Summary: IQ calmodulin-binding motif

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Wikipedia: IQ calmodulin-binding motif
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This is the Wikipedia entry entitled "IQ calmodulin-binding motif". More...

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IQ calmodulin-binding motif Edit Wikipedia article

IQ calmodulin-binding motif

Structure of the regulatory domain of scallop myosin at 2 A resolution.^[1]

Identifiers

Symbol

IQ

1wdc / SUPFAM

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	1b7t, 1br1, 1br2, 1br4, 1d0x, 1d0y, 1d0z, 1d1a,1d1b,1d1c, 1dfk, 1dfl, 1fmv, 1fmw, 1jwy, 1jx2, 1kk7, 1kk8,1kqm, 1kwo, 1l2o, 1lkx, 1lvk, 1mma, 1mmd, 1mmg, 1mmn,1mnd, 1mne, 1oe9, 1qvi, 1s5g, 1scm, 1sr6, 1vom, 1w7i,1w7j, 1wdc, 2mys

The IQ calmodulin-binding motif is an amino acid sequence motif containing the following sequence:

[FILV]Qxxx[RK]Gxxx[RK]xx[FILVWY]

The term "IQ" refers to the first two amino acids of the motif: isoleucine (commonly) and glutamine (invariably).

Function

Calmodulin (CaM) is recognized as a major calcium (Ca²⁺) sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. Three classes of recognition motifs exist for many of the known CaM binding proteins; the IQ motif as a consensus for Ca²⁺-independent binding and two related motifs for Ca²⁺-dependent binding, termed 1-14 and 1-5-10 based on the position of conserved hydrophobic residues.^[2]

Example

The regulatory domain of scallop myosin is a three-chain protein complex that switches on this motor in response to Ca²⁺ binding. Side-chain interactions link the two light chains in tandem to adjacent segments of the heavy chain bearing the IQ-sequence motif. The Ca²⁺-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.^[3]

References

^ Houdusse A, Cohen C (January 1996). "Structure of the regulatory domain of scallop myosin at 2 A resolution: implications for regulation". Structure. 4 (1): 21â€“32. doi:10.1016/S0969-2126(96)00006-8. PMID 8805510.
^ Rhoads AR, Friedberg F (April 1997). "Sequence motifs for calmodulin recognition". FASEB J. 11 (5): 331â€“40. doi:10.1096/fasebj.11.5.9141499. PMID 9141499.
^ Xie X, Harrison DH, Schlichting I, Sweet RM, Kalabokis VN, Szent-GyÃ¶rgyi AG, Cohen C (March 1994). "Structure of the regulatory domain of scallop myosin at 2.8 A resolution". Nature. 368 (6469): 306â€“12. doi:10.1038/368306a0. PMID 8127365.

This article incorporates text from the public domain Pfam and InterPro: IPR000048

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

IQ calmodulin-binding motif Provide feedback

Calmodulin-binding motif.

Literature references

Xie X, Harrison DH, Schlichting I, Sweet RM, Kalabokis VN, Szent-Gyorgyi AG, Cohen C; , Nature 1994;368:306-312.: Structure of the regulatory domain of scallop myosin at 2.8 A resolution. PUBMED:8127365 EPMC:8127365
Rhoads AR, Friedberg F; , FASEB J 1997;11:331-340.: Sequence motifs for calmodulin recognition. PUBMED:9141499 EPMC:9141499

Internal database links

SCOOP:

BAG Myosin_tail_1

External database links

HOMSTRAD:	MYSc
SCOP:	1wdc
SMART:	IQ

This tab holds annotation information from the InterPro database.

InterPro entry 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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function

protein binding (GO:0005515)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan EF_hand (CL0220), which has the following description:

The EF hand is a calcium binding domain found in a wide variety of proteins [1].

The clan contains the following 31 members:

Ca_chan_IQ Caleosin Cbl_N2 Cullin_binding DAG_kinase_N Dockerin_1 EF-hand_1 EF-hand_10 EF-hand_11 EF-hand_12 EF-hand_13 EF-hand_14 EF-hand_2 EF-hand_3 EF-hand_4 EF-hand_5 EF-hand_6 EF-hand_7 EF-hand_8 EF-hand_9 EF-hand_like EF_assoc_2 EFhand_Ca_insen Internalin_N IQ IQCJ-SCHIP1 NADPH_Ox p25-alpha S_100 SPARC_Ca_bdg WEF-hand

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

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PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

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Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (245)	Full (82891)	Representative proteomes				UniProt (151320)
	Seed (245)	Full (82891)	RP15 (11929)	RP35 (34195)	RP55 (67459)	RP75 (91969)	UniProt (151320)
Jalview	View	View	View	View	View	View	View
HTML	View
PP/heatmap	₁

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (245)	Full (82891)	Representative proteomes				UniProt (151320)
	Seed (245)	Full (82891)	RP15 (11929)	RP35 (34195)	RP55 (67459)	RP75 (91969)	UniProt (151320)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (245)	Full (82891)	Representative proteomes				UniProt (151320)
	Seed (245)	Full (82891)	RP15 (11929)	RP35 (34195)	RP55 (67459)	RP75 (91969)	UniProt (151320)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

SMART

Previous IDs:

none

Type:

Motif

Sequence Ontology:

SO:0001067

Author:

Ponting CP

, Schultz J, Bork P

Number in seed:

245

Number in full:

82891

Average length of the domain:

20.60 aa

Average identity of full alignment:

33 %

Average coverage of the sequence by the domain:

4.54 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.3	11.1
Trusted cut-off	20.3	11.1
Noise cut-off	20.2	11.0

Model length:

21

Family (HMM) version:

29

Download:

download the raw HMM for this family

Species distribution

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

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Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

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There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

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For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

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Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the IQ domain has been found. There are 60 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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Family: IQ (PF00612)

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