CR1 encodes complement receptor type 1/CD35, a large single-pass membrane receptor composed of complement-control protein repeat domains and expressed on erythrocytes, monocytes/macrophages, granulocytes, B cells, subsets of T cells, follicular dendritic cells, and other immune-associated cells. CR1 binds complement-opsonized ligands, especially C3b and C4b, allowing immune adherence and clearance of immune complexes and particles from the circulation. CR1 also regulates complement by accelerating decay of classical and alternative pathway convertases and acting as a factor I cofactor for cleavage of C3b and C4b. In specific immune-cell contexts, CR1 engagement can modulate T-cell, B-cell, and regulatory T-cell responses, while complement-pathway interactions with C1q, MBL, ficolins, and microbial ligands broaden its immune-recognition roles.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005576
extracellular region
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0005886
plasma membrane
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0045959
negative regulation of complement activation, classical pathway
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0002456
T cell mediated immunity
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: This adaptive immune-cell annotation is supported or plausible but represents T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b receptor/cofactor role.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0001848
complement binding
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: CR1 directly binds complement ligands, especially C3b and C4b, and functions as their cell-surface receptor.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0004875
complement receptor activity
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: CR1 directly binds complement ligands, especially C3b and C4b, and functions as their cell-surface receptor.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0005886
plasma membrane
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0006957
complement activation, alternative pathway
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: This complement activation/MAC annotation is supported in specific B-cell complement deposition contexts while remaining part of CR1 complement receptor biology.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0016020
membrane
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0030449
regulation of complement activation
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:1903659
regulation of complement-dependent cytotoxicity
|
IEA
GO_REF:0000117 |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0005515
protein binding
|
IPI
PMID:23460739 Deciphering complement receptor type 1 interactions with rec... |
MODIFY |
Summary: The MBL/ficolin/C1q interaction evidence supports complement-recognition ligand binding, but generic protein binding is too broad.
Reason: Replace generic protein binding with complement binding for CR1 interactions with recognition proteins of the lectin/classical complement pathways.
Proposed replacements:
complement binding
|
|
GO:0005515
protein binding
|
IPI
PMID:29563915 C1q and Mannose-Binding Lectin Interact with CR1 in the Same... |
MODIFY |
Summary: The MBL/ficolin/C1q interaction evidence supports complement-recognition ligand binding, but generic protein binding is too broad.
Reason: Replace generic protein binding with complement binding for CR1 interactions with recognition proteins of the lectin/classical complement pathways.
Proposed replacements:
complement binding
|
|
GO:0005886
plasma membrane
|
IDA
GO_REF:0000052 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0002251
organ or tissue specific immune response
|
IGI
PMID:20702729 Abnormal immune complex processing and spontaneous glomerulo... |
KEEP AS NON CORE |
Summary: This mouse disease/model annotation reflects complement-dependent immune-complex pathology and glomerular consequences rather than the primary molecular function of CR1.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0002434
immune complex clearance
|
IGI
PMID:20702729 Abnormal immune complex processing and spontaneous glomerulo... |
ACCEPT |
Summary: CR1 on erythrocytes and immune cells mediates immune adherence and clearance of complement-opsonized immune complexes/particles.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0006956
complement activation
|
IGI
PMID:20702729 Abnormal immune complex processing and spontaneous glomerulo... |
KEEP AS NON CORE |
Summary: This mouse disease/model annotation reflects complement-dependent immune-complex pathology and glomerular consequences rather than the primary molecular function of CR1.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0032835
glomerulus development
|
IGI
PMID:20702729 Abnormal immune complex processing and spontaneous glomerulo... |
KEEP AS NON CORE |
Summary: This mouse disease/model annotation reflects complement-dependent immune-complex pathology and glomerular consequences rather than the primary molecular function of CR1.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0016020
membrane
|
EXP
PMID:1385479 Expression and localization of proteins of the complement sy... |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:1903660
negative regulation of complement-dependent cytotoxicity
|
IDA
PMID:31862673 Complement Receptor 1 (CR1/CD35)-expressing retinal pigment ... |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0001970
positive regulation of activation of membrane attack complex
|
IMP
PMID:11981823 The role of complement receptors type 1 (CR1, CD35) and 2 (C... |
ACCEPT |
Summary: This complement activation/MAC annotation is supported in specific B-cell complement deposition contexts while remaining part of CR1 complement receptor biology.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0005515
protein binding
|
IPI
PMID:18684861 Ligation of erythrocyte CR1 induces its clustering in comple... |
MARK AS OVER ANNOTATED |
Summary: The FAP-1/scaffold interaction may be real in erythrocyte CR1 clustering, but generic protein binding does not define CR1 molecular function.
Reason: This annotation is less informative than specific CR1 complement-binding, complement receptor, immune-complex clearance, or complement-regulatory terms.
|
|
GO:0005856
cytoskeleton
|
IDA
PMID:18684861 Ligation of erythrocyte CR1 induces its clustering in comple... |
KEEP AS NON CORE |
Summary: This erythrocyte clustering, membrane organization, raft, ATP-release, or cytoskeletal annotation is relevant to immune-adherence transfer but is secondary to CR1 complement ligand binding.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0006957
complement activation, alternative pathway
|
IMP
PMID:11981823 The role of complement receptors type 1 (CR1, CD35) and 2 (C... |
ACCEPT |
Summary: This complement activation/MAC annotation is supported in specific B-cell complement deposition contexts while remaining part of CR1 complement receptor biology.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0008284
positive regulation of cell population proliferation
|
IDA
PMID:25742728 Complement receptor type 1 (CR1/CD35) expressed on activated... |
KEEP AS NON CORE |
Summary: This adaptive immune-cell annotation is supported or plausible but represents T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b receptor/cofactor role.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0009986
cell surface
|
IDA
PMID:25742728 Complement receptor type 1 (CR1/CD35) expressed on activated... |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0045591
positive regulation of regulatory T cell differentiation
|
IDA
PMID:25742728 Complement receptor type 1 (CR1/CD35) expressed on activated... |
KEEP AS NON CORE |
Summary: This adaptive immune-cell annotation is supported or plausible but represents T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b receptor/cofactor role.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0002435
immune complex clearance by erythrocytes
|
IDA
PMID:24022490 CR1-mediated ATP release by human red blood cells promotes C... |
ACCEPT |
Summary: CR1 on erythrocytes and immune cells mediates immune adherence and clearance of complement-opsonized immune complexes/particles.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0002430
complement receptor mediated signaling pathway
|
IDA
PMID:16360013 The complement receptor 1, CR1 (CD35), mediates inhibitory s... |
ACCEPT |
Summary: CR1 engagement can signal through complement receptor-mediated pathways in immune cells.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0002430
complement receptor mediated signaling pathway
|
IDA
PMID:22962438 Complement receptor type 1 (CR1, CD35) is a potent inhibitor... |
ACCEPT |
Summary: CR1 engagement can signal through complement receptor-mediated pathways in immune cells.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0002638
negative regulation of immunoglobulin production
|
IDA
PMID:22962438 Complement receptor type 1 (CR1, CD35) is a potent inhibitor... |
KEEP AS NON CORE |
Summary: This adaptive immune-cell annotation is supported or plausible but represents T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b receptor/cofactor role.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0007009
plasma membrane organization
|
IDA
PMID:24022490 CR1-mediated ATP release by human red blood cells promotes C... |
KEEP AS NON CORE |
Summary: This erythrocyte clustering, membrane organization, raft, ATP-release, or cytoskeletal annotation is relevant to immune-adherence transfer but is secondary to CR1 complement ligand binding.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0032689
negative regulation of type II interferon production
|
IDA
PMID:16360013 The complement receptor 1, CR1 (CD35), mediates inhibitory s... |
KEEP AS NON CORE |
Summary: This adaptive immune-cell annotation is supported or plausible but represents T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b receptor/cofactor role.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0032703
negative regulation of interleukin-2 production
|
IDA
PMID:16360013 The complement receptor 1, CR1 (CD35), mediates inhibitory s... |
KEEP AS NON CORE |
Summary: This adaptive immune-cell annotation is supported or plausible but represents T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b receptor/cofactor role.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0042130
negative regulation of T cell proliferation
|
IDA
PMID:16360013 The complement receptor 1, CR1 (CD35), mediates inhibitory s... |
KEEP AS NON CORE |
Summary: This adaptive immune-cell annotation is supported or plausible but represents T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b receptor/cofactor role.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0044853
plasma membrane raft
|
IDA
PMID:24022490 CR1-mediated ATP release by human red blood cells promotes C... |
KEEP AS NON CORE |
Summary: This erythrocyte clustering, membrane organization, raft, ATP-release, or cytoskeletal annotation is relevant to immune-adherence transfer but is secondary to CR1 complement ligand binding.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:1900099
negative regulation of plasma cell differentiation
|
IDA
PMID:22962438 Complement receptor type 1 (CR1, CD35) is a potent inhibitor... |
KEEP AS NON CORE |
Summary: This adaptive immune-cell annotation is supported or plausible but represents T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b receptor/cofactor role.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:1904669
ATP export
|
IDA
PMID:24022490 CR1-mediated ATP release by human red blood cells promotes C... |
KEEP AS NON CORE |
Summary: This erythrocyte clustering, membrane organization, raft, ATP-release, or cytoskeletal annotation is relevant to immune-adherence transfer but is secondary to CR1 complement ligand binding.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0001971
negative regulation of activation of membrane attack complex
|
IDA
PMID:31862673 Complement Receptor 1 (CR1/CD35)-expressing retinal pigment ... |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0045916
negative regulation of complement activation
|
IDA
PMID:31862673 Complement Receptor 1 (CR1/CD35)-expressing retinal pigment ... |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0030667
secretory granule membrane
|
TAS
Reactome:R-HSA-6798743 |
KEEP AS NON CORE |
Summary: This intracellular/granule localization is compatible with immune-cell trafficking context but is not the main functional site of CR1 complement receptor activity.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0101003
ficolin-1-rich granule membrane
|
TAS
Reactome:R-HSA-6800426 |
KEEP AS NON CORE |
Summary: This intracellular/granule localization is compatible with immune-cell trafficking context but is not the main functional site of CR1 complement receptor activity.
