Beta-2-microglobulin (B2M) is a 99-amino-acid secreted immunoglobulin-like C1-set domain protein that serves as the invariant, noncovalently associated light chain (beta chain) of major histocompatibility complex (MHC) class I and MHC class I-like heterodimers. Lacking a transmembrane domain, B2M pairs in the endoplasmic reticulum lumen with the alpha-3 domain and supports the alpha-1/alpha-2 platform of classical MHC class Ia heavy chains (HLA-A, HLA-B, HLA-C), non-classical MHC class Ib heavy chains (HLA-E, HLA-F, HLA-G), lipid-presenting CD1 glycoproteins (CD1a, CD1b, CD1c, CD1d), and the vitamin B metabolite-presenting receptor MR1. This structural pairing is essential for heavy-chain folding, incorporation into the endoplasmic reticulum peptide-loading complex, anterograde transport through the Golgi apparatus, and stable display of antigen-loaded complexes at the cell surface for recognition by T-cell and natural killer (NK) cell receptors. Beyond antigen presentation, B2M is an obligate structural subunit of the hereditary hemochromatosis protein HFEβenabling HFE cell-surface expression and association with transferrin receptors TFRC and TFR2 to regulate cellular iron homeostasisβand of the neonatal Fc receptor (FcRn/FCGRT), which mediates pH-dependent recycling and transcytosis of IgG and albumin. Free monomeric B2M is shed from cell surfaces into serum and body fluids and is normally cleared by the kidneys; in chronic renal failure, elevated circulating B2M can misfold and self-assemble into osteoarticular amyloid fibrils responsible for dialysis-related amyloidosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-182243 | ACCEPT | Summary: B2M-containing MHC class I complexes transit through the Golgi membrane en route to the cell surface. Reason: MHC class I-B2M complexes traffic through the Golgi apparatus and trans-Golgi network during biosynthetic maturation and secretory transport (Reactome:R-HSA-182243). Supporting Evidence: Reactome:R-HSA-182243 Nef disrupts the transport of major histocompatibility complex class I molecules by first binding to the the cytoplasmic side of the transmembrane complex. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-182279 | ACCEPT | Summary: B2M-containing MHC class I complexes transit through the Golgi membrane en route to the cell surface. Reason: MHC class I-B2M complexes traffic through the Golgi apparatus and trans-Golgi network during biosynthetic maturation and secretory transport (Reactome:R-HSA-182279). Supporting Evidence: Reactome:R-HSA-182279 The complex formed by Nef and the major histocompatibility complex class I molecules creates binding sites for PACS-1 and the AP-1 complex. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-182286 | ACCEPT | Summary: B2M-containing MHC class I complexes transit through the Golgi membrane en route to the cell surface. Reason: MHC class I-B2M complexes traffic through the Golgi apparatus and trans-Golgi network during biosynthetic maturation and secretory transport (Reactome:R-HSA-182286). Supporting Evidence: Reactome:R-HSA-182286 The complex of Nef, major histocompatibility complex class I molecules, PACS-1 and AP-1 is transported from the trans-Golgi network to an endosome, where the MHC I complex will be degraded. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-983421 | ACCEPT | Summary: B2M-containing MHC class I complexes transit through the Golgi membrane en route to the cell surface. Reason: MHC class I-B2M complexes traffic through the Golgi apparatus and trans-Golgi network during biosynthetic maturation and secretory transport (Reactome:R-HSA-983421). Supporting Evidence: Reactome:R-HSA-983421 Cargo must pass through the various compartments of the Golgi complex to reach the plasma membrane. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-983427 | ACCEPT | Summary: B2M-containing MHC class I complexes transit through the Golgi membrane en route to the cell surface. Reason: MHC class I-B2M complexes traffic through the Golgi apparatus and trans-Golgi network during biosynthetic maturation and secretory transport (Reactome:R-HSA-983427). Supporting Evidence: Reactome:R-HSA-983427 After passing through the Golgi complex, secretory cargo is packaged into post-Golgi transport intermediates (post-Golgi), which translocate plus-end directed along microtubules to the plasma membrane. |
| GO:0002477 antigen processing and presentation of exogenous peptide antigen via MHC class Ib | IDA PMID:10429675 Structure of human histocompatibility leukocyte antigen (HLA... | MODIFY | Summary: ComplexPortal annotation of exogenous peptide presentation via MHC class Ib on classical HLA-Cw4 should be retargeted to endogenous peptide presentation via MHC class I (GO:0019885). Reason: ComplexPortal annotated GO:0002477 (antigen processing and presentation of exogenous peptide antigen via MHC class Ib), whereas PMID:10429675 determines the crystal structure of classical MHC class Ia complex HLA-Cw4 bound to an endogenous nonameric consensus peptide (QYDDAVYKL). The term should be modified to GO:0019885 (antigen processing and presentation of endogenous peptide antigen via MHC class I), which is already accepted on this gene. Proposed replacements: antigen processing and presentation of endogenous peptide antigen via MHC class I Supporting Evidence: PMID:10429675 The crystal structure of the human class I major histocompatibility complex molecule, human histocompatibility leukocyte antigen (HLA)-Cw4, the ligand for a natural killer (NK) cell inhibitory receptor, has been determined, complexed with a nonameric consensus peptide (QYDDAVYKL). |
| GO:0002477 antigen processing and presentation of exogenous peptide antigen via MHC class Ib | IDA PMID:10843695 The structure and stability of an HLA-A*0201/octameric tax p... | MODIFY | Summary: ComplexPortal annotation of exogenous peptide presentation via MHC class Ib on classical HLA-A2 should be retargeted to endogenous peptide presentation via MHC class I (GO:0019885). Reason: ComplexPortal annotated GO:0002477 (antigen processing and presentation of exogenous peptide antigen via MHC class Ib), whereas PMID:10843695 determines the crystal structure of classical MHC class Ia complex HLA-A2 bound to an intracellular viral peptide (HTLV-1 Tax8, LFGYPVYV). The term should be modified to GO:0019885 (antigen processing and presentation of endogenous peptide antigen via MHC class I), which is already accepted on this gene. Proposed replacements: antigen processing and presentation of endogenous peptide antigen via MHC class I Supporting Evidence: PMID:10843695 The crystal structure of the human class I MHC molecule HLA-A2 complexed with of an octameric peptide, Tax8 (LFGYPVYV), from human T cell lymphotrophic virus-1 (HTLV-1) has been determined. |
| GO:0002477 antigen processing and presentation of exogenous peptide antigen via MHC class Ib | IDA PMID:15718280 Crystal structure of HLA-G: a nonclassical MHC class I molec... | MODIFY | Summary: ComplexPortal annotation of exogenous peptide presentation via MHC class Ib should be refined to endogenous peptide presentation via MHC class Ib (GO:0002476). Reason: ComplexPortal annotated GO:0002477 (antigen processing and presentation of exogenous peptide antigen via MHC class Ib), whereas PMID:15718280 determines the structure of HLA-G bound to a natural endogenous histone H2A self-peptide (RIIPRHLQL). The term should be modified to GO:0002476 (antigen processing and presentation of endogenous peptide antigen via MHC class Ib). Proposed replacements: antigen processing and presentation of endogenous peptide antigen via MHC class Ib Supporting Evidence: PMID:15718280 To gain further insights into HLA-G function, we determined the 1.9-A structure of a monomeric HLA-G complexed to a natural endogenous peptide ligand from histone H2A (RIIPRHLQL). |
| GO:0002477 antigen processing and presentation of exogenous peptide antigen via MHC class Ib | IDA PMID:28636952 Human Leukocyte Antigen F Presents Peptides and Regulates Im... | MODIFY | Summary: ComplexPortal annotation of exogenous peptide presentation via MHC class Ib should be refined to endogenous peptide presentation via MHC class Ib (GO:0002476). Reason: ComplexPortal annotated GO:0002477 (antigen processing and presentation of exogenous peptide antigen via MHC class Ib), whereas PMID:28636952 shows that B2M-HLA-F presents endogenous human proteomic peptides to LIR1. The term should be modified to GO:0002476 (antigen processing and presentation of endogenous peptide antigen via MHC class Ib). Proposed replacements: antigen processing and presentation of endogenous peptide antigen via MHC class Ib Supporting Evidence: PMID:28636952 The complex structure of peptide-loaded Ξ²2m-HLA-F bound to the inhibitory LIR1 revealed similarities to high-affinity recognition of the viral MHC-I mimic UL18 and a docking strategy that relies on contacts with HLA-F as well as Ξ²2m, thus precluding binding to HLA-F OCs. |
| GO:0002477 antigen processing and presentation of exogenous peptide antigen via MHC class Ib | IDA PMID:35705051 Primary and secondary functions of HLA-E are determined by s... | MODIFY | Summary: ComplexPortal annotation of exogenous peptide presentation via MHC class Ib should be refined to endogenous peptide presentation via MHC class Ib (GO:0002476). Reason: ComplexPortal annotated GO:0002477 (antigen processing and presentation of exogenous peptide antigen via MHC class Ib), whereas PMID:35705051 shows that HLA-E displays endogenous MHC class Ia signal peptides (VL9) and intracellular pathogen peptides. The term should be modified to GO:0002476 (antigen processing and presentation of endogenous peptide antigen via MHC class Ib). Proposed replacements: antigen processing and presentation of endogenous peptide antigen via MHC class Ib Supporting Evidence: PMID:35705051 MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8+ T cells. |
| GO:0002477 antigen processing and presentation of exogenous peptide antigen via MHC class Ib | IDA PMID:9892618 Structural evidence of T cell xeno-reactivity in the absence... | MODIFY | Summary: ComplexPortal annotation of exogenous peptide presentation via MHC class Ib on classical HLA-A2 should be retargeted to endogenous peptide presentation via MHC class I (GO:0019885). Reason: ComplexPortal annotated GO:0002477 (antigen processing and presentation of exogenous peptide antigen via MHC class Ib), whereas PMID:9892618 determines the crystal structure of classical MHC class Ia complex HLA-A2 bound to endogenous self-peptide p1049. The term should be modified to GO:0019885 (antigen processing and presentation of endogenous peptide antigen via MHC class I), which is already accepted on this gene. Proposed replacements: antigen processing and presentation of endogenous peptide antigen via MHC class I Supporting Evidence: PMID:9892618 To examine the mechanism of xeno-reactivity of AHIII12.2, we have determined the crystal structures of A2/p1049 and Db/p1027 to 2.5 A and 2.8 A resolution, respectively. |
| GO:0002502 peptide antigen assembly with MHC class I protein complex | IDA PMID:36104323 Structure of an MHC I-tapasin-ERp57 editing complex defines ... | ACCEPT | Summary: B2M is essential for stabilizing peptide-receptive MHC class I heavy chains during peptide antigen assembly and proofreading. Reason: The crystal structure of the tapasin-ERp57-MHC class I complex (PMID:36104323) demonstrates how B2M stabilizes the peptide-receptive MHC class I heavy chain and contacts tapasin during peptide loading and editing. Supporting Evidence: PMID:36104323 MHC I complexes are composed of a heavy chain (hc) and the light chain Ξ²2-microglobulin (Ξ²2m). |
| GO:0002503 peptide antigen assembly with MHC class II protein complex | IBA GO_REF:0000033 | REMOVE | Summary: Over-propagated MHC class II annotation (peptide antigen assembly with MHC class II protein complex) from PANTHER family PTN000460629. Reason: This IBA annotation was propagated from PANTHER node PTN000460629 (PTHR19944), which groups Ig-like C1-set domains across MHC class I and MHC class II chains (such as HLA-DRA, HLA-DRB1, HLA-DPB1, HLA-DMA, and HLA-DMB). B2M is exclusively the light chain of MHC class I and class I-like heterodimers and does not assemble with, bind, or traffic in MHC class II complexes. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000460629 Β· PTHR19944 ancestral node SUPPORTS SOURCE BUT NOT TARGET Propagated from MHC class II and HLA-DM paralogs within PTHR19944; B2M is restricted to MHC class I/Ib/I-like heterodimers. |
