Full text data of ATG3
ATG3
(APG3, APG3L)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquitin-like-conjugating enzyme ATG3; 6.3.2.- (Autophagy-related protein 3; APG3-like; hApg3; Protein PC3-96)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin-like-conjugating enzyme ATG3; 6.3.2.- (Autophagy-related protein 3; APG3-like; hApg3; Protein PC3-96)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9NT62
ID ATG3_HUMAN Reviewed; 314 AA.
AC Q9NT62; Q6PKC5; Q9H6L9;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 101.
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, ACTIVE SITE,
RP AND INTERACTION WITH ATG7 AND ATG12.
RC TISSUE=Brain;
RX 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 FUNCTION, AND INTERACTION WITH THE ATG12-ATG5 CONJUGATE.
RX PubMed=12207896; DOI=10.1016/S0006-291X(02)02057-0;
RA Tanida I., Nishitani T., Nemoto T., Ueno T., Kominami E.;
RT "Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3
RT processing.";
RL Biochem. Biophys. Res. Commun. 296:1164-1170(2002).
RN [7]
RP FUNCTION.
RX PubMed=12890687; DOI=10.1074/jbc.M300550200;
RA Nemoto T., Tanida I., Tanida-Miyake E., Minematsu-Ikeguchi N.,
RA Yokota M., Ohsumi M., Ueno T., Kominami E.;
RT "The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation,
RT facilitates MAP-LC3 modification.";
RL J. Biol. Chem. 278:39517-39526(2003).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [10]
RP FUNCTION.
RX PubMed=16704426; DOI=10.1111/j.1742-4658.2006.05260.x;
RA Tanida I., Sou Y.S., Minematsu-Ikeguchi N., Ueno T., Kominami E.;
RT "Atg8L/Apg8L is the fourth mammalian modifier of mammalian Atg8
RT conjugation mediated by human Atg4B, Atg7 and Atg3.";
RL FEBS J. 273:2553-2562(2006).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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 [12]
RP INTERACTION WITH FNBP1L.
RX PubMed=19342671; DOI=10.4049/jimmunol.0803050;
RA Huett A., Ng A., Cao Z., Kuballa P., Komatsu M., Daly M.J.,
RA Podolsky D.K., Xavier R.J.;
RT "A novel hybrid yeast-human network analysis reveals an essential role
RT for FNBP1L in antibacterial autophagy.";
RL J. Immunol. 182:4917-4930(2009).
RN [13]
RP FUNCTION, AND INTERACTION WITH ATG12.
RX PubMed=20723759; DOI=10.1016/j.cell.2010.07.018;
RA Radoshevich L., Murrow L., Chen N., Fernandez E., Roy S., Fung C.,
RA Debnath J.;
RT "ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and
RT cell death.";
RL Cell 142:590-600(2010).
RN [14]
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).
RN [15]
RP DOMAIN, AND CLEAVAGE BY CASP8.
RX PubMed=22644571; DOI=10.1007/s10495-012-0735-0;
RA Oral O., Oz-Arslan D., Itah Z., Naghavi A., Deveci R., Karacali S.,
RA Gozuacik D.;
RT "Cleavage of Atg3 protein by caspase-8 regulates autophagy during
RT receptor-activated cell death.";
RL Apoptosis 17:810-820(2012).
RN [16]
RP INTERACTION WITH ATG3 AND ATG12.
RX PubMed=22170151; DOI=10.4161/auto.8.1.18339;
RA Tanida I., Yamasaki M., Komatsu M., Ueno T.;
RT "The FAP motif within human ATG7, an autophagy-related E1-like enzyme,
RT is essential for the E2-substrate reaction of LC3 lipidation.";
RL Autophagy 8:88-97(2012).
CC -!- FUNCTION: E2 conjugating enzyme required for the cytoplasm to
CC vacuole transport (Cvt), autophagy, and mitochondrial homeostasis.
CC Responsible for the E2-like covalent binding of
CC phosphatidylethanolamine to the C-terminal Gly of ATG8-like
CC proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-
CC ATG5 conjugate plays a role of an E3 and promotes the transfer of
CC ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE).
