IRGM
entrez
345611
canonical
uniprot
A1A4Y4
canonical
ensembl
ENSG00000237693
resolver
ensp
ENSP00000428220
resolver
genesymbol
IRGM
resolver
genesymbol_syn
IFI1
resolver
genesymbol_syn
IRGM1
resolver
genesymbol_syn
LRG47
resolver
hgnc
HGNC:29597
resolver
uniprot
B3VEX0
resolver
uniprot
H0YBM2
resolver
uniprot_entry
IRGM_HUMAN
resolver
uniprot_sec
B3VEX0
resolver
uniprot_sec
H0YBM2
resolver
amino_acid_sequence
MEAMNVEKASADGNLPEVISNIKETLKIVSRTPVNITMAGDSGNGMSTFISALRNTGHEGKASPPTELVKATQRCASYFSSHFSNVVLWDLPGTGSATTTLENYLMEMQFNRYDFIMVASAQFSMNHVMLAKTAEDMGKKFYIVWTKLDMDLSTGALPEVQLLQIRENVLENLQKERVCEY
uniprot
proteins
disease_involvement
DISEASE: Inflammatory bowel disease 19 (IBD19) [MIM:612278]: A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. {ECO:0000269|PubMed:17554261, ECO:0000269|PubMed:19165925, ECO:0000269|PubMed:19174780, ECO:0000269|PubMed:20106866, ECO:0000269|PubMed:21278745}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
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:16888103, PubMed:19165925, PubMed:25891078). Acts as a dynamin-like protein that binds to intracellular membranes and promotes remodeling and trafficking of those membranes (By similarity). 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:16888103, PubMed:25891078, PubMed:29420192, PubMed:32939830). Regulates selective autophagy, including xenophagy and mitophagy, both directly and indirectly (PubMed:16888103, PubMed:25891078, PubMed:29420192, PubMed:32939830). Directly regulates autophagy by acting as a molecular adapter that promotes the coassembly of the core autophagy machinery to mediate antimicrobial defense: IRGM (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 (PubMed:25891078). Also activates autophagy by promoting recruitment of STX17 to autophagosomes (PubMed:29420192). In collaboration with ATG8 proteins, regulate lysosomal biogenesis, a fundamental process for any autophagic pathway, by promoting TFEB dephosphorylation (PubMed:32753672). Also modulates autophagy by assisting with autophagosome formation and preventing lysosomal deacidification (By similarity). 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:32715615, PubMed:36221902). Promotes degradation of damaged and IFNG/IFN-gamma-stressed mitochondria via mitophagy, preventing cytosolic release of ligands that activate inflammation (PubMed:32715615). 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 (PubMed:30612879, PubMed:32715615). Also directly inhibits assembly of the NLRP3 inflammasome by preventing the association between NLRP3 and PYCARD (PubMed:30612879). 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 (PubMed:34467632, PubMed:36221902). {ECO:0000250|UniProtKB:Q60766, ECO:0000269|PubMed:16888103, ECO:0000269|PubMed:19165925, ECO:0000269|PubMed:25891078, ECO:0000269|PubMed:29420192, ECO:0000269|PubMed:30612879, ECO:0000269|PubMed:32715615, ECO:0000269|PubMed:32753672, ECO:0000269|PubMed:32939830, ECO:0000269|PubMed:34467632, ECO:0000269|PubMed:36221902}.; FUNCTION: [Isoform IRGMd]: Acts as a positive regulator of mitophagy in response to intracellular mycobacteria infection: specifically binds cardiolipin, leading to its translocation to mitochondria, where it promotes affected mitochondrial fission and mitophagy. {ECO:0000269|PubMed:21102437}.; FUNCTION: (Microbial infection) Following infection by hepatitis C virus (HCV), promotes HCV-triggered membrane remodeling, leading to autophagy and Golgi fragmentation, a step required for HCV replication. {ECO:0000269|PubMed:28389568}.
uniprot
proteins
mass_dalton
20142
uniprot
proteins
mutagenesis
MUTAGEN 47; /note="S->N: Abolished GTPase activity, preventing interaction with STX17 and/or NLRP3."; /evidence="ECO:0000269|PubMed:29420192, ECO:0000269|PubMed:30612879
uniprot
proteins
post_translational_modification
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. {ECO:0000269|PubMed:25891078}.
uniprot
proteins
protein_family
IRG family
uniprot
proteins
protein_family
TRAFAC class dynamin-like GTPase superfamily
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16277747
uniprot
proteins
pubmed
16888103
uniprot
proteins
pubmed
17554261
uniprot
proteins
pubmed
19165925
uniprot
proteins
pubmed
19174780
uniprot
proteins
pubmed
19266026
uniprot
proteins
pubmed
19750224
uniprot
proteins
pubmed
20106866
uniprot
proteins
pubmed
21102437
uniprot
proteins
pubmed
21278745
uniprot
proteins
pubmed
25891078
uniprot
proteins
pubmed
28389568
uniprot
proteins
pubmed
29420192
uniprot
proteins
pubmed
30612879
uniprot
proteins
pubmed
32715615
uniprot
proteins
pubmed
32753672
uniprot
proteins
pubmed
32939830
uniprot
proteins
pubmed
34467632
uniprot
proteins
pubmed
36221902
uniprot
proteins
sequence_length
181
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000269|PubMed:28389568}. Cell membrane {ECO:0000250|UniProtKB:Q60766}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:Q60766}. Cytoplasmic vesicle, autophagosome membrane {ECO:0000269|PubMed:29420192}. Lysosome membrane {ECO:0000250|UniProtKB:Q60766}. Late endosome membrane {ECO:0000250|UniProtKB:Q60766}. Mitochondrion membrane {ECO:0000250|UniProtKB:Q60766}. Cell projection, phagocytic cup {ECO:0000250|UniProtKB:Q60766}. Note=Behaves like an integral membrane protein. Recruited to the plasma membrane around forming phagocytic cups, it remains associated with maturing phagosomes. Association with phagosomes is dependent on nucleotide-binding but is IFNG-independent. Also detected in late endosomes and lysosomes. {ECO:0000250|UniProtKB:Q60766}.; SUBCELLULAR LOCATION: [Isoform IRGMd]: Mitochondrion {ECO:0000269|PubMed:21102437}.
uniprot
proteins