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Protein

Ubiquitin-like-conjugating enzyme ATG3

Gene

ATG3

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

Functioni

E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). The ATG12-ATG5 conjugate plays a role of an E3 and promotes the transfer of ATG8-like proteins from ATG3 to phosphatidylethanolamine (PE). This step is required for the membrane association of ATG8-like proteins. The formation of the ATG8-phosphatidylethanolamine conjugates is essential for autophagy and for the cytoplasm to vacuole transport (Cvt). Preferred substrate is MAP1LC3A. Also acts as an autocatalytic E2-like enzyme, catalyzing the conjugation of ATG12 to itself, ATG12 conjugation to ATG3 playing a role in mitochondrial homeostasis but not in autophagy. ATG7 (E1-like enzyme) facilitates this reaction by forming an E1-E2 complex with ATG3. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei264Glycyl thioester intermediate1 Publication1

GO - Molecular functioni

  • Atg12 transferase activity Source: UniProtKB
  • Atg8 ligase activity Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • ubiquitin-like protein transferase activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processAutophagy, Protein transport, Transport, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-1632852 Macroautophagy
SIGNORiQ9NT62

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-conjugating enzyme ATG3 (EC:2.3.2.-)
Alternative name(s):
Autophagy-related protein 3
Short name:
APG3-like
Short name:
hApg3
Protein PC3-96
Gene namesi
Name:ATG3
Synonyms:APG3, APG3L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000144848.10
HGNCiHGNC:20962 ATG3
MIMi609606 gene
neXtProtiNX_Q9NT62

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
Mutagenesisi264C → S: Instead of the formation of an intermediate complex with a thiol ester bond between ATG3 (E2-like enzyme) and GABARAPL1/APG8L (substrate), a stable complex with an O-ester bond is formed. 1 Publication1

Organism-specific databases

DisGeNETi64422
OpenTargetsiENSG00000144848
PharmGKBiPA134883444

Polymorphism and mutation databases

BioMutaiATG3
DMDMi61212142

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002135691 – 314Ubiquitin-like-conjugating enzyme ATG3Add BLAST314

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Cross-linki243Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12)By similarity

Post-translational modificationi

Conjugated to ATG12 at Lys-243. ATG12-conjugation plays a role in regulation of mitochondrial homeostasis and cell death, while it is not involved in PE-conjugation to ATG8-like proteins and autophagy.
Cleaved by CASP8 upon death ligand binding such as tumor necrosis factor-alpha. CASP8 cleavage blocks survival-related autophagy and favors apoptosis.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei169 – 170Cleavage; by CASP82

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ9NT62
MaxQBiQ9NT62
PaxDbiQ9NT62
PeptideAtlasiQ9NT62
PRIDEiQ9NT62

PTM databases

iPTMnetiQ9NT62
PhosphoSitePlusiQ9NT62
SwissPalmiQ9NT62

Expressioni

Tissue specificityi

Widely expressed, with a highest expression in heart, skeletal muscle, kidney, liver and placenta.1 Publication

Gene expression databases

BgeeiENSG00000144848
CleanExiHS_ATG3
ExpressionAtlasiQ9NT62 baseline and differential
GenevisibleiQ9NT62 HS

Organism-specific databases

HPAiCAB037260
HPA040471

Interactioni

Subunit structurei

Interacts with ATG7 and ATG12. The complex, composed of ATG3 and ATG7, plays a role in the conjugation of ATG12 to ATG5. Interacts with FNBP1L.5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi122171, 47 interactors
DIPiDIP-35052N
IntActiQ9NT62, 25 interactors
STRINGi9606.ENSP00000283290

Structurei

Secondary structure

1314
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi157 – 163Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4NAWX-ray2.20D/H/L/P140-170[»]
ProteinModelPortaliQ9NT62
SMRiQ9NT62
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi166 – 169Caspase cleavage motif LETD4