Reason: Retain as non-core because the annotation is supported or plausible but reflects cell-type-specific adaptive immune modulation, disease/model context, erythrocyte clustering mechanics, or intracellular/granule localization rather than the primary C3b/C4b receptor and complement-regulatory function.
|
|
GO:0070062
extracellular exosome
|
HDA
PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... |
MARK AS OVER ANNOTATED |
Summary: High-throughput extracellular exosome localization is not central to CR1 complement receptor biology and is less informative than membrane/cell-surface annotations.
Reason: This annotation is less informative than specific CR1 complement-binding, complement receptor, immune-complex clearance, or complement-regulatory terms.
|
|
GO:0070062
extracellular exosome
|
HDA
PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... |
MARK AS OVER ANNOTATED |
Summary: High-throughput extracellular exosome localization is not central to CR1 complement receptor biology and is less informative than membrane/cell-surface annotations.
Reason: This annotation is less informative than specific CR1 complement-binding, complement receptor, immune-complex clearance, or complement-regulatory terms.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-3266557 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6798743 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-6800426 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-8939088 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-977375 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-977602 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-977615 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0005886
plasma membrane
|
TAS
Reactome:R-HSA-977629 |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0005886
plasma membrane
|
IDA
PMID:6910481 Complement receptor is an inhibitor of the complement cascad... |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0045957
negative regulation of complement activation, alternative pathway
|
IDA
PMID:10531307 Decay accelerating activity of complement receptor type 1 (C... |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0045959
negative regulation of complement activation, classical pathway
|
IDA
PMID:10531307 Decay accelerating activity of complement receptor type 1 (C... |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0045959
negative regulation of complement activation, classical pathway
|
IDA
PMID:6910481 Complement receptor is an inhibitor of the complement cascad... |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:1900004
negative regulation of serine-type endopeptidase activity
|
IDA
PMID:6910481 Complement receptor is an inhibitor of the complement cascad... |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0009986
cell surface
|
IDA
PMID:6978375 Complement receptor (CR1) deficiency in erythrocytes from pa... |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:0001851
complement component C3b binding
|
IDA
PMID:2972794 Identification of distinct C3b and C4b recognition sites in ... |
ACCEPT |
Summary: CR1 directly binds complement ligands, especially C3b and C4b, and functions as their cell-surface receptor.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0001855
complement component C4b binding
|
IDA
PMID:2972794 Identification of distinct C3b and C4b recognition sites in ... |
ACCEPT |
Summary: CR1 directly binds complement ligands, especially C3b and C4b, and functions as their cell-surface receptor.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0001861
complement component C4b receptor activity
|
IDA
PMID:2972794 Identification of distinct C3b and C4b recognition sites in ... |
ACCEPT |
Summary: CR1 directly binds complement ligands, especially C3b and C4b, and functions as their cell-surface receptor.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0004877
complement component C3b receptor activity
|
IDA
PMID:2972794 Identification of distinct C3b and C4b recognition sites in ... |
ACCEPT |
Summary: CR1 directly binds complement ligands, especially C3b and C4b, and functions as their cell-surface receptor.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
|
GO:0009986
cell surface
|
IDA
PMID:2972794 Identification of distinct C3b and C4b recognition sites in ... |
ACCEPT |
Summary: This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing single-pass complement receptor.
Reason: This location is consistent with CR1 acting as a single-pass cell-surface/plasma-membrane complement receptor.
|
|
GO:1900005
positive regulation of serine-type endopeptidase activity
|
IDA
PMID:2972794 Identification of distinct C3b and C4b recognition sites in ... |
ACCEPT |
Summary: CR1 regulates complement by accelerating convertase decay and serving as a cofactor for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.
Reason: This term captures the core CR1/CD35 role as a cell-surface complement receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance, and regulates complement convertase and factor I-dependent cleavage reactions.
|
Q: Should CR1 interactions with C1q, MBL, and ficolins be curated with more specific complement-recognition binding terms rather than generic protein binding?
