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Protein

Autophagy protein 5

Gene

Atg5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. The ATG12-ATG5 conjugate also negatively regulates the innate antiviral immune response by blocking the type I IFN production pathway through direct association with RARRES3 and MAVS. Also plays a role in translation or delivery of incoming viral RNA to the translation apparatus. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway.9 Publications
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. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD (By similarity).By similarity

GO - Biological processi

  • aggrephagy Source: ParkinsonsUK-UCL
  • antigen processing and presentation of endogenous antigen Source: MGI
  • apoptotic process Source: UniProtKB-KW
  • autophagosome assembly Source: UniProtKB
  • autophagy Source: UniProtKB
  • blood vessel remodeling Source: MGI
  • cellular homeostasis Source: MGI
  • cellular response to nitrogen starvation Source: GO_Central
  • cellular response to nitrosative stress Source: ParkinsonsUK-UCL
  • cellular response to starvation Source: MGI
  • heart contraction Source: MGI
  • innate immune response Source: UniProtKB-KW
  • macroautophagy Source: MGI
  • negative regulation of apoptotic process Source: ParkinsonsUK-UCL
  • negative regulation of cell death Source: MGI
  • negative regulation of histone H4-K16 acetylation Source: MGI
  • negative regulation of phagocytosis Source: MGI
  • negative regulation of protein ubiquitination Source: MGI
  • negative regulation of reactive oxygen species metabolic process Source: ParkinsonsUK-UCL
  • negative regulation of type I interferon production Source: Reactome
  • negative stranded viral RNA replication Source: MGI
  • negative thymic T cell selection Source: MGI
  • nucleophagy Source: GO_Central
  • otolith development Source: MGI
  • positive regulation of mitophagy Source: ParkinsonsUK-UCL
  • positive regulation of mucus secretion Source: MGI
  • post-translational protein modification Source: UniProtKB
  • protein lipidation involved in autophagosome assembly Source: MGI
  • regulation of cilium assembly Source: UniProtKB
  • regulation of cytokine secretion involved in immune response Source: MGI
  • regulation of reactive oxygen species metabolic process Source: MGI
  • regulation of release of sequestered calcium ion into cytosol Source: MGI
  • response to drug Source: MGI
  • response to fungus Source: MGI
  • vasodilation Source: MGI
  • ventricular cardiac muscle cell development Source: MGI
Complete GO annotation...

Keywords - Biological processi

Apoptosis, Autophagy, Immunity, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-1632852. Macroautophagy.
R-MMU-5205685. Pink/Parkin Mediated Mitophagy.
R-MMU-936440. Negative regulators of RIG-I/MDA5 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Autophagy protein 5
Alternative name(s):
APG5-like
Gene namesi
Name:Atg5
Synonyms:Apg5l
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1277186. Atg5.

Subcellular locationi

GO - Cellular componenti

  • Atg12-Atg5-Atg16 complex Source: GO_Central
  • autophagosome Source: MGI
  • axoneme Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • ER-mitochondrion membrane contact site Source: MGI
  • membrane Source: MGI
  • pre-autophagosomal structure membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi130 – 1301K → R: Loss of conjugation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 275275Autophagy protein 5PRO_0000218995Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Cross-linki130 – 130Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ATG12)By similarity

Post-translational modificationi

Conjugated to ATG12; which is essential for autophagy, but is not required for association with isolation membrane.
Acetylated by EP300.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

EPDiQ99J83.
MaxQBiQ99J83.
PaxDbiQ99J83.
PeptideAtlasiQ99J83.
PRIDEiQ99J83.

PTM databases

iPTMnetiQ99J83.
PhosphoSiteiQ99J83.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiQ99J83.
CleanExiMM_ATG5.
GenevisibleiQ99J83. MM.

Interactioni

Subunit structurei

Forms a conjugate with ATG12. The ATG5-ATG12 conjugate forms a complex with several units of ATG16L. Interacts with TECPR1; the interaction is direct and does not take place when ATG16 is associated with the ATG5-ATG12 conjugate (By similarity). ATG12-ATG5 also interacts with MAVS, MGA, and RARRES3 (By similarity). Interacts with ATG3, ATG7 and ATG10. Interacts with FADD (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Atg12Q9CQY14EBI-2911848,EBI-2911788
Atg16l1Q8C0J24EBI-2911848,EBI-769195

Protein-protein interaction databases

BioGridi198146. 7 interactions.
DIPiDIP-46420N.
IntActiQ99J83. 10 interactions.
MINTiMINT-4088049.
STRINGi10090.ENSMUSP00000044769.

