P01872 · IGHM_MOUSE
- ProteinImmunoglobulin heavy constant mu
- GeneIghm
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids454 (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 (By similarity).
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 (By similarity).
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 (By similarity).
Isoform 1
Constant region of secreted IgM (sIgM), also known as the Fc region of IgM antibody. Able to multimerize, forms high order polymers, mainly pentamers and occasionally hexamers, providing for multivalency and high avidity recognition of antigens (By similarity).
Natural sIgM are polyreactive and recognize conserved self- and pathogen-derived structures, whereas immune sIgM are secreted only upon exposure to pathogens and are antigen-specific. Both natural and immune sIgM are required for an efficient humoral immune response to infection (PubMed:10899913, PubMed:28135254, PubMed:34788614).
Mediates sIgM effector functions mostly via Fc receptors and the complement system. On lymphoid cells binds high-affinity Fc receptor FCMR and promotes induction of an efficient neutralizing IgG response while maintaining tolerance to self-antigens. Recruits C1q complement component to initiate the classical complement pathway, facilitating the recognition and neutralization of pathogens by the host. Together with C1q and mannose-binding lectin promotes the phagocytosis of apoptotic cells by macrophages, ensuring the clearance of potential autoimmune epitopes from tissues (By similarity) (PubMed:10899913, PubMed:11062505, PubMed:28135254).
Involved in mucosal immunity. It is transported by transcytosis across mucosal epithelium by PIGR and secreted on the apical side in complex with PIGR secretory component to scan mucosal lining for pathogens. IgM-antigen complexes undergo FCMR-mediated retrotranscytosis across mucosal M cells toward antigen-presenting cells in mucosal lymphoid tissues (PubMed:34788614).
Natural sIgM are polyreactive and recognize conserved self- and pathogen-derived structures, whereas immune sIgM are secreted only upon exposure to pathogens and are antigen-specific. Both natural and immune sIgM are required for an efficient humoral immune response to infection (PubMed:10899913, PubMed:28135254, PubMed:34788614).
Mediates sIgM effector functions mostly via Fc receptors and the complement system. On lymphoid cells binds high-affinity Fc receptor FCMR and promotes induction of an efficient neutralizing IgG response while maintaining tolerance to self-antigens. Recruits C1q complement component to initiate the classical complement pathway, facilitating the recognition and neutralization of pathogens by the host. Together with C1q and mannose-binding lectin promotes the phagocytosis of apoptotic cells by macrophages, ensuring the clearance of potential autoimmune epitopes from tissues (By similarity) (PubMed:10899913, PubMed:11062505, PubMed:28135254).
Involved in mucosal immunity. It is transported by transcytosis across mucosal epithelium by PIGR and secreted on the apical side in complex with PIGR secretory component to scan mucosal lining for pathogens. IgM-antigen complexes undergo FCMR-mediated retrotranscytosis across mucosal M cells toward antigen-presenting cells in mucosal lymphoid tissues (PubMed:34788614).
Isoform 2
Constant region of membrane-bound IgM, part of the B cell receptor complex (BCR). IgM BCR provides constitutive tonic signaling for B cell survival. Mediates pre-BCR signaling that regulates B cell selection and rearrangement of Ig genes via allelic exclusion.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 96-97 | Cleavage | ||||
Sequence: NR |
GO annotations
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameImmunoglobulin heavy constant mu
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP01872
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform 1
Note: During differentiation, B-lymphocytes switch from expression of membrane-bound IgM to secretion of IgM.
Isoform 2
Cell membrane ; Single-pass membrane protein
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Isoform 1
Increased mortality to influenza virus infection.
