AMR1B_DANRE
ID AMR1B_DANRE Reviewed; 1360 AA.
AC X1WHY6; I3IRN1;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 1.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=Activating molecule in BECN1-regulated autophagy protein 1B {ECO:0000303|PubMed:23348054};
GN Name=ambra1b {ECO:0000303|PubMed:23348054};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RC TISSUE=Embryo {ECO:0000312|EMBL:CCA61107.2};
RX PubMed=23348054; DOI=10.4161/auto.23278;
RA Benato F., Skobo T., Gioacchini G., Moro I., Ciccosanti F., Piacentini M.,
RA Fimia G.M., Carnevali O., Dalla Valle L.;
RT "Ambra1 knockdown in zebrafish leads to incomplete development due to
RT severe defects in organogenesis.";
RL Autophagy 9:476-495(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24922546; DOI=10.1371/journal.pone.0099210;
RA Skobo T., Benato F., Grumati P., Meneghetti G., Cianfanelli V.,
RA Castagnaro S., Chrisam M., Di Bartolomeo S., Bonaldo P., Cecconi F.,
RA Dalla Valle L.;
RT "Zebrafish ambra1a and ambra1b knockdown impairs skeletal muscle
RT development.";
RL PLoS ONE 9:e99210-e99210(2014).
CC -!- FUNCTION: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3
CC ubiquitin-protein ligase complex involved in cell cycle control and
CC autophagy (PubMed:23348054). The DCX(AMBRA1) complex specifically
CC mediates the polyubiquitination of target proteins (By similarity).
CC Acts as an upstream master regulator of the transition from G1 to S
CC cell phase: ambra1b specifically recognizes and binds phosphorylated
CC cyclin-D (ccnd1, ccnd2 and ccnd3), leading to cyclin-D ubiquitination
CC by the DCX(AMBRA1) complex and subsequent degradation (By similarity).
CC Acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase
CC complexes by mediating ubiquitination and degradation of Elongin-C
CC (eloc) component of CRL5 complexes (By similarity). Acts as a key
CC regulator of autophagy by modulating the BECN1-PIK3C3 complex: controls
CC protein turnover during neuronal development, and regulates normal cell
CC survival and proliferation (By similarity). In normal conditions,
CC ambra1b is tethered to the cytoskeleton via interaction with dyneins
CC light chains (By similarity). Upon autophagy induction, ambra1b is
CC released from the cytoskeletal docking site to induce autophagosome
CC nucleation by mediating ubiquitination of proteins involved in
CC autophagy (By similarity). Also acts as an activator of mitophagy (By
CC similarity). Required for skeletal muscle development
CC (PubMed:24922546). {ECO:0000250|UniProtKB:A2AH22,
CC ECO:0000250|UniProtKB:Q9C0C7, ECO:0000269|PubMed:23348054,
CC ECO:0000269|PubMed:24922546}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q9C0C7}.
CC -!- SUBUNIT: Component of the DCX(AMBRA1) E3 ubiquitin ligase complex.
CC {ECO:0000250|UniProtKB:Q9C0C7}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9C0C7}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q9C0C7}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:A2AH22}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q9C0C7}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:A2AH22}. Nucleus {ECO:0000250|UniProtKB:Q9C0C7}.
CC Cell junction, focal adhesion {ECO:0000250|UniProtKB:A2AH22}.
CC Note=Localizes to the cytoskeleton in absence of autophagy induction.
CC Upon autophagy induction, ambra1a relocalizes to the endoplasmic
CC reticulum to enable autophagosome nucleation. Partially localizes at
CC mitochondria in normal conditions. {ECO:0000250|UniProtKB:Q9C0C7}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Present
CC as maternal transcripts in the eggs and display a gradual decline until
CC 8 hours post-fertilization (hpf), being replaced by zygotic mRNAs from
CC 12 hpf onwards (PubMed:23348054). After 24 hpf, the transcripts are
CC mainly localized in the brain and otic vesicles (PubMed:23348054).
CC {ECO:0000269|PubMed:23348054}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of ambra1a and ambra1b
CC results in reduced autophagy and increased apoptosis during
CC embryogenesis (PubMed:23348054). Morpholino knockdown of ambra1a and
CC ambra1b results in reduced autophagy and increased apoptosis during
CC embryogenesis (PubMed:23348054). Morpholino knockdown of ambra1a and
CC ambra1b results in impaired locomotion, caused by abnormal myogenesis
CC (PubMed:24922546). {ECO:0000269|PubMed:23348054,
CC ECO:0000269|PubMed:24922546}.
CC -!- SIMILARITY: Belongs to the WD repeat AMBRA1 family. {ECO:0000305}.
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DR EMBL; FR846230; CCA61107.2; -; mRNA.
DR EMBL; CU181898; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001289149.1; NM_001302220.1.
DR AlphaFoldDB; X1WHY6; -.
DR STRING; 7955.ENSDARP00000129851; -.
DR PaxDb; X1WHY6; -.
DR Ensembl; ENSDART00000156761; ENSDARP00000129851; ENSDARG00000039878.
DR GeneID; 559106; -.
DR KEGG; dre:559106; -.
DR CTD; 559106; -.
DR ZFIN; ZDB-GENE-050208-235; ambra1b.
DR eggNOG; KOG0266; Eukaryota.
DR GeneTree; ENSGT00390000016223; -.
DR OMA; ICRPVDY; -.
DR OrthoDB; 488527at2759; -.
DR PhylomeDB; X1WHY6; -.
DR Reactome; R-DRE-1632852; Macroautophagy.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 25.
DR Bgee; ENSDARG00000039878; Expressed in mature ovarian follicle and 25 other tissues.
