IRX3

Iroquois-class homeodomain protein IRX-3, also known as Iroquois homeobox protein 3, is a protein that in humans is encoded by the IRX3 gene.[5]

IRX3
Identifiers
Aliases	IRX3, IRX-1, IRXB1, iroquois homeobox 3
External IDs	OMIM: 612985 MGI: 1197522 HomoloGene: 7385 GeneCards: IRX3
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q12.2 Start 54,283,304 bp[1] End 54,286,787 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 C5|8 44.55 cM Start 91,798,525 bp[2] End 91,802,067 bp[2]
Gene ontology Molecular function • sequence-specific DNA binding • DNA binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component • cytoplasm • axon • cell nucleus Biological process • multicellular organism development • mesoderm development • specification of loop of Henle identity • metanephros development • regulation of transcription, DNA-templated • negative regulation of neuron differentiation • positive regulation of neuron differentiation • transcription, DNA-templated • proximal/distal pattern formation involved in nephron development • regulation of transcription from RNA polymerase II promoter • energy homeostasis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	79191	16373
Ensembl	ENSG00000177508	ENSMUSG00000031734
UniProt	P78415	P81067
RefSeq (mRNA)	NM_024336	NM_001253822 NM_008393
RefSeq (protein)	NP_077312	NP_001240751 NP_032419
Location (UCSC)	Chr 16: 54.28 – 54.29 Mb	Chr 8: 91.8 – 91.8 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

IRX3 is a member of the Iroquois homeobox gene family and plays a role in an early step of neural development.[6] Members of this family appear to play multiple roles during pattern formation of vertebrate embryos.[5][7] Specifically, IRX3 contributes to pattern formation in the spinal cord where it translates a morphogen gradient into transcriptional events, and is directly regulated by NKX2-2.[8]

Clinical significance

Association with obesity

Obesity-associated noncoding sequences within FTO interact with the promoter of IRX3 and FTO in human, mouse, and zebrafish. Obesity-associated single nucleotide polymorphisms are related to the expression of IRX3 (not FTO) in the human brain. A direct connection between the expression of IRX3 and body mass and composition was shown through the decrease in body weight of 25-30% in IRX3-deficient mice. This suggests that IRX3 influences obesity.[9] Manipulation of IRX3 and IRX5 pathways has also been shown to decrease obesity markers in human cell cultures.[10] Genetic variants of FTO and IRX3 genes are in high linkage disequilibrium and are associated with obesity risk.[11]

References

1. GRCh38: Ensembl release 89: ENSG00000177508 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031734 - 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: iroquois homeobox 3".
6. Bellefroid EJ, Kobbe A, Gruss P, Pieler T, Gurdon JB, Papalopulu N (Jan 1998). "Xiro3 encodes a Xenopus homolog of the Drosophila Iroquois genes and functions in neural specification". The EMBO Journal. 17 (1): 191–203. doi:10.1093/emboj/17.1.191. PMC 1170370. PMID 9427753.
7. Lewis MT, Ross S, Strickland PA, Snyder CJ, Daniel CW (Jun 1999). "Regulated expression patterns of IRX-2, an Iroquois-class homeobox gene, in the human breast". Cell and Tissue Research. 296 (3): 549–54. doi:10.1007/s004410051316. PMID 10370142. S2CID 37046813.
8. Lovrics A, Gao Y, Juhász B, Bock I, Byrne HM, Dinnyés A, Kovács KA (November 2014). "Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord". PLOS ONE. 9 (11): e111430. Bibcode:2014PLoSO...9k1430L. doi:10.1371/journal.pone.0111430. PMC 4232242. PMID 25398016.
9. Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gómez-Marín C, et al. (Mar 2014). "Obesity-associated variants within FTO form long-range functional connections with IRX3". Nature. 507 (7492): 371–5. Bibcode:2014Natur.507..371S. doi:10.1038/nature13138. PMC 4113484. PMID 24646999.
10. Claussnitzer M, Dankel S, Kim KH, Quon G, Meuleman W, Haugen C, et al. (Aug 2015). "FTO Obesity Variant Circuitry and Adipocyte Browning in Humans". New England Journal of Medicine. 373 (10): 895–907. doi:10.1056/NEJMoa1502214. PMC 4959911. PMID 26287746. Lay summary – Boston Business Journal (20 Aug 2015).
11. Srivastava A, Mittal B, Prakash J, Srivastava P, Srivastava N, Srivastava N (2015). "Association of FTO and IRX3 genetic variants to obesity risk in north India". Annals of Human Biology. 43 (5): 1–6. doi:10.3109/03014460.2015.1103902. PMID 26440677. S2CID 19868664.

Further reading

• Trynka G, Zhernakova A, Romanos J, Franke L, Hunt KA, Turner G, et al. (Aug 2009). "Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling". Gut. 58 (8): 1078–83. doi:10.1136/gut.2008.169052. PMID 19240061. S2CID 17111427.
• Ragvin A, Moro E, Fredman D, Navratilova P, Drivenes Ø, Engström PG, et al. (Jan 2010). "Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3". Proceedings of the National Academy of Sciences of the United States of America. 107 (2): 775–80. Bibcode:2010PNAS..107..775R. doi:10.1073/pnas.0911591107. PMC 2818943. PMID 20080751.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.