CC This step is required for the membrane association of ATG8-like
CC proteins. The formation of the ATG8-phosphatidylethanolamine
CC conjugates is essential for autophagy and for the cytoplasm to
CC vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also
CC acts as an autocatalytic E2-like enzyme, catalyzing the
CC conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing
CC a role in mitochondrial homeostasis but not in autophagy. ATG7
CC (E1-like enzyme) facilitates this reaction by forming an E1-E2
CC complex with ATG3. Promotes primary ciliogenesis by removing OFD1
CC from centriolar satellites via the autophagic pathway.
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 Interacts with FNBP1L.
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=5; 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.
CC -!- PTM: Cleaved by CASP8 upon death ligand binding such as tumor
CC necrosis factor-alpha. CASP8 cleavage blocks survival-related
CC autophagy and favors apoptosis.
CC -!- SIMILARITY: Belongs to the ATG3 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02830.1; Type=Frameshift; Positions=290;
CC Sequence=BAB15237.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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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 PIR; T46276; T46276.
DR RefSeq; NP_001265641.1; NM_001278712.1.
DR RefSeq; NP_071933.2; NM_022488.4.
DR UniGene; Hs.477126; -.
DR PDB; 4NAW; X-ray; 2.20 A; D/H/L/P=140-170.
DR PDBsum; 4NAW; -.
DR ProteinModelPortal; Q9NT62; -.
DR SMR; Q9NT62; 28-84, 193-309.
DR DIP; DIP-35052N; -.
DR IntAct; Q9NT62; 20.
DR STRING; 9606.ENSP00000283290; -.
DR PhosphoSite; Q9NT62; -.
DR DMDM; 61212142; -.
DR PaxDb; Q9NT62; -.
DR PRIDE; Q9NT62; -.
DR DNASU; 64422; -.
DR Ensembl; ENST00000283290; ENSP00000283290; ENSG00000144848.
DR Ensembl; ENST00000402314; ENSP00000385943; ENSG00000144848.
DR GeneID; 64422; -.
DR KEGG; hsa:64422; -.
DR UCSC; uc003dzd.3; human.
DR CTD; 64422; -.
DR GeneCards; GC03M112251; -.
DR HGNC; HGNC:20962; ATG3.
DR HPA; CAB037260; -.
DR MIM; 609606; gene.
DR neXtProt; NX_Q9NT62; -.
DR PharmGKB; PA134883444; -.
DR eggNOG; NOG237080; -.
DR HOGENOM; HOG000234613; -.
DR HOVERGEN; HBG080876; -.
DR InParanoid; Q9NT62; -.
DR KO; K08343; -.
DR OMA; ADEWVET; -.
DR OrthoDB; EOG7VMP5R; -.
DR PhylomeDB; Q9NT62; -.
DR GenomeRNAi; 64422; -.
DR NextBio; 66413; -.
DR PRO; PR:Q9NT62; -.
DR ArrayExpress; Q9NT62; -.
DR Bgee; Q9NT62; -.
DR CleanEx; HS_ATG3; -.
DR Genevestigator; Q9NT62; -.
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:0000045; P:autophagic vacuole assembly; ISS:UniProtKB.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; 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 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 3D-structure; Acetylation; Alternative splicing; Autophagy;
KW Complete proteome; Cytoplasm; Isopeptide bond; Ligase;
KW Protein transport; Reference proteome; Transport; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1 314 Ubiquitin-like-conjugating enzyme ATG3.
FT /FTId=PRO_0000213569.
FT MOTIF 166 169 Caspase cleavage motif LETD.
FT ACT_SITE 264 264 Glycyl thioester intermediate (Probable).
FT SITE 169 170 Cleavage; by CASP8.
FT MOD_RES 1 1 N-acetylmethionine.
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
//
ID ATG3_HUMAN Reviewed; 314 AA.
AC Q9NT62; Q6PKC5; Q9H6L9;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 101.
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, ACTIVE SITE,
RP AND INTERACTION WITH ATG7 AND ATG12.
RC TISSUE=Brain;
RX 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 FUNCTION, AND INTERACTION WITH THE ATG12-ATG5 CONJUGATE.
RX PubMed=12207896; DOI=10.1016/S0006-291X(02)02057-0;
RA Tanida I., Nishitani T., Nemoto T., Ueno T., Kominami E.;
RT "Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3
RT processing.";
RL Biochem. Biophys. Res. Commun. 296:1164-1170(2002).