Suggested experts: Complement pathway experts, GO molecular-function curators
Q: Which CR1 immune-cell regulatory annotations should be considered core across species and cell types versus retained as human T-cell/B-cell context?
Suggested experts: CR1 immunology experts, GO immune process curators
Experiment: Use CR1 variants disrupting C3b/C4b sites, CCP24-25 defense-collagen binding, and cytoplasmic FAP-1 interaction in erythrocytes or engineered immune cells, then measure immune-complex binding, transfer to macrophages, factor I cofactor activity, and convertase decay.
Hypothesis: CR1 immune-adherence clearance and complement-regulatory functions can be separated from defense-collagen binding and erythrocyte clustering modules.
Type: domain-resolved complement receptor function assay
Experiment: Compare CR1 engagement on primary human T-cell and B-cell subsets with C3b/C4b ligands versus antibody crosslinking, quantifying cytokines, proliferation, Treg differentiation, plasma-cell differentiation, and complement receptor signaling markers.
Hypothesis: Adaptive immune-cell effects of CR1 are cell-context-specific signaling outcomes of complement ligand engagement rather than the universal core function of CR1.
Type: primary immune-cell receptor signaling assay
just deep-research-falcon human CR1 --fallback perplexity-lite timed out after 180 seconds with no generated research artifact, so this manual review uses cached UniProt, GOA, Reactome, PANTHER family, and publication evidence.protein binding is too broad. I marked the corresponding generic annotations as MODIFY to complement binding PMID:23460739.The second-pass audit confirmed the existing CR1 review and manual reference metadata. No annotation action changes were needed: CR1 remains curated as a C3b/C4b complement receptor and immune-adherence/complement-regulatory cofactor, with T-cell, B-cell, retinal-therapeutic, cytoskeletal, and generic high-throughput interaction contexts retained as non-core, modified, or over-annotated as already reviewed.
id: P17927
gene_symbol: CR1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: 'CR1 encodes complement receptor type 1/CD35, a large single-pass membrane receptor
composed of complement-control protein repeat domains and expressed on erythrocytes, monocytes/macrophages,
granulocytes, B cells, subsets of T cells, follicular dendritic cells, and other immune-associated
cells. CR1 binds complement-opsonized ligands, especially C3b and C4b, allowing immune adherence
and clearance of immune complexes and particles from the circulation. CR1 also regulates
complement by accelerating decay of classical and alternative pathway convertases and acting
as a factor I cofactor for cleavage of C3b and C4b. In specific immune-cell contexts, CR1
engagement can modulate T-cell, B-cell, and regulatory T-cell responses, while complement-pathway
interactions with C1q, MBL, ficolins, and microbial ligands broaden its immune-recognition
roles.'
existing_annotations:
- term:
id: GO:0005576
label: extracellular region
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0045959
label: negative regulation of complement activation, classical pathway
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0002456
label: T cell mediated immunity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: 'This adaptive immune-cell annotation is supported or plausible but represents
T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b
receptor/cofactor role.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0001848
label: complement binding
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: enables
review:
summary: 'CR1 directly binds complement ligands, especially C3b and C4b, and functions
as their cell-surface receptor.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0004875
label: complement receptor activity
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: enables
review:
summary: 'CR1 directly binds complement ligands, especially C3b and C4b, and functions
as their cell-surface receptor.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0006957
label: complement activation, alternative pathway
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'This complement activation/MAC annotation is supported in specific B-cell complement
deposition contexts while remaining part of CR1 complement receptor biology.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0016020
label: membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0030449
label: regulation of complement activation
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:1903659
label: regulation of complement-dependent cytotoxicity
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23460739
qualifier: enables
review:
summary: 'The MBL/ficolin/C1q interaction evidence supports complement-recognition ligand
binding, but generic protein binding is too broad.'
action: MODIFY
reason: Replace generic protein binding with complement binding for CR1 interactions
with recognition proteins of the lectin/classical complement pathways.
proposed_replacement_terms:
- id: GO:0001848
label: complement binding
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:29563915
qualifier: enables
review:
summary: 'The MBL/ficolin/C1q interaction evidence supports complement-recognition ligand
binding, but generic protein binding is too broad.'
action: MODIFY
reason: Replace generic protein binding with complement binding for CR1 interactions
with recognition proteins of the lectin/classical complement pathways.
