ID ATG7_HUMAN Reviewed; 703 AA. AC O95352; B4E170; E9PB95; Q7L8L0; Q9BWP2; Q9UFH4; DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 27-MAR-2024, entry version 192. DE RecName: Full=Ubiquitin-like modifier-activating enzyme ATG7 {ECO:0000305}; DE AltName: Full=ATG12-activating enzyme E1 ATG7; DE AltName: Full=Autophagy-related protein 7; DE Short=APG7-like; DE Short=hAGP7; DE AltName: Full=Ubiquitin-activating enzyme E1-like protein; GN Name=ATG7 {ECO:0000312|HGNC:HGNC:16935}; Synonyms=APG7L; 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). RC TISSUE=Brain; RX PubMed=10233149; DOI=10.1091/mbc.10.5.1353; RA Yuan W., Stromhaug P.E., Dunn W.A. Jr.; RT "Glucose-induced autophagy of peroxisomes in Pichia pastoris requires a RT unique E1-like protein."; RL Mol. Biol. Cell 10:1353-1366(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Kidney; 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 [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 179-703 (ISOFORM 1). RC TISSUE=Testis; 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 [6] RP FUNCTION, SUBUNIT, AND INTERACTION WITH ATG12; GABARAP; GABARAPL2 AND RP MAP1LC3A. RX PubMed=11096062; DOI=10.1074/jbc.c000752200; RA Tanida I., Tanida-Miyake E., Ueno T., Kominami E.; RT "The human homolog of Saccharomyces cerevisiae Apg7p is a Protein- RT activating enzyme for multiple substrates including human Apg12p, GATE-16, RT GABARAP, and MAP-LC3."; RL J. Biol. Chem. 276:1701-1706(2001). RN [7] RP TISSUE SPECIFICITY. RX PubMed=11890701; DOI=10.1006/bbrc.2002.6645; RA Tanida I., Tanida-Miyake E., Nishitani T., Komatsu M., Yamazaki H., RA Ueno T., Kominami E.; RT "Murine Apg12p has a substrate preference for murine Apg7p over three Apg8p RT homologs."; RL Biochem. Biophys. Res. Commun. 292:256-262(2002). RN [8] RP INTERACTION WITH ATG3 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 [9] RP FUNCTION, AND INTERACTION WITH GABARAP; GABARAPL2 AND MAP1LC3A. RX PubMed=16303767; DOI=10.1074/jbc.m505888200; RA Sou Y.S., Tanida I., Komatsu M., Ueno T., Kominami E.; RT "Phosphatidylserine in addition to phosphatidylethanolamine is an in vitro RT target of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-16."; RL J. Biol. Chem. 281:3017-3024(2006). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [11] RP ACETYLATION, AND INTERACTION WITH EP300. RX PubMed=19124466; DOI=10.1074/jbc.m807135200; RA Lee I.H., Finkel T.; RT "Regulation of autophagy by the p300 acetyltransferase."; RL J. Biol. Chem. 284:6322-6328(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] RP INTERACTION WITH FOXO1. RX PubMed=20543840; DOI=10.1038/ncb2069; RA Zhao Y., Yang J., Liao W., Liu X., Zhang H., Wang S., Wang D., Feng J., RA Yu L., Zhu W.G.; RT "Cytosolic FoxO1 is essential for the induction of autophagy and tumour RT suppressor activity."; RL Nat. Cell Biol. 12:665-675(2010). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [15] 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 [16] RP FUNCTION, AND MUTAGENESIS OF PHE-15; ALA-16 AND PRO-17. 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 ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 INDUCTION. RX PubMed=23386620; DOI=10.1074/jbc.m112.422071; RA Desai S., Liu Z., Yao J., Patel N., Chen J., Wu Y., Ahn E.E., Fodstad O., RA Tan M.; RT "Heat shock factor 1 (HSF1) controls chemoresistance and autophagy through RT transcriptional regulation of autophagy-related protein 7 (ATG7)."; RL J. Biol. Chem. 288:9165-9176(2013). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-698, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP INTERACTION WITH ATG3, AND MUTAGENESIS OF TRP-243 AND ARG-246. 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 [21] RP VARIANTS SCAR31 THR-234; ARG-261; ASP-511; PRO-512; HIS-576; MET-588; RP TYR-624 AND 659-ARG--ILE-703 DEL, INVOLVEMENT IN SCAR31, CHARACTERIZATION RP OF VARIANTS SCAR31 THR-234; ASP-511; HIS-576; MET-588 AND TYR-624, RP MUTAGENESIS OF CYS-572, AND FUNCTION. RX PubMed=34161705; DOI=10.1056/nejmoa1915722; RA Collier J.J., Guissart C., Olahova M., Sasorith S., Piron-Prunier F., RA Suomi F., Zhang D., Martinez-Lopez N., Leboucq N., Bahr A., RA Azzarello-Burri S., Reich S., Schoels L., Polvikoski T.M., Meyer P., RA Larrieu L., Schaefer A.M., Alsaif H.S., Alyamani S., Zuchner S., RA Barbosa I.A., Deshpande C., Pyle A., Rauch A., Synofzik M., Alkuraya F.S., RA Rivier F., Ryten M., McFarland R., Delahodde A., McWilliams T.G., RA Koenig M., Taylor R.W.; RT "Developmental Consequences of Defective ATG7-Mediated Autophagy in RT Humans."; RL N. Engl. J. Med. 384:2406-2417(2021). CC -!- FUNCTION: E1-like activating enzyme involved in the 2 ubiquitin-like CC systems required for cytoplasm to vacuole transport (Cvt) and CC autophagy. Activates ATG12 for its conjugation with ATG5 as well as the CC ATG8 family proteins for their conjugation with CC phosphatidylethanolamine. Both systems are needed for the ATG8 CC association to Cvt vesicles and autophagosomes membranes. Required for CC autophagic death induced by caspase-8 inhibition. Facilitates LC3-I CC lipidation with phosphatidylethanolamine to form LC3-II which is found CC on autophagosomal membranes (PubMed:34161705). Required for mitophagy CC which 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. Modulates CC p53/TP53 activity to regulate cell cycle and survival during metabolic CC stress. Also plays a key role in the maintenance of axonal homeostasis, CC the prevention of axonal degeneration, the maintenance of hematopoietic CC stem cells, the formation of Paneth cell granules, as well as in CC adipose differentiation. Plays a role in regulating the liver clock and CC glucose metabolism by mediating the autophagic degradation of CRY1 CC (clock repressor) in a time-dependent manner (By similarity). CC {ECO:0000250|UniProtKB:Q9D906, ECO:0000269|PubMed:11096062, CC ECO:0000269|PubMed:16303767, ECO:0000269|PubMed:22170151, CC ECO:0000269|PubMed:34161705}. CC -!- SUBUNIT: Homodimer (PubMed:11096062). Interacts with ATG3; this CC interaction is essential for the transfer of ATG8-like proteins's CC thioester from ATG7 to ATG3 and plays a role in the conjugation of CC ATG12 to ATG5 (PubMed:11825910, PubMed:26043688). Interacts with ATG12 CC (PubMed:11096062, PubMed:11825910). Forms intermediate conjugates with CC GABARAPL1 (By similarity). Forms intermediate conjugates with ATG8-like CC proteins such as GABARAP, GABARAPL2 or MAP1LC3A (PubMed:11096062, CC PubMed:16303767). Interacts with EP300 acetyltransferase CC (PubMed:19124466). Interacts with FOXO1 (PubMed:20543840). CC {ECO:0000250|UniProtKB:Q9D906, ECO:0000269|PubMed:11096062, CC ECO:0000269|PubMed:11825910, ECO:0000269|PubMed:16303767, CC ECO:0000269|PubMed:19124466, ECO:0000269|PubMed:20543840, CC ECO:0000269|PubMed:26043688}. CC -!- INTERACTION: CC O95352; P29692: EEF1D; NbExp=2; IntAct=EBI-987834, EBI-358607; CC O95352; O95166: GABARAP; NbExp=8; IntAct=EBI-987834, EBI-712001; CC O95352; Q9H0R8: GABARAPL1; NbExp=6; IntAct=EBI-987834, EBI-746969; CC O95352; P60520: GABARAPL2; NbExp=7; IntAct=EBI-987834, EBI-720116; CC O95352; P14316: IRF2; NbExp=2; IntAct=EBI-987834, EBI-2866589; CC O95352; Q9GZQ8: MAP1LC3B; NbExp=7; IntAct=EBI-987834, EBI-373144; CC O95352; Q96EB6: SIRT1; NbExp=3; IntAct=EBI-987834, EBI-1802965; CC O95352-2; Q13148: TARDBP; NbExp=3; IntAct=EBI-15980880, EBI-372899; CC O95352-2; P04637: TP53; NbExp=4; IntAct=EBI-15980880, EBI-366083; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Preautophagosomal CC structure {ECO:0000250}. Note=Localizes also to discrete punctae along CC the ciliary axoneme and to the base of the ciliary axoneme. CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O95352-1; Sequence=Displayed; CC Name=2; CC IsoId=O95352-2; Sequence=VSP_013205; CC Name=3; CC IsoId=O95352-3; Sequence=VSP_045206, VSP_045207; CC -!- TISSUE SPECIFICITY: Widely expressed, especially in kidney, liver, CC lymph nodes and bone marrow. {ECO:0000269|PubMed:11890701}. CC -!- INDUCTION: Expression is up-regulated by the transcription factor HSF1. CC {ECO:0000269|PubMed:23386620}. CC -!- DOMAIN: The C-terminal part of the protein is essential for the CC dimerization and interaction with ATG3 and ATG12. {ECO:0000250}. CC -!- DOMAIN: The N-terminal FAP motif (residues 15 to 17) is essential for CC the formation of the ATG89-PE and ATG5-ATG12 conjugates. CC {ECO:0000269|PubMed:22170151}. CC -!- PTM: Acetylated by EP300. {ECO:0000269|PubMed:19124466}. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 31 (SCAR31) CC [MIM:619422]: A form of spinocerebellar ataxia, a clinically and CC genetically heterogeneous group of cerebellar disorders due to CC degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCAR30 is characterized by global CC developmental delay, hypotonia, variably impaired intellectual and CC language development, ataxic gait, tremor, and dysarthria. Most CC affected individuals have optic atrophy. Additional features may CC include retinitis pigmentosa, sensorineural deafness, dysmorphic facial CC features, and possibly endocrine dysfunction. CC {ECO:0000269|PubMed:34161705}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ATG7 family. {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; AF094516; AAC69630.1; -; mRNA. DR EMBL; AK303694; BAG64682.1; -; mRNA. DR