Q9NT62 (ATG3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	314 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E2-like enzyme involved in autophagy and mitochondrial homeostasis. Catalyzes the conjugation of ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A) to phosphatidylethanolamine (PE). PE-conjugation to ATG8-like proteins is essential for autophagy. 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. Ref.1
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.8
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 By similarity.
Sequence similarities	Belongs to the ATG3 family.
Sequence caution	The sequence BAB15237.1 differs from that shown. Reason: Erroneous initiation. Isoform 2: The sequence AAH02830.1 differs from that shown. Reason: Frameshift at position 311.

Ontologies

Keywords
Biological process	Autophagy Protein transport Transport Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Molecular function	Ligase
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	autophagic vacuole assembly Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial fragmentation involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB protein targeting to membrane Inferred from sequence or structural similarity. Source: UniProtKB protein ubiquitination Inferred from direct assay Ref.1. Source: UniProtKB
Cellular_component	cytoplasmic ubiquitin ligase complex Inferred from physical interaction Ref.1. Source: MGI cytosol Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	Atg12 ligase activity Inferred from sequence or structural similarity. Source: UniProtKB Atg8 ligase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GABARAP	O95166	5	EBI-988094,EBI-712001
GABARAPL1	Q9H0R8	3	EBI-988094,EBI-746969
GABARAPL2	P60520	5	EBI-988094,EBI-720116
MAP1LC3B	Q9GZQ8	7	EBI-988094,EBI-373144
TECPR1	Q7Z6L1	3	EBI-988094,EBI-2946676

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 314	314	Ubiquitin-like-conjugating enzyme ATG3		PRO_0000213569
Sites
	Active site	264	1	Glycyl thioester intermediate Probable
Amino acid modifications
	Cross-link	243		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12) By similarity
Natural variations
	Alternative sequence	290 – 314	25	LLIFL…RHFTM → PSLYVRLVAKWLLTIFFLRN LV in isoform 2.		VSP_013037
Experimental info
	Mutagenesis	264	1	C → 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

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 40EFE88DB5FE3EAB	FASTA	314	35,864
	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
	Isoform 2 [UniParc]. Checksum: F15A9F8BCBD021A1	FASTA	311	35,467
	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 GGELGVHMYP SLYVRLVAKW 310 LLTIFFLRNL V

References

	« Hide 'large scale' referencesShow '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, 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. , 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]	"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.
[7]	"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].
[8]	"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.
[9]	"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].

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.
IPI	IPI00022254. IPI00449201.
PIR	T46276.
RefSeq	NP_071933.2. NM_022488.3.
UniGene	Hs.477126.
3D structure databases
ProteinModelPortal	Q9NT62.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NT62. 20 interactions.
STRING	9606.ENSP00000283290.
PTM databases
PhosphoSite	Q9NT62.
Polymorphism databases
DMDM	61212142.
Proteomic databases
PaxDb	Q9NT62.
PRIDE	Q9NT62.
Protocols and materials databases
DNASU	64422.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000283290; ENSP00000283290; ENSG00000144848. ENST00000402314; ENSP00000385943; ENSG00000144848.
GeneID	64422.
KEGG	hsa:64422.
UCSC	uc003dzc.3. human. uc003dzd.3. human.
Organism-specific databases
CTD	64422.
GeneCards	GC03M112251.
HGNC	HGNC:20962. ATG3.
HPA	CAB037260.
MIM	609606. gene.
neXtProt	NX_Q9NT62.
PharmGKB	PA134883444.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG237080.
HOGENOM	HOG000234613.
HOVERGEN	HBG080876.
InParanoid	Q9NT62.
KO	K08343.
OMA	CSALCDE.
OrthoDB	EOG4M398Z.
PhylomeDB	Q9NT62.
Gene expression databases
ArrayExpress	Q9NT62.
Bgee	Q9NT62.
CleanEx	HS_ATG3.
Genevestigator	Q9NT62.
GermOnline	ENSG00000144848. Homo sapiens.
Family and domain databases
InterPro	IPR007135. Autophagy-rel_prot_3. IPR019461. Autophagy-rel_prot_3_C. IPR007134. Autophagy-rel_prot_3_N. [Graphical view]
Pfam	PF03987. Autophagy_act_C. 1 hit. PF10381. Autophagy_Cterm. 1 hit. PF03986. Autophagy_N. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	64422.
NextBio	66413.
SOURCE	Search...

Entry information

Entry name

ATG3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.