UniProtKB - A1A4Y4 (IRGM_HUMAN)
Protein
Immunity-related GTPase family M protein
Gene
IRGM
Organism
Homo sapiens (Human)
Status
Functioni
Putative GTPase which is required for clearance of acute protozoan and bacterial infections. Functions in innate immune response probably through regulation of autophagy. May regulate proinflammatory cytokine production and prevent endotoxemia upon infection. May also play a role in macrophages adhesion and motility (By similarity).By similarity1 Publication
Miscellaneous
Depletion of IRGM by siRNA favors mycobacteria survival in macrophages.
There is a huge difference in terms of sequence and regulation of expression compared to the mouse ortholog and hence, the function might be slightly different.1 Publication
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 41 – 48 | GTPBy similarity | 8 | |
Nucleotide bindingi | 66 – 70 | GTPBy similarity | 5 | |
Nucleotide bindingi | 147 – 149 | GTPBy similarity | 3 |
GO - Molecular functioni
- BH3 domain binding Source: UniProtKB
- CARD domain binding Source: UniProtKB
- GTPase activity Source: GO_Central
- GTP binding Source: UniProtKB-KW
- protein kinase binding Source: UniProtKB
- protein serine/threonine kinase activator activity Source: UniProtKB
GO - Biological processi
- autophagosome assembly Source: UniProtKB
- CAMKK-AMPK signaling cascade Source: UniProtKB
- cellular response to interferon-beta Source: GO_Central
- cellular response to lipopolysaccharide Source: UniProtKB
- cellular response to virus Source: UniProtKB
- defense response Source: GO_Central
- defense response to bacterium Source: UniProtKB
- defense response to Gram-negative bacterium Source: UniProtKB
- inflammatory response Source: UniProtKB-KW
- innate immune response Source: UniProtKB
- nucleotide-binding oligomerization domain containing 2 signaling pathway Source: UniProtKB
- positive regulation by symbiont of host autophagy Source: UniProtKB
- positive regulation of autophagosome maturation Source: UniProtKB
- positive regulation of autophagy Source: UniProtKB
- positive regulation of interferon-gamma-mediated signaling pathway Source: UniProtKB
- positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
- positive regulation of peptidyl-threonine phosphorylation Source: UniProtKB
- positive regulation of protein phosphorylation Source: UniProtKB
- positive regulation of protein serine/threonine kinase activity Source: UniProtKB
- protein destabilization Source: UniProtKB
- protein lipidation involved in autophagosome assembly Source: UniProtKB
- protein stabilization Source: UniProtKB
- regulation of protein complex stability Source: UniProtKB
- regulation of protein-containing complex assembly Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Biological process | Autophagy, Immunity, Inflammatory response, Innate immunity |
Ligand | GTP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | A1A4Y4 |
Names & Taxonomyi
Protein namesi | Recommended name: Immunity-related GTPase family M protein (EC:3.6.5.-)Alternative name(s): Immunity-related GTPase family M protein 1 Interferon-inducible protein 1 LPS-stimulated RAW 264.7 macrophage protein 47 homolog Short name: LRG-47 |
Gene namesi | Name:IRGM Synonyms:IFI1, IRGM1, LRG47 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:29597, IRGM |
MIMi | 608212, gene |
neXtProti | NX_A1A4Y4 |
VEuPathDBi | HostDB:ENSG00000237693.4 |
Subcellular locationi
Golgi apparatus
- Golgi apparatus membrane By similarity
Plasma membrane
- Cell membrane By similarity
Other locations
- phagosome membrane By similarity
- autophagosome membrane By similarity
- phagocytic cup By similarity
