Interferon-inducible GTPase 5


Interferon-inducible GTPase 5 also known as immunity-related GTPase cinema 1 is an enzyme that in humans is coded by the IRGC gene. It is predicted to behave like other proteins in the p47-GTPase-like and IRG families. It is most expressed in the testis.

Gene

IRGC is located on chromosome 19 at position 19q13.31 and contains two exons. It is on the forward strand and is upstream of Phospholipase A2 Inhibitor and Ly6/PLAUR Domain-Containing Protein-Like and downstream of Nonsense Mediated mRNA Decay Factor.

Homology and Evolution

Paralog

There is one paralog for IRGC named IRGM. IRGM, or immunity related GTPase M, is associated with intracellular defense. Both are part of the p47-GTPase-like family and the P-loop NTPase domain superfamily. The paralog has 12% identity to IRGC.

Orthologs

IRGC was observed to be conserved in all vertebrates. The GTP/Magnesium and polypeptide binding regions and a transmembrane region are fairly conserved between species.

Evolution

IRGC is predicted to have evolved more rapidly than cytochrome c and β-hemoglobin when comparing the percent identity of the same species for each gene over 500 million years. It is likely that IRGC and IRGM diverged 350 to 375 million years ago.

Transcription

Promoter

There was one promoter region, GXP_311825, found for IRGC on chromosome 19. It is 1521 base pairs long and starts at base pair 43714694. It is conserved on all 7 orthologous sequences tested and has the most association with testis, at 8.090 tpm. Of the six potential transcripts, GXT_26231691 had the most CAGE tags. Testis was labeled on 839 of 873 CAGE tags.

mRNA

The most common transcript for IRGC is 1596 base pairs long and has the accession number NM_019612. Other transcripts include isoform X1, XM_005259058, isoform X2, XM_011527118, and isoform X3, XM_006723283.

Protein

Biochemistry

Interferon-inducible GTPase 5 is 463 amino acids long, has a molecular weight of 50.3 kDa, and a predicted isoelectric point of 5.22. It is unlikely to have a signal peptide. A transmembrane region is highly predicted between residues 364 and 384, with the first section of the sequence outside of the membrane and the second section within the membrane.

Secondary Structure

The secondary structure of the protein is expected to have more alpha helices than beta sheets, Close orthologs were observed to have highly similar secondary structures.

Tertiary Structure

The tertiary structure can be predicted with related X-ray crystallography structures. There was one hit for the protein, ligp1 , which had an E-value of 2E-76 and an 34% identity over 82% of the protein sequence.

Post-Translational Modifications

The protein is expected to be GTP and magnesium binding as it contains several related binding sites. It also has predicted homodimer interface regions for polypeptide binding between residues 153 and 163. There are two likely phosphine interaction sites at Ser247 and Ser304. Phosphorylation is expected to be common on serines and a few threonines throughout the sequence, though more are likely after residue 330. A few glyosylation and glycation sites are predicted, though some of the predictions overlap with potential phosphorylation sites.

Subcellular Location

The protein may be non-cytoplasmic though further localization is unknown at this time.

Clinical Significance

Expression

Interferon-inducible GTPase 5 is most highly expressed in the testis. The use of two antibodies demonstrated higher expression in elongated spermatids than round spermatids. Leydig cells, spermatogonia, and preleptotene spermatocytes were reported to have low expression. There was low to medium expression observed with both antibodies in the duodenum, small intestine, appendix, and kidney. There may be some expression in myocytes and the thyroid, parathyroid, and adrenal glands.

Pathology

Expression has been observed to decrease under cancer conditions. There is unknown clinical association with transcript variations both in the 3' and 5' UTR and within the coding region.