Summary: Izumo-like Immunoglobulin domain
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "Immunoglobulin superfamily". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Immunoglobulin superfamily Edit Wikipedia article
Antibody in complex with hen egg white lysozyme.
The immunoglobulin superfamily (IgSF) is a large protein superfamily of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins (also known as antibodies); they all possess a domain known as an immunoglobulin domain or fold. Members of the IgSF include cell surface antigen receptors, co-receptors and co-stimulatory molecules of the immune system, molecules involved in antigen presentation to lymphocytes, cell adhesion molecules, certain cytokine receptors and intracellular muscle proteins. They are commonly associated with roles in the immune system. The sperm-specific protein Izumo, a member of the immunoglobulin superfamily, has also been identified as the only sperm membrane protein essential for sperm-egg fusion.
Proteins of the IgSF possess a structural domain known as an immunoglobulin (Ig) domain. Ig domains are named after the immunoglobulin molecules. They contain about 70-110 amino acids and are categorized according to their size and function. Ig-domains possess a characteristic Ig-fold, which has a sandwich-like structure formed by two sheets of antiparallel beta strands. Interactions between hydrophobic amino acids on the inner side of the sandwich and highly conserved disulfide bonds formed between cysteine residues in the B and F strands, stabilize the Ig-fold. One end of the Ig domain has a section called the complementarity determining region that is important for the specificity of antibodies for their ligands. It is believed that the structure of variable subgenes of Ig and the surface immunoglobulin determine the propensity of chronic or tonic BCR signalling.
The Ig like domains can be classified as IgV, IgC1, IgC2, or IgI.
Most Ig domains are either variable (IgV) or constant (IgC).
- IgV: IgV domains with 9 beta strands are generally longer than IgC domains with 7 beta strands.
- IgC1 and IgC2: Ig domains of some members of the IgSF resemble IgV domains in the amino acid sequence, yet are similar in size to IgC domains. These are called IgC2 domains, while standard IgC domains are called IgC1 domains.
- IgI: Other Ig domains exist that are called intermediate (I) domains.
Members of the immunoglobulin superfamily
The Ig domain was reported to be the most populous family of proteins in the human genome with 765 members identified. Members of the family can be found even in the bodies of animals with a simple physiological structure such as poriferan sponges. They have also been found in bacteria, where their presence is thought to be due to horizontal gene transfer.
|Antigen receptors||Antigen receptors found on the surface of T and B lymphocytes in all jawed vertebrates belong to the IgSF. Immunoglobulin molecules (the antigen receptors of B cells) are the founding members of the IgSF. In humans, there are five distinct types of immunoglobulin molecule all containing a heavy chain with four Ig domains and a light chain with two Ig domains. The antigen receptor of T cells is the T cell receptor (TCR), which is composed of two chains, either the TCR-alpha and -beta chains, or the TCR-delta and gamma chains. All TCR chains contain two Ig domains in the extracellular portion; one IgV domain at the N-terminus and one IgC1 domain adjacent to the cell membrane.|
|Antigen presenting molecules||The ligands for TCRs are major histocompatibility complex (MHC) proteins. These come in two forms; MHC class I forms a dimer with a molecule called beta-2 microglobulin (β2M) and interacts with the TCR on cytotoxic T cells and MHC class II has two chains (alpha and beta) that interact with the TCR on helper T cells. MHC class I, MHC class II and β2M molecules all possess Ig domains and are therefore also members of the IgSF.|
|Co-receptors||Co-receptors and accessory molecules: Other molecules on the surfaces of T cells also interact with MHC molecules during TCR engagement. These are known as co-receptors. In lymphocyte populations, the co-receptor CD4 is found on helper T cells and the co-receptor CD8 is found on cytotoxic T cells. CD4 has four Ig domains in its extracellular portion and functions as a monomer. CD8, in contrast, functions as a dimer with either two identical alpha chains or, more typically, with an alpha and beta chain. CD8-alpha and CD8-beta each has one extracellular IgV domain in its extracellular portion. A co-receptor complex is also used by the BCR, including CD19, an IgSF molecule with two IgC2-domains.|
|Antigen receptor accessory molecules||A further molecule is found on the surface of T cells that is also involved in signaling from the TCR. CD3 is a molecule that helps to transmit a signal from the TCR following its interaction with MHC molecules. Three different chains make up CD3 in humans, the gamma chain, delta chain and epsilon chain, all of which are IgSF molecules with a single Ig domain.
Similar to the situation with T cells, B cells also have cell surface co-receptors and accessory molecules that assist with cell activation by the B Cell Receptor (BCR)/immunoglobulin. Two chains are used or signaling, CD79a and CD79b that both possess a single Ig domain.
|Co-stimulatory or inhibitory molecules||Co-stimulatory or inhibitory molecules: Co-stimulatory and inhibitory signaling receptors and ligands control the activation, expansion and effector functions of cells. One major group of IgSF co-stimulatory receptors are molecules of the CD28 family; CD28, CTLA-4, program death-1 (PD-1), the B- and T-lymphocyte attenuator (BTLA, CD272), and the inducible T-cell co-stimulator (ICOS, CD278); and their IgSF ligands belong to the B7 family; CD80 (B7-1), CD86 (B7-2), ICOS ligand, PD-L1 (B7-H1), PD-L2 (B7-DC), B7-H3, and B7-H4 (B7x/B7-S1).|
|Receptors on Natural killer cells|
|Receptors on Leukocytes|
|Growth factor receptors|
|Receptor tyrosine kinases/phosphatases|
|Ig binding receptors|
- Dall'Acqua W, Goldman ER, Lin W, et al. (June 1998). "A mutational analysis of binding interactions in an antigen-antibody protein-protein complex". Biochemistry. 37 (22): 7981–91. doi:10.1021/bi980148j. PMID 9609690.
- Barclay A (2003). "Membrane proteins with immunoglobulin-like domains--a master superfamily of interaction molecules". Semin Immunol. 15 (4): 215–23. doi:10.1016/S1044-5323(03)00047-2. PMID 14690046.
- Seda V, Mraz M (2015). "B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells". Eur. J. Haematol. 94 (3): 193–205. doi:10.1111/ejh.12427. PMID 25080849.
- B. D. Gomperts; Ijsbrand M. Kramer; Peter E. R. Tatham (1 July 2009). Signal transduction. Academic Press. pp. 378–. ISBN 978-0-12-369441-6. Retrieved 28 November 2010.
- Harpaz Y, Chothia C (May 1994). "Many of the immunoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains". J. Mol. Biol. 238 (4): 528–39. doi:10.1006/jmbi.1994.1312. PMID 8176743.
- Lander ES, Linton LM, Birren B, et al. (February 2001). "Initial sequencing and analysis of the human genome". Nature. 409 (6822): 860–921. doi:10.1038/35057062. PMID 11237011.
- Bateman A, Eddy SR, Chothia C (September 1996). "Members of the immunoglobulin superfamily in bacteria". Protein Sci. 5 (9): 1939–41. doi:10.1002/pro.5560050923. PMC . PMID 8880921.[permanent dead link]
- Peggs K, Allison J (2005). "Co-stimulatory pathways in lymphocyte regulation: the immunoglobulin superfamily". Br J Haematol. 130 (6): 809–24. doi:10.1111/j.1365-2141.2005.05627.x. PMID 16156851.
- Greenwald R, Freeman G, Sharpe A (2005). "The B7 family revisited". Annu Rev Immunol. 23: 515–48. doi:10.1146/annurev.immunol.23.021704.115611. PMID 15771580.
- Boles, KS.; Stepp, SE.; Bennett, M.; Kumar, V.; Mathew, PA. (Jun 2001). "2B4 (CD244) and CS1: novel members of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer cells and other leukocytes". Immunol Rev. 181: 234–49. doi:10.1034/j.1600-065X.2001.1810120.x. PMID 11513145.
