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Protein

Autophagy protein 5

Gene

ATG5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. The ATG12-ATG5 conjugate also negatively regulates the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Also plays a role in translation or delivery of incoming viral RNA to the translation apparatus. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway.
May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD.

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Autophagy, Immunity, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000057663-MONOMER.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-5205685. Pink/Parkin Mediated Mitophagy.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
SIGNORiQ9H1Y0.

Names & Taxonomyi

Protein namesi
Recommended name:
Autophagy protein 5
Alternative name(s):
APG5-like
Apoptosis-specific protein
Gene namesi
Name:ATG5
Synonyms:APG5L, ASP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:589. ATG5.

Subcellular locationi

GO - Cellular componenti

  • Atg12-Atg5-Atg16 complex Source: GO_Central
  • autophagosome Source: MGI
  • axoneme Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • membrane Source: MGI
  • phagocytic vesicle membrane Source: Reactome
  • pre-autophagosomal structure membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi130K → R: Loss of conjugation. 1 Publication1

Organism-specific databases

DisGeNETi9474.
OpenTargetsiENSG00000057663.
ENSG00000283623.
PharmGKBiPA24880.

Polymorphism and mutation databases

DMDMi17366828.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002189941 – 275Autophagy protein 5Add BLAST275

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Cross-linki130Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12)Curated

Post-translational modificationi

Conjugated to ATG12; which is essential for autophagy, but is not required for association with isolation membrane.
Acetylated by EP300.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ9H1Y0.
MaxQBiQ9H1Y0.
PaxDbiQ9H1Y0.
PeptideAtlasiQ9H1Y0.
PRIDEiQ9H1Y0.

PTM databases

iPTMnetiQ9H1Y0.
PhosphoSitePlusiQ9H1Y0.

Expressioni

Tissue specificityi

Ubiquitous. The mRNA is present at similar levels in viable and apoptotic cells, whereas the protein is dramatically highly expressed in apoptotic cells.

Inductioni

By apoptotic stimuli.

Gene expression databases

BgeeiENSG00000057663.
CleanExiHS_ATG5.
ExpressionAtlasiQ9H1Y0. baseline and differential.
GenevisibleiQ9H1Y0. HS.

Organism-specific databases

HPAiCAB034432.
CAB037309.
HPA042973.

Interactioni

Subunit structurei

Forms a conjugate with ATG12. The ATG5-ATG12 conjugate forms a complex with several units of ATG16L. Interacts with TECPR1; the interaction is direct and does not take place when ATG16L is associated with the ATG5-ATG12 conjugate. ATG12-ATG5 interacts with MAVS, MGA and RARRES3. Interacts with ATG3, ATG7 and ATG10. Interacts with FADD. Interacts transiently interacts with hepatitis C virus (HCV) protein NS5B during HCV infection.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GABARAPO951662EBI-1047414,EBI-712001
MAP1LC3BQ9GZQ82EBI-1047414,EBI-373144
TECPR1Q7Z6L18EBI-1047414,EBI-2946676
WDFY3Q8IZQ17EBI-1047414,EBI-1569256

Protein-protein interaction databases

BioGridi114859. 30 interactors.
DIPiDIP-29758N.
IntActiQ9H1Y0. 42 interactors.
STRINGi9606.ENSP00000343313.

Structurei

Secondary structure

1275
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 12Combined sources9
Beta strandi15 – 22Combined sources8
Beta strandi28 – 30Combined sources3
Beta strandi35 – 40Combined sources6
Helixi45 – 48Combined sources4
Helixi50 – 57Combined sources8
Helixi62 – 64Combined sources3
Beta strandi69 – 72Combined sources4
Helixi83 – 91Combined sources9
Beta strandi92 – 94Combined sources3
Beta strandi96 – 103Combined sources8
Turni109 – 111Combined sources3
Helixi118 – 137Combined sources20
Helixi140 – 144Combined sources5
Helixi147 – 158Combined sources12
Helixi162 – 172Combined sources11
Helixi177 – 179Combined sources3
Beta strandi187 – 192Combined sources6
Beta strandi194 – 196Combined sources3
Beta strandi208 – 210Combined sources3
Helixi215 – 222Combined sources8
Helixi224 – 226Combined sources3
Turni229 – 231Combined sources3
Beta strandi232 – 240Combined sources9
Helixi251 – 257Combined sources7
Beta strandi265 – 270Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4GDKX-ray2.70B/E1-275[»]
4GDLX-ray2.88B1-275[»]
4NAWX-ray2.20B/F/J/N1-275[»]
4TQ0X-ray2.70A/C/E1-275[»]
4TQ1X-ray1.80A1-275[»]
5D7GX-ray3.00A/C/E/G1-275[»]
ProteinModelPortaliQ9H1Y0.
SMRiQ9H1Y0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ATG5 family.Curated

