ITGAM encodes integrin alpha-M (CD11b), the alpha subunit of the leukocyte integrin alphaM-beta2 (Mac-1), also known as complement receptor 3 (CR3). It is a single-pass type I membrane glycoprotein that pairs non-covalently with ITGB2 (CD18) and is expressed on neutrophils, monocytes, macrophages, microglia, NK cells and subsets of lymphocytes, with reserve pools in neutrophil granule membranes that are mobilised to the cell surface on activation. The inserted von Willebrand factor A-like (alphaI) domain of CD11b carries a metal ion-dependent adhesion site that directly binds the C3d moiety of the complement opsonin iC3b, so CR3 recognises iC3b-coated microbes, apoptotic cells, immune complexes and other complement-tagged material and drives their phagocytosis. CR3 is also a promiscuous adhesion receptor that binds ICAM-1, JAM-3, Thy-1, fibrinogen, factor X and extracellular matrix proteins, mediating firm adhesion of activated leukocytes to endothelium, platelets and matrix, transmigration, and outside-in signalling that influences degranulation, superoxide production, cytokine output and neutrophil apoptosis. In the central nervous system, microglial CR3 mediates engulfment of C3-tagged synapses during developmental synaptic refinement and has been implicated in microglial uptake of amyloid-beta and in microglia-driven neuronal death. The coding variant R77H (rs1143679), which impairs iC3b-mediated phagocytosis and adhesion, is associated with systemic lupus erythematosus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001540 amyloid-beta binding | IC GO_REF:0000111 | MARK AS OVER ANNOTATED | Summary: Inferred by curator from ISS amyloid-beta clearance/phagocytosis annotations. Reason: CR3 contributes to microglial uptake of Abeta-coated particles and fibrillar Abeta, partly via C3 opsonisation (iC3b is the CR3 ligand). The cited studies show antibody blockade/knockout effects on uptake but not direct binding of Abeta by CD11b, so a direct amyloid-beta binding MF overstates the evidence. Supporting Evidence: PMID:20199584 antibodies against CD11b or CD18 reduced the uptake of the artificial amyloid deposit by microglial cell showing that CR3 is involved in the mechanism. PMID:22438044 these results demonstrate that C3 and Mac-1 are involved in phagocytosis and clearance of fAΞ² by microglia |
| GO:0001774 microglial cell activation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Itgam (MAC1 KO reduces MPTP-induced microgliosis). Reason: MAC1-deficient microglia show reduced activation in the MPTP model; CR3 signaling contributes to microglial activation, but this is a context-dependent, disease-model phenotype rather than the core receptor function. Supporting Evidence: PMID:18981141 Both in vivo and in vitro morphological and Western blot studies demonstrated that MPTP/MPP(+) produced less microglia activation in MAC1(-/-) mice than MAC1(+/+) mice. |
| GO:0001851 complement component C3b binding | ISS GO_REF:0000024 | MODIFY | Summary: ISS from mouse; CR3 binding of a C3 fragment. Reason: CR3 binds the iC3b fragment through the alphaM I-domain; structural work shows the binding site lies in the C3d moiety and explains CR3 selectivity for iC3b over C3b. iC3b binding is the accurate term. Proposed replacements: complement component iC3b binding Supporting Evidence: PMID:7524101 A recombinant fragment representing the CR3 A-domain, a 200-amino acid region in the ectodomain of the CD11b subunit, bound to iC3b directly and in a divalent cation-dependent manner. PMID:24065820 We demonstrate that the C3d moiety of iC3b harbors the binding site for the CR3 Ξ±I domain, and our structure of the C3d:Ξ±I domain complex rationalizes the CR3 selectivity for iC3b. |
| GO:0001975 response to amphetamine | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara projection of a rodent "response to amphetamine" annotation onto human ITGAM. Reason: "response to amphetamine" annotations in rodents typically record expression or phenotype changes after an experimental treatment, not a function executed by the gene product. No evidence that ITGAM performs a step of a response to amphetamine process; projection of such response terms is uninformative for the CR3 receptor. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens |
| GO:0002430 complement receptor mediated signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Itgam (CR3/C3-dependent microglial engulfment of synapses). Reason: CR3 is a complement receptor, and ligation by iC3b triggers phagocytic and other downstream signaling (e.g. CR3 engagement modulates TLR7/8 cytokine output in human monocytes). Microglial CR3/C3 signaling mediates engulfment of developing synapses. Supporting Evidence: PMID:22632727 Taken together, these data demonstrate that phagocytic signaling through CR3 and its ligand C3 is one molecular mechanism by which microglia engulf RGC inputs. PMID:22586164 A 31% reduction was observed in the phagocytosis of iC3b opsonised sheep erythrocytes (sRBC(iC3b)) by 77H cells (p=0.003) PMID:8485905 It has important functions both as an adhesion molecule and a membrane receptor mediating recognition of diverse ligands such as intercellular adhesion molecule-1 (ICAM-1) and fixed iC3b. |
| GO:0002931 response to ischemia | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara projection of a rodent "response to ischemia" annotation onto human ITGAM. Reason: "response to ischemia" annotations in rodents typically record expression or phenotype changes after an experimental treatment, not a function executed by the gene product. No evidence that ITGAM performs a step of a response to ischemia process; projection of such response terms is uninformative for the CR3 receptor. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens |
| GO:0004895 cell adhesion receptor activity | IDA PMID:1980124 ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). | ACCEPT | Summary: IDA (contributes_to): Mac-1 (CD11b/CD18) acts as adhesion receptor for ICAM-1. Reason: Mac-1 mediates cell adhesion to ICAM-1 and other counter-receptors as an alphaM-beta2 heterodimer; contributes_to correctly reflects that the activity requires the CD18 partner. Supporting Evidence: PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. PMID:1980124 COS cells cotransfected with the alpha and beta chain cDNAs of Mac-1 or LFA-1 attach to immunoaffinity-purified ICAM-1 substrates |
| GO:0005178 integrin binding | NAS PMID:20199584 Complement receptor 3 (CD11b/CD18) is implicated in the elim... | KEEP AS NON CORE | Summary: Author-statement annotation; ITGAM pairs with the integrin beta-2 subunit ITGB2 to form Mac-1 (CR3). Reason: ITGAM is the alpha-M integrin subunit and pairs non-covalently with the beta-2 subunit ITGB2 to form Mac-1, as the integrin alphaM-beta2 complex annotation of this review records. Integrin binding is defined simply as binding to an integrin and is commonly applied to the pairing of alpha and beta subunits as well as to ligands of integrins, so the statement is true of ITGAM even though the cited paper does not test it. Subunit pairing is implied by complex membership and adds little, so the row is kept as non-core rather than removed. Supporting Evidence: PMID:20199584 antibodies against CD11b or CD18 reduced the uptake of the artificial amyloid deposit by microglial cell showing that CR3 is involved in the mechanism. PMID:2563162 consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000) |
| GO:0005515 protein binding | IPI PMID:12208882 The junctional adhesion molecule 3 (JAM-3) on human platelet... | MODIFY | Summary: IPI with ICAM1 (reference ligand in JAM-3 study). Reason: ICAM-1 is a well-established counter-receptor of Mac-1; the interaction is adhesion-receptor/ligand binding, better captured by cell adhesion molecule binding than generic protein binding. Proposed replacements: cell adhesion molecule binding Supporting Evidence: PMID:12208882 JAM-3 directly bound to Mac-1, and this binding was similar in its extent to the binding of ICAM-1 or fibrinogen, which both are known ligands for Mac-1 PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. |
| GO:0005515 protein binding | IPI PMID:12208882 The junctional adhesion molecule 3 (JAM-3) on human platelet... | MODIFY | Summary: IPI with JAM3 (JAM-C). Reason: JAM-3 on platelets directly binds Mac-1 as a counter-receptor mediating leukocyte-platelet adhesion; cell adhesion molecule binding is the informative term. Proposed replacements: cell adhesion molecule binding Supporting Evidence: PMID:12208882 JAM-3 directly bound to Mac-1, and this binding was similar in its extent to the binding of ICAM-1 or fibrinogen, which both are known ligands for Mac-1 PMID:12208882 provide evidence that JAM-3 is a novel counterreceptor for the integrin Mac-1 (CD11b/CD18) thereby playing a critical role for plateletβleukocyte interactions. |
| GO:0005515 protein binding | IPI PMID:15004192 Human Thy-1 (CD90) on activated endothelial cells is a count... | MODIFY | Summary: IPI with THY1 (CD90). Reason: Thy-1 on activated endothelium is a counter-receptor for Mac-1 in leukocyte adhesion; cell adhesion molecule binding is the informative term. Proposed replacements: cell adhesion molecule binding Supporting Evidence: PMID:15004192 we have identified the specific interaction between human Thy-1 and the leukocyte integrin Mac-1 (CD11b/CD18; alphaMbeta2) both in cellular systems and in purified form. |
| GO:0005515 protein binding | IPI PMID:15194813 JAM-C is a component of desmosomes and a ligand for CD11b/CD... | MODIFY | Summary: IPI with JAM3 (JAM-C) on epithelium. Reason: JAM-C specifically binds CD11b/CD18 as an epithelial ligand for neutrophil transepithelial migration. Proposed replacements: cell adhesion molecule binding Supporting Evidence: PMID:15194813 Additional experiments revealed specific binding of JAM-C to CD11b/CD18 and provided evidence of other epithelial ligands for CD11b/CD18. |
| GO:0005515 protein binding | IPI PMID:16246332 Interactions of DC-SIGN with Mac-1 and CEACAM1 regulate cont... | REMOVE | Summary: IPI with DC-SIGN (CD209). Reason: Here Mac-1 is the glycan-bearing ligand recognised by the C-type lectin DC-SIGN; generic protein binding conveys no ITGAM molecular function. The interaction is real but not a function of ITGAM. Supporting Evidence: PMID:16246332 DC maturation by neutrophils also requires cellular interactions that are mediated by binding of the DC-specific receptor DC-SIGN to Mac-1 on the neutrophil. |
| GO:0005515 protein binding | IPI PMID:21193407 Complement receptor Mac-1 is an adaptor for NB1 (CD177)-medi... | REMOVE | Summary: IPI with ITGB2 and CD177 (NB1). Reason: Generic protein binding is uninformative. Pairing with ITGB2 is captured by integrin alphaM-beta2 complex; the CD177 association (Mac-1 as adaptor for NB1-PR3 signaling) is captured by the neutrophil degranulation/superoxide regulation annotations. Supporting Evidence: PMID:21193407 However, when these integrins were presented as heterodimeric transmembrane proteins on transfected cells, only CD11b/CD18 (Mac-1)-transfected cells adhered to immobilized NB1 protein. PMID:21193407 establish the pivotal role of the NB1-Mac-1 receptor interaction for PR3-ANCA-mediated neutrophil activation. |
| GO:0005515 protein binding | IPI PMID:28939773 Pleiotrophin, a multifunctional cytokine and growth factor, ... | REMOVE | Summary: IPI with pleiotrophin (PTN). Reason: Generic protein binding is uninformative; Mac-1 acts as the receptor mediating macrophage adhesion and migration to PTN, which is captured by the adhesion receptor annotations. Supporting Evidence: PMID:28939773 Here, we identified the integrin Mac-1 (Ξ±MΞ²2, CD11b/CD18) as the receptor mediating macrophage adhesion and migration to PTN. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: High-throughput yeast two-hybrid hit from the HuRI binary interactome screen. Reason: Generic protein binding is uninformative. This Y2H partner (largely ER/membrane proteins without known relation to leukocyte integrin biology) does not indicate a specific molecular function; removal does not assert the interaction is false. Supporting Evidence: PMID:32296183 reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:38730209 Deletion of Tmem268 in mice suppresses anti-infectious immun... | REMOVE | Summary: IPI with TMEM268. Reason: Generic protein binding is uninformative; TMEM268 binds the CD11b C-terminus and protects it from lysosomal degradation, which is a regulation of ITGAM, not a molecular function of ITGAM. Supporting Evidence: PMID:38730209 Furthermore, the findings suggest that TMEM268 interacts with the C-terminus of CD11b and inhibits its degradation via the endosomalβlysosomal pathway. |
| GO:0005576 extracellular region | IDA PMID:25645918 Human neutrophils secrete bioactive paucimannosidic proteins... | MARK AS OVER ANNOTATED | Summary: IDA from neutrophil/sputum glycoproteomics. Reason: ITGAM is a type I transmembrane receptor; detection in sputum likely reflects shed membrane/granule material from neutrophils rather than a secreted functional pool. Not a meaningful location for the receptor function. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0005886 plasma membrane | IDA PMID:16301335 Specific integrin alpha and beta chain phosphorylations regu... | ACCEPT | Summary: Plasma membrane location. Reason: ITGAM is a single-pass type I plasma membrane receptor on leukocytes; consistent with experimental data and Reactome. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0005886 plasma membrane | IDA PMID:21193407 Complement receptor Mac-1 is an adaptor for NB1 (CD177)-medi... | ACCEPT | Summary: Plasma membrane location. Reason: ITGAM is a single-pass type I plasma membrane receptor on leukocytes; consistent with experimental data and Reactome. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0005886 plasma membrane | IDA PMID:28807980 CD177 modulates human neutrophil migration through activatio... | ACCEPT | Summary: Plasma membrane location. Reason: ITGAM is a single-pass type I plasma membrane receptor on leukocytes; consistent with experimental data and Reactome. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane location. Reason: ITGAM is a single-pass type I plasma membrane receptor on leukocytes; consistent with experimental data and Reactome. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202727 | ACCEPT | Summary: Plasma membrane location. Reason: ITGAM is a single-pass type I plasma membrane receptor on leukocytes; consistent with experimental data and Reactome. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2559439 | ACCEPT | Summary: Plasma membrane location. Reason: ITGAM is a single-pass type I plasma membrane receptor on leukocytes; consistent with experimental data and Reactome. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6788346 | ACCEPT | Summary: Plasma membrane location. Reason: ITGAM is a single-pass type I plasma membrane receptor on leukocytes; consistent with experimental data and Reactome. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798747 | ACCEPT | Summary: Plasma membrane location. Reason: ITGAM is a single-pass type I plasma membrane receptor on leukocytes; consistent with experimental data and Reactome. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6799350 | ACCEPT | Summary: Plasma membrane location. Reason: ITGAM is a single-pass type I plasma membrane receptor on leukocytes; consistent with experimental data and Reactome. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0006898 receptor-mediated endocytosis | ISS GO_REF:0000024 | MODIFY | Summary: ISS from mouse (CR3-dependent uptake of fibrillar Abeta). Reason: The cited mouse studies describe phagocytic uptake of particulate/fibrillar material by microglia via CR3, which is better described as phagocytosis (engulfment) than receptor-mediated endocytosis. Proposed replacements: phagocytosis, engulfment Supporting Evidence: PMID:22438044 these results demonstrate that C3 and Mac-1 are involved in phagocytosis and clearance of fAΞ² by microglia PMID:20199584 antibodies against CD11b or CD18 reduced the uptake of the artificial amyloid deposit by microglial cell showing that CR3 is involved in the mechanism. |
| GO:0006911 phagocytosis, engulfment | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse (CR3-dependent phagocytosis by microglia). Reason: Phagocytosis of complement (iC3b)-opsonised particles is the defining function of CR3; supported for human cells (R77H reduces iC3b-mediated phagocytosis) and for microglial engulfment of C3-tagged synapses in mouse. Supporting Evidence: PMID:24065820 recognizes iC3b on complement-opsonized objects, enabling their phagocytosis. PMID:22586164 A 31% reduction was observed in the phagocytosis of iC3b opsonised sheep erythrocytes (sRBC(iC3b)) by 77H cells (p=0.003) PMID:22632727 Taken together, these data demonstrate that phagocytic signaling through CR3 and its ligand C3 is one molecular mechanism by which microglia engulf RGC inputs. |
| GO:0007155 cell adhesion | IEA GO_REF:0000002 | ACCEPT | Summary: Cell adhesion. Reason: Mac-1 is a leukocyte adhesion receptor; general but correct. Supporting Evidence: PMID:2563162 The amino acid sequence for the human neutrophil alpha M subunit contains regions that are closely related to amino acid sequences of adhesion receptors belonging to the integrin family. PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. |
