ID ATG3_HUMAN Reviewed; 314 AA. AC Q9NT62; C9JNW8; Q6PKC5; Q9H6L9; DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 27-MAR-2024, entry version 181. DE RecName: Full=Ubiquitin-like-conjugating enzyme ATG3 {ECO:0000305}; DE EC=2.3.2.- {ECO:0000269|PubMed:24191030, ECO:0000269|PubMed:33446636, ECO:0000269|PubMed:37252361}; DE AltName: Full=Autophagy-related protein 3; DE Short=APG3-like; DE Short=hApg3; DE AltName: Full=Protein PC3-96 {ECO:0000305|Ref.2}; GN Name=ATG3 {ECO:0000312|HGNC:HGNC:20962}; Synonyms=APG3, APG3L; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, MUTAGENESIS OF RP CYS-264, SUBCELLULAR LOCATION, FUNCTION, ACTIVE SITE, AND INTERACTION WITH RP 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 conjugation RT 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., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA 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 GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [5] 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [7] RP FUNCTION, AND INTERACTION WITH THE ATG12-ATG5 CONJUGATE AND ATG12. 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 [8] RP FUNCTION. RX PubMed=12890687; DOI=10.1074/jbc.m300550200; RA Nemoto T., Tanida I., Tanida-Miyake E., Minematsu-Ikeguchi N., Yokota M., RA 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 [9] 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 from RT human T cells using immobilized metal affinity chromatography and tandem RT mass spectrometry."; RL Anal. Chem. 76:2763-2772(2004). RN [10] 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 cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [11] 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 conjugation RT mediated by human Atg4B, Atg7 and Atg3."; RL FEBS J. 273:2553-2562(2006). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] 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., Podolsky D.K., RA Xavier R.J.; RT "A novel hybrid yeast-human network analysis reveals an essential role for RT FNBP1L in antibacterial autophagy."; RL J. Immunol. 182:4917-4930(2009). 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., Buerckstuemmer T., RA 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 MOTIF, PTM, 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 receptor- RT activated cell death."; RL Apoptosis 17:810-820(2012). RN [16] RP INTERACTION WITH ATG7 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, is RT essential for the E2-substrate reaction of LC3 lipidation."; RL Autophagy 8:88-97(2012). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [18] RP FUNCTION, AND INTERACTION WITH ATG7; ATG12; ATG5 AND ATG16L1. RX PubMed=24186333; DOI=10.1002/pro.2381; RA Qiu Y., Hofmann K., Coats J.E., Schulman B.A., Kaiser S.E.; RT "Binding to E1 and E3 is mutually exclusive for the human autophagy E2 RT Atg3."; RL Protein Sci. 22:1691-1697(2013). RN [19] RP INTERACTION WITH ATG7, AND MUTAGENESIS OF ASP-156; MET-157; TYR-160; RP GLU-167; ASP-169; ALA-171; THR-172 AND LEU-173. RX PubMed=26043688; DOI=10.1016/j.bbrc.2015.05.107; RA Ohashi K., Otomo T.; RT "Identification and characterization of the linear region of ATG3 that RT interacts with ATG7 in higher eukaryotes."; RL Biochem. Biophys. Res. Commun. 