Phylogenomic databases

eggNOGiKOG2976. Eukaryota.
ENOG410XQ71. LUCA.
GeneTreeiENSGT00390000004766.
HOGENOMiHOG000007893.
HOVERGENiHBG018731.
InParanoidiQ9H1Y0.
KOiK08339.
OMAiETPIQWL.
OrthoDBiEOG091G0JU7.
PhylomeDBiQ9H1Y0.
TreeFamiTF314415.

Family and domain databases

InterProiIPR007239. Atg5.
[Graphical view]
PANTHERiPTHR13040. PTHR13040. 1 hit.
PfamiPF04106. APG5. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: Q9H1Y0-1) [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
MTDDKDVLRD VWFGRIPTCF TLYQDEITER EAEPYYLLLP RVSYLTLVTD
60 70 80 90 100
KVKKHFQKVM RQEDISEIWF EYEGTPLKWH YPIGLLFDLL ASSSALPWNI
110 120 130 140 150
TVHFKSFPEK DLLHCPSKDA IEAHFMSCMK EADALKHKSQ VINEMQKKDH
160 170 180 190 200
KQLWMGLQND RFDQFWAINR KLMEYPAEEN GFRYIPFRIY QTTTERPFIQ
210 220 230 240 250
KLFRPVAADG QLHTLGDLLK EVCPSAIDPE DGEKKNQVMI HGIEPMLETP
260 270
LQWLSEHLSY PDNFLHISII PQPTD
Length:275
Mass (Da):32,447
Last modified:November 16, 2001 - v2
Checksum:iC33A1E0B3C1DBE5C
GO
Isoform Short (identifier: Q9H1Y0-2) [UniParc]FASTAAdd to basket
Also known as: APG5beta

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: MTDDKDVLRD...FEYEGTPLKW → M

Show »
Length:197
Mass (Da):22,931
Checksum:i05FC581F6EABB753
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti79W → M in CAC19459 (PubMed:14574404).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03624358K → M in a colorectal cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0037911 – 79MTDDK…TPLKW → M in isoform Short. 2 PublicationsAdd BLAST79

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11588 mRNA. Translation: CAA72327.1.
AF293841 mRNA. Translation: AAG44955.1.
CR749386 mRNA. Translation: CAH18236.1.
AL022067, AL133509, AL138917 Genomic DNA. Translation: CAI42297.1.
AL022067, AL133509, AL138917 Genomic DNA. Translation: CAI42298.1.
AL133509, AL022067, AL138917 Genomic DNA. Translation: CAC19459.2.
AL133509, AL022067, AL138917 Genomic DNA. Translation: CAI42831.1.
AL138917, AL133509, AL022067 Genomic DNA. Translation: CAI20313.1.
AL138917, AL022067, AL133509 Genomic DNA. Translation: CAI20314.1.
BC002699 mRNA. Translation: AAH02699.1.
BC093011 mRNA. Translation: AAH93011.1.
CCDSiCCDS5055.1. [Q9H1Y0-1]
CCDS69159.1. [Q9H1Y0-2]
RefSeqiNP_001273035.1. NM_001286106.1. [Q9H1Y0-1]
NP_001273036.1. NM_001286107.1. [Q9H1Y0-2]
NP_001273037.1. NM_001286108.1.
NP_001273040.1. NM_001286111.1.
NP_004840.1. NM_004849.3. [Q9H1Y0-1]
UniGeneiHs.486063.

