ID   ATG3_HUMAN              Reviewed;         314 AA.
AC   Q9NT62; Q6PKC5; Q9H6L9;
DT   15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   25-JAN-2012, entry version 83.
DE   RecName: Full=Ubiquitin-like-conjugating enzyme ATG3;
DE            EC=6.3.2.-;
DE   AltName: Full=Autophagy-related protein 3;
DE            Short=APG3-like;
DE            Short=hApg3;
DE   AltName: Full=Protein PC3-96;
GN   Name=ATG3; Synonyms=APG3, APG3L;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP   MUTAGENESIS OF CYS-264, SUBCELLULAR LOCATION, FUNCTION, AND
RP   INTERACTION WITH ATG7 AND ATG12.
RC   TISSUE=Brain;
RX   MEDLINE=21950715; PubMed=11825910; DOI=10.1074/jbc.M200385200;
RA   Tanida I., Tanida-Miyake E., Komatsu M., Ueno T., Kominami E.;
RT   "Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple
RT   substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the
RT   conjugation of hApg12p to hApg5p.";
RL   J. Biol. Chem. 277:13739-13744(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Retina;
RA   Wu B.X., Li Y., Laser M., Crosson C.E., Hazard E.S. III, Ma J.X.;
RT   "Cloning and characterization of human PC3-96 gene.";
RL   Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA   Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA   Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Lung, and Lymph;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 118-314 (ISOFORM 2).
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-18, AND MASS
RP   SPECTROMETRY.
RX   PubMed=15592455; DOI=10.1038/nbt1046;
RA   Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA   Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT   "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT   cells.";
RL   Nat. Biotechnol. 23:94-101(2005).
RN   [7]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
RC   TISSUE=Embryonic kidney;
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA   Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
CC   -!- FUNCTION: E2-like enzyme involved in autophagy and mitochondrial
CC       homeostasis. Catalyzes the conjugation of ATG8-like proteins
CC       (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A) to
CC       phosphatidylethanolamine (PE). PE-conjugation to ATG8-like
CC       proteins is essential for autophagy. Preferred substrate is
CC       MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing
CC       the conjugation of ATG12 to itself, ATG12 conjugation to ATG3
CC       playing a role in mitochondrial homeostasis but not in autophagy.
CC       ATG7 (E1-like enzyme) facilitates this reaction by forming an E1-
CC       E2 complex with ATG3.
CC   -!- SUBUNIT: Interacts with ATG7 and ATG12. The complex, composed of
CC       ATG3 and ATG7, plays a role in the conjugation of ATG12 to ATG5.
CC   -!- INTERACTION:
CC       O95166:GABARAP; NbExp=5; IntAct=EBI-988094, EBI-712001;
CC       Q9H0R8:GABARAPL1; NbExp=3; IntAct=EBI-988094, EBI-746969;
CC       P60520:GABARAPL2; NbExp=4; IntAct=EBI-988094, EBI-720116;
CC       Q9GZQ8:MAP1LC3B; NbExp=7; IntAct=EBI-988094, EBI-373144;
CC       Q7Z6L1:TECPR1; NbExp=3; IntAct=EBI-988094, EBI-2946676;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NT62-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NT62-2; Sequence=VSP_013037;
CC         Note=No experimental confirmation available. Ref.4 (AAH02830)
CC         sequence differs from that shown due to a frameshift in position
CC         311;
CC   -!- TISSUE SPECIFICITY: Widely expressed, with a highest expression in
CC       heart, skeletal muscle, kidney, liver and placenta.
CC   -!- PTM: Conjugated to ATG12 at Lys-243. ATG12-conjugation plays a
CC       role in regulation of mitochondrial homeostasis and cell death,
CC       while it is not involved in PE-conjugation to ATG8-like proteins
CC       and autophagy (By similarity).
CC   -!- SIMILARITY: Belongs to the ATG3 family.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB15237.1; Type=Erroneous initiation;
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DR   EMBL; AB079384; BAB90843.1; -; mRNA.
DR   EMBL; AF202092; AAG35611.1; -; mRNA.
DR   EMBL; AL137515; CAB70781.1; -; mRNA.
DR   EMBL; BC002830; AAH02830.1; ALT_FRAME; mRNA.
DR   EMBL; BC024221; AAH24221.1; -; mRNA.
DR   EMBL; AK025778; BAB15237.1; ALT_INIT; mRNA.
DR   IPI; IPI00022254; -.
DR   IPI; IPI00449201; -.
DR   PIR; T46276; T46276.
DR   RefSeq; NP_071933.2; NM_022488.3.
DR   UniGene; Hs.477126; -.
DR   ProteinModelPortal; Q9NT62; -.
DR   SMR; Q9NT62; 27-309.
DR   IntAct; Q9NT62; 23.
DR   STRING; Q9NT62; -.
DR   PhosphoSite; Q9NT62; -.
DR   DMDM; 61212142; -.
DR   PRIDE; Q9NT62; -.
DR   Ensembl; ENST00000283290; ENSP00000283290; ENSG00000144848.
DR   GeneID; 64422; -.
DR   KEGG; hsa:64422; -.
DR   UCSC; uc003dzc.2; human.
DR   UCSC; uc003dzd.1; human.
DR   CTD; 64422; -.
DR   GeneCards; GC03M112251; -.
DR   H-InvDB; HIX0003548; -.
DR   HGNC; HGNC:20962; ATG3.
DR   HPA; CAB037260; -.
DR   MIM; 609606; gene.
DR   neXtProt; NX_Q9NT62; -.
DR   PharmGKB; PA134883444; -.
DR   eggNOG; prNOG10145; -.
DR   GeneTree; ENSGT00390000010308; -.
DR   HOGENOM; HBG602769; -.
DR   HOVERGEN; HBG080876; -.
DR   InParanoid; Q9NT62; -.
DR   OMA; DTYHNAG; -.
DR   OrthoDB; EOG4M398Z; -.
DR   PhylomeDB; Q9NT62; -.
DR   NextBio; 66413; -.
DR   ArrayExpress; Q9NT62; -.
DR   Bgee; Q9NT62; -.
DR   CleanEx; HS_ATG3; -.
DR   Genevestigator; Q9NT62; -.
DR   GermOnline; ENSG00000144848; Homo sapiens.
DR   GO; GO:0000153; C:cytoplasmic ubiquitin ligase complex; IPI:MGI.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0019777; F:Atg12 ligase activity; ISS:UniProtKB.
DR   GO; GO:0019776; F:Atg8 ligase activity; ISS:UniProtKB.
DR   GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR   GO; GO:0000045; P:autophagic vacuole assembly; ISS:UniProtKB.
DR   GO; GO:0043653; P:mitochondrial fragmentation involved in apoptosis; ISS:UniProtKB.
DR   GO; GO:0006612; P:protein targeting to membrane; ISS:UniProtKB.
DR   GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR   InterPro; IPR007135; Autophagy-rel_prot_3.
DR   InterPro; IPR019461; Autophagy-rel_prot_3_C.
DR   InterPro; IPR007134; Autophagy-rel_prot_3_N.
DR   KO; K08343; -.
DR   Pfam; PF03987; Autophagy_act_C; 1.
DR   Pfam; PF10381; Autophagy_Cterm; 1.
DR   Pfam; PF03986; Autophagy_N; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Autophagy; Complete proteome;
KW   Cytoplasm; Isopeptide bond; Ligase; Phosphoprotein; Protein transport;
KW   Reference proteome; Transport; Ubl conjugation;
KW   Ubl conjugation pathway.
FT   CHAIN         1    314       Ubiquitin-like-conjugating enzyme ATG3.
FT                                /FTId=PRO_0000213569.
FT   ACT_SITE    264    264       Glycyl thioester intermediate (Probable).
FT   MOD_RES       1      1       N-acetylmethionine.
FT   MOD_RES      18     18       Phosphotyrosine.
FT   CROSSLNK    243    243       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ATG12) (By
FT                                similarity).
FT   VAR_SEQ     290    314       LLIFLKFVQAVIPTIEYDYTRHFTM -> PSLYVRLVAKWL
FT                                LTIFFLRNLV (in isoform 2).
FT                                /FTId=VSP_013037.
FT   MUTAGEN     264    264       C->S: Instead of the formation of an
FT                                intermediate complex with a thiol ester
FT                                bond between ATG3 (E2-like enzyme) and
FT                                GABARAPL1/APG8L (substrate), a stable
FT                                complex with an O-ester bond is formed.
SQ   SEQUENCE   314 AA;  35864 MW;  40EFE88DB5FE3EAB CRC64;
     MQNVINTVKG KALEVAEYLT PVLKESKFKE TGVITPEEFV AAGDHLVHHC PTWQWATGEE
     LKVKAYLPTG KQFLVTKNVP CYKRCKQMEY SDELEAIIEE DDGDGGWVDT YHNTGITGIT
     EAVKEITLEN KDNIRLQDCS ALCEEEEDED EGEAADMEEY EESGLLETDE ATLDTRKIVE
     ACKAKTDAGG EDAILQTRTY DLYITYDKYY QTPRLWLFGY DEQRQPLTVE HMYEDISQDH
     VKKTVTIENH PHLPPPPMCS VHPCRHAEVM KKIIETVAEG GGELGVHMYL LIFLKFVQAV
     IPTIEYDYTR HFTM
//