463:447-452(2015). RN [20] RP FUNCTION, AND MUTAGENESIS OF LYS-9 AND LYS-11. RX PubMed=29142222; DOI=10.1038/s41598-017-15057-6; RA Hervas J.H., Landajuela A., Anton Z., Shnyrova A.V., Goni F.M., Alonso A.; RT "Human ATG3 binding to lipid bilayers: role of lipid geometry, and electric RT charge."; RL Sci. Rep. 7:15614-15614(2017). RN [21] RP FUNCTION, DOMAIN, AND MUTAGENESIS OF VAL-8; VAL-15; PRO-21; LEU-23 AND RP GLU-25. RX PubMed=33446636; DOI=10.1038/s41467-020-20607-0; RA Ye Y., Tyndall E.R., Bui V., Tang Z., Shen Y., Jiang X., Flanagan J.M., RA Wang H.G., Tian F.; RT "An N-terminal conserved region in human Atg3 couples membrane curvature RT sensitivity to conjugase activity during autophagy."; RL Nat. Commun. 12:374-374(2021). RN [22] {ECO:0007744|PDB:4NAW} RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 140-170 IN COMPLEX WITH ATG12; RP ATG5 AND ATG16L1, FUNCTION, SUBUNIT, INTERACTION WITH ATG12, REGION, AND RP MUTAGENESIS OF 144-GLU--GLU-151; ASP-156; MET-157; TYR-160; GLU-161 AND RP CYS-264. RX PubMed=24191030; DOI=10.1073/pnas.1314755110; RA Metlagel Z., Otomo C., Takaesu G., Otomo T.; RT "Structural basis of ATG3 recognition by the autophagic ubiquitin-like RT protein ATG12."; RL Proc. Natl. Acad. Sci. U.S.A. 110:18844-18849(2013). RN [23] {ECO:0007744|PDB:8AFI} RP X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) OF 90-113 IN COMPLEX WITH GABARAP, RP FUNCTION, MOTIF, INTERACTION WITH GABARAP; MAP1LC3A; ATG12-ATG5 CONJUGATE; RP ATG16L1 AND ATG7, DOMAIN, AND MUTAGENESIS OF GLU-95; ILE-97; TRP-107; RP VAL-108 AND CYS-264. RX PubMed=37252361; DOI=10.1021/acscentsci.3c00009; RA Farnung J., Muhar M., Liang J.R., Tolmachova K.A., Benoit R.M., Corn J.E., RA Bode J.W.; RT "Semisynthetic LC3 Probes for Autophagy Pathways Reveal a Noncanonical LC3 RT Interacting Region Motif Crucial for the Enzymatic Activity of Human RT ATG3."; RL ACS Cent. Sci. 9:1025-1034(2023). CC -!- FUNCTION: E2 conjugating enzyme that catalyzes the covalent conjugation CC of the C-terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, CC GABARAPL2 or MAP1LC3A) to the amino group of phosphatidylethanolamine CC (PE)-containing lipids in the membrane resulting in membrane-bound CC ATG8-like proteins which is one of the key steps in the development of CC autophagic isolation membranes during autophagosome formation CC (PubMed:24191030, PubMed:37252361, PubMed:33446636). Cycles back and CC forth between binding to ATG7 for loading with the ATG8-like proteins CC and binding to E3 enzyme, composed of ATG12, ATG5 and ATG16L1 to CC promote ATG8-like proteins lipidation (PubMed:12207896, CC PubMed:24186333, PubMed:11825910, PubMed:12890687, PubMed:16704426). CC Also plays a role as a membrane curvature sensor that facilitates CC LC3/GABARAP lipidation by sensing local membrane stress associated with CC lipid-packing defects as occurs with high molar proportions of conical CC lipids or strident membrane curvature (By similarity). Interacts with CC negatively-charged membranes promoting membrane tethering and enhancing CC LC3/GABARAP lipidation (PubMed:29142222). Also acts as an autocatalytic CC E2-like enzyme by catalyzing the conjugation of ATG12 to itself in an CC ATG7-dependent manner, this complex thus formed, plays a role in CC mitochondrial homeostasis but not in autophagy (By similarity). ATG12- CC ATG3 conjugation promotes late endosome to lysosome trafficking and CC basal autophagosome maturation via its interaction with PDCD6IP (By CC similarity). ATG12-ATG3 conjugate is also formed upon viccina virus CC infection, leading to the disruption the cellular autophagy which is CC not necessary for vaccinia survival and proliferation (By similarity). CC Promotes primary ciliogenesis by removing OFD1 from centriolar CC satellites via the autophagic pathway (By similarity). CC {ECO:0000250|UniProtKB:Q9CPX6, ECO:0000269|PubMed:11825910, CC ECO:0000269|PubMed:12207896, ECO:0000269|PubMed:12890687, CC ECO:0000269|PubMed:16704426, ECO:0000269|PubMed:24186333, CC ECO:0000269|PubMed:24191030, ECO:0000269|PubMed:29142222, CC ECO:0000269|PubMed:33446636, ECO:0000269|PubMed:37252361}. CC -!