RN [7]
RP FUNCTION.
RX PubMed=12890687; DOI=10.1074/jbc.M300550200;
RA Nemoto T., Tanida I., Tanida-Miyake E., Minematsu-Ikeguchi N.,
RA Yokota M., Ohsumi M., Ueno T., Kominami E.;
RT "The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation,
RT facilitates MAP-LC3 modification.";
RL J. Biol. Chem. 278:39517-39526(2003).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [10]
RP FUNCTION.
RX PubMed=16704426; DOI=10.1111/j.1742-4658.2006.05260.x;
RA Tanida I., Sou Y.S., Minematsu-Ikeguchi N., Ueno T., Kominami E.;
RT "Atg8L/Apg8L is the fourth mammalian modifier of mammalian Atg8
RT conjugation mediated by human Atg4B, Atg7 and Atg3.";
RL FEBS J. 273:2553-2562(2006).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND MASS SPECTROMETRY.
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 [12]
RP INTERACTION WITH FNBP1L.
RX PubMed=19342671; DOI=10.4049/jimmunol.0803050;
RA Huett A., Ng A., Cao Z., Kuballa P., Komatsu M., Daly M.J.,
RA Podolsky D.K., Xavier R.J.;
RT "A novel hybrid yeast-human network analysis reveals an essential role
RT for FNBP1L in antibacterial autophagy.";
RL J. Immunol. 182:4917-4930(2009).
RN [13]
RP FUNCTION, AND INTERACTION WITH ATG12.
RX PubMed=20723759; DOI=10.1016/j.cell.2010.07.018;
RA Radoshevich L., Murrow L., Chen N., Fernandez E., Roy S., Fung C.,
RA Debnath J.;
RT "ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and
RT cell death.";
RL Cell 142:590-600(2010).
RN [14]
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).
RN [15]
RP DOMAIN, AND CLEAVAGE BY CASP8.
RX PubMed=22644571; DOI=10.1007/s10495-012-0735-0;
RA Oral O., Oz-Arslan D., Itah Z., Naghavi A., Deveci R., Karacali S.,
RA Gozuacik D.;
RT "Cleavage of Atg3 protein by caspase-8 regulates autophagy during
RT receptor-activated cell death.";
RL Apoptosis 17:810-820(2012).
RN [16]
RP INTERACTION WITH ATG3 AND ATG12.
RX PubMed=22170151; DOI=10.4161/auto.8.1.18339;
RA Tanida I., Yamasaki M., Komatsu M., Ueno T.;
RT "The FAP motif within human ATG7, an autophagy-related E1-like enzyme,
RT is essential for the E2-substrate reaction of LC3 lipidation.";
RL Autophagy 8:88-97(2012).
CC -!- FUNCTION: E2 conjugating enzyme required for the cytoplasm to
CC vacuole transport (Cvt), autophagy, and mitochondrial homeostasis.
CC Responsible for the E2-like covalent binding of
CC phosphatidylethanolamine to the C-terminal Gly of ATG8-like
CC proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-
CC ATG5 conjugate plays a role of an E3 and promotes the transfer of
CC ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE).
CC This step is required for the membrane association of ATG8-like
CC proteins. The formation of the ATG8-phosphatidylethanolamine
CC conjugates is essential for autophagy and for the cytoplasm to
CC vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also
CC acts as an autocatalytic E2-like enzyme, catalyzing the
CC conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing
CC a role in mitochondrial homeostasis but not in autophagy. ATG7
CC (E1-like enzyme) facilitates this reaction by forming an E1-E2
CC complex with ATG3. Promotes primary ciliogenesis by removing OFD1
CC from centriolar satellites via the autophagic pathway.
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 Interacts with FNBP1L.
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=5; 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.
CC -!- PTM: Cleaved by CASP8 upon death ligand binding such as tumor
CC necrosis factor-alpha. CASP8 cleavage blocks survival-related
CC autophagy and favors apoptosis.
CC -!- SIMILARITY: Belongs to the ATG3 family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02830.1; Type=Frameshift; Positions=290;
CC Sequence=BAB15237.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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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 PIR; T46276; T46276.
