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325  structures 441  species 0  interactions 16531  sequences 1663  architectures

Family: ig (PF00047)

Summary: Immunoglobulin domain

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This is the Wikipedia entry entitled "Immunoglobulin domain". More...

Immunoglobulin domain Edit Wikipedia article

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

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
SymbolIgSF
PfamPF00047
Pfam clanCL0011
InterProIPR013151
PROSITEPS50835
SCOPe1tlk / SUPFAM
OPM superfamily193
OPM protein3bib
CDDcd00096
Membranome2
Immunoglobulin-like (ligands)
Identifiers
SymbolIg protein ligands
Membranome64
Immunoglobulin-like adhesion molecules
Identifiers
SymbolIgSF CAM
Membranome110

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. Otherwise, the sperm-specific protein IZUMO1, 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. It is believed that the structure of variable subgenes of Ig and the surface immunoglobulin determine the propensity of chronic or tonic BCR signalling.

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

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 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
Cytoskeleton
Others

References

  1. ^ Dall'Acqua W, Goldman ER, Lin W, Teng C, Tsuchiya D, Li H, Ysern X, Braden BC, Li Y, Smith-Gill SJ, Mariuzza RA (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 AN (August 2003). "Membrane proteins with immunoglobulin-like domains--a master superfamily of interaction molecules". Seminars in Immunology. 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". Journal of Molecular Biology. 238 (4): 528–39. doi:10.1006/jmbi.1994.1312. PMID 8176743.
  5. ^ Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. (February 2001). "Initial sequencing and analysis of the human genome" (PDF). 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 Science. 5 (9): 1939–41. doi:10.1002/pro.5560050923. PMC 2143528. PMID 8880921.
  7. ^ Peggs KS, Allison JP (September 2005). "Co-stimulatory pathways in lymphocyte regulation: the immunoglobulin superfamily". British Journal of Haematology. 130 (6): 809–24. doi:10.1111/j.1365-2141.2005.05627.x. PMID 16156851.
  8. ^ Greenwald RJ, Freeman GJ, Sharpe AH (2005). "The B7 family revisited". Annual Review of Immunology. 23: 515–48. doi:10.1146/annurev.immunol.23.021704.115611. PMID 15771580.
  9. ^ Boles KS, Stepp SE, Bennett M, Kumar V, Mathew PA (June 2001). "2B4 (CD244) and CS1: novel members of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer cells and other leukocytes". Immunological Reviews. 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 (February 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 (September 2003). "Functional requirements for interactions between CD84 and Src homology 2 domain-containing proteins and their contribution to human T cell activation". Journal of Immunology. 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.

Immunoglobulin domain Provide feedback

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.

Literature references

  1. Bruemmendorf T, Rathjen FG; , Protein Profile 1995;2:963-1085.: Cell adhesion molecules 1: immunoglobulin superfamily. PUBMED:8574878 EPMC:8574878

  2. Bork P, Holm L, Sander C; , J Mol Biol 1994;242:309-320.: The immunoglobulin fold PUBMED:7932691 EPMC:7932691

  3. Williams AF, Barclay AN; , Annu Rev Immunol 1988;6:381-405.: The immunoglobulin superfamily--domains for cell surface recognition. PUBMED:3289571 EPMC:3289571

Internal database links

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

External database links

HOMSTRAD: igC1 igC2 igI igV igcon igvar-h igvar-l MHC_II_C MHC_II_alpha_NC MHC_II_beta_NC
PROSITE: PDOC00262
SCOP: 8fab

This tab holds annotation information from the InterPro database.

InterPro entry IPR013151

This entry represents the immunoglobulin domain that is 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. This domain does not include the first and last strand of the immunoglobulin-like domain.

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 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...

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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
(34)		 Full
(16531)		 Representative proteomes UniProt
(31417)
RP15
(1885)		 RP35
(4798)		 RP55
(12932)		 RP75
(18287)
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  Seed
(34)		 Full
(16531)		 Representative proteomes UniProt
(31417)
RP15
(1885)		 RP35
(4798)		 RP55
(12932)		 RP75
(18287)
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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
(34)		 Full
(16531)		 Representative proteomes UniProt
(31417)
RP15
(1885)		 RP35
(4798)		 RP55
(12932)		 RP75
(18287)
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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 View help on the curation process

Seed source: Bateman A
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Sonnhammer ELL
Number in seed: 34
Number in full: 16531
Average length of the domain: 83.50 aa
Average identity of full alignment: 16 %
Average coverage of the sequence by the domain: 11.55 %

HMM information View help on HMM parameters

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 21.8 21.8
Trusted cut-off 21.8 21.8
Noise cut-off 21.7 21.7
Model length: 87
Family (HMM) version: 27
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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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 ig domain has been found. There are 325 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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