| GO:0007155 cell adhesion | TAS PMID:2563162 cDNA sequence for the alpha M subunit of the human neutrophi... | ACCEPT | Summary: Cell adhesion. Reason: Mac-1 is a leukocyte adhesion receptor; general but correct. Supporting Evidence: PMID:2563162 The amino acid sequence for the human neutrophil alpha M subunit contains regions that are closely related to amino acid sequences of adhesion receptors belonging to the integrin family. PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. |
| GO:0007159 leukocyte cell-cell adhesion | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction: leukocyte cell-cell adhesion. Reason: Mac-1 mediates adhesion of leukocytes to endothelial cells (ICAM-1), platelets (JAM-3) and dendritic cells. Supporting Evidence: PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. PMID:12208882 provide evidence that JAM-3 is a novel counterreceptor for the integrin Mac-1 (CD11b/CD18) thereby playing a critical role for plateletβleukocyte interactions. |
| GO:0007160 cell-matrix adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: Cell-matrix adhesion. Reason: Mac-1 mediates monocyte adhesion to extracellular matrix ligands such as TGFBIp and fibrinogen. Supporting Evidence: PMID:18083624 mediates monocytes adhesion under both static and flow conditions mainly through integrin alphaMbeta2. PMID:12208882 JAM-3 directly bound to Mac-1, and this binding was similar in its extent to the binding of ICAM-1 or fibrinogen, which both are known ligands for Mac-1 |
| GO:0007160 cell-matrix adhesion | IDA PMID:18083624 Transforming growth factor-beta-induced gene product, as a n... | ACCEPT | Summary: Cell-matrix adhesion. Reason: Mac-1 mediates monocyte adhesion to extracellular matrix ligands such as TGFBIp and fibrinogen. Supporting Evidence: PMID:18083624 mediates monocytes adhesion under both static and flow conditions mainly through integrin alphaMbeta2. PMID:12208882 JAM-3 directly bound to Mac-1, and this binding was similar in its extent to the binding of ICAM-1 or fibrinogen, which both are known ligands for Mac-1 |
| GO:0007229 integrin-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Integrin-mediated signaling pathway. Reason: Mac-1 ligation triggers outside-in integrin signaling (e.g. Src/ERK, FAK/Src downstream of CD11b). Supporting Evidence: PMID:28807980 CD177-driven cell activation enhanced surface Ξ²2 integrin expression and affinity, impaired internalization of integrin attachments, and resulted in ERK-mediated attenuation of chemokine signaling. PMID:18083624 mediates monocytes adhesion under both static and flow conditions mainly through integrin alphaMbeta2. |
| GO:0007229 integrin-mediated signaling pathway | NAS PMID:18083624 Transforming growth factor-beta-induced gene product, as a n... | ACCEPT | Summary: Integrin-mediated signaling pathway. Reason: Mac-1 ligation triggers outside-in integrin signaling (e.g. Src/ERK, FAK/Src downstream of CD11b). Supporting Evidence: PMID:28807980 CD177-driven cell activation enhanced surface Ξ²2 integrin expression and affinity, impaired internalization of integrin attachments, and resulted in ERK-mediated attenuation of chemokine signaling. PMID:18083624 mediates monocytes adhesion under both static and flow conditions mainly through integrin alphaMbeta2. |
| GO:0008305 integrin complex | IEA GO_REF:0000120 | ACCEPT | Summary: Integrin complex. Reason: ITGAM is the alpha subunit of the alphaM-beta2 integrin heterodimer; the more specific integrin alphaM-beta2 complex term is also annotated. Supporting Evidence: PMID:2563162 consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000) file:human/ITGAM/ITGAM-uniprot.txt Heterodimer of an alpha and a beta subunit. |
| GO:0008305 integrin complex | TAS PMID:2563162 cDNA sequence for the alpha M subunit of the human neutrophi... | ACCEPT | Summary: Integrin complex. Reason: ITGAM is the alpha subunit of the alphaM-beta2 integrin heterodimer; the more specific integrin alphaM-beta2 complex term is also annotated. Supporting Evidence: PMID:2563162 consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000) file:human/ITGAM/ITGAM-uniprot.txt Heterodimer of an alpha and a beta subunit. |
| GO:0009612 response to mechanical stimulus | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara projection of a rodent "response to mechanical stimulus" annotation onto human ITGAM. Reason: "response to mechanical stimulus" annotations in rodents typically record expression or phenotype changes after an experimental treatment, not a function executed by the gene product. No evidence that ITGAM performs a step of a response to mechanical stimulus process; projection of such response terms is uninformative for the CR3 receptor. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens |
| GO:0009897 external side of plasma membrane | NAS PMID:20199584 Complement receptor 3 (CD11b/CD18) is implicated in the elim... | ACCEPT | Summary: NAS: external side of plasma membrane. Reason: The ligand-binding ectodomain of this type I membrane receptor faces the extracellular side of the plasma membrane. Supporting Evidence: PMID:20199584 antibodies against CD11b or CD18 reduced the uptake of the artificial amyloid deposit by microglial cell showing that CR3 is involved in the mechanism. file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0009986 cell surface | HDA PMID:23981064 Mycobacterium tuberculosis infection of human dendritic cell... | ACCEPT | Summary: Cell surface. Reason: CD11b is a cell surface receptor on leukocytes and microglia. Supporting Evidence: PMID:23981064 A corresponding reduction in the Ξ±L (CD11a) and Ξ±M (CD11b) subunits that associate with integrin Ξ² 2 was also observed. file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0009986 cell surface | IBA GO_REF:0000033 | ACCEPT | Summary: Cell surface. Reason: CD11b is a cell surface receptor on leukocytes and microglia. Supporting Evidence: PMID:23981064 A corresponding