ID   ATG3_NEUCR              Reviewed;         346 AA.
AC   Q7SDY2;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   19-FEB-2014, sequence version 2.
DT   25-MAY-2022, entry version 91.
DE   RecName: Full=Autophagy-related protein 3;
DE   AltName: Full=Autophagy-related E2-like conjugation enzyme atg3;
GN   Name=apg-3; Synonyms=atg3; ORFNames=NCU01955;
OS   Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS   FGSC 987).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX   NCBI_TaxID=367110;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX   PubMed=12712197; DOI=10.1038/nature01554;
RA   Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA   Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA   Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA   Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA   Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA   Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA   Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA   Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA   Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA   Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA   DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA   Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA   Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA   Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT   "The genome sequence of the filamentous fungus Neurospora crassa.";
RL   Nature 422:859-868(2003).
CC   -!- FUNCTION: E2 conjugating enzyme required for the cytoplasm to vacuole
CC       transport (Cvt) and autophagy. Required for selective autophagic
CC       degradation of the nucleus (nucleophagy) as well as for mitophagy which
CC       contributes to regulate mitochondrial quantity and quality by
CC       eliminating the mitochondria to a basal level to fulfill cellular
CC       energy requirements and preventing excess ROS production. Responsible
CC       for the E2-like covalent binding of phosphatidylethanolamine to the C-
CC       terminal Gly of apg-6/atg8. The atg12-apg-4/atg5 conjugate plays a role
CC       of an E3 and promotes the transfer of apg-6/atg8 from apg-3/atg3 to
CC       phosphatidylethanolamine (PE). This step is required for the membrane
CC       association of apg-6/atg8. The formation of the apg-6/atg8-
CC       phosphatidylethanolamine conjugate is essential for autophagy and for
CC       the cytoplasm to vacuole transport (Cvt). The apg-6/atg8-PE conjugate
CC       mediates tethering between adjacent membranes and stimulates membrane
CC       hemifusion, leading to expansion of the autophagosomal membrane during
CC       autophagy (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Monomer. Interacts with apg-6/atg8 through an intermediate
CC       thioester bond through the C-terminal Gly of apg-6/atg8. Also interacts
CC       with the 40 amino acid C-terminal region of the E1-like apg-5/atg7
CC       enzyme. Interacts also with the atg12-apg-4/atg5 conjugate.
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- DOMAIN: The N-terminal region is involved in phosphatidylethanolamine-
CC       binding and is required for apg-6/atg8-PE conjugation. {ECO:0000250}.
CC   -!- DOMAIN: The flexible region (FR) is required for apg-5/atg7-binding.
CC       {ECO:0000250}.
CC   -!- DOMAIN: The handle region (HR) contains the apg-6/atg8 interaction
CC       motif (AIM) and mediates binding to apg-6/atg8. It is crucial for the
CC       cytoplasm-to-vacuole targeting pathway (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the ATG3 family. {ECO:0000305}.
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DR   EMBL; CM002236; EAA35003.2; -; Genomic_DNA.
DR   RefSeq; XP_964239.2; XM_959146.2.
DR   AlphaFoldDB; Q7SDY2; -.
DR   SMR; Q7SDY2; -.
DR   STRING; 5141.EFNCRP00000001030; -.
DR   EnsemblFungi; EAA35003; EAA35003; NCU01955.
DR   GeneID; 3880388; -.
DR   KEGG; ncr:NCU01955; -.
DR   VEuPathDB; FungiDB:NCU01955; -.
DR   HOGENOM; CLU_027518_2_0_1; -.
DR   InParanoid; Q7SDY2; -.
DR   Proteomes; UP000001805; Chromosome 1, Linkage Group I.
DR   GO; GO:0000153; C:cytoplasmic ubiquitin ligase complex; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0061908; C:phagophore; IEA:EnsemblFungi.
DR   GO; GO:0000407; C:phagophore assembly site; IEA:EnsemblFungi.
DR   GO; GO:0019776; F:Atg8 ligase activity; IBA:GO_Central.
DR   GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR   GO; GO:0000422; P:autophagy of mitochondrion; IBA:GO_Central.
DR   GO; GO:0044804; P:autophagy of nucleus; IBA:GO_Central.
DR   GO; GO:0006501; P:C-terminal protein lipidation; IEA:EnsemblFungi.
DR   GO; GO:0044805; P:late nucleophagy; IEA:EnsemblFungi.
DR   GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IEA:EnsemblFungi.
DR   GO; GO:0006612; P:protein targeting to membrane; IEA:EnsemblFungi.
DR   InterPro; IPR007135; Atg3/Atg10.
DR   PANTHER; PTHR12866; PTHR12866; 1.
DR   Pfam; PF03987; Autophagy_act_C; 1.
PE   3: Inferred from homology;
KW   Autophagy; Cytoplasm; Protein transport; Reference proteome; Transport;
KW   Ubl conjugation pathway.
FT   CHAIN           1..346
FT                   /note="Autophagy-related protein 3"
FT                   /id="PRO_0000213583"
FT   REGION          85..161
FT                   /note="Flexible region"
FT                   /evidence="ECO:0000250"
FT   REGION          242..322
FT                   /note="Handle region"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        238
FT                   /note="Glycyl thioester intermediate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   346 AA;  38311 MW;  FDD253D606015984 CRC64;
     MNFLRSTAAT LLDKYTPVSH TSTFRNTGQI TPEEFVAAGD YLTFKFPSWS WADADSPSKR
     LPFLPPGKQF LVTRHVPCHR RLNDDFAGDA GHEEALVEGN KGGADDDGWL RTGSMTSSQP
     LRVREVRTVD DAGNVGDREV VDEDDIPDME DDDDDEAIIR AEGDNSNSGK RTYTLYITYA
     NAYKCPRMYM SGYLSNGQPL PPHLMMEDIV GDYKDKTVTL EDFPFFSHSV KMASVHPCRH
     ASVMKTLLDR ADAALKLRRE KMKAGQGSGS EQGMEGLVDE INKLDVSGAH ANAVEAAPGE
     DAEWEEVPHD VADQEVAIRV DQYLVVFLKF IASVTPGIEH DFTMGV