AMR1A_DANRE
ID AMR1A_DANRE Reviewed; 1315 AA.
AC E7FAG6; A0A1D5NSZ3; I3IRN2; L0N9D3; L0N9D4; L0N9K3;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 2.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Activating molecule in BECN1-regulated autophagy protein 1A {ECO:0000303|PubMed:23348054};
GN Name=ambra1a {ECO:0000303|PubMed:23348054,
GN ECO:0000312|ZFIN:ZDB-GENE-111104-2};
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] (ISOFORMS 1; 2; 3 AND 4), FUNCTION,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC TISSUE=Embryo {ECO:0000312|EMBL:CCE04070.1};
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: ambra1a 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 ambra1a is tethered to the cytoskeleton via interaction with dyneins
CC light chains (By similarity). Upon autophagy induction, ambra1a 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=ambra1a1 {ECO:0000303|PubMed:23348054};
CC IsoId=E7FAG6-1; Sequence=Displayed;
CC Name=2; Synonyms=ambra1a4 {ECO:0000303|PubMed:23348054};
CC IsoId=E7FAG6-2; Sequence=VSP_061152;
CC Name=3; Synonyms=ambra1a2 {ECO:0000303|PubMed:23348054};
CC IsoId=E7FAG6-3; Sequence=VSP_061155, VSP_061156;
CC Name=4; Synonyms=ambra1a3 {ECO:0000303|PubMed:23348054};
CC IsoId=E7FAG6-4; Sequence=VSP_061153, VSP_061154;
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 causes impaired
CC dorso-ventral patterning in embryos (PubMed:23348054). Morpholino
CC knockdown of ambra1a and ambra1b results in reduced autophagy and
CC increased apoptosis during embryogenesis (PubMed:23348054). Morpholino
CC knockdown of ambra1a and ambra1b results in impaired locomotion, caused
CC by abnormal myogenesis (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; HE602022; CCE04070.1; -; mRNA.
DR EMBL; HE602023; CCE04071.1; -; mRNA.
DR EMBL; HE602024; CCE04072.1; -; mRNA.
DR EMBL; FR846231; CCA61108.2; -; mRNA.
DR EMBL; CABZ01117708; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01117709; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CABZ01117710; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP103011; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; LO018322; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001268921.1; NM_001281992.1.
DR AlphaFoldDB; E7FAG6; -.
DR STRING; 7955.ENSDARP00000088806; -.
DR Ensembl; ENSDART00000098033; ENSDARP00000088806; ENSDARG00000008322. [E7FAG6-1]
DR Ensembl; ENSDART00000173466; ENSDARP00000142964; ENSDARG00000008322. [E7FAG6-4]
DR Ensembl; ENSDART00000173695; ENSDARP00000151820; ENSDARG00000008322. [E7FAG6-3]
DR Ensembl; ENSDART00000173734; ENSDARP00000151646; ENSDARG00000008322. [E7FAG6-2]
DR GeneID; 100332642; -.
DR KEGG; dre:100332642; -.
DR CTD; 100332642; -.
DR ZFIN; ZDB-GENE-111104-2; ambra1a.
DR eggNOG; KOG0266; Eukaryota.
DR GeneTree; ENSGT00390000016223; -.
DR HOGENOM; CLU_008882_0_0_1; -.
DR InParanoid; E7FAG6; -.
DR OMA; MFTINNG; -.
DR OrthoDB; 488527at2759; -.
DR TreeFam; TF328981; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 7.
DR Bgee; ENSDARG00000008322; Expressed in early embryo and 27 other tissues.
DR ExpressionAtlas; E7FAG6; 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 Alternative splicing; Autophagy; Cell cycle; Cell junction; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Endoplasmic reticulum; Mitochondrion;
KW Nucleus; Reference proteome; Repeat; Ubl conjugation pathway; WD repeat.
