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0  structures 29  species 0  interactions 129  sequences 2  architectures

Family: IZUMO (PF15005)

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
PDB 1a2y EBI.jpg
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

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.

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 categorized 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.

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]

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]

Members of the immunoglobulin superfamily
Molecule function/category Examples Description
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
  • CD28
  • CD80 and CD86 (also known as B7.1 and B7.2 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
  • NCAMs
  • ICAM-1
  • CD2 subset
  • Type IIa and Type IIb RPTPs, described in Receptor tyrosine kinases/phosphatases subsection below
Cytokine receptors
Growth factor receptors
Receptor tyrosine kinases/phosphatases
Ig binding receptors
Others

References

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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 2143528. PMID 8880921. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 

External links

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

  1. 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

  2. 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

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

Domain organisation

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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 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_CD47

Alignments

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(8)
Full
(129)
Representative proteomes NCBI
(139)
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(4)
RP35
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  Seed
(8)
Full
(129)
Representative proteomes NCBI
(139)
Meta
(0)
RP15
(4)
RP35
(4)
RP55
(8)
RP75
(53)
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  Seed
(8)
Full
(129)
Representative proteomes NCBI
(139)
Meta
(0)
RP15
(4)
RP35
(4)
RP55
(8)
RP75
(53)
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External links

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Curation and family details

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Curation View help on the curation process

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 View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 27.0
Trusted cut-off 42.4 41.8
Noise cut-off 22.6 22.0
Model length: 160
Family (HMM) version: 1
Download: download the raw HMM for this family

Species distribution

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