Browse B2M

Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted Cell surface Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). ; 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).
Domain PF07654 Immunoglobulin C1-set domain
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).

> Gene Ontology
 
Biological Process GO:0000041 transition metal ion transport
GO:0001819 positive regulation of cytokine production
GO:0001894 tissue homeostasis
GO:0001895 retina homeostasis
GO:0001906 cell killing
GO:0001909 leukocyte mediated cytotoxicity
GO:0001910 regulation of leukocyte mediated cytotoxicity
GO:0001912 positive regulation of leukocyte mediated cytotoxicity
GO:0001913 T cell mediated cytotoxicity
GO:0001914 regulation of T cell mediated cytotoxicity
GO:0001916 positive regulation of T cell mediated cytotoxicity
GO:0002237 response to molecule of bacterial origin
GO:0002250 adaptive immune response
GO:0002367 cytokine production involved in immune response
GO:0002369 T cell cytokine production
GO:0002428 antigen processing and presentation of peptide antigen via MHC class Ib
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002456 T cell mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002474 antigen processing and presentation of peptide antigen via MHC class I
GO:0002475 antigen processing and presentation via MHC class Ib
GO:0002477 antigen processing and presentation of exogenous peptide antigen via MHC class Ib
GO:0002478 antigen processing and presentation of exogenous peptide antigen
GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
GO:0002480 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
GO:0002481 antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent
GO:0002483 antigen processing and presentation of endogenous peptide antigen
GO:0002521 leukocyte differentiation
GO:0002697 regulation of immune effector process
GO:0002699 positive regulation of immune effector process
GO:0002700 regulation of production of molecular mediator of immune response
GO:0002702 positive regulation of production of molecular mediator of immune response
GO:0002703 regulation of leukocyte mediated immunity
GO:0002705 positive regulation of leukocyte mediated immunity
GO:0002706 regulation of lymphocyte mediated immunity
GO:0002708 positive regulation of lymphocyte mediated immunity
GO:0002709 regulation of T cell mediated immunity
GO:0002711 positive regulation of T cell mediated immunity
GO:0002718 regulation of cytokine production involved in immune response
GO:0002720 positive regulation of cytokine production involved in immune response
GO:0002724 regulation of T cell cytokine production
GO:0002726 positive regulation of T cell cytokine production
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002831 regulation of response to biotic stimulus
GO:0003254 regulation of membrane depolarization
GO:0006457 protein folding
GO:0006826 iron ion transport
GO:0006898 receptor-mediated endocytosis
GO:0006959 humoral immune response
GO:0007159 leukocyte cell-cell adhesion
GO:0009615 response to virus
GO:0010035 response to inorganic substance
GO:0010038 response to metal ion
GO:0010039 response to iron ion
GO:0010721 negative regulation of cell development
GO:0010959 regulation of metal ion transport
GO:0010975 regulation of neuron projection development
GO:0010977 negative regulation of neuron projection development
GO:0015684 ferrous iron transport
GO:0019730 antimicrobial humoral response
GO:0019731 antibacterial humoral response
GO:0019882 antigen processing and presentation
GO:0019883 antigen processing and presentation of endogenous antigen
GO:0019884 antigen processing and presentation of exogenous antigen
GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I
GO:0030098 lymphocyte differentiation
GO:0030100 regulation of endocytosis
GO:0030217 T cell differentiation
GO:0031341 regulation of cell killing
GO:0031343 positive regulation of cell killing
GO:0031345 negative regulation of cell projection organization
GO:0032091 negative regulation of protein binding
GO:0032092 positive regulation of protein binding
GO:0032496 response to lipopolysaccharide
GO:0032844 regulation of homeostatic process
GO:0033077 T cell differentiation in thymus
GO:0034341 response to interferon-gamma
GO:0034756 regulation of iron ion transport
GO:0034758 positive regulation of iron ion transport
GO:0042026 protein refolding
GO:0042110 T cell activation
GO:0042391 regulation of membrane potential
GO:0042493 response to drug
GO:0042590 antigen processing and presentation of exogenous peptide antigen via MHC class I
GO:0042742 defense response to bacterium
GO:0043270 positive regulation of ion transport
GO:0043393 regulation of protein binding
GO:0043900 regulation of multi-organism process
GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism
GO:0045665 negative regulation of neuron differentiation
GO:0045807 positive regulation of endocytosis
GO:0046686 response to cadmium ion
