Q9H1Y0 (ATG5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Autophagy protein 5

Alternative name(s):
APG5-like
Apoptosis-specific protein

Gene names

Name:	ATG5
Synonyms:	APG5L, ASP

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	275 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Required for autophagy. Conjugates to ATG12 and associates with isolation membrane to form cup-shaped isolation membrane and autophagosome. The conjugate detaches from the membrane immediately before or after autophagosome formation is completed By similarity. Ref.6 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. Ref.6
Subunit structure	The ATG5-ATG12 conjugate forms a complex with several units of ATG16. Interacts with TECPR1; the interaction is direct and does not take place when ATG16 is associated with the ATG5-ATG12 conjugate. Ref.10 Ref.11
Subcellular location	Cytoplasm. Note: Colocalizes with nonmuscle actin. Ref.8
Tissue specificity	Ubiquitous. The mRNA is present at similar levels in viable and apoptotic cells, whereas the protein is dramatically highly expressed in apoptotic cells.
Induction	By apoptotic stimuli.
Post-translational modification	Conjugated to ATG12; which is essential for autophagy, but is not required for association with isolation membrane.
Sequence similarities	Belongs to the ATG5 family.

Ontologies

Keywords
Biological process	Apoptosis Autophagy
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Isopeptide bond Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW autophagic vacuole assembly Inferred from sequence or structural similarity. Source: UniProtKB blood vessel remodeling Inferred from electronic annotation. Source: Compara heart contraction Inferred from electronic annotation. Source: Compara innate immune response Traceable author statement. Source: Reactome negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of protein ubiquitination Inferred from electronic annotation. Source: Compara negative regulation of type I interferon production Traceable author statement. Source: Reactome otolith development Inferred from electronic annotation. Source: Compara post-translational protein modification Inferred from sequence or structural similarity. Source: UniProtKB response to drug Inferred from electronic annotation. Source: Compara vasodilation Inferred from electronic annotation. Source: Compara ventricular cardiac muscle cell development Inferred from electronic annotation. Source: Compara
Cellular_component	autophagic vacuole Inferred from direct assay PubMed 15292400. Source: MGI pre-autophagosomal structure membrane Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GABARAP	O95166	2	EBI-1047414,EBI-712001
MAP1LC3B	Q9GZQ8	2	EBI-1047414,EBI-373144
TECPR1	Q7Z6L1	6	EBI-1047414,EBI-2946676
WDFY3	Q8IZQ1	6	EBI-1047414,EBI-1569256

Alternative products

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

Isoform Long (identifier: Q9H1Y0-1)

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 Short (identifier: Q9H1Y0-2)

Also known as: APG5beta;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 275

275

Autophagy protein 5

PRO_0000218994

Amino acid modifications

Cross-link

130

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12) Probable

Natural variations

Alternative sequence

1 – 79

79

MTDDK…TPLKW → M in isoform Short.

VSP_003791

Natural variant

58

1

K → M in a colorectal cancer sample; somatic mutation. Ref.12

VAR_036243

Experimental info

Mutagenesis

130

1

K → R: Loss of conjugation. Ref.7

Sequence conflict

79

1

W → M in CAC19459. Ref.4

Secondary structure

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275

Helix Strand Turn

Details...

