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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
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
Nervousbrainhindbraincerebellum highly Homo sapiensFetal
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
    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 Ca(+)-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