ATG3

{{Infobox protein family

| Symbol = Autophagy_N

| Name = Autophagocytosis associated protein N-terminal

| image =

| width =

| caption = the crystal structure of saccharomyces cerevisiae atg3

| Pfam = PF03986

| Pfam_clan =

| InterPro = IPR007134

| SMART =

| PROSITE =

| MEROPS =

| SCOP =

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

{{Infobox protein family

| Symbol = Autophagy_act_C

| Name = Autophagocytosis associated protein active site domain

| image =

| width =

| caption = the crystal structure of saccharomyces cerevisiae atg3

| Pfam = PF03987

| Pfam_clan =

| InterPro = IPR007135

| SMART =

| PROSITE =

| MEROPS =

| SCOP =

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

{{Infobox protein family

| Symbol = Autophagy_Cterm

| Name = Autophagocytosis associated protein C-terminal

| image =

| width =

| caption = the crystal structure of saccharomyces cerevisiae atg3

| Pfam = PF10381

| Pfam_clan =

| InterPro = IPR019461

| SMART =

| PROSITE =

| MEROPS =

| SCOP =

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

In molecular biology, autophagy related 3 (Atg3) is the E2 enzyme for the LC3 lipidation process.{{cite journal |vauthors=Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T | title = The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy | journal = Mol. Biol. Cell | volume = 19 | issue = 5 | pages = 2092–100 |date=May 2008 | pmid = 18321988 | pmc = 2366860 | doi = 10.1091/mbc.E07-12-1257 }} It is essential for autophagy. The super protein complex, the Atg16L complex, consists of multiple Atg12-Atg5 conjugates. Atg16L has an E3-like role in the LC3 lipidation reaction. The activated intermediate, LC3-Atg3 (E2), is recruited to the site where the lipidation takes place.{{cite journal |vauthors=Noda T, Fujita N, Yoshimori T | title = The Ubi brothers reunited | journal = Autophagy | volume = 4 | issue = 4 | pages = 540–1 |date=May 2008 | pmid = 18398292 | doi = 10.4161/auto.5973| doi-access = free }}

Atg3 catalyses the conjugation of Atg8 and phosphatidylethanolamine (PE). Atg3 has an alpha/beta-fold, and its core region is topologically similar to canonical E2 enzymes. Atg3 has two regions inserted in the core region and another with a long alpha-helical structure that protrudes from the core region as far as 30 A.{{cite journal |vauthors=Yamada Y, Suzuki NN, Hanada T, Ichimura Y, Kumeta H, Fujioka Y, Ohsumi Y, Inagaki F | title = The crystal structure of Atg3, an autophagy-related ubiquitin carrier protein (E2) enzyme that mediates Atg8 lipidation | journal = J. Biol. Chem. | volume = 282 | issue = 11 | pages = 8036–43 |date=March 2007 | pmid = 17227760 | doi = 10.1074/jbc.M611473200 | doi-access = free }} It interacts with atg8 through an intermediate thioester bond between Cys-288 and the C-terminal Gly of atg8. It also interacts with the C-terminal region of the E1-like atg7 enzyme.

Autophagocytosis is a starvation-induced process responsible for transport of cytoplasmic proteins to the lysosome/vacuole. Atg3 is a ubiquitin like modifier that is topologically similar to the canonical E2 enzyme.{{cite journal |vauthors=Tanida I, Tanida-Miyake E, Komatsu M, Ueno T, Kominami E | title = 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 | journal = J. Biol. Chem. | volume = 277 | issue = 16 | pages = 13739–44 |date=April 2002 | pmid = 11825910 | doi = 10.1074/jbc.M200385200 | doi-access = free }} It catalyses the conjugation of Atg8 and phosphatidylethanolamine.{{cite journal |vauthors=Schlumpberger M, Schaeffeler E, Straub M, Bredschneider M, Wolf DH, Thumm M | title = AUT1, a gene essential for autophagocytosis in the yeast Saccharomyces cerevisiae | journal = J. Bacteriol. | volume = 179 | issue = 4 | pages = 1068–76 |date=February 1997 | pmid = 9023185 | pmc = 178799 | doi = 10.1128/jb.179.4.1068-1076.1997}}

Atg3 consists of three domains, an N-terminal domain, a catalytic domain and a C-terminal domain. The catalytic domain contains a cysteine residue within an HPC motif, this is the putative active-site residue for recognition of the Apg5 subunit of the autophagosome complex.{{cite journal |vauthors=Mizushima N, Yoshimori T, Ohsumi Y | title = Mouse Apg10 as an Apg12-conjugating enzyme: analysis by the conjugation-mediated yeast two-hybrid method | journal = FEBS Lett. | volume = 532 | issue = 3 | pages = 450–4 |date=December 2002 | pmid = 12482611 | doi = 10.1016/S0014-5793(02)03739-0| s2cid = 37247321 | doi-access = }} The small C-terminal domain is likely to be a distinct binding region for the stability of the autophagosome complex.{{cite journal |vauthors=Mizushima N, Yoshimori T, Ohsumi Y | title = Role of the Apg12 conjugation system in mammalian autophagy | journal = Int. J. Biochem. Cell Biol. | volume = 35 | issue = 5 | pages = 553–61 |date=May 2003 | pmid = 12672448 | doi = 10.1016/S1357-2725(02)00343-6| doi-access = free }} It carries a highly characteristic conserved FLKF sequence motif.