Structurei

3D structure databases

ProteinModelPortaliQ99J83.
SMRiQ99J83. Positions 2-274.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ATG5 family.Curated

Phylogenomic databases

eggNOGiKOG2976. Eukaryota.
ENOG410XQ71. LUCA.
GeneTreeiENSGT00390000004766.
HOGENOMiHOG000007893.
HOVERGENiHBG018731.
InParanoidiQ99J83.
KOiK08339.
OMAiETPIQWL.
OrthoDBiEOG72C50T.
PhylomeDBiQ99J83.
TreeFamiTF314415.

Family and domain databases

InterProiIPR007239. Atg5.
[Graphical view]
PANTHERiPTHR13040. PTHR13040. 1 hit.
PfamiPF04106. APG5. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q99J83-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTDDKDVLRD VWFGRIPTCF TLYQDEITER EAEPYYLLLP RVSYLTLVTD
60 70 80 90 100
KVKKHFQKVM RQEDVSEIWF EYEGTPLKWH YPIGLLFDLL ASSSALPWNI
110 120 130 140 150
TVHFKSFPEK DLLHCPSKDA VEAHFMSCMK EADALKHKSQ VINEMQKKDH
160 170 180 190 200
KQLWMGLQND RFDQFWAINR KLMEYPPEEN GFRYIPFRIY QTTTERPFIQ
210 220 230 240 250
KLFRPVAADG QLHTLGDLLR EVCPSAVAPE DGEKRSQVMI HGIEPMLETP
260 270
LQWLSEHLSY PDNFLHISIV PQPTD
Length:275
Mass (Da):32,402
Last modified:June 1, 2001 - v1
Checksum:iF3FCE652D627B694
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB048349 mRNA. Translation: BAB33383.1.
AK028315 mRNA. Translation: BAC25874.1.
BC002166 mRNA. Translation: AAH02166.1.
CCDSiCCDS23824.1.
RefSeqiNP_001300942.1. NM_001314013.1.
NP_444299.1. NM_053069.6.
XP_011241410.1. XM_011243108.1.
UniGeneiMm.22264.

Genome annotation databases

EnsembliENSMUST00000039286; ENSMUSP00000044769; ENSMUSG00000038160.
GeneIDi11793.
KEGGimmu:11793.
UCSCiuc007ezt.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB048349 mRNA. Translation: BAB33383.1.
AK028315 mRNA. Translation: BAC25874.1.
BC002166 mRNA. Translation: AAH02166.1.
CCDSiCCDS23824.1.
RefSeqiNP_001300942.1. NM_001314013.1.
NP_444299.1. NM_053069.6.
XP_011241410.1. XM_011243108.1.
UniGeneiMm.22264.

3D structure databases

ProteinModelPortaliQ99J83.
SMRiQ99J83. Positions 2-274.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198146. 7 interactions.
DIPiDIP-46420N.
IntActiQ99J83. 10 interactions.
MINTiMINT-4088049.
STRINGi10090.ENSMUSP00000044769.

PTM databases

iPTMnetiQ99J83.
PhosphoSiteiQ99J83.

Proteomic databases

EPDiQ99J83.
MaxQBiQ99J83.
PaxDbiQ99J83.
PeptideAtlasiQ99J83.
PRIDEiQ99J83.

Protocols and materials databases

DNASUi11793.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000039286; ENSMUSP00000044769; ENSMUSG00000038160.
GeneIDi11793.
KEGGimmu:11793.
UCSCiuc007ezt.1. mouse.

Organism-specific databases

CTDi9474.
MGIiMGI:1277186. Atg5.