proposed_replacement_terms:
- id: GO:0001848
label: complement binding
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: GO_REF:0000052
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0002251
label: organ or tissue specific immune response
evidence_type: IGI
original_reference_id: PMID:20702729
qualifier: acts_upstream_of_or_within
review:
summary: 'This mouse disease/model annotation reflects complement-dependent immune-complex
pathology and glomerular consequences rather than the primary molecular function of
CR1.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0002434
label: immune complex clearance
evidence_type: IGI
original_reference_id: PMID:20702729
qualifier: acts_upstream_of_or_within
review:
summary: 'CR1 on erythrocytes and immune cells mediates immune adherence and clearance
of complement-opsonized immune complexes/particles.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0006956
label: complement activation
evidence_type: IGI
original_reference_id: PMID:20702729
qualifier: acts_upstream_of_or_within
review:
summary: 'This mouse disease/model annotation reflects complement-dependent immune-complex
pathology and glomerular consequences rather than the primary molecular function of
CR1.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0032835
label: glomerulus development
evidence_type: IGI
original_reference_id: PMID:20702729
qualifier: acts_upstream_of_or_within
review:
summary: 'This mouse disease/model annotation reflects complement-dependent immune-complex
pathology and glomerular consequences rather than the primary molecular function of
CR1.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0016020
label: membrane
evidence_type: EXP
original_reference_id: PMID:1385479
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:1903660
label: negative regulation of complement-dependent cytotoxicity
evidence_type: IDA
original_reference_id: PMID:31862673
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0001970
label: positive regulation of activation of membrane attack complex
evidence_type: IMP
original_reference_id: PMID:11981823
qualifier: involved_in
review:
summary: 'This complement activation/MAC annotation is supported in specific B-cell complement
deposition contexts while remaining part of CR1 complement receptor biology.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:18684861
qualifier: enables
review:
summary: 'The FAP-1/scaffold interaction may be real in erythrocyte CR1 clustering, but
generic protein binding does not define CR1 molecular function.'
action: MARK_AS_OVER_ANNOTATED
reason: This annotation is less informative than specific CR1 complement-binding,
complement receptor, immune-complex clearance, or complement-regulatory terms.
- term:
id: GO:0005856
label: cytoskeleton
evidence_type: IDA
original_reference_id: PMID:18684861
qualifier: located_in
review:
summary: 'This erythrocyte clustering, membrane organization, raft, ATP-release, or cytoskeletal
annotation is relevant to immune-adherence transfer but is secondary to CR1 complement
ligand binding.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0006957
label: complement activation, alternative pathway
evidence_type: IMP
original_reference_id: PMID:11981823
qualifier: involved_in
review:
summary: 'This complement activation/MAC annotation is supported in specific B-cell complement
deposition contexts while remaining part of CR1 complement receptor biology.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: IDA
original_reference_id: PMID:25742728
qualifier: involved_in
review:
summary: 'This adaptive immune-cell annotation is supported or plausible but represents
T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b
receptor/cofactor role.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0009986
label: cell surface
evidence_type: IDA
original_reference_id: PMID:25742728
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0045591
label: positive regulation of regulatory T cell differentiation
evidence_type: IDA
original_reference_id: PMID:25742728
qualifier: involved_in
review:
summary: 'This adaptive immune-cell annotation is supported or plausible but represents
T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b
receptor/cofactor role.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0002435
label: immune complex clearance by erythrocytes
evidence_type: IDA
original_reference_id: PMID:24022490
qualifier: involved_in
review:
summary: 'CR1 on erythrocytes and immune cells mediates immune adherence and clearance
of complement-opsonized immune complexes/particles.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0002430
label: complement receptor mediated signaling pathway
evidence_type: IDA
original_reference_id: PMID:16360013
qualifier: involved_in
review:
summary: 'CR1 engagement can signal through complement receptor-mediated pathways in immune
cells.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0002430
label: complement receptor mediated signaling pathway
evidence_type: IDA
original_reference_id: PMID:22962438
qualifier: involved_in
review:
summary: 'CR1 engagement can signal through complement receptor-mediated pathways in immune
cells.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0002638
label: negative regulation of immunoglobulin production
evidence_type: IDA
original_reference_id: PMID:22962438
qualifier: acts_upstream_of
review:
summary: 'This adaptive immune-cell annotation is supported or plausible but represents
T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b
receptor/cofactor role.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0007009
label: plasma membrane organization
evidence_type: IDA
original_reference_id: PMID:24022490
qualifier: involved_in
review:
summary: 'This erythrocyte clustering, membrane organization, raft, ATP-release, or cytoskeletal
annotation is relevant to immune-adherence transfer but is secondary to CR1 complement
ligand binding.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0032689
label: negative regulation of type II interferon production
evidence_type: IDA
original_reference_id: PMID:16360013
qualifier: acts_upstream_of_or_within
review:
summary: 'This adaptive immune-cell annotation is supported or plausible but represents
T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b
receptor/cofactor role.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0032703
label: negative regulation of interleukin-2 production
evidence_type: IDA
original_reference_id: PMID:16360013
qualifier: acts_upstream_of_or_within
review:
summary: 'This adaptive immune-cell annotation is supported or plausible but represents
T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b
receptor/cofactor role.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0042130
label: negative regulation of T cell proliferation
evidence_type: IDA
original_reference_id: PMID:16360013
