MAGI1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005737 cytoplasm	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic inference places MAGI1 activity in the cytoplasm. Human studies detect cytoplasmic pools, but the best-defined core activity is concentrated at junctional membrane sites. Reason: The location is plausible and experimentally compatible with MAGI1 trafficking and cytoplasmic interaction partners, but it is too broad to define the core junctional scaffold function.
GO:0005911 cell-cell junction	IBA GO_REF:0000033	ACCEPT	Summary: Cell-cell junction is the principal site of MAGI1 scaffold activity. Human experiments place MAGI1 at epithelial and endothelial contacts and show that junctional recruitment promotes actin polymerization and adhesion. Reason: The phylogenetic annotation is strongly corroborated by direct human localization and functional evidence (PMID:9647739; PMID:20298433). Supporting Evidence: PMID:9647739 both products were co-localized at the cytoplasmic membrane PMID:20298433 Overexpression of ESAM recruited MAGI-1 to the cell-cell contact area.
GO:0007165 signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: MAGI1 scaffolds RAPGEF2/Rap GEP at tight junctions and ESAM-dependent MAGI1 recruitment activates RhoA during junction maturation. Reason: Although broad, signal transduction accurately captures a core consequence of MAGI1 molecular-adaptor activity and is supported by two independent human junctional signaling studies. Supporting Evidence: PMID:11168587 serves as a scaffolding molecule for Rap GEP at tight junctions PMID:20298433 Interaction of ESAM with MAGI-1 activated RhoA
GO:0005737 cytoplasm	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: The ARBA prediction is compatible with experimental cytoplasmic MAGI1 pools, including cytoplasmic extensions in podocytes. Reason: Retain as a broad secondary location; the active junctional pools are more informative for the core function.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping places MAGI1 at the plasma membrane, consistent with direct localization at membrane-associated cell contacts. Reason: MAGI1 is a peripheral membrane scaffold recruited to the cytoplasmic face of junctional plasma membrane domains (PMID:9647739; PMID:20298433).
GO:0005911 cell-cell junction	IEA GO_REF:0000117	ACCEPT	Summary: ARBA predicts the experimentally established cell-cell-junction localization. Reason: Direct human experiments independently validate this location (PMID:9647739; PMID:20298433).
GO:0005923 bicellular tight junction	IEA GO_REF:0000044	ACCEPT	Summary: UniProt mapping assigns MAGI1 to bicellular tight junctions, the best-defined epithelial site of its scaffold activity. Reason: MAGI1 is directly localized to tight junctions, and MAGI1 loss disrupts tight- junction integrity (PMID:11168587; PMID:21123374). Supporting Evidence: PMID:21123374 MAGI-1 degradation is a loss of tight-junction integrity
GO:0016020 membrane	IEA GO_REF:0000117	MODIFY	Summary: The generic membrane prediction captures a real feature but loses the strong evidence for junctional plasma-membrane localization. Reason: Replace the overly broad membrane term with plasma membrane and bicellular tight junction, both already supported by direct and curated evidence. Proposed replacements: plasma membrane bicellular tight junction
GO:0005515 protein binding	IPI PMID:11168587 Membrane-associated guanylate kinase with inverted orientati...	MODIFY	Summary: MAGI1 interacts with RAPGEF2/Rap GEP and functions as its tight-junction scaffold. The experiment supports an adaptor activity more informative than generic protein binding. Reason: MAGI1's defining molecular role is to assemble interacting proteins into junctional complexes. Molecular adaptor activity captures this causal role without treating MAGI1 as an enzyme. Proposed replacements: molecular adaptor activity Supporting Evidence: PMID:11168587 MAGI-1/BAP1 serves as a scaffolding molecule for Rap GEP file:human/MAGI1/MAGI1-deep-research-manual.md The best-supported core role is organization of cell-cell junction complexes.
GO:0005515 protein binding	IPI PMID:12097473 Association of the kinesin superfamily motor protein KIF1Bal...	UNDECIDED	Summary: The abstract reports KIF1Balpha binding to the neuronal scaffold S-SCAM, but the cached text does not resolve the accession or older MAGI/S-SCAM nomenclature sufficiently to verify that the assayed product was human MAGI1 Q96QZ7. Reason: The full evidence needed to resolve the exact MAGI family member is unavailable. Per curation policy, the experimental annotation is not rejected from an abstract-level nomenclature ambiguity.
GO:0005515 protein binding	IPI PMID:12444549 Chimaeric HPV E6 proteins allow dissection of the proteolyti...	MARK AS OVER ANNOTATED	Summary: Papillomavirus E6 proteins carrying PDZ-binding sequences bind MAGI1 and may target it for degradation. Reason: The interaction is credible, but generic protein binding is uninformative for MAGI1's normal molecular function and the viral interaction is a perturbation rather than a core activity. Supporting Evidence: PMID:12444549 enables them to bind Dlg and a second MAGUK family member, MAGI-1
GO:0005515 protein binding	IPI PMID:14627983 Carom: a novel membrane-associated guanylate kinase-interact...	MARK AS OVER ANNOTATED	Summary: FCHSD2/Carom binds the fifth PDZ domain of MAGI1 in vitro and transiently overlaps MAGI1 before epithelial junction maturation. Reason: The domain-specific interaction supports the scaffold model, but the generic protein-binding term adds no informative molecular function. Supporting Evidence: PMID:14627983 Carom binds to the fifth PDZ domain of MAGI-1
GO:0005515 protein binding	IPI PMID:16316992 Proteomic analysis of beta1-adrenergic receptor interactions...	UNDECIDED	Summary: The cached abstract describes beta1-adrenergic receptor interactions with MAGI2 and MAGI3 but does not identify MAGI1; the MAGI1 evidence may be confined to the proteomic array or supplementary material. Reason: Without the accession-level result, the specific MAGI1 interaction cannot be verified. The experimental annotation is retained without alleging curator or paralog error.
GO:0005515 protein binding	IPI PMID:17267502 Structures of a human papillomavirus (HPV) E6 polypeptide bo...	MARK AS OVER ANNOTATED	Summary: Crystal structures establish direct recognition of an HPV18 E6 peptide by MAGI1 PDZ domains. Reason: The structural interaction is well supported but describes viral hijacking; generic protein binding should not be treated as the core MAGI1 function. Supporting Evidence: PMID:17267502 peptide from HPV18 E6 bound to three PDZ domains from MAGI-1
GO:0005515 protein binding	IPI PMID:22662192 IQGAP1 interacts with components of the slit diaphragm compl...	MARK AS OVER ANNOTATED	Summary: Co-immunoprecipitation and proximity assays detect MAGI1 association with IQGAP1 in cultured human podocytes. Reason: This supports a podocyte junctional complex context, but generic protein binding is not an informative molecular-function annotation for MAGI1. Supporting Evidence: PMID:22662192 interactions between IQGAP1 and SD proteins (nephrin, MAGI-1
GO:0005515 protein binding	IPI PMID:22898364 Comparative analysis of virus-host interactomes with a mamma...	MARK AS OVER ANNOTATED	Summary: This large-scale virus-host interaction study includes papillomavirus E6-MAGI1 pairs in its interaction dataset. Reason: A high-throughput viral interaction does not define MAGI1's physiological molecular activity, and protein binding is too generic to retain as core.
GO:0005515 protein binding	IPI PMID:23873930 Cellular localization and characterization of cytosolic bind...	MARK AS OVER ANNOTATED	Summary: WW-domain screening and follow-up assays identify PRRG4 as a MAGI1-interacting membrane protein. Reason: The interaction is compatible with multivalent adaptor activity, but generic protein binding does not describe the biological function of the complex.
GO:0005515 protein binding	IPI PMID:30126976 Proteome-wide analysis of phospho-regulated PDZ domain inter...	MARK AS OVER ANNOTATED	Summary: Proteome-wide peptide-phage screening maps PDZ-domain interactions and their phosphoregulation, including MAGI1 domain interactions in the dataset. Reason: The assay is valuable interaction evidence but generic protein binding is neither specific nor a core functional description.
GO:0005515 protein binding	IPI PMID:33208464 The ATPase ATP6V1A facilitates rabies virus replication by p...	UNDECIDED	Summary: MAGI1 appears in a rabies-virus matrix-protein interactome, but the cached article's validated mechanistic work focuses on ATP6V1A and does not expose the accession-level MAGI1 result in the main text. Reason: The exact MAGI1 evidence cannot be verified from the available article text; the experimental interaction is therefore retained without a confident functional interpretation.
GO:0005515 protein binding	IPI PMID:33864728 Host PDZ-containing proteins targeted by SARS-CoV-2.	UNDECIDED	Summary: A SARS-CoV-2 PDZome affinity screen is cited for MAGI1, but the abstract's named high-confidence binders do not include MAGI1 and the cache lacks the supplementary accession-level table. Reason: The specific MAGI1 interaction cannot be confirmed from the accessible abstract-only record. It is not removed because the curator may have used supplementary data unavailable here.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: BioPlex affinity-purification networks report MAGI1 interaction partners in cell-line-specific, proteome-scale datasets. Reason: The interactions may be valid, but a broad protein-binding label derived from a proteome-scale network does not identify MAGI1's molecular activity.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MARK AS OVER ANNOTATED	Summary: OpenCell combines endogenous tagging, microscopy, and interaction proteomics to map cellular organization; the MAGI1 pair is a high-throughput dataset result. Reason: This is useful interaction context but does not justify retaining generic protein binding as a defining MAGI1 molecular function.
GO:0005515 protein binding	IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ...	MARK AS OVER ANNOTATED	Summary: MAGI1 was recovered in CFTR proximity-labeling datasets. Reason: Proximity labeling does not by itself establish direct binding or a MAGI1 function, and the generic protein-binding term overstates the functional information supplied by the assay.
GO:0005515 protein binding	IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac...	MARK AS OVER ANNOTATED	Summary: Quantitative fragmentomics measured affinities for hundreds of MAGI1 PDZ-domain interactions with PDZ-binding motifs, providing extensive biochemical binding evidence. Reason: The dataset strongly supports MAGI1's multivalent interaction architecture, but collapsing hundreds of motif affinities into generic protein binding is not an informative functional annotation. Supporting Evidence: PMID:36115835 65,000 interactions involving PDZ domains and their target PDZ-binding motifs
GO:0005515 protein binding	IPI PMID:37100772 Large-scale phage-based screening reveals extensive pan-vira...	MARK AS OVER ANNOTATED	Summary: A pan-viral phage screen identifies viral short linear motifs that engage host interaction domains, including a MAGI1-virus pair. Reason: Viral motif mimicry is a perturbational interaction context, and generic protein binding is not a suitable core function for MAGI1.
GO:0030054 cell junction	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence detects MAGI1 at cell junctions. Reason: This direct localization is consistent with the independently established tight-junction and cell-cell-contact localization.
GO:0001886 endothelial cell morphogenesis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Orthology-based transfer assigns MAGI1 a role in endothelial cell morphogenesis, consistent with the conserved AMOTL2-MAGI1-CDH5 junction-actin complex. Reason: The process is biologically plausible but is a tissue-specific developmental consequence of the general junctional scaffold function and lacks direct human morphogenesis evidence in the cited transfer.
GO:0005737 cytoplasm	IDA PMID:20298433 Interaction of endothelial cell-selective adhesion molecule ...	KEEP AS NON CORE	Summary: ESAM-transfection experiments detect a non-junctional cytoplasmic MAGI1 pool in addition to recruitment at cell contacts. Reason: Retain the experimentally observed broad pool, but the contact-associated plasma-membrane localization is the functionally informative site.
GO:0005886 plasma membrane	IDA PMID:20298433 Interaction of endothelial cell-selective adhesion molecule ...	ACCEPT	Summary: ESAM recruits MAGI1 to the cell membrane and cell-cell contact area during mature adhesion. Reason: The localization is direct and mechanistically linked to RhoA-dependent adhesion maturation. Supporting Evidence: PMID:20298433 ESAM-mediated MAGI-1 recruitment to the cell membrane
GO:0005911 cell-cell junction	IDA PMID:20298433 Interaction of endothelial cell-selective adhesion molecule ...	ACCEPT	Summary: ESAM expression recruits MAGI1 to cell-cell contacts in a PDZ-dependent junctional adhesion system. Reason: This is direct localization at the core site of MAGI1 activity. Supporting Evidence: PMID:20298433 Overexpression of ESAM recruited MAGI-1 to the cell-cell contact area.
GO:0022409 positive regulation of cell-cell adhesion	IDA PMID:20298433 Interaction of endothelial cell-selective adhesion molecule ...	ACCEPT	Summary: ESAM-MAGI1 colocalization promotes actin polymerization and firm cell-cell adhesion through RhoA signaling. Reason: Functional adhesion and inhibitor experiments directly establish this as a core downstream process of junctional MAGI1 scaffolding. Supporting Evidence: PMID:20298433 resulted in firm cell-cell adhesion PMID:20298433 Interaction of ESAM with MAGI-1 activated RhoA
GO:0071944 cell periphery	IDA PMID:20298433 Interaction of endothelial cell-selective adhesion molecule ...	KEEP AS NON CORE	Summary: MAGI1 is detected at the cell periphery after recruitment by ESAM. Reason: The localization is valid but less specific than the accepted plasma-membrane and cell-cell-junction terms from the same study.
GO:0005912 adherens junction	ISS GO_REF:0000024	ACCEPT	Summary: Orthology transfer places MAGI1 at adherens junctions. Human cell studies show MAGI1 stabilizes E-cadherin and beta-catenin at cell-cell junctions. Reason: The transferred location is consistent with direct human functional evidence for adherens-junction stabilization (PMID:21666716). Supporting Evidence: PMID:21666716 stabilized E-cadherin and beta-catenin localization at cell-cell junctions
GO:0005515 protein binding	IPI PMID:16464232 Postsynaptic recruitment of Dendrin depends on both dendriti...	UNDECIDED	Summary: The abstract reports Dendrin interaction with MAGI/S-SCAM, but older nomenclature and the unavailable full text prevent accession-level confirmation for Q96QZ7. Reason: Retain the experimental annotation conservatively without claiming a wrong family member; the accessible evidence does not resolve the exact MAGI protein.
GO:0005737 cytoplasm	IDA PMID:16464232 Postsynaptic recruitment of Dendrin depends on both dendriti...	KEEP AS NON CORE	Summary: MAGI/S-SCAM retains Dendrin in the cytoplasm, but the abstract does not resolve whether the assayed scaffold corresponds specifically to MAGI1 Q96QZ7. Reason: Cytoplasmic MAGI1 is independently supported by other experimental and phylogenetic annotations, so the location can be retained as non-core even though this paper's historical MAGI/S-SCAM nomenclature is unresolved.
GO:0042995 cell projection	IDA PMID:16464232 Postsynaptic recruitment of Dendrin depends on both dendriti...	UNDECIDED	Summary: The study concerns postsynaptic Dendrin recruitment in neuronal projections, but the cached abstract does not provide accession-resolved MAGI1 localization. Reason: Neuronal/postsynaptic localization may be isoform-specific and the available text cannot distinguish the relevant MAGI family member.
GO:0051393 alpha-actinin binding	IPI PMID:16464232 Postsynaptic recruitment of Dendrin depends on both dendriti...	ACCEPT	Summary: The original abstract does not clearly establish a direct MAGI1-alpha-actinin interaction, but an independent human MAGI1 study directly maps alpha-actinin-4 binding to MAGI1's fifth PDZ domain. Reason: PMID:12042308 provides direct in-vitro binding and cellular colocalization evidence for the specific molecular-function term, rescuing the term despite limitations of the original cached abstract. Supporting Evidence: PMID:12042308 alpha-actinin-4 is also capable of binding to MAGI-1
GO:0005886 plasma membrane	TAS PMID:9647739 Cloning and characterization of BAI-associated protein 1: a ...	ACCEPT	Summary: Coexpressed BAI1 and MAGI1/BAP1 colocalize at the cytoplasmic membrane. Reason: The localization is directly reported and corroborated by later human studies. Supporting Evidence: PMID:9647739 both products were co-localized at the cytoplasmic membrane
GO:0005911 cell-cell junction	TAS PMID:9647739 Cloning and characterization of BAI-associated protein 1: a ...	ACCEPT	Summary: BAI1 and MAGI1/BAP1 colocalize preferentially at cell-cell junctions. Reason: This foundational observation is replicated and functionally extended by later adhesion studies. Supporting Evidence: PMID:9647739 especially at cell-cell junctions
GO:0007155 cell adhesion	TAS PMID:9647739 Cloning and characterization of BAI-associated protein 1: a ...	ACCEPT	Summary: The original paper proposed a cell-adhesion role from BAI1-MAGI1 interaction and junctional localization; later ESAM experiments directly demonstrate that MAGI1 recruitment promotes mature cell-cell adhesion. Reason: Later direct functional evidence resolves the initially tentative TAS claim and establishes adhesion as a core process (PMID:20298433). Supporting Evidence: PMID:20298433 subsequently promote actin polymerization and mature cell-cell adhesion
GO:0007166 cell surface receptor signaling pathway	TAS PMID:9647739 Cloning and characterization of BAI-associated protein 1: a ...	KEEP AS NON CORE	Summary: MAGI1 binds the cytoplasmic tail of the adhesion GPCR BAI1, and the original paper suggested a signaling role, but did not directly assay BAI1 signaling. Reason: Receptor-associated signaling is plausible for a junctional adaptor, but this broad pathway term is indirect and context-specific relative to the core adhesion/junction function.
GO:0065003 protein-containing complex assembly	NAS PMID:9647739 Cloning and characterization of BAI-associated protein 1: a ...	ACCEPT	Summary: PDZ-dependent BAI1-MAGI1 association and the many independently mapped MAGI1 complexes support a direct role in assembling protein-containing complexes. Reason: Multivalent complex assembly is the process-level consequence of MAGI1 molecular-adaptor activity, although molecular adaptor activity is the more informative molecular-function term. Supporting Evidence: PMID:9647739 Interaction between BAI1 and BAP1 was mediated by a QTEV motif
GO:0005515 protein binding	IPI PMID:9647693 Atrophin-1, the DRPLA gene product, interacts with two famil...	MARK AS OVER ANNOTATED	Summary: Yeast two-hybrid and in-vitro assays identify MAGI1/AIP3 as an atrophin-1 interactor through its WW-domain-containing architecture. Reason: The interaction is credible but generic protein binding is uninformative and the disease-protein interaction is not the defining physiological MAGI1 activity. Supporting Evidence: PMID:9647693 AIP3/WWP3 are MAGUK-like multidomain proteins
GO:0070830 bicellular tight junction assembly	IDA PMID:21123374 A systematic analysis of human papillomavirus (HPV) E6 PDZ s...	NEW	Summary: Proposed new annotation. HPV E6-mediated MAGI1 degradation disrupts ZO-1 organization, while E6 ablation restores tight junctions only when MAGI1 is present. Reason: This loss-and-restoration experiment establishes a direct requirement for MAGI1 in forming or restoring intact bicellular tight junctions and adds a process term missing from the seeded GOA set. Supporting Evidence: PMID:21123374 Ablation of E6 expression restores tight junctions PMID:21123374 restoration is dependent on the presence of MAGI-1
GO:0005634 nucleus	IDA PMID:21123374 A systematic analysis of human papillomavirus (HPV) E6 PDZ s...	NEW	Summary: Proposed new non-core localization annotation. The study directly reports preferential E6 targeting of MAGI1 in nuclear as well as membrane pools. Reason: The experimentally observed nuclear pool is absent from the seeded GOA review. It should remain non-core because its normal function is not established. Supporting Evidence: PMID:21123374 E6 preferentially targets MAGI-1 within the nucleus

📄 View Raw YAML

id: Q96QZ7
gene_symbol: MAGI1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  MAGI1 is a large, nonenzymatic membrane-associated guanylate kinase-family
  scaffold containing six PDZ domains, two WW domains, and a guanylate-kinase-like
  domain. It concentrates at epithelial tight and adherens junctions and other
  cell-cell contacts, where it recruits adhesion receptors, signaling regulators,
  and actin-associated proteins into multiprotein assemblies. Through these
  complexes MAGI1 couples junctions to the actin cytoskeleton, promotes mature
  cell-cell adhesion and tight-junction integrity, and modulates junctional RhoA,
  Rap, and Wnt/beta-catenin signaling. Tissue- and isoform-dependent roles also
  occur at podocyte slit-diaphragm and neuronal postsynaptic compartments. High-risk
  papillomavirus E6 proteins bind MAGI1 PDZ domains and can drive MAGI1 degradation,
  thereby disrupting tight junctions.
alternative_products:
- name: 1 (MAGI-1C-alpha-beta1)
  id: Q96QZ7-1
- name: 2 (MAGI-1C-beta)
  id: Q96QZ7-2
  sequence_note: VSP_011664, VSP_011666
- name: 3 (MAGI-1A-alpha-beta1)
  id: Q96QZ7-3
  sequence_note: VSP_011670, VSP_011671, VSP_011672
- name: 4 (MAGI-1A-alpha)
  id: Q96QZ7-4
  sequence_note: VSP_011664, VSP_011666, VSP_011667,
- name: 5 (MAGI-1B-alpha-beta)
  id: Q96QZ7-5
  sequence_note: VSP_011666, VSP_011669, VSP_011672
- name: 6 (MAGI-1C-beta2)
  id: Q96QZ7-6
  sequence_note: VSP_011664, VSP_011666, VSP_011667
- name: 7 (MAGI-1C-beta3)
  id: Q96QZ7-7
  sequence_note: VSP_011664, VSP_011665
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic inference places MAGI1 activity in the cytoplasm. Human studies
      detect cytoplasmic pools, but the best-defined core activity is concentrated
      at junctional membrane sites.
    action: KEEP_AS_NON_CORE
    reason: >-
      The location is plausible and experimentally compatible with MAGI1 trafficking
      and cytoplasmic interaction partners, but it is too broad to define the core
      junctional scaffold function.
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Cell-cell junction is the principal site of MAGI1 scaffold activity. Human
      experiments place MAGI1 at epithelial and endothelial contacts and show that
      junctional recruitment promotes actin polymerization and adhesion.
    action: ACCEPT
    reason: >-
      The phylogenetic annotation is strongly corroborated by direct human localization
      and functional evidence (PMID:9647739; PMID:20298433).
    additional_reference_ids:
    - PMID:9647739
    - PMID:20298433
    supported_by:
    - reference_id: PMID:9647739
      supporting_text: both products were co-localized at the cytoplasmic membrane
    - reference_id: PMID:20298433
      supporting_text: Overexpression of ESAM recruited MAGI-1 to the cell-cell contact area.
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      MAGI1 scaffolds RAPGEF2/Rap GEP at tight junctions and ESAM-dependent MAGI1
      recruitment activates RhoA during junction maturation.
    action: ACCEPT
    reason: >-
      Although broad, signal transduction accurately captures a core consequence of
      MAGI1 molecular-adaptor activity and is supported by two independent human
      junctional signaling studies.
    additional_reference_ids:
    - PMID:11168587
    - PMID:20298433
    supported_by:
    - reference_id: PMID:11168587
      supporting_text: serves as a scaffolding molecule for Rap GEP at tight junctions
    - reference_id: PMID:20298433
      supporting_text: Interaction of ESAM with MAGI-1 activated RhoA
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      The ARBA prediction is compatible with experimental cytoplasmic MAGI1 pools,
      including cytoplasmic extensions in podocytes.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retain as a broad secondary location; the active junctional pools are more
      informative for the core function.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt subcellular-location mapping places MAGI1 at the plasma membrane,
      consistent with direct localization at membrane-associated cell contacts.
    action: ACCEPT
    reason: >-
      MAGI1 is a peripheral membrane scaffold recruited to the cytoplasmic face of
      junctional plasma membrane domains (PMID:9647739; PMID:20298433).
    additional_reference_ids:
    - PMID:9647739
    - PMID:20298433
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      ARBA predicts the experimentally established cell-cell-junction localization.
    action: ACCEPT
    reason: >-
      Direct human experiments independently validate this location
      (PMID:9647739; PMID:20298433).
    additional_reference_ids:
    - PMID:9647739
    - PMID:20298433
- term:
    id: GO:0005923
    label: bicellular tight junction
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt mapping assigns MAGI1 to bicellular tight junctions, the best-defined
      epithelial site of its scaffold activity.
    action: ACCEPT
    reason: >-
      MAGI1 is directly localized to tight junctions, and MAGI1 loss disrupts tight-
      junction integrity (PMID:11168587; PMID:21123374).
    additional_reference_ids:
    - PMID:11168587
    - PMID:21123374
    supported_by:
    - reference_id: PMID:21123374
      supporting_text: MAGI-1 degradation is a loss of tight-junction integrity
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      The generic membrane prediction captures a real feature but loses the strong
      evidence for junctional plasma-membrane localization.
    action: MODIFY
    reason: >-
      Replace the overly broad membrane term with plasma membrane and bicellular
      tight junction, both already supported by direct and curated evidence.
    proposed_replacement_terms:
    - id: GO:0005886
      label: plasma membrane
    - id: GO:0005923
      label: bicellular tight junction
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11168587
  qualifier: enables
  review:
    summary: >-
      MAGI1 interacts with RAPGEF2/Rap GEP and functions as its tight-junction scaffold.
      The experiment supports an adaptor activity more informative than generic
      protein binding.
    action: MODIFY
    reason: >-
      MAGI1's defining molecular role is to assemble interacting proteins into
      junctional complexes. Molecular adaptor activity captures this causal role
      without treating MAGI1 as an enzyme.
    proposed_replacement_terms:
    - id: GO:0060090
      label: molecular adaptor activity
    additional_reference_ids:
    - file:human/MAGI1/MAGI1-deep-research-manual.md
    supported_by:
    - reference_id: PMID:11168587
      supporting_text: MAGI-1/BAP1 serves as a scaffolding molecule for Rap GEP
    - reference_id: file:human/MAGI1/MAGI1-deep-research-manual.md
      supporting_text: The best-supported core role is organization of cell-cell junction complexes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12097473
  qualifier: enables
  review:
    summary: >-
      The abstract reports KIF1Balpha binding to the neuronal scaffold S-SCAM, but
      the cached text does not resolve the accession or older MAGI/S-SCAM nomenclature
      sufficiently to verify that the assayed product was human MAGI1 Q96QZ7.
    action: UNDECIDED
    reason: >-
      The full evidence needed to resolve the exact MAGI family member is unavailable.
      Per curation policy, the experimental annotation is not rejected from an
      abstract-level nomenclature ambiguity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12444549
  qualifier: enables
  review:
    summary: >-
      Papillomavirus E6 proteins carrying PDZ-binding sequences bind MAGI1 and may
      target it for degradation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction is credible, but generic protein binding is uninformative for
      MAGI1's normal molecular function and the viral interaction is a perturbation
      rather than a core activity.
    supported_by:
    - reference_id: PMID:12444549
      supporting_text: enables them to bind Dlg and a second MAGUK family member, MAGI-1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14627983
  qualifier: enables
  review:
    summary: >-
      FCHSD2/Carom binds the fifth PDZ domain of MAGI1 in vitro and transiently
      overlaps MAGI1 before epithelial junction maturation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The domain-specific interaction supports the scaffold model, but the generic
      protein-binding term adds no informative molecular function.
    supported_by:
    - reference_id: PMID:14627983
      supporting_text: Carom binds to the fifth PDZ domain of MAGI-1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16316992
  qualifier: enables
  review:
    summary: >-
      The cached abstract describes beta1-adrenergic receptor interactions with
      MAGI2 and MAGI3 but does not identify MAGI1; the MAGI1 evidence may be confined
      to the proteomic array or supplementary material.
    action: UNDECIDED
    reason: >-
      Without the accession-level result, the specific MAGI1 interaction cannot be
      verified. The experimental annotation is retained without alleging curator or
      paralog error.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17267502
  qualifier: enables
  review:
    summary: >-
      Crystal structures establish direct recognition of an HPV18 E6 peptide by
      MAGI1 PDZ domains.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The structural interaction is well supported but describes viral hijacking;
      generic protein binding should not be treated as the core MAGI1 function.
    supported_by:
    - reference_id: PMID:17267502
      supporting_text: peptide from HPV18 E6 bound to three PDZ domains from MAGI-1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22662192
  qualifier: enables
  review:
    summary: >-
      Co-immunoprecipitation and proximity assays detect MAGI1 association with
      IQGAP1 in cultured human podocytes.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This supports a podocyte junctional complex context, but generic protein
      binding is not an informative molecular-function annotation for MAGI1.
