IRGM

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	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
Inferred from mutant phenotypeⁱ
- 25891078
CARD domain binding
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
GTPase activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
GTP binding Source: UniProtKB-KW
protein kinase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 25891078
protein serine/threonine kinase activator activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 28389568

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

autophagosome assembly
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 16888103
autophagy of host cells involved in interaction with symbiont
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 16888103
- 28389568
CAMKK-AMPK signaling cascade
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
cellular response to interferon-beta
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cellular response to lipopolysaccharide
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
cellular response to virus
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 28389568
defense response
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
defense response to bacterium
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 16888103
defense response to Gram-negative bacterium
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
inflammatory response Source: UniProtKB-KW
innate immune response
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 16888103
nucleotide-binding oligomerization domain containing 2 signaling pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
positive regulation of autophagosome maturation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 16888103
positive regulation of autophagy
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
positive regulation of interferon-gamma-mediated signaling pathway
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 16888103
positive regulation of peptidyl-serine phosphorylation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
positive regulation of peptidyl-threonine phosphorylation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
positive regulation of protein phosphorylation
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 28389568
positive regulation of protein serine/threonine kinase activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 28389568
protein destabilization
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
protein lipidation involved in autophagosome assembly
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 28389568
protein stabilization
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
regulation of protein complex assembly
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
regulation of protein complex stability
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Hydrolase
Biological process	Autophagy, Immunity, Inflammatory response, Innate immunity
Ligand	GTP-binding, Nucleotide-binding

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	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 5

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000237693.4
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:29597 IRGM
MIMⁱ	608212 gene
neXtProtⁱ	NX_A1A4Y4

Keywords - Cellular componentⁱ

Cell membrane, Cell projection, Cytoplasmic vesicle, Golgi apparatus, Membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Inflammatory bowel disease 19 (IBD19)3 Publications

Disease susceptibility is associated with variations 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.

Organism-specific databases

DisGeNET More...DisGeNETⁱ	345611
MalaCards human disease database More...MalaCardsⁱ	IRGM
MIMⁱ	612278 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000237693
Orphanetⁱ	206 NON RARE IN EUROPE: Crohn disease
PharmGKBⁱ	PA142671652

Polymorphism and mutation databases

BioMutaⁱ	IRGM

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 71 organ(s), highest expression level in leukocyte
CleanExⁱ	HS_IRGM
ExpressionAtlasⁱ	A1A4Y4 baseline and differential

Interactionⁱ

GO - Molecular functionⁱ

BH3 domain binding
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
CARD domain binding
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 25891078
protein kinase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 25891078

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	131358, 13 interactors
STRINGⁱ	9606.ENSP00000428220

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	A1A4Y4
SMRⁱ	A1A4Y4
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	32 – 181	IRG-type GAdd 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.Curated

Phylogenomic databases

eggNOGⁱ	ENOG410J94V Eukaryota ENOG4111A9F LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000014733
HOGENOMⁱ	HOG000200899
HOVERGENⁱ	HBG102117
InParanoidⁱ	A1A4Y4
KEGG Orthology (KO) More...KOⁱ	K14139
OMAⁱ	TPVNITM
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0L14
PhylomeDBⁱ	A1A4Y4

Family and domain databases

InterProⁱ	View protein in InterPro IPR030385 G_IRG_dom IPR007743 Immunity-related_GTPase-like IPR027417 P-loop_NTPase
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF05049 IIGP, 1 hit
SUPFAMⁱ	SSF52540 SSF52540, 1 hit
PROSITEⁱ	View protein in PROSITE PS51716 G_IRG, 1 hit

Sequence (1+)ⁱ

Sequence statusⁱ: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show all Align All

A1A4Y4-1 [UniParc]FASTA Add to basket

« Hide

        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

Length:181

Mass (Da):20,142

Last modified:March 18, 2008 - v2

Checksum:ⁱD8FB5A6D6968E2EE

GO

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation

	H0YBM2	H0YBM2_HUMAN		Immunity-related GTPase family M pr... Immunity-related GTPase family M protein	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.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS47313.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001139277.1, NM_001145805.1
UniGeneⁱ	Hs.519680 Hs.652148

Genome annotation databases

Ensemblⁱ	ENST00000522154; ENSP00000428220; ENSG00000237693
GeneIDⁱ	345611
KEGGⁱ	hsa:345611
UCSC genome browser More...UCSCⁱ	uc010jhk.3 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
A1A4Y4	Immunity related GTPase M		PANTR		214	UniRef90_A1A4Y4
Immunity related GTPase M		PANPA		195
Immunity-related GTPase M		NOMLE		181
Immunity-related GTPase M		PONPY		181
Immunity related GTPase M		GORGO		181
+9

Protein	Similar proteins		Species	Score	Length	Source
A1A4Y4	Immunity related GTPase M		PANTR		214	UniRef50_A1A4Y4
Immunity related GTPase M		PANPA		195
Immunity-related GTPase M		NOMLE		181
Immunity-related GTPase M		PONPY		181
Immunity related GTPase M		GORGO		181
+21

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
UniGeneⁱ	Hs.519680 Hs.652148

3D structure databases

ProteinModelPortalⁱ	A1A4Y4
SMRⁱ	A1A4Y4
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	131358, 13 interactors
STRINGⁱ	9606.ENSP00000428220

PTM databases

iPTMnetⁱ	A1A4Y4
PhosphoSitePlusⁱ	A1A4Y4

Polymorphism and mutation databases

BioMutaⁱ	IRGM

BioMutaⁱ

IRGM

Proteomic databases

PaxDbⁱ	A1A4Y4
PRIDEⁱ	A1A4Y4
ProteomicsDBⁱ	98

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000522154; ENSP00000428220; ENSG00000237693
GeneIDⁱ	345611
KEGGⁱ	hsa:345611
UCSCⁱ	uc010jhk.3 human

Organism-specific databases

CTDⁱ	345611
DisGeNETⁱ	345611
EuPathDBⁱ	HostDB:ENSG00000237693.4
GeneCardsⁱ	IRGM
H-InvDBⁱ	HIX0032427
HGNCⁱ	HGNC:29597 IRGM
MalaCardsⁱ	IRGM
MIMⁱ	608212 gene 612278 phenotype
neXtProtⁱ	NX_A1A4Y4
OpenTargetsⁱ	ENSG00000237693
Orphanetⁱ	206 NON RARE IN EUROPE: Crohn disease
PharmGKBⁱ	PA142671652
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410J94V Eukaryota ENOG4111A9F LUCA
GeneTreeⁱ	ENSGT00390000014733
HOGENOMⁱ	HOG000200899
HOVERGENⁱ	HBG102117
InParanoidⁱ	A1A4Y4
KOⁱ	K14139
OMAⁱ	TPVNITM
OrthoDBⁱ	EOG091G0L14
PhylomeDBⁱ	A1A4Y4

Miscellaneous databases

GeneWikiⁱ	IRGM
GenomeRNAiⁱ	345611
Protein Ontology More...PROⁱ	PR:A1A4Y4
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000237693 Expressed in 71 organ(s), highest expression level in leukocyte
CleanExⁱ	HS_IRGM
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...

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:	November 7, 2018
	This is version 99 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

Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM

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UniProtKB - A1A4Y4 (IRGM_HUMAN)

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Immunity-related GTPase family M protein

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Golgi apparatus

Plasma membrane

Other locations

Cytosol

Endoplasmic reticulum

Golgi apparatus

Mitochondrion

Plasma Membrane

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