Full text data of ATG7
ATG7
(APG7L)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquitin-like modifier-activating enzyme ATG7 (ATG12-activating enzyme E1 ATG7; Autophagy-related protein 7; APG7-like; hAGP7; Ubiquitin-activating enzyme E1-like protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquitin-like modifier-activating enzyme ATG7 (ATG12-activating enzyme E1 ATG7; Autophagy-related protein 7; APG7-like; hAGP7; Ubiquitin-activating enzyme E1-like protein)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O95352
ID ATG7_HUMAN Reviewed; 703 AA.
AC O95352; B4E170; E9PB95; Q7L8L0; Q9BWP2; Q9UFH4;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 115.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT a 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.,
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 [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.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA 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.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA 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
RT project: 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.,
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 [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,
RT GATE-16, 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
RT Apg8p 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
RT conjugation 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
RT vitro target of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-
RT 16.";
RL J. Biol. Chem. 281:3017-3024(2006).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [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 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(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 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,
RT is essential for the E2-substrate reaction of LC3 lipidation.";
RL Autophagy 8:88-97(2012).
RN [16]
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.,
RA Fodstad O., Tan M.;
RT "Heat shock factor 1 (HSF1) controls chemoresistance and autophagy
RT through transcriptional regulation of autophagy-related protein 7
RT (ATG7).";
RL J. Biol. Chem. 288:9165-9176(2013).
CC -!- FUNCTION: E1-like activating enzyme involved in the 2 ubiquitin-
CC like systems required for cytoplasm to vacuole transport (Cvt) and
CC autophagy. Activates ATG12 for its conjugation with ATG5 as well
CC as the 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
CC for autophagic death induced by caspase-8 inhibition. Required for
CC mitophagy which contributes to regulate mitochondrial quantity and
CC quality by eliminating the mitochondria to a basal level to
CC fulfill cellular energy requirements and preventing excess ROS
CC production. Modulates p53/TP53 activity to regulate cell cycle and
CC survival during metabolic stress. Plays also a key role in the
CC maintenance of axonal homeostasis, the prevention of axonal
CC degeneration, the maintenance of hematopoietic stem cells, the
CC formation of Paneth cell granules, as well as in adipose
CC differentiation.
CC -!- SUBUNIT: Homodimer. Interacts with ATG3 and ATG12. The complex,
CC composed of ATG3 and ATG7, plays a role in the conjugation of
CC ATG12 to ATG5. Forms intermediate conjugates with ATG8-like
CC proteins such as GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A.
CC Interacts with EP300 acetyltransferase.
CC -!- INTERACTION:
CC P29692:EEF1D; NbExp=2; IntAct=EBI-987834, EBI-358607;
CC O95166:GABARAP; NbExp=8; IntAct=EBI-987834, EBI-712001;
CC Q9H0R8:GABARAPL1; NbExp=6; IntAct=EBI-987834, EBI-746969;
CC P60520:GABARAPL2; NbExp=7; IntAct=EBI-987834, EBI-720116;
CC P14316:IRF2; NbExp=2; IntAct=EBI-987834, EBI-2866589;
CC Q9GZQ8:MAP1LC3B; NbExp=7; IntAct=EBI-987834, EBI-373144;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Preautophagosomal
CC structure (By similarity). Note=Localizes also to discrete punctae
CC along the ciliary axoneme and to the base of the ciliary axoneme
CC (By similarity).
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.
CC -!- INDUCTION: Expression is up-regulated by the transcription factor
CC HSF1.
CC -!- DOMAIN: The C-terminal part of the protein is essential for the
CC dimerization and interaction with ATG3 and ATG12 (By similarity).
CC -!- DOMAIN: The N-terminal FAP motif (residues 15 to 17) is essential
CC for the formation of the ATG89-PE and ATG5-ATG12 conjugates
CC (PubMed:22170151).
CC -!- PTM: Acetylated by EP300.
CC -!- SIMILARITY: Belongs to the ATG7 family.
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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 PIR; T34556; T34556.
DR RefSeq; NP_001129503.2; NM_001136031.2.
DR RefSeq; NP_001138384.1; NM_001144912.1.
DR RefSeq; NP_006386.1; NM_006395.2.
DR RefSeq; XP_005264857.1; XM_005264800.1.
DR RefSeq; XP_005264858.1; XM_005264801.1.
DR RefSeq; XP_005264859.1; XM_005264802.1.
DR UniGene; Hs.38032; -.
DR ProteinModelPortal; O95352; -.
DR SMR; O95352; 13-690.
DR DIP; DIP-29759N; -.
DR IntAct; O95352; 14.
DR STRING; 9606.ENSP00000346437; -.
DR ChEMBL; CHEMBL2321621; -.
DR PhosphoSite; O95352; -.
DR PaxDb; O95352; -.
DR PRIDE; O95352; -.
DR Ensembl; ENST00000354449; ENSP00000346437; ENSG00000197548.
DR Ensembl; ENST00000354956; ENSP00000347042; ENSG00000197548.
DR Ensembl; ENST00000446450; ENSP00000412580; ENSG00000197548.
DR GeneID; 10533; -.
DR KEGG; hsa:10533; -.
DR UCSC; uc011aum.2; human.
DR CTD; 10533; -.
DR GeneCards; GC03P011313; -.