| GO:0002715 regulation of natural killer cell mediated immunity | NAS PMID:10429675 Structure of human histocompatibility leukocyte antigen (HLA... | KEEP AS NON CORE | Summary: B2M-stabilized MHC class I complexes engage NK cell receptors to regulate NK cell-mediated immunity. Reason: Peptide-loaded B2M-MHC class I complexes (including HLA-Cw4, HLA-E, HLA-F, and HLA-G) serve as ligands for inhibitory and activating NK cell receptors (such as KIR2D in PMID:10429675, NKG2A:CD94 in PMID:35705051, and LIR1 in PMID:28636952), thereby regulating NK cell cytotoxicity; kept as a downstream non-core process. Supporting Evidence: PMID:10429675 The crystal structure of the human class I major histocompatibility complex molecule, human histocompatibility leukocyte antigen (HLA)-Cw4, the ligand for a natural killer (NK) cell inhibitory receptor, has been determined, complexed with a nonameric consensus peptide (QYDDAVYKL). |
| GO:0002715 regulation of natural killer cell mediated immunity | NAS PMID:10843695 The structure and stability of an HLA-A*0201/octameric tax p... | KEEP AS NON CORE | Summary: B2M-stabilized MHC class I complexes engage NK cell receptors to regulate NK cell-mediated immunity. Reason: ComplexPortal attached PMID:10843695 (crystal structure of HLA-A2/Tax8) as a complex-level structural reference for this NAS annotation; NK cell receptor engagement by B2M-associated MHC class I/Ib complexes is directly supported by PMID:10429675 (HLA-Cw4/KIR2D), PMID:28636952 (HLA-F/LIR1 and KIR3D), and PMID:35705051 (HLA-E/NKG2A:CD94). Kept as a downstream non-core process. Supporting Evidence: PMID:10843695 The crystal structure of the human class I MHC molecule HLA-A2 complexed with of an octameric peptide, Tax8 (LFGYPVYV), from human T cell lymphotrophic virus-1 (HTLV-1) has been determined. PMID:35705051 MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8+ T cells. |
| GO:0002715 regulation of natural killer cell mediated immunity | NAS PMID:15718280 Crystal structure of HLA-G: a nonclassical MHC class I molec... | KEEP AS NON CORE | Summary: B2M-stabilized MHC class I complexes engage NK cell receptors to regulate NK cell-mediated immunity. Reason: ComplexPortal attached PMID:15718280 (crystal structure of monomeric HLA-G/H2A peptide) as a complex-level structural reference for this NAS annotation; NK cell receptor engagement by B2M-associated MHC class I/Ib complexes is directly supported by PMID:10429675 (HLA-Cw4/KIR2D), PMID:28636952 (HLA-F/LIR1 and KIR3D), and PMID:35705051 (HLA-E/NKG2A:CD94). Kept as a downstream non-core process. Supporting Evidence: PMID:15718280 To gain further insights into HLA-G function, we determined the 1.9-A structure of a monomeric HLA-G complexed to a natural endogenous peptide ligand from histone H2A (RIIPRHLQL). PMID:35705051 MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8+ T cells. |
| GO:0002715 regulation of natural killer cell mediated immunity | NAS PMID:28636952 Human Leukocyte Antigen F Presents Peptides and Regulates Im... | KEEP AS NON CORE | Summary: B2M-stabilized MHC class I complexes engage NK cell receptors to regulate NK cell-mediated immunity. Reason: Peptide-loaded B2M-MHC class I complexes (including HLA-Cw4, HLA-E, HLA-F, and HLA-G) serve as ligands for inhibitory and activating NK cell receptors (such as LIR1 and KIR3D in PMID:28636952), thereby regulating NK cell cytotoxicity; kept as a downstream non-core process. Supporting Evidence: PMID:28636952 The complex structure of peptide-loaded Ξ²2m-HLA-F bound to the inhibitory LIR1 revealed similarities to high-affinity recognition of the viral MHC-I mimic UL18 and a docking strategy that relies on contacts with HLA-F as well as Ξ²2m, thus precluding binding to HLA-F OCs. |
| GO:0002715 regulation of natural killer cell mediated immunity | NAS PMID:35705051 Primary and secondary functions of HLA-E are determined by s... | KEEP AS NON CORE | Summary: B2M-stabilized MHC class I complexes engage NK cell receptors to regulate NK cell-mediated immunity. Reason: Peptide-loaded B2M-MHC class I complexes (including HLA-Cw4, HLA-E, HLA-F, and HLA-G) serve as ligands for inhibitory and activating NK cell receptors (such as NKG2A:CD94 in PMID:35705051), thereby regulating NK cell cytotoxicity; kept as a downstream non-core process. Supporting Evidence: PMID:35705051 MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8+ T cells. |
| GO:0002715 regulation of natural killer cell mediated immunity | NAS PMID:9892618 Structural evidence of T cell xeno-reactivity in the absence... | KEEP AS NON CORE | Summary: B2M-stabilized MHC class I complexes engage NK cell receptors to regulate NK cell-mediated immunity. Reason: ComplexPortal attached PMID:9892618 (crystal structure of HLA-A2/p1049 for T-cell xeno-reactivity) as a complex-level structural reference for this NAS annotation; NK cell receptor engagement by B2M-associated MHC class I/Ib complexes is directly supported by PMID:10429675 (HLA-Cw4/KIR2D), PMID:28636952 (HLA-F/LIR1 and KIR3D), and PMID:35705051 (HLA-E/NKG2A:CD94). Kept as a downstream non-core process. Supporting Evidence: PMID:9892618 To examine the mechanism of xeno-reactivity of AHIII12.2, we have determined the crystal structures of A2/p1049 and Db/p1027 to 2.5 A and 2.8 A resolution, respectively. PMID:35705051 MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8+ T cells. |
| GO:0002726 positive regulation of T cell cytokine production | IDA PMID:24643698 The WT hemochromatosis protein HFE inhibits CD8βΊ T-lymphocyt... | KEEP AS NON CORE | Summary: Downstream effect on CD8+ T cell cytokine secretion mediated by MHC class I antigen presentation and modulated by HFE. Reason: PMID:24643698 examines how wild-type HFE (which requires B2M for surface expression) modulates antigen-specific CD8+ T-lymphocyte activation and MIP-1beta secretion during MHC class I antigen presentation; kept as non-core. Supporting Evidence: PMID:24643698 Using transient HFE transfection assays in a model of APCs, we show that WT HFE (HFEWT ), but not C282Y-mutated HFE, inhibits secretion of MIP-1Ξ² from antigen-specific CD8(+) T lymphocytes. |
| GO:0003254 regulation of membrane depolarization | IDA PMID:23144825 Novel antibacterial activity of Ξ²(2)-microglobulin in human ... | MARK AS OVER ANNOTATED | Summary: Dissipation of bacterial transmembrane potential by exogenous amniotic-fluid B2M is over-annotated as endogenous regulation of membrane depolarization. Reason: PMID:23144825 shows that soluble human B2M isolated from amniotic fluid dissipates the transmembrane potential of target bacteria (Listeria monocytogenes and Escherichia coli) as part of its antibacterial activity; annotating this inter-species bactericidal effect to GO:0003254 (regulation of membrane depolarization, an endogenous cellular electrophysiology term) is an over-annotation when the antibacterial activity is already captured by GO:0050829, GO:0050830, and GO:0061844. Supporting Evidence: PMID:23144825 Interestingly, the antibacterial action of Ξ²(2)M was associated with dissipation of the transmembrane potential, but the protein did not cause damage to the membrane that would result in SYTOX green uptake. |
| GO:0005198 structural molecule activity | IDA PMID:36104323 Structure of an MHC I-tapasin-ERp57 editing complex defines ... | ACCEPT | Summary: B2M is the invariant structural beta-chain subunit that stabilizes MHC class I and class I-like heavy chains. Reason: Crystallographic analysis of the MHC class I editing complex (PMID:36104323) and extensive structural studies demonstrate that B2M folds as an immunoglobulin-like C1-set domain that noncovalently pairs with the alpha-3 and alpha-1/alpha-2 domains of MHC class I and class I-like heavy chains to stabilize their tertiary structure. Supporting Evidence: PMID:36104323 MHC I complexes are composed of a heavy chain (hc) and the light chain Ξ²2-microglobulin (Ξ²2m). |
| GO:0005515 protein binding | IPI PMID:12118248 Structure of human CD1b with bound ligands at 2.3 A, a maze ... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:P29016. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:P29016 in PMID:12118248 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:12833155 Crystal structure of CD1a in complex with a sulfatide self a... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:P06126. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:P06126 in PMID:12833155 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:14764708 The crystal structure of human CD1b with a bound bacterial g... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:P29016. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:P29016 in PMID:14764708 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:15723809 Molecular mechanism of lipopeptide presentation by CD1a. | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:P06126. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:P06126 in PMID:15723809 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:15965644 The Q283P amino-acid change in HFE leads to structural and f... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q30201. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q30201 in PMID:15965644 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:18802093 The varicellovirus UL49.5 protein blocks the transporter ass... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q03518. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q03518 in PMID:18802093 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:20164429 The association of MHC class I proteins with the 2B4 recepto... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q9BZW8. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q9BZW8 in PMID:20164429 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:20618438 N-glycosylation is important for the correct intracellular l... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q30201. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q30201 in PMID:20618438 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:23051753 MR1 presents microbial vitamin B metabolites to MAIT cells. | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q95460-1. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q95460-1 in PMID:23051753 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:23527218 Novel interaction between proliferating cell nuclear antigen... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:P12004. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:P12004 in PMID:23527218 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:26030842 A fluorescent bimolecular complementation screen reveals MAF... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:P12004. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:P12004 in PMID:26030842 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:27043408 The intracellular pathway for the presentation of vitamin B-... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q95460. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q95460 in PMID:27043408 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:P29016. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:P29016 in PMID:28514442 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q9Y3Y4. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q9Y3Y4 in PMID:32814053 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:P29016. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:P29016 in PMID:33961781 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q30201. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q30201 in PMID:33961781 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:9427624 TAP- and tapasin-dependent HLA-E surface expression correlat... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:P13747. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:P13747 in PMID:9427624 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:9465039 The hemochromatosis gene product complexes with the transfer... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q30201. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q30201 in PMID:9465039 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:9546397 Crystal structure of the hemochromatosis protein HFE and cha... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q30201. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q30201 in PMID:9546397 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005515 protein binding | IPI PMID:9990067 Association of HFE protein with transferrin receptor in cryp... | REMOVE | Summary: Uninformative bare protein binding annotation for interaction with UniProtKB:Q30201. Reason: Removed per the repository protein-binding policy: bare GO:0005515 (protein binding) with UniProtKB:Q30201 in PMID:9990067 is uninformative, whereas B2M's specific role as an obligate structural heterodimer subunit is captured by GO:0005198 (structural molecule activity) and complex terms GO:0042612, GO:0032398, GO:0042824, and GO:1990712. |