- Fraser, CC.; Howie, D.; Morra, M.; Qiu, Y.; Murphy, C.; Shen, Q.; Gutierrez-Ramos, JC.; Coyle, A.; Kingsbury, GA.; Terhorst, C (Feb 2002). "Identification and characterization of SF2000 and SF2001, two new members of the immune receptor SLAM/CD2 family". Immunogenetics. 53 (10–11): 843–50. doi:10.1007/s00251-001-0415-7. PMID 11862385.
- Tangye, SG.; Nichols, KE.; Hare, NJ.; Van De Weerdt, BC. (Sep 2003). "Functional requirements for interactions between CD84 and Src homology 2 domain-containing proteins and their contribution to human T cell activation". J Immunol. 171 (5): 2485–95. doi:10.4049/jimmunol.171.5.2485. PMID 12928397.
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.
Izumo-like Immunoglobulin domain Provide feedback
Izumo-Ig is the immunoglobulin domain on Izumo proteins from higher eukaryotes. Izumo is a typical type I membrane glycoprotein with one immunoglobulin-like domain and a putative N-glycoside link motif - glycosylation site. The full-length protein, eg Q8IYV9 is a molecule with a single immunoglobulin (Ig) domain. It is thought that Izumo proteins bind to putative Izumo receptors on the oocyte. Izumo is not detectable on the surface of fresh sperm but becomes exposed only after an exocytotic process, the acrosome reaction, has occurred. Studies have shown that knock-out mice (Izumo-/- males) were sterile despite normal mating behaviour and ejaculation, indicating the importance of the protein in fertilisation . There is a conserved GCL sequence motif. Izumo expression has been found to be testis-specific [1,2].
Internal database links
|SCOOP:||I-set ig Ig_2 Ig_3 V-set|
|Similarity to PfamA using HHSearch:||ig I-set V-set Ig_2 Ig_3|
This tab holds annotation information from the InterPro database.
InterPro entry IPR032699
This is the immunoglobulin domain on Izumo proteins from higher eukaryotes. Izumo is a typical type I membrane glycoprotein with one immunoglobulin-like domain and a putative N-glycoside link motif - glycosylation site. The full-length human IZUMO1 protein is a molecule with a single immunoglobulin (Ig) domain. It is thought that Izumo proteins bind to putative Izumo receptors on the oocyte. Izumo is not detectable on the surface of fresh sperm but becomes exposed only after an exocytotic process, the acrosome reaction, has occurred. Studies have shown that knock-out mice (Izumo-/- males) were sterile despite normal mating behaviour and ejaculation, indicating the importance of the protein in fertilisation [PUBMED:16574441]. There are cysteine residues thought to form a disulphide bridge. Izumo is a typical type I membrane glycoprotein with one immunoglobulin-like domain and a putative N-glycoside link motif (Asn 204) [PUBMED:15759005]. There is a conserved GCL sequence motif. Izumo expression has been found to be testis-specific [PUBMED:16574441, PUBMED:15759005].
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
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 . 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 . 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 26 members:Adeno_E3_CR1 Adhes-Ig_like C1-set C2-set C2-set_2 DUF1968 Herpes_gE Herpes_gI Herpes_glycop_D I-set ICAM_N ig Ig_2 Ig_3 Ig_4 Ig_5 Ig_Tie2_1 Izumo-Ig K1 Marek_A PTCRA Receptor_2B4 UL141 V-set V-set_2 V-set_CD47
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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics 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.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- 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
- 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.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
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.
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.
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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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...
If you find these logos useful in your own work, please consider citing the following article:
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.
|Author:||Coggill P, Bateman A|
|Number in seed:||17|
|Number in full:||44|
|Average length of the domain:||86.30 aa|
|Average identity of full alignment:||56 %|
|Average coverage of the sequence by the domain:||22.70 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||4|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the 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:
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".
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.
The tree shows the occurrence of this domain across different species. More...
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.
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
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.
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 Izumo-Ig domain has been found. There are 14 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...