    supported_by:
    - reference_id: PMID:22662192
      supporting_text: interactions between IQGAP1 and SD proteins (nephrin, MAGI-1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22898364
  qualifier: enables
  review:
    summary: >-
      This large-scale virus-host interaction study includes papillomavirus E6-MAGI1
      pairs in its interaction dataset.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      A high-throughput viral interaction does not define MAGI1's physiological
      molecular activity, and protein binding is too generic to retain as core.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23873930
  qualifier: enables
  review:
    summary: >-
      WW-domain screening and follow-up assays identify PRRG4 as a MAGI1-interacting
      membrane protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction is compatible with multivalent adaptor activity, but generic
      protein binding does not describe the biological function of the complex.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30126976
  qualifier: enables
  review:
    summary: >-
      Proteome-wide peptide-phage screening maps PDZ-domain interactions and their
      phosphoregulation, including MAGI1 domain interactions in the dataset.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The assay is valuable interaction evidence but generic protein binding is
      neither specific nor a core functional description.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33208464
  qualifier: enables
  review:
    summary: >-
      MAGI1 appears in a rabies-virus matrix-protein interactome, but the cached
      article's validated mechanistic work focuses on ATP6V1A and does not expose
      the accession-level MAGI1 result in the main text.
    action: UNDECIDED
    reason: >-
      The exact MAGI1 evidence cannot be verified from the available article text;
      the experimental interaction is therefore retained without a confident
      functional interpretation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33864728
  qualifier: enables
  review:
    summary: >-
      A SARS-CoV-2 PDZome affinity screen is cited for MAGI1, but the abstract's
      named high-confidence binders do not include MAGI1 and the cache lacks the
      supplementary accession-level table.
    action: UNDECIDED
    reason: >-
      The specific MAGI1 interaction cannot be confirmed from the accessible
      abstract-only record. It is not removed because the curator may have used
      supplementary data unavailable here.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      BioPlex affinity-purification networks report MAGI1 interaction partners in
      cell-line-specific, proteome-scale datasets.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interactions may be valid, but a broad protein-binding label derived from
      a proteome-scale network does not identify MAGI1's molecular activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: >-
      OpenCell combines endogenous tagging, microscopy, and interaction proteomics
      to map cellular organization; the MAGI1 pair is a high-throughput dataset result.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is useful interaction context but does not justify retaining generic
      protein binding as a defining MAGI1 molecular function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36012204
  qualifier: enables
  review:
    summary: >-
      MAGI1 was recovered in CFTR proximity-labeling datasets.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Proximity labeling does not by itself establish direct binding or a MAGI1
      function, and the generic protein-binding term overstates the functional
      information supplied by the assay.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36115835
  qualifier: enables
  review:
    summary: >-
      Quantitative fragmentomics measured affinities for hundreds of MAGI1 PDZ-domain
      interactions with PDZ-binding motifs, providing extensive biochemical binding
      evidence.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The dataset strongly supports MAGI1's multivalent interaction architecture,
      but collapsing hundreds of motif affinities into generic protein binding is
      not an informative functional annotation.
    supported_by:
    - reference_id: PMID:36115835
      supporting_text: 65,000 interactions involving PDZ domains and their target PDZ-binding motifs
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37100772
  qualifier: enables
  review:
    summary: >-
      A pan-viral phage screen identifies viral short linear motifs that engage host
      interaction domains, including a MAGI1-virus pair.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Viral motif mimicry is a perturbational interaction context, and generic
      protein binding is not a suitable core function for MAGI1.
- term:
    id: GO:0030054
    label: cell junction
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Human Protein Atlas immunofluorescence detects MAGI1 at cell junctions.
    action: ACCEPT
    reason: >-
      This direct localization is consistent with the independently established
      tight-junction and cell-cell-contact localization.
- term:
    id: GO:0001886
    label: endothelial cell morphogenesis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: >-
      Orthology-based transfer assigns MAGI1 a role in endothelial cell morphogenesis,
      consistent with the conserved AMOTL2-MAGI1-CDH5 junction-actin complex.
    action: KEEP_AS_NON_CORE
    reason: >-
      The process is biologically plausible but is a tissue-specific developmental
      consequence of the general junctional scaffold function and lacks direct human
      morphogenesis evidence in the cited transfer.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:20298433
  qualifier: located_in
  review:
    summary: >-
      ESAM-transfection experiments detect a non-junctional cytoplasmic MAGI1 pool
      in addition to recruitment at cell contacts.
    action: KEEP_AS_NON_CORE
    reason: >-
      Retain the experimentally observed broad pool, but the contact-associated
      plasma-membrane localization is the functionally informative site.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:20298433
  qualifier: located_in
  review:
    summary: >-
      ESAM recruits MAGI1 to the cell membrane and cell-cell contact area during
      mature adhesion.
    action: ACCEPT
    reason: >-
      The localization is direct and mechanistically linked to RhoA-dependent
      adhesion maturation.
    supported_by:
    - reference_id: PMID:20298433
      supporting_text: ESAM-mediated MAGI-1 recruitment to the cell membrane
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: IDA
  original_reference_id: PMID:20298433
  qualifier: located_in
  review:
    summary: >-
      ESAM expression recruits MAGI1 to cell-cell contacts in a PDZ-dependent
      junctional adhesion system.
    action: ACCEPT
    reason: >-
      This is direct localization at the core site of MAGI1 activity.
    supported_by:
    - reference_id: PMID:20298433
      supporting_text: Overexpression of ESAM recruited MAGI-1 to the cell-cell contact area.
- term:
    id: GO:0022409
    label: positive regulation of cell-cell adhesion
  evidence_type: IDA
  original_reference_id: PMID:20298433
  qualifier: involved_in
  review:
    summary: >-
      ESAM-MAGI1 colocalization promotes actin polymerization and firm cell-cell
      adhesion through RhoA signaling.
    action: ACCEPT
    reason: >-
      Functional adhesion and inhibitor experiments directly establish this as a
      core downstream process of junctional MAGI1 scaffolding.
    supported_by:
    - reference_id: PMID:20298433
      supporting_text: resulted in firm cell-cell adhesion
    - reference_id: PMID:20298433
      supporting_text: Interaction of ESAM with MAGI-1 activated RhoA
- term:
    id: GO:0071944
    label: cell periphery
  evidence_type: IDA
  original_reference_id: PMID:20298433
  qualifier: located_in
  review:
    summary: >-
      MAGI1 is detected at the cell periphery after recruitment by ESAM.
    action: KEEP_AS_NON_CORE
    reason: >-
      The localization is valid but less specific than the accepted plasma-membrane
      and cell-cell-junction terms from the same study.
- term:
    id: GO:0005912
    label: adherens junction
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Orthology transfer places MAGI1 at adherens junctions. Human cell studies show
      MAGI1 stabilizes E-cadherin and beta-catenin at cell-cell junctions.
    action: ACCEPT
    reason: >-
      The transferred location is consistent with direct human functional evidence
      for adherens-junction stabilization (PMID:21666716).
    additional_reference_ids:
    - PMID:21666716
    supported_by:
    - reference_id: PMID:21666716
      supporting_text: stabilized E-cadherin and beta-catenin localization at cell-cell junctions
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16464232
  qualifier: enables
  review:
    summary: >-
      The abstract reports Dendrin interaction with MAGI/S-SCAM, but older nomenclature
      and the unavailable full text prevent accession-level confirmation for Q96QZ7.
    action: UNDECIDED
    reason: >-
      Retain the experimental annotation conservatively without claiming a wrong
      family member; the accessible evidence does not resolve the exact MAGI protein.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:16464232
  qualifier: located_in
  review:
    summary: >-
      MAGI/S-SCAM retains Dendrin in the cytoplasm, but the abstract does not resolve
      whether the assayed scaffold corresponds specifically to MAGI1 Q96QZ7.
    action: KEEP_AS_NON_CORE
    reason: >-
      Cytoplasmic MAGI1 is independently supported by other experimental and
      phylogenetic annotations, so the location can be retained as non-core even
      though this paper's historical MAGI/S-SCAM nomenclature is unresolved.
- term:
    id: GO:0042995
    label: cell projection
  evidence_type: IDA
  original_reference_id: PMID:16464232
  qualifier: located_in
  review:
    summary: >-
      The study concerns postsynaptic Dendrin recruitment in neuronal projections,
      but the cached abstract does not provide accession-resolved MAGI1 localization.
    action: UNDECIDED
    reason: >-
      Neuronal/postsynaptic localization may be isoform-specific and the available
      text cannot distinguish the relevant MAGI family member.
- term:
    id: GO:0051393
    label: alpha-actinin binding
  evidence_type: IPI
  original_reference_id: PMID:16464232
  qualifier: enables
  review:
    summary: >-
      The original abstract does not clearly establish a direct MAGI1-alpha-actinin
      interaction, but an independent human MAGI1 study directly maps alpha-actinin-4
      binding to MAGI1's fifth PDZ domain.
    action: ACCEPT
    reason: >-
      PMID:12042308 provides direct in-vitro binding and cellular colocalization
      evidence for the specific molecular-function term, rescuing the term despite
      limitations of the original cached abstract.
    additional_reference_ids:
    - PMID:12042308
    supported_by:
    - reference_id: PMID:12042308
      supporting_text: alpha-actinin-4 is also capable of binding to MAGI-1
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:9647739
  qualifier: located_in
  review:
    summary: >-
      Coexpressed BAI1 and MAGI1/BAP1 colocalize at the cytoplasmic membrane.
    action: ACCEPT
    reason: >-
      The localization is directly reported and corroborated by later human studies.
    supported_by:
    - reference_id: PMID:9647739
      supporting_text: both products were co-localized at the cytoplasmic membrane
- term:
    id: GO:0005911
    label: cell-cell junction
  evidence_type: TAS
  original_reference_id: PMID:9647739
  qualifier: located_in
  review:
    summary: >-
      BAI1 and MAGI1/BAP1 colocalize preferentially at cell-cell junctions.
    action: ACCEPT
    reason: >-
      This foundational observation is replicated and functionally extended by
      later adhesion studies.
    supported_by:
    - reference_id: PMID:9647739
      supporting_text: especially at cell-cell junctions
- term:
    id: GO:0007155
    label: cell adhesion
  evidence_type: TAS
  original_reference_id: PMID:9647739
  qualifier: involved_in
  review:
    summary: >-
      The original paper proposed a cell-adhesion role from BAI1-MAGI1 interaction
      and junctional localization; later ESAM experiments directly demonstrate that
      MAGI1 recruitment promotes mature cell-cell adhesion.
    action: ACCEPT
    reason: >-
      Later direct functional evidence resolves the initially tentative TAS claim
      and establishes adhesion as a core process (PMID:20298433).
    additional_reference_ids:
    - PMID:20298433
    supported_by:
    - reference_id: PMID:20298433
      supporting_text: subsequently promote actin polymerization and mature cell-cell adhesion
- term:
    id: GO:0007166
    label: cell surface receptor signaling pathway
  evidence_type: TAS
  original_reference_id: PMID:9647739
  qualifier: involved_in
  review:
    summary: >-
      MAGI1 binds the cytoplasmic tail of the adhesion GPCR BAI1, and the original
      paper suggested a signaling role, but did not directly assay BAI1 signaling.
    action: KEEP_AS_NON_CORE
    reason: >-
      Receptor-associated signaling is plausible for a junctional adaptor, but this
      broad pathway term is indirect and context-specific relative to the core
      adhesion/junction function.
- term:
    id: GO:0065003
    label: protein-containing complex assembly
  evidence_type: NAS
  original_reference_id: PMID:9647739
  qualifier: involved_in
  review:
    summary: >-
      PDZ-dependent BAI1-MAGI1 association and the many independently mapped MAGI1
      complexes support a direct role in assembling protein-containing complexes.
    action: ACCEPT
    reason: >-
      Multivalent complex assembly is the process-level consequence of MAGI1
      molecular-adaptor activity, although molecular adaptor activity is the more
      informative molecular-function term.
    supported_by:
    - reference_id: PMID:9647739
      supporting_text: Interaction between BAI1 and BAP1 was mediated by a QTEV motif
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9647693
  qualifier: enables
  review:
    summary: >-
      Yeast two-hybrid and in-vitro assays identify MAGI1/AIP3 as an atrophin-1
      interactor through its WW-domain-containing architecture.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction is credible but generic protein binding is uninformative and
      the disease-protein interaction is not the defining physiological MAGI1 activity.
    supported_by:
    - reference_id: PMID:9647693
      supporting_text: AIP3/WWP3 are MAGUK-like multidomain proteins
- term:
    id: GO:0070830
    label: bicellular tight junction assembly
  evidence_type: IDA
  original_reference_id: PMID:21123374
  qualifier: involved_in
  review:
    summary: >-
      Proposed new annotation. HPV E6-mediated MAGI1 degradation disrupts ZO-1
      organization, while E6 ablation restores tight junctions only when MAGI1 is
      present.
    action: NEW
    reason: >-
      This loss-and-restoration experiment establishes a direct requirement for
      MAGI1 in forming or restoring intact bicellular tight junctions and adds a
      process term missing from the seeded GOA set.
    supported_by:
    - reference_id: PMID:21123374
      supporting_text: Ablation of E6 expression restores tight junctions
    - reference_id: PMID:21123374
      supporting_text: restoration is dependent on the presence of MAGI-1
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:21123374
  qualifier: located_in
  review:
    summary: >-
      Proposed new non-core localization annotation. The study directly reports
      preferential E6 targeting of MAGI1 in nuclear as well as membrane pools.
    action: NEW
    reason: >-
      The experimentally observed nuclear pool is absent from the seeded GOA review.
      It should remain non-core because its normal function is not established.
    supported_by:
    - reference_id: PMID:21123374
      supporting_text: E6 preferentially targets MAGI-1 within the nucleus
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- 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:11168587
  title: Membrane-associated guanylate kinase with inverted orientation (MAGI)-1/brain
    angiogenesis inhibitor 1-associated protein (BAP1) as a scaffolding molecule for
    Rap small G protein GDP/GTP exchange protein at tight junctions.
  findings:
  - statement: >-
      Human MAGI1 directly interacts with RAPGEF2/Rap GEP and acts as its scaffold
      at epithelial tight junctions.
    supporting_text: MAGI-1/BAP1 serves as a scaffolding molecule for Rap GEP
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified primary human study; direct support for molecular adaptor
      activity, tight-junction localization, and junctional Rap signaling. The cache
      is abstract-only.
- id: PMID:12097473
  title: Association of the kinesin superfamily motor protein KIF1Balpha with postsynaptic
    density-95 (PSD-95), synapse-associated protein-97, and synaptic scaffolding molecule
    PSD-95/discs large/zona occludens-1 proteins.
  findings:
  - statement: >-
      KIF1Balpha binds neuronal PDZ scaffolds including S-SCAM and may use them as
      cargo receptors.
    supporting_text: S-SCAM have a novel function as KIF1Balpha receptors
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: >-
      The paper is real and relevant to neuronal PDZ scaffolds, but the abstract-only
      cache does not resolve older S-SCAM/MAGI nomenclature or verify Q96QZ7 at the
      accession level.