GO:0048002 antigen processing and presentation of peptide antigen
GO:0048259 regulation of receptor-mediated endocytosis
GO:0048260 positive regulation of receptor-mediated endocytosis
GO:0048871 multicellular organismal homeostasis
GO:0050688 regulation of defense response to virus
GO:0050690 regulation of defense response to virus by virus
GO:0050768 negative regulation of neurogenesis
GO:0050792 regulation of viral process
GO:0050829 defense response to Gram-negative bacterium
GO:0050830 defense response to Gram-positive bacterium
GO:0051098 regulation of binding
GO:0051099 positive regulation of binding
GO:0051100 negative regulation of binding
GO:0051607 defense response to virus
GO:0051899 membrane depolarization
GO:0051961 negative regulation of nervous system development
GO:0055072 iron ion homeostasis
GO:0055076 transition metal ion homeostasis
GO:0060249 anatomical structure homeostasis
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0060627 regulation of vesicle-mediated transport
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070627 ferrous iron import
GO:0070838 divalent metal ion transport
GO:0071216 cellular response to biotic stimulus
GO:0071219 cellular response to molecule of bacterial origin
GO:0071222 cellular response to lipopolysaccharide
GO:0071241 cellular response to inorganic substance
GO:0071248 cellular response to metal ion
GO:0071281 cellular response to iron ion
GO:0071346 cellular response to interferon-gamma
GO:0071396 cellular response to lipid
GO:0071593 lymphocyte aggregation
GO:0071594 thymocyte aggregation
GO:0072511 divalent inorganic cation transport
GO:0097286 iron ion import
GO:0097459 iron ion import into cell
GO:0097460 ferrous iron import into cell
GO:0098542 defense response to other organism
GO:0098657 import into cell
GO:0098659 inorganic cation import into cell
GO:0099587 inorganic ion import into cell
GO:1900120 regulation of receptor binding
GO:1900121 negative regulation of receptor binding
GO:1900122 positive regulation of receptor binding
GO:1900390 regulation of iron ion import
GO:1903989 regulation of ferrous iron import into cell
GO:1903991 positive regulation of ferrous iron import into cell
GO:1904432 regulation of ferrous iron binding
GO:1904434 positive regulation of ferrous iron binding
GO:1904435 regulation of transferrin receptor binding
GO:1904437 positive regulation of transferrin receptor binding
GO:1990267 response to transition metal nanoparticle
GO:2000021 regulation of ion homeostasis
Molecular Function GO:0001948 glycoprotein binding
Cellular Component GO:0005769 early endosome
GO:0005775 vacuolar lumen
GO:0005788 endoplasmic reticulum lumen
GO:0005924 cell-substrate adherens junction
GO:0005925 focal adhesion
GO:0009897 external side of plasma membrane
GO:0010008 endosome membrane
GO:0012507 ER to Golgi transport vesicle membrane
GO:0030055 cell-substrate junction
GO:0030133 transport vesicle
GO:0030134 ER to Golgi transport vesicle
GO:0030135 coated vesicle
GO:0030139 endocytic vesicle
GO:0030658 transport vesicle membrane
GO:0030659 cytoplasmic vesicle membrane
GO:0030662 coated vesicle membrane
GO:0030666 endocytic vesicle membrane
GO:0030670 phagocytic vesicle membrane
GO:0031901 early endosome membrane
GO:0031904 endosome lumen
GO:0031905 early endosome lumen
GO:0042611 MHC protein complex
GO:0042612 MHC class I protein complex
GO:0043235 receptor complex
GO:0044440 endosomal part
GO:0045335 phagocytic vesicle
GO:0098552 side of membrane
GO:0098802 plasma membrane receptor complex
GO:1990712 HFE-transferrin receptor complex
> KEGG and Reactome Pathway
 
KEGG hsa04612 Antigen processing and presentation
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-977225: Amyloid fiber formation
R-HSA-983170: Antigen Presentation
R-HSA-1236975: Antigen processing-Cross presentation
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-1643685: Disease
R-HSA-1236974: ER-Phagosome pathway
R-HSA-1236977: Endosomal/Vacuolar pathway
R-HSA-162906: HIV Infection
R-HSA-162909: Host Interactions of HIV factors
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-913531: Interferon Signaling
R-HSA-877300: Interferon gamma signaling
R-HSA-392499: Metabolism of proteins
R-HSA-164940: Nef mediated downregulation of MHC class I complex cell surface expression
R-HSA-164938: Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters
R-HSA-6798695: Neutrophil degranulation
R-HSA-164952: The role of Nef in HIV-1 replication and disease pathogenesis
Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between B2M and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between B2M and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25294906Thyroid Gland Papillary CarcinomaPromote immunity (infiltration)Both MHC class I and β2-microglobulin expression was reduced or absent in 76% of PTC specimens and was associated with reduced tumor-infiltrating immune cells, including effector (CD3(+), CD8(+), CD16(+)) and suppressor (FoxP3(+)) populations.