qualifier: involved_in
review:
summary: 'This adaptive immune-cell annotation is supported or plausible but represents
T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b
receptor/cofactor role.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0044853
label: plasma membrane raft
evidence_type: IDA
original_reference_id: PMID:24022490
qualifier: located_in
review:
summary: 'This erythrocyte clustering, membrane organization, raft, ATP-release, or cytoskeletal
annotation is relevant to immune-adherence transfer but is secondary to CR1 complement
ligand binding.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:1900099
label: negative regulation of plasma cell differentiation
evidence_type: IDA
original_reference_id: PMID:22962438
qualifier: acts_upstream_of
review:
summary: 'This adaptive immune-cell annotation is supported or plausible but represents
T-cell/B-cell regulatory consequences of CR1 engagement rather than the primary C3b/C4b
receptor/cofactor role.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:1904669
label: ATP export
evidence_type: IDA
original_reference_id: PMID:24022490
qualifier: acts_upstream_of_or_within
review:
summary: 'This erythrocyte clustering, membrane organization, raft, ATP-release, or cytoskeletal
annotation is relevant to immune-adherence transfer but is secondary to CR1 complement
ligand binding.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0001971
label: negative regulation of activation of membrane attack complex
evidence_type: IDA
original_reference_id: PMID:31862673
qualifier: acts_upstream_of
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0045916
label: negative regulation of complement activation
evidence_type: IDA
original_reference_id: PMID:31862673
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0030667
label: secretory granule membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6798743
qualifier: located_in
review:
summary: 'This intracellular/granule localization is compatible with immune-cell trafficking
context but is not the main functional site of CR1 complement receptor activity.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0101003
label: ficolin-1-rich granule membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6800426
qualifier: located_in
review:
summary: 'This intracellular/granule localization is compatible with immune-cell trafficking
context but is not the main functional site of CR1 complement receptor activity.'
action: KEEP_AS_NON_CORE
reason: Retain as non-core because the annotation is supported or plausible but
reflects cell-type-specific adaptive immune modulation, disease/model context,
erythrocyte clustering mechanics, or intracellular/granule localization rather
than the primary C3b/C4b receptor and complement-regulatory function.
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: HDA
original_reference_id: PMID:23533145
qualifier: located_in
review:
summary: 'High-throughput extracellular exosome localization is not central to CR1 complement
receptor biology and is less informative than membrane/cell-surface annotations.'
action: MARK_AS_OVER_ANNOTATED
reason: This annotation is less informative than specific CR1 complement-binding,
complement receptor, immune-complex clearance, or complement-regulatory terms.
- term:
id: GO:0070062
label: extracellular exosome
evidence_type: HDA
original_reference_id: PMID:19056867
qualifier: located_in
review:
summary: 'High-throughput extracellular exosome localization is not central to CR1 complement
receptor biology and is less informative than membrane/cell-surface annotations.'
action: MARK_AS_OVER_ANNOTATED
reason: This annotation is less informative than specific CR1 complement-binding,
complement receptor, immune-complex clearance, or complement-regulatory terms.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-3266557
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6798743
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-6800426
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-8939088
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-977375
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-977602
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-977615
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-977629
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0005886
label: plasma membrane
evidence_type: IDA
original_reference_id: PMID:6910481
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0045957
label: negative regulation of complement activation, alternative pathway
evidence_type: IDA
original_reference_id: PMID:10531307
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0045959
label: negative regulation of complement activation, classical pathway
evidence_type: IDA
original_reference_id: PMID:10531307
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0045959
label: negative regulation of complement activation, classical pathway
evidence_type: IDA
original_reference_id: PMID:6910481
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:1900004
label: negative regulation of serine-type endopeptidase activity
evidence_type: IDA
original_reference_id: PMID:6910481
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0009986
label: cell surface
evidence_type: IDA
original_reference_id: PMID:6978375
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:0001851
label: complement component C3b binding
evidence_type: IDA
original_reference_id: PMID:2972794
qualifier: enables
review:
summary: 'CR1 directly binds complement ligands, especially C3b and C4b, and functions
as their cell-surface receptor.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0001855
label: complement component C4b binding
evidence_type: IDA
original_reference_id: PMID:2972794
qualifier: enables
review:
summary: 'CR1 directly binds complement ligands, especially C3b and C4b, and functions
as their cell-surface receptor.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0001861
label: complement component C4b receptor activity
evidence_type: IDA
original_reference_id: PMID:2972794
qualifier: enables
review:
summary: 'CR1 directly binds complement ligands, especially C3b and C4b, and functions
as their cell-surface receptor.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0004877
label: complement component C3b receptor activity
evidence_type: IDA
original_reference_id: PMID:2972794
qualifier: enables
review:
summary: 'CR1 directly binds complement ligands, especially C3b and C4b, and functions
as their cell-surface receptor.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
- term:
id: GO:0009986
label: cell surface
evidence_type: IDA
original_reference_id: PMID:2972794
qualifier: located_in
review:
summary: 'This membrane/extracellular location is consistent with CR1 as a large ectodomain-containing
single-pass complement receptor.'
