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Overview

Uniprot IDO95352
Protein NameUbiquitin-like modifier-activating enzyme ATG7
Gene NameATG7
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
309 VGWEKNQKGGMGPRM

Function

E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Facilitates LC3-I lipidation with phosphatidylethanolamine to form LC3-II which is found on autophagosomal membranes (PubMed:34161705). Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress. Also plays a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration, the maintenance of hematopoietic stem cells, the formation of Paneth cell granules, as well as in adipose differentiation. Plays a role in regulating the liver clock and glucose metabolism by mediating the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner (By similarity)

Protein Sequence

10 MAAATGDPGL 20 SKLQFAPFSS 30 ALDVGFWHEL 40 TQKKLNEYRL 50 DEAPKDIKGY 60 YYNGDSAGLP 70 ARLTLEFSAF 80 DMSAPTPARC 90 CPAIGTLYNT 100 NTLESFKTAD 110 KKLLLEQAAN 120 EIWESIKSGT 130 ALENPVLLNK 140 FLLLTFADLK 150 KYHFYYWFCY 160 PALCLPESLP 170 LIQGPVGLDQ 180 RFSLKQIEAL 190 ECAYDNLCQT 200 EGVTALPYFL 210 IKYDENMVLV 220 SLLKHYSDFF 230 QGQRTKITIG 240 VYDPCNLAQY 250 PGWPLRNFLV 260 LAAHRWSSSF 270 QSVEVVCFRD 280 RTMQGARDVA 290 HSIIFEVKLP 300 EMAFSPDCPK 310 AVGWEKNQKG 320 GMGPRMVNLS 330 ECMDPKRLAE 340 SSVDLNLKLM 350 CWRLVPTLDL 360 DKVVSVKCLL 370 LGAGTLGCNV 380 ARTLMGWGVR 390 HITFVDNAKI 400 SYSNPVRQPL 410 YEFEDCLGGG 420 KPKALAAADR 430 LQKIFPGVNA 440 RGFNMSIPMP 450 GHPVNFSSVT 460 LEQARRDVEQ 470 LEQLIESHDV 480 VFLLMDTRES 490 RWLPAVIAAS 500 KRKLVINAAL 510 GFDTFVVMRH 520 GLKKPKQQGA 530 GDLCPNHPVA 540 SADLLGSSLF 550 ANIPGYKLGC 560 YFCNDVVAPG 570 DSTRDRTLDQ 580 QCTVSRPGLA 590 VIAGALAVEL 600 MVSVLQHPEG 610 GYAIASSSDD 620 RMNEPPTSLG 630 LVPHQIRGFL 640 SRFDNVLPVS 650 LAFDKCTACS 660 SKVLDQYERE 670 GFNFLAKVFN 680 SSHSFLEDLT 690 GLTLLHQETQ 700 AAEIWDMSDD ETI

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005930 axoneme
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005576 extracellular region
Cellular Component GO:1904813 ficolin-1-rich granule lumen
Cellular Component GO:0000407 phagophore assembly site
Cellular Component GO:0034774 secretory granule lumen
Molecular Function GO:0019778 Atg12 activating enzyme activity
Molecular Function GO:0019779 Atg8 activating enzyme activity
Molecular Function GO:0042803 protein homodimerization activity
Biological Process GO:0000045 autophagosome assembly
Biological Process GO:0006914 autophagy
Biological Process GO:0071455 cellular response to hyperoxia
Biological Process GO:0006995 cellular response to nitrogen starvation
Biological Process GO:0009267 cellular response to starvation
Biological Process GO:0033554 cellular response to stress
Biological Process GO:0051607 defense response to virus
Biological Process GO:0016236 macroautophagy
Biological Process GO:0000423 mitophagy
Biological Process GO:0034727 piecemeal microautophagy of the nucleus
Biological Process GO:0043065 positive regulation of apoptotic process
Biological Process GO:0045732 positive regulation of protein catabolic process
Biological Process GO:0031401 positive regulation of protein modification process
Biological Process GO:0006497 protein lipidation
Biological Process GO:0061739 protein lipidation involved in autophagosome assembly
Biological Process GO:0032446 protein modification by small protein conjugation
Biological Process GO:0015031 protein transport
Biological Process GO:0042752 regulation of circadian rhythm
Biological Process GO:0048511 rhythmic process

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.