Irgm1
entrez
15944
canonical
uniprot
Q60766
canonical
ensembl
ENSMUSG00000046879
resolver
ensp
ENSMUSP00000050446
resolver
ensp
ENSMUSP00000094870
resolver
ensp
ENSMUSP00000183649
resolver
genesymbol
Irgm1
resolver
genesymbol_syn
Ifggd3
resolver
genesymbol_syn
Ifi1
resolver
genesymbol_syn
Iigp3
resolver
genesymbol_syn
Irgm
resolver
uniprot
J7NUP1
resolver
uniprot
Q3TJ73
resolver
uniprot
Q5NCB5
resolver
uniprot_entry
IRGM1_MOUSE
resolver
uniprot_entry
J7NUP1_MOUSE
resolver
uniprot_sec
Q3TJ73
resolver
uniprot_sec
Q5NCB5
resolver
amino_acid_sequence
MKPSHSSCEAAPLLPNMAETHYAPLSSAFPFVTSYQTGSSRLPEVSRSTERALREGKLLELVYGIKETVATLSQIPVSIFVTGDSGNGMSSFINALRVIGHDEDASAPTGVVRTTKTRTEYSSSHFPNVVLWDLPGLGATAQTVEDYVEEMKFSTCDLFIIIASEQFSSNHVKLSKIIQSMGKRFYIVWTKLDRDLSTSVLSEVRLLQNIQENIRENLQKEKVKYPPVFLVSSLDPLLYDFPKLRDTLHKDLSNIRCCEPLKTLYGTYEKIVGDKVAVWKQRIANESLKNSLGVRDDDNMGECLKVYRLIFGVDDESVQQVAQSMGTVVMEYKDNMKSQNFYTLRREDWKLRLMTCAIVNAFFRLLRFLPCVCCCLRRLRHKRMLFLVAQDTKNILEKILRDSIFPPQI
uniprot
proteins
ec_number
3.6.5.-
uniprot
proteins
function
FUNCTION: Immunity-related GTPase that plays important roles in innate immunity and inflammatory response (PubMed:11457893, PubMed:14576437, PubMed:14707092, PubMed:15908352, PubMed:16339555, PubMed:17911638, PubMed:17982087, PubMed:19620982, PubMed:19920210). Acts as a dynamin-like protein that binds to intracellular membranes and promotes remodeling and trafficking of those membranes (PubMed:19620982, PubMed:27098192). Required for clearance of acute protozoan and bacterial infections by interacting with autophagy and lysosome regulatory proteins, thereby promoting the fusion of phagosomes with lysosomes for efficient degradation of cargo including microbes (PubMed:11457893, PubMed:14576437, PubMed:14707092, PubMed:15607973, PubMed:15908352, PubMed:16339555, PubMed:17982087, PubMed:19620982, PubMed:19920210, PubMed:21757726, PubMed:22874556, PubMed:24751652, PubMed:32453761). Regulates selective autophagy, including xenophagy and mitophagy, both directly and indirectly (PubMed:15607973, PubMed:21757726). Directly regulates autophagy by acting as a molecular adapter that promotes the coassembly of the core autophagy machinery to mediate antimicrobial defense: Irgm1 (1) activates AMPK, which in turn phosphorylates ULK1 and BECN1 to induce autophagy, (2) promotes the coassembly of ULK1 and BECN1, enhancing BECN1-interacting partners and (3) influences the composition of the BECN1 complex, by competing with the negative regulators BCL2 and RUBCN, to trigger autophagy (By similarity). Also activates autophagy by promoting recruitment of STX17 to autophagosomes (By similarity). In collaboration with ATG8 proteins, regulate lysosomal biogenesis, a fundamental process for any autophagic pathway, by promoting TFEB dephosphorylation (By similarity). Also modulates autophagy by assisting with autophagosome formation and preventing lysosomal deacidification (PubMed:21757726). Regulates autophagy by affecting mitochondrial fusion and fission (PubMed:24751652). Also involved in M1 macrophage activation for the production of proinflammatory cytokines (PubMed:15908352, PubMed:27439214, PubMed:27443879). While activating autophagy, acts as a key negative regulator of the inflammatory and interferon responses both by (1) promoting mitophagy and (2) mediating autophagy-dependent degradation of effectors of the inflammatory response (PubMed:30612879, PubMed:33510463, PubMed:34467632). Promotes degradation of damaged and IFNG/IFN-gamma-stressed mitochondria via mitophagy, preventing cytosolic release of ligands that activate inflammation (PubMed:32715615, PubMed:33510463). Negatively regulates interferon-signaling in hematopoietic stem cells, preserving hematopoietic stem cell number and function (PubMed:18371424, PubMed:21633090). Promotes expansion of activated CD4(+) T-cells by inhibiting IFNG/IFN-gamma signaling, thereby preventing Ifng-mediated cell death of CD4(+) T-cells (PubMed:18806793). Acts as a suppressor of inflammation by promoting recruitment of inflammation effectors, such as CGAS, RIGI/RIG-I and NLRP3, to autophagosome membranes, leading to their SQSTM1/p62-dependent autophagic degradation (By similarity). Also directly inhibits assembly of the NLRP3 inflammasome by preventing the association between NLRP3 and PYCARD (By similarity). Acts as a negative regulator of antiviral innate immune response by suppressing the RIPK2-dependent pro-inflammatory response: mediates recruitment of RIPosomes, composed of RIPK2 and NOD1 or NOD2, to autophagosome