Interferon-inducible GTPase 5

Interferon-inducible GTPase 5 also known as immunity-related GTPase cinema 1 (IRGC1) is an enzyme that in humans is coded by the IRGC gene.[5][6] It is predicted to behave like other proteins in the p47-GTPase-like and IRG families. It is most expressed in the testis.[6][7]

IRGC
Identifiers
Aliases	IRGC, CINEMA, IFGGE, IRGC1, Iigp5, R30953_1, immunity related GTPase cinema
External IDs	MGI: 2685948 HomoloGene: 10486 GeneCards: IRGC
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.31 Start 43,716,076 bp[1] End 43,720,021 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 A3 Start 24,431,922 bp[2] End 24,452,297 bp[2]
Orthologs
Species	Human	Mouse
Entrez	56269	210145
Ensembl	ENSG00000124449	ENSMUSG00000062028
UniProt	Q6NXR0	Q8C262
RefSeq (mRNA)	NM_019612	NM_199013 NM_001358033 NM_001358034
RefSeq (protein)	NP_062558	n/a
Location (UCSC)	Chr 19: 43.72 – 43.72 Mb	Chr 7: 24.43 – 24.45 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Gene

NCBI IRGC gene location on chromosome, includes nearby genes.

IRGC is located on chromosome 19 at position 19q13.31 and contains two exons.[5][8] It is on the forward strand and is upstream of Phospholipase A2 Inhibitor and Ly6/PLAUR Domain-Containing Protein-Like (LOC105372412) and downstream of Nonsense Mediated mRNA Decay Factor (SMG9).[7]

Homology and Evolution

Paralog

There is one paralog for IRGC named IRGM. IRGM, or immunity related GTPase M, is associated with intracellular defense.[9][10] Both are part of the p47-GTPase-like family and the P-loop NTPase domain superfamily. The paralog has 12% identity to IRGC.

Orthologs

Sample of eukaryotes with orthologous sequences for IRGC, includes sequence identity, estimated date of divergence, and color coded for animal class.

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.[11]

Evolution

For three genes - IRGC, beta-hemoglobin, and cytochrome c, several distant orthologs of the same type were compared to human sequences for their percent identity. This was plotted and compared to time in millions of years. IRGC is seen to have diverged more rapidly than the other genes.

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.[12] It is 1521 base pairs long and starts at base pair 43714694.[12] It is conserved on all 7 orthologous sequences tested and has the most association with testis, at 8.090 tpm.[12] Of the six potential transcripts, GXT_26231691 had the most CAGE tags.[12] Testis was labeled on 839 of 873 CAGE tags.[12]

mRNA

The most common transcript for IRGC is 1596 base pairs long and has the accession number NM_019612.[13] Other transcripts include isoform X1, XM_005259058, isoform X2, XM_011527118, and isoform X3, XM_006723283.[14][15][16]

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.[17] It is unlikely to have a signal peptide.[18][19] 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.[20][21][17][18]

Secondary Structure

The secondary structure of the protein is expected to have more alpha helices than beta sheets,[22][23] Close orthologs were observed to have highly similar secondary structures.

Tertiary Structure

NCBI X-ray crystallography structure for ITQD_A, Chain A for Interferon-inducible GTPase found in mice. It is predicted to be similar in structure to interferon-inducible GTPase 5.

The tertiary structure can be predicted with related X-ray crystallography structures. There was one hit for the protein, ligp1 [Mus musculus], which had an E-value of 2E-76 and an 34% identity over 82% of the protein sequence.[24]

Post-Translational Modifications

The protein is expected to be GTP and magnesium binding as it contains several related binding sites.[6] It also has predicted homodimer interface regions for polypeptide binding between residues 153 and 163.[6] There are two likely phosphine interaction sites at Ser247 and Ser304.[6] Phosphorylation is expected to be common on serines and a few threonines throughout the sequence, though more are likely after residue 330.[25] A few glyosylation and glycation sites are predicted, though some of the predictions overlap with potential phosphorylation sites.[26][27]

Subcellular Location

The protein may be non-cytoplasmic though further localization is unknown at this time.[18][28]

