Protein: Immunity-related GTPase family M protein 1 (Q60766)
Organism: Mus musculus (Mouse)
Function: Immunity-related GTPase that plays important roles in innate immunity and inflammatory response. Acts as a dynamin- like protein that binds to intracellular membranes and promotes remodeling and trafficking of those membranes. 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. Regulates selective autophagy, including xenophagy and mitophagy, both directly and indirectly. 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. Regulates autophagy by affecting mitochondrial fusion and fission. Also involved in M1 macrophage activation for the production of proinflammatory cytokines. 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. Promotes degradation of damaged and IFNG/IFN-gamma-stressed mitochondria via mitophagy, preventing cytosolic release of ligands that activate inflammation. Negatively regulates interferon- signaling in hematopoietic stem cells, preserving hematopoietic stem cell number and function. Promotes expansion of activated CD4(+) T-cells by inhibiting IFNG/IFN-gamma signaling, thereby preventing Ifng-mediated cell death of CD4(+) T- cells. 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)
Subcellular location: Golgi apparatus membrane. Cell membrane. Cytoplasmic vesicle, phagosome membrane. Cytoplasmic vesicle, autophagosome membrane. Lysosome membrane. Late endosome membrane. Mitochondrion membrane. Lipid droplet. Cell projection, phagocytic cup. 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: lysosomal localization is IFN-gamma-induced during bacterial infections such as S.typhimurium infection. Associates with lipid droplets and 'self' cytoplasmic vacuoles, while it does not coat 'non- self' pathogen-containing vacuoles
Sequence: MKPSHSSCEAAPLLPNMAETHYAPLSSAFPFVTSYQTGSSRLPEVSRSTERALREGKLLELVYGIKETVATLSQIPVSIFVTGDSGNGMSSFINALRVIGHDEDASAPTGVVRTTKTRTEYSSSHFPNVVLWDLPGLGATAQTVEDYVEEMKFSTCDLFIIIASEQFSSNHVKLSKIIQSMGKRFYIVWTKLDRDLSTSVLSEVRLLQNIQENIRENLQKEKVKYPPVFLVSSLDPLLYDFPKLRDTLHKDLSNIRCCEPLKTLYGTYEKIVGDKVAVWKQRIANESLKNSLGVRDDDNMGECLKVYRLIFGVDDESVQQVAQSMGTVVMEYKDNMKSQNFYTLRREDWKLRLMTCAIVNAFFRLLRFLPCVCCCLRRLRHKRMLFLVAQDTKNILEKILRDSIFPPQI
InterPro domains: - IPR030385: IRG-type guanine nucleotide-binding (G) domain (domain) [75-251]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [52-339]
- IPR051515: Immunity-related GTPase (family) [33-404]
- IPR007743: Immunity-related GTPases-like (family) [43-399]
Interaction partners: - Autophagy protein 5
- Ubiquitin-like-conjugating enzyme ATG10
- Immunity-related GTPase family M protein 2
- Autophagy-related protein 16-1
- Guanylate-binding protein 3
- Signal transducer and activator of transcription 1
- Guanylate-binding protein 2
- Nucleotide-binding oligomerization domain-containing protein 2
- Beclin-1
- Guanylate-binding protein 7
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0097367 (carbohydrate derivative binding), GO:0036094 (small molecule binding), GO:1901363 (heterocyclic compound binding), GO:0016787 (hydrolase activity), GO:0043167 (ion binding), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0016817 (hydrolase activity, acting on acid anhydrides), GO:1901265 (nucleoside phosphate binding), GO:0043168 (anion binding), GO:0042802 (identical protein binding), GO:0000166 (nucleotide binding), GO:0032553 (ribonucleotide binding), GO:0035639 (purine ribonucleoside triphosphate binding), GO:0019003 (GDP binding), GO:0032555 (purine ribonucleotide binding), GO:0016818 (hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides), GO:0017076 (purine nucleotide binding), GO:0016462 (pyrophosphatase activity), GO:0005525 (GTP binding), GO:0019001 (guanyl nucleotide binding), GO:0032561 (guanyl ribonucleotide binding), GO:0017111 (ribonucleoside triphosphate phosphatase activity), GO:0003924 (GTPase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0009605 (response to external stimulus), GO:0023056 (positive regulation of signaling), GO:0042221 (response to chemical), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0006955 (immune response), GO:0002684 (positive regulation of immune system