Summary: Immunoglobulin I-set domain

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Wikipedia: Immunoglobulin I-set domain
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This is the Wikipedia entry entitled "Immunoglobulin I-set domain". More...

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Immunoglobulin I-set domain Edit Wikipedia article

Immunoglobulin I-set domain

Identifiers

Symbol

I-set

Available protein structures:
Pfam Â	structures / ECOD Â
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	1ry7B:157-245 1qctE:153-241 1fq9C:159-247 1evtD:159-247 1cvsC:159-247 1cs6A:322-407 1wf5A:306-320 1bihB:327-412 1tnm :33489-3357 1tnn :33489-33571qz1A:214-305 1ie5A:214-304 1fhgA:42-132 1tlk :42-132 1u2hA:43-113 1wwcA:325-352 1koa :6585-6674 2cqvA:1238-1327 1x44A:342-430 1pd6A:363-448 1gxeA:652-767 1wit :4150-4239 1wiu :4150-4239 2cryA:419-516 1epfB:20-114 2ncm :20-114 1vcaA:25-112 1ij9A:25-112 1vscA:25-112

I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM). I-set domains are also present in several other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1^[1], and the signalling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis^[2].

Human proteins containing this domain

ADAMTSL1; ADAMTSL3; ALPK3; AXL; BOC; C9orf94; CADM2; CADM4; CCDC141; CDON; CEACAM7; CHL1; CILP2; CNTN1; CNTN2; CNTN3; CNTN4; CNTN5; CNTN6; CXADR; DCC; DSCAM; DSCAML1; ESAM; FGFR1; FGFR3; FGFR4; FGFRL1; FLT1; FLT4; FSTL4; FSTL5; HMCN1; HNT; HSPG2; ICAM5; IGFBP7; IGFBPL1; IGSF10; IGSF22; IGSF9; ISLR; KALRN; KAZALD1; KDR; KIAA0626; KIRREL; KIRREL2; KIRREL3; L1CAM; LINGO1; LINGO2; LRFN2; LRFN3; LRFN4; LRFN5; LRIG1; LRIG2; LRIG3; LRIT2; LRIT3; LRRC24; LRRC4B; LRRC4C; LRRN1; LRRN3; LRRN5; LSAMP; MAG; MDGA2; MFAP3L; MUSK; MXRA5; MYBPC1; MYBPC2; MYBPC3; MYBPH; MYBPHL; MYLK; MYOM1; MYOM2; MYOM3; MYOT; MYPN; NCAM1; NCAM2; NEGR1; NEO1; NEXN; NFASC; NGL1; NOPE; NPHS1; NPTN; NRCAM; NRG2; NT; NTRK2; NTRK3; OBSCN; OBSL1; OPCML; PALLD; PAPLN; PDGFRA; PRODH2; PTK7; PTPRD; PTPRF; PTPRS; PTPsigma; PUNC; ROBO1; ROBO2; ROBO3; ROBO4; ROR1; ROR2; SDK1; SDK2; SIGLEC1; SIGLEC6; SPEG; TRIO; TTN; UNC5A; UNC5B; UNC5C; VCAM1; WFIKKN1; WFIKKN2;

References

^ Sonderegger P, Welte W, Diederichs K, Freigang J, Proba K, Leder L (2000). "The crystal structure of the ligand binding module of axonin-1/TAG-1 suggests a zipper mechanism for neural cell adhesion". Cell. 101 (4): -. PMIDÂ 10830169.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Stuart DI, Jones EY, Harlos K, Esnouf RM, Love CA (2006). "Structure determination of human semaphorin 4D as an example of the use of MAD in non-optimal cases". Acta Crystallogr. D. 62: -. PMIDÂ 16369100.{{cite journal}}: CS1 maint: multiple names: authors list (link)

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This article incorporates text from the public domain Pfam and InterPro: IPR013098

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Immunoglobulin I-set domain Provide feedback

No Pfam abstract.

Internal database links

SCOOP:	Adeno_E3_CR1 C1-set C2-set_2 fn3 ICAM_N ig Ig_2 Ig_3 Ig_4 Ig_5 Ig_6 Ig_7 Ig_C17orf99 Izumo-Ig Podoplanin Pur_ac_phosph_N Receptor_2B4 RIFIN SprB V-set V-set_CD47
Similarity to PfamA using HHSearch:	ig C1-set V-set V-set_CD47 C2-set_2 Receptor_2B4 Ig_2 Ig_3 Ig_4 Ig_5 Izumo-Ig Ig_6

This tab holds annotation information from the InterPro database.

InterPro entry IPR013098

The basic structure of immunoglobulin (Ig) molecules is a tetramer of two light chains and two heavy chains linked by disulphide bonds. There are two types of light chains: kappa and lambda, each composed of a constant domain (CL) and a variable domain (VL). There are five types of heavy chains: alpha, delta, epsilon, gamma and mu, all consisting of a variable domain (VH) and three (in alpha, delta and gamma) or four (in epsilon and mu) constant domains (CH1 to CH4). Ig molecules are highly modular proteins, in which the variable and constant domains have clear, conserved sequence patterns. The domains in Ig and Ig-like molecules are grouped into four types: V-set (variable; INTERPRO ), C1-set (constant-1; INTERPRO ), C2-set (constant-2; INTERPRO ) and I-set (intermediate; INTERPRO ) [ PUBMED:9417933 ]. Structural studies have shown that these domains share a common core Greek-key beta-sandwich structure, with the types differing in the number of strands in the beta-sheets as well as in their sequence patterns [ PUBMED:15327963 , PUBMED:11377196 ].

