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FLASH GENE
Symbol CALM1 contributors: mct/npt/shn - updated : 25-10-2017
HGNC name calmodulin 1 (phosphorylase kinase, delta)
HGNC id 1442
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
    intracellular,nucleus
    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
  • is an intracellular Ca2+ transducer involved in numerous activities in a broad Ca2+ signaling network
  • 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 suppresses SYTL2 transcription in cortical neurons
  • 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 in complex with the first IQ motif of MYO5A functions as an intact calcium sensor
  • CALM1 does stimulate PI3K lipid kinase activity by binding MARCKS and displacing it from PIP2 headgroups
  • interaction between CALM1 and GJC1 in cells is strongly dependent on intracellular Ca2+ concentration and can be blocked by the CALM1 inhibitor
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CPVT4 , LQT14
    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