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Q9NT62 (ATG3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin-like-conjugating enzyme ATG3

EC=6.3.2.-
Alternative name(s):
Autophagy-related protein 3
Short name=APG3-like
Short name=hApg3
Protein PC3-96
Gene names
Name:ATG3
Synonyms:APG3, APG3L
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length314 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.6 Ref.7 Ref.10 Ref.13

Subunit structure

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. Ref.1 Ref.6 Ref.12 Ref.13 Ref.16

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

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

Post-translational modification

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.

Sequence similarities

Belongs to the ATG3 family.

Sequence caution

The sequence AAH02830.1 differs from that shown. Reason: Frameshift at position 290.

The sequence BAB15237.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Isoform 2: The sequence AAH02830.1 differs from that shown. Reason: Frameshift at position 311.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NT62-1)

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.
Isoform 2 (identifier: Q9NT62-2)

The sequence of this isoform differs from the canonical sequence as follows:
     290-314: LLIFLKFVQAVIPTIEYDYTRHFTM → PSLYVRLVAKWLLTIFFLRNLV
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 314314Ubiquitin-like-conjugating enzyme ATG3
PRO_0000213569

Regions

Motif166 – 1694Caspase cleavage motif LETD

Sites

Active site2641Glycyl thioester intermediate Probable
Site169 – 1702Cleavage; by CASP8

Amino acid modifications

Modified residue11N-acetylmethionine Ref.11 Ref.17
Cross-link243Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12) By similarity

Natural variations

Alternative sequence290 – 31425LLIFL…RHFTM → PSLYVRLVAKWLLTIFFLRN LV in isoform 2.
VSP_013037

Experimental info

Mutagenesis2641C → 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. Ref.1

Secondary structure

... 314
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 40EFE88DB5FE3EAB

FASTA31435,864
        10         20         30         40         50         60 
MQNVINTVKG KALEVAEYLT PVLKESKFKE TGVITPEEFV AAGDHLVHHC PTWQWATGEE 

        70         80         90        100        110        120 
LKVKAYLPTG KQFLVTKNVP CYKRCKQMEY SDELEAIIEE DDGDGGWVDT YHNTGITGIT 

       130        140        150        160        170        180 
EAVKEITLEN KDNIRLQDCS ALCEEEEDED EGEAADMEEY EESGLLETDE ATLDTRKIVE 

       190        200        210        220        230        240 
ACKAKTDAGG EDAILQTRTY DLYITYDKYY QTPRLWLFGY DEQRQPLTVE HMYEDISQDH 

       250        260        270        280        290        300 
VKKTVTIENH PHLPPPPMCS VHPCRHAEVM KKIIETVAEG GGELGVHMYL LIFLKFVQAV 

       310 
IPTIEYDYTR HFTM 

« Hide

Isoform 2 [UniParc].

Checksum: F15A9F8BCBD021A1
Show »

FASTA31135,467

References

« Hide 'large scale' references
[1]"Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5p."
Tanida I., Tanida-Miyake E., Komatsu M., Ueno T., Kominami E.
J. Biol. Chem. 277:13739-13744(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, MUTAGENESIS OF CYS-264, SUBCELLULAR LOCATION, FUNCTION, ACTIVE SITE, INTERACTION WITH ATG7 AND ATG12.
Tissue: Brain.
[2]"Cloning and characterization of human PC3-96 gene."
Wu B.X., Li Y., Laser M., Crosson C.E., Hazard E.S. III, Ma J.X.
Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Retina.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Lung and Lymph.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 118-314 (ISOFORM 2).
[6]"Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3 processing."
Tanida I., Nishitani T., Nemoto T., Ueno T., Kominami E.
Biochem. Biophys. Res. Commun. 296:1164-1170(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH THE ATG12-ATG5 CONJUGATE.
[7]"The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation, facilitates MAP-LC3 modification."
Nemoto T., Tanida I., Tanida-Miyake E., Minematsu-Ikeguchi N., Yokota M., Ohsumi M., Ueno T., Kominami E.
J. Biol. Chem. 278:39517-39526(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[9]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Atg8L/Apg8L is the fourth mammalian modifier of mammalian Atg8 conjugation mediated by human Atg4B, Atg7 and Atg3."
Tanida I., Sou Y.S., Minematsu-Ikeguchi N., Ueno T., Kominami E.
FEBS J. 273:2553-2562(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy."
Huett A., Ng A., Cao Z., Kuballa P., Komatsu M., Daly M.J., Podolsky D.K., Xavier R.J.
J. Immunol. 182:4917-4930(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FNBP1L.
[13]"ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death."
Radoshevich L., Murrow L., Chen N., Fernandez E., Roy S., Fung C., Debnath J.
Cell 142:590-600(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ATG12.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"Cleavage of Atg3 protein by caspase-8 regulates autophagy during receptor-activated cell death."
Oral O., Oz-Arslan D., Itah Z., Naghavi A., Deveci R., Karacali S., Gozuacik D.
Apoptosis 17:810-820(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, CLEAVAGE BY CASP8.
[16]"The FAP motif within human ATG7, an autophagy-related E1-like enzyme, is essential for the E2-substrate reaction of LC3 lipidation."
Tanida I., Yamasaki M., Komatsu M., Ueno T.
Autophagy 8:88-97(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATG3 AND ATG12.
[17]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRT46276.
RefSeqNP_001265641.1. NM_001278712.1.
NP_071933.2. NM_022488.4.
UniGeneHs.477126.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4NAWX-ray2.20D/H/L/P140-170[»]
ProteinModelPortalQ9NT62.
SMRQ9NT62. Positions 27-309.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122171. 29 interactions.
DIPDIP-35052N.
IntActQ9NT62. 20 interactions.
STRING9606.ENSP00000283290.

PTM databases

PhosphoSiteQ9NT62.

Polymorphism databases

DMDM61212142.

Proteomic databases

PaxDbQ9NT62.
PRIDEQ9NT62.

Protocols and materials databases

DNASU64422.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000283290; ENSP00000283290; ENSG00000144848. [Q9NT62-1]
ENST00000402314; ENSP00000385943; ENSG00000144848. [Q9NT62-2]
GeneID64422.
KEGGhsa:64422.
UCSCuc003dzc.3. human. [Q9NT62-2]
uc003dzd.3. human. [Q9NT62-1]

Organism-specific databases

CTD64422.
GeneCardsGC03M112251.
HGNCHGNC:20962. ATG3.
HPACAB037260.
MIM609606. gene.
neXtProtNX_Q9NT62.
PharmGKBPA134883444.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG237080.
HOGENOMHOG000234613.
HOVERGENHBG080876.
InParanoidQ9NT62.
KOK08343.
OMAADEWVET.
OrthoDBEOG7VMP5R.
PhylomeDBQ9NT62.
TreeFamTF105903.

Gene expression databases

ArrayExpressQ9NT62.
BgeeQ9NT62.
CleanExHS_ATG3.
GenevestigatorQ9NT62.

Family and domain databases

InterProIPR007135. Autophagy-rel_prot_3.
IPR019461. Autophagy-rel_prot_3_C.
IPR007134. Autophagy-rel_prot_3_N.
[Graphical view]
PfamPF03987. Autophagy_act_C. 1 hit.
PF10381. Autophagy_Cterm. 1 hit.
PF03986. Autophagy_N. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi64422.
NextBio66413.
PROQ9NT62.
SOURCESearch...

Entry information

Entry nameATG3_HUMAN
AccessionPrimary (citable) accession number: Q9NT62
Secondary accession number(s): Q6PKC5, Q9H6L9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM