GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000041

Gene Ontology annotation based on UniPathway vocabulary mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:17589504

Ambra1 regulates autophagy and development of the nervous system.

AMBRA1 was identified as a WD40-domain positive regulator of BECN1-dependent autophagy and neural development.

PMID:20562859

Network organization of the human autophagy system.

A human autophagy interaction-network study placed AMBRA1/DCAF3 with DDB1-CUL4-DDA1 and the PIK3C3-BECN1 complex.

PMID:20921139

The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy.

AMBRA1 links the dynein-tethered BECN1-VPS34 complex to ULK1-dependent release and ER-associated autophagosome nucleation.

PMID:21358617

Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy.

AMBRA1 interacts with mitochondrial BCL2 and supports BECN1-dependent autophagy regulation.

PMID:21753002

Parkin interacts with Ambra1 to induce mitophagy.

AMBRA1 interacts with Parkin and is required for efficient mitochondrial clearance after depolarization.

PMID:22190034

Global landscape of HIV-human protein complexes.

PMID:23524951

mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6.

AMBRA1 and TRAF6 support K63-linked ULK1 ubiquitylation during autophagy induction.

PMID:23954414

Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism.

PMID:23974797

WASH inhibits autophagy through suppression of Beclin 1 ubiquitination.

PMID:25127057

TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.

PMID:25215947

AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1.

AMBRA1 promotes LC3-dependent mitophagy through a LIR motif in Parkin-dependent and Parkin-independent settings.

PMID:25438055

AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation.

AMBRA1 interacts with PP2A and promotes PP2A-dependent MYC dephosphorylation and degradation.

PMID:25499913

AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics.

Cullin-4 and Cullin-5 dynamically interact with AMBRA1 to regulate onset and termination of autophagy.

PMID:25891078

IRGM governs the core autophagy machinery to conduct antimicrobial defense.

The cached IRGM paper supports IRGM organization of autophagy regulators but does not establish AMBRA1 GTPase-binding activity.

PMID:30166453

CRL4(AMBRA1) targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling.

CRL4AMBRA1 targets ELOC for ubiquitination and degradation, modulating CRL5 signaling.

PMID:30217973

HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα.

HUWE1 and IKKa regulate AMBRA1-mediated mitophagy and MFN2 degradation.

PMID:30513302

AMBRA1 Controls Regulatory T-Cell Differentiation and Homeostasis Upstream of the FOXO3-FOXP3 Axis.

AMBRA1 supports regulatory T-cell differentiation through PP2A- and FOXO3-associated mechanisms.

PMID:31123703

Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains.

TRIM32 binds AMBRA1 and ULK1 and stimulates ULK1 activity through unanchored K63-linked polyubiquitin in atrophic muscle cells.

PMID:32333458

Rare mutations in the autophagy-regulating gene AMBRA1 contribute to human neural tube defects.

Human AMBRA1 variants impair autophagy initiation and may contribute to neural tube defects.

PMID:32616651

The autophagy protein Ambra1 regulates gene expression by supporting novel transcriptional complexes.

AMBRA1 has nuclear scaffolding roles at chromatin-associated transcriptional complexes.

PMID:33854232

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.

AMBRA1 regulates cyclin D abundance to guard S-phase entry and genomic integrity.

PMID:33854235

CRL4(AMBRA1) is a master regulator of D-type cyclins.

CRL4AMBRA1 targets all three D-type cyclins for degradation.

PMID:33854239

The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.

AMBRA1 mediates ubiquitylation and proteasomal degradation of cyclin D as a CRL4 substrate receptor.

PMID:34362797

AMBRA1 Promotes TGFβ Signaling via Nonproteolytic Polyubiquitylation of Smad4.

AMBRA1 acts as the CRL4 (CRL4-AMBRA1/DCAF3) substrate receptor for Smad4 and mediates nonproteolytic polyubiquitylation of Smad4 that enhances its transcriptional functions and potentiates TGFbeta signaling.

PMID:37993427

Structure of the DDB1-AMBRA1 E3 ligase receptor complex linked to cell cycle regulation.

A 3.08 Angstrom cryo-EM structure shows AMBRA1 N- and C-terminal regions fold together into a split WD40 domain that binds DDB1, and DDB1 binding-defective AMBRA1 mutants prevent Cyclin D1 ubiquitination and increase cell cycle progression.

Reactome:R-HSA-1632843

AMBRA1 binds DYNLL1,DYNLL2

Reactome represents cytosolic AMBRA1 binding to dynein light chains DYNLL1 and DYNLL2.

Reactome:R-HSA-1632857

ULK1 phosphorylates AMBRA1:BECN1 complex

Reactome represents ULK1 phosphorylation of the AMBRA1:BECN1 complex.

Reactome:R-HSA-5678313

AMBRA1:DYNLL1,DYNLL2 binds BECN1 complex

Reactome represents AMBRA1:DYNLL1,DYNLL2 binding to the BECN1 complex.

Reactome:R-HSA-5678315

BECN1 complex, p-AMBRA1 dissociate from DYNLL1,DYNLL2

Reactome represents dissociation of the BECN1 complex and phosphorylated AMBRA1 from dynein light chains.

file:human/AMBRA1/AMBRA1-uniprot.txt

UniProtKB record for human AMBRA1

UniProt summarizes AMBRA1 as a DCX/DDB1-CUL4 substrate-recognition component involved in autophagy and cell-cycle control.
UniProt lists cytoskeleton, ER, mitochondrion, nucleus, focal adhesion, and by-similarity ciliary axoneme localizations.

file:human/AMBRA1/AMBRA1-notes.md

Manual AMBRA1 PN review notes

Notes record the failed Falcon/fallback deep-research attempt, literature synthesis, and conservative PN projection assessment.

file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv

Proteostasis PN projected annotations report

The PN projection lists AMBRA1 as already matching GO:1990756 and as a candidate for GO:1904716 from a CMA enhancer branch.

file:projects/PROTEOSTASIS/mappings/autophagy_lysosome_pathway.yaml

Proteostasis autophagy-lysosome pathway mapping

The AMBRA1-specific CMA enhancer leaf is marked no_mapping as contextual and not sufficient for universal GO assertion.

file:projects/PROTEOSTASIS/mappings/ubiquitin_proteasome_system.yaml

Proteostasis ubiquitin-proteasome system mapping

The Cul4A/Cul4B substrate receptor group maps to GO:1990756 and covers CRL4 substrate receptors/adaptors.