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Recombinant Human Activating molecule in BECN1-regulated autophagy protein 1 (AMBRA1), partial

Recombinant Human Activating molecule in BECN1-regulated autophagy protein 1 (AMBRA1), partial

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MSDS	MSDS Datasheet
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Source
Conjugate
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Target Background

Product Details

Abbreviation

AMBRA1

Purity

>85% (SDS-PAGE)

Target Names

AMBRA1

Uniprot NO.

Q9C0C7

Alternative Names

Activating molecule in beclin 1 regulated autophagy; Activating molecule in BECN1 regulated autophagy protein 1; Activating molecule in BECN1-regulated autophagy protein 1; Ambra1; AMRA1_HUMAN; Autophagy and beclin 1 regulator 1; DCAF3; FLJ20294; Hypothetical protein FLJ20294; Hypothetical protein LOC55626; KIAA1736; MGC33725; WDR94

Species

Homo sapiens (Human)

Source

Yeast

Expression Region

1-1298

Target Protein Sequence

MKVVPEKNAV RILWGRERGA RAMGAQRLLQ ELVEDKTRWM KWEGKRVELP DSPRSTFLLA FSPDRTLLAS THVNHNIYIT EVKTGKCVHS LIGHRRTPWC VTFHPTISGL IASGCLDGEV RIWDLHGGSE SWFTDSNNAI ASLAFHPTAQ LLLIATANEI HFWDWSRREP FAVVKTASEM ERVRLVRFDP LGHYLLTAIV NPSNQQGDDE PEIPIDGTEL SHYRQRALLQ SQPVRRTPLL HNFLHMLSSR SSGIQVGEQS TVQDSATPSP PPPPPQPSTE RPRTSAYIRL RQRVSYPTAE CCQHLGILCL CSRCSGTRVP SLLPHQDSVP PASARATTPS FSFVQTEPFH PPEQASSTQQ DQGLLNRPSA FSTVQSSTAG NTLRNLSLGP TRRSLGGPLS SHPSRYHREI APGLTGSEWT RTVLSLNSRS EAESMPPPRT SASSVSLLSV LRQQEGGSQA SVYTSATEGR GFPASGLATE SDGGNGSSQN NSGSIRHELQ CDLRRFFLEY DRLQELDQSL SGEAPQTQQA QEMLNNNIES ERPGPSHQPT PHSSENNSNL SRGHLNRCRA CHNLLTFNND TLRWERTTPN YSSGEASSSW QVPSSFESVP SSGSQLPPLE RTEGQTPSSS RLELSSSASP QEERTVGVAF NQETGHWERI YTQSSRSGTV SQEALHQDMP EESSEEDSLR RRLLESSLIS LSRYDGAGSR EHPIYPDPAR LSPAAYYAQR MIQYLSRRDS IRQRSMRYQQ NRLRSSTSSS SSDNQGPSVE GTDLEFEDFE DNGDRSRHRA PRNARMSAPS LGRFVPRRFL LPEYLPYAGI FHERGQPGLA THSSVNRVLA GAVIGDGQSA VASNIANTTY RLQWWDFTKF DLPEISNASV NVLVQNCKIY NDASCDISAD GQLLAAFIPS SQRGFPDEGI LAVYSLAPHN LGEMLYTKRF GPNAISVSLS PMGRYVMVGL ASRRILLHPS TEHMVAQVFR LQQAHGGETS MRRVFNVLYP MPADQRRHVS INSARWLPEP GLGLAYGTNK GDLVICRPEA LNSGVEYYWD QLNETVFTVH SNSRSSERPG TSRATWRTDR DMGLMNAIGL QPRNPATSVT SQGTQTLALQ LQNAETQTER EVPEPGTAAS GPGEGEGSEY GASGEDALSR IQRLMAEGGM TAVVQREQST TMASMGGFGN NIIVSHRIHR SSQTGTEPGA AHTSSPQPST SRGLLPEAGQ LAERGLSPRT ASWDQPGTPG REPTQPTLPS SSPVPIPVSL PSAEGPTLHC ELTNNNHLLD GGSSRGDAAG PRGEPRNR
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.