DR HGNC; HGNC:16935; ATG7.
DR HPA; CAB018771; -.
DR HPA; HPA007639; -.
DR MIM; 608760; gene.
DR neXtProt; NX_O95352; -.
DR PharmGKB; PA134983397; -.
DR eggNOG; COG0476; -.
DR HOGENOM; HOG000162379; -.
DR HOVERGEN; HBG080877; -.
DR InParanoid; O95352; -.
DR KO; K08337; -.
DR OMA; CTGCSET; -.
DR OrthoDB; EOG7X0VGG; -.
DR PhylomeDB; O95352; -.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; ATG7; -.
DR GenomeRNAi; 10533; -.
DR NextBio; 39961; -.
DR PRO; PR:O95352; -.
DR ArrayExpress; O95352; -.
DR Bgee; O95352; -.
DR CleanEx; HS_ATG7; -.
DR Genevestigator; O95352; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0000407; C:pre-autophagosomal structure; IEA:UniProtKB-SubCell.
DR GO; GO:0019778; F:APG12 activating enzyme activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004839; F:ubiquitin activating enzyme activity; TAS:ProtInc.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0055013; P:cardiac muscle cell development; IEA:Ensembl.
DR GO; GO:0006520; P:cellular amino acid metabolic process; IEA:Ensembl.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; IEA:Ensembl.
DR GO; GO:0021680; P:cerebellar Purkinje cell layer development; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0061025; P:membrane fusion; TAS:ProtInc.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0050877; P:neurological system process; IEA:Ensembl.
DR GO; GO:0006996; P:organelle organization; IEA:Ensembl.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:BHF-UCL.
DR GO; GO:0031401; P:positive regulation of protein modification process; IDA:MGI.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0006497; P:protein lipidation; IDA:MGI.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0021860; P:pyramidal neuron development; IEA:Ensembl.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR006285; Atg7.
DR InterPro; IPR009036; Molybdenum_cofac_synth_MoeB.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR PANTHER; PTHR10953:SF3; PTHR10953:SF3; 1.
DR Pfam; PF00899; ThiF; 1.
DR SUPFAM; SSF69572; SSF69572; 2.
DR TIGRFAMs; TIGR01381; E1_like_apg7; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Autophagy; Complete proteome;
KW Cytoplasm; Polymorphism; Protein transport; Reference proteome;
KW Transport; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 703 Ubiquitin-like modifier-activating enzyme
FT ATG7.
FT /FTId=PRO_0000212806.
FT MOTIF 15 17 FAP motif.
FT ACT_SITE 572 572 Glycyl thioester intermediate (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 138 176 Missing (in isoform 3).
FT /FTId=VSP_045206.
FT VAR_SEQ 626 652 Missing (in isoform 2).
FT /FTId=VSP_013205.
FT VAR_SEQ 653 693 Missing (in isoform 3).
FT /FTId=VSP_045207.
FT VARIANT 471 471 V -> A (in dbSNP:rs36117895).
FT /FTId=VAR_053014.
FT MUTAGEN 15 15 F->D: Impairs conjugation activity; when
FT associated with D-16 and D-17.
FT MUTAGEN 16 16 A->D: Impairs conjugation activity; when
FT associated with D-15 and D-17.
FT MUTAGEN 17 17 P->D: Impairs conjugation activity; when
FT associated with D-15 and D-16.
FT CONFLICT 210 210 V -> A (in Ref. 2; BAG64682).
FT CONFLICT 346 346 P -> L (in Ref. 2; BAG64682).
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
//
ID ATG7_HUMAN Reviewed; 703 AA.
AC O95352; B4E170; E9PB95; Q7L8L0; Q9BWP2; Q9UFH4;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 115.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT a 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.,
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 [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.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA 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.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA 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
RT project: 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.,
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 [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,
RT GATE-16, 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
RT Apg8p 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
RT conjugation 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
RT vitro target of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-
RT 16.";
RL J. Biol. Chem. 281:3017-3024(2006).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [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 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(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 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,
RT is essential for the E2-substrate reaction of LC3 lipidation.";
RL Autophagy 8:88-97(2012).
RN [16]
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.,
RA Fodstad O., Tan M.;
RT "Heat shock factor 1 (HSF1) controls chemoresistance and autophagy
RT through transcriptional regulation of autophagy-related protein 7
RT (ATG7).";
RL J. Biol. Chem. 288:9165-9176(2013).
CC -!- FUNCTION: E1-like activating enzyme involved in the 2 ubiquitin-
CC like systems required for cytoplasm to vacuole transport (Cvt) and
CC autophagy. Activates ATG12 for its conjugation with ATG5 as well
CC as the 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
CC for autophagic death induced by caspase-8 inhibition. Required for
CC mitophagy which contributes to regulate mitochondrial quantity and
CC quality by eliminating the mitochondria to a basal level to
CC fulfill cellular energy requirements and preventing excess ROS
CC production. Modulates p53/TP53 activity to regulate cell cycle and
CC survival during metabolic stress. Plays also a key role in the
CC maintenance of axonal homeostasis, the prevention of axonal
CC degeneration, the maintenance of hematopoietic stem cells, the
CC formation of Paneth cell granules, as well as in adipose
CC differentiation.
