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Protein

Immunity-related GTPase family M protein

Gene

IRGM

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi41 – 48GTPBy similarity8
Nucleotide bindingi66 – 70GTPBy similarity5
Nucleotide bindingi147 – 149GTPBy similarity3

GO - Molecular functioni

  • BH3 domain binding Source: UniProtKB
  • CARD domain binding Source: UniProtKB
  • GTP binding Source: UniProtKB-KW
  • hydrolase activity Source: UniProtKB-KW
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activator activity Source: UniProtKB

GO - Biological processi

  • autophagosome assembly Source: UniProtKB
  • autophagy of host cells involved in interaction with symbiont Source: UniProtKB
  • CAMKK-AMPK signaling cascade Source: UniProtKB
  • cellular response to lipopolysaccharide Source: UniProtKB
  • cellular response to virus Source: UniProtKB
  • 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 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 assembly Source: UniProtKB
  • regulation of protein complex stability Source: UniProtKB

Keywordsi

Molecular functionHydrolase
Biological processAutophagy, Immunity, Inflammatory response, Innate immunity
LigandGTP-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000237693.4.
HGNCiHGNC:29597. IRGM.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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.
See also OMIM:612278

Organism-specific databases

DisGeNETi345611.
MalaCardsiIRGM.
MIMi612278. phenotype.
OpenTargetsiENSG00000237693.
Orphaneti206. Crohn disease.
PharmGKBiPA142671652.

Polymorphism and mutation databases

BioMutaiIRGM.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003257491 – 181Immunity-related GTPase family M proteinAdd BLAST181

Proteomic databases

PaxDbiA1A4Y4.
PRIDEiA1A4Y4.

PTM databases

iPTMnetiA1A4Y4.
PhosphoSitePlusiA1A4Y4.

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

BgeeiENSG00000237693.
CleanExiHS_IRGM.
ExpressionAtlasiA1A4Y4. baseline and differential.

Interactioni

GO - Molecular functioni

  • BH3 domain binding Source: UniProtKB
  • CARD domain binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi131358. 13 interactors.
STRINGi9606.ENSP00000428220.

Structurei

3D structure databases

ProteinModelPortaliA1A4Y4.
SMRiA1A4Y4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 181IRG-type GAdd BLAST150

Domaini

The G5 motif of the IRG-type G domain is missing because the IRGM protein is truncated in anthropoids.

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410J94V. Eukaryota.
ENOG4111A9F. LUCA.
GeneTreeiENSGT00390000014733.
HOGENOMiHOG000200899.
HOVERGENiHBG102117.
InParanoidiA1A4Y4.
KOiK14139.
OMAiMVASAQF.
OrthoDBiEOG091G0L14.
PhylomeDBiA1A4Y4.

Family and domain databases

InterProiView protein in InterPro
IPR030385. G_IRG_dom.
IPR007743. Immunity-related_GTPase-like.
IPR027417. P-loop_NTPase.
PfamiView protein in Pfam
PF05049. IIGP. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS51716. G_IRG. 1 hit.

Sequencei

Sequence statusi: Complete.

A1A4Y4-1 [UniParc]FASTAAdd 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

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 keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03989917E → D1 PublicationCorresponds to variant dbSNP:rs180802994Ensembl.1
Natural variantiVAR_03990094T → 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.
CCDSiCCDS47313.1.
RefSeqiNP_001139277.1. NM_001145805.1.
UniGeneiHs.519680.
Hs.652148.

Genome annotation databases

EnsembliENST00000522154; ENSP00000428220; ENSG00000237693.
GeneIDi345611.
KEGGihsa:345611.
UCSCiuc010jhk.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIRGM_HUMAN
AccessioniPrimary (citable) accession number: A1A4Y4
Secondary accession number(s): B3VEX0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 18, 2008
Last modified: September 27, 2017
This is version 96 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

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