reduction in the Ξ±L (CD11a) and Ξ±M (CD11b) subunits that associate with integrin Ξ² 2 was also observed. file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0009986 cell surface | IDA PMID:19234460 A point mutation in KINDLIN3 ablates activation of three int... | ACCEPT | Summary: Cell surface. Reason: CD11b is a cell surface receptor on leukocytes and microglia. Supporting Evidence: PMID:23981064 A corresponding reduction in the Ξ±L (CD11a) and Ξ±M (CD11b) subunits that associate with integrin Ξ² 2 was also observed. file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0009986 cell surface | IEA GO_REF:0000120 | ACCEPT | Summary: Cell surface. Reason: CD11b is a cell surface receptor on leukocytes and microglia. Supporting Evidence: PMID:23981064 A corresponding reduction in the Ξ±L (CD11a) and Ξ±M (CD11b) subunits that associate with integrin Ξ² 2 was also observed. file:human/ITGAM/ITGAM-uniprot.txt SUBCELLULAR LOCATION: Cell membrane |
| GO:0010668 ectodermal cell differentiation | IEP PMID:23154389 Regulation of endodermal differentiation of human embryonic ... | MARK AS OVER ANNOTATED | Summary: IEP from hESC differentiation integrin/ECM study. Reason: IEP records only an expression change during in vitro stem-cell differentiation; ITGAM is a myeloid leukocyte integrin and there is no evidence that it performs a step of ectodermal cell differentiation. Supporting Evidence: PMID:23154389 From this screen we identified fibronectin (FN) and vitronectin (VTN) |
| GO:0030900 forebrain development | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS from mouse (CD11b required for developmental hippocampal neuronal death). Reason: Microglial CD11b/DAP12-driven superoxide promotes developmental neuronal apoptosis; this is a microglial effector role, and the broad "forebrain development" process overstates the contribution of ITGAM. Supporting Evidence: PMID:18685038 we show that DAP12 and CD11b control the production of microglial superoxide ions, which kill the neurons. PMID:18685038 We demonstrate that developmental apoptosis decreases in mice deficient for CD11b or DAP12. |
| GO:0031072 heat shock protein binding | IPI PMID:12496435 Identification of heat shock protein 60 as the ligand on His... | KEEP AS NON CORE | Summary: IPI: CR3 binds Histoplasma capsulatum hsp60. Reason: Purified CR3 recognised fungal hsp60 on the yeast surface, mediating macrophage attachment. This reflects CR3 acting as a pattern-recognition/attachment receptor for a microbial ligand, not binding of host chaperones; retained as non-core. Supporting Evidence: PMID:12496435 Thus, Hc hsp60 appears to be a major ligand that mediates attachment of Hc to Mphi CD11/CD18, whereas DC recognize Hc via a different ligand(s). |
| GO:0032355 response to estradiol | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara projection of a rodent "response to estradiol" annotation onto human ITGAM. Reason: "response to estradiol" annotations in rodents typically record expression or phenotype changes after an experimental treatment, not a function executed by the gene product. No evidence that ITGAM performs a step of a response to estradiol process; projection of such response terms is uninformative for the CR3 receptor. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens |
| GO:0032930 positive regulation of superoxide anion generation | IGI PMID:21193407 Complement receptor Mac-1 is an adaptor for NB1 (CD177)-medi... | KEEP AS NON CORE | Summary: Positive regulation of superoxide anion generation. Reason: CD11b is required for NB1/PR3-ANCA-induced superoxide production in human neutrophils and for microglial superoxide production in mouse; a downstream signaling consequence of CR3 engagement. Supporting Evidence: PMID:21193407 Stimulation with NB1-activating mAb triggered degranulation and superoxide production in mNB1(pos)/mPR3(high) neutrophils, and this effect was reduced using blocking antibodies to CD11b. PMID:18685038 we show that DAP12 and CD11b control the production of microglial superoxide ions, which kill the neurons. |
| GO:0032930 positive regulation of superoxide anion generation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Positive regulation of superoxide anion generation. Reason: CD11b is required for NB1/PR3-ANCA-induced superoxide production in human neutrophils and for microglial superoxide production in mouse; a downstream signaling consequence of CR3 engagement. Supporting Evidence: PMID:21193407 Stimulation with NB1-activating mAb triggered degranulation and superoxide production in mNB1(pos)/mPR3(high) neutrophils, and this effect was reduced using blocking antibodies to CD11b. PMID:18685038 we show that DAP12 and CD11b control the production of microglial superoxide ions, which kill the neurons. |
| GO:0033631 cell-cell adhesion mediated by integrin | IDA PMID:1980124 ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). | ACCEPT | Summary: Cell-cell adhesion mediated by integrin. Reason: Mac-1 mediates adhesion between stimulated neutrophils and activated endothelial cells via ICAM-1. Supporting Evidence: PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. |
| GO:0033631 cell-cell adhesion mediated by integrin | IEA GO_REF:0000117 | ACCEPT | Summary: Cell-cell adhesion mediated by integrin. Reason: Mac-1 mediates adhesion between stimulated neutrophils and activated endothelial cells via ICAM-1. Supporting Evidence: PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. |
| GO:0034113 heterotypic cell-cell adhesion | IEA GO_REF:0000107 | ACCEPT | Summary: Heterotypic cell-cell adhesion (Ensembl projection). Reason: Mac-1 mediates adhesion of leukocytes to other cell types (endothelial cells via ICAM-1, platelets via JAM-3). Supporting Evidence: PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. PMID:12208882 provide evidence that JAM-3 is a novel counterreceptor for the integrin Mac-1 (CD11b/CD18) thereby playing a critical role for plateletβleukocyte interactions. |
