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Protein

Ubiquitin-like modifier-activating enzyme ATG7

Gene

ATG7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei572Glycyl thioester intermediateBy similarity1

GO - Molecular functioni

  • Atg12 activating enzyme activity Source: UniProtKB
  • Atg8 activating enzyme activity Source: GO_Central
  • protein homodimerization activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB
  • ubiquitin activating enzyme activity Source: ProtInc

GO - Biological processi

Keywordsi

Biological processAutophagy, Protein transport, Transport, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-1632852 Macroautophagy
R-HSA-6798695 Neutrophil degranulation
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiO95352

Protein family/group databases

TCDBi9.A.15.2.1 the autophagy-related phagophore-formation transporter (apt) family

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:
hAGP7
Ubiquitin-activating enzyme E1-like protein
Gene namesi
Name:ATG7
Synonyms:APG7L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000197548.12
HGNCiHGNC:16935 ATG7
MIMi608760 gene
neXtProtiNX_O95352

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi15F → D: Impairs conjugation activity; when associated with D-16 and D-17. 1 Publication1
Mutagenesisi16A → D: Impairs conjugation activity; when associated with D-15 and D-17. 1 Publication1
Mutagenesisi17P → D: Impairs conjugation activity; when associated with D-15 and D-16. 1 Publication1

Organism-specific databases

DisGeNETi10533
OpenTargetsiENSG00000197548
PharmGKBiPA134983397

Chemistry databases

ChEMBLiCHEMBL2321621

Polymorphism and mutation databases

BioMutaiATG7

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002128062 – 703Ubiquitin-like modifier-activating enzyme ATG7Add BLAST702

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei698PhosphoserineCombined sources1

Post-translational modificationi

Acetylated by EP300.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO95352
MaxQBiO95352
PaxDbiO95352
PeptideAtlasiO95352
PRIDEiO95352
ProteomicsDBi50814
50815 [O95352-2]

PTM databases

iPTMnetiO95352
PhosphoSitePlusiO95352
SwissPalmiO95352

Expressioni

Tissue specificityi

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

Inductioni

Expression is up-regulated by the transcription factor HSF1.1 Publication

Gene expression databases

BgeeiENSG00000197548 Expressed in 186 organ(s), highest expression level in corpus callosum
CleanExiHS_ATG7
ExpressionAtlasiO95352 baseline and differential
GenevisibleiO95352 HS

Organism-specific databases

HPAiCAB018771
HPA007639

Interactioni

Subunit structurei

Homodimer. Interacts with ATG3 and ATG12. The complex, composed of ATG3 and ATG7, plays a role in the conjugation of ATG12 to ATG5. Forms intermediate conjugates with ATG8-like proteins such as GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A. Interacts with EP300 acetyltransferase. Interacts with FOXO1.5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115787, 71 interactors
DIPiDIP-29759N
IntActiO95352, 16 interactors
STRINGi9606.ENSP00000346437

Chemistry databases

BindingDBiO95352

Structurei

3D structure databases

ProteinModelPortaliO95352
SMRiO95352
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi15 – 17FAP 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 15 to 17) is essential for the formation of the ATG89-PE and ATG5-ATG12 conjugates.1 Publication

Sequence similaritiesi

Belongs to the ATG7 family.Curated

Phylogenomic databases

eggNOGiKOG2337 Eukaryota
COG0476 LUCA
GeneTreeiENSGT00390000017509
HOGENOMiHOG000162379
HOVERGENiHBG080877
InParanoidiO95352
KOiK08337
OMAiSYYYWFA
OrthoDBiEOG091G0628
PhylomeDBiO95352
TreeFamiTF105689

Family and domain databases

InterProiView protein in InterPro
IPR006285 Atg7
IPR032197 Atg7_N
IPR000594 ThiF_NAD_FAD-bd
IPR035985 Ubiquitin-activating_enz
PANTHERiPTHR10953:SF3 PTHR10953:SF3, 1 hit
PfamiView protein in Pfam
PF16420 ATG7_N, 1 hit
PF00899 ThiF, 1 hit
SUPFAMiSSF69572 SSF69572, 1 hit
TIGRFAMsiTIGR01381 E1_like_apg7, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O95352-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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

ETI
Length:703
Mass (Da):77,960
Last modified:May 1, 1999 - v1
Checksum:iABBD1A29A6C58356
GO
Isoform 2 (identifier: O95352-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     626-652: Missing.

Show »
Length:676
Mass (Da):75,002
Checksum:i184E1A7A3B989524
GO
Isoform 3 (identifier: O95352-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     138-176: Missing.
     653-693: Missing.

Show »
Length:623
Mass (Da):68,618
Checksum:i2186C29D24B11D6E
GO

Computationally mapped potential isoform sequencesi

There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8WDY9F8WDY9_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
76Annotation score:
C9JFF4C9JFF4_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
176Annotation score:
C9JKA3C9JKA3_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
93Annotation score:
C9JE55C9JE55_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
126Annotation score:
C9JGL2C9JGL2_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
66Annotation score:
C9JNU2C9JNU2_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
89Annotation score:
C9J415C9J415_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
152Annotation score:
H7C2J8H7C2J8_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
139Annotation score:
H7BZ92H7BZ92_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
96Annotation score:
H7C2R3H7C2R3_HUMAN
Ubiquitin-like modifier-activating ...
ATG7
95Annotation score:
There are more potential isoformsShow all

