P01880 · IGHD_HUMAN
- ProteinImmunoglobulin heavy constant delta
- GeneIGHD
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids430 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Constant region of immunoglobulin heavy chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414).
The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268).
IgD is the major antigen receptor isotype on the surface of most peripheral B-cells, where it is coexpressed with IgM. The membrane-bound IgD (mIgD) induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. Soluble IgD (sIgD) concentration in serum below those of IgG, IgA, and IgM but much higher than that of IgE. IgM and IgD molecules present on B cells have identical V regions and antigen-binding sites. After the antigen binds to the B-cell receptor, the secreted form sIgD is shut off. IgD is a potent inducer of TNF, IL1B, and IL1RN. IgD also induces release of IL6, IL10, and LIF from peripheral blood mononuclear cells. Monocytes seem to be the main producers of cytokines in vitro in the presence of IgD (PubMed:10702483, PubMed:11282392, PubMed:8774350).
The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268).
IgD is the major antigen receptor isotype on the surface of most peripheral B-cells, where it is coexpressed with IgM. The membrane-bound IgD (mIgD) induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. Soluble IgD (sIgD) concentration in serum below those of IgG, IgA, and IgM but much higher than that of IgE. IgM and IgD molecules present on B cells have identical V regions and antigen-binding sites. After the antigen binds to the B-cell receptor, the secreted form sIgD is shut off. IgD is a potent inducer of TNF, IL1B, and IL1RN. IgD also induces release of IL6, IL10, and LIF from peripheral blood mononuclear cells. Monocytes seem to be the main producers of cytokines in vitro in the presence of IgD (PubMed:10702483, PubMed:11282392, PubMed:8774350).
Miscellaneous
IgD is not present in every species and this does not relate to phylogeny and evolution. IgD is present in primates, dog, mouse and rat whereas it is undetectable in rabbit, guinea pig, swine, cattle, sheep and Xenopus.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | blood microparticle | |
Cellular Component | extracellular exosome | |
Cellular Component | extracellular space | |
Cellular Component | IgD immunoglobulin complex | |
Cellular Component | plasma membrane | |
Molecular Function | antigen binding | |
Biological Process | adaptive immune response | |
Biological Process | B cell receptor signaling pathway | |
Biological Process | immune response | |
Biological Process | immunoglobulin mediated immune response | |
Biological Process | positive regulation of interleukin-1 production |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameImmunoglobulin heavy constant delta
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP01880
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform 1
Isoform 2
Cell membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-406 | Extracellular | ||||
Sequence: APTKAPDVFPIISGCRHPKDNSPVVLACLITGYHPTSVTVTWYMGTQSQPQRTFPEIQRRDSYYMTSSQLSTPLQQWRQGEYKCVVQHTASKSKKEIFRWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGRGGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAVQDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGVEEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPSLPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCEVSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPRSTTFWAWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVSYLAMTPLIPQSKDENSDDYTTFDDVGSLWTT | ||||||
Transmembrane | 407-427 | Helical | ||||
Sequence: LSTFVALFILTLLYSGIVTFI | ||||||
Topological domain | 428-430 | Cytoplasmic | ||||
Sequence: KVK |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000153570 | 1-430 | Immunoglobulin heavy constant delta | |||
Sequence: APTKAPDVFPIISGCRHPKDNSPVVLACLITGYHPTSVTVTWYMGTQSQPQRTFPEIQRRDSYYMTSSQLSTPLQQWRQGEYKCVVQHTASKSKKEIFRWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGRGGEEKKKEKEKEEQEERETKTPECPSHTQPLGVYLLTPAVQDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGVEEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPSLPPQRLMALREPAAQAPVKLSLNLLASSDPPEAASWLLCEVSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPRSTTFWAWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLEVSYLAMTPLIPQSKDENSDDYTTFDDVGSLWTTLSTFVALFILTLLYSGIVTFIKVK | ||||||
Disulfide bond | 15 | Interchain (with light chain) | ||||
Sequence: C | ||||||
Disulfide bond | 28↔84 | |||||
Sequence: CLITGYHPTSVTVTWYMGTQSQPQRTFPEIQRRDSYYMTSSQLSTPLQQWRQGEYKC | ||||||
Glycosylation | 109 | O-linked (GalNAc...) serine | ||||
Sequence: S | ||||||
Glycosylation | 110 | O-linked (GalNAc...) serine | ||||
Sequence: S | ||||||
Glycosylation | 113 | O-linked (GalNAc...) threonine | ||||
Sequence: T | ||||||
Glycosylation | 126 | O-linked (GalNAc...) threonine | ||||
Sequence: T | ||||||
Glycosylation | 127 | O-linked (GalNAc...) threonine | ||||
Sequence: T | ||||||
Glycosylation | 131 | O-linked (GalNAc...) threonine | ||||
Sequence: T | ||||||
Glycosylation | 132 | O-linked (GalNAc...) threonine | ||||
Sequence: T | ||||||
Disulfide bond | 161 | Interchain (with heavy chain) | ||||
Sequence: C | ||||||
Disulfide bond | 190↔249 | |||||
Sequence: CFVVGSDLKDAHLTWEVAGKVPTGGVEEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTC | ||||||
Glycosylation | 225 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 294↔355 | |||||
Sequence: CEVSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPRSTTFWAWSVLRVPAPPSPQPATYTC | ||||||
Glycosylation | 316 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 367 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Immunoglobulins are composed of two identical heavy chains and two identical light chains; disulfide-linked (PubMed:20176268).