CC -!- SUBUNIT: Homodimer. Interacts with ATG3 and ATG12. The complex,
CC composed of ATG3 and ATG7, plays a role in the conjugation of
CC ATG12 to ATG5. Forms intermediate conjugates with ATG8-like
CC proteins such as GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A.
CC Interacts with EP300 acetyltransferase.
CC -!- INTERACTION:
CC P29692:EEF1D; NbExp=2; IntAct=EBI-987834, EBI-358607;
CC O95166:GABARAP; NbExp=8; IntAct=EBI-987834, EBI-712001;
CC Q9H0R8:GABARAPL1; NbExp=6; IntAct=EBI-987834, EBI-746969;
CC P60520:GABARAPL2; NbExp=7; IntAct=EBI-987834, EBI-720116;
CC P14316:IRF2; NbExp=2; IntAct=EBI-987834, EBI-2866589;
CC Q9GZQ8:MAP1LC3B; NbExp=7; IntAct=EBI-987834, EBI-373144;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Preautophagosomal
CC structure (By similarity). Note=Localizes also to discrete punctae
CC along the ciliary axoneme and to the base of the ciliary axoneme
CC (By similarity).
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.
CC -!- INDUCTION: Expression is up-regulated by the transcription factor
CC HSF1.
CC -!- DOMAIN: The C-terminal part of the protein is essential for the
CC dimerization and interaction with ATG3 and ATG12 (By similarity).
CC -!- DOMAIN: The N-terminal FAP motif (residues 15 to 17) is essential
CC for the formation of the ATG89-PE and ATG5-ATG12 conjugates
CC (PubMed:22170151).
CC -!- PTM: Acetylated by EP300.
CC -!- SIMILARITY: Belongs to the ATG7 family.
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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 PIR; T34556; T34556.
DR RefSeq; NP_001129503.2; NM_001136031.2.
DR RefSeq; NP_001138384.1; NM_001144912.1.
DR RefSeq; NP_006386.1; NM_006395.2.
DR RefSeq; XP_005264857.1; XM_005264800.1.
DR RefSeq; XP_005264858.1; XM_005264801.1.
DR RefSeq; XP_005264859.1; XM_005264802.1.
DR UniGene; Hs.38032; -.
DR ProteinModelPortal; O95352; -.
DR SMR; O95352; 13-690.
DR DIP; DIP-29759N; -.
DR IntAct; O95352; 14.
DR STRING; 9606.ENSP00000346437; -.
DR ChEMBL; CHEMBL2321621; -.
DR PhosphoSite; O95352; -.
DR PaxDb; O95352; -.
DR PRIDE; O95352; -.
DR Ensembl; ENST00000354449; ENSP00000346437; ENSG00000197548.
DR Ensembl; ENST00000354956; ENSP00000347042; ENSG00000197548.
DR Ensembl; ENST00000446450; ENSP00000412580; ENSG00000197548.
DR GeneID; 10533; -.
DR KEGG; hsa:10533; -.
DR UCSC; uc011aum.2; human.
DR CTD; 10533; -.
DR GeneCards; GC03P011313; -.
DR HGNC; HGNC:16935; ATG7.
DR HPA; CAB018771; -.
DR HPA; HPA007639; -.
DR MIM; 608760; gene.
DR neXtProt; NX_O95352; -.
DR PharmGKB; PA134983397; -.
DR eggNOG; COG0476; -.
DR HOGENOM; HOG000162379; -.
DR HOVERGEN; HBG080877; -.
DR InParanoid; O95352; -.
DR KO; K08337; -.
DR OMA; CTGCSET; -.
DR OrthoDB; EOG7X0VGG; -.
DR PhylomeDB; O95352; -.
DR Reactome; REACT_6900; Immune System.
DR GeneWiki; ATG7; -.
DR GenomeRNAi; 10533; -.
DR NextBio; 39961; -.
DR PRO; PR:O95352; -.
DR ArrayExpress; O95352; -.
DR Bgee; O95352; -.
DR CleanEx; HS_ATG7; -.
DR Genevestigator; O95352; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0000407; C:pre-autophagosomal structure; IEA:UniProtKB-SubCell.
DR GO; GO:0019778; F:APG12 activating enzyme activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004839; F:ubiquitin activating enzyme activity; TAS:ProtInc.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0055013; P:cardiac muscle cell development; IEA:Ensembl.
DR GO; GO:0006520; P:cellular amino acid metabolic process; IEA:Ensembl.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; IEA:Ensembl.
DR GO; GO:0021680; P:cerebellar Purkinje cell layer development; IEA:Ensembl.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEA:Ensembl.
DR GO; GO:0061025; P:membrane fusion; TAS:ProtInc.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0050877; P:neurological system process; IEA:Ensembl.
DR GO; GO:0006996; P:organelle organization; IEA:Ensembl.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:BHF-UCL.
DR GO; GO:0031401; P:positive regulation of protein modification process; IDA:MGI.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0006497; P:protein lipidation; IDA:MGI.
DR GO; GO:0032446; P:protein modification by small protein conjugation; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0021860; P:pyramidal neuron development; IEA:Ensembl.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0042594; P:response to starvation; IEA:Ensembl.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR006285; Atg7.
DR InterPro; IPR009036; Molybdenum_cofac_synth_MoeB.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR PANTHER; PTHR10953:SF3; PTHR10953:SF3; 1.
DR Pfam; PF00899; ThiF; 1.
DR SUPFAM; SSF69572; SSF69572; 2.
DR TIGRFAMs; TIGR01381; E1_like_apg7; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Autophagy; Complete proteome;
KW Cytoplasm; Polymorphism; Protein transport; Reference proteome;
KW Transport; Ubl conjugation pathway.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 703 Ubiquitin-like modifier-activating enzyme
FT ATG7.
FT /FTId=PRO_0000212806.
FT MOTIF 15 17 FAP motif.
FT ACT_SITE 572 572 Glycyl thioester intermediate (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 138 176 Missing (in isoform 3).
FT /FTId=VSP_045206.
FT VAR_SEQ 626 652 Missing (in isoform 2).
FT /FTId=VSP_013205.
FT VAR_SEQ 653 693 Missing (in isoform 3).
FT /FTId=VSP_045207.
FT VARIANT 471 471 V -> A (in dbSNP:rs36117895).
FT /FTId=VAR_053014.
FT MUTAGEN 15 15 F->D: Impairs conjugation activity; when
FT associated with D-16 and D-17.
FT MUTAGEN 16 16 A->D: Impairs conjugation activity; when
FT associated with D-15 and D-17.
FT MUTAGEN 17 17 P->D: Impairs conjugation activity; when
FT associated with D-15 and D-16.
FT CONFLICT 210 210 V -> A (in Ref. 2; BAG64682).
FT CONFLICT 346 346 P -> L (in Ref. 2; BAG64682).
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
//
MIM
608760
*RECORD*
*FIELD* NO
608760
*FIELD* TI
*608760 AUTOPHAGY 7, S. CEREVISIAE, HOMOLOG OF; ATG7
;;APG7, S. CEREVISIAE, HOMOLOG OF, APG7;;
read moreAPG7-LIKE; APG7L;;
GSA7
*FIELD* TX
DESCRIPTION
Autophagy is a process of bulk degradation of cytoplasmic components by
the lysosomal/vacuolar system. ATG7 is a ubiquitin-activating enzyme E1
(see 314370)-like protein essential for the Apg12 (ATG12; 609608)
conjugation system that mediates membrane fusion in autophagy (Tanida et
al., 2001).
CLONING
Yuan et al. (1999) identified several APG7L ESTs by searching a database
for sequences similar to P. pastoris Apg7, and they sequenced an APG7L
cDNA from an infant brain cDNA library. The deduced 703-amino acid
protein contains a central putative E1-like ATP-binding site (GxGxxG),
conserved charged amino acids flanking the GxGxxG motif, and a putative
E1 active site with a conserved catalytic cysteine. APG7L shares
similarity with the E1 enzymes UBA2 and UBA3 (UBE1C; 603172), and it
shares 38% identity with yeast Apg7. EST database analysis indicated
that APG7L is expressed by many diverse tissues.
Tanida et al. (2001) found that APG7L expressed by transfected human
embryonic kidney cells had an apparent molecular mass of about 80 kD.
MAPPING
Gross (2012) mapped the ATG7 gene to chromosome 3p25.3 based on an
alignment of the ATG7 sequence (GenBank GENBANK BC000091) with the
genomic sequence (GRCh37).
GENE FUNCTION
Using yeast 2-hybrid analysis, Tanida et al. (2001) found that APG7L
interacts with APG12L. Site-directed mutagenesis revealed that cys572 of
APG7L is an active site cysteine essential for formation of the
APG7L-APG12L intermediate. Overexpression of APG7L enhanced the
formation of the APG5L (ATG5; 604261)-APG12L conjugate, indicating that
APG7L is an E1-like enzyme essential for the APG12 conjugation system.
Cross-linking experiments and glycerol-gradient centrifugation analysis
showed that APG7L forms homodimers. Coimmunoprecipitation studies
indicated that 3 human Apg8 counterparts, GATE16 (GABARAPL2; 607452),
GABARAP (605125), and MAP1ALC3 (601242), also form conjugates with
APG7L. Like E1 enzymes, APG7L carrying a mutation of the active site
cysteine (cys572 to ser) formed a stable intermediate via an O-ester
bond instead of a thioester bond.
Tanida et al. (2002) found that ATG7 coimmunoprecipitated with ATG3
(609606), indicating that ATG3 forms an E1-E2 complex with ATG7, similar
to the yeast Apg3-Apg7 complex.
Yu et al. (2004) defined a novel molecular pathway in which activation
of the receptor-interacting protein (RIP; 603453), a serine-threonine
kinase, and Jun amino-terminal kinase (601158) induced cell death with
the morphology of autophagy. Autophagic death required the genes ATG7
(GSA7) and beclin-1 (604378) and was induced by caspase-8 (601763)
inhibition. Yu et al. (2004) cautioned that clinical therapies involving
caspase inhibitors may arrest apoptosis but also have the unanticipated
effect of promoting autophagic cell death.
Sanjuan et al. (2007) demonstrated that a particle that engages
Toll-like receptors on a murine macrophage while it is phagocytosed
triggers the autophagosome marker LC3 (601242) to be rapidly recruited
to the phagosome in a manner that depends on the autophagy pathway
proteins ATG5 and ATG7; this process is preceded by recruitment of
beclin-1 and phosphoinositide-3-OH kinase activity. Translocation of
beclin-1 and LC3 to the phagosome was not associated with observable
double-membrane structures characteristic of conventional
autophagosomes, but was associated with phagosome fusion with lysosomes,
leading to rapid acidification and enhanced killing of the ingested
organism.
Nishida et al. (2009) showed that mouse cells lacking Atg5 or Atg7 can
still form autophagosomes/autolysosomes and perform autophagy-mediated
protein degradation when subjected to certain stressors. Lipidation of
LC3 to form LC3-II, generally considered to be a good indicator of
macroautophagy, did not occur during the Atg5/Atg7-independent
alternative process of macroautophagy. Nishida et al. (2009) also found
that this alternative process of macroautophagy was regulated by several
autophagic proteins, including Unc51-like kinase-1 (ULK1; 603168) and
beclin-1. Unlike conventional macroautophagy, autophagosomes seemed to
be generated in a Rab9 (300284)-dependent manner by the fusion of
isolation membranes with vesicles derived from the trans-Golgi and late
endosomes. In vivo, Atg5-independent alternative macroautophagy was
detected in several embryonic tissues. It also had a function in
clearing mitochondria during erythroid maturation. Nishida et al. (2009)
concluded that their results indicate that mammalian macroautophagy can
occur through at least 2 different pathways: an Atg5/Atg7-dependent
conventional pathway and an Atg5/Atg7-independent alternative pathway.
Lee et al. (2012) found that starved mouse embryonic fibroblasts lacking
the essential autophagy gene product Atg7 failed to undergo cell cycle
arrest. Independent of its E1-like enzymatic activity, Atg7 could bind
to the tumor suppressor p53 (191170) to regulate the transcription of
the gene encoding the cell cycle inhibitor p21(CDKN1A) (116899). With
prolonged metabolic stress, the absence of Atg7 resulted in augmented
DNA damage with increased p53-dependent apoptosis. Inhibition of the DNA
damage response by deletion of the protein kinase Chk2 (604373)
partially rescued postnatal lethality in Atg7 -/- mice. Thus, Lee et al.
(2012) concluded that when nutrients are limited, Atg7 regulates
p53-dependent cell cycle and cell death pathways.
ANIMAL MODEL
Komatsu et al. (2006) reported that loss of ATG7, a gene essential for
autophagy, leads to neurodegeneration. They found that mice lacking Atg7
specifically in the central nervous system showed behavioral defects,
including abnormal limb clasping reflexes and a reduction in coordinated
movement, and died with 28 weeks of birth. Atg7 deficiency caused
massive neuronal loss in the cerebral and cerebellar cortices. Notably,
polyubiquitinated proteins accumulated in autophagy-deficient neurons as
inclusion bodies, which increased in size and number with aging. Komatsu
et al. (2006) commented that there was no obvious alteration in
proteasome function. The authors concluded that autophagy is essential
for the survival of neural cells, and that impairment of autophagy is
implicated in the pathogenesis of neurodegenerative disorders involving
ubiquitin-containing inclusion bodies.
Komatsu et al. (2007) found that conditional knockout mice with Purkinje
cell-specific deletion of Atg7 developed abnormal axonal swellings and
dystrophy of Purkinje cell axon terminals in the deep cerebellar nuclei.
The distal axons of Purkinje cells in the knockout mice accumulated
aberrant membranous structures that were different from double-membrane
vacuole-like structures found in the distal axons of Purkinje cells from
wildtype animals. The findings indicated impaired autophagic activity in
the axons of mutant cells, which resulted in cell-autonomous axonopathy
and Purkinje cell death. Dendritic spines were comparatively much less
affected. Mutant mice subsequently developed deficits in locomotion and
motor coordination. Komatsu et al. (2007) concluded that autophagy is
required for normal axon terminal membrane trafficking and turnover and
plays an essential role in the maintenance of axonal homeostasis and
prevention of axonal degeneration.
Cadwell et al. (2009) generated mice with a conditional deletion of Atg7
in the intestinal epithelium and observed that the ileal pathology was
indistinguishable from that of mice with disruption of Atg16l1 (610767)
or Atg5: the Paneth cells displayed a reduced number of granules,
dramatically increased cytoplasmic vesicles, abnormal mitochondria, and
lysozyme (153450) with striking defects in distribution including
diffuse cytoplasmic expression. Cadwell et al. (2009) concluded that a
defect in the autophagy pathway in the intestinal epithelium is
responsible for the observed Paneth cell pathology.
*FIELD* RF
1. Cadwell, K.; Patel, K. K.; Komatsu, M.; Virgin, H. W., IV; Stappenbeck,
T. S.: A common role for Atg16l1, Atg5 and Atg7 in small intestinal
Paneth cells and Crohn disease. Autophagy 5: 250-252, 2009.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 5/9/2012.
3. Komatsu, M.; Waguri, S.; Chiba, T.; Murata, S.; Iwata, J.; Tanida,
I.; Ueno, T.; Koike, M.; Uchiyama, Y.; Kominami, E.; Tanaka, K.:
Loss of autophagy in the central nervous system causes neurodegeneration
in mice. Nature 441: 880-884, 2006.