| GO:0005576 extracellular region | EXP PMID:7554280 Amino acid sequence of a modified beta 2-microglobulin in re... | ACCEPT | Summary: B2M is a secreted protein lacking a transmembrane anchor that circulates as a soluble monomer in extracellular body fluids. Reason: B2M possesses an N-terminal signal peptide, lacks a transmembrane domain, and is shed from cell surfaces into extracellular fluids including serum, urine, colostrum, and tear fluid (PMID:7554280). Supporting Evidence: PMID:7554280 We isolated and analyzed beta 2-microglobulin (BM) in urine of two renal failure patients and in ultrafiltrate from long-term dialysis patients. |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | ACCEPT | Summary: B2M is a secreted protein lacking a transmembrane anchor that circulates as a soluble monomer in extracellular body fluids. Reason: B2M possesses an N-terminal signal peptide, lacks a transmembrane domain, and is shed from cell surfaces into extracellular fluids including serum, urine, colostrum, and tear fluid (PMID:16502470). Supporting Evidence: PMID:16502470 We have investigated the low abundance proteins in the aqueous phase of human colostrum, after depletion of the major proteins secretory IgA, lactoferrin, alpha-lactalbumin and HSA by immunoabsorption, using 2-D LC and gel-based proteomic methods. |
| GO:0005576 extracellular region | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | ACCEPT | Summary: B2M is a secreted protein lacking a transmembrane anchor that circulates as a soluble monomer in extracellular body fluids. Reason: B2M possesses an N-terminal signal peptide, lacks a transmembrane domain, and is shed from cell surfaces into extracellular fluids including serum, urine, colostrum, and tear fluid (PMID:22664934). Supporting Evidence: PMID:22664934 Herein, we report on an analysis of proteins in the tear fluid from breast carcinoma patients and healthy women using a de novo proteomic approach and 25 mixed samples from each group. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: B2M is a secreted protein lacking a transmembrane anchor that circulates as a soluble monomer in extracellular body fluids. Reason: B2M possesses an N-terminal signal peptide, lacks a transmembrane domain, and is shed from cell surfaces into extracellular fluids including serum, urine, colostrum, and tear fluid (GO_REF:0000044). Supporting Evidence: file:human/B2M/B2M-uniprot.txt Secreted. Cell surface. Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798745 | ACCEPT | Summary: B2M is a secreted protein lacking a transmembrane anchor that is released into the extracellular space upon neutrophil tertiary granule exocytosis. Reason: Reactome:R-HSA-6798745 models exocytosis of neutrophil tertiary (gelatinase) granule lumen proteins into the extracellular space, where luminal B2M is released as a soluble secreted protein. Supporting Evidence: Reactome:R-HSA-6798745 Tertiary (gelatinase) granules are part of a continuum of peroxidase-negative granules formed in myelocytes, metamyelocytes, band cells and segmented neutrophils. file:human/B2M/B2M-uniprot.txt Secreted. Cell surface. Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798749 | ACCEPT | Summary: B2M is a secreted protein lacking a transmembrane anchor that is released into the extracellular space upon neutrophil specific granule exocytosis. Reason: Reactome:R-HSA-6798749 models exocytosis of neutrophil secondary (specific) granule lumen proteins into the extracellular space, where luminal B2M is released as a soluble secreted protein. Supporting Evidence: Reactome:R-HSA-6798749 Secondary (specific) granules are peroxidase-negative and rich in antimicrobial substances (Joiner et al. file:human/B2M/B2M-uniprot.txt Secreted. Cell surface. Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-977136 | ACCEPT | Summary: B2M is a secreted protein lacking a transmembrane anchor that circulates in extracellular fluids and can deposit as extracellular amyloid fibrils. Reason: Reactome:R-HSA-977136 models extracellular aggregation and deposition of soluble secreted B2M into amyloid fibrils in the extracellular space. Supporting Evidence: Reactome:R-HSA-977136 Amyloid fibril formation is associated with a wide range of diseases (Chiti & Dobson 2006), though the accumulation and deposition of fibrillar material does not correlate well with disease pathogenesis and it is now widely believed that oligomeric amyloid forms are largely responsible for the cytotoxic effects of amyloid (Glabe 2009). file:human/B2M/B2M-uniprot.txt Secreted. Cell surface. Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). |
| GO:0005765 lysosomal membrane | IBA GO_REF:0000033 | REMOVE | Summary: Over-propagated MHC class II annotation (lysosomal membrane) from PANTHER family PTN000460629. Reason: This IBA annotation was propagated from PANTHER node PTN000460629 (PTHR19944), which groups Ig-like C1-set domains across MHC class I and MHC class II chains (such as HLA-DRA, HLA-DRB1, HLA-DPB1, HLA-DMA, and HLA-DMB). B2M is exclusively the light chain of MHC class I and class I-like heterodimers and does not assemble with, bind, or traffic in MHC class II complexes. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000460629 Β· PTHR19944 ancestral node SUPPORTS SOURCE BUT NOT TARGET Propagated from MHC class II and HLA-DM paralogs within PTHR19944; B2M is a soluble luminal/extracellular beta chain without a transmembrane anchor. |
| GO:0005783 endoplasmic reticulum | IC PMID:36104323 Structure of an MHC I-tapasin-ERp57 editing complex defines ... | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (PMID:36104323). Supporting Evidence: PMID:36104323 MHC I complexes are composed of a heavy chain (hc) and the light chain Ξ²2-microglobulin (Ξ²2m). |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-1031716 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-1031716). Supporting Evidence: Reactome:R-HSA-1031716 IFN-gamma stimulates gene expression of about 200 genes which include the primary response genes like IRFs, Fc-gamma receptor (FCGR), GBPs (guanylate-binding proteins) and also major histocompatibility complex (MHC) class I and class II molecules, proteins involved in antigen presentation, antiviral proteins like PKR, OAS proteins etc. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8951499 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-8951499). Supporting Evidence: Reactome:R-HSA-8951499 MHC class I heterodimers are only stable in peptide bound form and only as a trimer (with bound peptide) present on the cell surface. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-9637635 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-9637635). Supporting Evidence: Reactome:R-HSA-9637635 Mtb 6 kDa early secretory antigenic target (EsxA) binds to freely available human beta-2-microglobulin (B2M) in the endoplasmic reticulum lumen, inhibiting the loading of antigen-derived peptides to B2M, a component of the class I major histocompatibility complex (MHC-I complex) (Sreejit et al. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-9755328 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-9755328). Supporting Evidence: Reactome:R-HSA-9755328 During viral infection, T cells recognize the viral antigens presented by class I MHC. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-9755359 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-9755359). Supporting Evidence: Reactome:R-HSA-9755359 SARS-CoV-2 ORF8 (8), which has no orthologous protein in SARS-CoV-1 (Li T et al. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-983138 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-983138). Supporting Evidence: Reactome:R-HSA-983138 When the loaded peptide is of a sufficiently high-affinity the trimeric complex is transported to a special ER exit site by a putative cargo receptor, B cell receptor-associated protein (BAP31), where it translocates to the cell surface, possibly by transport in COPII-coated vesicles. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-983142 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-983142). Supporting Evidence: Reactome:R-HSA-983142 Upon interaction of Beta-2-microglobin (B2M) with MHC class I Heavy Chain (HC), calnexin is fully replaced by its soluble ortholog calreticulin (CRT) and this complex is incorporated into the peptide loading complex (PLC). |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-983146 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-983146). Supporting Evidence: Reactome:R-HSA-983146 Interaction of calnexin (CNX) with MHC class I HC stabilizes it and facilitates the association of the beta2 microglobulin component (B2M). |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-983161 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-983161). Supporting Evidence: Reactome:R-HSA-983161 Upon peptide binding the class I MHC molecule releases from the peptide loading complex (PLC) and clusters at ER exit sites and is finally exported to the cell surface.<br>MHC I molecules bound to low-affinity peptides are not transferred to the cell surface and are instead cycled back to ER. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-983424 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-983424). Supporting Evidence: Reactome:R-HSA-983424 Once the entire COPII coat has been assembled, the bud is separated from the ER membrane in the form of a COPII coated vesicle. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-983425 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-983425). Supporting Evidence: Reactome:R-HSA-983425 Sec13-Sec31 binds the prebudding complex and this Sec13-Sec31 heterotetramer forms the outer structural scaffold of the coat. Sec13-Sec31 is likely to crosslink the prebudding complexes generating COPII-coated vesicles. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-983426 | ACCEPT | Summary: B2M localizes to the endoplasmic reticulum lumen where it assembles with newly synthesized MHC class I and class I-like heavy chains. Reason: Newly translocated B2M resides in the ER lumen where it pairs with MHC class I heavy chains and enters the peptide-loading complex prior to secretory export (Reactome:R-HSA-983426). Supporting Evidence: Reactome:R-HSA-983426 The cytoplasmic tails of MHC class I molecules do not possess any of the known ER export sequences. |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | ACCEPT | Summary: B2M-containing MHC class I complexes transit through the Golgi apparatus en route to the cell surface. Reason: MHC class I-B2M complexes traffic through the Golgi apparatus and trans-Golgi network during biosynthetic maturation and secretory transport (GO_REF:0000052). Supporting Evidence: file:human/B2M/B2M-uniprot.txt Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (GO_REF:0000052); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: file:human/B2M/B2M-uniprot.txt Secreted. Cell surface. Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1236964 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-1236964); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-1236964 Peptide-loaded MHC class I complexes are transported by an undefined mechanism back to the cell surface for cross-presentation to T cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1236965 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-1236965); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-1236965 Exogenous antigen loaded class I MHC molecules in phagosomes may be delivered to the surface by membrane recycling machinery. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-198955 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-198955); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-198955 T cells distinguish foreign material from self through presentation of fragments of the antigen by the MHC cell surface receptors. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-198958 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-198958); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-198958 A hallmark of human NK cells is the expression of HLA class I-specific killer-cell immunoglobulin-like receptors (KIR). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199043 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-199043); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-199043 Leukocyte immunoglobulin (Ig)-like receptors [LILRs, also known as Ig-like transcripts (ILTs)] are a family of inhibitory and stimulatory receptors encoded within the leukocyte receptor complex and are expressed by immune cell types of both myeloid and lymphoid lineage. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199062 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-199062); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-199062 After interaction with its ligand HLA-E, which is expressed on normal cells, the C-type lectin inhibitory receptor CD94/NKG2A suppresses activation signaling processes. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199169 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-199169); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-199169 CD160 is a GPI-anchored lymphocyte surface receptor in which expression is mostly restricted to the highly cytotoxic NK cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199558 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-199558); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-199558 A hallmark of human NK cells is the expression of HLA class I-specific killer-cell immunoglobulin-like receptors (KIR). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199566 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-199566); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-199566 A hallmark of human NK cells is the expression of HLA class I-specific killer-cell immunoglobulin-like receptors (KIR). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199576 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-199576); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-199576 A hallmark of human NK cells is the expression of HLA class I-specific killer-cell immunoglobulin-like receptors (KIR). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199579 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-199579); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-199579 A hallmark of human NK cells is the expression of HLA class I-specific killer-cell immunoglobulin-like receptors (KIR). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199583 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-199583); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-199583 A hallmark of human NK cells is the expression of HLA class I-specific killer-cell immunoglobulin-like receptors (KIR). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-199587 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-199587); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-199587 A hallmark of human NK cells is the expression of HLA class I-specific killer-cell immunoglobulin-like receptors (KIR). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-210289 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-210289); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-210289 Phosphorylated ITAM on DAP12 serves as the docking site for the two SH2 domains of SYK or ZAP70. Binding leads to SYK activation (Lanier et al. 1998, McVicar et al. 1998). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-210309 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-210309); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-210309 Killer cell immunoglobulin-like two-domain short-tail receptor 2 (KIR2DS2) is an activating KIR receptor invariably expressed on the cell surface of NK cells and subsets of T cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2172126 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2172126); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2172126 NKG2C, a C-type lectin-like surface receptor, is a member of the NKG2 family and forms heterodimers with CD94 that is expressed on NK cells and a subset of T cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2272753 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2272753); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2272753 Killer cell immunoglobulin-like two-domain short-tail receptor 4 (KIR2DS4) is the most prevalent lineage III-activating KIR receptor. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2272795 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2272795); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2272795 Killer cell immunoglobulin-like two-domain short-tail receptor 1 (KIR2DS1) is one of the activating KIR receptors expressed on the surface of NK cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2395412 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2395412); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2395412 The binding of SYK to DAP12 induces conformational changes that result in SYK activation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2395801 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2395801); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2395801 LAT is palmitoylated and membrane-associated adaptor protein. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2396594 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2396594); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2396594 SLP-76 lacks intrinsic catalytic activity and acts as a scaffold, recruiting other proteins for correct localization during molecular signal transduction (Bogin et al. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2424480 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2424480); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2424480 Activated PI3K phosphorylates phosphatidylinositol (PI) 4-phosphate and PI 4,5-bisphosphate (PIP2) to generate PI 3,4-bisphosphate and PI 3,4,5-triphosphate (PIP3) and these second messengers recruit other signaling proteins containing plecstrin homology (PH) domain. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2424482 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2424482); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2424482 Phosphoinositide 3-kinases (PI3Ks) are one of the downstream effectors of activated SYK. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2424484 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2424484); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2424484 In myeloid cells BTK is phosphorylated on Y551 upon DAP12 activation in a SYK kinase-dependent manner. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2424486 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2424486); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2424486 VAV exists in an auto-inhibitory state, folded in such a way as to inhibit the GEF activity of its DH domain. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2424487 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-2424487); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-2424487 Three tyrosine residues at positions 771, 783 and 1254 in PLCgamma1 have been identified as the sites of receptor tyrosine kinase phosphorylation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8850326 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-8850326); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-8850326 T lymphocytes have developed the capacity to recognize as antigens a large variety of molecules including peptides, lipids, and vitamin metabolites (Moody DB et al. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8850356 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-8850356); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-8850356 The hallmark of T cell activation is the direct binding of T-cell receptor (TCR) to an antigen that is presented by an antigen-presenting molecule. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-976734 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-976734); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-976734 In addition to the main fibril peptide, mature amyloid fibrils have additional components. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-977136 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-977136); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-977136 Amyloid fibril formation is associated with a wide range of diseases (Chiti & Dobson 2006), though the accumulation and deposition of fibrillar material does not correlate well with disease pathogenesis and it is now widely believed that oligomeric amyloid forms are largely responsible for the cytotoxic effects of amyloid (Glabe 2009). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-983427 | MODIFY | Summary: B2M localizes to the external side of the plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: B2M lacks a transmembrane domain and associates noncovalently on the extracellular face of the plasma membrane with membrane-anchored MHC class I, CD1, MR1, HFE, and FcRn heavy chains (Reactome:R-HSA-983427); this broad plasma membrane term should be refined to its specific child term GO:0009897 (external side of plasma membrane, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: Reactome:R-HSA-983427 After passing through the Golgi complex, secretory cargo is packaged into post-Golgi transport intermediates (post-Golgi), which translocate plus-end directed along microtubules to the plasma membrane. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | MARK AS OVER ANNOTATED | Summary: High-throughput focal adhesion proteomics hit reflecting abundant cell-surface MHC class I contaminant. Reason: B2M was identified by shotgun proteomics of isolated focal adhesions (PMID:21423176). The detection is a real observation, but B2M is an abundant extracellular-facing MHC class I light chain with no known structural or functional role at integrin adhesion plaques, and nothing else supports the location; it is most likely co-isolated plasma-membrane material. The term therefore over-reads the proteomic hit rather than describing where B2M acts. |
| GO:0006879 intracellular iron ion homeostasis | IDA PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | KEEP AS NON CORE | Summary: B2M participates in intracellular iron ion homeostasis as the obligate structural beta chain of the iron-regulatory protein HFE. Reason: B2M heterodimerization with HFE is required for HFE folding, ER exit, and interaction with TFRC (TfR1) and TFR2 to regulate receptor-mediated transferrin endocytosis and cellular iron homeostasis (PMID:18353247); kept as non-core because the iron-regulatory activity resides in the HFE-TFRC/TFR2 complex while B2M provides structural stabilization. Supporting Evidence: PMID:18353247 The co-expression of HFE in cells expressing TfR2 led to increased affinity for diferric transferrin, increased transferrin-dependent iron uptake, and relative resistance to iron chelation. |
| GO:0006955 immune response | IEA GO_REF:0000002 | TOO GENERAL | Summary: Broad immune response term subsumed by specific accepted MHC class I antigen presentation terms. Reason: True of B2M, but uninformative because it is entailed by the specific accepted child terms GO:0019885 (antigen processing and presentation of endogenous peptide antigen via MHC class I) and GO:0002502 (peptide antigen assembly with MHC class I protein complex), as well as the modified child term GO:0002476 (antigen processing and presentation of endogenous peptide antigen via MHC class Ib). |
| GO:0007608 sensory perception of smell | IEA GO_REF:0000107 | UNDECIDED | Summary: Ensembl Compara projection of sensory perception of smell from mouse B2m lacks supporting human evidence in the cached literature. Reason: GO_REF:0000107 projects GO:0007608 from mouse B2m (UniProtKB:P01887 / ensembl:ENSMUSP00000099534). Because no supporting experimental evidence for human B2M in sensory perception of smell is accessible in the cached publications, this annotation is marked UNDECIDED. |