| GO:0034688 integrin alphaM-beta2 complex | IBA GO_REF:0000033 | ACCEPT | Summary: Integrin alphaM-beta2 complex. Reason: ITGAM pairs with ITGB2 to form Mac-1/CR3. Supporting Evidence: PMID:2563162 consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000) PMID:1980124 COS cells cotransfected with the alpha and beta chain cDNAs of Mac-1 or LFA-1 attach to immunoaffinity-purified ICAM-1 substrates |
| GO:0034688 integrin alphaM-beta2 complex | IDA PMID:1980124 ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). | ACCEPT | Summary: Integrin alphaM-beta2 complex. Reason: ITGAM pairs with ITGB2 to form Mac-1/CR3. Supporting Evidence: PMID:2563162 consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000) PMID:1980124 COS cells cotransfected with the alpha and beta chain cDNAs of Mac-1 or LFA-1 attach to immunoaffinity-purified ICAM-1 substrates |
| GO:0034688 integrin alphaM-beta2 complex | IPI PMID:18083624 Transforming growth factor-beta-induced gene product, as a n... | ACCEPT | Summary: Integrin alphaM-beta2 complex. Reason: ITGAM pairs with ITGB2 to form Mac-1/CR3. Supporting Evidence: PMID:2563162 consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000) PMID:1980124 COS cells cotransfected with the alpha and beta chain cDNAs of Mac-1 or LFA-1 attach to immunoaffinity-purified ICAM-1 substrates |
| GO:0034688 integrin alphaM-beta2 complex | ISS GO_REF:0000024 | ACCEPT | Summary: Integrin alphaM-beta2 complex. Reason: ITGAM pairs with ITGB2 to form Mac-1/CR3. Supporting Evidence: PMID:2563162 consists of two noncovalently associated subunits, designated alpha M (Mac-1 alpha, Mol alpha, or CD11b; Mr, 170,000) and beta (Mac-1 beta, Mol beta, or CD18; Mr, 100,000) PMID:1980124 COS cells cotransfected with the alpha and beta chain cDNAs of Mac-1 or LFA-1 attach to immunoaffinity-purified ICAM-1 substrates |
| GO:0035579 specific granule membrane | TAS Reactome:R-HSA-6799350 | ACCEPT | Summary: Reactome TAS: specific granule membrane. Reason: CD11b/CD18 is stored in neutrophil granule membranes and mobilised to the surface upon activation (Reactome exocytosis of specific granule membrane proteins). Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens |
| GO:0038023 signaling receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: signaling receptor activity. Reason: Integrin heterodimers including Mac-1 transduce ligand binding into outside-in signals; the specific receptor activity of CR3 is complement component iC3b receptor activity (contributed with ITGB2). Supporting Evidence: PMID:8485905 It has important functions both as an adhesion molecule and a membrane receptor mediating recognition of diverse ligands such as intercellular adhesion molecule-1 (ICAM-1) and fixed iC3b. PMID:28807980 CD177-driven cell activation enhanced surface Ξ²2 integrin expression and affinity, impaired internalization of integrin attachments, and resulted in ERK-mediated attenuation of chemokine signaling. |
| GO:0038024 cargo receptor activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS from mouse (CR3 in uptake of fibrillar Abeta). Reason: GO cargo receptor activity describes receptors that select cargo for vesicular transport. CR3 is a phagocytic complement receptor; its role in Abeta uptake is better captured by complement component iC3b receptor activity and phagocytosis, engulfment. Supporting Evidence: PMID:22438044 these results demonstrate that C3 and Mac-1 are involved in phagocytosis and clearance of fAΞ² by microglia PMID:24065820 recognizes iC3b on complement-opsonized objects, enabling their phagocytosis. |
| GO:0038024 cargo receptor activity | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS from mouse (CR3 in uptake of fibrillar Abeta). Reason: GO cargo receptor activity describes receptors that select cargo for vesicular transport. CR3 is a phagocytic complement receptor; its role in Abeta uptake is better captured by complement component iC3b receptor activity and phagocytosis, engulfment. Supporting Evidence: PMID:22438044 these results demonstrate that C3 and Mac-1 are involved in phagocytosis and clearance of fAΞ² by microglia PMID:24065820 recognizes iC3b on complement-opsonized objects, enabling their phagocytosis. |
| GO:0043315 positive regulation of neutrophil degranulation | IGI PMID:21193407 Complement receptor Mac-1 is an adaptor for NB1 (CD177)-medi... | KEEP AS NON CORE | Summary: IGI: positive regulation of neutrophil degranulation. Reason: CD11b blockade reduced NB1-triggered degranulation in neutrophils; Mac-1 acts as the transmembrane adaptor for the CD177/PR3 complex. A context-specific consequence of Mac-1 signaling. Supporting Evidence: PMID:21193407 Stimulation with NB1-activating mAb triggered degranulation and superoxide production in mNB1(pos)/mPR3(high) neutrophils, and this effect was reduced using blocking antibodies to CD11b. PMID:21193407 establish the pivotal role of the NB1-Mac-1 receptor interaction for PR3-ANCA-mediated neutrophil activation. |
| GO:0044853 plasma membrane raft | IDA PMID:21193407 Complement receptor Mac-1 is an adaptor for NB1 (CD177)-medi... | ACCEPT | Summary: IDA: plasma membrane raft. Reason: Mac-1 co-localises with NB1 and PR3 in neutrophil lipid rafts. Supporting Evidence: PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl projection: protein-containing complex binding. Reason: Very general term with no functional content beyond complex membership and ligand binding already captured by more specific terms. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Heterodimer of an alpha and a beta subunit. |
