Summary: Izumo sperm-egg fusion
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This is the Wikipedia entry entitled "Immunoglobulin superfamily". More...
Immunoglobulin superfamily Edit Wikipedia article
| Immunoglobulin superfamily | |||||||||
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| Antibody in complex with hen egg white lysozyme.[1] | |||||||||
| Identifiers | |||||||||
| Symbol | IgSF | ||||||||
| Pfam | PF00047 | ||||||||
| Pfam clan | CL0011 | ||||||||
| InterPro | IPR013151 | ||||||||
| PROSITE | PS50835 | ||||||||
| SCOP | 1tlk | ||||||||
| SUPERFAMILY | 1tlk | ||||||||
| OPM superfamily | 230 | ||||||||
| OPM protein | 3bib | ||||||||
| CDD | cd00096 | ||||||||
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The immunoglobulin superfamily (IgSF) is a large group 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.
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[edit] Immunoglobulin domains
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 categorised according to their size and function.[2] 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.
[edit] Classification
The Ig like domains can be classified as IgV, IgC1, IgC2, or IgI.[3]
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.[4]
[edit] 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.[5] 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.[6]
| Molecule function/category | Examples | Description |
|---|---|---|
| Antigen receptors |
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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. |
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| 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);[7] 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).[8] | |
| Receptors on Natural killer cells | ||
| Receptors on Leukocytes | ||
| IgSF CAMs | ||
| Cytokine receptors | ||
| Growth factor receptors |
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| Receptor tyrosine kinases/phosphatases |
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| Ig binding receptors |
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| Others |
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[edit] References
- ^ 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): 7981â91. 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): 215â23. doi:10.1016/S1044-5323(03)00047-2. PMID 14690046.
- ^ B. D. Gomperts; Ijsbrand M. Kramer; Peter E. R. Tatham (1 July 2009). Signal transduction. Academic Press. pp. 378â. ISBN 978-0-12-369441-6. http://books.google.com/books?id=izTeyIj5mM0C&pg=PA378. 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): 528â39. 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): 860â921. 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): 1939â41. doi:10.1002/pro.5560050923. PMC 2143528. PMID 8880921. http://www.proteinscience.org/cgi/pmidlookup?view=long&pmid=8880921.
- ^ Peggs K, Allison J (2005). "Co-stimulatory pathways in lymphocyte regulation: the immunoglobulin superfamily". Br J Haematol 130 (6): 809â24. 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: 515â48. doi:10.1146/annurev.immunol.23.021704.115611. PMID 15771580.
[edit] External links
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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.
Izumo sperm-egg fusion Provide feedback
Izumo is a molecule with a single immunoglobulin (Ig) domain. It is thought that Izumo 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 fertilization [1]. 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) [2]. There is a conserved GCL sequence motif. Izumo expression has been found to be testis-specific [1,2]. This family of proteins is found in eukaryotes and are typically between 193 and 305 amino acids in length.
Literature references
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Rubinstein E, Ziyyat A, Wolf JP, Le Naour F, Boucheix C;, Semin Cell Dev Biol. 2006;17:254-263.: The molecular players of sperm-egg fusion in mammals. PUBMED:16574441 EPMC:16574441
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Inoue N, Ikawa M, Isotani A, Okabe M;, Nature. 2005;434:234-238.: The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. PUBMED:15759005 EPMC:15759005
External database links
| PANDIT: | PF15005 |
| Pseudofam: | PF15005 |
| SYSTERS: | IZUMO |
This tab holds annotation information from the InterPro database.
No InterPro data for this Pfam family.
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 Ig (CL0011), which contains the following 24 members:
A2M Adeno_E3_CR1 Adhes-Ig_like C1-set C2-set C2-set_2 Herpes_gE Herpes_gI Herpes_glycop_D I-set ICAM_N ig Ig_2 Ig_3 Ig_Tie2_1 IZUMO K1 Lep_receptor_Ig Marek_A PTCRA Receptor_2B4 SVA V-set V-set_CD47Alignments
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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
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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 (8) |
Full (129) |
Representative proteomes | NCBI (139) |
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| RP15 (4) |
RP35 (4) |
RP55 (8) |
RP75 (53) |
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| PP/heatmap | 1 | |||||||
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| Seed (8) |
Full (129) |
Representative proteomes | NCBI (139) |
Meta (0) |
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| RP15 (4) |
RP35 (4) |
RP55 (8) |
RP75 (53) |
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| Raw Stockholm | ||||||||
| Gzipped | ||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
External links
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
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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.
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Curation and family details
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Curation
This family is new in this Pfam release.
| Seed source: | Jackhmmer:Q6UXV1 |
| Previous IDs: | none |
| Type: | Family |
| Author: | Coggill P, Hetherington K |
| Number in seed: | 8 |
| Number in full: | 129 |
| Average length of the domain: | 145.10 aa |
| Average identity of full alignment: | 28 % |
| Average coverage of the sequence by the domain: | 60.57 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 160 | ||||||||||||
| Family (HMM) version: | 1 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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