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FLASH GENE
Symbol CALM1 contributors: mct/npt/shn - updated : 25-10-2015
HGNC name calmodulin 1 (phosphorylase kinase, delta)
HGNC id 1442
Corresponding disease
CPVT4 catecholaminergic polymorphic ventricular tachycardia 4
Location 14q32.11      Physical location : 90.863.326 - 90.874.617
Synonym name
  • phosphorylase kinase, delta subunit
  • calmodulin
  • Synonym symbol(s) CAMI, PHKD, DD132, CALML2, CALM, CALM3, CAM, CAM1, CAM2, CAM3, CAMB
    EC.number 2.7.1.38
    DNA
    TYPE functioning gene
    STRUCTURE 11.30 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    MAPPING cloned Y linked N status confirmed
    Map cen - D14S1066 - D14S1044 - CALM1 - D14S291 - D14S995 - qter
    Physical map
    EML5 14q31.3 echinoderm microtubule associated protein like 5 TTC8 14q31.3 tetratricopeptide repeat domain 8 LOC390501 14 similar to MPPE1 protein CHES1 14q24.3-q31 checkpoint suppressor 1 C14orf116 14q31.3 chromosome 14 open reading frame 116 CAP2P1 14 CAP, adenylate cyclase-associated protein, 2 (yeast) pseudogene 1 PRO1768 14q32.11 PRO1768 protein CHORDC2P 14 cysteine and histidine-rich domain (CHORD)-containing 2 pseudogene C14orf143 14q32.11 chromosome 14 open reading frame 143 TDP1 14q32.11 tyrosyl-DNA phosphodiesterase 1 KCNK13 14q24.1-q24.3 potassium channel, subfamily K, member 13 GLRXP2 14q32.13-q32.2 glutaredoxin pseudogene 2 PSMC1 19p13.3 proteasome (prosome, macropain) 26S subunit, ATPase, 1 C14orf102 14q32.11 chromosome 14 open reading frame 102 RPL21P11 14q32.11 ribosomal protein L21 pseudogene 11 CALM1 14q24-q31 calmodulin 1 (phosphorylase kinase, delta) TTC7L1 14q32.12 tetratricopeptide repeat domain 7 like 1 RPS18P2 14 ribosomal protein S18 pseudogene 2 LOC283588 14q32.12 hypothetical protein LOC283588 RPS6KA5 14q31-q32.1 ribosomal protein S6 kinase, 90kDa, polypeptide 5 C14orf159 14q32.12 chromosome 14 open reading frame 159 GPR68 14q31 G protein-coupled receptor 68 KIAA1509 14q32.12 KIAA1509 LOC388005 14 similar to RIKEN cDNA 0610010D24 KIAA2010 14q32.12 KIAA2010 C14orf161 14q32.12 chromosome 14 open reading frame 161 MTAC2D1 14q32.12 membrane targeting (tandem) C2 domain containing 1 FBLN5 14q32.1 fibulin 5 TRIP11 14q31-q32 thyroid hormone receptor interactor 11 PTMAP7 14 prothymosin, alpha pseudogene 7 MJD 14q24.4-q32.1 Machado-Joseph disease (spinocerebellar ataxia 3, olivopontocerebellar ataxia 3, autosomal dominant, ataxin 3)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 4268 16.8 149 - 2003 12707260
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinesmall intestine  highly
    Nervousbrain   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivecartilage   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    not specificchondrocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two Ca2+ binding sites at the N terminus of CALM1 and two at the C terminus (N- and C-lobes)
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to Calm1, Mus musculus
    ortholog to Calm1, Rattusnorvegicus
    Homologene
    FAMILY
  • calmodulin family
  • CATEGORY enzyme , regulatory , signaling , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text
  • colocalized with KRAS mainly at the plasma membrane
  • major calcium sensor in neurons when is present in the cytoplasm
  • basic FUNCTION
  • involved in G1 progression
  • mediates osteoclast differentiation, possibly via modulating specific receptor activator of NF-kappaB-signaling pathways
  • calcium modulated protein
  • regulating RYR1 and RYR2 by binding to a single, highly conserved calmodulin binding site
  • playing an essential role in activation of JAK2-mediated EPOR signaling
  • role in Fas signalling
