P01871
uniprot
P01871
canonical
amino_acid_sequence
GSASAPTLFPLVSCENSPSDTSSVAVGCLAQDFLPDSITFSWKYKNNSDISSTRGFPSVLRGGKYAATSQVLLPSKDVMQGTDEHVVCKVQHPNGNKEKNVPLPVIAELPPKVSVFVPPRDGFFGNPRKSKLICQATGFSPRQIQVSWLREGKQVGSGVTTDQVQAEAKESGPTTYKVTSTLTIKESDWLGQSMFTCRVDHRGLTFQQNASSMCVPDQDTAIRVFAIPPSFASIFLTKSTKLTCLVTDLTTYDSVTISWTRQNGEAVKTHTNISESHPNATFSAVGEASICEDDWNSGERFTCTVTHTDLPSPLKQTISRPKGVALHRPDVYLLPPAREQLNLRESATITCLVTGFSPADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSILTVSEEEWNTGETYTCVVAHEALPNRVTERTVDKSTEGEVSADEEGFENLWATASTFIVLFLLSLFYSTTVTLFKVK
uniprot
proteins
disease_involvement
DISEASE: Agammaglobulinemia 1, autosomal recessive (AGM1) [MIM:601495]: A primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. {ECO:0000269|PubMed:8890099}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
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). {ECO:0000303|PubMed:17576170, ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}.; FUNCTION: [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 (PubMed:32029689, PubMed:37095205). 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 (By similarity). 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:12847249, PubMed:19006321, PubMed:28230186, PubMed:32029689). 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 (By similarity) (PubMed:32029689). {ECO:0000250|UniProtKB:P01872, ECO:0000269|PubMed:12847249, ECO:0000269|PubMed:19006321, ECO:0000269|PubMed:28230186, ECO:0000269|PubMed:32029689, ECO:0000269|PubMed:37095205}.; FUNCTION: [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. {ECO:0000250|UniProtKB:P01872, ECO:0000269|PubMed:35981043}.
uniprot
proteins
mass_dalton
51924
uniprot
proteins
mutagenesis
MUTAGEN 364; /note="Q->A: Has no effect on IgMBCR assembly; when associated with A-470."; /evidence="ECO:0000269|PubMed:35981043"; MUTAGEN 370; /note="Q->A: Has no effect on IgMBCR assembly; when associated with A-364."; /evidence="ECO:0000269|PubMed:35981043"; MUTAGEN 407; /note="T->A: Has little effect on IgMBCR assembly; when associated with A-410."; /evidence="ECO:0000269|PubMed:35981043"; MUTAGEN 410; /note="T->A: Has little effect on IgMBCR assembly; when associated with A-407."; /evidence="ECO:0000269|PubMed:35981043"; MUTAGEN 430; /note="D->A: Blocks IgMBCR assembly; when associated with A-442."; /evidence="ECO:0000269|PubMed:35981043"; MUTAGEN 442; /note="E->A: Blocks IgMBCR assembly; when associated with A-430."; /evidence="ECO:0000269|PubMed:35981043"; MUTAGEN 450; /note="T->A: Blocks IgMBCR assembly; when associated with A-464."; /evidence="ECO:0000269|PubMed:35981043"; MUTAGEN 454; /note="F->W: Blocks IgMBCR assembly."; /evidence="ECO:0000269|PubMed:35981043"; MUTAGEN 458; /note="F->W: Blocks IgMBCR assembly."; /evidence="ECO:0000269|PubMed:35981043"; MUTAGEN 464; /note="Y->A: Blocks IgMBCR assembly; when associated with A-450."; /evidence="ECO:0000269|PubMed:35981043
uniprot
proteins
post_translational_modification
PTM: N-glycosylated; important for IgM secretion and its localization at the plasma membrane. The interaction with FCMR is glycan-independent. {ECO:0000269|PubMed:28230186, ECO:0000269|PubMed:32029689, ECO:0000269|PubMed:35981043}.
uniprot
proteins
pubmed
11340299
uniprot
proteins
pubmed
11587642
uniprot
proteins
pubmed
12508121
uniprot
proteins
pubmed
12847249
uniprot
proteins
pubmed
1472500
uniprot
proteins
pubmed
14760718
uniprot
proteins
pubmed
16422668
uniprot
proteins
pubmed
16895553
uniprot
proteins
pubmed
17576170
uniprot
proteins
pubmed
19006321
uniprot
proteins
pubmed
19139490
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
20176268
uniprot
proteins
pubmed
2115996
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22158414
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
2505237
uniprot
proteins
pubmed
28230186
uniprot
proteins
pubmed
30324136
uniprot
proteins
pubmed
3137579
uniprot
proteins
pubmed
32029689
uniprot
proteins
pubmed
35981043
uniprot
proteins
pubmed
36949194
uniprot
proteins
pubmed
37095205
uniprot
proteins
pubmed
4742735
uniprot
proteins
pubmed
4803843
uniprot
proteins
pubmed
6425189
uniprot
proteins
pubmed
6777162
uniprot
proteins
pubmed
6777778
uniprot
proteins
pubmed
6795593
uniprot
proteins
pubmed
8890099
uniprot
proteins
sequence_length
474
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Secreted. Note=During differentiation, B-lymphocytes switch from expression of membrane-bound IgM to secretion of IgM. {ECO:0000305}.; SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 451..471; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins