AMBRA1 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0008285Biological processnegative regulation of cell population proliferation
GO_0000209Biological processprotein polyubiquitination
GO_0000045Biological processautophagosome assembly
GO_0006357Biological processregulation of transcription by RNA polymerase II
GO_2000045Biological processregulation of G1/S transition of mitotic cell cycle
GO_0009267Biological processcellular response to starvation
GO_0030154Biological processcell differentiation
GO_0010508Biological processpositive regulation of autophagy
GO_1901526Biological processpositive regulation of mitophagy
GO_0051897Biological processpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
GO_0000423Biological processmitophagy
GO_0010667Biological processnegative regulation of cardiac muscle cell apoptotic process
GO_0043524Biological processnegative regulation of neuron apoptotic process
GO_0021915Biological processneural tube development
GO_0045591Biological processpositive regulation of regulatory T cell differentiation
GO_0043161Biological processproteasome-mediated ubiquitin-dependent protein catabolic process
GO_1904544Biological processpositive regulation of free ubiquitin chain polymerization
GO_0035307Biological processpositive regulation of protein dephosphorylation
GO_0098780Biological processresponse to mitochondrial depolarisation
GO_0005856Cellular componentcytoskeleton
GO_0048471Cellular componentperinuclear region of cytoplasm
GO_0005739Cellular componentmitochondrion
GO_0080008Cellular componentCul4-RING E3 ubiquitin ligase complex
GO_0005925Cellular componentfocal adhesion
GO_0005930Cellular componentaxoneme
GO_0005783Cellular componentendoplasmic reticulum
GO_0005829Cellular componentcytosol
GO_0045335Cellular componentphagocytic vesicle
GO_0005776Cellular componentautophagosome
GO_0005737Cellular componentcytoplasm
GO_0043231Cellular componentintracellular membrane-bounded organelle
GO_0005741Cellular componentmitochondrial outer membrane
GO_0005634Cellular componentnucleus
GO_1990756Molecular functionubiquitin-like ligase-substrate adaptor activity
GO_0019903Molecular functionprotein phosphatase binding
GO_0051020Molecular functionGTPase binding
GO_0031625Molecular functionubiquitin protein ligase binding
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameAMBRA1
Protein nameActivating molecule in BECN1-regulated autophagy protein 1 (DDB1- and CUL4-associated factor 3)
Autophagy and beclin 1 regulator 1
SynonymsDCAF3
KIAA1736
DescriptionFUNCTION: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy . The DCX(AMBRA1) complex specifically mediates the polyubiquitination of target proteins such as BECN1, CCND1, CCND2, CCND3, ELOC and ULK1 . Acts as an upstream master regulator of the transition from G1 to S cell phase: AMBRA1 specifically recognizes and binds phosphorylated cyclin-D (CCND1, CCND2 and CCND3), leading to cyclin-D ubiquitination by the DCX(AMBRA1) complex and subsequent degradation . By controlling the transition from G1 to S phase and cyclin-D degradation, AMBRA1 acts as a tumor suppressor that promotes genomic integrity during DNA replication and counteracts developmental abnormalities and tumor growth . AMBRA1 also regulates the cell cycle by promoting MYC dephosphorylation and degradation independently of the DCX(AMBRA1) complex: acts via interaction with the catalytic subunit of protein phosphatase 2A (PPP2CA), which enhances interaction between PPP2CA and MYC, leading to MYC dephosphorylation and degradation . Acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes . Acts as a key regulator of autophagy by modulating the BECN1-PIK3C3 complex: controls protein turnover during neuronal development, and regulates normal cell survival and proliferation . In normal conditions, AMBRA1 is tethered to the cytoskeleton via interaction with dyneins DYNLL1 and DYNLL2 . Upon autophagy induction, AMBRA1 is released from the cytoskeletal docking site to induce autophagosome nucleation by mediating ubiquitination of proteins involved in autophagy . The DCX(AMBRA1) complex mediates 'Lys-63'-linked ubiquitination of BECN1, increasing the association between BECN1 and PIK3C3 to promote PIK3C3 activity (By similarity). In collaboration with TRAF6, AMBRA1 mediates 'Lys-63'-linked ubiquitination of ULK1 following autophagy induction, promoting ULK1 stability and kinase activity . Also activates ULK1 via interaction with TRIM32: TRIM32 stimulates ULK1 through unanchored 'Lys-63'-linked polyubiquitin chains . Also acts as an activator of mitophagy via interaction with PRKN and LC3 proteins (MAP1LC3A, MAP1LC3B or MAP1LC3C); possibly by bringing damaged mitochondria onto autophagosomes . Also activates mitophagy by acting as a cofactor for HUWE1; acts by promoting HUWE1-mediated ubiquitination of MFN2 . AMBRA1 is also involved in regulatory T-cells (Treg) differentiation by promoting FOXO3 dephosphorylation independently of the DCX(AMBRA1) complex: acts via interaction with PPP2CA, which enhances interaction between PPP2CA and FOXO3, leading to FOXO3 dephosphorylation and stabilization . May act as a regulator of intracellular trafficking, regulating the localization of active PTK2/FAK and SRC (By similarity). Also involved in transcription regulation by acting as a scaffold for protein complexes at chromatin (By similarity). .

AccessionsQ9C0C7
ENST00000458649.6 [Q9C0C7-1]
H0YE34
ENST00000526545.5
ENST00000314845.7 [Q9C0C7-4]
ENST00000534300.5 [Q9C0C7-2]
ENST00000683756.1 [Q9C0C7-1]
ENST00000533727.5
ENST00000526606.1
E9PL55
ENST00000528950.1 [Q9C0C7-3]
A0A075B6T1