Protein: Activating molecule in BECN1-regulated autophagy protein 1A (E7FAG6)
Organism: Danio rerio (Zebrafish) (Brachydanio rerio)
Function: 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 (By similarity). Acts as an upstream master regulator of the transition from G1 to S cell phase: ambra1a 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 similarity). 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 (By similarity). 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 (By similarity). In normal conditions, ambra1a is tethered to the cytoskeleton via interaction with dyneins light chains (By similarity). Upon autophagy induction, ambra1a is released from the cytoskeletal docking site to induce autophagosome nucleation by mediating ubiquitination of proteins involved in autophagy (By similarity). Also acts as an activator of mitophagy (By similarity). Required for skeletal muscle development.
Subcellular location: Endoplasmic reticulum {ECO:0000250|UniProtKB:Q9C0C7}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q9C0C7}. Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:A2AH22}. Mitochondrion {ECO:0000250|UniProtKB:Q9C0C7}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:A2AH22}. Nucleus {ECO:0000250|UniProtKB:Q9C0C7}. Cell junction, focal adhesion {ECO:0000250|UniProtKB:A2AH22}. Note=Localizes to the cytoskeleton in absence of autophagy induction. Upon autophagy induction, ambra1a relocalizes to the endoplasmic reticulum to enable autophagosome nucleation. Partially localizes at mitochondria in normal conditions. {ECO:0000250|UniProtKB:Q9C0C7}.
Interaction partners:
- Beclin-1
- TNF receptor-associated factor 6
- E3 ubiquitin-protein ligase parkin
- non-specific serine/threonine protein kinase
- non-specific serine/threonine protein kinase
- Unc-51-like autophagy-activating kinase 1a.
- Phosphoinositide-3-kinase, regulatory subunit 4.
- Beclin 1-associated autophagy-related key regulator
- Activating molecule in BECN1-regulated autophagy protein 1B
- UV radiation resistance-associated gene.
Sequence:
MKLGQRNSVCILSSRERGAPGLASYRVLQQLVEEKTQRMKWQSQKVELPDSPRSTFLLAFSPDRSLMASTHVNHNIYITEVKSGKCVHSLVGHRRTPWCLTFHPIIPGLIASGCLDGEVRIWDLHGGSESWLTESNSAIASLAFHPTAQLLLIATNNEVHLWDWSRKEPFTVVKTASETERVRLVRFDPLGHYLLTAIVNPSNQPNDDDPEIPMDSVEMPHLRQRSFLQSQPARRTPILHNFLHILTSRNSVPQAGGAHSASTDGSSDSSGPYTLMCVQPLGMVCFCSRCSAARVPSPPDEDPSDSASLEAQAHTFSSARTEPLQMSRFSVESRAANRSSAFSSVYGGGSNMRNHSSSSGRRGVTGMAPVPHFRQHPPGREGGGRHPGADWTVSGLNGQSSSMTPQRTGASSVSLLSVLRQQETSFQSPVYTSASDRWGSTPGTSSSRHRPPEEEGQSSSSSIHSVLRCNLYRYFMDYEGTQDTVQPLDGSRQDQQTQEMLNNNMDPEQPGPSHYQSPYSGENPPHSHMNRCRVCHNLFTYNQGSRRWDRTGQPSSTERNTPWQPSSSAFHSVAPVSQSNEHLLEHRPIESTPNTPEPHVPFSQRTDTGQHEEQAVGLVFNQETGQLERVYRQSASSRSANISQGALNQEMPEDTPDNDYLRRLSPAAYYAQRMIQYLSRRDSVRQHSHRPPSRPRPLSSNPSSLSPSPVPNAESSEVDFEEFEENGSRYRTPRNARMSAPSLGRFVGTRRFLLPEFLPYAGIFHERGQPGLATHSSVNRVLAGAVIGDGQSAVASNIANTTYRLQWWDFTKFDLPEISNASVNVLVPNCKIYNDASCDISADGQLLAVFIPSSQRGFPDEGILAVYSLAPHNLGEMLYSKRFGPNAISVSLSPMGRYVMVGLASRRILLHQISDHMVAQVFRLQQPHAGETSMRRVFDVVYPMAPDQRRHVSINSARWLPDPGLGLAYGTNKGDLVICRPVDVHSDGSSTSEHSERMFTINNGGGVGPSSSRSGDRAGSSRTDRRSRRDIGLMNGVGLQPQPPAASVTSQGTQTQNQRLQHAETQTDRDLPDDPQQPSTSQGSQVTDATESLDFETLPEDSGSEVVPETPPHSRPQEDEGSDPSEPSTDSTGQAEYVSRIRRLMAEGGMTAVVQREQSTTMASMGSFGNNIIVSHRIHRGSQTGADAQNRTRLSPIPGPSSGAPESLAAASYSRVLTNTLGFRGDTAQGIDLTEQERLHTSFFTPEFSPLFSSAVDATGPSSSIGADSVLEGEDFHDFASLPPSLLSSSPSLSPVNNSNYSNSDSSYLGDEYGR