| GO:0007611 learning or memory | IDA PMID:26147761 Ξ²2-microglobulin is a systemic pro-aging factor that impairs... | KEEP AS NON CORE | Summary: Downstream neurobiological aging phenotype (learning or memory) linked to systemic B2M accumulation. Reason: Reflects a downstream neurobiological aging phenotype of systemic circulating B2M accumulation in the adult hippocampus (PMID:26147761) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:26147761 Here we identify Ξ²2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. |
| GO:0007611 learning or memory | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Downstream neurobiological aging phenotype (learning or memory) linked to systemic B2M accumulation. Reason: Reflects a downstream neurobiological aging phenotype of systemic circulating B2M accumulation in the adult hippocampus (GO_REF:0000107, supported by PMID:26147761) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:26147761 Here we identify Ξ²2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. |
| GO:0007611 learning or memory | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Downstream neurobiological aging phenotype (learning or memory) linked to systemic B2M accumulation. Reason: Reflects a downstream neurobiological aging phenotype of systemic circulating B2M accumulation in the adult hippocampus (GO_REF:0000024, supported by PMID:26147761) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:26147761 Here we identify Ξ²2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. |
| GO:0009897 external side of plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: B2M localizes to the external side of plasma membrane as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: Mature B2M-associated MHC class I, CD1, MR1, HFE, and FcRn complexes are displayed on the external face of the plasma membrane (GO_REF:0000107). Supporting Evidence: file:human/B2M/B2M-uniprot.txt Secreted. Cell surface. Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). |
| GO:0009986 cell surface | EXP PMID:25356553 The ESAT-6 protein of Mycobacterium tuberculosis interacts w... | ACCEPT | Summary: B2M localizes to the cell surface as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: Mature B2M-associated MHC class I, CD1, MR1, HFE, and FcRn complexes are displayed on the external face of the plasma membrane (PMID:25356553). Supporting Evidence: PMID:25356553 We found that ESAT-6/ESAT-6:CFP-10 can enter into the endoplasmic reticulum where it sequesters Ξ²2M to inhibit cell surface expression of MHC-I-Ξ²2M complexes, resulting in downregulation of class I-mediated antigen presentation. |
| GO:0009986 cell surface | IEA GO_REF:0000044 | ACCEPT | Summary: B2M localizes to the cell surface as the luminal/extracellular beta chain of membrane-anchored MHC class I and class I-like receptors. Reason: Mature B2M-associated MHC class I, CD1, MR1, HFE, and FcRn complexes are displayed on the external face of the plasma membrane (GO_REF:0000044). Supporting Evidence: file:human/B2M/B2M-uniprot.txt Secreted. Cell surface. Note=Detected in serum and urine (PubMed:1336137, PubMed:7554280). |
| GO:0010038 response to metal ion | IEA GO_REF:0000117 | TOO GENERAL | Summary: Broad metal ion response term subsumed by cellular response to iron ion. Reason: True of B2M via its obligate partnership with HFE, but uninformative because the more specific descendant term GO:0071281 (cellular response to iron ion) is already asserted in this review. |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-983421 | ACCEPT | Summary: Peptide-loaded MHC class I-B2M complexes traffic from the ER to the Golgi via COPII-coated transport vesicles. Reason: Following dissociation from the ER peptide-loading complex, mature MHC class I-B2M heterotrimers are packaged into COPII ER-to-Golgi transport vesicles for anterograde secretory transport (Reactome:R-HSA-983421). Supporting Evidence: Reactome:R-HSA-983421 Cargo must pass through the various compartments of the Golgi complex to reach the plasma membrane. |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-983422 | ACCEPT | Summary: Peptide-loaded MHC class I-B2M complexes traffic from the ER to the Golgi via COPII-coated transport vesicles. Reason: Following dissociation from the ER peptide-loading complex, mature MHC class I-B2M heterotrimers are packaged into COPII ER-to-Golgi transport vesicles for anterograde secretory transport (Reactome:R-HSA-983422). Supporting Evidence: Reactome:R-HSA-983422 Before the cargo vesicle can fuse with target membrane, the COPII protein coat must be disassembled and its components released into cytosol. |
| GO:0012507 ER to Golgi transport vesicle membrane | TAS Reactome:R-HSA-983424 | ACCEPT | Summary: Peptide-loaded MHC class I-B2M complexes traffic from the ER to the Golgi via COPII-coated transport vesicles. Reason: Following dissociation from the ER peptide-loading complex, mature MHC class I-B2M heterotrimers are packaged into COPII ER-to-Golgi transport vesicles for anterograde secretory transport (Reactome:R-HSA-983424). Supporting Evidence: Reactome:R-HSA-983424 Once the entire COPII coat has been assembled, the bud is separated from the ER membrane in the form of a COPII coated vesicle. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | MODIFY | Summary: Broad membrane localization from NK cell membrane proteomics is better captured by external side of plasma membrane. Reason: PMID:19946888 identified B2M in the membrane proteome of NK-like YTS cells; because B2M lacks a transmembrane domain and associates peripherally with membrane-anchored MHC class I heavy chains at the cell surface, this broad term should be refined to external side of plasma membrane (GO:0009897, already accepted on this gene). Proposed replacements: external side of plasma membrane Supporting Evidence: PMID:19946888 The present study was initiated to define the composition of the membrane proteome of the Natural Killer (NK) like cell line YTS. |
| GO:0019731 antibacterial humoral response | IDA PMID:23144825 Novel antibacterial activity of Ξ²(2)-microglobulin in human ... | KEEP AS NON CORE | Summary: Soluble B2M in human amniotic fluid exhibits potassium-dependent antibacterial activity (antibacterial humoral response). Reason: PMID:23144825 demonstrated that soluble B2M isolated from human amniotic fluid is upregulated by LPS in amniotic epithelial cells and exerts potassium-dependent antibacterial activity against Gram-positive and Gram-negative bacteria by dissipating bacterial transmembrane potential; kept as a specialized non-core function. Supporting Evidence: PMID:23144825 This antibacterial protein, Ξ²(2)M, possessed potent antibacterial activity against pathogenic bacteria. |
| GO:0019885 antigen processing and presentation of endogenous peptide antigen via MHC class I | IGI PMID:24643698 The WT hemochromatosis protein HFE inhibits CD8βΊ T-lymphocyt... | ACCEPT | Summary: B2M is required for MHC class I presentation of endogenous peptide antigens to CD8+ T cells. Reason: B2M is an essential structural subunit required for folding, peptide loading, and surface expression of MHC class I molecules that present endogenous peptides to CD8+ T lymphocytes (PMID:24643698). Supporting Evidence: PMID:24643698 MHC class I (MHC I) antigen presentation is a ubiquitous process by which cells present endogenous proteins to CD8(+) T lymphocytes during immune surveillance and response. |
| GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II | IBA GO_REF:0000033 | REMOVE | Summary: Over-propagated MHC class II annotation (antigen processing and presentation of exogenous peptide antigen via MHC class II) from PANTHER family PTN000460629. Reason: This IBA annotation was propagated from PANTHER node PTN000460629 (PTHR19944), which groups Ig-like C1-set domains across MHC class I and MHC class II chains (such as HLA-DRA, HLA-DRB1, HLA-DPB1, HLA-DMA, and HLA-DMB). B2M is exclusively the light chain of MHC class I and class I-like heterodimers and does not assemble with, bind, or traffic in MHC class II complexes. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000460629 Β· PTHR19944 ancestral node SUPPORTS SOURCE BUT NOT TARGET Propagated from MHC class II paralogs within PTHR19944; B2M is restricted to MHC class I/Ib/I-like heterodimers. |
| GO:0023026 MHC class II protein complex binding | IBA GO_REF:0000033 | REMOVE | Summary: Over-propagated MHC class II annotation (MHC class II protein complex binding) from PANTHER family PTN000460629. Reason: This IBA annotation was propagated from PANTHER node PTN000460629 (PTHR19944), which groups Ig-like C1-set domains across MHC class I and MHC class II chains (such as HLA-DRA, HLA-DRB1, HLA-DPB1, HLA-DMA, and HLA-DMB). B2M is exclusively the light chain of MHC class I and class I-like heterodimers and does not assemble with, bind, or traffic in MHC class II complexes. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000460629 Β· PTHR19944 ancestral node SUPPORTS SOURCE BUT NOT TARGET Propagated from HLA-DM/MHC class II paralogs within PTHR19944; B2M binds MHC class I and class I-like heavy chains. |
| GO:0030670 phagocytic vesicle membrane | TAS Reactome:R-HSA-1236965 | KEEP AS NON CORE | Summary: B2M is present in phagocytic vesicle membrane during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-1236965); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-1236965 Exogenous antigen loaded class I MHC molecules in phagosomes may be delivered to the surface by membrane recycling machinery. |
| GO:0030670 phagocytic vesicle membrane | TAS Reactome:R-HSA-8863973 | KEEP AS NON CORE | Summary: B2M is present in phagocytic vesicle membrane during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-8863973); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-8863973 Recycling endosome-localized R-SNARE protein like RAB11a, VAMP3, and VAMP8 dock with target phagosome membrane Q-SNARE protein SNAP23. |
| GO:0031901 early endosome membrane | TAS Reactome:R-HSA-182263 | KEEP AS NON CORE | Summary: B2M is present in early endosome membrane during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-182263); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-182263 Once the complex of Nef, major histocompatibility complex class I molecules, PACS-1 and AP-1 arrives at the endosome, the MHC I complex is targeted for degradation. |
| GO:0031901 early endosome membrane | TAS Reactome:R-HSA-182286 | KEEP AS NON CORE | Summary: B2M is present in early endosome membrane during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-182286); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-182286 The complex of Nef, major histocompatibility complex class I molecules, PACS-1 and AP-1 is transported from the trans-Golgi network to an endosome, where the MHC I complex will be degraded. |
| GO:0031902 late endosome membrane | IBA GO_REF:0000033 | REMOVE | Summary: Over-propagated MHC class II annotation (late endosome membrane) from PANTHER family PTN000460629. Reason: This IBA annotation was propagated from PANTHER node PTN000460629 (PTHR19944), which groups Ig-like C1-set domains across MHC class I and MHC class II chains (such as HLA-DRA, HLA-DRB1, HLA-DPB1, HLA-DMA, and HLA-DMB). B2M is exclusively the light chain of MHC class I and class I-like heterodimers and does not assemble with, bind, or traffic in MHC class II complexes. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000460629 Β· PTHR19944 ancestral node SUPPORTS SOURCE BUT NOT TARGET Propagated from MHC class II and HLA-DM paralogs within PTHR19944; B2M is a soluble luminal/extracellular beta chain without a transmembrane anchor. |
| GO:0031905 early endosome lumen | TAS Reactome:R-HSA-1236943 | KEEP AS NON CORE | Summary: B2M is present in early endosome lumen during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-1236943); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-1236943 Peptides generated by Cathepsin S or IRAP-mediated proteolysis in the endosomes are loaded onto MHC class I molecules, which are internalized and transported to early and late endosomal compartments where antigenic peptides can be loaded. |
| GO:0031905 early endosome lumen | TAS Reactome:R-HSA-1236954 | KEEP AS NON CORE | Summary: B2M is present in early endosome lumen during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-1236954); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-1236954 While it is established that cathepsin S is involved in antigen processing in endocytotic vesicles, it is less certain whether other proteases present in endocytic vesicles are also involved in generating the peptide fragments. |