Phylogenomic databases

eggNOGiKOG2976. Eukaryota.
ENOG410XQ71. LUCA.
GeneTreeiENSGT00390000004766.
HOGENOMiHOG000007893.
HOVERGENiHBG018731.
InParanoidiQ99J83.
KOiK08339.
OMAiETPIQWL.
OrthoDBiEOG72C50T.
PhylomeDBiQ99J83.
TreeFamiTF314415.

Enzyme and pathway databases

ReactomeiR-MMU-1632852. Macroautophagy.
R-MMU-5205685. Pink/Parkin Mediated Mitophagy.
R-MMU-936440. Negative regulators of RIG-I/MDA5 signaling.

Miscellaneous databases

PROiQ99J83.
SOURCEiSearch...

Gene expression databases

BgeeiQ99J83.
CleanExiMM_ATG5.
GenevisibleiQ99J83. MM.

Family and domain databases

InterProiIPR007239. Atg5.
[Graphical view]
PANTHERiPTHR13040. PTHR13040. 1 hit.
PfamiPF04106. APG5. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CONJUGATION TO ATG12, MUTAGENESIS OF LYS-130.
    Tissue: Embryonic stem cell.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain.
  3. "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].
  4. "Mouse Apg10 as an Apg12-conjugating enzyme: analysis by the conjugation-mediated yeast two-hybrid method."
    Mizushima N., Yoshimori T., Ohsumi Y.
    FEBS Lett. 532:450-454(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ATG10, CONJUGATION TO ATG12.
  5. "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: CONJUGATION TO ATG12 BY ATG10, FUNCTION.
  6. "Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate."
    Mizushima N., Kuma A., Kobayashi Y., Yamamoto A., Matsubae M., Takao T., Natsume T., Ohsumi Y., Yoshimori T.
    J. Cell Sci. 116:1679-1688(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH ATG12 AND ATG16L.
  7. "Aberrant membranes and double-membrane structures accumulate in the axons of Atg5-null Purkinje cells before neuronal death."
    Nishiyama J., Miura E., Mizushima N., Watanabe M., Yuzaki M.
    Autophagy 3:591-596(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "A critical role for the autophagy gene Atg5 in T cell survival and proliferation."
    Pua H.H., Dzhagalov I., Chuck M., Mizushima N., He Y.W.
    J. Exp. Med. 204:25-31(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "The autophagy gene ATG5 plays an essential role in B lymphocyte development."
    Miller B.C., Zhao Z., Stephenson L.M., Cadwell K., Pua H.H., Lee H.K., Mizushima N.N., Iwasaki A., He Y.W., Swat W., Virgin H.W.
    Autophagy 4:309-314(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice."
    Sou Y.S., Waguri S., Iwata J., Ueno T., Fujimura T., Hara T., Sawada N., Yamada A., Mizushima N., Uchiyama Y., Kominami E., Tanaka K., Komatsu M.
    Mol. Biol. Cell 19:4762-4775(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: CONJUGATION TO ATG12.
  11. "Mitochondrial clearance is regulated by Atg7-dependent and -independent mechanisms during reticulocyte maturation."
    Zhang J., Randall M.S., Loyd M.R., Dorsey F.C., Kundu M., Cleveland J.L., Ney P.A.
    Blood 114:157-164(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: CONJUGATION TO ATG12.
  12. "Targeted deletion of autophagy-related 5 (atg5) impairs adipogenesis in a cellular model and in mice."
    Baerga R., Zhang Y., Chen P.H., Goldman S., Jin S.
    Autophagy 5:1118-1130(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Lung, Pancreas, Spleen and Testis.
  14. "In vivo requirement for Atg5 in antigen presentation by dendritic cells."
    Lee H.K., Mattei L.M., Steinberg B.E., Alberts P., Lee Y.H., Chervonsky A., Mizushima N., Grinstein S., Iwasaki A.
    Immunity 32:227-239(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  15. Cited for: SUBCELLULAR LOCATION, FUNCTION.
  16. "Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites."
    Tang Z., Lin M.G., Stowe T.R., Chen S., Zhu M., Stearns T., Franco B., Zhong Q.
    Nature 502:254-257(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiATG5_MOUSE
AccessioniPrimary (citable) accession number: Q99J83
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 16, 2001
Last sequence update: June 1, 2001
Last modified: July 6, 2016
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.