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti210V → A in BAG64682 (PubMed:14702039).Curated1
Sequence conflicti346P → L in BAG64682 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053014471V → A. Corresponds to variant dbSNP:rs36117895Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045206138 – 176Missing in isoform 3. 1 PublicationAdd BLAST39
Alternative sequenceiVSP_013205626 – 652Missing in isoform 2. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_045207653 – 693Missing in isoform 3. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF094516 mRNA Translation: AAC69630.1
AK303694 mRNA Translation: BAG64682.1
AC020750 Genomic DNA No translation available.
AC022001 Genomic DNA No translation available.
AC026185 Genomic DNA No translation available.
AC083855 Genomic DNA No translation available.
BC000091 mRNA Translation: AAH00091.1
AL122075 mRNA Translation: CAB59250.1
CCDSiCCDS2605.1 [O95352-1]
CCDS46752.1 [O95352-2]
CCDS46753.1 [O95352-3]
PIRiT34556
RefSeqiNP_001129503.2, NM_001136031.2 [O95352-2]
NP_001138384.1, NM_001144912.1 [O95352-3]
NP_006386.1, NM_006395.2 [O95352-1]
XP_011531584.1, XM_011533282.2
XP_011531588.1, XM_011533286.2 [O95352-2]
XP_016861033.1, XM_017005544.1
XP_016861034.1, XM_017005545.1
XP_016861035.1, XM_017005546.1
UniGeneiHs.38032

Genome annotation databases

EnsembliENST00000354449; ENSP00000346437; ENSG00000197548 [O95352-1]
ENST00000354956; ENSP00000347042; ENSG00000197548 [O95352-2]
ENST00000446450; ENSP00000412580; ENSG00000197548 [O95352-3]
GeneIDi10533
KEGGihsa:10533
UCSCiuc003bwc.4 human [O95352-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF094516 mRNA Translation: AAC69630.1
AK303694 mRNA Translation: BAG64682.1
AC020750 Genomic DNA No translation available.
AC022001 Genomic DNA No translation available.
AC026185 Genomic DNA No translation available.
AC083855 Genomic DNA No translation available.
BC000091 mRNA Translation: AAH00091.1
AL122075 mRNA Translation: CAB59250.1
CCDSiCCDS2605.1 [O95352-1]
CCDS46752.1 [O95352-2]
CCDS46753.1 [O95352-3]
PIRiT34556
RefSeqiNP_001129503.2, NM_001136031.2 [O95352-2]
NP_001138384.1, NM_001144912.1 [O95352-3]
NP_006386.1, NM_006395.2 [O95352-1]
XP_011531584.1, XM_011533282.2
XP_011531588.1, XM_011533286.2 [O95352-2]
XP_016861033.1, XM_017005544.1
XP_016861034.1, XM_017005545.1
XP_016861035.1, XM_017005546.1
UniGeneiHs.38032

3D structure databases

ProteinModelPortaliO95352
SMRiO95352
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115787, 71 interactors
DIPiDIP-29759N
IntActiO95352, 16 interactors
STRINGi9606.ENSP00000346437

Chemistry databases

BindingDBiO95352
ChEMBLiCHEMBL2321621

Protein family/group databases

TCDBi9.A.15.2.1 the autophagy-related phagophore-formation transporter (apt) family

PTM databases

iPTMnetiO95352
PhosphoSitePlusiO95352
SwissPalmiO95352

Polymorphism and mutation databases

BioMutaiATG7

Proteomic databases

EPDiO95352
MaxQBiO95352
PaxDbiO95352
PeptideAtlasiO95352
PRIDEiO95352
ProteomicsDBi50814
50815 [O95352-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000354449; ENSP00000346437; ENSG00000197548 [O95352-1]
ENST00000354956; ENSP00000347042; ENSG00000197548 [O95352-2]
ENST00000446450; ENSP00000412580; ENSG00000197548 [O95352-3]
GeneIDi10533
KEGGihsa:10533
UCSCiuc003bwc.4 human [O95352-1]

Organism-specific databases

CTDi10533
DisGeNETi10533
EuPathDBiHostDB:ENSG00000197548.12
GeneCardsiATG7
HGNCiHGNC:16935 ATG7
HPAiCAB018771
HPA007639
MIMi608760 gene
neXtProtiNX_O95352
OpenTargetsiENSG00000197548
PharmGKBiPA134983397
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2337 Eukaryota
COG0476 LUCA
GeneTreeiENSGT00390000017509
HOGENOMiHOG000162379
HOVERGENiHBG080877
InParanoidiO95352
KOiK08337
OMAiSYYYWFA
OrthoDBiEOG091G0628
PhylomeDBiO95352
TreeFamiTF105689

Enzyme and pathway databases

ReactomeiR-HSA-1632852 Macroautophagy
R-HSA-6798695 Neutrophil degranulation
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SIGNORiO95352

Miscellaneous databases

ChiTaRSiATG7 human
GeneWikiiATG7
GenomeRNAii10533
PROiPR:O95352
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197548 Expressed in 186 organ(s), highest expression level in corpus callosum
CleanExiHS_ATG7
ExpressionAtlasiO95352 baseline and differential
GenevisibleiO95352 HS

Family and domain databases

InterProiView protein in InterPro
IPR006285 Atg7
IPR032197 Atg7_N
IPR000594 ThiF_NAD_FAD-bd
IPR035985 Ubiquitin-activating_enz
PANTHERiPTHR10953:SF3 PTHR10953:SF3, 1 hit
PfamiView protein in Pfam
PF16420 ATG7_N, 1 hit
PF00899 ThiF, 1 hit
SUPFAMiSSF69572 SSF69572, 1 hit
TIGRFAMsiTIGR01381 E1_like_apg7, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiATG7_HUMAN
AccessioniPrimary (citable) accession number: O95352
Secondary accession number(s): B4E170
, E9PB95, Q7L8L0, Q9BWP2, Q9UFH4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: May 1, 1999
Last modified: November 7, 2018
This is version 161 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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