EMBL; AC020750; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC022001; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC026185; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC083855; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000091; AAH00091.1; -; mRNA. DR EMBL; AL122075; CAB59250.1; -; mRNA. DR CCDS; CCDS2605.1; -. [O95352-1] DR CCDS; CCDS46752.1; -. [O95352-2] DR CCDS; CCDS46753.1; -. [O95352-3] DR PIR; T34556; T34556. DR RefSeq; NP_001129503.2; NM_001136031.2. [O95352-2] DR RefSeq; NP_001138384.1; NM_001144912.1. [O95352-3] DR RefSeq; NP_006386.1; NM_006395.2. [O95352-1] DR RefSeq; XP_011531584.1; XM_011533282.2. DR RefSeq; XP_011531588.1; XM_011533286.2. DR RefSeq; XP_016861033.1; XM_017005544.1. DR RefSeq; XP_016861034.1; XM_017005545.1. DR RefSeq; XP_016861035.1; XM_017005546.1. DR AlphaFoldDB; O95352; -. DR SMR; O95352; -. DR BioGRID; 115787; 417. DR DIP; DIP-29759N; -. DR IntAct; O95352; 34. DR STRING; 9606.ENSP00000346437; -. DR BindingDB; O95352; -. DR ChEMBL; CHEMBL2321621; -. DR TCDB; 9.A.15.2.1; the autophagy-related phagophore-formation transporter (apt) family. DR iPTMnet; O95352; -. DR MetOSite; O95352; -. DR PhosphoSitePlus; O95352; -. DR SwissPalm; O95352; -. DR BioMuta; ATG7; -. DR EPD; O95352; -. DR jPOST; O95352; -. DR MassIVE; O95352; -. DR MaxQB; O95352; -. DR PaxDb; 9606-ENSP00000346437; -. DR PeptideAtlas; O95352; -. DR ProteomicsDB; 19175; -. DR ProteomicsDB; 50814; -. [O95352-1] DR ProteomicsDB; 50815; -. [O95352-2] DR Pumba; O95352; -. DR Antibodypedia; 1972; 929 antibodies from 45 providers. DR DNASU; 10533; -. DR Ensembl; ENST00000354449.7; ENSP00000346437.3; ENSG00000197548.13. [O95352-1] DR Ensembl; ENST00000354956.9; ENSP00000347042.5; ENSG00000197548.13. [O95352-2] DR Ensembl; ENST00000446450.6; ENSP00000412580.2; ENSG00000197548.13. [O95352-3] DR Ensembl; ENST00000685771.1; ENSP00000509725.1; ENSG00000197548.13. [O95352-1] DR Ensembl; ENST00000693202.1; ENSP00000510336.1; ENSG00000197548.13. [O95352-1] DR GeneID; 10533; -. DR KEGG; hsa:10533; -. DR MANE-Select; ENST00000693202.1; ENSP00000510336.1; NM_001349232.2; NP_001336161.1. DR UCSC; uc003bwc.4; human. [O95352-1] DR AGR; HGNC:16935; -. DR CTD; 10533; -. DR DisGeNET; 10533; -. DR GeneCards; ATG7; -. DR HGNC; HGNC:16935; ATG7. DR HPA; ENSG00000197548; Low tissue specificity. DR MalaCards; ATG7; -. DR MIM; 608760; gene. DR MIM; 619422; phenotype. DR neXtProt; NX_O95352; -. DR OpenTargets; ENSG00000197548; -. DR PharmGKB; PA134983397; -. DR VEuPathDB; HostDB:ENSG00000197548; -. DR eggNOG; KOG2337; Eukaryota. DR GeneTree; ENSGT00390000017509; -. DR HOGENOM; CLU_012998_1_0_1; -. DR InParanoid; O95352; -. DR OMA; RQIWDAI; -. DR OrthoDB; 1128973at2759; -. DR PhylomeDB; O95352; -. DR TreeFam; TF105689; -. DR PathwayCommons; O95352; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; O95352; -. DR SIGNOR; O95352; -. DR BioGRID-ORCS; 10533; 31 hits in 1171 CRISPR screens. DR ChiTaRS; ATG7; human. DR GeneWiki; ATG7; -. DR GenomeRNAi; 10533; -. DR Pharos; O95352; Tchem. DR PRO; PR:O95352; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; O95352; Protein. DR Bgee; ENSG00000197548; Expressed in monocyte and 152 other cell types or tissues. DR ExpressionAtlas; O95352; baseline and differential. DR GO; GO:0005930; C:axoneme; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0019778; F:Atg12 activating enzyme activity; IMP:UniProt. DR GO; GO:0019779; F:Atg8 activating enzyme activity; IBA:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0000045; P:autophagosome assembly; IMP:UniProt. DR GO; GO:0006914; P:autophagy; IMP:GO_Central. DR GO; GO:0071455; P:cellular response to hyperoxia; IDA:UniProtKB. DR GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central. DR GO; GO:0009267; P:cellular response to starvation; IDA:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IMP:CACAO. DR GO; GO:0016236; P:macroautophagy; IMP:BHF-UCL. DR GO; GO:0000423; P:mitophagy; IGI:ParkinsonsUK-UCL. DR GO; GO:0044804; P:nucleophagy; IBA:GO_Central. DR GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IBA:GO_Central. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:UniProtKB. DR GO; GO:0031401; P:positive regulation of protein modification process; IDA:MGI. DR GO; GO:0006497; P:protein lipidation; IDA:MGI. DR GO; GO:0032446; P:protein modification by small protein conjugation; IBA:GO_Central. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR CDD; cd01486; Apg7; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 3.40.140.100; Ubiquitin-like modifier-activating enzyme ATG7 C-terminal domain; 1. DR Gene3D; 3.40.140.70; Ubiquitin-like modifier-activating enzyme ATG7 N-terminal domain; 1. DR InterPro; IPR006285; Atg7. DR InterPro; IPR032197; Atg7_N. DR InterPro; IPR042522; Atg7_N_1. DR InterPro; IPR042523; Atg7_N_2. DR InterPro; IPR045886; ThiF/MoeB/HesA. DR InterPro; IPR000594; ThiF_NAD_FAD-bd. DR InterPro; IPR035985; Ubiquitin-activating_enz. DR NCBIfam; TIGR01381; E1_like_apg7; 1. DR PANTHER; PTHR10953; UBIQUITIN-ACTIVATING ENZYME E1; 1. DR PANTHER; PTHR10953:SF3; UBIQUITIN-LIKE MODIFIER-ACTIVATING ENZYME ATG7; 1. DR Pfam; PF16420; ATG7_N; 1. DR Pfam; PF00899; ThiF; 1. DR SUPFAM; SSF69572; Activating enzymes of the ubiquitin-like proteins; 1. DR Genevisible; O95352; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Autophagy; Biological rhythms; KW Cytoplasm; Disease variant; Neurodegeneration; Phosphoprotein; KW Protein transport; Reference proteome; Transport; Ubl conjugation pathway. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895" FT CHAIN 2..703 FT /note="Ubiquitin-like modifier-activating enzyme ATG7" FT /id="PRO_0000212806" FT MOTIF 15..17 FT /note="FAP motif" FT ACT_SITE 572 FT /note="Glycyl thioester intermediate" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895" FT MOD_RES 698 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VAR_SEQ 138..176 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045206" FT VAR_SEQ 626..652 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013205" FT VAR_SEQ 653..693 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045207" FT VARIANT 234 FT /note="P -> T (in SCAR31; results in decreased LC3-I FT lipidation to form LC3-II)" FT /evidence="ECO:0000269|PubMed:34161705" FT /id="VAR_085979" FT VARIANT 261 FT /note="Q -> R (in SCAR31; uncertain significance)" FT /evidence="ECO:0000269|PubMed:34161705" FT /id="VAR_085980" FT VARIANT 471 FT /note="V -> A (in dbSNP:rs36117895)" FT /id="VAR_053014" FT VARIANT 511 FT /note="G -> D (in SCAR31; results in severely decreased FT LC3-I lipidation to form LC3-II)" FT /evidence="ECO:0000269|PubMed:34161705" FT /id="VAR_085981" FT VARIANT 512 FT /note="L -> P (in SCAR31; in homozygous patient cells it FT results in diminished autophagic flux)" FT /evidence="ECO:0000269|PubMed:34161705" FT /id="VAR_085982" FT VARIANT 576 FT /note="R -> H (in SCAR31; results in decreased LC3-I FT lipidation to form LC3-II)" FT /evidence="ECO:0000269|PubMed:34161705" FT /id="VAR_085983" FT VARIANT 588 FT /note="V -> M (in SCAR31; results in severely decreased FT LC3-I lipidation to form LC3-II)" FT /evidence="ECO:0000269|PubMed:34161705" FT /id="VAR_085984" FT VARIANT 624 FT /note="H -> Y (in SCAR31; results in decreased LC3-I FT lipidation to form LC3-II)" FT /evidence="ECO:0000269|PubMed:34161705" FT /id="VAR_085985" FT VARIANT 659..703 FT /note="Missing (in SCAR31)" FT /evidence="ECO:0000269|PubMed:34161705" FT /id="VAR_085986" FT MUTAGEN 15 FT /note="F->D: Impairs conjugation activity; when associated FT with D-16 and D-17." FT /evidence="ECO:0000269|PubMed:22170151" FT MUTAGEN 16 FT /note="A->D: Impairs conjugation activity; when associated FT with D-15 and D-17." FT /evidence="ECO:0000269|PubMed:22170151" FT MUTAGEN 17 FT /note="P->D: Impairs conjugation activity; when associated FT with D-15 and D-16." FT /evidence="ECO:0000269|PubMed:22170151" FT MUTAGEN 243 FT /note="W->A: Moderately impairs ATG3 binding. Moderately FT reduces GABARAP-ATG3 thioester bond formation. Moderately FT reduces GABARAP lipidation." FT /evidence="ECO:0000269|PubMed:26043688" FT MUTAGEN 246 FT /note="R->D: Almost completely impairs ATG3 binding. FT Severely reduces GABARAP-ATG3 thioester bond formation. FT Severely reduces GABARAP lipidation." FT /evidence="ECO:0000269|PubMed:26043688" FT MUTAGEN 572 FT /note="C->A: Loss of LC3-I lipidation to form LC3-II." FT /evidence="ECO:0000269|PubMed:34161705" FT CONFLICT 210 FT /note="V -> A (in Ref. 2; BAG64682)" FT /evidence="ECO:0000305" FT CONFLICT 346 FT /note="P -> L (in Ref. 2; BAG64682)" FT /evidence="ECO:0000305" SQ SEQUENCE 703 AA; 77960 MW; ABBD1A29A6C58356 CRC64; MAAATGDPGL SKLQFAPFSS ALDVGFWHEL TQKKLNEYRL DEAPKDIKGY YYNGDSAGLP ARLTLEFSAF DMSAPTPARC CPAIGTLYNT NTLESFKTAD KKLLLEQAAN EIWESIKSGT ALENPVLLNK FLLLTFADLK KYHFYYWFCY PALCLPESLP LIQGPVGLDQ RFSLKQIEAL ECAYDNLCQT EGVTALPYFL IKYDENMVLV SLLKHYSDFF QGQRTKITIG VYDPCNLAQY PGWPLRNFLV LAAHRWSSSF QSVEVVCFRD RTMQGARDVA HSIIFEVKLP EMAFSPDCPK AVGWEKNQKG GMGPRMVNLS ECMDPKRLAE SSVDLNLKLM CWRLVPTLDL DKVVSVKCLL LGAGTLGCNV ARTLMGWGVR HITFVDNAKI SYSNPVRQPL YEFEDCLGGG KPKALAAADR LQKIFPGVNA RGFNMSIPMP GHPVNFSSVT LEQARRDVEQ LEQLIESHDV VFLLMDTRES RWLPAVIAAS KRKLVINAAL GFDTFVVMRH GLKKPKQQGA GDLCPNHPVA SADLLGSSLF ANIPGYKLGC YFCNDVVAPG DSTRDRTLDQ QCTVSRPGLA VIAGALAVEL MVSVLQHPEG GYAIASSSDD RMNEPPTSLG LVPHQIRGFL SRFDNVLPVS LAFDKCTACS SKVLDQYERE GFNFLAKVFN SSHSFLEDLT GLTLLHQETQ AAEIWDMSDD ETI //