- SUBUNIT: Homdimer (PubMed:24191030). Interacts with ATG7; this CC interaction forms an E1-E2 complex that is essential for the transfer CC of GABARAP thioester from ATG7 to ATG3 and disrupts interaction with CC the E3 enzyme complex (PubMed:11825910, PubMed:22170151, CC PubMed:26043688, PubMed:37252361, PubMed:24186333). Interacts with CC ATG12; this interaction is ATG7-dependent, essential for CC phosphatidylethanolamine (PE)-conjugated ATG8-like proteins formation CC and also mediates the autoconjugation of ATG12 on ATG3 CC (PubMed:11825910, PubMed:22170151, PubMed:24191030, PubMed:12207896). CC Interacts with FNBP1L (PubMed:19342671). Interacts with the E3 enzyme CC complex composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa); this CC interaction disrupts interaction with ATG7 and promotes ATG8-like CC proteins lipidation (PubMed:24191030, PubMed:37252361, CC PubMed:24186333). Interacts with GABARAP and MAP1LC3A CC (PubMed:37252361). Interacts with the ATG12-ATG5 conjugate; this CC interaction inhibits ATG8-like proteins lipidation (PubMed:12207896). CC Interacts (ATG12-ATG3 conjugate form) with PDCD6IP (via the BRO1 CC domain); this interaction is bridged by ATG12 and promotes multiple CC PDCD6IP-mediated functions such as endolysosomal trafficking, CC macroautophagy and exosome biogenesis (By similarity). CC {ECO:0000250|UniProtKB:Q9CPX6, ECO:0000269|PubMed:11825910, CC ECO:0000269|PubMed:12207896, ECO:0000269|PubMed:19342671, CC ECO:0000269|PubMed:22170151, ECO:0000269|PubMed:24186333, CC ECO:0000269|PubMed:24191030, ECO:0000269|PubMed:26043688, CC ECO:0000269|PubMed:37252361}. CC -!- INTERACTION: CC Q9NT62; O94817: ATG12; NbExp=6; IntAct=EBI-988094, EBI-746742; CC Q9NT62; O95166: GABARAP; NbExp=5; IntAct=EBI-988094, EBI-712001; CC Q9NT62; Q9H0R8: GABARAPL1; NbExp=3; IntAct=EBI-988094, EBI-746969; CC Q9NT62; P60520: GABARAPL2; NbExp=5; IntAct=EBI-988094, EBI-720116; CC Q9NT62; P62879: GNB2; NbExp=3; IntAct=EBI-988094, EBI-356942; CC Q9NT62; Q9GZQ8: MAP1LC3B; NbExp=7; IntAct=EBI-988094, EBI-373144; CC Q9NT62; Q70IA6: MOB2; NbExp=3; IntAct=EBI-988094, EBI-2558739; CC Q9NT62; Q7Z6L1: TECPR1; NbExp=3; IntAct=EBI-988094, EBI-2946676; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11825910}. 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 -!- TISSUE SPECIFICITY: Widely expressed, with a highest expression in CC heart, skeletal muscle, kidney, liver and placenta. CC {ECO:0000269|PubMed:11825910}. CC -!- DOMAIN: The N-terminal region works in concert with its geometry- CC selective amphipathic helix (AH) to promote LC3-PE conjugation activity CC only on the target membrane. {ECO:0000269|PubMed:33446636}. CC -!- DOMAIN: The LC3 interacting regions (LIR) motif mediates interaction CC with GABARAP and MAP1LC3A in a beta-sheet conformation-dependent manner CC (PubMed:37252361). The LIR motif is required for LC3 lipidation and CC ATG3~LC3 thioester formation (PubMed:37252361). CC {ECO:0000269|PubMed:37252361}. CC -!