| GO:0045121 membrane raft | EXP PMID:21193407 Complement receptor Mac-1 is an adaptor for NB1 (CD177)-medi... | ACCEPT | Summary: Membrane raft. Reason: Mac-1 located within lipid rafts of neutrophils. Supporting Evidence: PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | ACCEPT | Summary: Membrane raft. Reason: Mac-1 located within lipid rafts of neutrophils. Supporting Evidence: PMID:21193407 NB1, PR3, and Mac-1 were located within lipid rafts. |
| GO:0045963 negative regulation of dopamine metabolic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Negative regulation of dopamine metabolic process (ISS), inferred from mouse Itgam, where MAC1 deficiency preserves dopamine content in the MPTP model by reducing microglial neurotoxicity (PMID:18981141). Reason: The row is inferred from mouse Itgam, annotated by direct assay in a study showing that MAC1 deficiency attenuates MPTP-induced dopaminergic neurodegeneration through reduced microgliosis and superoxide production (PMID:18981141), so the claim has an experimental basis. The preserved dopamine content of MAC1-deficient animals is, however, a consequence of reduced neurotoxicity, not of ITGAM acting on dopamine metabolism. The term over-reads the phenotype rather than being unsupported, so it is marked as an over-annotation instead of removed. Supporting Evidence: PMID:18981141 MAC1 deficiency greatly attenuated the DAergic neurodegeneration induced by MPTP or 1-methyl-4-phenyl-pyridium iodide (MPP(+)) exposure both in vivo and in vitro, respectively. |
| GO:0061756 leukocyte adhesion to vascular endothelial cell | IDA PMID:1980124 ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18). | ACCEPT | Summary: IDA: leukocyte adhesion to vascular endothelial cell. Reason: Mac-1/ICAM-1 interaction mediates adhesion of stimulated neutrophils to activated endothelium; CD11b-deficient mice show reduced leukocyte adhesion to microvascular endothelium. Supporting Evidence: PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. PMID:8986723 In mice selectively deficient in CD11b/CD18, a beta 2 integrin, chemoattractant-induced leukocyte adhesion to microvascular endothelium in vivo was reduced. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: HDA from urinary exosome proteomics. Reason: High-throughput detection in exosome preparations; plausible for a membrane protein of leukocytes but not functionally informative. |
| GO:0070821 tertiary granule membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Tertiary granule membrane. Reason: CD11b/CD18 is present in neutrophil tertiary granule membranes and translocates to the plasma membrane upon exocytosis. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens |
| GO:0070821 tertiary granule membrane | TAS Reactome:R-HSA-6798747 | ACCEPT | Summary: Tertiary granule membrane. Reason: CD11b/CD18 is present in neutrophil tertiary granule membranes and translocates to the plasma membrane upon exocytosis. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens |
| GO:0090314 positive regulation of protein targeting to membrane | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS from mouse (reduced p47phox membrane translocation in MAC1-/- microglia). Reason: Reduced p47phox translocation is an indirect consequence of absent CR3 signaling to NADPH oxidase; the broad term "positive regulation of protein targeting to membrane" over-interprets this observation. Supporting Evidence: PMID:18981141 The stunted production of superoxide in MAC1(-/-) microglia is likely linked to the lack of translocation of the cytosolic NADPH oxidase (PHOX) subunit (p47(phox)) to the membrane. |
| GO:0097242 amyloid-beta clearance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse (C3/Mac-1-dependent clearance of fibrillar Abeta). Reason: CR3 participates as a phagocytic receptor in microglial uptake and clearance of fibrillar Abeta, together with C3 and scavenger receptors; a disease-context instance of its phagocytic function. Supporting Evidence: PMID:22438044 these results demonstrate that C3 and Mac-1 are involved in phagocytosis and clearance of fAΞ² by microglia PMID:20199584 antibodies against CD11b or CD18 reduced the uptake of the artificial amyloid deposit by microglial cell showing that CR3 is involved in the mechanism. |
| GO:0098609 cell-cell adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: Cell-cell adhesion. Reason: Mac-1 mediates leukocyte adhesion to endothelial cells, platelets and epithelial cells. Supporting Evidence: PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. PMID:15194813 Additional experiments revealed specific binding of JAM-C to CD11b/CD18 and provided evidence of other epithelial ligands for CD11b/CD18. |
| GO:0098609 cell-cell adhesion | NAS PMID:20199584 Complement receptor 3 (CD11b/CD18) is implicated in the elim... | ACCEPT | Summary: Cell-cell adhesion. Reason: Mac-1 mediates leukocyte adhesion to endothelial cells, platelets and epithelial cells. Supporting Evidence: PMID:1980124 we conclude that ICAM-1 is a counter receptor for Mac-1 and that this receptor pair is responsible, in part, for the adhesion between stimulated neutrophils and stimulated endothelial cells. PMID:15194813 Additional experiments revealed specific binding of JAM-C to CD11b/CD18 and provided evidence of other epithelial ligands for CD11b/CD18. |
| GO:0140459 response to Gram-positive bacterium | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl projection: response to Gram-positive bacterium. Reason: CR3 recognises opsonised and some unopsonised microbes, but the rodent-derived "response to" annotation is phenotype-level; the relevant activity is captured by complement receptor and phagocytosis terms. Supporting Evidence: PMID:8485905 It has important functions both as an adhesion molecule and a membrane receptor mediating recognition of diverse ligands such as intercellular adhesion molecule-1 (ICAM-1) and fixed iC3b. |