FT CHAIN 1..1315
FT /note="Activating molecule in BECN1-regulated autophagy
FT protein 1A"
FT /id="PRO_0000453463"
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 294..322
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 342..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 426..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 502..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 545..610
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 630..660
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 681..736
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 985..1134
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1181..1208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1286..1315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1053..1055
FT /note="TQT motif 1"
FT /evidence="ECO:0000250|UniProtKB:Q9C0C7"
FT MOTIF 1065..1067
FT /note="TQT motif 2"
FT /evidence="ECO:0000250|UniProtKB:Q9C0C7"
FT COMPBIAS 308..322
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 342..363
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 393..409
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 426..447
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 502..524
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 545..579
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 596..610
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 630..651
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 993..1017
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1042..1062
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1072..1092
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1181..1197
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1286..1309
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 725..1315
FT /note="Missing (in isoform 2)"
FT /id="VSP_061152"
FT VAR_SEQ 785..788
FT /note="AVIG -> MFAL (in isoform 4)"
FT /id="VSP_061153"
FT VAR_SEQ 789..1315
FT /note="Missing (in isoform 4)"
FT /id="VSP_061154"
FT VAR_SEQ 1089..1098
FT /note="ATESLDFETL -> GKTLSVNQIL (in isoform 3)"
FT /id="VSP_061155"
FT VAR_SEQ 1099..1315
FT /note="Missing (in isoform 3)"
FT /id="VSP_061156"
FT CONFLICT 727
FT /note="G -> E (in Ref. 1; CCA61108)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1315 AA; 144049 MW; 110A24E067FB6429 CRC64;
MKLGQRNSVC ILSSRERGAP GLASYRVLQQ LVEEKTQRMK WQSQKVELPD SPRSTFLLAF
SPDRSLMAST HVNHNIYITE VKSGKCVHSL VGHRRTPWCL TFHPIIPGLI ASGCLDGEVR
IWDLHGGSES WLTESNSAIA SLAFHPTAQL LLIATNNEVH LWDWSRKEPF TVVKTASETE
RVRLVRFDPL GHYLLTAIVN PSNQPNDDDP EIPMDSVEMP HLRQRSFLQS QPARRTPILH
NFLHILTSRN SVPQAGGAHS ASTDGSSDSS GPYTLMCVQP LGMVCFCSRC SAARVPSPPD
EDPSDSASLE AQAHTFSSAR TEPLQMSRFS VESRAANRSS AFSSVYGGGS NMRNHSSSSG
RRGVTGMAPV PHFRQHPPGR EGGGRHPGAD WTVSGLNGQS SSMTPQRTGA SSVSLLSVLR
QQETSFQSPV YTSASDRWGS TPGTSSSRHR PPEEEGQSSS SSIHSVLRCN LYRYFMDYEG
TQDTVQPLDG SRQDQQTQEM LNNNMDPEQP GPSHYQSPYS GENPPHSHMN RCRVCHNLFT
YNQGSRRWDR TGQPSSTERN TPWQPSSSAF HSVAPVSQSN EHLLEHRPIE STPNTPEPHV
PFSQRTDTGQ HEEQAVGLVF NQETGQLERV YRQSASSRSA NISQGALNQE MPEDTPDNDY
LRRLSPAAYY AQRMIQYLSR RDSVRQHSHR PPSRPRPLSS NPSSLSPSPV PNAESSEVDF
EEFEENGSRY RTPRNARMSA PSLGRFVGTR RFLLPEFLPY AGIFHERGQP GLATHSSVNR
VLAGAVIGDG QSAVASNIAN TTYRLQWWDF TKFDLPEISN ASVNVLVPNC KIYNDASCDI
SADGQLLAVF IPSSQRGFPD EGILAVYSLA PHNLGEMLYS KRFGPNAISV SLSPMGRYVM
VGLASRRILL HQISDHMVAQ VFRLQQPHAG ETSMRRVFDV VYPMAPDQRR HVSINSARWL
PDPGLGLAYG TNKGDLVICR PVDVHSDGSS TSEHSERMFT INNGGGVGPS SSRSGDRAGS
SRTDRRSRRD IGLMNGVGLQ PQPPAASVTS QGTQTQNQRL QHAETQTDRD LPDDPQQPST
SQGSQVTDAT ESLDFETLPE DSGSEVVPET PPHSRPQEDE GSDPSEPSTD STGQAEYVSR
IRRLMAEGGM TAVVQREQST TMASMGSFGN NIIVSHRIHR GSQTGADAQN RTRLSPIPGP
SSGAPESLAA ASYSRVLTNT LGFRGDTAQG IDLTEQERLH TSFFTPEFSP LFSSAVDATG
PSSSIGADSV LEGEDFHDFA SLPPSLLSSS PSLSPVNNSN YSNSDSSYLG DEYGR