  • regulating intracellular trafficking of epidermal growth factor receptor and the MAPK signaling pathway
  • involved in the Ca(2+)-dependent activation of CERK
  • inhibits KRAS phosphorylation at Ser 181 and consequently modulates the functionality of both the wild type and the oncogenic form of this small GTPase
  • regulating skeletal muscle isoform of the ryanodine receptor CaČ(+)-release channel (RYR1)
  • the N-lobe of CaM binds Ca2+ faster than previously determined for any calcium-binding protein (
  • nuclear calmodulin could act as a co-transcription factor regulating the expression of neuronal proteins, like calbindin, facilitating the process of neuron differentiation, in which MAPT expression may play a role
  • appears to regulate tail-anchored insertion into the ER membrane in a Ca(2+) dependent manner
  • CALM1 is a very important regulator of TRP channels, and it is therefore highly probable that, together with other Ca2+-binding proteins, it could play an important role in the regulation of the TRPM3 ion channel via binding to its intracellular termini
  • likely a negative feedback of cooperative action of CALM1, GAP43, and PPP3CA on P/Q and L-type channels activity
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text detector and Ca2+ binding
    PATHWAY
    metabolism
    signaling
  • receptor for Ca(2+) signals
  • EDF1/CALM1/PPP3CA/NFATC1 pathway
  • a component
  • GJB1 exists in a complex with DLG1 and CALM1
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • troponin I (
  • lactoferrin, LTF (
  • major intrinsic protein of lens fiber MIP26 (
  • in endothelial cells, EDF1 bound with CALM1, through its IQ domain sequestering this complex in the cytoplasm of endothelial cells
  • tubulin binding site on tau protein (
  • Smooth muscle calponin, Sm-Calp (
  • p68 RNA helicase, p68 (
  • CaM-dependent protein kinase I, CaMKI (
  • clathrin-coated vesicles, triskelions, and light chains (
  • glucocorticoid receptor, GR (
  • NR1 subunit (
  • IQ motif containing GTPase activating protein 1, IQGAP1 (
  • Q motif containing GTPase activating protein 2, IQGAP2 (
  • Ric (Drosophila)-like, expressed in neurons, RIN (
  • growth associated protein 43, GAP43 (
  • caldesmon, CALD1 (
  • GRK4alpha (
  • Rad and Rad-related GTPases (
  • v-ral simian leukemia viral oncogene homolog A (ras related), RAlA (
  • A-kinase anchor protein 79 kDa, AKAP79 (
  • prooncoprotein EWS (
  • alpha1-syntrophin (
  • GRK1, GRK2, and GRK5 (
  • cyclin-dependent kinase 4, CDK4 and cyclin D1, CCND1 (
  • intermediate conductance KCa channel, hIKCa1 (
  • synapse-associated protein 102, NE-dlg/SAP102 (
  • neurogranin, NRGN (
  • adenylyl cyclase type VIII, ACVIII (
  • 14-3-3 epsilon isoform protein (
  • myosin light chain kinase (MLCK), 3'-5'-cyclic nucleotide phosphodiesterase (PDE), plasma membrane (PM) Ca2+-ATPase, Ca2+-CaM dependent protein phosphatase 2B (calcineurin); neuronal nitric oxide synthase, NOS and type II Ca2+-calmodulin dependent protein kinase, CaM kinase II (
  • bHLH proteins (
  • endothelial differentiation-related factor-1, EDF1 (
  • protein kinase C, PKC (
  • Zinedin, SG2NA, and striatin (
  • protein-tyrosine phosphatase alpha, PTPalpha (
  • Myosin VIIA, MYO7A (
  • human cardiac titin kinase, hTK (
  • CaT-L (
  • SK channel (
  • mu opioid receptor, MOR (
  • K-Ras (
  • RAB3B, member RAS oncogene family (
  • Estrogen receptor alpha, ERalpha (
  • KCNQ2, KCNQ3, or KCNQ5 (
  • v-ral simian leukemia viral oncogene homolog B (ras related), RALB (
  • protein phosphatase, EF-hand calcium binding domain 1, PPEF1 and protein phosphatase, EF-hand calcium binding domain 2, PPEF2 (