DR RefSeq; NP_001265641.1; NM_001278712.1.
DR RefSeq; NP_071933.2; NM_022488.4.
DR UniGene; Hs.477126; -.
DR PDB; 4NAW; X-ray; 2.20 A; D/H/L/P=140-170.
DR PDBsum; 4NAW; -.
DR ProteinModelPortal; Q9NT62; -.
DR SMR; Q9NT62; 28-84, 193-309.
DR DIP; DIP-35052N; -.
DR IntAct; Q9NT62; 20.
DR STRING; 9606.ENSP00000283290; -.
DR PhosphoSite; Q9NT62; -.
DR DMDM; 61212142; -.
DR PaxDb; Q9NT62; -.
DR PRIDE; Q9NT62; -.
DR DNASU; 64422; -.
DR Ensembl; ENST00000283290; ENSP00000283290; ENSG00000144848.
DR Ensembl; ENST00000402314; ENSP00000385943; ENSG00000144848.
DR GeneID; 64422; -.
DR KEGG; hsa:64422; -.
DR UCSC; uc003dzd.3; human.
DR CTD; 64422; -.
DR GeneCards; GC03M112251; -.
DR HGNC; HGNC:20962; ATG3.
DR HPA; CAB037260; -.
DR MIM; 609606; gene.
DR neXtProt; NX_Q9NT62; -.
DR PharmGKB; PA134883444; -.
DR eggNOG; NOG237080; -.
DR HOGENOM; HOG000234613; -.
DR HOVERGEN; HBG080876; -.
DR InParanoid; Q9NT62; -.
DR KO; K08343; -.
DR OMA; ADEWVET; -.
DR OrthoDB; EOG7VMP5R; -.
DR PhylomeDB; Q9NT62; -.
DR GenomeRNAi; 64422; -.
DR NextBio; 66413; -.
DR PRO; PR:Q9NT62; -.
DR ArrayExpress; Q9NT62; -.
DR Bgee; Q9NT62; -.
DR CleanEx; HS_ATG3; -.
DR Genevestigator; Q9NT62; -.
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:0000045; P:autophagic vacuole assembly; ISS:UniProtKB.
DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; 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 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 3D-structure; Acetylation; Alternative splicing; Autophagy;
KW Complete proteome; Cytoplasm; Isopeptide bond; Ligase;
KW Protein transport; Reference proteome; Transport; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1 314 Ubiquitin-like-conjugating enzyme ATG3.
FT /FTId=PRO_0000213569.
FT MOTIF 166 169 Caspase cleavage motif LETD.
FT ACT_SITE 264 264 Glycyl thioester intermediate (Probable).
FT SITE 169 170 Cleavage; by CASP8.
FT MOD_RES 1 1 N-acetylmethionine.
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
//
MIM
609606
*RECORD*
*FIELD* NO
609606
*FIELD* TI
*609606 AUTOPHAGY 3, S. CEREVISIAE, HOMOLOG OF; ATG3
;;APG3, S. CEREVISIAE, HOMOLOG OF; APG3;;
read moreAPG3-LIKE; APG3L
*FIELD* TX
DESCRIPTION
Autophagy is a process of bulk degradation of cytoplasmic components by
the lysosome or vacuole. Human ATG3 displays the same enzymatic
characteristics in vitro as yeast Apg3, a protein-conjugating enzyme
essential for autophagy (Tanida et al., 2002).
CLONING
By searching an EST database for sequences similar to yeast Apg3,
followed by 5-prime RACE of a brain cDNA library, Tanida et al. (2002)
cloned ATG3. The deduced 314-amino acid protein has a calculated
molecular mass of 35.8 kD. Yeast and human ATG3 share 34.1% amino acid
identity, with highest similarity in a region containing the predicted
active-site cysteine (cys264 in human). Northern blot analysis detected
ATG3 expression in all tissues examined, with highest levels in heart,
skeletal muscle, kidney, liver, and placenta. Fluorescence-tagged ATG3
was expressed in the cytosol of transfected human embryonic kidney
cells.