An IgD molecule contains thus a delta heavy chain combined with either a kappa or a lambda light chains. Kappa light chains are found predominantly on the membrane IgD (mIgD) form and lambda on the secreted IgD (sIgD) form, this fact is poorly understood. Membrane-bound IgD molecules are non-covalently associated with a heterodimer of CD79A and CD79B (PubMed:11282392).
An IgD molecule contains thus a delta heavy chain combined with either a kappa or a lambda light chains. Kappa light chains are found predominantly on the membrane IgD (mIgD) form and lambda on the secreted IgD (sIgD) form, this fact is poorly understood. Membrane-bound IgD molecules are non-covalently associated with a heterodimer of CD79A and CD79B (PubMed:11282392).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 6-98 | Ig-like 1 | ||||
Sequence: PDVFPIISGCRHPKDNSPVVLACLITGYHPTSVTVTWYMGTQSQPQRTFPEIQRRDSYYMTSSQLSTPLQQWRQGEYKCVVQHTASKSKKEIF | ||||||
Region | 96-167 | Disordered | ||||
Sequence: EIFRWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNTGRGGEEKKKEKEKEEQEERETKTPECPSHTQP | ||||||
Compositional bias | 106-134 | Polar residues | ||||
Sequence: AQASSVPTAQPQAEGSLAKATTAPATTRN | ||||||
Compositional bias | 136-160 | Basic and acidic residues | ||||
Sequence: GRGGEEKKKEKEKEEQEERETKTPE | ||||||
Domain | 175-263 | Ig-like 2 | ||||
Sequence: PAVQDLWLRDKATFTCFVVGSDLKDAHLTWEVAGKVPTGGVEEGLLERHSNGSQSQHSRLTLPRSLWNAGTSVTCTLNHPSLPPQRLMA | ||||||
Domain | 267-373 | Ig-like 3 | ||||
Sequence: PAAQAPVKLSLNLLASSDPPEAASWLLCEVSGFSPPNILLMWLEDQREVNTSGFAPARPPPQPRSTTFWAWSVLRVPAPPSPQPATYTCVVSHEDSRTLLNASRSLE |
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P01880-2
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name2
- SynonymsMembrane-bound, mIgD
- Length430
- Mass (Da)47,500
- Last updated2023-05-03 v4
- ChecksumE1F53C43C5AF144B
P01880-1
- Name1
- SynonymsSecreted, sIgD
- Differences from canonical
- 377-430: LAMTPLIPQSKDENSDDYTTFDDVGSLWTTLSTFVALFILTLLYSGIVTFIKVK → VTDHGPMK
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0A0MS09 | A0A0A0MS09_HUMAN | IGHD | 430 |
Features
Showing features for non-terminal residue, compositional bias, sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Non-terminal residue | 1 | |||||
Sequence: A | ||||||
Compositional bias | 106-134 | Polar residues | ||||
Sequence: AQASSVPTAQPQAEGSLAKATTAPATTRN | ||||||
Compositional bias | 136-160 | Basic and acidic residues | ||||
Sequence: GRGGEEKKKEKEKEEQEERETKTPE | ||||||
Sequence conflict | 247 | in Ref. 4; BC063384 | ||||
Sequence: V → I | ||||||
Sequence conflict | 330 | in Ref. 7; AA sequence and 8; AA sequence | ||||
Sequence: R → G | ||||||
Alternative sequence | VSP_061837 | 377-430 | in isoform 1 | |||
Sequence: LAMTPLIPQSKDENSDDYTTFDDVGSLWTTLSTFVALFILTLLYSGIVTFIKVK → VTDHGPMK |
Polymorphism
There are several alleles. The sequence shown is that of IMGT allele IGHD*02.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
K02880 EMBL· GenBank· DDBJ | AAA52770.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
K02875 EMBL· GenBank· DDBJ | AAA52770.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
K02876 EMBL· GenBank· DDBJ | AAA52770.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
K02877 EMBL· GenBank· DDBJ | AAA52770.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
K02878 EMBL· GenBank· DDBJ | AAA52770.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
K02879 EMBL· GenBank· DDBJ | AAA52770.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X57331 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC246787 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC021276 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
BC063384 EMBL· GenBank· DDBJ | - | mRNA | No translation available. |