Protein Length

Partial

Tag Info

N-terminal His-tagged/Tag-Free
The tag type will be determined during production process. If you have specified tag type, please tell us and we will develop the specified tag preferentially.

Storage Condition

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Shelf Life

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

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Target Background

Function(From Uniprot)

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. 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. Also involved in transcription regulation by acting as a scaffold for protein complexes at chromatin.

Gene References into Functions

Ambra1 plays an important role in regulating the sensitivity of breast cancer cells to epirubicin. Regulatory effect of Ambra1 on epirubicin sensitivity is achieved through the regulation of autophagy by targeting ATG12. PMID:30027574
Results showed that AMBRA1 is a novel hub binding protein of alpha-synuclein and plays a central role in the pathogenesis of multiple system atrophy through the degradative dynamics of alpha-synuclein. PMID:27875637
Data support a role of AMBRA1/Ambra1 partial loss-of-function genotypes for female autistic traits. Moreover, they suggest Ambra1 heterozygous mice as a novel multifaceted and construct-valid genetic mouse model for female autism. PMID:28994820
These data suggest a new and interesting role of MIR7-3HG as an anti-autophagic MIRNA that may affect oncogenesis through the regulation of the tumor suppressor AMBRA1. PMID:28059583
Results show that the expression of AMBRA1 and Beclin-1 is increased in human gastric adenocarcinoma (GC) tissues. High protein expression of AMBRA1 and Beclin-1 is correlated with tumor invasion and is an independent poor prognostic marker in GC patients. PMID:28224423
Ambra1 is a crucial regulator of autophagy and apoptosis in ovarian cancer cells subject to cisplatin to maintain the balance between autophagy and apoptosis. Ambra1-targeting inhibition might sensitize ovarian cancer cells to chemotherapy. PMID:26763392
An increased expression of AMBRA1 and SQSTM1. PMID:26423274
a de-regulation of c-Myc correlates with increased tumorigenesis in AMBRA1-defective systems, thus supporting a role for AMBRA1 as a haploinsufficient tumour suppressor gene. PMID:25438055
Ambra1 mRNA translocation to P-bodies and translational suppression correlated with increased cell death. PMID:26086269
Both AMBRA1 and BECLIN 1 affect c-Myc regulation, but through two different pathways. PMID:25803737
AMBRA1 interacts with cullin E3 ubiquitin ligases to regulate autophagy dynamics PMID:25499913
Ambra1 is a crucial regulator of autophagy and apoptosis in colorectal cancer cells PMID:24587252
A schizophrenia-related risk variant in AMBRA1 (rs11819869) is involved in various aspects of impulsivity, and this involvement occurs on a behavioral as well as an imaging genetics level. PMID:23551272
Data suggest that activated autophagy is associated with the progression of pancreatic ductal adenocarcinoma and that the overexpression of autophagy-related proteins Atg5, Ambra1, beclin-1, LC3B and Bif-1 is significantly correlated with poor outcome. PMID:23429496
role that Ambra1 in the switch between autophagy and apoptosis PMID:23069654
findings show under non-autophagic conditions, mTOR inhibits AMBRA1 by phosphorylation, whereas on autophagy induction, AMBRA1 is dephosphorylated; in this condition, AMBRA1, interacting with TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its stabilization, self-association and function PMID:23524951
Ambra1 is an important target of apoptotic proteases resulting in the dismantling of the autophagic machinery and the accomplishment of the cell death program PMID:22441670
In this study, the authors show that AMBRA1 binds preferentially the mitochondrial pool of the antiapoptotic factor BCL-2, and that this interaction is disrupted following autophagy induction. PMID:21358617
When autophagy is induced, ULK1 phosphorylates AMBRA1, releasing the autophagy core complex from dynein. PMID:20921139

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Subcellular Location

Endoplasmic reticulum. Cytoplasm, cytoskeleton. Cytoplasmic vesicle, autophagosome. Mitochondrion. Cytoplasm, cytosol. Nucleus. Cell junction, focal adhesion.

Database Links

HGNC: 25990

UNIGENE: Hs.654644

KEGG: hsa:55626

STRING: 9606.ENSP00000318313

OMIM: 611359

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