454; AAH00454.1; -; mRNA.
DR EMBL; BC003354; AAH03354.1; -; mRNA.
DR EMBL; BC005137; AAH05137.1; -; mRNA.
DR EMBL; BC006464; AAH06464.1; -; mRNA.
DR EMBL; BC008437; AAH08437.1; -; mRNA.
DR EMBL; BC008597; AAH08597.1; -; mRNA.
DR EMBL; BC011834; AAH11834.1; -; mRNA.
DR EMBL; BC017385; AAH17385.1; -; mRNA.
DR EMBL; BC018677; AAH18677.1; -; mRNA.
DR EMBL; BC026065; AAH26065.1; -; mRNA.
DR EMBL; BC047523; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; S48728; MCHU.
DR RefSeq; NP_001734.1; NM_001743.4.
DR RefSeq; NP_005175.2; NM_005184.2.
DR RefSeq; NP_008819.1; NM_006888.4.
DR RefSeq; XP_005259336.1; XM_005259279.1.
DR UniGene; Hs.282410; -.
DR UniGene; Hs.468442; -.
DR UniGene; Hs.515487; -.
DR PDB; 1AJI; Model; -; A=5-148.
DR PDB; 1CDL; X-ray; 2.00 A; A/B/C/D=2-148.
DR PDB; 1CLL; X-ray; 1.70 A; A=2-149.
DR PDB; 1CTR; X-ray; 2.45 A; A=2-149.
DR PDB; 1IWQ; X-ray; 2.00 A; A=2-149.
DR PDB; 1J7O; NMR; -; A=2-77.
DR PDB; 1J7P; NMR; -; A=83-149.
DR PDB; 1K90; X-ray; 2.75 A; D/E/F=2-149.
DR PDB; 1K93; X-ray; 2.95 A; D/E/F=6-149.
DR PDB; 1L7Z; X-ray; 2.30 A; A=2-148.
DR PDB; 1LVC; X-ray; 3.60 A; D/E/F=1-149.
DR PDB; 1NKF; NMR; -; A=94-105.
DR PDB; 1PK0; X-ray; 3.30 A; D/E/F=2-148.
DR PDB; 1S26; X-ray; 3.00 A; D/E/F=2-148.
DR PDB; 1SK6; X-ray; 3.20 A; D/E/F=2-149.
DR PDB; 1SW8; NMR; -; A=2-80.
DR PDB; 1WRZ; X-ray; 2.00 A; A=1-149.
DR PDB; 1XFU; X-ray; 3.35 A; O/P/Q/R/S/T=1-149.
DR PDB; 1XFV; X-ray; 3.35 A; O/P/Q/R/S/T=1-149.
DR PDB; 1XFW; X-ray; 3.40 A; O/P/Q/R/S/T=1-149.
DR PDB; 1XFX; X-ray; 3.20 A; O/P/Q/R/S/T=1-149.
DR PDB; 1XFY; X-ray; 3.30 A; O/P/Q/R/S/T=1-149.
DR PDB; 1XFZ; X-ray; 3.25 A; O/P/Q/R/S/T=1-149.
DR PDB; 1Y6W; X-ray; 2.40 A; A=2-148.
DR PDB; 1YR5; X-ray; 1.70 A; A=2-148.
DR PDB; 1YRT; X-ray; 2.10 A; B=76-149.
DR PDB; 1YRU; X-ray; 2.50 A; B=76-149.
DR PDB; 1ZOT; X-ray; 2.20 A; B=80-148.
DR PDB; 1ZUZ; X-ray; 1.91 A; A=1-148.
DR PDB; 2BE6; X-ray; 2.00 A; A/B/C=1-149.
DR PDB; 2F3Y; X-ray; 1.45 A; A=2-148.
DR PDB; 2F3Z; X-ray; 1.60 A; A=2-148.
DR PDB; 2HF5; NMR; -; A=47-113.
DR PDB; 2I08; X-ray; 2.00 A; A=3-78.
DR PDB; 2JZI; NMR; -; A=2-149.
DR PDB; 2K0E; NMR; -; A=2-149.
DR PDB; 2K0F; NMR; -; A=2-149.
DR PDB; 2K0J; NMR; -; A=2-149.
DR PDB; 2K61; NMR; -; A=2-149.
DR PDB; 2KNE; NMR; -; A=2-149.
DR PDB; 2KUG; NMR; -; A=2-77.
DR PDB; 2KUH; NMR; -; A=83-149.
DR PDB; 2L53; NMR; -; A=2-149.
DR PDB; 2L7L; NMR; -; A=2-149.
DR PDB; 2LGF; NMR; -; A=4-149.
DR PDB; 2LL6; NMR; -; A=2-149.
DR PDB; 2LL7; NMR; -; A=2-149.
DR PDB; 2LQC; NMR; -; A=2-78.
DR PDB; 2LQP; NMR; -; A=79-149.
DR PDB; 2LV6; Other; -; A=2-149.
DR PDB; 2M0J; NMR; -; A=2-149.
DR PDB; 2M0K; NMR; -; A=2-149.
DR PDB; 2M55; NMR; -; A=2-149.
DR PDB; 2R28; X-ray; 1.86 A; A/B=1-149.
DR PDB; 2V01; X-ray; 2.15 A; A=1-149.
DR PDB; 2V02; X-ray; 2.20 A; A=1-149.
DR PDB; 2VAY; X-ray; 1.94 A; A=4-148.
DR PDB; 2W73; X-ray; 1.45 A; A/B/E/F=1-149.
DR PDB; 2WEL; X-ray; 1.90 A; D=1-149.
DR PDB; 2X0G; X-ray; 2.20 A; B=2-149.
DR PDB; 2Y4V; X-ray; 1.80 A; A=1-149.
DR PDB; 3BYA; X-ray; 1.85 A; A=2-149.
DR PDB; 3DVE; X-ray; 2.35 A; A=2-149.
DR PDB; 3DVJ; X-ray; 2.80 A; A=2-149.
DR PDB; 3DVK; X-ray; 2.30 A; A=2-149.
DR PDB; 3DVM; X-ray; 2.60 A; A=2-149.
DR PDB; 3EWT; X-ray; 2.40 A; A=2-149.
DR PDB; 3EWV; X-ray; 2.60 A; A=2-149.
DR PDB; 3G43; X-ray; 2.10 A; A/B/C/D=2-149.
DR PDB; 3HR4; X-ray; 2.50 A; B/D/F/H=1-149.
DR PDB; 3J41; EM; 25.0 A; E/F=1-149.
DR PDB; 3O77; X-ray; 2.35 A; A=3-149.
DR PDB; 3O78; X-ray; 2.60 A; A/B=3-149.
DR PDB; 3OXQ; X-ray; 2.55 A; A/B/C/D=1-149.
DR PDB; 3SUI; X-ray; 1.95 A; A=1-149.
DR PDB; 3UCT; X-ray; 1.90 A; A/B=2-80.
DR PDB; 3UCW; X-ray; 1.76 A; A/B/C/D=2-80.
DR PDB; 3UCY; X-ray; 1.80 A; A=2-80.
DR PDB; 4DCK; X-ray; 2.20 A; B=1-149.
DR PDB; 4DJC; X-ray; 1.35 A; A=1-149.
DR PDB; 4GOW; X-ray; 2.60 A; D=4-147.
DR PDBsum; 1AJI; -.
DR PDBsum; 1CDL; -.
DR PDBsum; 1CLL; -.
DR PDBsum; 1CTR; -.
DR PDBsum; 1IWQ; -.
DR PDBsum; 1J7O; -.
DR PDBsum; 1J7P; -.
DR PDBsum; 1K90; -.
DR PDBsum; 1K93; -.
DR PDBsum; 1L7Z; -.
DR PDBsum; 1LVC; -.
DR PDBsum; 1NKF; -.
DR PDBsum; 1PK0; -.
DR PDBsum; 1S26; -.
DR PDBsum; 1SK6; -.
DR PDBsum; 1SW8; -.
DR PDBsum; 1WRZ; -.
DR PDBsum; 1XFU; -.
