P01872 · IGHM_MOUSE

  • Protein
    Immunoglobulin heavy constant mu
  • Gene
    Ighm
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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).

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.

TypeIDPosition(s)Description
Site96-97Cleavage

GO annotations

AspectTerm
Cellular ComponentB cell receptor complex
Cellular Componentcell surface
Cellular Componentcytoplasm
Cellular Componentexternal side of plasma membrane
Cellular Componentextracellular space
Cellular ComponentIgM B cell receptor complex
Cellular Componentimmunoglobulin complex, circulating
Cellular Componentmembrane
Cellular Componentpentameric IgM immunoglobulin complex
Cellular Componentperinuclear region of cytoplasm
Cellular Componentplasma membrane
Molecular Functionantigen binding
Molecular Functionidentical protein binding
Molecular Functionimmunoglobulin receptor binding
Molecular Functiontransmembrane signaling receptor activity
Biological Processantibacterial humoral response
Biological Processantigen processing and presentation
Biological ProcessB cell activation
Biological ProcessB cell affinity maturation
Biological ProcessB cell proliferation
Biological ProcessB cell receptor signaling pathway
Biological Processcomplement activation, classical pathway
Biological Processdefense response to Gram-negative bacterium
Biological Processearly endosome to late endosome transport
Biological Processhumoral immune response mediated by circulating immunoglobulin
Biological Processimmunoglobulin mediated immune response
Biological ProcessMAPK cascade
Biological Processpositive regulation of B cell activation
Biological Processpositive regulation of B cell proliferation
Biological Processpositive regulation of endocytosis
Biological Processpositive regulation of immune response
Biological Processpositive regulation of MAPK cascade
Biological Processpositive regulation of peptidyl-tyrosine phosphorylation
Biological Processpre-B cell allelic exclusion
Biological Processregulation of cell morphogenesis
Biological Processregulation of immunoglobulin production

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Immunoglobulin heavy constant mu
  • Cleaved into 1 chains
    • Mu' chain
      Alternative names: 55 kDa mu' chain

Gene names

    • Name
      Ighm
    • Synonyms
      Igh-6

Organism names

  • Taxonomic identifier
  • Strain
    • BALB/cJ
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P01872
  • Secondary accessions
    • P01873

Proteomes

Organism-specific databases

Subcellular Location

Isoform 1

Secreted
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

Phenotypes & Variants

Disruption phenotype

Isoform 1

Increased mortality to influenza virus infection.

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variant77in MOPC 104E
Mutagenesis96Abolishes formation of 55 kDa cleavage product.
Natural variant100in MOPC 104E
Mutagenesis215Impairs dimerization.
Natural variant225in TEPC183 and MOPC 104E
Natural variant257in TEPC183
Natural variant257in MOPC 104E
Mutagenesis292Impairs dimerization.
Natural variant367in TEPC183 and MOPC 104E; requires 2 nucleotide substitutions
Mutagenesis414Abolishes interaction with CD5L.
Mutagenesis453Impairs dimerization and oligomerization.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, disulfide bond, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00001536231-454Immunoglobulin heavy constant mu
Disulfide bond13Interchain (with light chain)
Disulfide bond27↔88
Glycosylation45N-linked (GlcNAc...) asparagine
ChainPRO_000044395197-454Mu' chain
Disulfide bond135↔198
Glycosylation210N-linked (GlcNAc...) asparagine
Disulfide bond215Interchain (with heavy chain)
Glycosylation242N-linked (GlcNAc...) asparagine
Disulfide bond245↔304
Glycosylation257N-linked (GlcNAc...) asparagine
Glycosylation280N-linked (GlcNAc...) asparagine
Disulfide bond292Interchain (with heavy chain)
Disulfide bond352↔414
Disulfide bond414Interchain (with C-194 of CD5L)
Glycosylation441N-linked (GlcNAc...) asparagine
Disulfide bond453Interchain (with heavy chain)

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

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).

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

TypeEntry 1Entry 2Number of experimentsIntact
BINARY P01872Ighm P018729EBI-645833, EBI-645833

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region1-104CH1
Region105-216CH2
Region217-323CH3
Region324-435CH4
Region324-454Important for oligomerization

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

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

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.

  • Name
    1
  • Synonyms
    Secreted
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    454
  • Mass (Da)
    49,972
  • Last updated
    2005-02-01 v2
  • Checksum
    EBCCA6E8569AEEC5
SQSFPNVFPLVSCESPLSDKNLVAMGCLARDFLPSTISFTWNYQNNTEVIQGIRTFPTLRTGGKYLATSQVLLSPKSILEGSDEYLVCKIHYGGKNRDLHVPIPAVAEMNPNVNVFVPPRDGFSGPAPRKSKLICEATNFTPKPITVSWLKDGKLVESGFTTDPVTIENKGSTPQTYKVISTLTISEIDWLNLNVYTCRVDHRGLTFLKNVSSTCAASPSTDILTFTIPPSFADIFLSKSANLTCLVSNLATYETLNISWASQSGEPLETKIKIMESHPNGTFSAKGVASVCVEDWNNRKEFVCTVTHRDLPSPQKKFISKPNEVHKHPPAVYLLPPAREQLNLRESATVTCLVKGFSPADISVQWLQRGQLLPQEKYVTSAPMPEPGAPGFYFTHSILTVTEEEWNSGETYTCVVGHEALPHLVTERTVDKSTGKPTLYNVSLIMSDTGGTCY

P01872-2

  • Name
    2
  • Synonyms
    Membrane-bound
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 435-454: GKPTLYNVSLIMSDTGGTCY → EGEVNAEEEGFENLWTTASTFIVLFLLSLFYSTTVTLFKVK

Computationally mapped potential isoform sequences

There are 2 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A075B6A0A0A075B6A0_MOUSEIghm476
A0A075B5P6A0A075B5P6_MOUSEIghm455

Features

Showing features for non-terminal residue, alternative sequence.

TypeIDPosition(s)Description
Non-terminal residue1
Alternative sequenceVSP_053388435-454in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Similar Proteins

Disclaimer

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