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Protein

Ubiquitin-like modifier-activating enzyme ATG7

Gene

Atg7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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. Plays also 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.13 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei567Glycyl thioester intermediateCurated1

GO - Molecular functioni

  • Atg12 activating enzyme activity Source: UniProtKB
  • Atg8 activating enzyme activity Source: MGI
  • protein homodimerization activity Source: MGI
  • transcription factor binding Source: MGI

GO - Biological processi

  • adult walking behavior Source: MGI
  • autophagosome assembly Source: ParkinsonsUK-UCL
  • autophagy Source: ParkinsonsUK-UCL
  • cardiac muscle cell development Source: MGI
  • cellular amino acid metabolic process Source: MGI
  • cellular homeostasis Source: MGI
  • cellular response to hyperoxia Source: UniProtKB
  • cellular response to nitrogen starvation Source: GO_Central
  • cellular response to reactive oxygen species Source: MGI
  • cellular response to starvation Source: UniProtKB
  • cellular sphingolipid homeostasis Source: MGI
  • central nervous system neuron axonogenesis Source: MGI
  • cerebellar Purkinje cell layer development Source: MGI
  • cerebral cortex development Source: MGI
  • C-terminal protein lipidation Source: GO_Central
  • defense response to virus Source: MGI
  • late nucleophagy Source: GO_Central
  • liver development Source: MGI
  • macroautophagy Source: MGI
  • membrane organization Source: MGI
  • mitochondrion organization Source: MGI
  • mitophagy Source: ParkinsonsUK-UCL
  • negative regulation of apoptotic process Source: ParkinsonsUK-UCL
  • negative regulation of cell death Source: ParkinsonsUK-UCL
  • negative regulation of histone H4-K16 acetylation Source: MGI
  • negative regulation of phagocytosis Source: MGI
  • negative regulation of sphingolipid biosynthesis involved in cellular sphingolipid homeostasis Source: MGI
  • negative stranded viral RNA replication Source: MGI
  • neurological system process Source: MGI
  • neuron projection development Source: MGI
  • organelle organization Source: MGI
  • piecemeal microautophagy of nucleus Source: GO_Central
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: MGI
  • positive regulation of macroautophagy Source: MGI
  • positive regulation of mucus secretion Source: MGI
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • positive regulation of protein catabolic process Source: UniProtKB
  • positive regulation of protein modification process Source: MGI
  • post-embryonic development Source: MGI
  • protein catabolic process Source: MGI
  • protein lipidation Source: MGI
  • protein modification by small protein conjugation Source: MGI
  • protein transport Source: UniProtKB-KW
  • pyramidal neuron development Source: MGI
  • regulation of cell development Source: ParkinsonsUK-UCL
  • regulation of hemopoiesis Source: ParkinsonsUK-UCL
  • regulation of mitophagy Source: MGI
  • regulation of protein ubiquitination Source: MGI
  • response to starvation Source: MGI
  • suppression by virus of host autophagy Source: MGI
Complete GO annotation...

Keywords - Biological processi

Autophagy, Protein transport, Transport, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-1632852. Macroautophagy.
R-MMU-6798695. Neutrophil degranulation.
R-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-like modifier-activating enzyme ATG7
Alternative name(s):
ATG12-activating enzyme E1 ATG7
Autophagy-related protein 7
Short name:
APG7-like
Short name:
mAGP7
Ubiquitin-activating enzyme E1-like protein
Gene namesi
Name:Atg7
Synonyms:Apg7l
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1921494. Atg7.

Subcellular locationi

GO - Cellular componenti

  • axoneme Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: GO_Central
  • pre-autophagosomal structure Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Leads to hepatomegaly in liver and accumulation of abnormal organelles in hepatic cells.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi567C → S: Instead of the formation of an intermediate complex with a thiol ester bond between ATG7 (E1-like enzyme) and GABARAPL1 (MAP1LC3, GABARAP or GABARAPL; substrates), a stable complex with an O-ester bond is formed. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002128071 – 698Ubiquitin-like modifier-activating enzyme ATG7Add BLAST698

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei693PhosphoserineBy similarity1

Post-translational modificationi

Acetylated by EP300.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9D906.
MaxQBiQ9D906.
PaxDbiQ9D906.
PRIDEiQ9D906.

PTM databases

iPTMnetiQ9D906.
PhosphoSitePlusiQ9D906.
SwissPalmiQ9D906.