DR PDBsum; 1XFV; -.
DR PDBsum; 1XFW; -.
DR PDBsum; 1XFX; -.
DR PDBsum; 1XFY; -.
DR PDBsum; 1XFZ; -.
DR PDBsum; 1Y6W; -.
DR PDBsum; 1YR5; -.
DR PDBsum; 1YRT; -.
DR PDBsum; 1YRU; -.
DR PDBsum; 1ZOT; -.
DR PDBsum; 1ZUZ; -.
DR PDBsum; 2BE6; -.
DR PDBsum; 2F3Y; -.
DR PDBsum; 2F3Z; -.
DR PDBsum; 2HF5; -.
DR PDBsum; 2I08; -.
DR PDBsum; 2JZI; -.
DR PDBsum; 2K0E; -.
DR PDBsum; 2K0F; -.
DR PDBsum; 2K0J; -.
DR PDBsum; 2K61; -.
DR PDBsum; 2KNE; -.
DR PDBsum; 2KUG; -.
DR PDBsum; 2KUH; -.
DR PDBsum; 2L53; -.
DR PDBsum; 2L7L; -.
DR PDBsum; 2LGF; -.
DR PDBsum; 2LL6; -.
DR PDBsum; 2LL7; -.
DR PDBsum; 2LQC; -.
DR PDBsum; 2LQP; -.
DR PDBsum; 2LV6; -.
DR PDBsum; 2M0J; -.
DR PDBsum; 2M0K; -.
DR PDBsum; 2M55; -.
DR PDBsum; 2R28; -.
DR PDBsum; 2V01; -.
DR PDBsum; 2V02; -.
DR PDBsum; 2VAY; -.
DR PDBsum; 2W73; -.
DR PDBsum; 2WEL; -.
DR PDBsum; 2X0G; -.
DR PDBsum; 2Y4V; -.
DR PDBsum; 3BYA; -.
DR PDBsum; 3DVE; -.
DR PDBsum; 3DVJ; -.
DR PDBsum; 3DVK; -.
DR PDBsum; 3DVM; -.
DR PDBsum; 3EWT; -.
DR PDBsum; 3EWV; -.
DR PDBsum; 3G43; -.
DR PDBsum; 3HR4; -.
DR PDBsum; 3J41; -.
DR PDBsum; 3O77; -.
DR PDBsum; 3O78; -.
DR PDBsum; 3OXQ; -.
DR PDBsum; 3SUI; -.
DR PDBsum; 3UCT; -.
DR PDBsum; 3UCW; -.
DR PDBsum; 3UCY; -.
DR PDBsum; 4DCK; -.
DR PDBsum; 4DJC; -.
DR PDBsum; 4GOW; -.
DR ProteinModelPortal; P62158; -.
DR SMR; P62158; 1-149.
DR DIP; DIP-31794N; -.
DR IntAct; P62158; 192.
DR MINT; MINT-4999725; -.
DR BindingDB; P62158; -.
DR ChEMBL; CHEMBL6093; -.
DR DrugBank; DB01429; Aprindine.
DR DrugBank; DB01244; Bepridil.
DR DrugBank; DB00527; Dibucaine.
DR DrugBank; DB01023; Felodipine.
DR DrugBank; DB04841; Flunarizine.
DR DrugBank; DB00623; Fluphenazine.
DR DrugBank; DB00753; Isoflurane.
DR DrugBank; DB00836; Loperamide.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00850; Perphenazine.
DR DrugBank; DB00925; Phenoxybenzamine.
DR DrugBank; DB01100; Pimozide.
DR DrugBank; DB01069; Promethazine.
DR TCDB; 9.C.15.1.1; the animal calmodulin-dependent e.r. secretion pathway (csp) family.
DR PhosphoSite; P62158; -.
DR DOSAC-COBS-2DPAGE; P62158; -.
DR OGP; P02593; -.
DR SWISS-2DPAGE; P62158; -.
DR PaxDb; P62158; -.
DR PRIDE; P62158; -.
DR DNASU; 801; -.
DR DNASU; 805; -.
DR DNASU; 808; -.
DR Ensembl; ENST00000272298; ENSP00000272298; ENSG00000143933.
DR Ensembl; ENST00000291295; ENSP00000291295; ENSG00000160014.
DR Ensembl; ENST00000356978; ENSP00000349467; ENSG00000198668.
DR Ensembl; ENST00000596362; ENSP00000472141; ENSG00000160014.
DR GeneID; 801; -.
DR GeneID; 805; -.
DR GeneID; 808; -.
DR KEGG; hsa:801; -.
DR KEGG; hsa:805; -.
DR KEGG; hsa:808; -.
DR UCSC; uc001xyl.2; human.
DR CTD; 801; -.
DR CTD; 805; -.
DR CTD; 808; -.
DR GeneCards; GC02M047272; -.
DR GeneCards; GC14P090863; -.
DR GeneCards; GC19P047105; -.
DR HGNC; HGNC:1442; CALM1.
DR HGNC; HGNC:1445; CALM2.
DR HGNC; HGNC:1449; CALM3.
DR HPA; CAB007790; -.
DR HPA; CAB018558; -.
DR MIM; 114180; gene.
DR MIM; 114182; gene.
DR MIM; 114183; gene.
DR MIM; 614916; phenotype.
DR neXtProt; NX_P62158; -.
DR Orphanet; 3286; Catecholaminergic polymorphic ventricular tachycardia.
DR Orphanet; 768; Familial long QT syndrome.
DR PharmGKB; PA26042; -.
DR eggNOG; COG5126; -.
DR HOVERGEN; HBG012180; -.
DR InParanoid; P62158; -.
DR KO; K02183; -.
DR OMA; NEVDEMI; -.
DR BioCyc; MetaCyc:ENSG00000143933-MONOMER; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_11123; Membrane Trafficking.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_118664; Calcineurin Dephosphorylates NFATC1,2,3.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_17044; Muscle contraction.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; CALM1; human.
DR ChiTaRS; CALM3; human.
DR EvolutionaryTrace; P62158; -.
DR GeneWiki; CALM2; -.
DR GeneWiki; CALM3; -.
DR GeneWiki; Calmodulin_1; -.
DR NextBio; 3264; -.
DR PRO; PR:P62158; -.
DR ArrayExpress; P62158; -.
DR Bgee; P62158; -.
DR CleanEx; HS_CALM1; -.
DR CleanEx; HS_CALM2; -.
DR Genevestigator; P62158; -.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
DR GO; GO:0030017; C:sarcomere; IDA:BHF-UCL.
DR GO; GO:0005876; C:spindle microtubule; IDA:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:BHF-UCL.
DR GO; GO:0072542; F:protein phosphatase activator activity; IDA:BHF-UCL.
DR GO; GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
DR GO; GO:0005513; P:detection of calcium ion; IMP:BHF-UCL.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0006006; P:glucose metabolic process; TAS:Reactome.
DR GO; GO:0005980; P:glycogen catabolic process; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0006936; P:muscle contraction; TAS:Reactome.
DR GO; GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; ISS:BHF-UCL.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0046209; P:nitric oxide metabolic process; TAS:Reactome.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0030801; P:positive regulation of cyclic nucleotide metabolic process; IDA:BHF-UCL.
DR GO; GO:0051343; P:positive regulation of cyclic-nucleotide phosphodiesterase activity; IDA:BHF-UCL.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IDA:BHF-UCL.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IDA:BHF-UCL.
DR GO; GO:0060316; P:positive regulation of ryanodine-sensitive calcium-release channel activity; IDA:BHF-UCL.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IC:BHF-UCL.
DR GO; GO:1901844; P:regulation of cell communication by electrical coupling involved in cardiac conduction; IC:BHF-UCL.
DR GO; GO:0032465; P:regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0002027; P:regulation of heart rate; IMP:BHF-UCL.
DR GO; GO:0050999; P:regulation of nitric-oxide synthase activity; TAS:Reactome.
DR GO; GO:0022400; P:regulation of rhodopsin mediated signaling pathway; TAS:Reactome.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0051412; P:response to corticosterone stimulus; IEA:Ensembl.
DR GO; GO:0016056; P:rhodopsin mediated signaling pathway; TAS:Reactome.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR Gene3D; 1.10.238.10; -; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001125; Recoverin_like.
DR Pfam; PF13499; EF-hand_7; 2.
DR PRINTS; PR00450; RECOVERIN.
DR SMART; SM00054; EFh; 4.
DR PROSITE; PS00018; EF_HAND_1; 4.
DR PROSITE; PS50222; EF_HAND_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Calcium; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Isopeptide bond;
KW Metal-binding; Methylation; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Ubl conjugation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 149 Calmodulin.
FT /FTId=PRO_0000198223.
FT DOMAIN 8 43 EF-hand 1.
FT DOMAIN 44 79 EF-hand 2.
FT DOMAIN 81 116 EF-hand 3.
FT DOMAIN 117 149 EF-hand 4.
FT CA_BIND 21 32 1.
FT CA_BIND 57 68 2.
FT CA_BIND 94 105 3.
FT CA_BIND 130 141 4.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 22 22 N6-acetyllysine; alternate.
FT MOD_RES 45 45 Phosphothreonine; by CaMK4 (By
FT similarity).
FT MOD_RES 95 95 N6-acetyllysine.
FT MOD_RES 100 100 Phosphotyrosine.
FT MOD_RES 102 102 Phosphoserine.
FT MOD_RES 116 116 N6,N6,N6-trimethyllysine.
FT MOD_RES 139 139 Phosphotyrosine.
FT CROSSLNK 22 22 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin);
FT alternate (By similarity).
FT VARIANT 54 54 N -> I (in CPVT4; the mutant has
FT significantly reduced Ca(2+) affinity
FT compared to wild-type).
FT /FTId=VAR_069222.
FT VARIANT 73 73 M -> T (in dbSNP:rs41389749).
FT /FTId=VAR_048585.
FT VARIANT 98 98 N -> S (in CPVT4; the mutant has
FT significantly reduced Ca(2+) affinity
FT compared to wild-type; calmodulin-RYR2
FT interaction is defective at low
FT intracellular Ca(2+) concentrations and
FT restored at moderate to high Ca(2+)
FT concentrations).
FT /FTId=VAR_069223.
FT CONFLICT 124 124 E -> Q (in Ref. 12; AAH08437).
FT HELIX 2 4
FT HELIX 7 20
FT STRAND 25 28
FT HELIX 30 39
FT HELIX 46 56
FT TURN 57 59
FT STRAND 61 65
FT HELIX 66 93
FT STRAND 94 96
FT STRAND 97 101
FT HELIX 103 112
FT STRAND 113 115
FT HELIX 119 129
FT TURN 130 132
FT STRAND 133 138
FT HELIX 139 146
SQ SEQUENCE 149 AA; 16838 MW; 6B4BC3FCDE10727B CRC64;
MADQLTEEQI AEFKEAFSLF DKDGDGTITT KELGTVMRSL GQNPTEAELQ DMINEVDADG
NGTIDFPEFL TMMARKMKDT DSEEEIREAF RVFDKDGNGY ISAAELRHVM TNLGEKLTDE
EVDEMIREAD IDGDGQVNYE EFVQMMTAK
//

