AMBRA1 Antibody
(Synonyms: DCAF3, KIAA1736, AMBRA1, Activating molecule in BECN1-regulated autophagy protein 1, DDB1- and CUL4-associated factor 3)AMBRA1 Antibody (YA7097) is a Rabbit-derived and non-conjugated IgG polyclonal antibody, targeting to AMBRA1.
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Host:
Rabbit
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Isotype:
IgG
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Application:
WB, IHC-P
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Reactivity :
Human
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Formulation:
Supplied in PBS with 0.05% sodium azide,1%BSA and 50% glycerol
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Conjugation:
Non-conjugated
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
Applications
| Application |
WB
WB: Western Blot
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IHC-P
IHC-P: Immunohistochemistry-Paraffin
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|---|---|---|
| Dilution Ratio | 1:1000-2000 | 1:100-500 |
Product Details
AMBRA1 Antibody (YA7097) is a Rabbit-derived and non-conjugated IgG polyclonal antibody, targeting to AMBRA1.
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Host Rabbit
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Clonality Polyclonal
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Species ReactivityHuman
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Calculated Molecular Weight Predicted band size: 142.5kDa;
SwissProt: SwissProt: Q9C0C7
Purified recombinant fragment of human AMBRA1 (aa 25-60) expressed in E. Coli.
Endogenous
affinity purified.
Non-conjugated
Unmodified
IgG
Product Properties
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Appearance
Solution
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Formulation
Supplied in PBS with 0.05% sodium azide,1%BSA and 50% glycerol
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Storage & Stability
Stored at -20°C for 1 year. Avoid repeated freeze / thaw cycles.
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Shipping
Shipping with blue ice.
Background
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Function
AMBRA1 is a 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)[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17].
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Subcellular Localization
Endoplasmic reticulum; Cytoplasm, cytoskeleton; Cytoplasmic vesicle, autophagosome; Mitochondrion; Cytoplasm, cytosol; Nucleus; Cell junction, focal adhesion
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Expression
Induction: Negatively regulated by microRNA 7-3HG (miR7-3HG), which targets the 3' untranslated (3'-UTR) region of AMBRA1 transcripts, leading to a decrease of AMBRA1 mRNA and protein levels, thereby inhibiting autophagy. Strongly up-regulated during egulatory T-cells (Treg) differentiation. -
Isoforms & Post-Translational Modification
AMBRA1 has 6 isoforms, Q9C0C7-1: amino acid length is 1298, molecular weight is 142507 Da (predicted); Q9C0C7-2: amino acid length is 1238, molecular weight is 135528 Da (predicted); Q9C0C7-3: amino acid length is 1269, molecular weight is 139269 Da (predicted); Q9C0C7-4: amino acid length is 1208, molecular weight is 132837 Da (predicted); Q9C0C7-5: amino acid length is 1301, molecular weight is 142585 Da (predicted); Q9C0C7-6: amino acid length is 761, molecular weight is 84428 Da (predicted).
Phosphorylation at Ser-52 by MTOR inhibits its ability to regulate autophagy and mediate ubiquitination of ULK1. Phosphorylation by ULK1 in response to autophagy induction abolishes interaction with DYNLL1 and DYNLL2, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation. Phosphorylation by MTOR inhibits interaction with PPP2CA and subsequent dephosphorylation of MYC. Phosphorylation at Ser-1043 by CHUK/IKKA promotes its interaction with ATG8 family proteins GABARAP and MAP1LC3B and its mitophagic activity -
Subunit
Component of the DCX(AMBRA1) E3 ubiquitin ligase complex, also named CRL4(AMBRA1), at least composed of CUL4 (CUL4A or CUL4B), DDB1, AMBRA1 and RBX1.
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SwissProt ID
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Synonyms
DCAF3, KIAA1736, AMBRA1, Activating molecule in BECN1-regulated autophagy protein 1, DDB1- and CUL4-associated factor 3
Documentation
References
[1]. Di Bartolomeo S, et al. The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. J Cell Biol. 2010 Oct 4;191(1):155-68. [Content Brief]
[2]. Nazio F, et al. mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol. 2013 Apr;15(4):406-16. [Content Brief]
[3]. Gu W, et al. Ambra1 is an essential regulator of autophagy and apoptosis in SW620 cells: pro-survival role of Ambra1. PLoS One. 2014;9(2):e90151. [Content Brief]
[4]. Ye J, et al. Rare mutations in the autophagy-regulating gene AMBRA1 contribute to human neural tube defects. Hum Mutat. 2020 Aug;41(8):1383-1393. [Content Brief]
[5]. Maiani E, et al. AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity. Nature. 2021 Apr;592(7856):799-803. [Content Brief]
[6]. Simoneschi D, et al. CRL4(AMBRA1) is a master regulator of D-type cyclins. Nature. 2021 Apr;592(7856):789-793. [Content Brief]
[7]. Chaikovsky AC, et al. The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D. Nature. 2021 Apr;592(7856):794-798. [Content Brief]
[8]. Cianfanelli V, et al. AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nat Cell Biol. 2015 Jan;17(1):20-30. [Content Brief]
[9]. Cianfanelli V, et al. AMBRA1 and BECLIN 1 interplay in the crosstalk between autophagy and cell proliferation. Cell Cycle. 2015;14(7):959-63. [Content Brief]
[10]. Antonioli M, et al. AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics. Dev Cell. 2014 Dec 22;31(6):734-46. [Content Brief]
[11]. Chen SH, et al. CRL4(AMBRA1) targets Elongin C for ubiquitination and degradation to modulate CRL5 signaling. EMBO J. 2018 Sep 14;37(18):. [Content Brief]
[12]. Strappazzon F, et al. Mitochondrial BCL-2 inhibits AMBRA1-induced autophagy. EMBO J. 2011 Apr 6;30(7):1195-208. [Content Brief]
[13]. Di Rienzo M, et al. Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains. Sci Adv. 2019 May;5(5):eaau8857. [Content Brief]
[14]. Van Humbeeck C, et al. Parkin interacts with Ambra1 to induce mitophagy. J Neurosci. 2011 Jul 13;31(28):10249-61. [Content Brief]
[15]. Strappazzon F, et al. AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1. Cell Death Differ. 2015 Mar;22(3):419-32. [Content Brief]
[16]. Di Rita A, et al. HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα. Nat Commun. 2018 Sep 14;9(1):3755. [Content Brief]
[17]. Becher J, et al. AMBRA1 Controls Regulatory T-Cell Differentiation and Homeostasis Upstream of the FOXO3-FOXP3 Axis. Dev Cell. 2018 Dec 3;47(5):592-607.e6. [Content Brief]
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