Genome annotation databases

EnsembliENST00000343245; ENSP00000343313; ENSG00000057663. [Q9H1Y0-1]
ENST00000369076; ENSP00000358072; ENSG00000057663. [Q9H1Y0-1]
GeneIDi9474.
KEGGihsa:9474.
UCSCiuc003prf.4. human. [Q9H1Y0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11588 mRNA. Translation: CAA72327.1.
AF293841 mRNA. Translation: AAG44955.1.
CR749386 mRNA. Translation: CAH18236.1.
AL022067, AL133509, AL138917 Genomic DNA. Translation: CAI42297.1.
AL022067, AL133509, AL138917 Genomic DNA. Translation: CAI42298.1.
AL133509, AL022067, AL138917 Genomic DNA. Translation: CAC19459.2.
AL133509, AL022067, AL138917 Genomic DNA. Translation: CAI42831.1.
AL138917, AL133509, AL022067 Genomic DNA. Translation: CAI20313.1.
AL138917, AL022067, AL133509 Genomic DNA. Translation: CAI20314.1.
BC002699 mRNA. Translation: AAH02699.1.
BC093011 mRNA. Translation: AAH93011.1.
CCDSiCCDS5055.1. [Q9H1Y0-1]
CCDS69159.1. [Q9H1Y0-2]
RefSeqiNP_001273035.1. NM_001286106.1. [Q9H1Y0-1]
NP_001273036.1. NM_001286107.1. [Q9H1Y0-2]
NP_001273037.1. NM_001286108.1.
NP_001273040.1. NM_001286111.1.
NP_004840.1. NM_004849.3. [Q9H1Y0-1]
UniGeneiHs.486063.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4GDKX-ray2.70B/E1-275[»]
4GDLX-ray2.88B1-275[»]
4NAWX-ray2.20B/F/J/N1-275[»]
4TQ0X-ray2.70A/C/E1-275[»]
4TQ1X-ray1.80A1-275[»]
5D7GX-ray3.00A/C/E/G1-275[»]
ProteinModelPortaliQ9H1Y0.
SMRiQ9H1Y0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114859. 30 interactors.
DIPiDIP-29758N.
IntActiQ9H1Y0. 42 interactors.
STRINGi9606.ENSP00000343313.

PTM databases

iPTMnetiQ9H1Y0.
PhosphoSitePlusiQ9H1Y0.

Polymorphism and mutation databases

DMDMi17366828.

Proteomic databases

EPDiQ9H1Y0.
MaxQBiQ9H1Y0.
PaxDbiQ9H1Y0.
PeptideAtlasiQ9H1Y0.
PRIDEiQ9H1Y0.

Protocols and materials databases

DNASUi9474.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000343245; ENSP00000343313; ENSG00000057663. [Q9H1Y0-1]
ENST00000369076; ENSP00000358072; ENSG00000057663. [Q9H1Y0-1]
GeneIDi9474.
KEGGihsa:9474.
UCSCiuc003prf.4. human. [Q9H1Y0-1]

Organism-specific databases

CTDi9474.
DisGeNETi9474.
GeneCardsiATG5.
HGNCiHGNC:589. ATG5.
HPAiCAB034432.
CAB037309.
HPA042973.
MIMi604261. gene.
neXtProtiNX_Q9H1Y0.
OpenTargetsiENSG00000057663.
ENSG00000283623.
PharmGKBiPA24880.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2976. Eukaryota.
ENOG410XQ71. LUCA.
GeneTreeiENSGT00390000004766.
HOGENOMiHOG000007893.
HOVERGENiHBG018731.
InParanoidiQ9H1Y0.
KOiK08339.
OMAiETPIQWL.
OrthoDBiEOG091G0JU7.
PhylomeDBiQ9H1Y0.
TreeFamiTF314415.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000057663-MONOMER.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-5205685. Pink/Parkin Mediated Mitophagy.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
SIGNORiQ9H1Y0.

Miscellaneous databases

ChiTaRSiATG5. human.
GeneWikiiATG5.
GenomeRNAii9474.
PROiQ9H1Y0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000057663.
CleanExiHS_ATG5.
ExpressionAtlasiQ9H1Y0. baseline and differential.
GenevisibleiQ9H1Y0. HS.

Family and domain databases

InterProiIPR007239. Atg5.
[Graphical view]
PANTHERiPTHR13040. PTHR13040. 1 hit.
PfamiPF04106. APG5. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATG5_HUMAN
AccessioniPrimary (citable) accession number: Q9H1Y0
Secondary accession number(s): O60875
, Q5JVR2, Q68DI4, Q9H2B8, Q9HCZ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: November 16, 2001
Last modified: November 30, 2016
This is version 146 of the entry and version 2 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.