MIM 114180
*RECORD*
*FIELD* NO
114180
*FIELD* TI
*114180 CALMODULIN 1; CALM1
;;PHOSPHORYLASE KINASE, DELTA SUBUNIT; PHKD
*FIELD* TX
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DESCRIPTION

Calmodulin is the archetype of the family of calcium-modulated proteins
of which nearly 20 members have been found. They are identified by their
occurrence in the cytosol or on membranes facing the cytosol and by a
high affinity for calcium. Calmodulin contains 149 amino acids and has 4
calcium-binding domains. Its functions include roles in growth and the
cell cycle as well as in signal transduction and the synthesis and
release of neurotransmitters.

CLONING

Until the studies of Sen Gupta et al. (1987), only 1 human calmodulin
cDNA had been reported. These authors found evidence of a second
actively transcribed calmodulin gene in man. Calmodulin is the delta
subunit of phosphorylase kinase, which has 3 other types of subunits.
Although only 1 form of calmodulin has been found in humans, 3 distinct
human cDNAs have been isolated that encode the identical polypeptide
(Koller et al., 1990; Pegues and Friedberg, 1990). The existence of 3
expressible genes for calmodulin may indicate that one is a housekeeping
gene and that the additional copies are differentially regulated to
modulate calmodulin function.

Rhyner et al. (1994) detected expression of CALM1 in all human tissues
tested, although at varying levels. They identified 2 different
CALM1-related pseudogenes.

Toutenhoofd et al. (1998) found that all 3 CALM genes were expressed in
human teratocarcinoma cells. CALM1 was expressed as a major 1.7-kb
transcript and a minor 4.1-kb transcript. CALM1 was at least 5-fold less
actively transcribed than CALM3 (114183).

BIOCHEMICAL FEATURES

To determine how calcium/calmodulin activates
calcium/calmodulin-dependent protein kinase I (CAMK1; 604998), Chin et
al. (1997) characterized CAMK1 activation by calmodulin mutants with
substitutions at hydrophobic residues. They found that CAMK1 activity is
dependent on met124 within the C-terminal domain of calmodulin as well
as on N-terminal hydrophobic residues of calmodulin.

Kretsinger et al. (1986) described the crystal structure of calmodulin
to 3.6-angstrom resolution.

Schumacher et al. (2001) determined the crystal structure of calmodulin
bound to KCNN2 (605879). The calmodulin-binding domain forms an
elongated dimer with a calmodulin molecule bound at each end; each
calmodulin wraps around 3 alpha-helices, 2 from 1 calmodulin-binding
domain subunit and 1 from the other.

Edema factor, the exotoxin of the anthrax bacillus, is transported into
host cells by an anthrax-derived transporter, protective antigen.
Together with lethal factor (see 603060), edema factor contributes
significantly to both cutaneous and systemic anthrax and is an adenylyl
cyclase activated by CALM1. Drum et al. (2002) described the crystal
structures of edema factor alone and edema factor with CALM1 and
3-prime-deoxy-ATP. On calmodulin binding, an edema factor helical domain
of 15 kD undergoes a 15-angstrom translation and a 30-degree rotation
away from the edema factor catalytic core, which stabilizes a disordered
loop and leads to enzyme activation.

GENE STRUCTURE

Rhyner et al. (1994) found that the CALM1 gene contains 6 exons spread
over about 10 kb of genomic DNA. The exon-intron structure was identical
to that of CALM3. A cluster of transcription-start sites was identified
200 bp upstream of the ATG translation-start codon, and several putative
regulatory elements were found in the 5-prime flanking region, as well
as in intron 1. A short CAG trinucleotide repeat region was identified
in the 5-prime untranslated region of the gene.

Toutenhoofd et al. (1998) determined that of the 3 CALM genes, only
CALM1 contains a canonical TATA box. Like CALM3, the 5-prime region of
CALM1 is highly GC rich.

MAPPING

McPherson et al. (1991) used a panel of human/rodent somatic cell
hybrids to demonstrate that the cDNA probe for CALM1 was localized to
chromosome 14 with cross-hybridization evident on chromosome 7 and very
weak on the X chromosome. The assignments to chromosomes 14 and 7
confirmed an earlier report by Scambler et al. (1987). McPherson et al.
(1991) tentatively assigned the CALM2 (114182) gene to chromosome 10,
but the gene was subsequently shown to be on chromosome 2. They assigned
the cDNA probe for CALM3 unequivocally to chromosome 19. There was no
apparent cross-hybridization to other chromosomes. A calmodulin
pseudogene is located on chromosome 17 (Sen Gupta et al., 1989) and
there are probably more on several other chromosomes. Berchtold et al.
(1993) assigned the CALM1 gene to chromosome 14 by PCR-based
amplification of CALM1-specific sequences using DNA from human/hamster
cell hybrids as template. Regional sublocalization was performed by in
situ hybridization using CALM1-specific DNA probes of intronic or
flanking parts of the gene; the regional localization was found to be
14q24-q31.

GENE FUNCTION

To understand the relationship between the number of calmodulin
molecules regulating each L-type calcium channel (see 114205) and the
number of calmodulin molecules privy to the local calcium signal from
each channel, Mori et al. (2004) fused L-type calcium channels to single
calmodulin molecules. These chimeric molecules revealed that a single
calmodulin molecule directs L-type channel regulation. Similar fusion
molecules were used to estimate the local calmodulin concentration near
calcium channels. This estimate indicates marked enrichment of local
calmodulin, as if a school of nearby calmodulins were poised to enhance
the transduction of local calcium entry into diverse signaling pathways.

Junge et al. (2004) identified a conserved calmodulin-binding site in
Munc13s (see 605836), which are essential regulators of synaptic vesicle
priming and synaptic efficacy. They showed that Ca(2+) sensor/effector
complexes consisting of calmodulin and Munc13s regulate synaptic vesicle
priming and synaptic efficacy in response to a residual Ca(2+)
concentration signal and thus shape short-term plasticity
characteristics during periods of sustained synaptic activity.

Dick et al. (2008) showed that the spatial calcium ion selectivity of
N-lobe calmodulin regulation is not invariably global but can be
switched by a novel calcium ion/calmodulin binding site within the amino
terminus of channels (NSCaTE, for N-terminal spatial calcium ion
transforming element). Native Ca(v)2.2 channels lack this element and
show N-lobe regulation with a global selectivity. On the introduction of
NSCaTE into these channels, spatial calcium ion selectivity transforms
from a global to local profile. Given this effect, Dick et al. (2008)
examined Ca(v)1.2/Ca(v)1.3 channels, which naturally contain NSCaTE, and
found that their N-lobe selectivity is indeed local. Disruption of this
element produces a global selectivity, confirming the native function of
NSCaTE. Thus, Dick et al. (2008) concluded that differences in spatial
selectivity between advanced Ca(v)1 and Ca(v)2 channel isoforms are
explained by the presence or absence of NSCaTE. Beyond functional
effects, the position of NSCaTE on the channel's amino terminus
indicates that calmodulin can bridge the amino terminus and carboxy
terminus of channels. Finally, the modularity of NSCaTE offers practical
means for understanding the basis of global calcium ion selectivity.