4. Komatsu, M.; Wang, Q. J.; Holstein, G. R.; Friedrich, V. L., Jr.;
Iwata, J.; Kominami, E.; Chait, B. T.; Tanaka, K.; Yue, Z: Essential
role for autophagy protein Atg7 in the maintenance of axonal homeostasis
and the prevention of axonal degeneration. Proc. Nat. Acad. Sci. 104:
14489-14494, 2007.
5. Lee, I. H.; Kawai, Y.; Fergusson, M. M.; Rovira, I. I.; Bishop,
A. J. R.; Motoyama, N.; Cao, L.; Finkel, T.: Atg7 modulates p53 activity
to regulate cell cycle and survival during metabolic stress. Science 336:
225-228, 2012. Note: Erratum: Science 337: 910 only, 2012. Note: Erratum:
Science 341: 457 only, 2013.
6. Nishida, Y.; Arakawa, S.; Fujitani, K.; Yamaguchi, H.; Mizuta,
T.; Kanaseki, T.; Komatsu, M.; Otsu, K.; Tsujimoto, Y.; Shimizu, S.
: Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 461:
654-658, 2009.
7. Sanjuan, M. A.; Dillon, C. P.; Tait, S. W. G.; Moshiach, S.; Dorsey,
F.; Connell, S.; Komatsu, M.; Tanaka, K.; Cleveland, J. L.; Withoff,
S.; Green, D. R.: Toll-like receptor signalling in macrophages links
the autophagy pathway to phagocytosis. Nature 450: 1253-1257, 2007.
8. 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.
9. Tanida, I.; Tanida-Miyake, T.; Ueno, T.; Kominami, E.: The human
homolog of Saccharomyces cerevisiae Apg7p is a protein-activating
enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP,
and MAP-LC3. J. Biol. Chem. 276: 1701-1706, 2001.
10. Yu, L.; Alva, A.; Su, H.; Dutt, P.; Freundt, E.; Welsh, S.; Baehrecke,
E. H.; Lenardo, M. J.: Regulation of an ATG7-beclin 1 program of
autophagic cell death by caspase-8. Science 304: 1500-1502, 2004.
11. Yuan, W.; Stromhaug, P. E.; Dunn, W. A., Jr.: Glucose-induced
autophagy of peroxisomes in Pichia pastoris requires a unique E1-like
protein. Molec. Biol. Cell 10: 1353-1366, 1999.
*FIELD* CN
Matthew B. Gross - updated: 5/9/2012
Ada Hamosh - updated: 5/8/2012
Ada Hamosh - updated: 11/16/2009
Marla J. F. O'Neill - updated: 5/29/2009
Cassandra L. Kniffin - updated: 2/11/2008
Ada Hamosh - updated: 1/24/2008
Ada Hamosh - updated: 7/21/2006
Patricia A. Hartz - updated: 9/26/2005
*FIELD* CD
Patricia A. Hartz: 6/22/2004
*FIELD* ED
mgross: 10/14/2013
tpirozzi: 10/1/2013
mgross: 5/9/2012
alopez: 5/8/2012
terry: 5/8/2012
alopez: 11/18/2009
terry: 11/16/2009
wwang: 6/8/2009
terry: 5/29/2009
wwang: 3/19/2008
ckniffin: 2/11/2008
alopez: 2/5/2008
terry: 1/24/2008
alopez: 7/26/2006
terry: 7/21/2006
mgross: 9/26/2005
alopez: 6/22/2004
mgross: 6/22/2004
*RECORD*
*FIELD* NO
608760
*FIELD* TI
*608760 AUTOPHAGY 7, S. CEREVISIAE, HOMOLOG OF; ATG7
;;APG7, S. CEREVISIAE, HOMOLOG OF, APG7;;
read moreAPG7-LIKE; APG7L;;
GSA7
*FIELD* TX
DESCRIPTION
Autophagy is a process of bulk degradation of cytoplasmic components by
the lysosomal/vacuolar system. ATG7 is a ubiquitin-activating enzyme E1
(see 314370)-like protein essential for the Apg12 (ATG12; 609608)
conjugation system that mediates membrane fusion in autophagy (Tanida et
al., 2001).
CLONING
Yuan et al. (1999) identified several APG7L ESTs by searching a database
for sequences similar to P. pastoris Apg7, and they sequenced an APG7L
cDNA from an infant brain cDNA library. The deduced 703-amino acid
protein contains a central putative E1-like ATP-binding site (GxGxxG),
conserved charged amino acids flanking the GxGxxG motif, and a putative
E1 active site with a conserved catalytic cysteine. APG7L shares
similarity with the E1 enzymes UBA2 and UBA3 (UBE1C; 603172), and it
shares 38% identity with yeast Apg7. EST database analysis indicated
that APG7L is expressed by many diverse tissues.
Tanida et al. (2001) found that APG7L expressed by transfected human
embryonic kidney cells had an apparent molecular mass of about 80 kD.
MAPPING
Gross (2012) mapped the ATG7 gene to chromosome 3p25.3 based on an
alignment of the ATG7 sequence (GenBank GENBANK BC000091) with the
genomic sequence (GRCh37).
GENE FUNCTION
Using yeast 2-hybrid analysis, Tanida et al. (2001) found that APG7L
interacts with APG12L. Site-directed mutagenesis revealed that cys572 of
APG7L is an active site cysteine essential for formation of the
APG7L-APG12L intermediate. Overexpression of APG7L enhanced the
formation of the APG5L (ATG5; 604261)-APG12L conjugate, indicating that
APG7L is an E1-like enzyme essential for the APG12 conjugation system.
Cross-linking experiments and glycerol-gradient centrifugation analysis
showed that APG7L forms homodimers. Coimmunoprecipitation studies
indicated that 3 human Apg8 counterparts, GATE16 (GABARAPL2; 607452),
GABARAP (605125), and MAP1ALC3 (601242), also form conjugates with
APG7L. Like E1 enzymes, APG7L carrying a mutation of the active site
cysteine (cys572 to ser) formed a stable intermediate via an O-ester
bond instead of a thioester bond.
Tanida et al. (2002) found that ATG7 coimmunoprecipitated with ATG3
(609606), indicating that ATG3 forms an E1-E2 complex with ATG7, similar
to the yeast Apg3-Apg7 complex.
Yu et al. (2004) defined a novel molecular pathway in which activation
of the receptor-interacting protein (RIP; 603453), a serine-threonine
kinase, and Jun amino-terminal kinase (601158) induced cell death with
the morphology of autophagy. Autophagic death required the genes ATG7
(GSA7) and beclin-1 (604378) and was induced by caspase-8 (601763)
inhibition. Yu et al. (2004) cautioned that clinical therapies involving
caspase inhibitors may arrest apoptosis but also have the unanticipated
effect of promoting autophagic cell death.
Sanjuan et al. (2007) demonstrated that a particle that engages
Toll-like receptors on a murine macrophage while it is phagocytosed
triggers the autophagosome marker LC3 (601242) to be rapidly recruited
to the phagosome in a manner that depends on the autophagy pathway
proteins ATG5 and ATG7; this process is preceded by recruitment of
beclin-1 and phosphoinositide-3-OH kinase activity. Translocation of
beclin-1 and LC3 to the phagosome was not associated with observable
double-membrane structures characteristic of conventional
autophagosomes, but was associated with phagosome fusion with lysosomes,
leading to rapid acidification and enhanced killing of the ingested
organism.
Nishida et al. (2009) showed that mouse cells lacking Atg5 or Atg7 can
still form autophagosomes/autolysosomes and perform autophagy-mediated
protein degradation when subjected to certain stressors. Lipidation of
LC3 to form LC3-II, generally considered to be a good indicator of
macroautophagy, did not occur during the Atg5/Atg7-independent
alternative process of macroautophagy. Nishida et al. (2009) also found
that this alternative process of macroautophagy was regulated by several
autophagic proteins, including Unc51-like kinase-1 (ULK1; 603168) and
beclin-1. Unlike conventional macroautophagy, autophagosomes seemed to
be generated in a Rab9 (300284)-dependent manner by the fusion of
isolation membranes with vesicles derived from the trans-Golgi and late
endosomes. In vivo, Atg5-independent alternative macroautophagy was
detected in several embryonic tissues. It also had a function in
clearing mitochondria during erythroid maturation. Nishida et al. (2009)
concluded that their results indicate that mammalian macroautophagy can
occur through at least 2 different pathways: an Atg5/Atg7-dependent
conventional pathway and an Atg5/Atg7-independent alternative pathway.
Lee et al. (2012) found that starved mouse embryonic fibroblasts lacking
the essential autophagy gene product Atg7 failed to undergo cell cycle
arrest. Independent of its E1-like enzymatic activity, Atg7 could bind
to the tumor suppressor p53 (191170) to regulate the transcription of
the gene encoding the cell cycle inhibitor p21(CDKN1A) (116899). With
prolonged metabolic stress, the absence of Atg7 resulted in augmented
DNA damage with increased p53-dependent apoptosis. Inhibition of the DNA
damage response by deletion of the protein kinase Chk2 (604373)
partially rescued postnatal lethality in Atg7 -/- mice. Thus, Lee et al.
(2012) concluded that when nutrients are limited, Atg7 regulates
p53-dependent cell cycle and cell death pathways.
ANIMAL MODEL
Komatsu et al. (2006) reported that loss of ATG7, a gene essential for
autophagy, leads to neurodegeneration. They found that mice lacking Atg7
specifically in the central nervous system showed behavioral defects,
including abnormal limb clasping reflexes and a reduction in coordinated
movement, and died with 28 weeks of birth. Atg7 deficiency caused
massive neuronal loss in the cerebral and cerebellar cortices. Notably,
polyubiquitinated proteins accumulated in autophagy-deficient neurons as
inclusion bodies, which increased in size and number with aging. Komatsu
et al. (2006) commented that there was no obvious alteration in
proteasome function. The authors concluded that autophagy is essential
for the survival of neural cells, and that impairment of autophagy is
implicated in the pathogenesis of neurodegenerative disorders involving
ubiquitin-containing inclusion bodies.
Komatsu et al. (2007) found that conditional knockout mice with Purkinje
cell-specific deletion of Atg7 developed abnormal axonal swellings and
dystrophy of Purkinje cell axon terminals in the deep cerebellar nuclei.