| GO:0150062 complement-mediated synapse pruning | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse (Schafer et al. 2012). Reason: Microglial CR3 engages C3 on synaptic inputs and is required for engulfment of retinogeniculate inputs; CR3 KO mice have sustained deficits in synaptic refinement. CR3 is the receptor that executes the engulfment step of complement-mediated pruning. Also required for oligomeric Abeta-induced synapse engulfment in AD mouse models. Supporting Evidence: PMID:22632727 Taken together, these data demonstrate that phagocytic signaling through CR3 and its ligand C3 is one molecular mechanism by which microglia engulf RGC inputs. PMID:22632727 Consistent with the hypothesis that microglia mediate complement-dependent synaptic pruning, a statistically significant increase in ipsilateral and contralateral input overlap was observed in P10 and P30 CR3 KOs as compared to WT littermate controls PMID:27033548 These data demonstrate that CR3 is necessary for oAΞ²-dependent engulfment of synapses by microglia. |
| GO:0150064 vertebrate eye-specific patterning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse (CR3 KO eye-specific segregation defect). Reason: CR3 KO mice show increased ipsilateral/contralateral overlap in the dLGN; this developmental outcome results from CR3-mediated synapse pruning and is retained as non-core. Supporting Evidence: PMID:22632727 Consistent with the hypothesis that microglia mediate complement-dependent synaptic pruning, a statistically significant increase in ipsilateral and contralateral input overlap was observed in P10 and P30 CR3 KOs as compared to WT littermate controls |
| GO:0160108 animal gross anatomical part developmental process | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA prediction: animal gross anatomical part developmental process. Reason: The broad developmental term is entailed by the vertebrate eye-specific patterning annotation kept in this review, so it is consistent with a kept row and cannot be removed while that row stands. It adds nothing to it: the machine-generated term carries no ITGAM-specific evidence. It is recorded as too general. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens |
| GO:1904151 positive regulation of microglial cell mediated cytotoxicity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse (CD11b/DAP12 control microglial superoxide that kills neurons). Reason: Supported by mouse genetic and antibody-blocking data; a microglial effector consequence of CD11b signaling in development. Supporting Evidence: PMID:18685038 we show that DAP12 and CD11b control the production of microglial superoxide ions, which kill the neurons. PMID:18685038 We demonstrate that developmental apoptosis decreases in mice deficient for CD11b or DAP12. |
| GO:1904643 response to curcumin | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara projection of a rodent "response to curcumin" annotation onto human ITGAM. Reason: "response to curcumin" annotations in rodents typically record expression or phenotype changes after an experimental treatment, not a function executed by the gene product. No evidence that ITGAM performs a step of a response to curcumin process; projection of such response terms is uninformative for the CR3 receptor. Supporting Evidence: file:human/ITGAM/ITGAM-uniprot.txt Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens |
| GO:0006910 phagocytosis, recognition | IDA PMID:24065820 Structural insight on the recognition of surface-bound opson... | NEW | Summary: Proposed: CR3 recognises iC3b deposited on complement-opsonised targets, the recognition step of complement-mediated phagocytosis. Reason: The CD11b alphaI domain itself binds the C3d moiety of surface-bound iC3b, so ITGAM performs the recognition step (participation test passed: the receptor does the binding of the opsonised particle). Comparator check: other phagocytic receptors (CLEC7A, SCARB1, TREM2) carry GO:0006910 in human GOA. Human R77H data show reduced iC3b-mediated phagocytosis. Supporting Evidence: PMID:24065820 recognizes iC3b on complement-opsonized objects, enabling their phagocytosis. PMID:22586164 A 31% reduction was observed in the phagocytosis of iC3b opsonised sheep erythrocytes (sRBC(iC3b)) by 77H cells (p=0.003) |
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Download this section (compressed HTML)Q: Does CR3 participate in human microglial engulfment of complement-tagged synapses in the adult or Alzheimer disease brain, and is the iC3b-binding alphaI domain sufficient for this, or do co-receptors (e.g. CR4/ITGAX, TREM2/TYROBP) contribute?
Suggested experts: microglia biologists, complement biologists
Q: Is direct binding of amyloid-beta by CD11b/CD18 established, or does CR3-dependent amyloid-beta uptake depend entirely on iC3b opsonisation of amyloid?
Suggested experts: neuroimmunology experts
Q: Should GO represent CR3 recognition of non-complement microbial ligands (e.g. fungal hsp60, beta-glucan) with a pattern recognition receptor term rather than heat shock protein binding?
Suggested experts: GO immune curators
Experiment: In human iPSC-derived microglia carrying ITGAM knockout, R77H, or alphaI-domain MIDAS mutations, quantify engulfment of C3-opsonised versus C3-depleted synaptosomes and of fibrillar amyloid-beta with and without serum complement.
Hypothesis: Microglial synapse and amyloid uptake via CR3 depends on iC3b recognition by the alphaI domain and is reduced by the lupus-associated R77H variant.
Type: genetic perturbation with phagocytosis assays
Experiment: Surface plasmon resonance with purified activated alphaI domain against monomeric, oligomeric and fibrillar amyloid-beta in the absence of complement.
Hypothesis: CD11b does not bind amyloid-beta directly with appreciable affinity; uptake requires opsonisation.
Type: biophysical binding assay
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