Liu et al. (2010) combined electrophysiology to characterize channel
regulation with optical fluorescence resonance energy transfer (FRET)
sensor determination of free-apoCaM concentration in live cells. This
approach translates quantitative calmodulin biochemistry from the
traditional test-tube context into the realm of functioning holochannels
within intact cells. From this perspective, Liu et al. (2010) found that
long splice forms of Ca(V)1.3 (CACNA1D; 114206) and Ca(V)1.4 (CACNA1F;
300110) channels include a distal carboxy tail that resembles an enzyme
competitive inhibitor that retunes channel affinity for apocalmodulin
such that natural calmodulin variations affect the strength of Ca(2+)
feedback modulation. Given the ubiquity of these channels, the
connection between ambient calmodulin levels and Ca(2+) entry through
channels is broadly significant for Ca(2+) homeostasis.

MOLECULAR GENETICS

- Catecholaminergic Polymorphic Ventricular Tachycardia 4

In a large 4-generation Swedish family with autosomal dominant
catecholaminergic polymorphic ventricular tachycardia (CPVT4; 614916),
Nyegaard et al. (2012) identified heterozygosity for a missense mutation
in the CALM1 gene (N53I; 114180.0001) that segregated fully with disease
in the family and was not found in 1,200 controls. A de novo missense
mutation in CALM1 (N97S; 114180.0002) was subsequently identified in a
23-year-old Iraqi woman with a history of cardiac arrest at 4 years of
age due to ventricular fibrillation while running. Both substitutions
demonstrated compromised calcium binding.

- Association with Osteoarthritis

In 2 independent Japanese populations totaling 428 osteoarthritis (OA;
165720) patients and 1,008 controls, Mototani et al. (2005) identified
significant association between hip OA and a -16C-T promoter SNP (dbSNP
rs12885713) in the CALM1 gene. Functional analysis indicated that the
-16T allele decreased CALM1 transcription in vitro and in vivo. CALM1
was expressed in cultured chondrocytes and articular cartilage, and its
expression was increased in OA. Inhibition of CALM1 in chondrogenic
cells reduced expression of the major cartilage matrix genes COL2A1
(120140) and AGC1 (155760). Mototani et al. (2005) suggested that the
transcriptional level of CALM1 may be associated with susceptibility for
hip OA through modulation of chondrogenic activity.

ANIMAL MODEL

A classic textbook example of adaptive radiation under natural selection
is the evolution of 14 closely related species of Darwin's finches,
whose primary diversity lies in the size and shape of their beaks. The
precise dimensions (length, depth, and width) of each species' beak are
crucial to their lifestyle and survival, and fluctuations in the
environment lead to selection that changes the relative success of birds
with various beak shapes. These evolutionary processes are evident in
real time on the Galapagos Islands (Grant and Grant, 2006). Abzhanov et
al. (2004) showed that the BMP4 gene (112262), which plays a role in
skeletal and cartilaginous development in mice, is more broadly
expressed during the embryonic development of the deep and wide beaks of
ground finches than during the development of finches with narrower
beaks. Using a cDNA microarray analysis of the transcripts expressed in
the beak primordia to find previously unknown genes and pathways whose
expression correlates with specific beak morphologies, Abzhanov et al.
(2006) found that calmodulin is expressed at much higher levels in the
long and pointed beaks of cactus finch embryos than in the beaks of
other finch embryos. They showed further that when upregulation of the
calmodulin-dependent pathway is artificially replicated in the chick
frontonasal prominence, it causes an elongation of the upper beak,
recapitulating the beak morphology of the cactus finches. The results
indicated that local upregulation of the calmodulin-dependent pathway is
likely to have been a component in the evolution of Darwin's finch
species with elongated beak morphology and provide a mechanistic
explanation for the independence of beak evolution along different axes,
e.g., broad versus elongated. More generally, their results implicated
the calmodulin-dependent pathway in the developmental regulation of
craniofacial skeletal structures.

HISTORY

Scambler et al. (1987) identified a calmodulin-like locus, designated
CALML1, on chromosome 7pter-p13 by study of somatic cell hybrids. Based
on map and other indirect evidence, Scott (2007) concluded that this
locus is a pseudogene (CALM1P2).

*FIELD* AV
.0001
VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 4
CALM1, ASN53ILE

In 10 affected members of a large 4-generation Swedish family with
catecholaminergic polymorphic ventricular tachycardia (CPVT4; 614916),
Nyegaard et al. (2012) identified heterozygosity for a 161A-T
transversion in exon 3 of the CALM1 gene, resulting in an asn53-to-ile
(N53I) substitution at a highly conserved residue within the first
alpha-helix of Ca(2+)-binding site II. The mutation was not found in
unaffected family members or in 1,200 controls. Functional analysis
demonstrated that the mutant had significantly reduced Ca(2+) affinity
compared to wildtype.

.0002
VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 4
CALM1, ASN97SER

In a 23-year-old Iraqi woman with catecholaminergic polymorphic
ventricular tachycardia (CPVT4; 614916), Nyegaard et al. (2012)
identified heterozygosity for a de novo 293A-G transition in exon 5 of
the CALM1 gene, resulting in an asn97-to-ser (N97S) substitution at a
highly conserved Ca(2+)-binding residue within the high-affinity
binding-site III in the calmodulin C domain. The mutation was not found
in her unaffected parents or in 500 Danish controls, and the patient was
negative for mutation in 8 other arrhythmia-associated genes. At age 4
years, the patient underwent cardiac arrest due to ventricular
fibrillation while running; she was stabilized by treatment with a
beta-1 adrenergic receptor blocker. Electrocardiography (ECG) showed
prominent U-waves in anterior leads but no evidence for long QT or
Brugada syndromes. At 12 years of age, an off-medication exercise ECG
demonstrated ventricular ectopy with couplets and triplets of varying
morphology, which appeared to be bidirectional at times. At age 15, she
suffered a second cardiac arrest and underwent implantation of an
internal cardiac defibrillator (ICD). Functional analysis demonstrated
that the mutant had significantly reduced Ca(2+) affinity compared to
wildtype calmodulin. In addition, for the N97S mutant, calmodulin-RYR2
(180902) interaction was defective at low intracellular Ca(2+)
concentrations and restored at moderate to high Ca(2+) concentrations.

*FIELD* RF
1. Abzhanov, A.; Kuo, W. P.; Hartmann, C.; Grant, B. R.; Grant, P.
R.; Tabin, C. J.: The calmodulin pathway and evolution of elongated
beak morphology in Darwin's finches. Nature 442: 563-567, 2006.

2. Abzhanov, A.; Protas, M.; Grant, R. B.; Grant, P. R.; Tabin, C.
J.: Bmp4 and morphological variation of beaks in Darwin's finches. Science 305:
1462-1465, 2004.

3. Berchtold, M. W.; Egli, R.; Rhyner, J. A.; Hameister, H.; Strehler,
E. E.: 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:
461-465, 1993.

4. Chin, D.; Winkler, K. E.; Means, A. R.: Characterization of substrate
phosphorylation and use of calmodulin mutants to address implications
from the enzyme crystal structure of calmodulin-dependent protein
kinase I. J. Biol. Chem. 272: 31235-31240, 1997.

5. Dick, I. E.; Tadross, M. R.; Liang, H.; Tay, L. H.; Yang, W.; Yue,
D. T.: A modular switch for spatial Ca(2+) selectivity in the calmodulin
regulation of Ca(v) channels. Nature 451: 830-834, 2008.

6. Drum, C. L.; Yan, S.-Z.; Bard, J.; Shen, Y.-Q.; Lu, D.; Soelaiman,
S.; Grabarek, Z.; Bohm, A.; Tang, W.-J.: Structural basis for the
activation of anthrax adenylyl cyclase exotoxin by calmodulin. Nature 415:
396-402, 2002.

7. Grant, P. R.; Grant, B. R.: Evolution of character displacement
in Darwin's finches. Science 313: 224-226, 2006.

8. Junge, H. J.; Rhee, J.-S.; Jahn, O.; Varoqueaux, F.; Spiess, J.;
Waxham, M. N.; Rosenmund, C.; Brose, N.: Calmodulin and Munc13 form
a Ca(2+) sensor/effector complex that controls short-term synaptic
plasticity. Cell 118: 389-401, 2004.

9. Koller, M.; Schnyder, B.; Strehler, E. E.: Structural organization
of the human CaMIII calmodulin gene. Biochim. Biophys. Acta 1087:
180-189, 1990.

10. Kretsinger, R. H.; Rudnick, S. E.; Weissman, L. J.: Crystal structure
of calmodulin. J. Inorganic Biochem. 28: 289-302, 1986.

11. Liu, X.; Yang, P. S.; Yang, W.; Yue, D. T.: Enzyme-inhibitor-like
tuning of Ca(2+) channel connectivity with calmodulin. Nature 463:
968-972, 2010. Note: Erratum: Nature 464: 1390 only, 2010.

12. McPherson, J. D.; Hickie, R. A.; Wasmuth, J. J.; Meyskens, F.
L.; Perham, R. N.; Strehler, E. E.; Graham, M. T.: Chromosomal localization
of multiple genes encoding calmodulin. (Abstract) Cytogenet. Cell
Genet. 58: 1951 only, 1991.

13. Mori, M. X.; Erickson, M. G.; Yue, D. T.: Functional stoichiometry
and local enrichment of calmodulin interacting with Ca(2+) channels. Science 304:
432-435, 2004.

14. Mototani, H.; Mabuchi, A.; Saito, S.; Fujioka, M.; Iida, A.; Takatori,
Y.; Kotani, A.; Kubo, T.; Nakamura, K.; Sekine, A.; Murakami, Y.;
Tsunoda, T.; Notoya, K.; Nakamura, Y.; Ikegawa, S.: A functional
single nucleotide polymorphism in the core promoter region of CALM1
is associated with hip osteoarthritis in Japanese. Hum. Molec. Genet. 14:
1009-1017, 2005.

15. Nyegaard, M.; Overgaard, M. T.; Sondergaard, M. T.; Vranas, M.;
Behr, E. R.; Hildebrandt, L. L.; Lund, J.; Hedley, P. L.; Camm, A.
J.; Wettrell, G.; Fosdal, I.; Christiansen, M.; Borglum, A. D.: Mutations
in calmodulin cause ventricular tachycardia and sudden cardiac death. Am.
J. Hum. Genet. 91: 703-712, 2012.

16. Pegues, J. C.; Friedberg, F.: Multiple mRNAs encoding human calmodulin. Biochem.
Biophys. Res. Commun. 172: 1145-1149, 1990.

17. Rhyner, J. A.; Ottiger, M.; Wicki, R.; Greenwood, T. M.; Strehler,
E. E.: Structure of the human CALM1 calmodulin gene and identification
of two CALM1-related pseudogenes CALM1P1 and CALM1P2. Europ. J. Biochem. 225:
71-82, 1994.

18. Scambler, P. J.; McPherson, M. A.; Bates, G.; Bradbury, N. A.;
Dormer, R. L.; Williamson, R.: Biochemical and genetic exclusion
of calmodulin as the site of the basic defect in cystic fibrosis. Hum.
Genet. 76: 278-282, 1987.

19. Scambler, P. J.; McPherson, M. A.; Bates, G.; Bradbury, N. A.;
Dormer, R. L.; Williamson, R.: Biochemical and genetic exclusion
of calmodulin as the site of the basic defect in cystic fibrosis. Hum.
Genet. 76: 278-282, 1987.

20. Schumacher, M. A.; Rivard, A. F.; Bachinger, H. P.; Adelman, J.
P.: Structure of the gating domain of a Ca(2+)-activated K+ channel
complexed with Ca(2+)/calmodulin. Nature 410: 1120-1124, 2001.

21. Scott, A. F.: Personal Communication. Baltimore, Md. 2/8/2007.

22. Sen Gupta, B.; Detera-Wadleigh, S. D.; McBride, O. W.; Friedberg,
F.: A calmodulin pseudogene on human chromosome 17. Nucleic Acids
Res. 17: 2868 only, 1989.

23. Sen Gupta, B.; Friedberg, F.; Detera-Wadleigh, S. D.: Molecular
analysis of human and rat calmodulin complementary DNA clones: evidence
for additional active genes in these species. J. Biol. Chem. 262:
16663-16670, 1987.

24. Toutenhoofd, S. L.; Foletti, D.; Wicki, R.; Rhyner, J. A.; Garcia,
F.; Tolon, R.; Strehler, E. E.: Characterization of the human CALM2
calmodulin gene and comparison of the transcriptional activity of
CALM1, CALM2, and CALM3. Cell Calcium 23: 323-338, 1998.