GENE FUNCTION
Tanida et al. (2002) identified ATG3 as an E2-like protein-conjugating
enzyme for 3 homologs of yeast Apg8, MAPLC3 (see 601242), GATE16
(GABARAPL2; 607452), and GABARAP (605125). ATG3 formed an
enzyme-substrate intermediate via a thiol ester bond that showed rapid
turnover. Replacement of the active-site cysteine of ATG3 with serine
(C264S) resulted in the formation of a stable O-ester bond that allowed
visualization of stable intermediates. Overexpression of ATG7 (608760)
enhanced the formation of stable E2-substrate complexes between
ATG3-C264S and each of the Apg8 homologs. MAPLC3 was the preferred
substrate, and the reaction with MAPLC3 occurred predominantly in the
cytosol. Coimmunoprecipitation of ATG7 with ATG3 indicated that ATG3
forms an E1-E2 complex with ATG7, similar to the yeast Apg3-Apg7
complex. Overexpression of ATG3 facilitated formation of the ATG12
(609608)-ATG5 (604261) conjugate, suggesting that ATG3 cross-talks with
the ATG12 conjugation system.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ATG3
gene to chromosome 3 (TMAP RH120928).
*FIELD* RF
1. Tanida, I.; Tanida-Miyake, E.; Komatsu, M.; Ueno, T.; Kominami,
E.: Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple
substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation
of hApg12p to hApg5p. J. Biol. Chem. 277: 13739-13744, 2002.
*FIELD* CD
Patricia A. Hartz: 9/26/2005
*FIELD* ED
mgross: 09/26/2005
*RECORD*
*FIELD* NO
609606
*FIELD* TI
*609606 AUTOPHAGY 3, S. CEREVISIAE, HOMOLOG OF; ATG3
;;APG3, S. CEREVISIAE, HOMOLOG OF; APG3;;
read moreAPG3-LIKE; APG3L
*FIELD* TX
DESCRIPTION
Autophagy is a process of bulk degradation of cytoplasmic components by
the lysosome or vacuole. Human ATG3 displays the same enzymatic
characteristics in vitro as yeast Apg3, a protein-conjugating enzyme
essential for autophagy (Tanida et al., 2002).
CLONING
By searching an EST database for sequences similar to yeast Apg3,
followed by 5-prime RACE of a brain cDNA library, Tanida et al. (2002)
cloned ATG3. The deduced 314-amino acid protein has a calculated
molecular mass of 35.8 kD. Yeast and human ATG3 share 34.1% amino acid
identity, with highest similarity in a region containing the predicted
active-site cysteine (cys264 in human). Northern blot analysis detected
ATG3 expression in all tissues examined, with highest levels in heart,
skeletal muscle, kidney, liver, and placenta. Fluorescence-tagged ATG3
was expressed in the cytosol of transfected human embryonic kidney
cells.
GENE FUNCTION
Tanida et al. (2002) identified ATG3 as an E2-like protein-conjugating
enzyme for 3 homologs of yeast Apg8, MAPLC3 (see 601242), GATE16
(GABARAPL2; 607452), and GABARAP (605125). ATG3 formed an
enzyme-substrate intermediate via a thiol ester bond that showed rapid
turnover. Replacement of the active-site cysteine of ATG3 with serine
(C264S) resulted in the formation of a stable O-ester bond that allowed
visualization of stable intermediates. Overexpression of ATG7 (608760)
enhanced the formation of stable E2-substrate complexes between
ATG3-C264S and each of the Apg8 homologs. MAPLC3 was the preferred
substrate, and the reaction with MAPLC3 occurred predominantly in the
cytosol. Coimmunoprecipitation of ATG7 with ATG3 indicated that ATG3
forms an E1-E2 complex with ATG7, similar to the yeast Apg3-Apg7
complex. Overexpression of ATG3 facilitated formation of the ATG12
(609608)-ATG5 (604261) conjugate, suggesting that ATG3 cross-talks with
the ATG12 conjugation system.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the ATG3
gene to chromosome 3 (TMAP RH120928).
*FIELD* RF
1. Tanida, I.; Tanida-Miyake, E.; Komatsu, M.; Ueno, T.; Kominami,
E.: Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple
substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation
of hApg12p to hApg5p. J. Biol. Chem. 277: 13739-13744, 2002.
*FIELD* CD
Patricia A. Hartz: 9/26/2005
*FIELD* ED
mgross: 09/26/2005