Sequence similaritiesi

Belongs to the ATG3 family.Curated

Phylogenomic databases

eggNOGiKOG2981 Eukaryota
ENOG410Y3BC LUCA
GeneTreeiENSGT00390000010308
HOGENOMiHOG000234613
HOVERGENiHBG080876
InParanoidiQ9NT62
KOiK08343
OMAiYEDVSQD
OrthoDBiEOG091G0H8F
PhylomeDBiQ9NT62
TreeFamiTF105903

Family and domain databases

InterProiView protein in InterPro
IPR007135 Autophagy-rel_prot_3
IPR019461 Autophagy-rel_prot_3_C
IPR007134 Autophagy-rel_prot_3_N
PfamiView protein in Pfam
PF03987 Autophagy_act_C, 1 hit
PF10381 Autophagy_C, 1 hit
PF03986 Autophagy_N, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9NT62-1) [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
MQNVINTVKG KALEVAEYLT PVLKESKFKE TGVITPEEFV AAGDHLVHHC
60 70 80 90 100
PTWQWATGEE LKVKAYLPTG KQFLVTKNVP CYKRCKQMEY SDELEAIIEE
110 120 130 140 150
DDGDGGWVDT YHNTGITGIT EAVKEITLEN KDNIRLQDCS ALCEEEEDED
160 170 180 190 200
EGEAADMEEY EESGLLETDE ATLDTRKIVE ACKAKTDAGG EDAILQTRTY
210 220 230 240 250
DLYITYDKYY QTPRLWLFGY DEQRQPLTVE HMYEDISQDH VKKTVTIENH
260 270 280 290 300
PHLPPPPMCS VHPCRHAEVM KKIIETVAEG GGELGVHMYL LIFLKFVQAV
310
IPTIEYDYTR HFTM
Length:314
Mass (Da):35,864
Last modified:October 1, 2000 - v1
Checksum:i40EFE88DB5FE3EAB
GO
Isoform 2 (identifier: Q9NT62-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     290-314: LLIFLKFVQAVIPTIEYDYTRHFTM → PSLYVRLVAKWLLTIFFLRNLV

Note: No experimental confirmation available.Curated
Show »
Length:311
Mass (Da):35,467
Checksum:iF15A9F8BCBD021A1
GO

Sequence cautioni

The sequence AAH02830 differs from that shown. Reason: Frameshift at position 290.Curated
Isoform 2 : The sequence AAH02830 differs from that shown. Reason: Frameshift at position 311.Curated
The sequence BAB15237 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013037290 – 314LLIFL…RHFTM → PSLYVRLVAKWLLTIFFLRN LV in isoform 2. 2 PublicationsAdd BLAST25

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB079384 mRNA Translation: BAB90843.1
AF202092 mRNA Translation: AAG35611.1
AL137515 mRNA Translation: CAB70781.1
BC002830 mRNA Translation: AAH02830.1 Frameshift.
BC024221 mRNA Translation: AAH24221.1
AK025778 mRNA Translation: BAB15237.1 Different initiation.
CCDSiCCDS2966.1 [Q9NT62-1]
CCDS63721.1 [Q9NT62-2]
PIRiT46276
RefSeqiNP_001265641.1, NM_001278712.1 [Q9NT62-2]
NP_071933.2, NM_022488.4 [Q9NT62-1]
UniGeneiHs.477126

Genome annotation databases

EnsembliENST00000283290; ENSP00000283290; ENSG00000144848 [Q9NT62-1]
ENST00000402314; ENSP00000385943; ENSG00000144848 [Q9NT62-2]
GeneIDi64422
KEGGihsa:64422
UCSCiuc003dzc.5 human [Q9NT62-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiATG3_HUMAN
AccessioniPrimary (citable) accession number: Q9NT62
Secondary accession number(s): Q6PKC5, Q9H6L9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 1, 2000
Last modified: May 23, 2018
This is version 145 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

3D-structure, Complete proteome, Reference proteome

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