Note: Behaves like an integral membrane protein. Recruited to the plasma membrane around forming phagocytic cups, it remains associated with maturing autophagosomes. Preferentially associated with cis- and medial-Golgi.By similarity
Cytosol
- cytosol Source: UniProtKB
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: GO_Central
Golgi apparatus
- Golgi apparatus Source: UniProtKB
- Golgi membrane Source: UniProtKB
Mitochondrion
- mitochondrion Source: UniProtKB
Plasma Membrane
- phagocytic cup Source: UniProtKB-SubCell
Other locations
- autophagosome membrane Source: UniProtKB-SubCell
- cell projection Source: UniProtKB-KW
- phagocytic vesicle membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasmic vesicle, Golgi apparatus, MembranePathology & Biotechi
Involvement in diseasei
Inflammatory bowel disease 19 (IBD19)3 Publications
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMOrganism-specific databases
DisGeNETi | 345611 |
MalaCardsi | IRGM |
MIMi | 612278, phenotype |
OpenTargetsi | ENSG00000237693 |
Orphaneti | 206, NON RARE IN EUROPE: Crohn disease |
PharmGKBi | PA142671652 |
Miscellaneous databases
Pharosi | A1A4Y4, Tbio |
Genetic variation databases
BioMutai | IRGM |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000325749 | 1 – 181 | Immunity-related GTPase family M proteinAdd BLAST | 181 |
Proteomic databases
PaxDbi | A1A4Y4 |
PRIDEi | A1A4Y4 |
ProteomicsDBi | 98 |
PTM databases
iPTMneti | A1A4Y4 |
PhosphoSitePlusi | A1A4Y4 |
Expressioni
Tissue specificityi
Widely expressed (at protein level). Expressed in several tissues including colon, small bowel and peripheral blood leukocytes.2 Publications
Inductioni
Not up-regulated by IFNG/IFN-gamma.1 Publication
Gene expression databases
Bgeei | ENSG00000237693, Expressed in calcaneal tendon and 101 other tissues |
ExpressionAtlasi | A1A4Y4, baseline and differential |
Organism-specific databases
HPAi | ENSG00000237693, Tissue enhanced (blood) |
Interactioni
Binary interactionsi
A1A4Y4
With | #Exp. | IntAct |
---|---|---|
OPTN [Q96CV9] | 3 | EBI-20844678,EBI-748974 |
GO - Molecular functioni
- BH3 domain binding Source: UniProtKB
- CARD domain binding Source: UniProtKB
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 131358, 20 interactors |
IntActi | A1A4Y4, 2 interactors |
STRINGi | 9606.ENSP00000428220 |
Miscellaneous databases
RNActi | A1A4Y4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 32 – 181 | IRG-type GPROSITE-ProRule annotationAdd BLAST | 150 |
Domaini
The G5 motif of the IRG-type G domain is missing because the IRGM protein is truncated in anthropoids.
Sequence similaritiesi
Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.PROSITE-ProRule annotationCurated
Phylogenomic databases
eggNOGi | ENOG502QS9R, Eukaryota |
GeneTreei | ENSGT00950000183007 |
HOGENOMi | CLU_015342_0_0_1 |
InParanoidi | A1A4Y4 |
OMAi | EMQFNQY |
OrthoDBi | 688334at2759 |
PhylomeDBi | A1A4Y4 |
Family and domain databases
InterProi | View protein in InterPro IPR030385, G_IRG_dom IPR007743, Immunity-related_GTPase-like IPR027417, P-loop_NTPase |
Pfami | View protein in Pfam PF05049, IIGP, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in PROSITE PS51716, G_IRG, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
A1A4Y4-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEAMNVEKAS ADGNLPEVIS NIKETLKIVS RTPVNITMAG DSGNGMSTFI
60 70 80 90 100
SALRNTGHEG KASPPTELVK ATQRCASYFS SHFSNVVLWD LPGTGSATTT
110 120 130 140 150
LENYLMEMQF NRYDFIMVAS AQFSMNHVML AKTAEDMGKK FYIVWTKLDM
160 170 180
DLSTGALPEV QLLQIRENVL ENLQKERVCE Y
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketH0YBM2 | H0YBM2_HUMAN | Immunity-related GTPase family M pr... | IRGM | 71 | Annotation score: |
Sequence cautioni
The sequence AAI28169 differs from that shown. Reason: Erroneous initiation.Curated
The sequence EAW61704 differs from that shown. Reason: Erroneous initiation.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_039899 | 17 | E → D1 PublicationCorresponds to variant dbSNP:rs180802994Ensembl. | 1 | |
Natural variantiVAR_039900 | 94 | T → K1 PublicationCorresponds to variant dbSNP:rs72553867Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | EU742619 mRNA Translation: ACF21844.1 FJ824056 Genomic DNA Translation: ACO88909.1 CH471062 Genomic DNA Translation: EAW61704.1 Different initiation. BC128167 mRNA Translation: AAI28168.1 BC128168 mRNA Translation: AAI28169.1 Different initiation. |
CCDSi | CCDS47313.1 |
RefSeqi | NP_001139277.1, NM_001145805.1 |
Genome annotation databases
Ensembli | ENST00000522154; ENSP00000428220; ENSG00000237693 |
GeneIDi | 345611 |
KEGGi | hsa:345611 |
UCSCi | uc010jhk.3, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | EU742619 mRNA Translation: ACF21844.1 FJ824056 Genomic DNA Translation: ACO88909.1 CH471062 Genomic DNA Translation: EAW61704.1 Different initiation. BC128167 mRNA Translation: AAI28168.1 BC128168 mRNA Translation: AAI28169.1 Different initiation. |
CCDSi | CCDS47313.1 |
RefSeqi | NP_001139277.1, NM_001145805.1 |
3D structure databases
SMRi | A1A4Y4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 131358, 20 interactors |
IntActi | A1A4Y4, 2 interactors |
STRINGi | 9606.ENSP00000428220 |
PTM databases
iPTMneti | A1A4Y4 |
PhosphoSitePlusi | A1A4Y4 |
Genetic variation databases
BioMutai | IRGM |
Proteomic databases
PaxDbi | A1A4Y4 |
PRIDEi | A1A4Y4 |
ProteomicsDBi | 98 |
Protocols and materials databases
Antibodypediai | 28102, 273 antibodies |
Genome annotation databases
Ensembli | ENST00000522154; ENSP00000428220; ENSG00000237693 |
GeneIDi | 345611 |
KEGGi | hsa:345611 |
UCSCi | uc010jhk.3, human |
Organism-specific databases
CTDi | 345611 |
DisGeNETi | 345611 |
GeneCardsi | IRGM |
HGNCi | HGNC:29597, IRGM |
HPAi | ENSG00000237693, Tissue enhanced (blood) |
MalaCardsi | IRGM |
MIMi | 608212, gene 612278, phenotype |
neXtProti | NX_A1A4Y4 |
OpenTargetsi | ENSG00000237693 |
Orphaneti | 206, NON RARE IN EUROPE: Crohn disease |
PharmGKBi | PA142671652 |
VEuPathDBi | HostDB:ENSG00000237693.4 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QS9R, Eukaryota |
GeneTreei | ENSGT00950000183007 |
HOGENOMi | CLU_015342_0_0_1 |
InParanoidi | A1A4Y4 |
OMAi | EMQFNQY |
OrthoDBi | 688334at2759 |
PhylomeDBi | A1A4Y4 |
Enzyme and pathway databases
PathwayCommonsi | A1A4Y4 |
Miscellaneous databases
BioGRID-ORCSi | 345611, 2 hits in 990 CRISPR screens |
ChiTaRSi | IRGM, human |
GeneWikii | IRGM |
GenomeRNAii | 345611 |
Pharosi | A1A4Y4, Tbio |
PROi | PR:A1A4Y4 |
RNActi | A1A4Y4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000237693, Expressed in calcaneal tendon and 101 other tissues |
ExpressionAtlasi | A1A4Y4, baseline and differential |
Family and domain databases
InterProi | View protein in InterPro IPR030385, G_IRG_dom IPR007743, Immunity-related_GTPase-like IPR027417, P-loop_NTPase |
Pfami | View protein in Pfam PF05049, IIGP, 1 hit |
SUPFAMi | SSF52540, SSF52540, 1 hit |
PROSITEi | View protein in PROSITE PS51716, G_IRG, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | IRGM_HUMAN | |
Accessioni | A1A4Y4Primary (citable) accession number: A1A4Y4 Secondary accession number(s): B3VEX0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 18, 2008 |
Last sequence update: | March 18, 2008 | |
Last modified: | April 7, 2021 | |
This is version 117 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families