  • phosphodiesterase 1A calmodulin-dependent, PDE1A (
  • ryanodine receptor 1 (skeletal), RYR1 (
  • c-Rel and RelA (
  • cyclic nucleotide gated channel alpha 2, CNGA2 and cyclic nucleotide gated channel beta 1, CNGB1 (
  • estrogen-related receptor gamma, ERR-gamma (
  • transient receptor potential cation channel, subfamily V, member 4, TRPV4 (
  • transient receptor potential cation channel, subfamily V, member 1, TRPV1 (
  • Fas?, APO-1/CD95 (
  • androgen receptor in prostate cancer cells (
  • epidermal growth factor receptor, EGFR (
  • transglutaminase 2 and huntingtin (
  • parathyroid hormone 1 receptor, PTH1R (
  • C-terminal domains of adult skeletal (NaV1.4) and cardiac (NaV1.5) muscle NaChs (
  • growth factor receptor-bound protein 7, GRB7 (
  • PLC-delta1 (
  • cyclin-dependent kinase 2, CDK2 (
  • CALM1 associated with AKAP5 is able to activate anchored PP2B within the same signaling complex
  • MAPT interacts with CALM1 (the lack of MAPT in neurons changes the subcellular localization of CALM1 and that it correlates with a change in the expression of calbindin)
  • S100A1 and CALM1 bind to an overlapping domain on the ryanodine receptor type 1 to tune the Ca2+ release process, and thereby regulate skeletal muscle function
  • CALM1 and S100A1 serve as important regulators of TRPM3, which is known to play an important role in Ca2+ homeostasis
  • interaction between CALM1 and ARHGEF7 (CALM1 participates in a multi-protein complex involving ARHGEF7 and CBL, which may play a critical role in receptor tyrosine kinase regulation and downstream signaling)
  • CALM1- activation of Aurora-A kinase (AURKA) is required during ciliary disassembly and in mitosis
  • is a known interaction partner of AKAP5 that has been shown to regulate activity of the kinase PKC in a Ca(2+) -dependent manner
  • CALM1 may act as a structural conduit that links MYBPC3 with Ca(2+) signaling pathways to help coordinate phosphorylation events and synchronize the multiple interactions between MYBPC3, myosin, and actin during the heart muscle contraction
  • binds directly to RYR2
  • interaction of KCNIP3 with the important EF-hand protein, CALM1, and this interaction alters calcineurin (CN) activity
  • CALM1 is known to modulate the inactivation kinetics of SCN8A by interacting with its IQ motif
  • CALM1 binds PPP3CA regulatory domain (RD) and causes a conformational change that removes PPP3CA autoinhibitory domain (AID) from its catalytic site, activating PPP3CA
  • CALM1 is involved in the Ca(2+)-dependent regulation of TRPV1 via its binding to the TRPV1 C-terminal region
  • CALM1 and CAMK2A modulate SCNN1A activity by destabilizing the association between the actin cytoskeleton, SCNN1A, and MARCKS, or MARCKSL1 at the apical membrane
  • CALM1 and S100A1 can concurrently bind to and functionally modulate RYR1 and RYR2, but this does not involve direct competition at the RYR CALM binding site
  • CALM1 does stimulate PI3K lipid kinase activity by binding MARCKS and displacing it from PIP2 headgroups
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CPVT4
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    age-downregulated in the frontal cortex
    constitutional     --over  
    induces cardiac hypertrophy by a calcineurin-dependent pathway
    Susceptibility to hip osteoarthritis(OA)
    Variant & Polymorphism SNP 293C>T associated with hip osteoarthritis
    Candidate gene
    Marker
    Therapy target
  • CALM1-mediated signaling pathway in chondrocytes as a novel potential target for treatment of OA
  • biology of CALM1-CFLAR binding may provide new therapeutic targets for cholangiocarcinoma and possibly other cancers
  • ANIMAL & CELL MODELS