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 77 | in MOPC 104E | ||||
Sequence: S → N | ||||||
Mutagenesis | 96 | Abolishes formation of 55 kDa cleavage product. | ||||
Sequence: N → A | ||||||
Natural variant | 100 | in MOPC 104E | ||||
Sequence: H → Q | ||||||
Mutagenesis | 215 | Impairs dimerization. | ||||
Sequence: C → S | ||||||
Natural variant | 225 | in TEPC183 and MOPC 104E | ||||
Sequence: T → N | ||||||
Natural variant | 257 | in TEPC183 | ||||
Sequence: N → S | ||||||
Natural variant | 257 | in MOPC 104E | ||||
Sequence: N → T | ||||||
Mutagenesis | 292 | Impairs dimerization. | ||||
Sequence: C → S | ||||||
Natural variant | 367 | in TEPC183 and MOPC 104E; requires 2 nucleotide substitutions | ||||
Sequence: L → K | ||||||
Mutagenesis | 414 | Abolishes interaction with CD5L. | ||||
Sequence: C → S | ||||||
Mutagenesis | 453 | Impairs dimerization and oligomerization. | ||||
Sequence: C → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 6 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000153623 | 1-454 | Immunoglobulin heavy constant mu | |||
Sequence: SQSFPNVFPLVSCESPLSDKNLVAMGCLARDFLPSTISFTWNYQNNTEVIQGIRTFPTLRTGGKYLATSQVLLSPKSILEGSDEYLVCKIHYGGKNRDLHVPIPAVAEMNPNVNVFVPPRDGFSGPAPRKSKLICEATNFTPKPITVSWLKDGKLVESGFTTDPVTIENKGSTPQTYKVISTLTISEIDWLNLNVYTCRVDHRGLTFLKNVSSTCAASPSTDILTFTIPPSFADIFLSKSANLTCLVSNLATYETLNISWASQSGEPLETKIKIMESHPNGTFSAKGVASVCVEDWNNRKEFVCTVTHRDLPSPQKKFISKPNEVHKHPPAVYLLPPAREQLNLRESATVTCLVKGFSPADISVQWLQRGQLLPQEKYVTSAPMPEPGAPGFYFTHSILTVTEEEWNSGETYTCVVGHEALPHLVTERTVDKSTGKPTLYNVSLIMSDTGGTCY | ||||||
Disulfide bond | 13 | Interchain (with light chain) | ||||
Sequence: C | ||||||
Disulfide bond | 27↔88 | |||||
Sequence: CLARDFLPSTISFTWNYQNNTEVIQGIRTFPTLRTGGKYLATSQVLLSPKSILEGSDEYLVC | ||||||
Glycosylation | 45 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Chain | PRO_0000443951 | 97-454 | Mu' chain | |||
Sequence: RDLHVPIPAVAEMNPNVNVFVPPRDGFSGPAPRKSKLICEATNFTPKPITVSWLKDGKLVESGFTTDPVTIENKGSTPQTYKVISTLTISEIDWLNLNVYTCRVDHRGLTFLKNVSSTCAASPSTDILTFTIPPSFADIFLSKSANLTCLVSNLATYETLNISWASQSGEPLETKIKIMESHPNGTFSAKGVASVCVEDWNNRKEFVCTVTHRDLPSPQKKFISKPNEVHKHPPAVYLLPPAREQLNLRESATVTCLVKGFSPADISVQWLQRGQLLPQEKYVTSAPMPEPGAPGFYFTHSILTVTEEEWNSGETYTCVVGHEALPHLVTERTVDKSTGKPTLYNVSLIMSDTGGTCY | ||||||
Disulfide bond | 135↔198 | |||||
Sequence: CEATNFTPKPITVSWLKDGKLVESGFTTDPVTIENKGSTPQTYKVISTLTISEIDWLNLNVYTC | ||||||
Glycosylation | 210 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 215 | Interchain (with heavy chain) | ||||
Sequence: C | ||||||
Glycosylation | 242 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 245↔304 | |||||
Sequence: CLVSNLATYETLNISWASQSGEPLETKIKIMESHPNGTFSAKGVASVCVEDWNNRKEFVC | ||||||
Glycosylation | 257 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 280 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 292 | Interchain (with heavy chain) | ||||
Sequence: C | ||||||
Disulfide bond | 352↔414 | |||||
Sequence: CLVKGFSPADISVQWLQRGQLLPQEKYVTSAPMPEPGAPGFYFTHSILTVTEEEWNSGETYTC | ||||||
Disulfide bond | 414 | Interchain (with C-194 of CD5L) | ||||
Sequence: C | ||||||
Glycosylation | 441 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 453 | Interchain (with heavy chain) | ||||
Sequence: C |
Post-translational modification
Cleaved by a non-enzymatic process after Asn-96, yielding a glycosylated protein of 55 kDa. The process is induced by other proteins, and requires neutral or alkaline pH.