Immunoglobulin-like domains that are related in both sequence and structure can be found in several diverse protein families. Ig-like domains are involved in a variety of functions, including cell-cell recognition, cell-surface receptors, muscle structure and the immune system [ PUBMED:10698639 ].

This entry represents I-set domains, which are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM). I-set domains are also present in several other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1 [ PUBMED:10830169 ], the signalling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis [ PUBMED:16369100 ] and the Zwei Ig domain proteins zig involved in the postembriogenic neuronal soma and axon position maintenance [ PUBMED:11809975 , PUBMED:22829780 ].

Domain organisation

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

Loading domain graphics...

Pfam Clan

This family is a member of clan Ig (CL0011), which has the following description:

Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions. The superfamily can be divided into discrete structural sets, by the presence or absence of beta-strands in the structure and the length of the domains [1]. Proteins containing domains of the C1 and V-sets are mostly molecules of the vertebrate immune system. Proteins of the C2-set are mainly lymphocyte antigens, this differs from the composition of the C2-set as originally proposed [1]. The I-set is intermediate in structure between the C1 and V-sets and is found widely in cell surface proteins as well as intracellular muscle proteins.

The clan contains the following 34 members:

Adeno_E3_CR1 Adhes-Ig_like bCoV_NS7A bCoV_NS8 C1-set C2-set C2-set_2 CD4-extracel DUF1968 Herpes_gE Herpes_gI Herpes_glycop_D I-set ICAM_N ig Ig_2 Ig_3 Ig_4 Ig_5 Ig_6 Ig_7 Ig_C17orf99 Ig_C19orf38 Ig_Tie2_1 Izumo-Ig K1 Marek_A ObR_Ig PTCRA Receptor_2B4 UL141 V-set V-set_2 V-set_CD47

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:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
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.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

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 (48)	Full (379774)	Representative proteomes				UniProt (579471)
	Seed (48)	Full (379774)	RP15 (43389)	RP35 (115132)	RP55 (274355)	RP75 (381589)	UniProt (579471)
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 (48)	Full (379774)	Representative proteomes				UniProt (579471)
	Seed (48)	Full (379774)	RP15 (43389)	RP35 (115132)	RP55 (274355)	RP75 (381589)	UniProt (579471)
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 (48)	Full (379774)	Representative proteomes				UniProt (579471)
	Seed (48)	Full (379774)	RP15 (43389)	RP35 (115132)	RP55 (274355)	RP75 (381589)	UniProt (579471)
Raw Stockholm	Download		Download	Download	Download
Gzipped	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:

Bateman A

Previous IDs:

none

Type:

Domain

Sequence Ontology:

SO:0000417

Author:

Bateman A

Number in seed:

48

Number in full:

379774

Average length of the domain:

88.7 aa

Average identity of full alignment:

21 %

Average coverage of the sequence by the domain:

25.05 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	23.7	23.7
Trusted cut-off	23.7	23.7
Noise cut-off	23.6	23.6

Model length:

90

Family (HMM) version:

19

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

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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.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

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.

Anomalies in the taxonomy tree

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

Missing taxonomic levels

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.

Too many species/sequences

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.

Loading sunburst data...

Tree controls

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The tree shows the occurrence of this domain across different species. More...

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:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

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 I-set domain has been found. There are 741 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.

Loading structure mapping...

AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein	Predicted structure	External Information
A0A044QKH1	View 3D Structure	Click here
A0A044QQM7	View 3D Structure	Click here
A0A044R9D0	View 3D Structure	Click here
A0A044RYL9	View 3D Structure	Click here
A0A044S247	View 3D Structure	Click here
A0A044S2H5	View 3D Structure	Click here
A0A044S4W0	View 3D Structure	Click here
A0A044SKA2	View 3D Structure	Click here
A0A044SX34	View 3D Structure	Click here
A0A044T3B3	View 3D Structure	Click here
A0A044T3S7	View 3D Structure	Click here
A0A044T607	View 3D Structure	Click here
A0A044TBE7	View 3D Structure	Click here
A0A044TD32	View 3D Structure	Click here
A0A044TG54	View 3D Structure	Click here
A0A044TGP3	View 3D Structure	Click here
A0A044TJ59	View 3D Structure	Click here
A0A044TL59	View 3D Structure	Click here
A0A044TP14	View 3D Structure	Click here
A0A044TPB0	View 3D Structure	Click here
A0A044U4T6	View 3D Structure	Click here
A0A044U682	View 3D Structure	Click here
A0A044UGZ6	View 3D Structure	Click here
A0A044UIA8	View 3D Structure	Click here
A0A044UZ90	View 3D Structure	Click here
A0A044VJ14	View 3D Structure	Click here
A0A077YVH5	View 3D Structure	Click here
A0A077YZ00	View 3D Structure	Click here
A0A077YZT2	View 3D Structure	Click here
A0A077Z0D0	View 3D Structure	Click here
A0A077Z1Z5	View 3D Structure	Click here
A0A077Z2G9	View 3D Structure	Click here
A0A077Z2W6	View 3D Structure	Click here
A0A077Z2X9	View 3D Structure	Click here
A0A077Z2Y8	View 3D Structure	Click here
A0A077Z3G5	View 3D Structure	Click here
A0A077Z3H0	View 3D Structure	Click here
A0A077Z3S0	View 3D Structure	Click here
A0A077Z439	View 3D Structure	Click here
A0A077Z450	View 3D Structure	Click here

Showing 40 matches

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Family: I-set (PF07679)

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