O95352 (ATG7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	ATG7
Synonyms:	APG7L

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	703 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as an E1 enzyme essential for multisubstrates such as ATG8-like proteins and ATG12. Forms intermediate conjugates with ATG8-like proteins (GABARAP, GABARAPL1, GABARAPL2 or MAP1LC3A). PE-conjugation to ATG8-like proteins is essential for autophagy. Also acts as an E1 enzyme for ATG12 conjugation to ATG5 and ATG3 By similarity.
Subunit structure	Homodimer By similarity. Interacts with ATG3 and ATG12. The complex, composed of ATG3 and ATG7, plays a role in the conjugation of ATG12 to ATG5. Ref.5
Subcellular location	Cytoplasm Probable.
Tissue specificity	Widely expressed, especially in kidney, liver, lymph nodes and bone marrow. Ref.4
Domain	The C-terminal part of the protein is essential for the dimerization and interaction with ATG3 and ATG12 By similarity.
Sequence similarities	Belongs to the ATG7 family.

Ontologies

Keywords
Biological process	Autophagy Protein transport Transport Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	autophagy Inferred from electronic annotation. Source: UniProtKB-KW cellular membrane fusion Traceable author statement. Source: ProtInc positive regulation of protein modification process Inferred from direct assay. Source: MGI protein lipidation Inferred from direct assay. Source: MGI protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: HPA
Molecular function	APG12 activating enzyme activity Inferred from sequence or structural similarity. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro protein homodimerization activity Inferred from direct assay. Source: UniProtKB ubiquitin activating enzyme activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EEF1D	P29692	2	EBI-987834,EBI-358607
GABARAP	O95166	8	EBI-987834,EBI-712001
GABARAPL1	Q9H0R8	6	EBI-987834,EBI-746969
GABARAPL2	P60520	4	EBI-987834,EBI-720116
MAP1LC3B	Q9GZQ8	7	EBI-987834,EBI-373144

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95352-1)

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: O95352-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed
	Chain	2 – 703	702	Ubiquitin-like modifier-activating enzyme ATG7		PRO_0000212806
Sites
	Active site	572	1	Glycyl thioester intermediate By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.6
	Modified residue	306	1	N6-acetyllysine Ref.7
Natural variations
	Alternative sequence	626 – 652	27	Missing in isoform 2.		VSP_013205
	Natural variant	471	1	V → A. Corresponds to variant rs36117895 [ dbSNP | Ensembl ].		VAR_053014