action: ACCEPT
reason: This location is consistent with CR1 acting as a single-pass
cell-surface/plasma-membrane complement receptor.
- term:
id: GO:1900005
label: positive regulation of serine-type endopeptidase activity
evidence_type: IDA
original_reference_id: PMID:2972794
qualifier: involved_in
review:
summary: 'CR1 regulates complement by accelerating convertase decay and serving as a cofactor
for factor I-mediated C3b/C4b cleavage, limiting complement activation and cytotoxicity.'
action: ACCEPT
reason: This term captures the core CR1/CD35 role as a cell-surface complement
receptor that binds C3b/C4b-bearing ligands, supports immune adherence/clearance,
and regulates complement convertase and factor I-dependent cleavage reactions.
references:
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: PMID:10531307
title: Decay accelerating activity of complement receptor type 1 (CD35). Two active
sites are required for dissociating C5 convertases.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Abstract cached; supports decay-accelerating activity against C3/C5
convertases.
- id: PMID:11981823
title: The role of complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) in
promoting C3 fragment deposition and membrane attack complex formation on normal
peripheral human B cells.
findings: []
- id: PMID:1385479
title: Expression and localization of proteins of the complement system in human skin.
findings: []
- id: PMID:16360013
title: The complement receptor 1, CR1 (CD35), mediates inhibitory signals in human
T-lymphocytes.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Abstract cached; supports inhibitory CR1 signaling in human T
lymphocytes.
- id: PMID:18684861
title: Ligation of erythrocyte CR1 induces its clustering in complex with scaffolding
protein FAP-1.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Abstract cached; supports erythrocyte CR1 cytoskeletal association and
FAP-1 scaffold interaction as non-core clustering context.
- id: PMID:19056867
title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
findings: []
- id: PMID:20702729
title: Abnormal immune complex processing and spontaneous glomerulonephritis in
complement factor H-deficient mice with human complement receptor 1 on erythrocytes.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Abstract cached; supports human erythrocyte CR1 immune-complex
processing/glomerular disease model context.
- id: PMID:22962438
title: Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell
functions in rheumatoid arthritis patients.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Abstract cached; supports inhibitory B-cell effects of CR1 engagement.
- id: PMID:23460739
title: Deciphering complement receptor type 1 interactions with recognition proteins
of the lectin complement pathway.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Abstract cached; supports CR1 binding to MBL and ficolins through
CCP22-30/CCP24-25.
- id: PMID:23533145
title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
secretions in urine.
findings: []
- id: PMID:24022490
title: CR1-mediated ATP release by human red blood cells promotes CR1 clustering and
modulates the immune transfer process.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Abstract cached; supports erythrocyte immune-adherence clearance, ATP
release, membrane mobility, and CR1 clustering.
- id: PMID:25742728
title: Complement receptor type 1 (CR1/CD35) expressed on activated human CD4+ T cells
contributes to generation of regulatory T cells.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Abstract cached; supports activated CD4 T-cell CR1 roles in regulatory
T-cell generation.
- id: PMID:29563915
title: C1q and Mannose-Binding Lectin Interact with CR1 in the Same Region on CCP24-25
Modules.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Full text cached; supports C1q and MBL interaction with CR1 CCP24-25
modules.
- id: PMID:2972794
title: Identification of distinct C3b and C4b recognition sites in the human C3b/C4b
receptor (CR1, CD35) by deletion mutagenesis.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Abstract cached; supports C3b/C4b receptor activity, multivalent
binding sites, and factor I cofactor activity.
- id: PMID:31862673
title: Complement Receptor 1 (CR1/CD35)-expressing retinal pigment epithelial cells as
a potential therapy for age-related macular degeneration.
findings: []
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Abstract cached; supports CR1 complement-inhibitory activity in
engineered RPE context.
- id: PMID:6910481
title: Complement receptor is an inhibitor of the complement cascade.
findings: []
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Abstract/full abstract cached; supports CR1 inhibition of alternative
and classical convertases and factor I cofactor activity.