- DOMAIN: The membrane-curvature-sensing motif targets curved membranes. CC {ECO:0000250|UniProtKB:Q9CPX6}. CC -!- PTM: Cleaved by CASP8 upon death ligand binding such as tumor necrosis CC factor-alpha (PubMed:22644571). CASP8 cleavage blocks survival-related CC autophagy and favors apoptosis (PubMed:22644571). CC {ECO:0000269|PubMed:22644571}. CC -!- PTM: Conjugated to ATG12 at Lys-243. ATG12-conjugation plays a role in CC regulation of mitochondrial homeostasis and cell death, while it is not CC involved in phosphatidylethanolamine-conjugation to ATG8-like proteins CC and autophagy. {ECO:0000250|UniProtKB:Q9CPX6}. CC -!- SIMILARITY: Belongs to the ATG3 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH02830.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAB15237.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH02830.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB079384; BAB90843.1; -; mRNA. DR EMBL; AF202092; AAG35611.1; -; mRNA. DR EMBL; AL137515; CAB70781.1; -; mRNA. DR EMBL; AC092692; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC002830; AAH02830.1; ALT_FRAME; mRNA. DR EMBL; BC024221; AAH24221.1; -; mRNA. DR EMBL; AK025778; BAB15237.1; ALT_INIT; mRNA. DR CCDS; CCDS2966.1; -. [Q9NT62-1] DR CCDS; CCDS63721.1; -. [Q9NT62-2] DR PIR; T46276; T46276. DR RefSeq; NP_001265641.1; NM_001278712.1. [Q9NT62-2] DR RefSeq; NP_071933.2; NM_022488.4. [Q9NT62-1] DR PDB; 4NAW; X-ray; 2.20 A; D/H/L/P=140-170. DR PDB; 8AFI; X-ray; 2.66 A; B/D/F/H/J/L/N/P=90-113. DR PDB; 8FKM; NMR; -; A=25-314. DR PDBsum; 4NAW; -. DR PDBsum; 8AFI; -. DR PDBsum; 8FKM; -. DR AlphaFoldDB; Q9NT62; -. DR SMR; Q9NT62; -. DR BioGRID; 122171; 281. DR DIP; DIP-35052N; -. DR IntAct; Q9NT62; 38. DR STRING; 9606.ENSP00000283290; -. DR TCDB; 9.A.15.2.1; the autophagy-related phagophore-formation transporter (apt) family. DR GlyGen; Q9NT62; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NT62; -. DR PhosphoSitePlus; Q9NT62; -. DR SwissPalm; Q9NT62; -. DR BioMuta; ATG3; -. DR DMDM; 61212142; -. DR EPD; Q9NT62; -. DR jPOST; Q9NT62; -. DR MassIVE; Q9NT62; -. DR MaxQB; Q9NT62; -. DR PaxDb; 9606-ENSP00000283290; -. DR PeptideAtlas; Q9NT62; -. DR ProteomicsDB; 82601; -. [Q9NT62-1] DR ProteomicsDB; 82602; -. [Q9NT62-2] DR Pumba; Q9NT62; -. DR Antibodypedia; 32502; 844 antibodies from 39 providers. DR DNASU; 64422; -. DR Ensembl; ENST00000283290.10; ENSP00000283290.5; ENSG00000144848.11. [Q9NT62-1] DR Ensembl; ENST00000402314.6; ENSP00000385943.2; ENSG00000144848.11. [Q9NT62-2] DR GeneID; 64422; -. DR KEGG; hsa:64422; -. DR MANE-Select; ENST00000283290.10; ENSP00000283290.5; NM_022488.5; NP_071933.2. DR UCSC; uc003dzc.5; human. [Q9NT62-1] DR AGR; HGNC:20962; -. DR CTD; 64422; -. DR DisGeNET; 64422; -. DR GeneCards; ATG3; -. DR HGNC; HGNC:20962; ATG3. DR HPA; ENSG00000144848; Low tissue specificity. DR MIM; 609606; gene. DR neXtProt; NX_Q9NT62; -. DR OpenTargets; ENSG00000144848; -. DR PharmGKB; PA134883444; -. DR VEuPathDB; HostDB:ENSG00000144848; -. DR eggNOG; KOG2981; Eukaryota. DR GeneTree; ENSGT00390000010308; -. DR HOGENOM; CLU_027518_0_0_1; -. DR InParanoid; Q9NT62; -. DR OMA; YDKYYQV; -. DR OrthoDB; 179871at2759; -. DR PhylomeDB; Q9NT62; -. DR TreeFam; TF105903; -. DR PathwayCommons; Q9NT62; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR SignaLink; Q9NT62; -. DR SIGNOR; Q9NT62; -. DR BioGRID-ORCS; 64422; 37 hits in 1165 CRISPR screens. DR ChiTaRS; ATG3; human. DR GenomeRNAi; 64422; -. DR Pharos; Q9NT62; Tbio. DR PRO; PR:Q9NT62; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9NT62; Protein. DR Bgee; ENSG00000144848; Expressed in monocyte and 212 other cell types or tissues. DR ExpressionAtlas; Q9NT62; baseline and differential. DR GO; GO:0034274; C:Atg12-Atg5-Atg16 complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProt. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central. DR GO; GO:0019777; F:Atg12 transferase activity; ISS:UniProtKB. DR GO; GO:0141046; F:Atg8-family conjugating enzyme activity; IDA:UniProtKB. DR GO; GO:0019776; F:Atg8-family ligase activity; ISS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0019787; F:ubiquitin-like protein transferase activity; IDA:MGI. DR GO; GO:0000045; P:autophagosome assembly; IMP:UniProt. DR GO; GO:0043653; P:mitochondrial fragmentation involved in apoptotic process; ISS:UniProtKB. DR GO; GO:0050765; P:negative regulation of phagocytosis; IEA:Ensembl. DR GO; GO:0044804; P:nucleophagy; IBA:GO_Central. DR GO; GO:0006612; P:protein targeting to membrane; ISS:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:1902017; P:regulation of cilium assembly; ISS:UniProtKB. DR DisProt; DP01720; -. DR Gene3D; 3.30.1460.50; -; 1. DR InterPro; IPR046962; Atg3. DR InterPro; IPR007135; Atg3/Atg10. DR PANTHER; PTHR12866; UBIQUITIN-LIKE-CONJUGATING ENZYME ATG3; 1. DR PANTHER; PTHR12866:SF2; UBIQUITIN-LIKE-CONJUGATING ENZYME ATG3; 1. DR Pfam; PF03987; Autophagy_act_C; 1. DR Genevisible; Q9NT62; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Autophagy; Cytoplasm; KW Isopeptide bond; Protein transport; Reference proteome; Transferase; KW Transport; Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..314 FT /note="Ubiquitin-like-conjugating enzyme ATG3" FT /id="PRO_0000213569" FT REGION 140..170 FT /note="Interaction with ATG12" FT /evidence="ECO:0000269|PubMed:24191030" FT REGION 143..163 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 4..19 FT /note="Membrane-curvature-sensing motif" FT /evidence="ECO:0000250|UniProtKB:Q9CPX6" FT MOTIF 101..103 FT /note="Increases ATG3 translation efficiency by the FT ribomome assisted of EIF5A" FT /evidence="ECO:0000250|UniProtKB:Q9CPX6" FT MOTIF 104..110 FT /note="LIR motif" FT /evidence="ECO:0000269|PubMed:37252361, FT ECO:0007744|PDB:8AFI" FT MOTIF 166..169 FT /note="Caspase cleavage motif LETD" FT /evidence="ECO:0000269|PubMed:22644571" FT ACT_SITE 264 FT /note="Glycyl thioester intermediate" FT /evidence="ECO:0000305|PubMed:11825910" FT SITE 169..170 FT /note="Cleavage; by CASP8" FT /evidence="ECO:0000269|PubMed:22644571" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895" FT CROSSLNK 243 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ATG12)" FT /evidence="ECO:0000250|UniProtKB:Q9CPX6" FT VAR_SEQ 290..314 FT /note="LLIFLKFVQAVIPTIEYDYTRHFTM -> PSLYVRLVAKWLLTIFFLRNLV FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_013037" FT MUTAGEN 8 FT /note="V->D: Significantly reduces ATG8-family conjugating FT enzyme activity; when associated with K-15. Decreases FT protein membrane interactions; when associated with K-15. FT Does not affect formation of the covalent thioester FT intermediate with MAP1LC3B; when associated with K-15." FT /evidence="ECO:0000269|PubMed:33446636" FT MUTAGEN 9 FT /note="K->D: Slightly decreases interaction with lipid FT monolayers; when associated with D-11. Slightly decreases FT insertion