membranes, promoting their SQSTM1/p62-dependent autophagic degradation (By similarity). {ECO:0000250|UniProtKB:A1A4Y4, ECO:0000269|PubMed:11457893, ECO:0000269|PubMed:14576437, ECO:0000269|PubMed:14707092, ECO:0000269|PubMed:15607973, ECO:0000269|PubMed:15908352, ECO:0000269|PubMed:16339555, ECO:0000269|PubMed:17911638, ECO:0000269|PubMed:17982087, ECO:0000269|PubMed:18371424, ECO:0000269|PubMed:18806793, ECO:0000269|PubMed:19620982, ECO:0000269|PubMed:19920210, ECO:0000269|PubMed:21633090, ECO:0000269|PubMed:21757726, ECO:0000269|PubMed:22874556, ECO:0000269|PubMed:24751652, ECO:0000269|PubMed:27098192, ECO:0000269|PubMed:27439214, ECO:0000269|PubMed:27443879, ECO:0000269|PubMed:30612879, ECO:0000269|PubMed:32453761, ECO:0000269|PubMed:32715615, ECO:0000269|PubMed:33510463, ECO:0000269|PubMed:34467632}.
uniprot
proteins
mass_dalton
46552
uniprot
proteins
mutagenesis
MUTAGEN 8; /note="C->A: Does not affect palmitoylation."; /evidence="ECO:0000269|PubMed:24751652"; MUTAGEN 90; /note="S->N: Loss of targeting to plasma membrane and phagosomes."; /evidence="ECO:0000269|PubMed:15294976"; MUTAGEN 257..258; /note="CC->AA: Does not affect palmitoylation."; /evidence="ECO:0000269|PubMed:24751652"; MUTAGEN 270; /note="K->A: Abolished ubiquitination by the DCX(WDR77) complex."; /evidence="ECO:0000269|PubMed:35197566"; MUTAGEN 275; /note="K->A: Does not affect ubiquitination by the DCX(WDR77) complex."; /evidence="ECO:0000269|PubMed:35197566"; MUTAGEN 350..356; /note="KLRLMTC->ALALATA: Abolished lipid-binding and subsequent recruitment to phagosome membranes, leading to impaired innate immunity."; /evidence="ECO:0000269|PubMed:19620982"; MUTAGEN 356; /note="C->A: No effect on subcellular location."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 358; /note="I->A: No effect on subcellular location."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 359; /note="V->A: No effect on subcellular location."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 360; /note="N->A: No effect on subcellular location. Abolishes Golgi and lysosomal localization; when associated with A-364."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 362..367; /note="FFRLLR->EFRLLE: Abolished lipid-binding and subsequent recruitment to phagosome membranes, leading to impaired innate immunity."; /evidence="ECO:0000269|PubMed:19620982"; MUTAGEN 362; /note="F->A: No effect on subcellular location."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 362; /note="F->E: Decreased lipid-binding."; /evidence="ECO:0000269|PubMed:19620982"; MUTAGEN 362; /note="F->EF: Disrupts amphipathicity and abolishes Golgi localization; when associated with Glu-367."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 363; /note="F->A: No effect on subcellular location."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 364; /note="R->A: No effect on subcellular location. Abolishes Golgi and lysosomal localization; when associated with A-360 or A-367."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 365; /note="L->A: No effect on subcellular location."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 366; /note="L->A: No effect on subcellular location."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 367; /note="R->A: No effect on subcellular location. Abolishes Golgi and lysosomal localization; when associated with A-364."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 367; /note="R->ER: Disrupts amphipathicity and abolishes Golgi localization; when associated with Glu-362."; /evidence="ECO:0000269|PubMed:20072621"; MUTAGEN 371..375; /note="CVCCC->AVAAA: Abolished palmitoylation and localization to membranes."; /evidence="ECO:0000269|PubMed:24751652"; MUTAGEN 398; /note="K->A: Does not affect ubiquitination by the DCX(WDR77) complex."; /evidence="ECO:0000269|PubMed:35197566
uniprot
proteins
post_translational_modification
PTM: Palmitoylated on C-terminal Cys residues (PubMed:24751652). Palmitoylation, together with the alpha-K amphipathic helix, which binds phosphatidylinositol, mediate binding to membranes (PubMed:24751652). {ECO:0000269|PubMed:24751652}.; PTM: Ubiquitinated via 'Lys-63'-linked polyubiquitination in a NOD2-dependent process. 'Lys-63'-linked polyubiquitination is required for interactions with the core autophagy factors (By similarity). Ubiquitination at Lys-270 by the DCX(WDR77) complex, also named CLR4(WDR77) complex, in intestinal cells, leading to its degradation by the proteasome (PubMed:35197566). {ECO:0000250|UniProtKB:A1A4Y4, ECO:0000269|PubMed:35197566}.