| GO:0031905 early endosome lumen | TAS Reactome:R-HSA-1236964 | KEEP AS NON CORE | Summary: B2M is present in early endosome lumen during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-1236964); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-1236964 Peptide-loaded MHC class I complexes are transported by an undefined mechanism back to the cell surface for cross-presentation to T cells. |
| GO:0032398 MHC class Ib protein complex | IPI PMID:10429675 Structure of human histocompatibility leukocyte antigen (HLA... | ACCEPT | Summary: B2M is the invariant beta-chain subunit of non-classical MHC class Ib complexes (HLA-E, HLA-F, HLA-G). Reason: While PMID:10429675 structurally characterizes a classical MHC class Ia complex (HLA-Cw4 in PMID:10429675; HLA-A2 in PMID:10843695 and PMID:9892618), B2M is genuinely an obligate structural subunit of non-classical MHC class Ib complexes (HLA-E, HLA-F, HLA-G), so this term is accepted across all rows for consistency. Supporting Evidence: PMID:10429675 The crystal structure of the human class I major histocompatibility complex molecule, human histocompatibility leukocyte antigen (HLA)-Cw4, the ligand for a natural killer (NK) cell inhibitory receptor, has been determined, complexed with a nonameric consensus peptide (QYDDAVYKL). |
| GO:0032398 MHC class Ib protein complex | IPI PMID:10843695 The structure and stability of an HLA-A*0201/octameric tax p... | ACCEPT | Summary: B2M is the invariant beta-chain subunit of non-classical MHC class Ib complexes (HLA-E, HLA-F, HLA-G). Reason: While PMID:10843695 structurally characterizes a classical MHC class Ia complex (HLA-Cw4 in PMID:10429675; HLA-A2 in PMID:10843695 and PMID:9892618), B2M is genuinely an obligate structural subunit of non-classical MHC class Ib complexes (HLA-E, HLA-F, HLA-G), so this term is accepted across all rows for consistency. Supporting Evidence: PMID:10843695 The crystal structure of the human class I MHC molecule HLA-A2 complexed with of an octameric peptide, Tax8 (LFGYPVYV), from human T cell lymphotrophic virus-1 (HTLV-1) has been determined. |
| GO:0032398 MHC class Ib protein complex | IPI PMID:15718280 Crystal structure of HLA-G: a nonclassical MHC class I molec... | ACCEPT | Summary: B2M is the invariant beta-chain subunit of non-classical MHC class Ib complexes (HLA-E, HLA-F, HLA-G). Reason: Crystallographic and biophysical analyses in PMID:15718280 directly demonstrate that B2M is the invariant light-chain subunit of non-classical MHC class Ib complexes (HLA-G in PMID:15718280, HLA-F in PMID:28636952, and HLA-E in PMID:35705051). Supporting Evidence: PMID:15718280 To gain further insights into HLA-G function, we determined the 1.9-A structure of a monomeric HLA-G complexed to a natural endogenous peptide ligand from histone H2A (RIIPRHLQL). |
| GO:0032398 MHC class Ib protein complex | IPI PMID:28636952 Human Leukocyte Antigen F Presents Peptides and Regulates Im... | ACCEPT | Summary: B2M is the invariant beta-chain subunit of non-classical MHC class Ib complexes (HLA-E, HLA-F, HLA-G). Reason: Crystallographic and biophysical analyses in PMID:28636952 directly demonstrate that B2M is the invariant light-chain subunit of non-classical MHC class Ib complexes (HLA-G in PMID:15718280, HLA-F in PMID:28636952, and HLA-E in PMID:35705051). Supporting Evidence: PMID:28636952 The complex structure of peptide-loaded Ξ²2m-HLA-F bound to the inhibitory LIR1 revealed similarities to high-affinity recognition of the viral MHC-I mimic UL18 and a docking strategy that relies on contacts with HLA-F as well as Ξ²2m, thus precluding binding to HLA-F OCs. |
| GO:0032398 MHC class Ib protein complex | IPI PMID:35705051 Primary and secondary functions of HLA-E are determined by s... | ACCEPT | Summary: B2M is the invariant beta-chain subunit of non-classical MHC class Ib complexes (HLA-E, HLA-F, HLA-G). Reason: Crystallographic and biophysical analyses in PMID:35705051 directly demonstrate that B2M is the invariant light-chain subunit of non-classical MHC class Ib complexes (HLA-G in PMID:15718280, HLA-F in PMID:28636952, and HLA-E in PMID:35705051). Supporting Evidence: PMID:35705051 MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8+ T cells. |
| GO:0032398 MHC class Ib protein complex | IPI PMID:9892618 Structural evidence of T cell xeno-reactivity in the absence... | ACCEPT | Summary: B2M is the invariant beta-chain subunit of non-classical MHC class Ib complexes (HLA-E, HLA-F, HLA-G). Reason: While PMID:9892618 structurally characterizes a classical MHC class Ia complex (HLA-Cw4 in PMID:10429675; HLA-A2 in PMID:10843695 and PMID:9892618), B2M is genuinely an obligate structural subunit of non-classical MHC class Ib complexes (HLA-E, HLA-F, HLA-G), so this term is accepted across all rows for consistency. Supporting Evidence: PMID:9892618 To examine the mechanism of xeno-reactivity of AHIII12.2, we have determined the crystal structures of A2/p1049 and Db/p1027 to 2.5 A and 2.8 A resolution, respectively. |
| GO:0033572 transferrin transport | IDA PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | KEEP AS NON CORE | Summary: B2M participates in transferrin transport as the obligate structural beta chain of the iron-regulatory protein HFE. Reason: B2M heterodimerization with HFE is required for HFE folding, ER exit, and interaction with TFRC (TfR1) and TFR2 to regulate receptor-mediated transferrin endocytosis and cellular iron homeostasis (PMID:18353247); kept as non-core because the iron-regulatory activity resides in the HFE-TFRC/TFR2 complex while B2M provides structural stabilization. Supporting Evidence: PMID:18353247 The co-expression of HFE in cells expressing TfR2 led to increased affinity for diferric transferrin, increased transferrin-dependent iron uptake, and relative resistance to iron chelation. |
| GO:0034756 regulation of iron ion transport | IGI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | KEEP AS NON CORE | Summary: B2M participates in regulation of iron ion transport as the obligate structural beta chain of the iron-regulatory protein HFE. Reason: B2M heterodimerization with HFE is required for HFE folding, ER exit, and interaction with TFRC (TfR1) and TFR2 to regulate receptor-mediated transferrin endocytosis and cellular iron homeostasis (PMID:18353247); kept as non-core because the iron-regulatory activity resides in the HFE-TFRC/TFR2 complex while B2M provides structural stabilization. Supporting Evidence: PMID:18353247 The co-expression of HFE in cells expressing TfR2 led to increased affinity for diferric transferrin, increased transferrin-dependent iron uptake, and relative resistance to iron chelation. |
| GO:0034757 negative regulation of iron ion transport | IDA PMID:9465039 The hemochromatosis gene product complexes with the transfer... | KEEP AS NON CORE | Summary: B2M participates in negative regulation of iron ion transport as the obligate structural beta chain of the iron-regulatory protein HFE. Reason: B2M heterodimerization with HFE is required for HFE folding, ER exit, and interaction with TFRC (TfR1) and TFR2 to regulate receptor-mediated transferrin endocytosis and cellular iron homeostasis (PMID:9465039); kept as non-core because the iron-regulatory activity resides in the HFE-TFRC/TFR2 complex while B2M provides structural stabilization. Supporting Evidence: PMID:9465039 Addition of soluble wild-type HFE/beta2m heterodimers to cultured cells also decreased the apparent affinity of the TfR for its ligand under steady-state conditions, both in 293 cells and in HeLa cells. |
| GO:0035580 specific granule lumen | TAS Reactome:R-HSA-6798749 | KEEP AS NON CORE | Summary: B2M is present in specific granule lumen during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-6798749); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-6798749 Secondary (specific) granules are peroxidase-negative and rich in antimicrobial substances (Joiner et al. |
| GO:0042605 peptide antigen binding | IBA GO_REF:0000033 | REMOVE | Summary: Over-propagated IBA annotation for peptide antigen binding from MHC class II beta chains. Reason: Propagated via PANTHER PTN000460629 from MHC class II groove-forming chains. Within MHC class I complexes, the antigenic peptide-binding cleft is formed entirely by the alpha-1 and alpha-2 domains of the heavy chain, whereas B2M is a single Ig-like C1-set domain that underpins the alpha-1/alpha-2 platform without directly binding the antigenic peptide. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG ROLE CONFLATION Sources checked: PANTHER:PTN000460629 Β· PTHR19944 ancestral node SUPPORTS SOURCE BUT NOT TARGET Propagated from MHC class II groove-forming beta chains within PTHR19944; B2M lacks an antigen-binding groove domain and underpins the heavy-chain alpha-1/alpha-2 platform. |
| GO:0042612 MHC class I protein complex | IEA GO_REF:0000002 | ACCEPT | Summary: B2M is the obligate light-chain subunit of the MHC class I protein complex. Reason: B2M noncovalently associates with MHC class I alpha heavy chains to form the mature heterodimeric MHC class I complex (GO_REF:0000002). Supporting Evidence: file:human/B2M/B2M-uniprot.txt Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. |
| GO:0042612 MHC class I protein complex | NAS PMID:26248266 Breaking bad blood: Ξ²2-microglobulin as a pro-aging factor i... | ACCEPT | Summary: B2M is the obligate light-chain subunit of the MHC class I protein complex. Reason: PMID:26248266 is a News & Views commentary on PMID:26147761 with no abstract text in PubMed; B2M's identity as the invariant beta-chain subunit of the MHC class I protein complex is directly supported by PMID:26147761 and UniProtKB. Supporting Evidence: PMID:26248266 Breaking bad blood: Ξ²2-microglobulin as a pro-aging factor in blood. PMID:26147761 Here we identify Ξ²2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. file:human/B2M/B2M-uniprot.txt Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. |
| GO:0042612 MHC class I protein complex | TAS PMID:28213472 Ξ²(2)-Microglobulin participates in development of lung emphy... | ACCEPT | Summary: B2M is the obligate light-chain subunit of the MHC class I protein complex. Reason: B2M noncovalently associates with MHC class I alpha heavy chains to form the mature heterodimeric MHC class I complex (PMID:28213472). Supporting Evidence: PMID:28213472 Ξ²2-Microglobulin (Ξ²2M), the light chain of the major histocompatibility complex class I (MHC I), has been identified as a proaging factor and is involved in the pathogenesis of neurodegenerative disorders by driving cognitive and regenerative impairments. |
| GO:0042613 MHC class II protein complex | IBA GO_REF:0000033 | REMOVE | Summary: Over-propagated MHC class II annotation (MHC class II protein complex) from PANTHER family PTN000460629. Reason: This IBA annotation was propagated from PANTHER node PTN000460629 (PTHR19944), which groups Ig-like C1-set domains across MHC class I and MHC class II chains (such as HLA-DRA, HLA-DRB1, HLA-DPB1, HLA-DMA, and HLA-DMB). B2M is exclusively the light chain of MHC class I and class I-like heterodimers and does not assemble with, bind, or traffic in MHC class II complexes. Propagation Review Root cause: PROPAGATION BAD Failure modes: WRONG ORTHOLOG OR PARALOG COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000460629 Β· PTHR19944 ancestral node SUPPORTS SOURCE BUT NOT TARGET Propagated from MHC class II paralogs within PTHR19944; B2M is exclusively a subunit of MHC class I/Ib/I-like heterodimers. |
| GO:0042802 identical protein binding | IPI PMID:17108084 3D structure of amyloid protofilaments of beta2-microglobuli... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:17108084), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:17108084 We have combined solid-state NMR, x-ray fiber diffraction, and atomic force microscopy to reveal the 3D structure of amyloid protofilament-like fibrils formed by a 22-residue K3 peptide (Ser(20)-Lys(41)) of beta(2)-microglobulin, a protein responsible for dialysis-related amyloidosis. |
| GO:0042802 identical protein binding | IPI PMID:18579777 Systematic analysis of nucleation-dependent polymerization r... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:18579777), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:18579777 Using this approach, we have characterized the mechanism of the nucleation-dependent formation of beta(2)-microglobulin (beta(2)m) amyloid fibrils. |