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: ABBD1A29A6C58356	FASTA	703	77,960
	10 20 30 40 50 60 MAAATGDPGL SKLQFAPFSS ALDVGFWHEL TQKKLNEYRL DEAPKDIKGY YYNGDSAGLP 70 80 90 100 110 120 ARLTLEFSAF DMSAPTPARC CPAIGTLYNT NTLESFKTAD KKLLLEQAAN EIWESIKSGT 130 140 150 160 170 180 ALENPVLLNK FLLLTFADLK KYHFYYWFCY PALCLPESLP LIQGPVGLDQ RFSLKQIEAL 190 200 210 220 230 240 ECAYDNLCQT EGVTALPYFL IKYDENMVLV SLLKHYSDFF QGQRTKITIG VYDPCNLAQY 250 260 270 280 290 300 PGWPLRNFLV LAAHRWSSSF QSVEVVCFRD RTMQGARDVA HSIIFEVKLP EMAFSPDCPK 310 320 330 340 350 360 AVGWEKNQKG GMGPRMVNLS ECMDPKRLAE SSVDLNLKLM CWRLVPTLDL DKVVSVKCLL 370 380 390 400 410 420 LGAGTLGCNV ARTLMGWGVR HITFVDNAKI SYSNPVRQPL YEFEDCLGGG KPKALAAADR 430 440 450 460 470 480 LQKIFPGVNA RGFNMSIPMP GHPVNFSSVT LEQARRDVEQ LEQLIESHDV VFLLMDTRES 490 500 510 520 530 540 RWLPAVIAAS KRKLVINAAL GFDTFVVMRH GLKKPKQQGA GDLCPNHPVA SADLLGSSLF 550 560 570 580 590 600 ANIPGYKLGC YFCNDVVAPG DSTRDRTLDQ QCTVSRPGLA VIAGALAVEL MVSVLQHPEG 610 620 630 640 650 660 GYAIASSSDD RMNEPPTSLG LVPHQIRGFL SRFDNVLPVS LAFDKCTACS SKVLDQYERE 670 680 690 700 GFNFLAKVFN SSHSFLEDLT GLTLLHQETQ AAEIWDMSDD ETI
	Isoform 2 [UniParc]. Checksum: 184E1A7A3B989524	FASTA	676	75,002
	10 20 30 40 50 60 MAAATGDPGL SKLQFAPFSS ALDVGFWHEL TQKKLNEYRL DEAPKDIKGY YYNGDSAGLP 70 80 90 100 110 120 ARLTLEFSAF DMSAPTPARC CPAIGTLYNT NTLESFKTAD KKLLLEQAAN EIWESIKSGT 130 140 150 160 170 180 ALENPVLLNK FLLLTFADLK KYHFYYWFCY PALCLPESLP LIQGPVGLDQ RFSLKQIEAL 190 200 210 220 230 240 ECAYDNLCQT EGVTALPYFL IKYDENMVLV SLLKHYSDFF QGQRTKITIG VYDPCNLAQY 250 260 270 280 290 300 PGWPLRNFLV LAAHRWSSSF QSVEVVCFRD RTMQGARDVA HSIIFEVKLP EMAFSPDCPK 310 320 330 340 350 360 AVGWEKNQKG GMGPRMVNLS ECMDPKRLAE SSVDLNLKLM CWRLVPTLDL DKVVSVKCLL 370 380 390 400 410 420 LGAGTLGCNV ARTLMGWGVR HITFVDNAKI SYSNPVRQPL YEFEDCLGGG KPKALAAADR 430 440 450 460 470 480 LQKIFPGVNA RGFNMSIPMP GHPVNFSSVT LEQARRDVEQ LEQLIESHDV VFLLMDTRES 490 500 510 520 530 540 RWLPAVIAAS KRKLVINAAL GFDTFVVMRH GLKKPKQQGA GDLCPNHPVA SADLLGSSLF 550 560 570 580 590 600 ANIPGYKLGC YFCNDVVAPG DSTRDRTLDQ QCTVSRPGLA VIAGALAVEL MVSVLQHPEG 610 620 630 640 650 660 GYAIASSSDD RMNEPPTSLG LVPHQVLDQY EREGFNFLAK VFNSSHSFLE DLTGLTLLHQ 670 ETQAAEIWDM SDDETI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Glucose-induced autophagy of peroxisomes in Pichia pastoris requires a unique E1-like protein." Yuan W., Stromhaug P.E., Dunn W.A. Jr. Mol. Biol. Cell 10:1353-1366(1999) [PubMed: 10233149] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta.
[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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 179-703 (ISOFORM 1). Tissue: Testis.
[4]	"Murine Apg12p has a substrate preference for murine Apg7p over three Apg8p homologs." Tanida I., Tanida-Miyake E., Nishitani T., Komatsu M., Yamazaki H., Ueno T., Kominami E. Biochem. Biophys. Res. Commun. 292:256-262(2002) [PubMed: 11890701] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"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: 11825910] [Abstract] Cited for: INTERACTION WITH ATG3 AND ATG12. Tissue: Brain.
[6]	"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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-306, MASS SPECTROMETRY.
[8]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF094516 mRNA. Translation: AAC69630.1. BC000091 mRNA. Translation: AAH00091.1. AL122075 mRNA. Translation: CAB59250.1.
IPI	IPI00007404. IPI00479911.
PIR	T34556.
RefSeq	NP_001129503.2. NM_001136031.2. NP_001138384.1. NM_001144912.1. NP_006386.1. NM_006395.2.
UniGene	Hs.38032.
3D structure databases
ProteinModelPortal	O95352.
SMR	O95352. Positions 11-683.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29759N.
IntAct	O95352. 16 interactions.
STRING	O95352.
PTM databases
PhosphoSite	O95352.
Proteomic databases
PRIDE	O95352.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000354449; ENSP00000346437; ENSG00000197548.
GeneID	10533.
KEGG	hsa:10533.
UCSC	uc003bwc.1. human. uc003bwd.1. human.
Organism-specific databases
CTD	10533.
GeneCards	GC03P011290.
H-InvDB	HIX0003055.
HGNC	HGNC:16935. ATG7.
HPA	CAB018771. HPA007639.
MIM	608760. gene.
neXtProt	NX_O95352.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15924.
GeneTree	ENSGT00390000017509.
HOGENOM	HBG619497.
HOVERGEN	HBG080877.
InParanoid	O95352.
OMA	ANEIWES.
OrthoDB	EOG43N7C8.
PhylomeDB	O95352.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	O95352.
Bgee	O95352.
CleanEx	HS_ATG7.
Genevestigator	O95352.
GermOnline	ENSG00000197548. Homo sapiens.
Family and domain databases
InterPro	IPR006285. E1-like_Apg7. IPR009036. Molybdenum_cofac_synth_MoeB. IPR016040. NAD(P)-bd_dom. IPR000594. ThiF_NAD_FAD-bd. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 2 hits.
KO	K08337.
Pfam	PF00899. ThiF. 1 hit. [Graphical view]
SUPFAM	SSF69572. MoeB. 1 hit.
TIGRFAMs	TIGR01381. E1_like_apg7. 1 hit.
ProtoNet	Search...
Other
NextBio	39961.
SOURCE	Search...

Entry information

Entry name

ATG7_HUMAN

Accession

Primary (citable) accession number: O95352
Secondary accession number(s): Q7L8L0, Q9BWP2, Q9UFH4

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2005
Last sequence update:	May 1, 1999
Last modified:	January 25, 2012
This is version 93 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.