*FIELD* CN
Marla J. F. O'Neill - updated: 11/6/2012
Ada Hamosh - updated: 4/22/2010
Ada Hamosh - updated: 3/7/2008
George E. Tiller - updated: 2/7/2008
Victor A. McKusick - updated: 9/26/2006
Stylianos E. Antonarakis - updated: 2/15/2005
Ada Hamosh - updated: 4/29/2004
Patricia A. Hartz - updated: 11/18/2002
Paul J. Converse - updated: 1/23/2002
Ada Hamosh - updated: 4/23/2001
Paul J. Converse - updated: 5/24/2000

*FIELD* CD
Victor A. McKusick: 2/9/1987

*FIELD* ED
carol: 11/06/2012
terry: 11/6/2012
alopez: 6/17/2010
alopez: 4/26/2010
terry: 4/22/2010
alopez: 3/20/2008
terry: 3/7/2008
wwang: 2/14/2008
terry: 2/7/2008
terry: 9/17/2007
carol: 2/8/2007
carol: 10/13/2006
terry: 9/26/2006
mgross: 2/15/2005
alopez: 5/4/2004
terry: 4/29/2004
mgross: 11/18/2002
alopez: 1/23/2002
alopez: 4/25/2001
terry: 4/23/2001
mgross: 5/24/2000
terry: 11/13/1998
mark: 11/11/1997
mark: 12/29/1996
carol: 1/19/1995
carol: 12/23/1993
carol: 5/26/1993
carol: 8/14/1992
supermim: 3/16/1992
carol: 3/9/1992

MIM 114182
*RECORD*
*FIELD* NO
114182
*FIELD* TI
*114182 CALMODULIN 2; CALM2
;;PHKD2
*FIELD* TX

CLONING

Sen Gupta et al. (1987) first identified and cloned the second
read morecalmodulin gene. Fischer et al. (1988) noted that, although the CALM1
(114180), CALM2, and CALM3 (114183) proteins are identical, at the
nucleotide level they share only about 80% identity within their coding
regions, and they contain no significant homology within their noncoding
regions.

Using a sequence from CALM3 as probe, Toutenhoofd et al. (1998) cloned
CALM2 from a small intestine mucosa cDNA library. Northern blot analysis
revealed a major 1.4-kb transcript in all tissues tested, with highest
expression in brain. High levels of expression were also found in heart,
placenta, lung, liver, skeletal muscle, and kidney, with lowest levels
found in pancreas.

GENE STRUCTURE

Toutenhoofd et al. (1998) determined that the CALM2 gene contains 6
exons and spans more than 16 kb. Within the 5-prime flanking region,
CALM2 contains a TATA-like sequence, a far upstream CCAAT box, several
AP1 (165160)-, AP2 (see 107580)-, and CRE (see 123811)-binding sites,
and a repeated AGGGA motif that is found in other CALM genes.

MAPPING

McPherson et al. (1991) tentatively assigned the CALM2 gene to
chromosome 10 by study of somatic cell hybrids. However, by PCR-based
amplification of CALM2-specific sequences using DNA from human/hamster
cell hybrids as template, Berchtold et al. (1993) found that the CALM2
gene is located on chromosome 2. They regionalized the gene to
2p21.3-p21.1 by in situ hybridization.

*FIELD* RF
1. Berchtold, M. W.; Egli, R.; Rhyner, J. A.; Hameister, H.; Strehler,
E. E.: 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:
461-465, 1993.

2. Fischer, R.; Koller, M.; Flura, M.; Mathews, S.; Strehler-Page,
M.-A.; Krebs, J.; Penniston, J. T.; Carafoli, E.; Strehler, E. E.
: Multiple divergent mRNAs code for a single human calmodulin. J.
Biol. Chem. 263: 17055-17062, 1988.

3. McPherson, J. D.; Hickie, R. A.; Wasmuth, J. J.; Meyskens, F. L.;
Perham, R. N.; Strehler, E. E.; Graham, M. T.: Chromosomal localization
of multiple genes encoding calmodulin. (Abstract) Cytogenet. Cell
Genet. 58: 1951 only, 1991.

4. Sen Gupta, B.; Friedberg, F.; Detera-Wadleigh, S. D.: Molecular
analysis of human and rat calmodulin complementary DNA clones: evidence
for additional active genes in these species. J. Biol. Chem. 262:
16663-16670, 1987.

5. Toutenhoofd, S. L.; Foletti, D.; Wicki, R.; Rhyner, J. A.; Garcia,
F.; Tolon, R.; Strehler, E. E.: Characterization of the human CALM2
calmodulin gene and comparison of the transcriptional activity of
CALM1, CALM2, and CALM3. Cell Calcium 23: 323-338, 1998.

*FIELD* CN
Patricia A. Hartz - updated: 11/18/2002

*FIELD* CD
Victor A. McKusick: 3/8/1992

*FIELD* ED
mgross: 11/18/2002
terry: 10/31/1996
carol: 5/26/1993
supermim: 3/16/1992
carol: 3/8/1992

MIM 114183
*RECORD*
*FIELD* NO
114183
*FIELD* TI
*114183 CALMODULIN 3; CALM3
;;PHKD3
*FIELD* TX

CLONING

Fischer et al. (1988) cloned CALM3 from human brain and teratoma cDNA
read morelibraries. CALM3 is identical in amino acid sequence to CALM1 (114180)
and CALM2 (114182), but within the coding regions, CALM3 shares only 82%
and 81% nucleotide identity with CALM1 and CALM2, respectively. The
untranslated regions contain no significant homologies. Using an
N-terminal sequence to probe a Northern blot, Fischer et al. (1988)
detected 0.8- and 2.3-kb transcripts in fibroblast, erythroleukemia, and
teratoma cell lines. Only the 2.3-kb transcript was revealed with a
C-terminal probe, suggesting use of an alternate polyadenylation signal.

Toutenhoofd et al. (1998) measured the mRNA abundance and
transcriptional activity of the 3 CALM genes in proliferating human
teratoma cells. All 5 possible mRNA transcripts were detected in these
cells, with highest abundance of CALM3. CALM3 was 5-fold more actively
transcribed than CALM1 and CALM2.

GENE STRUCTURE

Fischer et al. (1988) determined that the CALM3 gene contains 6 exons.

Koller and Strehler (1993) determined that the 5-prime flanking region
of CALM3 is GC rich and contains a canonical CAAT box but no TATA box.
There are several clustered SP1 (189906)-binding sites and 7 AGGA
elements, which are found in genes encoding Ca(2+)-binding proteins.
Using a promoter-reporter construct transfected into several cell lines,
Koller and Strehler (1993) found that CALM3 promoter activity was
neither cell type nor species specific.

MAPPING

McPherson et al. (1991) assigned the CALM3 gene to chromosome 19 by
study of somatic cell hybrids. By PCR-based amplification of
CALM3-specific sequences using DNA from human/hamster cell hybrids as
template, Berchtold et al. (1993) confirmed the assignment to chromosome
19 and regionalized the gene to 19q13.2-q13.3 by in situ hybridization.