Expressioni

Tissue specificityi

Widely expressed, especially in kidney, liver, lymph nodes and bone marrow.1 Publication

Gene expression databases

BgeeiENSMUSG00000030314.
CleanExiMM_ATG7.
ExpressionAtlasiQ9D906. baseline and differential.
GenevisibleiQ9D906. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with ATG3, FOXO1 and EP300 acetyltransferase. The complex, composed of ATG3 and ATG7, plays a role in the conjugation of ATG12 to ATG5. Interacts with FOXO1 (By similarity). Forms intermediate conjugates with ATG8 family proteins such as GABARAP, GABARAPL1, GABARAPL2, MAP1LC3A, or GABARAPL1. Interacts with ATG12.By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi216602. 6 interactors.
IntActiQ9D906. 2 interactors.
MINTiMINT-4615793.
STRINGi10090.ENSMUSP00000032457.

Structurei

3D structure databases

ProteinModelPortaliQ9D906.
SMRiQ9D906.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi11 – 13FAP motif3

Domaini

The C-terminal part of the protein is essential for the dimerization and interaction with ATG3 and ATG12.By similarity
The N-terminal FAP motif (residues 11 to 13) is essential for the formation of the ATG89-PE and ATG5-ATG12 conjugates.By similarity

Sequence similaritiesi

Belongs to the ATG7 family.Curated

Phylogenomic databases

eggNOGiKOG2337. Eukaryota.
COG0476. LUCA.
GeneTreeiENSGT00390000017509.
HOGENOMiHOG000162379.
HOVERGENiHBG080877.
InParanoidiQ9D906.
KOiK08337.
PhylomeDBiQ9D906.
TreeFamiTF105689.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR006285. Atg7.
IPR032197. Atg7_N.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
[Graphical view]
PANTHERiPTHR10953:SF3. PTHR10953:SF3. 2 hits.
PfamiPF16420. ATG7_N. 1 hit.
PF00899. ThiF. 1 hit.
[Graphical view]
SUPFAMiSSF69572. SSF69572. 2 hits.
TIGRFAMsiTIGR01381. E1_like_apg7. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9D906-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGDPGLAKLQ FAPFNSALDV GFWHELTQKK LNEYRLDEAP KDIKGYYYNG
60 70 80 90 100
DSAGLPTRLT LEFSAFDMSA STPAHCCPAM GTLHNTNTLE AFKTADKKLL
110 120 130 140 150
LEQSANEIWE AIKSGAALEN PMLLNKFLLL TFADLKKYHF YYWFCCPALC
160 170 180 190 200
LPESIPLIRG PVSLDQRLSP KQIQALEHAY DDLCRAEGVT ALPYFLFKYD
210 220 230 240 250
DDTVLVSLLK HYSDFFQGQR TKITVGVYDP CNLAQYPGWP LRNFLVLAAH
260 270 280 290 300
RWSGSFQSVE VLCFRDRTMQ GARDVTHSII FEVKLPEMAF SPDCPKAVGW
310 320 330 340 350
EKNQKGGMGP RMVNLSGCMD PKRLAESSVD LNLKLMCWRL VPTLDLDKVV
360 370 380 390 400
SVKCLLLGAG TLGCNVARTL MGWGVRHVTF VDNAKISYSN PVRQPLYEFE
410 420 430 440 450
DCLGGGKPKA LAAAERLQKI FPGVNARGFN MSIPMPGHPV NFSDVTMEQA
460 470 480 490 500
RRDVEQLEQL IDNHDVIFLL MDTRESRWLP TVIAASKRKL VINAALGFDT
510 520 530 540 550
FVVMRHGLKK PKQQGAGDLC PSHLVAPADL GSSLFANIPG YKLGCYFCND
560 570 580 590 600
VVAPGDSTRD RTLDQQCTVS RPGLAVIAGA LAVELMVSVL QHPEGGYAIA
610 620 630 640 650
SSSDDRMNEP PTSLGLVPHQ IRGFLSRFDN VLPVSLAFDK CTACSPKVLD
660 670 680 690
QYEREGFTFL AKVFNSSHSF LEDLTGLTLL HQETQAAEIW DMSDEETV
Length:698
Mass (Da):77,520
Last modified:June 1, 2001 - v1
Checksum:i79D94EA7464C6ADB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti22F → L in BAC10416 (PubMed:11890701).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079385 mRNA. Translation: BAC10416.1.
AK007484 mRNA. Translation: BAB25060.1.
AK035604 mRNA. Translation: BAC29122.1.
AK161133 mRNA. Translation: BAE36208.1.
AK170769 mRNA. Translation: BAE42018.1.
AK172272 mRNA. Translation: BAE42917.1.
BC058597 mRNA. Translation: AAH58597.1.
CCDSiCCDS39598.1.
RefSeqiNP_001240646.1. NM_001253717.1.
NP_001240647.1. NM_001253718.1.
NP_083111.1. NM_028835.4.
XP_006506772.1. XM_006506709.2.
XP_006506773.1. XM_006506710.3.
XP_011239796.1. XM_011241494.2.
XP_011239797.1. XM_011241495.2.
UniGeneiMm.275332.