28783722MelanomaPromote immunity (T cell function); essential for immunotherapyFor example, loss-of-function mutations in β -2-microglobulin (B2M) and Janus kinases (JAK1 and JAK2) have been reported in patients unresponsive to immunotherapies.; We observed that the reduction in the overall survival of these patients was significantly associated with loss of expression of B2M and TAP1 in tumours biopsied before ipilimumab treatment.; On the basis of our initial optimization of the 2CT-CRISPR assay, we expected that genes directly associated with MHC class I antigen processing and presentation would be enriched in our screens, and found that HLA-A, B2M, TAP1, TAP2, and TAPBP were among the most highly-enriched genes in our screen. Significant resistance was detected in the cells transduced with B2M sgRNAs (72 ± 5%) and with TAP2 sgRNAs (13 ± 2%) against the cytolytic activity of ESO T cells. Loss of expression of these 19 genes within tumours could diminish or extinguish the presentation of tumour antigens (including HLA-A, HLA-F, B2M, TAP1 and TAP2); T cell co- stimulation (ICAM1, CLECL1, LILRA1 and LILRA3); or cytokine production and signalling (JAK2 and STAT1) in the tumour microenvironment that drive infiltration and activation of T cells, and thus serve as a principal mechanism in immune evasion.
27433843MelanomaPromote immunityThe B2M truncating mutation led to loss of surface expression of major histocompatibility complex class I.
27785783Lung CarcinomaPromote immunityTumor tissues obtained from 57 patients diagnosed with lung carcinomas were analyzed for HLA expression and leukocyte infiltration. The HLA-I negative phenotype was produced by a combination of HLA haplotype loss and a transcriptional downregulation of β2-microglobulin (β2-m) and LMP2 and LMP7 antigen presentation machinery genes.
29308317Colorectal Carcinoma (MMR-deficient)Promote immunityIncreasing PDCD1 (PD-1)-positive T-cell infiltration was significantly related to an increased likelihood of B2M mutations (OR = 1.81). HLA class II antigen expression status was significantly associated with enhanced overall T-cell infiltration, but not related to PDCD1 (PD-1)-positive T-cells. These results suggest that immune evasion mediated by B2M mutation-induced loss of HLA class I antigen expression predominantly occurs in an environment of activated PDCD1 (PD-1)-positive T cell infiltration.
17541610AstrocytomaPromote immunityAmong human WHO grade II-IV astrocytomas, downregulation of LMP2, TAP1 and beta2m correlated with grade of malignancy. Our results support the hypothesis that coordinated downregulation or impaired upregulation of certain HLA class I APM components may serve as a mechanism for astrocytoma cells to evade the host's immune response, even if HLA class I antigen surface expression is not altered.
Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of B2M in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: 3.72; FDR: 0.000150 Sensitive to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell logFC: 5.36; FDR: 0.000381 Sensitive to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR Second most enriched score: 2.11 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of B2M in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.2760.472
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1930.973
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.3520.93
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.6650.225
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1020.968
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.3810.673
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1560.838
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4910.878
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.3340.928
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9430.826
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.7860.909
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.2240.0552
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of B2M in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277304.1-4.10.561
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275903.4-3.41
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131109.1-9.10.458
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of B2M. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of B2M. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by B2M.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of B2M. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of B2M expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between B2M and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolB2M
Namebeta-2-microglobulin
Aliases beta chain of MHC class I molecules; beta-2-microglobin
Chromosomal Location15q21.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting B2M collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting B2M.
ID Name Drug Type Targets #Targets
DB00254DoxycyclineSmall MoleculeB2M, PADI42
DB027403-Indolebutyric AcidSmall MoleculeB2M1
DB04464N-FormylmethionineSmall MoleculeB2M, CLPP, COX4I1, COX5A, COX5B, COX6A2, COX6B1, COX6C, COX7A1, CO ......23
DB09130CopperSmall MoleculeA1BG, ACTG1, ACTN1, ACY1, AFM, AGT, AHCY, AHSG, AKR1A1, ANXA4, ANX ......141