SMART: IQ domain annotation

The domain within your query sequence starts at position and ends at position ; the E-value for the IQ domain shown below is < 1e-12.

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IQ Short calmodulin-binding motif containing conserved Ile and Gln residues.

SMART accession number:	SM00015
Description:	Calmodulin-binding motif.
Interpro abstract (IPR000048):	The IQ motif is an extremely basic unit of about 23 amino acids, whose conserved core usually fits the consensus A-x(3)-I-Q-x(2)-F-R-x(4)-K-K. The IQ motif, which can be present in one or more copies, serves as a binding site for different EF-hand proteins including the essential and regulatory myosin light chains, calmodulin (CaM), and CaM-like proteins [(PUBMED:1558751), (PUBMED:9141499)].Many IQ motifs are protein kinase C (PKC) phosphorylation sites [(PUBMED:1824695), (PUBMED:8424932)]. Resolution of the 3D structure of scallop myosin has shown that the IQ motif forms a basic amphipathic helix [(PUBMED:8127365)]. Some proteins known to contain an IQ motif are listed below: A number of conventional and unconventional myosins. Neuromodulin (GAP-43). This protein is associated with nerve growth. It is a major component of the motile "growth cones" that form the tips of elongating axons. Neurogranin (NG/p17). Acts as a "third messenger" substrate of protein kinase C-mediated molecular cascades during synaptic development and remodeling. Sperm surface protein Sp17. Ras GTPase-activating-like protein IQGAP1. IQGAP1 contains 4 IQ motifs. This entry covers the entire IQ motif.
GO function:	protein binding (GO:0005515)
Family alignment:	View or

There are 16022 IQ domains in 5497 proteins in SMART's nrdb database.

Click on the following links for more information.

Evolution (species in which this domain is found)
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This tree shows only several representative species. The complete taxonomic breakdown of all proteins with IQ domain is also avaliable.

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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
Cellular role (predicted cellular role)
Binding / catalysis: Ca2+-binding
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Deloulme JC, Prichard L, Delattre O, Storm DR
- The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain.
- J Biol Chem. 1997; 272: 27369-77
- Display abstract
- A growing family of proteins is regulated by protein kinase C and calmodulin through IQ domains, a regulatory motif originally identified in neuromodulin (Alexander, K. A., Wakim, B. T., Doyle, G. S., Walsh, K. A., and Storm, D. R. (1988) J. Biol. Chem. 263, 7544-7549). Here we report that EWS, a nuclear RNA-binding prooncoprotein, contains an IQ domain, is phosphorylated by protein kinase C, and interacts with calmodulin. Interestingly, PKC phosphorylation of EWS inhibits its binding to RNA homopolymers, and conversely, RNA binding to EWS interferes with PKC phosphorylation. Several other RNA-binding proteins, including TLS/FUS and PSF, co-purify with EWS. PKC phosphorylation of these proteins also inhibits their binding to RNA in vitro. These data suggest that PKC may regulate interactions of EWS and other RNA-binding proteins with their RNA targets and that IQ domains may provide a regulatory link between Ca2+ signal transduction pathways and RNA processing.
- Rhoads AR, Friedberg F
- Sequence motifs for calmodulin recognition.
- FASEB J. 1997; 11: 331-40
- Display abstract
- Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. Many investigations have focused on defining the region of interaction between CaM and its cellular targets and the action of CaM on target protein function. Because CaM can bind with high affinity to a relatively small alpha-helical region of many proteins, success in clearly defining the essential elements of CaM binding motifs seems feasible and should provide a means of identifying CaM binding proteins. Three recognition motifs for CaM interaction are discussed in the context of experimental investigations of a variety of CaM target proteins. A modified version of the IQ motif as a consensus for Ca2+-independent binding and two related motifs for Ca2+-dependent binding, termed 18-14 and 1-5-10 based on the position of conserved hydrophobic residues, are proposed. Although considerable sequence diversity is observed among the different binding regions, these three classes of recognition motifs exist for many of the known CaM binding proteins.
- Houdusse A, Silver M, Cohen C
- A model of Ca(2+)-free calmodulin binding to unconventional myosins reveals how calmodulin acts as a regulatory switch.
- Structure. 1996; 4: 1475-90
- Display abstract
- BACKGROUND: In contrast to conventional muscle myosins, where two different light chains (LCs) stabilize the elongated regulatory domain (RD) region of the head portion of the molecule, unconventional myosins are a diverse group of motors in which from one to six calmodulin (CaM) subunits are bound tandemly to the RD. In both cases, the heavy chains of the RDs have special sequences called "IQ motifs' to which the LCs or CaM bind. A previously puzzling aspect of certain unconventional myosins is their unusual mode of regulation, where activation of motility occurs at low levels of Ca2+. Although the atomic structure of the conventional muscle myosin RD has been determined, no crystallographic structure of the RD of an unconventional myosin is yet available. RESULTS: We have constructed a model of vertebrate CaM bound to the first IQ motif present in the neck region of an unconventional myosin (chicken brush border myosin I), using strict binding rules derived from the crystal structure of the scallop RD. The model accounts for aspects of the regulation of many unconventional myosins where CaM is bound at low levels of Ca2+ and released or changed in conformation at high levels of Ca2+. The conformational changes as a function of Ca2+ depend not only on the precise sequence of the IQ motifs but also on the interactions between CaM molecules bound to adjacent sites on the myosin heavy chain. CONCLUSIONS: According to our model, the full versatility of CaM binding to target peptides is displayed in the regulation of unconventional myosins. At low concentrations of Ca2+, CaM binds in a manner similar to the LCs of conventional myosins. At higher Ca2+ concentrations, CaM changes conformation and acts as a switch to regulate the activity of the unconventional myosin molecules.
- Xie X et al.
- Structure of the regulatory domain of scallop myosin at 2.8 A resolution.
- Nature. 1994; 368: 306-12
- Display abstract
- The regulatory domain of scallop myosin is a three-chain protein complex that switches on this motor in response to Ca2+ binding. This domain has been crystallized and the structure solved to 2.8 A resolution. Side-chain interactions link the two light chains in tandem to adjacent segments of the heavy chain bearing the IQ-sequence motif. The Ca(2+)-binding site is a novel EF-hand motif on the essential light chain and is stabilized by linkages involving the heavy chain and both light chains, accounting for the requirement of all three chains for Ca2+ binding and regulation in the intact myosin molecule.
- Mercer JA, Seperack PK, Strobel MC, Copeland NG, Jenkins NA
- Novel myosin heavy chain encoded by murine dilute coat colour locus.
- Nature. 1991; 349: 709-13
- Display abstract
- Hundreds of murine dilute mutations have been identified and analysed, making dilute one of the best genetically characterized of all mammalian loci. The recessive dilute (d) coat colour mutation carried by many inbred strains of mice produces a lightening of coat colour, caused by an abnormal adendritic melanocyte morphology that results in an uneven release of pigment granules into the developing hair shaft. Most dilute alleles (dilute-lethal) also produce a neurological defect, characterized by convulsions and opisthotonus, apparent at 8-10 days of age and continuing until the death of the animal at 2-3 weeks of age. The discovery that the original dilute allele (now termed dilute-viral or dV) is the result of the integration of an ecotropic murine leukaemia provirus has allowed the cloning of genomic DNA and in this study complementary DNA, from the dilute locus. The predicted dilute amino-acid sequence indicates that dilute encodes a novel type of myosin heavy chain, with a tail, or C-terminal, region that has elements of both type II (alpha-helical coiled-coil) and type I (non-coiled-coil) myosin heavy chains. Dilute transcripts are differentially expressed in both embryonic and adult tissues and are very abundant in neurons of the central nervous system, cephalic ganglia, and spinal ganglia. These results suggest an important role for the dilute gene product in the elaboration, maintenance, or function of cellular processes of melanocytes and neurons.
Disease (disease genes where sequence variants are found in this domain)

Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

Protein	Disease
UNKNOWN (SMART)	OMIM:160760: Cardiomyopathy, familial hypertrophic, 1 OMIM:192600: ?Central core disease, one form
Myosin-VIIa (Q13402) (SMART)	OMIM:276903: Usher syndrome, type 1B ; Deafness, autosomal recessive 2, neurosensory OMIM:600060: Deafness, autosomal dominant 11, neurosensory OMIM:601317:

3D Structures of IQ domains in PDB

PDB code	Main view	Title
1b7t		Myosin digested by papain
1br1		Smooth muscle myosin motor domain-essential light chain complex with mgadp.alf4 bound at the active site
1br4		Smooth muscle myosin motor domain-essential light chain complex with mgadp.bef3 bound at the active site
1dfk		Nucleotide-free scallop myosin s1-near rigor state
1dfl		Scallop myosin s1 complexed with mgadp:vanadate-transition state
1i84		Cryo-em structure of the heavy meromyosin subfragment of chicken gizzard smooth muscle myosin with regulatory light chain in the dephosphorylated state. only c alphas provided for regulatory light chain. only backbone atoms provided for s2 fragment.
1kk7		Scallop myosin in the near rigor conformation
1kk8		Scallop myosin (s1-adp-befx) in the actin-detached conformation
1kqm		Scallop myosin s1-amppnp in the actin-detached conformation
1kwo		Scallop myosin s1-atpgammas-p-pdm in the actin-detached conformation
1l2o		Scallop myosin s1-adp-p-pdm in the actin-detached conformation
1m45		Crystal structure of mlc1p bound to iq2 of myo2p, a class v myosin
1m8q		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1mvw		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1n2d		Ternary complex of mlc1p bound to iq2 and iq3 of myo2p, a class v myosin
1o18		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o19		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1a		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1b		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1c		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1d		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1e		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1f		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1o1g		Molecular models of averaged rigor crossbridges from tomograms of insect flight muscle
1oe9		Crystal structure of myosin v motor with essential light chain - nucleotide-free
1qvi		Crystal structure of scallop myosin s1 in the pre-power stroke state to 2.6 angstrom resolution: flexibility and function in the head
1s5g		Structure of scallop myosin s1 reveals a novel nucleotide conformation
1scm		Structure of the regulatory domain of scallop myosin at 2.8 angstroms resolution
1sr6		Structure of nucleotide-free scallop myosin s1
1w7i		Crystal structure of myosin v motor without nucleotide soaked in 10 mm mgadp
1w7j		Crystal structure of myosin v motor with essential light chain + adp-befx - near rigor
1wdc		Scallop myosin regulatory domain
2bki		Myosin vi nucleotide-free (mdinsert2-iq) crystal structure
2bl0		Physarum polycephalum myosin ii regulatory domain
2dfs		3-d structure of myosin-v inhibited state
2ec6		Placopecten striated muscle myosin ii
2ekv		The crystal structure of rigor like squid myosin s1 in the absence of nucleotide
2ekw		The crystal structure of squid myosin s1 in the presence of so4 2-
2ix7		Structure of apo-calmodulin bound to unconventional myosin v
2mys		Myosin subfragment-1, alpha carbon coordinates only for the two light chains
2os8		Rigor-like structures of muscle myosins reveal key mechanical elements in the transduction pathways of this allosteric motor
2otg		Rigor-like structures of muscle myosins reveal key mechanical elements in the transduction pathways of this allosteric motor
2ovk		Crystal structure of rigor-like squid myosin s1
2oy6		Crystal structure of squid mg.adp myosin s1
3dtp		Tarantula heavy meromyosin obtained by flexible docking to tarantula muscle thick filament cryo-em 3d-map
3gn4		Myosin lever arm
3i5f		Crystal structure of squid mg.adp myosin s1
3i5g		Crystal structure of rigor-like squid myosin s1
3i5h		The crystal structure of rigor like squid myosin s1 in the absence of nucleotide
3i5i		The crystal structure of squid myosin s1 in the presence of so4 2-

Links (links to other resources describing this domain)
INTERPRO IPR000048