N-glycosylated; important for IgM secretion and its localization at the plasma membrane. The interaction with FCMR is glycan-independent.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in bone marrow.
Isoform 1
Expressed in B-1 and B-2 cells (at protein level).
Interaction
Subunit
The basic structural unit of both sIgM and mIgM molecules consists of two identical heavy chains and two identical light chains; disulfide-linked. N-terminal variable regions of the heavy and light chains form the antigen binding sites, whereas the C-terminal constant regions of the heavy chains interact with immune receptors to mediate effector functions.
Isoform 1
Part of IgM antibody. Forms high order oligomers, homopentamers stabilized by the JCHAIN and homohexamers that lack JCHAIN (PubMed:30324136).
The oligomerization amplifies an inherently low affinity of IgM antibodies for the antigen by multi-point attachment. Adjacent IgM protomers associate via interchain disulfide links to form an asymmetric pentameric structure with a 50 degree gap. A single copy of JCHAIN is covalently linked to the first and the fifth IgM monomers via interchain disulfide bonds thus closing the pentamer ring. Only JCHAIN-containing IgM binds PIGR secretory component (via D1-CDR1 region); this interaction is a prerequisite for IgM transcytosis across mucosal epithelium. Pentameric sIgM interacts (via CH4 domain) with FCRM (via Ig-like domain); the interaction is glycan-independent and multivalent theoretically involving up to eight binding sites for the IgM pentamer (PubMed:23733956).
Interacts with FCAMR; this interaction facilitates the endocytosis of IgM-coated microbes or IgM-antigen immune complexes (PubMed:11062505).
Antigen-bound IgM (via the Fc region) binds to globular domains of C1q component of the complement system, all three modules C1QA, C1QB and C1QC being involved in IgM binding; this interaction is multivalent. Pentameric sIgM (via Fc region) interacts with CD5L (via SRCR2 and SRCR3); disulfide linked (PubMed:30324136).
The oligomerization amplifies an inherently low affinity of IgM antibodies for the antigen by multi-point attachment. Adjacent IgM protomers associate via interchain disulfide links to form an asymmetric pentameric structure with a 50 degree gap. A single copy of JCHAIN is covalently linked to the first and the fifth IgM monomers via interchain disulfide bonds thus closing the pentamer ring. Only JCHAIN-containing IgM binds PIGR secretory component (via D1-CDR1 region); this interaction is a prerequisite for IgM transcytosis across mucosal epithelium. Pentameric sIgM interacts (via CH4 domain) with FCRM (via Ig-like domain); the interaction is glycan-independent and multivalent theoretically involving up to eight binding sites for the IgM pentamer (PubMed:23733956).
Interacts with FCAMR; this interaction facilitates the endocytosis of IgM-coated microbes or IgM-antigen immune complexes (PubMed:11062505).
Antigen-bound IgM (via the Fc region) binds to globular domains of C1q component of the complement system, all three modules C1QA, C1QB and C1QC being involved in IgM binding; this interaction is multivalent. Pentameric sIgM (via Fc region) interacts with CD5L (via SRCR2 and SRCR3); disulfide linked (PubMed:30324136).