The distal axons of Purkinje cells in the knockout mice accumulated
aberrant membranous structures that were different from double-membrane
vacuole-like structures found in the distal axons of Purkinje cells from
wildtype animals. The findings indicated impaired autophagic activity in
the axons of mutant cells, which resulted in cell-autonomous axonopathy
and Purkinje cell death. Dendritic spines were comparatively much less
affected. Mutant mice subsequently developed deficits in locomotion and
motor coordination. Komatsu et al. (2007) concluded that autophagy is
required for normal axon terminal membrane trafficking and turnover and
plays an essential role in the maintenance of axonal homeostasis and
prevention of axonal degeneration.
Cadwell et al. (2009) generated mice with a conditional deletion of Atg7
in the intestinal epithelium and observed that the ileal pathology was
indistinguishable from that of mice with disruption of Atg16l1 (610767)
or Atg5: the Paneth cells displayed a reduced number of granules,
dramatically increased cytoplasmic vesicles, abnormal mitochondria, and
lysozyme (153450) with striking defects in distribution including
diffuse cytoplasmic expression. Cadwell et al. (2009) concluded that a
defect in the autophagy pathway in the intestinal epithelium is
responsible for the observed Paneth cell pathology.
*FIELD* RF
1. Cadwell, K.; Patel, K. K.; Komatsu, M.; Virgin, H. W., IV; Stappenbeck,
T. S.: A common role for Atg16l1, Atg5 and Atg7 in small intestinal
Paneth cells and Crohn disease. Autophagy 5: 250-252, 2009.
2. Gross, M. B.: Personal Communication. Baltimore, Md. 5/9/2012.
3. Komatsu, M.; Waguri, S.; Chiba, T.; Murata, S.; Iwata, J.; Tanida,
I.; Ueno, T.; Koike, M.; Uchiyama, Y.; Kominami, E.; Tanaka, K.:
Loss of autophagy in the central nervous system causes neurodegeneration
in mice. Nature 441: 880-884, 2006.
4. Komatsu, M.; Wang, Q. J.; Holstein, G. R.; Friedrich, V. L., Jr.;
Iwata, J.; Kominami, E.; Chait, B. T.; Tanaka, K.; Yue, Z: Essential
role for autophagy protein Atg7 in the maintenance of axonal homeostasis
and the prevention of axonal degeneration. Proc. Nat. Acad. Sci. 104:
14489-14494, 2007.
5. Lee, I. H.; Kawai, Y.; Fergusson, M. M.; Rovira, I. I.; Bishop,
A. J. R.; Motoyama, N.; Cao, L.; Finkel, T.: Atg7 modulates p53 activity
to regulate cell cycle and survival during metabolic stress. Science 336:
225-228, 2012. Note: Erratum: Science 337: 910 only, 2012. Note: Erratum:
Science 341: 457 only, 2013.
6. Nishida, Y.; Arakawa, S.; Fujitani, K.; Yamaguchi, H.; Mizuta,
T.; Kanaseki, T.; Komatsu, M.; Otsu, K.; Tsujimoto, Y.; Shimizu, S.
: Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 461:
654-658, 2009.
7. Sanjuan, M. A.; Dillon, C. P.; Tait, S. W. G.; Moshiach, S.; Dorsey,
F.; Connell, S.; Komatsu, M.; Tanaka, K.; Cleveland, J. L.; Withoff,
S.; Green, D. R.: Toll-like receptor signalling in macrophages links
the autophagy pathway to phagocytosis. Nature 450: 1253-1257, 2007.
8. 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.
9. Tanida, I.; Tanida-Miyake, T.; Ueno, T.; Kominami, E.: The human
homolog of Saccharomyces cerevisiae Apg7p is a protein-activating
enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP,
and MAP-LC3. J. Biol. Chem. 276: 1701-1706, 2001.
10. Yu, L.; Alva, A.; Su, H.; Dutt, P.; Freundt, E.; Welsh, S.; Baehrecke,
E. H.; Lenardo, M. J.: Regulation of an ATG7-beclin 1 program of
autophagic cell death by caspase-8. Science 304: 1500-1502, 2004.
11. Yuan, W.; Stromhaug, P. E.; Dunn, W. A., Jr.: Glucose-induced
autophagy of peroxisomes in Pichia pastoris requires a unique E1-like
protein. Molec. Biol. Cell 10: 1353-1366, 1999.
*FIELD* CN
Matthew B. Gross - updated: 5/9/2012
Ada Hamosh - updated: 5/8/2012
Ada Hamosh - updated: 11/16/2009
Marla J. F. O'Neill - updated: 5/29/2009
Cassandra L. Kniffin - updated: 2/11/2008
Ada Hamosh - updated: 1/24/2008
Ada Hamosh - updated: 7/21/2006
Patricia A. Hartz - updated: 9/26/2005
*FIELD* CD
Patricia A. Hartz: 6/22/2004
*FIELD* ED
mgross: 10/14/2013
tpirozzi: 10/1/2013
mgross: 5/9/2012
alopez: 5/8/2012
terry: 5/8/2012
alopez: 11/18/2009
terry: 11/16/2009
wwang: 6/8/2009
terry: 5/29/2009
wwang: 3/19/2008
ckniffin: 2/11/2008
alopez: 2/5/2008
terry: 1/24/2008
alopez: 7/26/2006
terry: 7/21/2006
mgross: 9/26/2005
alopez: 6/22/2004
mgross: 6/22/2004