*FIELD* RF
1. Berchtold, M. W.; Egli, R.; Rhyner, J. A.; Hameister, H.; Strehler,
E. E.: 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:
461-465, 1993.

2. Fischer, R.; Koller, M.; Flura, M.; Mathews, S.; Strehler-Page,
M.-A.; Krebs, J.; Penniston, J. T.; Carafoli, E.; Strehler, E. E.
: Multiple divergent mRNAs code for a single human calmodulin. J.
Biol. Chem. 263: 17055-17062, 1988.

3. Koller, M.; Strehler, E. E.: Functional analysis of the promoters
of the human CaMIII calmodulin gene and of the intronless gene coding
for a calmodulin-like protein. Biochim. Biophys. Acta 1163: 1-9,
1993.

4. McPherson, J. D.; Hickie, R. A.; Wasmuth, J. J.; Meyskens, F. L.;
Perham, R. N.; Strehler, E. E.; Graham, M. T.: Chromosomal localization
of multiple genes encoding calmodulin. (Abstract) Cytogenet. Cell
Genet. 58: 1951 only, 1991.

5. Toutenhoofd, S. L.; Foletti, D.; Wicki, R.; Rhyner, J. A.; Garcia,
F.; Tolon, R.; Strehler, E. E.: Characterization of the human CALM2
calmodulin gene and comparison of the transcriptional activity of
CALM1, CALM2, and CALM3. Cell Calcium 23: 323-338, 1998.

*FIELD* CN
Patricia A. Hartz - updated: 11/18/2002

*FIELD* CD
Victor A. McKusick: 3/8/1992

*FIELD* ED
mgross: 11/18/2002
terry: 10/31/1996
carol: 5/26/1993
supermim: 3/16/1992
carol: 3/8/1992

MIM 614916
*RECORD*
*FIELD* NO
614916
*FIELD* TI
#614916 VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 4; CPVT4
*FIELD* TX
read moreA number sign (#) is used with this entry because of evidence that
catecholaminergic polymorphic ventricular tachycardia (CPVT4) can be
caused by heterozygous mutation in the calmodulin gene (CALM1; 114180)
on chromosome 14q32.

For a general phenotypic description and a discussion of genetic
heterogeneity of CPVT, see 604772.

CLINICAL FEATURES

Nyegaard et al. (2012) studied a large 4-generation Swedish family with
a history of ventricular arrhythmias, syncope, and sudden death,
predominantly in association with physical exercise or stress. The
proband was a 42-year-old man who first developed syncope at 12 years of
age while playing football; electrocardiogram (ECG) at that time showed
bradycardia with a prominent U-wave in leads V2 and V3, without evidence
of QT prolongation. He had a history of loss of consciousness on at
least 4 occasions during physical activity and once in connection with a
fire alarm. A 24-hour ECG recording revealed premature ventricular
contractions (PVCs), bigeminy, and paired PVCs during football training,
but no symptoms were reported. An older brother with a history of
repeated syncope during exercise was reported to show polymorphic
ventricular tachycardia on an exercise ECG; a follow-up ECG while on a
beta-1 adrenergic receptor blocker showed PVCs at high loads. He had a
son with syncope. The proband also had a brother who had drowned at 15
years of age during a swimming competition after prior episodes of
syncope, and an older sister who had episodic syncope and was later
found to have ventricular fibrillation, but stabilized on a beta-1
adrenergic receptor blocker and became asymptomatic. In addition, a
younger sister presented at 7 years of age with repeated syncope during
intense physical activity, and she also had a son with syncope. Their
mother, who died at age 60, had multiple episodes of syncope in her
youth for which she received medication. The proband's older sister had
6 children, 4 of whom were affected, including a son who died suddenly
at 13 years of age while on a beta-1 adrenergic receptor blocker for
syncopal episodes that had started at 2.5 years of age. A daughter, who
began having syncope at 4 years of age and was asymptomatic on a beta-1
adrenergic receptor blocker, suffered cardiac arrest at age 16, was
resuscitated, and received an implantable cardiac defibrillator (ICD).
Two more daughters also presented with syncope within the first decade
of life, and 1 had a son with syncope.

MAPPING

In a large 4-generation Swedish family segregating autosomal dominant
catecholaminergic polymorphic ventricular tachycardia (CPVT), in which
the proband was negative for mutation in known arrhythmia-associated
genes, including RYR2 (180902) and CASQ2 (114251), Nyegaard et al.
(2012) performed genomewide linkage analysis and obtained a lod score of
3.9 for a 21-cM interval on chromosome 14, from SNP dbSNP rs9323782 to
SNP dbSNP rs721403. The disease haplotype was present in all affected
members but not in any unaffected members of the family, suggesting 100%
penetrance of the mutation in the family.

MOLECULAR GENETICS

In a large 4-generation Swedish family with CPVT mapping to chromosome
14q31-q32, Nyegaard et al. (2012) identified a heterozygous missense
mutation in the candidate gene calmodulin (CALM1; 114180.0001) that
segregated fully with the disease and was not found in 1,200 Danish
controls. Analysis of CALM1 in 61 additional arrhythmia patients who
were negative for mutation in the RYR2 gene revealed another
heterozygous missense mutation (114180.0002), in an Iraqi woman with a
history of syncope beginning at 4 years of age who ultimately underwent
implantation of an ICD after cardiac arrest at age 15.

*FIELD* RF
1. Nyegaard, M.; Overgaard, M. T.; Sondergaard, M. T.; Vranas, M.;
Behr, E. R.; Hildebrandt, L. L.; Lund, J.; Hedley, P. L.; Camm, A.
J.; Wettrell, G.; Fosdal, I.; Christiansen, M.; Borglum, A. D.: Mutations
in calmodulin cause ventricular tachycardia and sudden cardiac death. Am.
J. Hum. Genet. 91: 703-712, 2012.

*FIELD* CS
INHERITANCE:
Autosomal dominant

CARDIOVASCULAR:
[Heart];
Polymorphic ventricular tachycardia induced by physical activity or
stress;
Dizziness;
Syncope;
Cardiac arrest;
Sudden death;
Prominent U-waves in anterior leads on electrocardiogram;
Premature ventricular contractions, including couplets and triplets
of variable morphology

MISCELLANEOUS:
Onset within the first decade of life

MOLECULAR BASIS:
Caused by mutation in the calmodulin-1 gene (CALM1, 114180.0001)

*FIELD* CD
Marla J. F. O'Neill: 11/13/2012

*FIELD* ED
joanna: 11/13/2012

*FIELD* CD
Marla J. F. O'Neill: 11/6/2012

*FIELD* ED
carol: 11/06/2012