Immunoglobulin heavy constant mu (IGHM)
The protein contains 452 amino acids for an estimated molecular weight of 49307 Da.
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:22158414, PubMed:20176268). 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). IgM antibodies play an important role in primary defense mechanisms. They have been shown to be involved in early recognition of external invaders like bacteria and viruses, cellular waste and modified self, as well as in recognition and elimination of precancerous and cancerous lesions. The membrane-bound form is found in the majority of normal B-cells alongside with IgD. Membrane-bound IgM induces the phosphorylation (updated: Jan. 31, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| IMGT allele IGHM*03 | |
| dbSNP:rs12365 | |
| IMGT allele IGHM*01 | |
| IMGT allele IGHM*02 |
No binding partner found
Biological Process
Adaptive immune response
Antibacterial humoral response
B cell receptor signaling pathway
Complement activation, classical pathway
Defense response to bacterium
Defense response to Gram-negative bacterium
Innate immune response
Leukocyte migration
Phagocytosis, engulfment
Phagocytosis, recognition
Positive regulation of B cell activation
The reference OMIM entry for this protein is 147020
Immunoglobulin heavy chain constant region mu; ighm
Immunoglobulin heavy chain mu constant region
Igm heavy chain constant region
DESCRIPTION
Immunoglobulins (Ig) are the antigen recognition molecules of B cells. An Ig molecule is made up of 2 identical heavy chains and 2 identical light chains (see 147200) joined by disulfide bonds so that each heavy chain is linked to a light chain and the 2 heavy chains are linked together. Each Ig heavy chain has an N-terminal variable (V) region containing the antigen-binding site and a C-terminal constant (C) region, encoded by an individual C region gene, that determines the isotype of the antibody and provides effector or signaling functions. The heavy chain V region is encoded by 1 each of 3 types of genes: V genes (see 147070), joining (J) genes (see 147010), and diversity (D) genes (see 146910). The C region genes are clustered downstream of the V region genes within the heavy chain locus on chromosome 14. The IGHM gene encodes the C region of the mu heavy chain, which defines the IgM isotype. Naive B cells express the transmembrane forms of IgM and IgD (see IGHD; 1471770) on their surface. During an antibody response, activated B cells can switch to the expression of individual downstream heavy chain C region genes by a process of somatic recombination known as isotype switching. In addition, secreted Ig forms that act as antibodies can be produced by alternative RNA processing of the heavy chain C region sequences. Although the membrane forms of all Ig isotypes are monomeric, secreted IgM forms pentamers, and occasionally hexamers, in plasma (summary by Janeway et al., 2005).CLONING
Friedlander et al. (1990) reported the complete nucleotide sequence of the membrane form of the human IgM heavy chain.MAPPING
Rabbitts et al. (1981) demonstrated that the gene for the mu constant (C) region contains 4 domains separated by short intervening sequences. They also showed that the C(mu) and C(delta) (IGHD; 147170) genes are closely linked, with the C(delta) gene located about 5 kb downstream from C(mu); one clone contained both a 3-prime part of the mu gene and a 5-prime part of the delta gene. Erikson et al. (1982) showed that in Burkitt tumor cell lines the 14q+ chromosome retains the genes coding for the constant region of the immunoglobulin heavy chains, whereas genes coding for all or a portion of the variable region translocate to the 8q- chromosome. This suggests that the orientation in relation to the centromere is cen-IGHC-IGHV-ter. Lefranc et al. (1982) showed, by Southern analysis, that a single BamHI band hybridized to a C(mu) probe. This group of workers and others using different enzymes have found the same (Lefranc, 1991). Wabl et al. (1980) found that in the mouse both IgM and IgD were expressed by a hybrid hamster-mouse subclone that contained only one mouse chromosome 12.GENE STRUCTURE
Liu et al. (2005) analyzed the putative promoter regions (PPRs) of 333 Ig genes to determine their CpG island content. CpG islands are regions of about 200 bp rich in CpG dinucleotides that are typically associated with housekeeping genes. Liu et al. (2005) noted that IGK light chain genes are located on the plus and minus strands of chromosome 2, IGH heavy chain genes are located on the minus strand only of chromosome 14, and IGL light chain genes are located on the plus strand only of chromosome 22. They found that none of the joining region genes have CpG islands in their PPRs. While IGKC (147200) and 6 of 11 IGHC constant region genes have CpG islands, none of the 7 IGLC (IGLC1; ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for IGHM
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 147020 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed