CYFIP2

Cytoplasmic FMR1-interacting protein 2 is a protein that in humans is encoded by the CYFIP2 gene.[5][6] Cytoplasmic FMR1 interacting protein is a 1253 amino acid long protein and is highly conserved sharing 99% sequence identity to the mouse protein.[5][7] It is expressed mainly in brain tissues, white blood cells and the kidney.[8]

CYFIP2
Identifiers
Aliases	CYFIP2, PIR121, cytoplasmic FMR1 interacting protein 2, EIEE65
External IDs	OMIM: 606323 MGI: 1924134 HomoloGene: 7936 GeneCards: CYFIP2
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q33.3 Start 157,266,079 bp[1] End 157,395,595 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B1.1 Start 46,193,850 bp[2] End 46,312,859 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding • RNA 7-methylguanosine cap binding Cellular component • cytoplasm • perinuclear region of cytoplasm • neuron projection • cytosol • cell junction • synapse • extracellular exosome • membrane • cell nucleus • SCAR complex Biological process • vascular endothelial growth factor receptor signaling pathway • activation of cysteine-type endopeptidase activity • cell adhesion • Fc-gamma receptor signaling pathway involved in phagocytosis • positive regulation of proteolysis • apoptotic process • neuron projection development • positive regulation of neurotrophin TRK receptor signaling pathway • dendrite extension • cell-cell adhesion • cell morphogenesis • axon guidance • cell projection assembly Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	26999	76884
Ensembl	ENSG00000055163	ENSMUSG00000020340
UniProt	Q96F07	Q5SQX6
RefSeq (mRNA)	NM_001037332 NM_001037333 NM_001291721 NM_001291722 NM_014376	NM_001252459 NM_001252460 NM_133769
RefSeq (protein)	NP_001032410 NP_001278650 NP_001278651 NP_055191	NP_001239388 NP_001239389 NP_598530
Location (UCSC)	Chr 5: 157.27 – 157.4 Mb	Chr 11: 46.19 – 46.31 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Interactions

CYFIP2 has been shown to interact with FMR1.[5][9] CYFIP2 is a p-53 inducible protein[10] and also interacts with the Fragile=X mental retardation protein.[11]

RNA editing

The pre-mRNA of this protein is subject to RNA editing.[12] The editing site was previously recorded as a single nucleotide polymorphism (rs3207362) in the dbSNP.[12]

Type

A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3 with ADAR1 and ADAR2 being the only enzymatically active members. ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR 2 are widely expressed in tissues while ADAR3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).

Site

An editing site was found in the pre-mRNA of this protein. The substitution occurs within amino acid position 320 in humans and also in mice. A possible double stranded RNA region has not been detected for this pre-mRNA.[12] No double stranded region required by ADARs has predicted. Immunoprecipitation experiments and RNA interference have shown that ADAR 2 is likely to be the main editing enzyme for this site with ADAR 1 having a minor role.[13][14]

Regulation

Editing seems to be differentially regulated in different tissues. The highest level of editing occurs in the cerebellum with lower frequency of editing detected in human lung, prostrate and uterus tissues. Editing frequency varies from 30-85% depending on tissue.[12][13]{[14] There is some evidence for a decrease in CYFIP2 editing with increased age.[15]

Conservation

Editing of the pre-mRNA of this gene has been detected in mouse and chicken.[12]

Effects of RNA editing

Structural

Editing results in a codon change resulting in a glutamic acid being translated instead of a lysine.[12]

Functional

Currently unknown but editing may have role in regulation of apoptotic functions of this protein. It is thought that since the protein is p53 inducible that the protein may be pro-apopototic. Also ADAR1 knock out mice show increase in apoptosis which indicates editing may be involved in regulation of the cellular process.[10][12]

References

1. GRCh38: Ensembl release 89: ENSG00000055163 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020340 - 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. Schenck A, Bardoni B, Moro A, Bagni C, Mandel JL (Jul 2001). "A highly conserved protein family interacting with the fragile X genetic condition protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P". Proc Natl Acad Sci U S A. 98 (15): 8844–9. doi:10.1073/pnas.151231598. PMC 37523. PMID 11438699.
6. "Entrez Gene: CYFIP2 cytoplasmic FMR1 interacting protein 2".
7. https://www.genecards.org/cgi-bin/carddisp.pl?gene=GRIA4
8. Su AI, Wiltshire T, Batalov S, et al. (April 2004). "A gene atlas of the mouse and human protein-encoding transcriptomes". Proc. Natl. Acad. Sci. U.S.A. 101 (16): 6062–7. doi:10.1073/pnas.0400782101. PMC 395923. PMID 15075390.
9. Bardoni B, Castets M, Huot ME, Schenck A, Adinolfi S, Corbin F, Pastore A, Khandjian EW, Mandel JL (July 2003). "82-FIP, a novel FMRP (fragile X mental retardation protein) interacting protein, shows a cell cycle-dependent intracellular localization". Hum. Mol. Genet. 12 (14): 1689–98. doi:10.1093/hmg/ddg181. PMID 12837692.
10. Saller E, Tom E, Brunori M, et al. (August 1999). "Increased apoptosis induction by 121F mutant p53". EMBO J. 18 (16): 4424–37. doi:10.1093/emboj/18.16.4424. PMC 1171517. PMID 10449408.
11. Schenck, A., Bardoni, B., Moro, A., Bagni, C., Mandel, J.-L. (2001) Proceedings of the National Academy of Sciences of the United States of America, 98, 8844-8849.
12. Levanon EY, Hallegger M, Kinar Y, Shemesh R, Djinovic-Carugo K, Rechavi G, Jantsch MF, Eisenberg E (2005). "Evolutionarily conserved human targets of adenosine to inosine RNA editing". Nucleic Acids Res. 33 (4): 1162–8. doi:10.1093/nar/gki239. PMC 549564. PMID 15731336.
13. Riedmann EM, Schopoff S, Hartner JC, Jantsch MF (June 2008). "Specificity of ADAR-mediated RNA editing in newly identified targets". RNA. 14 (6): 1110–8. doi:10.1261/rna.923308. PMC 2390793. PMID 18430892.
14. Nishimoto Y, Yamashita T, Hideyama T, Tsuji S, Suzuki N, Kwak S (June 2008). "Determination of editors at the novel A-to-I editing positions". Neurosci. Res. 61 (2): 201–6. doi:10.1016/j.neures.2008.02.009. PMID 18407364.
15. Nicholas A, de Magalhaes JP, Kraytsberg Y, Richfield EK, Levanon EY, Khrapko K (June 2010). "Age-related gene-specific changes of A-to-I mRNA editing in the human brain". Mech. Ageing Dev. 131 (6): 445–7. doi:10.1016/j.mad.2010.06.001. PMC 2915444. PMID 20538013.

External links

• Human CYFIP2 genome location and CYFIP2 gene details page in the UCSC Genome Browser.

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Kitamura T, Kitamura Y, Yonezawa K, et al. (1996). "Molecular cloning of p125Nap1, a protein that associates with an SH3 domain of Nck". Biochem. Biophys. Res. Commun. 219 (2): 509–14. doi:10.1006/bbrc.1996.0264. PMID 8605018.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Witke W, Podtelejnikov AV, Di Nardo A, et al. (1998). "In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly". EMBO J. 17 (4): 967–76. doi:10.1093/emboj/17.4.967. PMC 1170446. PMID 9463375.
• Saller E, Tom E, Brunori M, et al. (1999). "Increased apoptosis induction by 121F mutant p53". EMBO J. 18 (16): 4424–37. doi:10.1093/emboj/18.16.4424. PMC 1171517. PMID 10449408.
• Hirosawa M, Nagase T, Ishikawa K, et al. (2000). "Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain". DNA Res. 6 (5): 329–36. doi:10.1093/dnares/6.5.329. PMID 10574461.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Wiemann S, Weil B, Wellenreuther R, et al. (2001). "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Eden S, Rohatgi R, Podtelejnikov AV, et al. (2002). "Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck". Nature. 418 (6899): 790–3. doi:10.1038/nature00859. PMID 12181570.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Salazar MA, Kwiatkowski AV, Pellegrini L, et al. (2004). "Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton". J. Biol. Chem. 278 (49): 49031–43. doi:10.1074/jbc.M308104200. PMID 14506234.
• Brajenovic M, Joberty G, Küster B, et al. (2004). "Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network". J. Biol. Chem. 279 (13): 12804–11. doi:10.1074/jbc.M312171200. PMID 14676191.
• Innocenti M, Zucconi A, Disanza A, et al. (2004). "Abi1 is essential for the formation and activation of a WAVE2 signalling complex". Nat. Cell Biol. 6 (4): 319–27. doi:10.1038/ncb1105. PMID 15048123.
• Mayne M, Moffatt T, Kong H, et al. (2004). "CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion". Eur. J. Immunol. 34 (4): 1217–27. doi:10.1002/eji.200324726. PMID 15048733.
• Jin J, Smith FD, Stark C, et al. (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Curr. Biol. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to Biology: A Functional Genomics Pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Levanon EY, Hallegger M, Kinar Y, et al. (2005). "Evolutionarily conserved human targets of adenosine to inosine RNA editing". Nucleic Acids Res. 33 (4): 1162–8. doi:10.1093/nar/gki239. PMC 549564. PMID 15731336.
• Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.