- id: PMID:6978375
title: Complement receptor (CR1) deficiency in erythrocytes from patients with
systemic lupus erythematosus.
findings: []
- id: Reactome:R-HSA-3266557
title: Factor I cleaves iC3b
findings: []
- id: Reactome:R-HSA-6798743
title: Exocytosis of secretory granule membrane proteins
findings: []
- id: Reactome:R-HSA-6800426
title: Exocytosis of ficolin-rich granule membrane proteins
findings: []
- id: Reactome:R-HSA-8939088
title: CR1 gene expression is stimulated by RUNX1
findings: []
- id: Reactome:R-HSA-977375
title: CR1 binds C3bBb/C4bC2a
findings: []
- id: Reactome:R-HSA-977602
title: Complement factor I binds to MCP, CR1:C4b, C3b
findings: []
- id: Reactome:R-HSA-977615
title: Factor I inactivates MCP/CR1-bound C4b/C3b
findings: []
- id: Reactome:R-HSA-977629
title: Displacement of C2a/Bb by CR1
findings: []
core_functions:
- molecular_function:
id: GO:0004875
label: complement receptor activity
description: CR1 acts as a cell-surface receptor for complement-opsonized ligands,
binding C3b and C4b through extracellular CCP/Sushi domains to support immune
adherence and clearance of immune complexes and complement-tagged particles,
especially on human erythrocytes and myeloid/immune cells.
directly_involved_in:
- id: GO:0002434
label: immune complex clearance
- id: GO:0002435
label: immune complex clearance by erythrocytes
- id: GO:0002430
label: complement receptor mediated signaling pathway
locations:
- id: GO:0005886
label: plasma membrane
- id: GO:0009986
label: cell surface
supported_by:
- reference_id: PMID:2972794
supporting_text: mediated rosette formation with sheep erythrocytes bearing C4b and
C3b
- reference_id: PMID:24022490
supporting_text: This process is called immune-adherence clearance
- reference_id: PMID:18684861
supporting_text: The primary identified function of complement receptor 1 (CR1/CD35)
on primate erythrocytes is to bind complement-tagged inflammatory particles
- molecular_function:
id: GO:0001851
label: complement component C3b binding
description: 'CR1 binding to C3b/C4b also provides complement-regulatory activity: CR1 accelerates
decay of classical and alternative pathway C3/C5 convertases and acts as a factor I cofactor
for cleavage of C3b and C4b, limiting complement activation and complement-dependent cytotoxicity
on cells bearing complement-tagged ligands.'
directly_involved_in:
- id: GO:0045957
label: negative regulation of complement activation, alternative pathway
- id: GO:0045959
label: negative regulation of complement activation, classical pathway
- id: GO:0045916
label: negative regulation of complement activation
- id: GO:0001971
label: negative regulation of activation of membrane attack complex
- id: GO:1900005
label: positive regulation of serine-type endopeptidase activity
locations:
- id: GO:0005886
label: plasma membrane
- id: GO:0009986
label: cell surface
supported_by:
- reference_id: PMID:6910481
supporting_text: It promotes the dissociation of the alternative pathway C3
convertase C3b,Bb and the cleavage of C3b by C3b/C4b inactivator
- reference_id: PMID:6910481
supporting_text: CR1 also inactivates the C3 and C5 convertases of the classical
pathway
- reference_id: PMID:10531307
supporting_text: Site 1 (CCPs 1-3) alone mediated the decay acceleration of the
classical and alternative pathway C3 convertases
proposed_new_terms: []
suggested_questions:
- question: Should CR1 interactions with C1q, MBL, and ficolins be curated with more
specific complement-recognition binding terms rather than generic protein binding?
experts:
- Complement pathway experts
- GO molecular-function curators
- question: Which CR1 immune-cell regulatory annotations should be considered core
across species and cell types versus retained as human T-cell/B-cell context?
experts:
- CR1 immunology experts
- GO immune process curators
suggested_experiments:
- description: Use CR1 variants disrupting C3b/C4b sites, CCP24-25 defense-collagen
binding, and cytoplasmic FAP-1 interaction in erythrocytes or engineered immune
cells, then measure immune-complex binding, transfer to macrophages, factor I
cofactor activity, and convertase decay.
hypothesis: CR1 immune-adherence clearance and complement-regulatory functions can be
separated from defense-collagen binding and erythrocyte clustering modules.
experiment_type: domain-resolved complement receptor function assay
- description: Compare CR1 engagement on primary human T-cell and B-cell subsets with
C3b/C4b ligands versus antibody crosslinking, quantifying cytokines, proliferation,
Treg differentiation, plasma-cell differentiation, and complement receptor signaling
markers.
hypothesis: Adaptive immune-cell effects of CR1 are cell-context-specific signaling
outcomes of complement ligand engagement rather than the universal core function of
CR1.
experiment_type: primary immune-cell receptor signaling assay