Helix

4 – 12

9

Beta strand

15 – 22

8

Beta strand

28 – 30

3

Beta strand

35 – 40

6

Helix

45 – 48

4

Helix

50 – 57

8

Helix

62 – 64

3

Beta strand

69 – 72

4

Helix

83 – 91

9

Beta strand

96 – 103

8

Turn

109 – 111

3

Helix

118 – 137

20

Turn

138 – 143

6

Helix

147 – 158

12

Helix

162 – 169

8

Helix

171 – 173

3

Beta strand

179 – 181

3

Beta strand

187 – 190

4

Beta strand

194 – 199

6

Beta strand

208 – 210

3

Helix

215 – 222

8

Helix

224 – 226

3

Beta strand

236 – 240

5

Helix

251 – 257

7

Beta strand

265 – 271

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified November 16, 2001. Version 2. Checksum: C33A1E0B3C1DBE5C	FASTA	275	32,447
	10 20 30 40 50 60 MTDDKDVLRD VWFGRIPTCF TLYQDEITER EAEPYYLLLP RVSYLTLVTD KVKKHFQKVM 70 80 90 100 110 120 RQEDISEIWF EYEGTPLKWH YPIGLLFDLL ASSSALPWNI TVHFKSFPEK DLLHCPSKDA 130 140 150 160 170 180 IEAHFMSCMK EADALKHKSQ VINEMQKKDH KQLWMGLQND RFDQFWAINR KLMEYPAEEN 190 200 210 220 230 240 GFRYIPFRIY QTTTERPFIQ KLFRPVAADG QLHTLGDLLK EVCPSAIDPE DGEKKNQVMI 250 260 270 HGIEPMLETP LQWLSEHLSY PDNFLHISII PQPTD
	Isoform Short (APG5beta) [UniParc]. Checksum: 05FC581F6EABB753	FASTA	197	22,931
	10 20 30 40 50 60 MHYPIGLLFD LLASSSALPW NITVHFKSFP EKDLLHCPSK DAIEAHFMSC MKEADALKHK 70 80 90 100 110 120 SQVINEMQKK DHKQLWMGLQ NDRFDQFWAI NRKLMEYPAE ENGFRYIPFR IYQTTTERPF 130 140 150 160 170 180 IQKLFRPVAA DGQLHTLGDL LKEVCPSAID PEDGEKKNQV MIHGIEPMLE TPLQWLSEHL 190 SYPDNFLHIS IIPQPTD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Homology between a human apoptosis specific protein and the product of APG5, a gene involved in autophagy in yeast." Hammond E.M., Brunet C.L., Johnson G.D., Parkhill J., Milner A.E., Brady G., Gregory C.D., Grand R.J.A. FEBS Lett. 425:391-395(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). Tissue: Fetal liver.
[2]	"A novel splicing isoform of human APG5." Chen Y., Piao Y.J., Jiang Y. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
[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 SHORT). Tissue: Fetal brain.
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM LONG). Tissue: Endometrium and Placenta.
[6]	"A novel protein expressed in mammalian cells undergoing apoptosis." Grand R.J.A., Milner A.E., Mustoe T., Johnson G.D., Owen D., Grant M.L., Gregory C.D. Exp. Cell Res. 218:439-451(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN APOPTOSIS.
[7]	"A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy." Mizushima N., Sugita H., Yoshimori T., Ohsumi Y. J. Biol. Chem. 273:33889-33892(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CONJUGATION TO ATG12 AT LYS-130, MUTAGENESIS OF LYS-130.
[8]	"Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells." Mizushima N., Yamamoto A., Hatano M., Kobayashi Y., Kabeya Y., Suzuki K., Tokuhisa T., Ohsumi Y., Yoshimori T. J. Cell Biol. 152:657-668(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CONJUGATION TO ATG12, SUBCELLULAR LOCATION. Tissue: Embryonic stem cell.
[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].
[10]	"A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens." Ogawa M., Yoshikawa Y., Kobayashi T., Mimuro H., Fukumatsu M., Kiga K., Piao Z., Ashida H., Yoshida M., Kakuta S., Koyama T., Goto Y., Nagatake T., Nagai S., Kiyono H., Kawalec M., Reichhart J.M., Sasakawa C. Cell Host Microbe 9:376-389(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TECPR1.
[11]	"A mammalian autophagosome maturation mechanism mediated by TECPR1 and the Atg12-Atg5 conjugate." Chen D., Fan W., Lu Y., Ding X., Chen S., Zhong Q. Mol. Cell 45:629-641(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TECPR1.
[12]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] MET-58.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00006800.
IPI00220640.

RefSeq

NP_004840.1. NM_004849.2.

UniGene

Hs.486063.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4GDK	X-ray	2.70	B/E	1-275	[»]
4GDL	X-ray	2.88	B	1-275	[»]

ProteinModelPortal

Q9H1Y0.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29758N.

IntAct

Q9H1Y0. 29 interactions.

STRING

9606.ENSP00000343313.

PTM databases

PhosphoSite

Q9H1Y0.

Polymorphism databases

DMDM

17366828.

Proteomic databases

PaxDb

Q9H1Y0.

PRIDE

Q9H1Y0.

Protocols and materials databases

DNASU

9474.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000343245; ENSP00000343313; ENSG00000057663.
ENST00000369070; ENSP00000358066; ENSG00000057663.
ENST00000369076; ENSP00000358072; ENSG00000057663.

GeneID

9474.

KEGG

hsa:9474.

UCSC

uc003prf.3. human.
uc003prg.3. human.

Organism-specific databases

CTD

9474.

GeneCards

GC06M106632.

HGNC

HGNC:589. ATG5.

HPA

CAB034432.
CAB037309.
HPA042973.

MIM

604261. gene.

neXtProt

NX_Q9H1Y0.

PharmGKB

PA24880.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG271554.

HOGENOM

HOG000007893.

HOVERGEN

HBG018731.

InParanoid

Q9H1Y0.

KO

K08339.

OMA

HYPIGVL.

OrthoDB

EOG4T783Z.

PhylomeDB

Q9H1Y0.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9H1Y0.

Bgee

Q9H1Y0.

CleanEx

HS_ATG5.

Genevestigator

Q9H1Y0.

GermOnline

ENSG00000057663. Homo sapiens.

Family and domain databases

InterPro

IPR007239. Atg5.
[Graphical view]

PANTHER

PTHR13040. PTHR13040. 1 hit.

Pfam

PF04106. APG5. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

ATG5. human.

GenomeRNAi

9474.

NextBio

35504.

SOURCE

Search...

Entry information

Entry name

ATG5_HUMAN

Accession

Primary (citable) accession number: Q9H1Y0
Secondary accession number(s): O60875 , Q5JVR2, Q68DI4, Q9H2B8, Q9HCZ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	November 16, 2001
Last modified:	May 1, 2013
This is version 108 of the entry and version 2 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.