Medicine:AFF2
 Generic protein structure example |
AF4/FMR2 family member 2 is a protein that in humans is encoded by the AFF2 gene.[1] Mutations in AFF2 are implicated in cases of breast cancer.[2]
CCG repeat expansions in this gene are associated with X-linked intellectual disability and specifically a syndrome known as Fragile XE mental retardation (FRAXE). FRAXE is one of the most common forms of non-syndromic X-linked intellectual disability. The gene is also known as FMR2 (Fragile Mental Retardation 2) after this condition.[3]
Genomics
This gene is located on the long arm of chromosome X (Xq27.3-Xq28) It has 22 exons spanning at least 500 kb. Alternative splicing may occur and involve exons 2, 3, 5, 7 and 21. The normal encoded protein is 1311 codons in length. It is expressed as an 8.7 kilobase transcript in the placenta and adult brain.[citation needed]
The normal 5' untranslated region has 10-35 CCG repeats and more frequently 15–20. Pathogenic expansions have typically over 200 repeats and are methylated.[citation needed]
This gene belongs to the AFF family of genes which currently has four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31.[4] All AFF proteins are localized in the nucleus and have a role as transcriptional activators with a positive action on RNA elongation. AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31 localize in nuclear speckles (subnuclear structures considered to be storage/modification sites of pre-mRNA splicing factors) and are able to bind RNA with a high apparent affinity for the G-quadruplex structure. They appear to modulate alternative splicing via the interaction with the G-quadruplex RNA-forming structure.
The other members of this family have been reported to form fusion genes as a consequence of chromosome translocations and are involved in the pathogenesis of myeloid/lymphoid or mixed lineage leukemia.
References
- ↑ "Entrez Gene: AFF2 AF4/FMR2 family, member 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2334.
- ↑ The Cancer Genome Atlas Network (October 2012). "Comprehensive molecular portraits of human breast tumours". Nature 490 (7418): 61–70. doi:10.1038/nature11412. PMID 23000897. Bibcode: 2012Natur.490...61T.
- ↑ "Familial intellectual disability and autistic behavior caused by a small FMR2 gene deletion". American Journal of Medical Genetics. Part A 155A (8): 2003–7. August 2011. doi:10.1002/ajmg.a.34122. PMID 21739600.
- ↑ "Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability". Human Molecular Genetics 20 (10): 1873–85. May 2011. doi:10.1093/hmg/ddr069. PMID 21330300.
Further reading
- "FRAXE and mental retardation". Journal of Medical Genetics 32 (3): 162–9. March 1995. doi:10.1136/jmg.32.3.162. PMID 7783162.
- "Identification of the gene FMR2, associated with FRAXE mental retardation". Nature Genetics 13 (1): 105–8. May 1996. doi:10.1038/ng0596-105. PMID 8673085.
- "Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island". Nature Genetics 13 (1): 109–13. May 1996. doi:10.1038/ng0596-109. PMID 8673086.
- "A candidate gene for mild mental handicap at the FRAXE fragile site". Human Molecular Genetics 5 (2): 275–82. February 1996. doi:10.1093/hmg/5.2.275. PMID 8824884.
- "FMR2 expression in families with FRAXE mental retardation". Human Molecular Genetics 6 (3): 435–41. March 1997. doi:10.1093/hmg/6.3.435. PMID 9147647.
- "Gene structure and subcellular localization of FMR2, a member of a new family of putative transcription activators". Genomics 44 (2): 201–13. September 1997. doi:10.1006/geno.1997.4867. PMID 9299237.
- "Expression of the murine homologue of FMR2 in mouse brain and during development". Human Molecular Genetics 7 (3): 441–8. March 1998. doi:10.1093/hmg/7.3.441. PMID 9467002.
- "Characterisation and expression of a large, 13.7 kb FMR2 isoform". European Journal of Human Genetics 7 (2): 157–62. 1999. doi:10.1038/sj.ejhg.5200279. PMID 10196698.
- "Microdeletions in FMR2 may be a significant cause of premature ovarian failure". Journal of Medical Genetics 36 (10): 767–70. October 1999. doi:10.1136/jmg.36.10.767. PMID 10528856.
- "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America 97 (7): 3491–6. March 2000. doi:10.1073/pnas.97.7.3491. PMID 10737800. Bibcode: 2000PNAS...97.3491D.
- "FRAXE mutation in a mentally retarded subject and in his phenotypically normal twin brother". European Journal of Human Genetics 8 (3): 157–62. March 2000. doi:10.1038/sj.ejhg.5200425. PMID 10780779.
- "Implication of screening for FMR1 and FMR2 gene mutation in individuals with nonspecific mental retardation in Taiwan". Diagnostic Molecular Pathology 9 (2): 75–80. June 2000. doi:10.1097/00019606-200006000-00002. PMID 10850542.
- "Does a peculiar EEG pattern exist also for FRAXE mental retardation?". Clinical Neurophysiology 111 (9): 1632–6. September 2000. doi:10.1016/S1388-2457(00)00367-9. PMID 10964075.
- "Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator". Journal of Human Genetics 46 (5): 251–9. 2001. doi:10.1007/s100380170074. PMID 11355014.
- "Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees". Molecular Biology and Evolution 20 (8): 1281–9. August 2003. doi:10.1093/molbev/msg134. PMID 12777533.
- "Mapping of an origin of DNA replication in the promoter of fragile X gene FMR1". Experimental and Molecular Pathology 82 (2): 190–6. April 2007. doi:10.1016/j.yexmp.2006.10.004. PMID 17196195.
External links
- Human AFF2 genome location and AFF2 gene details page in the UCSC Genome Browser.
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