UniProt functional annotation for P61769



	UniProt functional annotation for P61769

UniProt codes: P61769, P01884.

Organism: Homo sapiens (Human).

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

Function: Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation (PubMed:25356553). {ECO:0000269|PubMed:25356553}.

Subunit: Heterodimer of an alpha chain and a beta chain. Beta-2- microglobulin is the beta-chain of major histocompatibility complex class I molecules. Polymers of beta 2-microglobulin can be found in tissues from patients on long-term hemodialysis. B2M alone (not in complex with HLA-I) interacts with M.tuberculosis EsxA (ESAT-6) and an EsxA-EsxB (CFP-10) complex; the tripartite complex can be detected in the host endoplasmic reticulum (PubMed:25356553). The B2M-EsxA complex can be detected in patients with pleural tuberculosis and is stable from pH 4.0 to 8.0 and in the presence of 2M NaCl (PubMed:25356553). Forms a heterotrimer with HLA-E and a self- or a foreign peptide (PubMed:9427624). Forms a heterotrimer with HLA-G and a self-peptide (PubMed:17056715). Forms a heterotrimer with HLA-F and a self-peptide (PubMed:10605026). Forms a heterotrimer with MR1 and a metabolite antigen. {ECO:0000269|PubMed:10605026, ECO:0000269|PubMed:12796775, ECO:0000269|PubMed:17056715, ECO:0000269|PubMed:24695216, ECO:0000269|PubMed:25356553, ECO:0000269|PubMed:3532124, ECO:0000269|PubMed:9427624}.

Subcellular location: Secreted {ECO:0000269|PubMed:1336137, ECO:0000269|PubMed:7554280}. Cell surface {ECO:0000269|PubMed:25356553}. Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). {ECO:0000269|PubMed:7554280, ECO:0000269|Ref.6}.

Subcellular location: Note=(Microbial infection) In the presence of M.tuberculosis EsxA-EsxB complex decreased amounts of B2M are found on the cell surface (PubMed:25356553). {ECO:0000269|PubMed:25356553}.

Ptm: Glycation of Ile-21 is observed in long-term hemodialysis patients.

Disease: Immunodeficiency 43 (IMD43) [MIM:241600]: A disorder characterized by marked reduction in serum concentrations of immunoglobulins and albumin, and hypoproteinemia due to hypercatabolism. Patients may suffer from recurrent respiratory tract infections and severe skin disease. {ECO:0000269|PubMed:16549777}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Amyloidosis 8 (AMYL8) [MIM:105200]: A form of hereditary generalized amyloidosis. Clinical features include extensive visceral amyloid deposits, renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash. There is no involvement of the nervous system. {ECO:0000269|PubMed:22693999}. Note=The disease is caused by variants affecting the gene represented in this entry. Apart from the presence of causative mutations, beta-2-microglobulin may adopt the fibrillar configuration of amyloid when its serum levels are persistently high. High beta(2)-microglobulin serum levels result in amyloidosis in patients on long-term hemodialysis (PubMed:7918443). In contrast to patients with dialysis-related amyloidosis, patients with hereditary amyloidosis have normal circulating concentrations of beta2- microglobulin (PubMed:22693999). {ECO:0000269|PubMed:22693999, ECO:0000269|PubMed:7918443}.

Similarity: Belongs to the beta-2-microglobulin family. {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:		Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation (PubMed:25356553). {ECO:0000269\|PubMed:25356553}.


Subunit:		Heterodimer of an alpha chain and a beta chain. Beta-2- microglobulin is the beta-chain of major histocompatibility complex class I molecules. Polymers of beta 2-microglobulin can be found in tissues from patients on long-term hemodialysis. B2M alone (not in complex with HLA-I) interacts with M.tuberculosis EsxA (ESAT-6) and an EsxA-EsxB (CFP-10) complex; the tripartite complex can be detected in the host endoplasmic reticulum (PubMed:25356553). The B2M-EsxA complex can be detected in patients with pleural tuberculosis and is stable from pH 4.0 to 8.0 and in the presence of 2M NaCl (PubMed:25356553). Forms a heterotrimer with HLA-E and a self- or a foreign peptide (PubMed:9427624). Forms a heterotrimer with HLA-G and a self-peptide (PubMed:17056715). Forms a heterotrimer with HLA-F and a self-peptide (PubMed:10605026). Forms a heterotrimer with MR1 and a metabolite antigen. {ECO:0000269\|PubMed:10605026, ECO:0000269\|PubMed:12796775, ECO:0000269\|PubMed:17056715, ECO:0000269\|PubMed:24695216, ECO:0000269\|PubMed:25356553, ECO:0000269\|PubMed:3532124, ECO:0000269\|PubMed:9427624}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:1336137, ECO:0000269\|PubMed:7554280}. Cell surface {ECO:0000269\|PubMed:25356553}. Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). {ECO:0000269\|PubMed:7554280, ECO:0000269\|Ref.6}.
Subcellular location:		Note=(Microbial infection) In the presence of M.tuberculosis EsxA-EsxB complex decreased amounts of B2M are found on the cell surface (PubMed:25356553). {ECO:0000269\|PubMed:25356553}.
Ptm:		Glycation of Ile-21 is observed in long-term hemodialysis patients.
Disease:		Immunodeficiency 43 (IMD43) [MIM:241600]: A disorder characterized by marked reduction in serum concentrations of immunoglobulins and albumin, and hypoproteinemia due to hypercatabolism. Patients may suffer from recurrent respiratory tract infections and severe skin disease. {ECO:0000269\|PubMed:16549777}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Amyloidosis 8 (AMYL8) [MIM:105200]: A form of hereditary generalized amyloidosis. Clinical features include extensive visceral amyloid deposits, renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash. There is no involvement of the nervous system. {ECO:0000269\|PubMed:22693999}. Note=The disease is caused by variants affecting the gene represented in this entry. Apart from the presence of causative mutations, beta-2-microglobulin may adopt the fibrillar configuration of amyloid when its serum levels are persistently high. High beta(2)-microglobulin serum levels result in amyloidosis in patients on long-term hemodialysis (PubMed:7918443). In contrast to patients with dialysis-related amyloidosis, patients with hereditary amyloidosis have normal circulating concentrations of beta2- microglobulin (PubMed:22693999). {ECO:0000269\|PubMed:22693999, ECO:0000269\|PubMed:7918443}.
Similarity:		Belongs to the beta-2-microglobulin family. {ECO:0000305}.