Isoform 2
Part of IgM B cell receptor complex on pre-B cells, immature and mature B cells. The BCR complex consists of one membrane-bound IgM molecule responsible for antigen binding, non-covalently associated with CD79A and CD79B signaling chains. Interacts with FCMR.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P01872 | Ighm P01872 | 9 | EBI-645833, EBI-645833 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-104 | CH1 | ||||
Sequence: SQSFPNVFPLVSCESPLSDKNLVAMGCLARDFLPSTISFTWNYQNNTEVIQGIRTFPTLRTGGKYLATSQVLLSPKSILEGSDEYLVCKIHYGGKNRDLHVPIP | ||||||
Region | 105-216 | CH2 | ||||
Sequence: AVAEMNPNVNVFVPPRDGFSGPAPRKSKLICEATNFTPKPITVSWLKDGKLVESGFTTDPVTIENKGSTPQTYKVISTLTISEIDWLNLNVYTCRVDHRGLTFLKNVSSTCA | ||||||
Region | 217-323 | CH3 | ||||
Sequence: ASPSTDILTFTIPPSFADIFLSKSANLTCLVSNLATYETLNISWASQSGEPLETKIKIMESHPNGTFSAKGVASVCVEDWNNRKEFVCTVTHRDLPSPQKKFISKPN | ||||||
Region | 324-435 | CH4 | ||||
Sequence: EVHKHPPAVYLLPPAREQLNLRESATVTCLVKGFSPADISVQWLQRGQLLPQEKYVTSAPMPEPGAPGFYFTHSILTVTEEEWNSGETYTCVVGHEALPHLVTERTVDKSTG | ||||||
Region | 324-454 | Important for oligomerization | ||||
Sequence: EVHKHPPAVYLLPPAREQLNLRESATVTCLVKGFSPADISVQWLQRGQLLPQEKYVTSAPMPEPGAPGFYFTHSILTVTEEEWNSGETYTCVVGHEALPHLVTERTVDKSTGKPTLYNVSLIMSDTGGTCY |
Domain
Isoform 1
The C-terminal beta-strands mediate sIgM oligomerization.
Isoform 1
The CH4 domains of pentameric IgM mediate multivalent interactions with the Ig-like domain of FCMR, thereby facilitating receptor clustering and signaling.
Isoform 2
The transmembrane helices of two heavy chains and CD79A and CD79B chains assembly in a four-helix bundle structure that appears to be conserved among different BCR isotypes.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P01872-1
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.
- Name1
- SynonymsSecreted
- Length454
- Mass (Da)49,972
- Last updated2005-02-01 v2
- ChecksumEBCCA6E8569AEEC5
P01872-2
- Name2
- SynonymsMembrane-bound
- Differences from canonical
- 435-454: GKPTLYNVSLIMSDTGGTCY → EGEVNAEEEGFENLWTTASTFIVLFLLSLFYSTTVTLFKVK
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A075B6A0 | A0A075B6A0_MOUSE | Ighm | 476 | ||
A0A075B5P6 | A0A075B5P6_MOUSE | Ighm | 455 |
Features
Showing features for non-terminal residue, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Non-terminal residue | 1 | |||||
Sequence: S | ||||||
Alternative sequence | VSP_053388 | 435-454 | in isoform 2 | |||
Sequence: GKPTLYNVSLIMSDTGGTCY → EGEVNAEEEGFENLWTTASTFIVLFLLSLFYSTTVTLFKVK |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
V00821 EMBL· GenBank· DDBJ | CAA24202.1 EMBL· GenBank· DDBJ | mRNA | ||
V00827 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
J00443 EMBL· GenBank· DDBJ | AAB59650.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
J00444 EMBL· GenBank· DDBJ | AAB59650.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
J00443 EMBL· GenBank· DDBJ | AAB59651.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
J00444 EMBL· GenBank· DDBJ | AAB59651.1 EMBL· GenBank· DDBJ | Genomic DNA |