process), GO:0002682 (regulation of immune system process), GO:0071840 (cellular component organization or biogenesis), GO:0009056 (catabolic process), GO:0044237 (cellular metabolic process), GO:0009607 (response to biotic stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0006950 (response to stress), GO:0061919 (process utilizing autophagic mechanism), GO:0051707 (response to other organism), GO:0048522 (positive regulation of cellular process), GO:0009967 (positive regulation of signal transduction), GO:0060759 (regulation of response to cytokine stimulus), GO:0032103 (positive regulation of response to external stimulus), GO:0044085 (cellular component biogenesis), GO:0043207 (response to external biotic stimulus), GO:0080134 (regulation of response to stress), GO:0044248 (cellular catabolic process), GO:0009966 (regulation of signal transduction), GO:0006952 (defense response), GO:0032101 (regulation of response to external stimulus), GO:0060760 (positive regulation of response to cytokine stimulus), GO:0051130 (positive regulation of cellular component organization), GO:0010033 (response to organic substance), GO:0045087 (innate immune response), GO:0006914 (autophagy), GO:0098542 (defense response to other organism), GO:0009894 (regulation of catabolic process), GO:0002831 (regulation of response to biotic stimulus), GO:0050776 (regulation of immune response), GO:0031325 (positive regulation of cellular metabolic process), GO:0010646 (regulation of cell communication), GO:0002833 (positive regulation of response to biotic stimulus), GO:0070887 (cellular response to chemical stimulus), GO:0009617 (response to bacterium), GO:0050778 (positive regulation of immune response), GO:0031323 (regulation of cellular metabolic process), GO:0010647 (positive regulation of cell communication), GO:0016043 (cellular component organization), GO:0031349 (positive regulation of defense response), GO:0051128 (regulation of cellular component organization), GO:0009896 (positive regulation of catabolic process), GO:0031347 (regulation of defense response), GO:0001961 (positive regulation of cytokine-mediated signaling pathway), GO:0034097 (response to cytokine), GO:0045089 (positive regulation of innate immune response), GO:0045088 (regulation of innate immune response), GO:0001959 (regulation of cytokine-mediated signaling pathway), GO:0071310 (cellular response to organic substance), GO:0043244 (regulation of protein-containing complex disassembly), GO:0010506 (regulation of autophagy), GO:0022607 (cellular component assembly), GO:0016236 (macroautophagy), GO:0010508 (positive regulation of autophagy), GO:0033043 (regulation of organelle organization), GO:0031331 (positive regulation of cellular catabolic process), GO:0060330 (regulation of response to type II interferon), GO:0043243 (positive regulation of protein-containing complex disassembly), GO:0034341 (response to type II interferon), GO:0031329 (regulation of cellular catabolic process), GO:0006996 (organelle organization), GO:0010638 (positive regulation of organelle organization), GO:0070925 (organelle assembly), GO:1901098 (positive regulation of autophagosome maturation), GO:0016241 (regulation of macroautophagy), GO:1905037 (autophagosome organization), GO:0071345 (cellular response to cytokine stimulus), GO:1901096 (regulation of autophagosome maturation), GO:0007033 (vacuole organization), GO:0060334 (regulation of type II interferon-mediated signaling pathway), GO:0071346 (cellular response to type II interferon), GO:0016239 (positive regulation of macroautophagy), GO:0000045 (autophagosome assembly)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005773 (vacuole), GO:0005783 (endoplasmic reticulum), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0043227 (membrane-bounded organelle), GO:0000323 (lytic vacuole), GO:0030139 (endocytic vesicle), GO:0005776 (autophagosome), GO:0043231 (intracellular membrane-bounded organelle), GO:0031982 (vesicle), GO:0005770 (late endosome), GO:0005764 (lysosome), GO:0045335 (phagocytic vesicle), GO:0044754 (autolysosome), GO:0097708 (intracellular vesicle), GO:0005767 (secondary lysosome)