| GO:0042802 identical protein binding | IPI PMID:19172750 A regulatable switch mediates self-association in an immunog... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:19172750), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:19172750 Beta-2 microglobulin (beta2m) is a globular protein that self-associates into fibrillar amyloid deposits in patients undergoing hemodialysis therapy. |
| GO:0042802 identical protein binding | IPI PMID:19564620 Ultrasonication-dependent production and breakdown lead to m... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:19564620), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:19564620 Here, combining these 2 opposing effects on beta(2)-microglobulin (beta2-m), a protein responsible for dialysis-related amyloidosis, we present that ultrasonication pulses are useful for preparing monodispersed amyloid fibrils of minimal size with an average molecular weight of approximately 1,660,000 (140-mer). |
| GO:0042802 identical protein binding | IPI PMID:20826442 Protein-induced photophysical changes to the amyloid indicat... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:20826442), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:20826442 Here, we report the co-crystal structures of ThT with two alternative states of Ξ²-2 microglobulin (Ξ²2m); one monomeric, the other an amyloid-like oligomer. |
| GO:0042802 identical protein binding | IPI PMID:21131979 Ξ²β-microglobulin forms three-dimensional domain-swapped amyl... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:21131979), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:21131979 Here we show that Ξ²βm can oligomerize and fibrillize via three-dimensional domain swapping. Isolating a covalently bound, domain-swapped dimer from Ξ²βm oligomers on the pathway to fibrils, we were able to determine its crystal structure. |
| GO:0042802 identical protein binding | IPI PMID:21220305 Atomic structure of a nanobody-trapped domain-swapped dimer ... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:21220305), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:21220305 The crystal structure of ΞN6Ξ²2m in complex with one of these nanobodies (Nb24) identifies domain swapping as a plausible mechanism of self-association of this amyloidogenic protein. |
| GO:0042802 identical protein binding | IPI PMID:21569201 D-strand perturbation and amyloid propensity in beta-2 micro... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:21569201), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:21569201 Human beta-2 microglobulin (Ξ²2m) displays a typical immunoglobulin fold and is known to be amyloidogenic in vivo. |
| GO:0042802 identical protein binding | IPI PMID:22289140 A recurrent D-strand association interface is observed in Ξ²-... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:22289140), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:22289140 The X-ray structures of DIMC20 and DIMC50 show that the two engineered dimers form a tetrameric assembly; for both tetrameric species, the noncovalent association interface is based on the interaction of facing Ξ²2m D-strands and is conserved. |
| GO:0042802 identical protein binding | IPI PMID:22575645 Fibrillogenic propensity of the GroEL apical domain: a Janus... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (identical protein binding) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:22575645), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:22575645 We also found, however, that despite its fibrillation propensity, the apical domain exhibits a pronounced inhibitory effect on the fibril growth of Ξ²(2)-microglobulin. |
| GO:0042803 protein homodimerization activity | IPI PMID:28468825 Small molecule-mediated inhibition of Ξ²-2-microglobulin-base... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (protein homodimerization activity) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:28468825), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:28468825 Using ion mobility mass spectrometry, we show that both inhibitors promote the compaction of the initially formed Ξ²2m dimer, which causes the formation of other off-pathway and amyloid-incompetent oligomers that are isomeric with amyloid-competent oligomers in some cases. |
| GO:0042824 MHC class I peptide loading complex | IDA PMID:21263072 Distinct functions for the glycans of tapasin and heavy chai... | ACCEPT | Summary: B2M-bound MHC class I heavy chains are core clients assembled within the ER peptide-loading complex. Reason: Biochemical and cryo-EM structural analyses (PMID:21263072) show that heterodimers of MHC class I heavy chain and B2M are recruited into the multiprotein ER peptide-loading complex (with tapasin, ERp57/PDIA3, calreticulin, and TAP1/TAP2) for peptide proofreading and loading. Supporting Evidence: PMID:21263072 Furthermore, the ERp57 binding site and the glycan of tapasin enhance Ξ²(2)m and MHC class I heavy (H) chain recruitment to the PLC, with the ERp57 binding site having the dominant effect. |
| GO:0042824 MHC class I peptide loading complex | IDA PMID:35948544 Molecular basis of MHC I quality control in the peptide load... | ACCEPT | Summary: B2M-bound MHC class I heavy chains are core clients assembled within the ER peptide-loading complex. Reason: Biochemical and cryo-EM structural analyses (PMID:35948544) show that heterodimers of MHC class I heavy chain and B2M are recruited into the multiprotein ER peptide-loading complex (with tapasin, ERp57/PDIA3, calreticulin, and TAP1/TAP2) for peptide proofreading and loading. Supporting Evidence: PMID:35948544 Here, we determine the multi-chaperone-client interaction network of the peptide loading complex (PLC) and report the PLC editing module structure by cryogenic electron microscopy at 3.7 Γ
resolution. |
| GO:0045087 innate immune response | IDA PMID:23144825 Novel antibacterial activity of Ξ²(2)-microglobulin in human ... | KEEP AS NON CORE | Summary: Soluble B2M in human amniotic fluid exhibits potassium-dependent antibacterial activity (innate immune response). Reason: PMID:23144825 demonstrated that soluble B2M isolated from human amniotic fluid is upregulated by LPS in amniotic epithelial cells and exerts potassium-dependent antibacterial activity against Gram-positive and Gram-negative bacteria by dissipating bacterial transmembrane potential; kept as a specialized non-core function. Supporting Evidence: PMID:23144825 This antibacterial protein, Ξ²(2)M, possessed potent antibacterial activity against pathogenic bacteria. |
| GO:0048260 positive regulation of receptor-mediated endocytosis | IGI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | KEEP AS NON CORE | Summary: B2M participates in positive regulation of receptor-mediated endocytosis as the obligate structural beta chain of the iron-regulatory protein HFE. Reason: B2M heterodimerization with HFE is required for HFE folding, ER exit, and interaction with TFRC (TfR1) and TFR2 to regulate receptor-mediated transferrin endocytosis and cellular iron homeostasis (PMID:18353247); kept as non-core because the iron-regulatory activity resides in the HFE-TFRC/TFR2 complex while B2M provides structural stabilization. Supporting Evidence: PMID:18353247 The co-expression of HFE in cells expressing TfR2 led to increased affinity for diferric transferrin, increased transferrin-dependent iron uptake, and relative resistance to iron chelation. |
| GO:0048261 negative regulation of receptor-mediated endocytosis | IDA PMID:9465039 The hemochromatosis gene product complexes with the transfer... | KEEP AS NON CORE | Summary: B2M participates in negative regulation of receptor-mediated endocytosis as the obligate structural beta chain of the iron-regulatory protein HFE. Reason: B2M heterodimerization with HFE is required for HFE folding, ER exit, and interaction with TFRC (TfR1) and TFR2 to regulate receptor-mediated transferrin endocytosis and cellular iron homeostasis (PMID:9465039); kept as non-core because the iron-regulatory activity resides in the HFE-TFRC/TFR2 complex while B2M provides structural stabilization. Supporting Evidence: PMID:9465039 Addition of soluble wild-type HFE/beta2m heterodimers to cultured cells also decreased the apparent affinity of the TfR for its ligand under steady-state conditions, both in 293 cells and in HeLa cells. |
| GO:0050680 negative regulation of epithelial cell proliferation | IDA PMID:28213472 Ξ²(2)-Microglobulin participates in development of lung emphy... | KEEP AS NON CORE | Summary: Downstream organismal or aging-associated phenotype (negative regulation of epithelial cell proliferation) linked to systemic B2M accumulation or MHC class I signaling. Reason: Reflects downstream organismal, neurobiological, or pulmonary senescence phenotypes of circulating B2M accumulation or B2m deficiency (PMID:28213472) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:28213472 Exposure to recombinant human Ξ²2M and cigarette smoke extract (CSE) in vitro enhanced cellular senescence and inhibited proliferation of A549 cells, which was partially reversed by the presence of anti-Ξ²2M antibody. |
| GO:0050768 negative regulation of neurogenesis | IDA PMID:26147761 Ξ²2-microglobulin is a systemic pro-aging factor that impairs... | KEEP AS NON CORE | Summary: Downstream organismal or aging-associated phenotype (negative regulation of neurogenesis) linked to systemic B2M accumulation or MHC class I signaling. Reason: Reflects downstream organismal, neurobiological, or pulmonary senescence phenotypes of circulating B2M accumulation or B2m deficiency (PMID:26147761) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:26147761 Here we identify Ξ²2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. |
| GO:0050768 negative regulation of neurogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Downstream organismal or aging-associated phenotype (negative regulation of neurogenesis) linked to systemic B2M accumulation or MHC class I signaling. Reason: Reflects downstream organismal, neurobiological, or pulmonary senescence phenotypes of circulating B2M accumulation or B2m deficiency (GO_REF:0000107) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:26147761 Here we identify Ξ²2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. |
| GO:0050778 positive regulation of immune response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically inferred role in positive regulation of immune response downstream of MHC class I antigen presentation. Reason: By stabilizing MHC class I, CD1, and MR1 antigen-presenting complexes on the cell surface, B2M is essential for T cell activation and downstream adaptive immune responses (grounded by experimental annotations on descendant nodes including B2M/B2m). Supporting Evidence: file:human/B2M/B2M-uniprot.txt Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. |
| GO:0050829 defense response to Gram-negative bacterium | IDA PMID:23144825 Novel antibacterial activity of Ξ²(2)-microglobulin in human ... | KEEP AS NON CORE | Summary: Soluble B2M in human amniotic fluid exhibits potassium-dependent antibacterial activity (defense response to Gram-negative bacterium). Reason: PMID:23144825 demonstrated that soluble B2M isolated from human amniotic fluid is upregulated by LPS in amniotic epithelial cells and exerts potassium-dependent antibacterial activity against Gram-positive and Gram-negative bacteria by dissipating bacterial transmembrane potential; kept as a specialized non-core function. Supporting Evidence: PMID:23144825 The antibacterial activity of the purified protein was then assayed against L. monocytogenes and Escherichia coli, and was found to potently inhibit the growth of both organisms (Fig. 2). |
| GO:0050830 defense response to Gram-positive bacterium | IDA PMID:23144825 Novel antibacterial activity of Ξ²(2)-microglobulin in human ... | KEEP AS NON CORE | Summary: Soluble B2M in human amniotic fluid exhibits potassium-dependent antibacterial activity (defense response to Gram-positive bacterium). Reason: PMID:23144825 demonstrated that soluble B2M isolated from human amniotic fluid is upregulated by LPS in amniotic epithelial cells and exerts potassium-dependent antibacterial activity against Gram-positive and Gram-negative bacteria by dissipating bacterial transmembrane potential; kept as a specialized non-core function. Supporting Evidence: PMID:23144825 The antibacterial activity of the purified protein was then assayed against L. monocytogenes and Escherichia coli, and was found to potently inhibit the growth of both organisms (Fig. 2). |
| GO:0050870 positive regulation of T cell activation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically inferred role in positive regulation of T cell activation downstream of MHC class I antigen presentation. Reason: By stabilizing MHC class I, CD1, and MR1 antigen-presenting complexes on the cell surface, B2M is essential for T cell activation and downstream adaptive immune responses (grounded by experimental annotations on descendant nodes including B2M/B2m). Supporting Evidence: file:human/B2M/B2M-uniprot.txt Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. |
| GO:0051289 protein homotetramerization | IPI PMID:28468825 Small molecule-mediated inhibition of Ξ²-2-microglobulin-base... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (protein homotetramerization) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:28468825), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:28468825 Using ion mobility mass spectrometry, we show that both inhibitors promote the compaction of the initially formed Ξ²2m dimer, which causes the formation of other off-pathway and amyloid-incompetent oligomers that are isomeric with amyloid-competent oligomers in some cases. |
| GO:0055038 recycling endosome membrane | TAS Reactome:R-HSA-8863973 | KEEP AS NON CORE | Summary: B2M is present in recycling endosome membrane during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-8863973); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-8863973 Recycling endosome-localized R-SNARE protein like RAB11a, VAMP3, and VAMP8 dock with target phagosome membrane Q-SNARE protein SNAP23. |
| GO:0061844 antimicrobial humoral immune response mediated by antimicrobial peptide | IDA PMID:23144825 Novel antibacterial activity of Ξ²(2)-microglobulin in human ... | KEEP AS NON CORE | Summary: Soluble B2M in human amniotic fluid exhibits potassium-dependent antibacterial activity (antimicrobial humoral immune response mediated by antimicrobial peptide). Reason: PMID:23144825 demonstrated that soluble B2M isolated from human amniotic fluid is upregulated by LPS in amniotic epithelial cells and exerts potassium-dependent antibacterial activity against Gram-positive and Gram-negative bacteria by dissipating bacterial transmembrane potential; kept as a specialized non-core function. Supporting Evidence: PMID:23144825 This antibacterial protein, Ξ²(2)M, possessed potent antibacterial activity against pathogenic bacteria. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: B2M is present in extracellular exosome during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (PMID:19056867); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: PMID:19056867 Here, we used LC-MS/MS to profile the proteome of human urinary exosomes. Overall, the analysis identified 1132 proteins unambiguously, including 177 that are represented on the Online Mendelian Inheritance in Man database of disease-related genes, suggesting that exosome analysis is a potential approach to discover urinary biomarkers. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: B2M is present in extracellular exosome during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (PMID:19199708); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: PMID:19199708 Using MudPIT (multidimensional protein identification technology) mass spectrometry, we catalogued 491 proteins in the exosome fraction of human parotid saliva. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: B2M is present in extracellular exosome during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (PMID:23533145); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: PMID:23533145 Using expressed prostatic secretions in urine (EPS-urine), exosome preparations were characterized by a shotgun proteomics procedure. In pooled EPS-urine exosome samples, ~900 proteins were detected. |
| GO:0071222 cellular response to lipopolysaccharide | IDA PMID:23144825 Novel antibacterial activity of Ξ²(2)-microglobulin in human ... | KEEP AS NON CORE | Summary: Soluble B2M in human amniotic fluid is transcriptionally upregulated in response to bacterial lipopolysaccharide (cellular response to lipopolysaccharide). Reason: PMID:23144825 demonstrated that stimulation of WISH amniotic epithelial cells with bacterial endotoxin lipopolysaccharide (LPS) induces dose-dependent upregulation of B2M mRNA expression; kept as a specialized non-core function. Supporting Evidence: PMID:23144825 In addition, stimulation of WISH amniotic epithelial cells with the bacterial endotoxin lipopolysaccharide (LPS) induced dose-dependent upregulation of Ξ²(2)M mRNA expression. |
| GO:0071281 cellular response to iron ion | IGI PMID:18353247 HFE association with transferrin receptor 2 increases cellul... | KEEP AS NON CORE | Summary: B2M participates in cellular response to iron ion as the obligate structural beta chain of the iron-regulatory protein HFE. Reason: B2M heterodimerization with HFE is required for HFE folding, ER exit, and interaction with TFRC (TfR1) and TFR2 to regulate receptor-mediated transferrin endocytosis and cellular iron homeostasis (PMID:18353247); kept as non-core because the iron-regulatory activity resides in the HFE-TFRC/TFR2 complex while B2M provides structural stabilization. Supporting Evidence: PMID:18353247 The co-expression of HFE in cells expressing TfR2 led to increased affinity for diferric transferrin, increased transferrin-dependent iron uptake, and relative resistance to iron chelation. |
| GO:0071316 cellular response to nicotine | IMP PMID:28213472 Ξ²(2)-Microglobulin participates in development of lung emphy... | KEEP AS NON CORE | Summary: Downstream pulmonary senescence phenotype (cellular response to nicotine) linked to extracellular B2M exposure in alveolar epithelial cells. Reason: Reflects a downstream pulmonary epithelial senescence phenotype induced by cigarette smoke extract and elevated B2M in A549 cells (PMID:28213472) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:28213472 Exposure to recombinant human Ξ²2M and cigarette smoke extract (CSE) in vitro enhanced cellular senescence and inhibited proliferation of A549 cells, which was partially reversed by the presence of anti-Ξ²2M antibody. |
| GO:1904724 tertiary granule lumen | TAS Reactome:R-HSA-6798745 | KEEP AS NON CORE | Summary: B2M is present in tertiary granule lumen during endocytic recycling, cross-presentation, or vesicular/exosomal release. Reason: Cell-surface MHC class I-B2M complexes and soluble B2M enter endosomal, phagosomal, granule, and exosomal compartments (Reactome:R-HSA-6798745); this reflects valid trafficking and vesicular release downstream of B2M's core structural role. Supporting Evidence: Reactome:R-HSA-6798745 Tertiary (gelatinase) granules are part of a continuum of peroxidase-negative granules formed in myelocytes, metamyelocytes, band cells and segmented neutrophils. |
| GO:1990000 amyloid fibril formation | IDA PMID:28468825 Small molecule-mediated inhibition of Ξ²-2-microglobulin-base... | KEEP AS NON CORE | Summary: Pathological self-association and amyloidogenesis of B2M (amyloid fibril formation) in dialysis-related amyloidosis. Reason: In chronic renal failure and in vitro biophysical assays (PMID:28468825), elevated or destabilized B2M undergoes Cu(II)-, acid-, or truncation-induced domain swapping and self-association into homodimers, homotetramers, oligomers, and amyloid fibrils; kept as non-core because native physiological B2M functions as a monomer heterodimerized with heavy chains. Supporting Evidence: PMID:28468825 Using ion mobility mass spectrometry, we show that both inhibitors promote the compaction of the initially formed Ξ²2m dimer, which causes the formation of other off-pathway and amyloid-incompetent oligomers that are isomeric with amyloid-competent oligomers in some cases. |
| GO:1990712 HFE-transferrin receptor complex | IDA PMID:9990067 Association of HFE protein with transferrin receptor in cryp... | ACCEPT | Summary: B2M is an obligate subunit of the HFE-B2M heterodimer that complexes with transferrin receptor (TFRC). Reason: Co-immunoprecipitation and immunocytochemical studies in human duodenal crypt enterocytes and placenta (PMID:9990067) demonstrate that HFE physically associates with B2M and transferrin receptor (TFRC) in a ternary complex. Supporting Evidence: PMID:9990067 Western blots showed that, as was the case in human placenta, the HFE protein in crypt enterocytes is physically associated with the TfR and with beta2-microglobulin. |
| GO:2000774 positive regulation of cellular senescence | IDA PMID:28213472 Ξ²(2)-Microglobulin participates in development of lung emphy... | KEEP AS NON CORE | Summary: Downstream pulmonary senescence phenotype (positive regulation of cellular senescence) linked to extracellular B2M exposure in alveolar epithelial cells. Reason: Reflects a downstream pulmonary epithelial senescence phenotype induced by cigarette smoke extract and elevated B2M in A549 cells (PMID:28213472) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:28213472 Exposure to recombinant human Ξ²2M and cigarette smoke extract (CSE) in vitro enhanced cellular senescence and inhibited proliferation of A549 cells, which was partially reversed by the presence of anti-Ξ²2M antibody. |
| GO:2000978 negative regulation of forebrain neuron differentiation | IDA PMID:26147761 Ξ²2-microglobulin is a systemic pro-aging factor that impairs... | KEEP AS NON CORE | Summary: Downstream neurobiological aging phenotype (negative regulation of forebrain neuron differentiation) linked to systemic B2M accumulation. Reason: Reflects a downstream neurobiological aging phenotype of systemic circulating B2M accumulation in the adult hippocampus (PMID:26147761) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:26147761 Here we identify Ξ²2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. |
| GO:2000978 negative regulation of forebrain neuron differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Downstream neurobiological aging phenotype (negative regulation of forebrain neuron differentiation) linked to systemic B2M accumulation. Reason: Reflects a downstream neurobiological aging phenotype of systemic circulating B2M accumulation in the adult hippocampus (GO_REF:0000107, supported by PMID:26147761) rather than a direct cell-autonomous molecular function of B2M. Supporting Evidence: PMID:26147761 Here we identify Ξ²2-microglobulin (B2M), a component of major histocompatibility complex class 1 (MHC I) molecules, as a circulating factor that negatively regulates cognitive and regenerative function in the adult hippocampus in an age-dependent manner. |
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Download this section (compressed HTML)Q: How is the stoichiometric supply of nascent B2M partitioned in the endoplasmic reticulum among competing heavy-chain partners (classical HLA-A/B/C, non-classical HLA-E/F/G, CD1a-d, MR1, HFE, and FCGRT/FcRn) under basal versus interferon-stimulated conditions?
Suggested experts: Robert Tampe, Pamela J. Bjorkman, Jamie Rossjohn
Q: By what molecular mechanism does elevated circulating soluble B2M in aging plasma impair adult hippocampal neurogenesis and synaptic plasticityβvia exchange onto cell-surface neuronal MHC class I heavy chains or via an MHC class I-independent receptor?
Suggested experts: Saul A. Villeda, Tony Wyss-Coray
Experiment: Perform pulse-chase metabolic labeling and quantitative co-immunoprecipitation mass spectrometry of newly synthesized B2M complexes in primary human endothelial and epithelial cells across graded IFN-gamma doses with and without B2M overexpression.
Hypothesis: Cytokine-induced upregulation of classical MHC class Ia heavy chains alters the relative ER assembly flux of B2M into non-classical receptors (FCGRT/FcRn, HFE, and MR1) when B2M levels become limiting.
Type: Pulse-chase co-immunoprecipitation and quantitative mass spectrometry
Experiment: Use hydrogen-deuterium exchange mass spectrometry (HDX-MS) and native ion-mobility mass spectrometry to compare monomer dissociation rates and D-strand conformational fluctuations of wild-type versus pathologically truncated (DeltaN6) and hereditary amyloidogenic (D76N) B2M.
Hypothesis: Allosteric stabilization of the native B2M monomer-heavy chain interface prevents shedding of free amyloidogenic B2M and inhibits Cu(II)- or DeltaN6-nucleated fibrillogenesis.
Type: HDX-MS and native ion-mobility mass spectrometry
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