into lipid monolayers; when associated with D-11. FT Decreases affinity for monolayers containing cardiolipin FT (CL); when associated with D-11. Cancels selectivity for FT anionic phospholipids; when associated with D-11. Impairs FT binding to lipid bilayers; when associated with D-11. FT Impairs insertion into lipid bilayers; when associated with FT D-11. Does not induce vesicle tethering; when associated FT with D-11." FT /evidence="ECO:0000269|PubMed:29142222" FT MUTAGEN 11 FT /note="K->D: Slightly decreases interaction with lipid FT monolayers; when associated with D-9. Slightly decreases FT insertion into lipid monolayers; when associated with D-9. FT Decreases affinity for monolayers containing cardiolipin FT (CL); when associated with D-9. Cancels selectivity for FT anionic phospholipids; when associated with D-11. Impairs FT binding to lipid bilayers; when associated with D-11. FT Impairs insertion into lipid bilayers; when associated with FT D-11. Does not induce vesicle tethering; when associated FT with D-11." FT /evidence="ECO:0000269|PubMed:29142222" FT MUTAGEN 15 FT /note="V->K: Significantly reduces ATG8-family conjugating FT enzyme activity; when associated with D-8. Decreases FT protein membrane interactions; when associated with D-8. FT Does not affect formation of the covalent thioester FT intermediate with MAP1LC3B; when associated with D-8." FT /evidence="ECO:0000269|PubMed:33446636" FT MUTAGEN 21 FT /note="P->A: Impairs ATG8-family conjugating enzyme FT activity. Does not affect protein membrane interactions. FT Does not affect formation of the covalent thioester FT intermediate with MAP1LC3B. Partially rescues MAP1LC3B FT lipidation in cell lacking ATG3." FT /evidence="ECO:0000269|PubMed:33446636" FT MUTAGEN 23 FT /note="L->T: Severely reduces ATG8-family conjugating FT enzyme activity. Reduces of about 40% protein membrane FT interactions. Does not affect formation of the covalent FT thioester intermediate with MAP1LC3B. Completely fails to FT induce membrane-bound MAP1LC3B (MAP1LC3B-II) and autophagic FT flux when expressed in cell lacking ATG3." FT /evidence="ECO:0000269|PubMed:33446636" FT MUTAGEN 25 FT /note="E->K: Increases of about 30% more ATG8-family FT conjugating enzyme activity. Does not affect protein FT membrane interactions. Does not affect formation of the FT covalent thioester intermediate with MAP1LC3B." FT /evidence="ECO:0000269|PubMed:33446636" FT MUTAGEN 95 FT /note="E->A: Severely diminish GABARAP:ATG3 conjugation." FT /evidence="ECO:0000269|PubMed:37252361" FT MUTAGEN 97 FT /note="I->A: Severely diminish GABARAP:ATG3 conjugation." FT /evidence="ECO:0000269|PubMed:37252361" FT MUTAGEN 107 FT /note="W->A: Almost completely abrogates GABARAP:ATG3 FT conjugation." FT /evidence="ECO:0000269|PubMed:37252361" FT MUTAGEN 108 FT /note="V->A: Significantly reduces GABARAP:ATG3 FT conjugation." FT /evidence="ECO:0000269|PubMed:37252361" FT MUTAGEN 144..151 FT /note="EEEEDEDE->AAAAAAAA: Strongly decreases affinity for FT the complex ATG12:ATG5:ATG16L1. Severely decreases FT phosphatidylethanolamine (PE)-conjugated ATG8-like proteins FT formation." FT /evidence="ECO:0000269|PubMed:24191030" FT MUTAGEN 156 FT /note="D->A: Strongly decreases affinity for the complex FT ATG12:ATG5:ATG16L1. Impairs interaction with the complex FT ATG12:ATG5:ATG16L1; when associated with A-157. Impairs FT phosphatidylethanolamine (PE)-conjugated ATG8-like protein FT formation. Loss of phosphatidylethanolamine (PE)-conjugated FT ATG8-like proteins formation; when associated with A-157. FT Impairs interaction with ATG12:ATG5; when associated with FT A-157. Does not affect interaction with ATG7; when FT associated with A-157. Does not affect the formation of the FT ATG8-like protein:ATG3 intermediate complex; when FT associated with A-157. Affects modestly the ATG3-ATG7 FT interaction; when associated with A-157. Reduces the FT thioester-linkage formation with GABARAP; when associated FT with A-157." FT /evidence="ECO:0000269|PubMed:24191030, FT ECO:0000269|PubMed:26043688" FT MUTAGEN 157 FT /note="M->A: Strongly decreases affinity for the complex FT ATG12:ATG5:ATG16L1. Impairs interaction with the complex FT ATG12:ATG5:ATG16L1; when associated with A-156. Impairs FT phosphatidylethanolamine (PE)-conjugated ATG8-like proteins FT formation. Loss of phosphatidylethanolamine (PE)-conjugated FT ATG8-like proteins formation; when associated with A-156. FT Impairs interaction with ATG12:ATG5; when associated with FT A-156. Does not affect interaction with ATG7; when FT associated with A-156. Does not affect the formation of the FT ATG8-like protein:ATG3 intermediate complex; when FT associated with A-156. Affects modestly the ATG3-ATG7 FT interaction; when associated with A-156. Reduces the FT thioester-linkage formation with GABARAP; when associated FT with A-156." FT /evidence="ECO:0000269|PubMed:24191030, FT ECO:0000269|PubMed:26043688" FT MUTAGEN 160 FT /note="Y->A: Strongly decreases affinity for the complex FT ATG12:ATG5:ATG16L1. Affects modestly the ATG3-ATG7 FT interaction. Reduces the thioester-linkage formation with FT GABARAP." FT /evidence="ECO:0000269|PubMed:24191030, FT ECO:0000269|PubMed:26043688" FT MUTAGEN 161 FT /note="E->A: Strongly decreases affinity for the complex FT ATG12:ATG5:ATG16L1." FT /evidence="ECO:0000269|PubMed:24191030" FT MUTAGEN 167 FT /note="E->A: Weakens the ATG3-ATG7 interaction. Reduces the FT thioester-linkage formation with GABARAP." FT /evidence="ECO:0000269|PubMed:26043688" FT MUTAGEN 169 FT /note="D->A: Weakens the ATG3-ATG7 interaction. Severly FT reduces the thioester-linkage formation with GABARAP." FT /evidence="ECO:0000269|PubMed:26043688" FT MUTAGEN 171 FT /note="A->A: Weakens the ATG3-ATG7 interaction. Reduces the FT thioester-linkage formation with GABARAP." FT /evidence="ECO:0000269|PubMed:26043688" FT MUTAGEN 172 FT /note="T->A: Weakens the ATG3-ATG7 interaction. FT Significantly reduces the thioester-linkage formation with FT GABARAP." FT /evidence="ECO:0000269|PubMed:26043688" FT MUTAGEN 173 FT /note="L->A: Weakens the ATG3-ATG7 interaction. FT Significantly reduces the thioester-linkage formation with FT GABARAP." FT /evidence="ECO:0000269|PubMed:26043688" FT MUTAGEN 264 FT /note="C->A: Does not affect interaction with ATG12:ATG5. FT Impairs MAP1LC3A lipidation. Impairs MAP1LC3B lipidation. FT Impairs ATG3:ATG8-like proteins thioester complex FT formation." FT /evidence="ECO:0000269|PubMed:24191030, FT ECO:0000269|PubMed:37252361" FT MUTAGEN 264 FT /note="C->S: Instead of the formation of an intermediate FT complex with a thiol ester bond between ATG3 (E2-like FT enzyme) and GABARAPL1/APG8L (substrate), a stable complex FT with an O-ester bond is formed." FT /evidence="ECO:0000269|PubMed:11825910" FT HELIX 157..163 FT /evidence="ECO:0007829|PDB:4NAW" 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 //