- id: PMID:12444549
  title: Chimaeric HPV E6 proteins allow dissection of the proteolytic pathways regulating
    different E6 cellular target proteins.
  findings:
  - statement: >-
      Papillomavirus E6 PDZ-binding sequences confer MAGI1 binding, with virus-type-
      specific consequences for MAGI1 degradation.
    supporting_text: enables them to bind Dlg and a second MAGUK family member, MAGI-1
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified primary study; supports viral PDZ-mediated interaction but not
      MAGI1's normal core function. Abstract-only in cache.
- id: PMID:14627983
  title: 'Carom: a novel membrane-associated guanylate kinase-interacting protein
    with two SH3 domains.'
  findings:
  - statement: >-
      FCHSD2/Carom binds MAGI1 PDZ5 and transiently overlaps MAGI1 during epithelial
      junction maturation.
    supporting_text: Carom binds to the fifth PDZ domain of MAGI-1
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified direct interaction study. It informs MAGI1 scaffold architecture
      but not a distinct molecular function. Abstract-only in cache.
- id: PMID:16316992
  title: Proteomic analysis of beta1-adrenergic receptor interactions with PDZ scaffold
    proteins.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: >-
      The cached abstract names MAGI2 and MAGI3, not MAGI1. The accession-level MAGI1
      result may be in an unavailable proteomic table, so the GOA interaction cannot
      be independently verified and is not called miscited.
- id: PMID:16464232
  title: Postsynaptic recruitment of Dendrin depends on both dendritic mRNA transport
    and synaptic anchoring.
  findings:
  - statement: >-
      Dendrin associates with MAGI/S-SCAM, which retains it in the cytoplasm and
      contributes to postsynaptic recruitment.
    supporting_text: Dendrin interacts with the cytoskeletal components alpha-actinin and Maguk
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: >-
      The paper is relevant, but the abstract-only cache and historical MAGI/S-SCAM
      naming do not resolve the exact MAGI family member or isoform. Experimental
      annotations are conservatively left undecided.
- id: PMID:17267502
  title: 'Structures of a human papillomavirus (HPV) E6 polypeptide bound to MAGUK
    proteins: mechanisms of targeting tumor suppressors by a high-risk HPV oncoprotein.'
  findings:
  - statement: >-
      Crystal structures define direct HPV18 E6 peptide recognition by MAGI1 PDZ
      domains and the molecular determinants of E6-mediated targeting.
    supporting_text: peptide from HPV18 E6 bound to three PDZ domains from MAGI-1
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified structural study; strong biochemical evidence for a viral
      interaction, but secondary to normal MAGI1 function. Cached record is
      abstract-only despite a PMCID.
- id: PMID:20298433
  title: Interaction of endothelial cell-selective adhesion molecule and MAGI-1 promotes
    mature cell-cell adhesion via activation of RhoA.
  findings:
  - statement: >-
      ESAM recruits MAGI1 to cell contacts, where the complex activates RhoA,
      promotes actin polymerization, and strengthens cell-cell adhesion.
    supporting_text: Interaction of ESAM with MAGI-1 activated RhoA
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified direct human-function study; central evidence for junctional
      localization, RhoA-linked signaling, actin remodeling, and adhesion. The cache
      is abstract-only.
- id: PMID:22662192
  title: IQGAP1 interacts with components of the slit diaphragm complex in podocytes
    and is involved in podocyte migration and permeability in vitro.
  findings:
  - statement: >-
      MAGI1 localizes to the membrane and cytoplasmic extensions of human podocytes
      and associates with IQGAP1 in immunoprecipitation and proximity assays.
    supporting_text: MAGI-1 was localized at cell membrane and cytoplasmic extensions.
    reference_section_type: RESULTS
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Full-text primary study; verifies a podocyte-specific localization and
      interaction context, although the functional perturbation targets IQGAP1
      rather than MAGI1.
- id: PMID:22898364
  title: Comparative analysis of virus-host interactomes with a mammalian high-throughput
    protein complementation assay based on Gaussia princeps luciferase.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: >-
      Proteome-scale papillomavirus-host interaction mapping. The MAGI1 pairs are
      dataset-level and not exposed in the cached abstract, so this is weak evidence
      for normal gene function.
- id: PMID:23873930
  title: Cellular localization and characterization of cytosolic binding partners
    for Gla domain-containing proteins PRRG4 and PRRG2.
  findings:
  - statement: >-
      WW-domain screening and follow-up assays identify MAGI1 among PRRG4-interacting
      cytosolic proteins.
    supporting_text: We screened WW domain arrays for cytosolic binding partners for PRRG4
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Full-text primary interaction study; supports the PRRG4-MAGI1 interaction and
      MAGI1 WW-domain scaffold context, but not a separate core function.
- id: PMID:30126976
  title: Proteome-wide analysis of phospho-regulated PDZ domain interactions.
  findings:
  - statement: >-
      Proteome-wide peptide-phage display maps PDZ-motif interactions and identifies
      phosphorylation-dependent interaction switches.
    supporting_text: Proteome-wide analysis of phospho-regulated PDZ domain interactions.
    reference_section_type: TITLE
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Full-text high-throughput PDZ interaction study. MAGI1 evidence is dataset-level
      and informative for domain specificity rather than gene-level core function.
- id: PMID:33208464
  title: The ATPase ATP6V1A facilitates rabies virus replication by promoting virion
    uncoating and interacting with the viral matrix protein.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: >-
      Full-text rabies-virus interactome paper; mechanistic validation concerns
      ATP6V1A. The MAGI1 dataset row is not apparent in the main cached text.
- id: PMID:33864728
  title: Host PDZ-containing proteins targeted by SARS-CoV-2.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: >-
      Abstract-only PDZome screen. MAGI1 is not among the binders named in the
      abstract, and the accession-level supplementary result is unavailable.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Full-text BioPlex study; source of cell-line-specific MAGI1 interaction pairs.
      Useful network context but not a specific molecular function.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Full-text high-throughput localization/interactome resource. The MAGI1 pair is
      dataset-level and does not define core function.
- id: PMID:36012204
  title: Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment
    in Multiple SLC Transporters.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Full-text proximity-labeling study. Proximity to CFTR does not establish direct
      MAGI1 binding or a physiological MAGI1 activity.
- id: PMID:36115835
  title: Quantitative fragmentomics allow affinity mapping of interactomes.
  findings:
  - statement: >-
      Quantitative fragmentomics measures a large PDZ-PBM affinity landscape that
      includes extensive MAGI1 domain interactions.
    supporting_text: 65,000 interactions involving PDZ domains and their target PDZ-binding motifs
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Full-text biochemical resource with direct affinity measurements. Strong
      support for multivalent PDZ binding, but generic protein binding remains an
      uninformative GO molecular function.
- id: PMID:37100772
  title: Large-scale phage-based screening reveals extensive pan-viral mimicry of
    host short linear motifs.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Full-text pan-viral motif screen; the MAGI1 interaction is a perturbational
      dataset result rather than evidence for normal core function.
- id: PMID:9647693
  title: Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing
    proteins.
  findings:
  - statement: >-
      MAGI1/AIP3 is a WW-domain-containing atrophin-1 interactor with multiple
      protein-interaction modules.
    supporting_text: AIP3/WWP3 are MAGUK-like multidomain proteins
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified original interaction/cloning context; relevant to architecture
      but not to the core junctional function. Abstract-only in cache.
- id: PMID:9647739
  title: 'Cloning and characterization of BAI-associated protein 1: a PDZ domain-containing
    protein that interacts with BAI1.'
  findings:
  - statement: >-
      The original human MAGI1/BAP1 study identifies PDZ-dependent BAI1 binding and
      colocalization at the plasma membrane, especially cell-cell junctions.
    supporting_text: both products were co-localized at the cytoplasmic membrane
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified foundational human cloning and interaction study; direct support
      for plasma-membrane/cell-cell-junction localization and complex assembly.
      Abstract-only in cache.
- id: PMID:12042308
  title: Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-4,
    with the tight junction protein MAGI-1.
  findings:
  - statement: >-
      MAGI1 binds synaptopodin through WW2 and alpha-actinin-4 through PDZ5, and all
      three proteins colocalize at epithelial tight junctions.
    supporting_text: alpha-actinin-4 is also capable of binding to MAGI-1
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified direct human MAGI1 interaction study; decisive support for
      alpha-actinin binding and for coupling junctions to actin-associated proteins.
      Abstract-only in cache.
- id: PMID:21123374
  title: A systematic analysis of human papillomavirus (HPV) E6 PDZ substrates identifies
    MAGI-1 as a major target of HPV type 16 (HPV-16) and HPV-18 whose loss accompanies
    disruption of tight junctions.
  findings:
  - statement: >-
      HPV16/18 E6 degrades MAGI1 at nuclear and membrane sites; MAGI1 loss disrupts
      tight-junction integrity and MAGI1 is required for junction restoration.
    supporting_text: restoration is dependent on the presence of MAGI-1
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified direct loss/restoration study; strong support for tight-junction
      assembly/integrity and a nuclear MAGI1 pool. Abstract-only in cache despite PMCID.
- id: PMID:21666716
  title: Identification of MAGI1 as a tumor-suppressor protein induced by cyclooxygenase-2
    inhibitors in colorectal cancer cells.
  findings:
  - statement: >-
      MAGI1 gain and loss reciprocally regulate E-cadherin/beta-catenin junctional
      localization, actin organization, adhesion, Wnt signaling, migration, and invasion.
    supporting_text: stabilized E-cadherin and beta-catenin localization at cell-cell junctions
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified human gain/loss functional study; supports adherens-junction
      stabilization and junction-associated signaling. Abstract-only in cache.
- id: file:human/MAGI1/MAGI1-uniprot.txt
  title: UniProt entry Q96QZ7 (MAGI1_HUMAN), Membrane-associated guanylate kinase,
    WW and PDZ domain-containing protein 1
  findings:
  - statement: >-
      Reviewed UniProt identifies six PDZ domains, two WW domains, a guanylate-
      kinase-like domain, tight-junction/cell-membrane localization, and numerous
      domain-mapped interaction partners.
    supporting_text: Localizes to epithelial cells tight junctions.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Reviewed UniProt record Q96QZ7; authoritative source for domain architecture,
      isoforms, and curated subcellular/interactor summaries.
- id: file:human/MAGI1/MAGI1-deep-research-manual.md
  title: MAGI1 manual literature and annotation synthesis
  findings:
  - statement: >-
      Manual synthesis identifies junctional molecular-adaptor activity as the
      best-supported core function and separates it from generic interaction records.
    supporting_text: The best-supported core role is organization of cell-cell junction complexes.
    reference_section_type: LITERATURE_REVIEW
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Manually assembled from cached primary publications and reviewed UniProt after
      both configured deep-research providers failed.
core_functions:
- description: >-
    Functions as a multivalent molecular adaptor at epithelial and endothelial
    cell-cell junctions: PDZ and WW domains recruit adhesion receptors, signaling
    regulators, and actin-associated proteins into junctional assemblies that couple
    the plasma membrane to the cytoskeleton, promote tight-junction assembly and
    integrity, and strengthen mature cell-cell adhesion.
  molecular_function:
    id: GO:0060090
    label: molecular adaptor activity
  directly_involved_in:
  - id: GO:0070830
    label: bicellular tight junction assembly
  - id: GO:0022409
    label: positive regulation of cell-cell adhesion
  - id: GO:0065003
    label: protein-containing complex assembly
  locations:
  - id: GO:0005923
    label: bicellular tight junction
  - id: GO:0005912
    label: adherens junction
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: PMID:11168587
    supporting_text: MAGI-1/BAP1 serves as a scaffolding molecule for Rap GEP
  - reference_id: PMID:20298433
    supporting_text: Interaction of ESAM with MAGI-1 activated RhoA
  - reference_id: PMID:12042308
    supporting_text: alpha-actinin-4 is also capable of binding to MAGI-1
  - reference_id: PMID:21123374
    supporting_text: restoration is dependent on the presence of MAGI-1
proposed_new_terms: []
suggested_questions:
- question: >-
    Which MAGI1 isoforms execute epithelial tight-junction, podocyte slit-diaphragm,
    and neuronal postsynaptic scaffold functions, and which interactions are genuinely
    isoform-specific rather than simply assayed with one isoform?
  experts:
  - epithelial junction biologists
  - podocyte biologists
  - neuronal MAGI scaffold specialists
- question: >-
    Does the MAGI1 guanylate-kinase-like domain bind nucleotides or partners under
    physiological conditions, and should ATP binding remain annotated without a
    demonstrated catalytic role?
  experts:
  - MAGUK structural biologists
  - GO molecular-function curators
- question: >-
    Which of the hundreds of PDZ-motif interactions detected by fragmentomics occur
    at endogenous abundance in polarized tissues and contribute to junction function?
  experts:
  - quantitative interactomics experts
  - epithelial polarity experts
suggested_experiments:
- description: >-
    Create isoform-specific MAGI1 knockout/rescue panels in human epithelial cells,
    podocytes, and neurons; quantify junction or synapse localization, barrier
    resistance, actin coupling, and endogenous partner recruitment.
  hypothesis: >-
    Alternative MAGI1 termini and internal segments partition a shared molecular-
    adaptor activity into tissue-specific junctional and postsynaptic complexes.
  experiment_type: isoform-specific endogenous rescue and functional imaging
- description: >-
    Reconstitute selected endogenous MAGI1 PDZ/WW interactions at native expression
    levels using domain-selective mutations, proximity labeling, quantitative
    co-immunoprecipitation, and junction barrier assays.
  hypothesis: >-
    A small subset of high-affinity interactions, rather than the full fragmentomics
    interactome, is required for MAGI1-dependent tight-junction assembly and adhesion.
  experiment_type: domain-resolved interaction-to-function perturbation
- description: >-
    Compare purified MAGI1 guanylate-kinase-like domain with canonical guanylate
    kinases using nucleotide-binding, catalytic, and structural assays, followed by
    rescue with nucleotide-pocket mutants in polarized cells.
  hypothesis: >-
    The MAGI1 guanylate-kinase-like domain functions as a noncatalytic interaction
    module rather than an active guanylate kinase.
  experiment_type: biochemical activity and structure-function rescue

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Manual

MAGI1 manual deep research

Scope and provenance

Biological synthesis

Curation conclusions

Evidence limitations

📚 Additional Documentation

Notes

MAGI1 review notes

2026-07-18

📄 View Raw YAML