Summary: Immunoglobulin C2-set domain
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Immunoglobulin C2-set domain Edit Wikipedia article
|Immunoglobulin C2-set domain|
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:Â IPR013106), C1-set (constant-1; InterPro:Â IPR003597), C2-set (constant-2; InterPro:Â IPR008424) and I-set (intermediate; InterPro:Â IPR013098). 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.
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 cellâ€“cell recognition, cell-surface receptors, muscle structure and the immune system.
C2-set domains, which are Ig-like domains resembling the antibody constant domain. C2-set domains are found primarily in the mammalian T-cell surface antigens CD2 (Cluster of Differentiation 2), CD4 and CD80, as well as in vascular (VCAM) and intercellular (ICAM) cell adhesion molecules.
CD2 mediates T-cell adhesion via its ectodomain, and signal transduction utilising its 117-amino acid cytoplasmic tail. CD2 displays structural and functional similarities with African swine fever virus (ASFV) LMW8-DR, a protein that is involved in cellâ€“cell adhesion and immune response modulation, suggesting a possible role in the pathogenesis of ASFV infection. CD4 is the primary receptor for HIV-1. CD4 has four immunoglobulin-like domains in its extracellular region that share the same structure, but can differ in sequence. Certain extracellular domains may be involved in dimerisation.
Human proteins containing this domain
- Smith DK, Xue H (1997). "Sequence profiles of immunoglobulin and immunoglobulin-like domains". J. Mol. Biol. 274 (4): 530â€“545. doi:10.1006/jmbi.1997.1432. PMIDÂ 9417933.
- Potapov V, Sobolev V, Edelman M, Kister A, Gelfand I (2004). "Protein-Protein Recognition: Juxtaposition of Domain and Interface Cores in Immunoglobulins and Other Sandwich-like Proteins". J. Mol. Biol. 342 (2): 665â€“679. doi:10.1016/j.jmb.2004.06.072. PMIDÂ 15327963.
- Clarke J, Fowler SB (2001). "Mapping the folding pathway of an immunoglobulin domain: structural detail from Phi value analysis and movement of the transition state". Structure. 9 (5): 355â€“366. doi:10.1016/S0969-2126(01)00596-2. PMIDÂ 11377196.
- Chothia C, Teichmann SA (2000). "Immunoglobulin superfamily proteins in Caenorhabditis elegans". J. Mol. Biol. 296 (5): 1367â€“83. CiteSeerXÂ 10.1.1.327.6917. doi:10.1006/jmbi.1999.3497. PMIDÂ 10698639.
- Reinherz EL, Yang H (2001). "Dynamic recruitment of human CD2 into lipid rafts. Linkage to T cell signal transduction". J. Biol. Chem. 276 (22): 18775â€“18785. doi:10.1074/jbc.M009852200. PMIDÂ 11376005.
- Kutish GF, Rock DL, Afonso CL, Borca MV, Irusta P, Carrillo C, Brun A, Sussman M (1994). "An African swine fever virus gene with similarity to the T-lymphocyte surface antigen CD2 mediates hemadsorption". Virology. 199 (2): 463â€“468. doi:10.1006/viro.1994.1146. PMIDÂ 7907198.
- Sanejouand YH (2004). "Domain swapping of CD4 upon dimerization". Proteins. 57 (1): 205â€“12. doi:10.1002/prot.20197. PMIDÂ 15326605.
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Internal database links
|SCOOP:||ig Ig_2 Ig_3|
This tab holds annotation information from the InterPro database.
InterPro entry IPR008424
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 C2-set domains, which are Ig-like domains resembling the antibody constant domain. C2-set domains are found primarily in the mammalian T-cell surface antigens CD2 (Cluster of Differentiation 2), CD4 and CD80, as well as in vascular (VCAM) and intercellular (ICAM) cell adhesion molecules.
CD2 mediates T-cell adhesion via its ectodomain, and signal transduction utilising its 117-amino acid cytoplasmic tail [ PUBMED:11376005 ]. CD2 displays structural and functional similarities with African swine fever virus (ASFV) LMW8-DR, a protein that is involved in cell-cell adhesion and immune response modulation, suggesting a possible role in the pathogenesis of ASFV infection [ PUBMED:7907198 ]. CD4 is the primary receptor for HIV-1. CD4 has four immunoglobulin-like domains in its extracellular region that share the same structure, but can differ in sequence. Certain extracellular domains may be involved in dimerisation [ PUBMED:15326605 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||integral component of membrane (GO:0016021)|
|Biological process||cell adhesion (GO:0007155)|
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:
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This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
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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 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
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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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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|Seed source:||Bateman A|
|Author:||Bateman A , Finn RD , Moxon SJ|
|Number in seed:||27|
|Number in full:||809|
|Average length of the domain:||82.90 aa|
|Average identity of full alignment:||29 %|
|Average coverage of the sequence by the domain:||24.83 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||18|
|Download:||download the raw HMM for this family|
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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 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:
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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.
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The tree shows the occurrence of this domain across different species. More...
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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.
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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 C2-set domain has been found. There are 93 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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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.