DR ExpressionAtlas; X1WHY6; baseline.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0043009; P:chordate embryonic development; IMP:ZFIN.
DR GO; GO:0007626; P:locomotory behavior; IMP:ZFIN.
DR GO; GO:1904544; P:positive regulation of free ubiquitin chain polymerization; ISS:UniProtKB.
DR GO; GO:1901526; P:positive regulation of mitophagy; ISS:UniProtKB.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:ZFIN.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF00400; WD40; 1.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 2: Evidence at transcript level;
KW Autophagy; Cell cycle; Cell junction; Cytoplasm; Cytoplasmic vesicle;
KW Cytoskeleton; Endoplasmic reticulum; Mitochondrion; Nucleus;
KW Reference proteome; Repeat; Ubl conjugation pathway; WD repeat.
FT CHAIN 1..1360
FT /note="Activating molecule in BECN1-regulated autophagy
FT protein 1B"
FT /id="PRO_0000453464"
FT REPEAT 50..89
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 92..132
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 134..174
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REGION 249..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 315..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 412..490
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 514..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 587..616
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 664..688
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 754..796
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1120..1142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1241..1360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1109..1111
FT /note="TQT motif 1"
FT /evidence="ECO:0000250|UniProtKB:Q9C0C7"
FT MOTIF 1121..1123
FT /note="TQT motif 2"
FT /evidence="ECO:0000250|UniProtKB:Q9C0C7"
FT COMPBIAS 315..360
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 421..453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 469..490
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 542..573
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 587..605
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 754..772
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1325..1344
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1345..1360
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 326
FT /note="P -> T (in Ref. 1; CCA61107)"
FT /evidence="ECO:0000305"
FT CONFLICT 536
FT /note="T -> N (in Ref. 1; CCA61107)"
FT /evidence="ECO:0000305"
FT CONFLICT 618
FT /note="T -> S (in Ref. 1; CCA61107)"
FT /evidence="ECO:0000305"
FT CONFLICT 1257
FT /note="M -> T (in Ref. 1; CCA61107)"
FT /evidence="ECO:0000305"
FT CONFLICT 1289
FT /note="L -> F (in Ref. 1; CCA61107)"
FT /evidence="ECO:0000305"
FT CONFLICT 1321
FT /note="R -> H (in Ref. 1; CCA61107)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1360 AA; 148984 MW; 0A31DEA0C54BFFA6 CRC64;
MAVQNRNSVL ILSGRERGAR MLGSQRLLQQ LVEDRTRWMK WQSQKVELPD NPRSTFLLAF
SPDRNLVAST HVNHNIYITD VKTGKCLHSL VGHRRTPWCV TFHPTIPGLV ASGCLDGEVR
IWDLHGGSES WFTESNVAIA SLAFHPTAQL LLIATNNELH FWDWSRPEPF AVVKTASETE
RVRLVRFDPL GHNLLTAIVN PSNQQNEDDS EVPMDSMEMA LFRQRSLLRS PPVRRTPILH
NFLHILSSRS SGAQANDQSR PAPEPREPPS IPRFQYPVRT EPADRPALQG CTQHLGLGCL
CSRCAASRNL FTQNPTGLQP SDSTQPQTQS GPSAFSPAPS QTRTSDRPSA FSSVFSGTAG
NSAHRGLLPL RTIDPLGSQV PSHLEAPGRL PGADWSGSLL STGHEHGLGA IGVETSSGRG
VVPPPRTSSS SMDLLSLRRF PDGSSSSPIY TSATEGRGLV LPGTEPNRGR PNDGTSSGHH
PFYDNTQRNN PASIRNVLQC NLSRYFMEYE RMQELERPGG SREVAGGPGP MQELLTSSMD
AERPGPSHNG SSHTGNGGAV ATPSQNHPNR CRSCHNLLTF NHDTQRWERS GQTSSSSSSQ
EGPSWPLSVP PFEDPGQTAR VEAQAPEMRP MELGEASSGL QGQQPMGLVY NQETGQWESV
YRQPTVSASS EAAEDALNPE VPVDNPDEDS LRRRLLESSL FPFSRYDMSS SRDHPIYPDP
ARLSPAAYYA QRMIQYLSRR ESIRQRSLQN RLRTLSNSQA DSQSNNPSSV PPEASDGDYE
DIEEPGDRTR HRMPRNARMS APSLGRFVPR RFLLPEYLPY AGLFHERGQS GLATHSSINR
VLAGASIGDG QSAVASNIAN TTYRLQWWDF TKFDLPEISN ATVNVLVPHC KIYNDASCDI
SADGQLLAVF IPSSQRGFAD EGILAVYSLA PHNLGEMLYT KRFGPNAISV SLSPMGCYVM
VGLASRRILL HPTTDHMVAQ VFRLQQPHGG ETSIRMMFNV VYPMAPDQRR HVSINSARWL
PEPGMGLAYG TNKGDLVICR PVDFRSDGDN PSDLNADSLF TINSSSRTRG VERPGTSRSG
WRFDRDMGLM NAIGLQPRQA APSVTSQGTQ TPVVRLQNAE TQTERELPSA STFQNTHTTS
RHTVQTASTS TERHTHPEMT HTLVQASVSE GSLNRTNLPA TYHVESAAEP GTGEDALSRI
RRLMAEGGMT AVVQRERSTT MASMGGFGNN IVVSHRIHRG SQTSVRTAQG GNPTPEMPAG
LGVSTLFHTE PLVDSLEAPG PSGSSGAPLP TPFTNRSEFA GVSPMVESDL FGDRQPDDVQ
RRPSRGGLNM SNHSNNNNND HSNSYSESRS RDYPDDLYGR