Genome annotation databases

EnsembliENSMUST00000032457; ENSMUSP00000032457; ENSMUSG00000030314.
ENSMUST00000182793; ENSMUSP00000138137; ENSMUSG00000030314.
ENSMUST00000182902; ENSMUSP00000138651; ENSMUSG00000030314.
GeneIDi74244.
KEGGimmu:74244.
UCSCiuc009dhz.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079385 mRNA. Translation: BAC10416.1.
AK007484 mRNA. Translation: BAB25060.1.
AK035604 mRNA. Translation: BAC29122.1.
AK161133 mRNA. Translation: BAE36208.1.
AK170769 mRNA. Translation: BAE42018.1.
AK172272 mRNA. Translation: BAE42917.1.
BC058597 mRNA. Translation: AAH58597.1.
CCDSiCCDS39598.1.
RefSeqiNP_001240646.1. NM_001253717.1.
NP_001240647.1. NM_001253718.1.
NP_083111.1. NM_028835.4.
XP_006506772.1. XM_006506709.2.
XP_006506773.1. XM_006506710.3.
XP_011239796.1. XM_011241494.2.
XP_011239797.1. XM_011241495.2.
UniGeneiMm.275332.

3D structure databases

ProteinModelPortaliQ9D906.
SMRiQ9D906.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi216602. 6 interactors.
IntActiQ9D906. 2 interactors.
MINTiMINT-4615793.
STRINGi10090.ENSMUSP00000032457.

PTM databases

iPTMnetiQ9D906.
PhosphoSitePlusiQ9D906.
SwissPalmiQ9D906.

Proteomic databases

EPDiQ9D906.
MaxQBiQ9D906.
PaxDbiQ9D906.
PRIDEiQ9D906.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032457; ENSMUSP00000032457; ENSMUSG00000030314.
ENSMUST00000182793; ENSMUSP00000138137; ENSMUSG00000030314.
ENSMUST00000182902; ENSMUSP00000138651; ENSMUSG00000030314.
GeneIDi74244.
KEGGimmu:74244.
UCSCiuc009dhz.2. mouse.

Organism-specific databases

CTDi10533.
MGIiMGI:1921494. Atg7.

Phylogenomic databases

eggNOGiKOG2337. Eukaryota.
COG0476. LUCA.
GeneTreeiENSGT00390000017509.
HOGENOMiHOG000162379.
HOVERGENiHBG080877.
InParanoidiQ9D906.
KOiK08337.
PhylomeDBiQ9D906.
TreeFamiTF105689.

Enzyme and pathway databases

ReactomeiR-MMU-1632852. Macroautophagy.
R-MMU-6798695. Neutrophil degranulation.
R-MMU-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiAtg7. mouse.
PROiQ9D906.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030314.
CleanExiMM_ATG7.
ExpressionAtlasiQ9D906. baseline and differential.
GenevisibleiQ9D906. MM.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR006285. Atg7.
IPR032197. Atg7_N.
IPR016040. NAD(P)-bd_dom.
IPR000594. ThiF_NAD_FAD-bd.
[Graphical view]
PANTHERiPTHR10953:SF3. PTHR10953:SF3. 2 hits.
PfamiPF16420. ATG7_N. 1 hit.
PF00899. ThiF. 1 hit.
[Graphical view]
SUPFAMiSSF69572. SSF69572. 2 hits.
TIGRFAMsiTIGR01381. E1_like_apg7. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiATG7_MOUSE
AccessioniPrimary (citable) accession number: Q9D906
Secondary accession number(s): Q3TCD9, Q8K4Q5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: June 1, 2001
Last modified: November 30, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.