UniProt functional annotation for P01871



	UniProt functional annotation for P01871

UniProt code: P01871.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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: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 of CD79A and CD79B by the Src family of protein tyrosine kinases. It may cause death of cells by apoptosis. It is also found in soluble form, which represents about 30% of the total serum immunoglobulins where it is found almost exclusively as a homopentamer. After the antigen binds to the B-cell receptor, the secreted form is secreted in large amounts (PubMed:3137579, PubMed:16895553). {ECO:0000269|PubMed:3137579, ECO:0000303|PubMed:16895553, ECO:0000303|PubMed:17576170, ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}.

Subunit: Immunoglobulins are composed of two identical heavy chains and two identical light chains; disulfide-linked. {ECO:0000303|PubMed:20176268}.

Subcellular location: [Isoform 1]: Secreted. Note=During differentiation, B-lymphocytes switch from expression of membrane-bound IgM to secretion of IgM.

Subcellular location: [Isoform 2]: Cell membrane; Single-pass type I membrane protein.

Polymorphism: There are several alleles. The sequence shown is that of IMGT allele IGHM*04. {ECO:0000305}.

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.

Sequence caution: Sequence=CAA33065.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAA33069.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAA33071.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAA34971.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAE82013.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAE82014.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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: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 of CD79A and CD79B by the Src family of protein tyrosine kinases. It may cause death of cells by apoptosis. It is also found in soluble form, which represents about 30% of the total serum immunoglobulins where it is found almost exclusively as a homopentamer. After the antigen binds to the B-cell receptor, the secreted form is secreted in large amounts (PubMed:3137579, PubMed:16895553). {ECO:0000269\|PubMed:3137579, ECO:0000303\|PubMed:16895553, ECO:0000303\|PubMed:17576170, ECO:0000303\|PubMed:20176268, ECO:0000303\|PubMed:22158414}.


Subunit:		Immunoglobulins are composed of two identical heavy chains and two identical light chains; disulfide-linked. {ECO:0000303\|PubMed:20176268}.
Subcellular location:		[Isoform 1]: Secreted. Note=During differentiation, B-lymphocytes switch from expression of membrane-bound IgM to secretion of IgM.
Subcellular location:		[Isoform 2]: Cell membrane; Single-pass type I membrane protein.
Polymorphism:		There are several alleles. The sequence shown is that of IMGT allele IGHM*04. {ECO:0000305}.
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.
Sequence caution:		Sequence=CAA33065.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAA33069.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAA33071.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAA34971.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAE82013.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAE82014.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};