uniprot
proteins
protein_family
IRG family
uniprot
proteins
protein_family
TRAFAC class dynamin-like GTPase superfamily
uniprot
proteins
pubmed
11457893
uniprot
proteins
pubmed
14576437
uniprot
proteins
pubmed
14707092
uniprot
proteins
pubmed
15294976
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15607973
uniprot
proteins
pubmed
15908352
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16339555
uniprot
proteins
pubmed
17911638
uniprot
proteins
pubmed
17982087
uniprot
proteins
pubmed
18371424
uniprot
proteins
pubmed
18806793
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19620982
uniprot
proteins
pubmed
19920210
uniprot
proteins
pubmed
20072621
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21633090
uniprot
proteins
pubmed
21757726
uniprot
proteins
pubmed
22874556
uniprot
proteins
pubmed
23785284
uniprot
proteins
pubmed
24751652
uniprot
proteins
pubmed
27098192
uniprot
proteins
pubmed
27439214
uniprot
proteins
pubmed
27443879
uniprot
proteins
pubmed
28154172
uniprot
proteins
pubmed
28814662
uniprot
proteins
pubmed
30612879
uniprot
proteins
pubmed
32453761
uniprot
proteins
pubmed
32715615
uniprot
proteins
pubmed
33510463
uniprot
proteins
pubmed
34467632
uniprot
proteins
pubmed
35197566
uniprot
proteins
pubmed
36629440
uniprot
proteins
pubmed
7561525
uniprot
proteins
sequence_length
409
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000269|PubMed:15294976, ECO:0000269|PubMed:15908352, ECO:0000269|PubMed:20072621, ECO:0000269|PubMed:24751652}. Cell membrane {ECO:0000269|PubMed:15294976}. Cytoplasmic vesicle, phagosome membrane {ECO:0000269|PubMed:15294976, ECO:0000269|PubMed:19620982}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:15294976}. Lysosome membrane {ECO:0000269|PubMed:17982087, ECO:0000269|PubMed:20072621, ECO:0000269|PubMed:27098192}. Late endosome membrane {ECO:0000269|PubMed:20072621}. Mitochondrion membrane {ECO:0000269|PubMed:24751652}. Lipid droplet {ECO:0000269|PubMed:23785284}. Cell projection, phagocytic cup {ECO:0000269|PubMed:15294976}. Note=Behaves like an integral membrane protein (PubMed:15294976). Recruited to the plasma membrane around forming phagocytic cups, it remains associated with maturing phagosomes (PubMed:15294976). Association with phagosomes is dependent on nucleotide-binding but is IFNG-independent (PubMed:15294976). Also detected in late endosomes and lysosomes: lysosomal localization is IFN-gamma-induced during bacterial infections such as S.typhimurium infection (PubMed:17982087, PubMed:20072621). Associates with lipid droplets and 'self' cytoplasmic vacuoles, while it does not coat 'non-self' pathogen-containing vacuoles (PubMed:23785284). {ECO:0000269|PubMed:15294976, ECO:0000269|PubMed:17982087, ECO:0000269|PubMed:20072621, ECO:0000269|PubMed:23785284}.
uniprot
proteins