ATG7_HUMAN
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 03-AUG-2022, entry version 183.
DE RecName: Full=Ubiquitin-like modifier-activating enzyme ATG7;
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; 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 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 and ATG12
CC (PubMed:11096062, PubMed:11825910). The complex, composed of ATG3 and
CC ATG7, plays a role in the conjugation of ATG12 to ATG5
CC (PubMed:11825910). Forms intermediate conjugates with ATG8-like
CC proteins such as GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A
CC (PubMed:11096062, PubMed:16303767). Interacts with EP300
CC acetyltransferase (PubMed:19124466). Interacts with FOXO1
CC (PubMed:20543840). {ECO:0000269|PubMed:11096062,
CC ECO:0000269|PubMed:11825910, ECO:0000269|PubMed:16303767,
CC ECO:0000269|PubMed:19124466, ECO:0000269|PubMed:20543840}.
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}.
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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. [O95352-2]
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; 393.
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 GlyGen; O95352; 1 site, 1 O-linked glycan (1 site).
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; O95352; -.
DR PeptideAtlas; O95352; -.
DR PRIDE; O95352; -.
DR ProteomicsDB; 19175; -.
DR ProteomicsDB; 50814; -. [O95352-1]
DR ProteomicsDB; 50815; -. [O95352-2]
DR Antibodypedia; 1972; 855 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 CTD; 10533; -.
DR DisGeNET; 10533; -.
DR GeneCards; ATG7; -.
DR HGNC; HGNC:16935; ATG7.
DR HPA; ENSG00000197548; Low tissue specificity.
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; VQTWRYS; -.
DR OrthoDB; 549762at2759; -.
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; 30 hits in 1092 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 150 other tissues.
DR ExpressionAtlas; O95352; baseline and differential.
DR Genevisible; O95352; HS.
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; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IMP:GO_Central.
DR GO; GO:0000422; P:autophagy of mitochondrion; IGI:ParkinsonsUK-UCL.
DR GO; GO:0006501; P:C-terminal protein lipidation; IBA: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:0044805; P:late nucleophagy; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; IMP:BHF-UCL.
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 GO; GO:0039521; P:suppression by virus of host autophagy; IMP:CACAO.
DR Gene3D; 3.40.140.100; -; 1.
DR Gene3D; 3.40.140.70; -; 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 PANTHER; PTHR10953; PTHR10953; 1.
DR Pfam; PF16420; ATG7_N; 1.
DR Pfam; PF00899; ThiF; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
DR TIGRFAMs; TIGR01381; E1_like_apg7; 1.
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; unknown pathological
FT 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 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