Clinical Significance

Expression

Interferon-inducible GTPase 5 is most highly expressed in the testis.[6] The use of two antibodies (HPA046769 and HPA060064) demonstrated higher expression in elongated spermatids than round spermatids.[29] Leydig cells, spermatogonia, and preleptotene spermatocytes were reported to have low expression.[29] There was low to medium expression observed with both antibodies in the duodenum, small intestine, appendix, and kidney.[30] There may be some expression in myocytes and the thyroid, parathyroid, and adrenal glands.[30]

Pathology

Expression has been observed to decrease under cancer conditions.[31][32] There is unknown clinical association with transcript variations both in the 3' and 5' UTR and within the coding region.[33]

1. GRCh38: Ensembl release 89: ENSG00000124449 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000062028 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Immunity-related GTPase family, cinema". Retrieved 2011-12-16.
6. "interferon-inducible GTPase 5 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-05.
7. "IRGC immunity related GTPase cinema [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-06.
8. "Gene: IRGC (ENSG00000124449) - Summary - Homo sapiens - Ensembl genome browser 96". uswest.ensembl.org. Retrieved 2019-05-05.
9. Singh SB, Davis AS, Taylor GA, Deretic V (September 2006). "Human IRGM induces autophagy to eliminate intracellular mycobacteria". Science. 313 (5792): 1438–41. doi:10.1126/science.1129577. PMID 16888103.
10. Bekpen C, Xavier RJ, Eichler EE (December 2010). "Human IRGM gene "to be or not to be"". Seminars in Immunopathology. 32 (4): 437–44. doi:10.1007/s00281-010-0224-x. PMID 20737271.
11. "Clustal Omega < Multiple Sequence Alignment < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-05-06.
12. "Genomatix: Retrieve and analyze promoters: Query Input". www.genomatix.de. Retrieved 2019-05-06.
13. "Homo sapiens immunity related GTPase cinema (IRGC), mRNA". 2019-05-02. Cite journal requires |journal= (help)
14. "PREDICTED: Homo sapiens immunity related GTPase cinema (IRGC), transcript variant X1, mRNA". 2018-03-26. Cite journal requires |journal= (help)
15. "PREDICTED: Homo sapiens immunity related GTPase cinema (IRGC), transcript variant X2, mRNA". 2018-03-26. Cite journal requires |journal= (help)
16. "PREDICTED: Homo sapiens immunity related GTPase cinema (IRGC), transcript variant X3, mRNA". 2018-03-26. Cite journal requires |journal= (help)
17. "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-05-05.
18. "Phobius". phobius.sbc.su.se. Retrieved 2019-05-05.
19. "TOPCONS: Consensus prediction of membrane protein topology and signal peptides". topcons.cbr.su.se. Retrieved 2019-05-05.
20. "TMpred Server". embnet.vital-it.ch. Retrieved 2019-05-05.
21. "TMHMM Server, v. 2.0". www.cbs.dtu.dk. Retrieved 2019-05-05.
22. "NPS@ : GOR4 secondary structure prediction". npsa-prabi.ibcp.fr. Retrieved 2019-05-05.
23. "COILS Server". embnet.vital-it.ch. Retrieved 2019-05-05.
24. "1TQD: Crystal Structure Of Iigp1: A Paradigm For Interferon Inducible P47 Resistance Gtpases". www.ncbi.nlm.nih.gov. Retrieved 2019-05-05.
25. "NetPhos 3.1 Server". www.cbs.dtu.dk. Retrieved 2019-05-05.
26. "NetOGlyc 4.0 Server". www.cbs.dtu.dk. Retrieved 2019-05-05.
27. "NetGlycate 1.0 Server". www.cbs.dtu.dk. Retrieved 2019-05-05.
28. "SOSUI WWW Server". harrier.nagahama-i-bio.ac.jp. Retrieved 2019-05-05.
29. "Tissue expression of IRGC - Staining in testis - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2019-05-12.
30. "Tissue expression of IRGC - Primary data - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2019-05-12.
31. "Expression of IRGC in cancer - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2019-05-12.
32. "GDS2842 / 38579_at". www.ncbi.nlm.nih.gov. Retrieved 2019-05-12.
33. "SNP linked to Gene (geneID:56269) Via Contig Annotation". www.ncbi.nlm.nih.gov. Retrieved 2019-05-12.

References

Further reading