RBFOX1

Fox-1 homolog A, also known as ataxin 2-binding protein 1 (A2BP1) or hexaribonucleotide-binding protein 1 (HRNBP1) or RNA binding protein, fox-1 homolog (Rbfox1), is a protein that in humans is encoded by the RBFOX1 gene.[5]

RBFOX1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2ERR, 4ZKA, 2N82
Identifiers
Aliases	RBFOX1, 2BP1, A2BP1, FOX-1, FOX1, HRNBP1, RNA binding protein, fox-1 homolog 1, RNA binding fox-1 homolog 1
External IDs	OMIM: 605104 MGI: 1926224 HomoloGene: 69339 GeneCards: RBFOX1
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p13.3 Start 5,239,802 bp[1] End 7,713,340 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 A1|16 3.34 cM Start 5,885,355 bp[2] End 7,411,526 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein C-terminus binding • GO:0001948 protein binding • mRNA binding • RNA binding • nucleic acid binding Cellular component • cytoplasm • trans-Golgi network • cell nucleus Biological process • regulation of RNA splicing • mRNA processing • regulation of alternative mRNA splicing, via spliceosome • RNA splicing • nervous system development • RNA transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	54715	268859
Ensembl	ENSG00000078328	ENSMUSG00000008658
UniProt	Q9NWB1	Q9JJ43
RefSeq (mRNA)	NM_001142333 NM_001142334 NM_001308117 NM_018723 NM_145891 NM_145892 NM_145893 NM_001364800	NM_021477 NM_183188 NM_001359723 NM_001359724 NM_001359725 NM_001359726 NM_001359728 NM_001359729 NM_001359730
RefSeq (protein)	NP_001135805 NP_001135806 NP_001295046 NP_061193 NP_665898 NP_665899 NP_665900 NP_001351729	NP_067452 NP_899011 NP_001346652 NP_001346653 NP_001346654 NP_001346655 NP_001346657 NP_001346658 NP_001346659
Location (UCSC)	Chr 16: 5.24 – 7.71 Mb	Chr 16: 5.89 – 7.41 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Rbfox1 has an RNA recognition motif that is highly conserved among RNA-binding proteins. Rbfox1, and the related protein Rbfox2, bind the consensus RNA sequence motif (U)GCAUG within introns to exert their functions as alternative splicing factors.[6][7]

Additionally, the Rbfox1/A2BP1 protein binds to the C-terminus of ataxin-2, and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is the gene product of the SCA2 gene which causes familial neurodegenerative diseases. Several alternatively spliced transcript variants have been found for this gene. Some of these variants localize to the nucleus and some other to the cytoplasm. Nuclear variants have a well-established role in tissue specific alternative splicing.[8] Rbfox1 cytoplasmic variants modulate mRNA stability and translation.[9][10] In stressed cells, Rbfox1 has been demonstrated to localize to cytoplasmic stress granules.[11][12]

See also

• Alternative splicing
• RNA-binding protein

References

1. GRCh38: Ensembl release 89: ENSG00000078328 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000008658 - 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: A2BP1 ataxin 2-binding protein 1".
6. Jin, Y. (2003-02-17). "A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG". The EMBO Journal. 22 (4): 905–912. doi:10.1093/emboj/cdg089. ISSN 1460-2075. PMC 145449. PMID 12574126.
7. Ponthier, Julie L.; Schluepen, Christina; Chen, Weiguo; Lersch, Robert A.; Gee, Sherry L.; Hou, Victor C.; Lo, Annie J.; Short, Sarah A.; Chasis, Joel A.; Winkelmann, John C.; Conboy, John G. (2006-03-14). "Fox-2 Splicing Factor Binds to a Conserved Intron Motif to Promote Inclusion of Protein 4.1R Alternative Exon 16". Journal of Biological Chemistry. 281 (18): 12468–12474. doi:10.1074/jbc.m511556200. ISSN 0021-9258. PMID 16537540.
8. Kuroyanagi H (2009). "Fox-1 family of RNA-binding proteins". Cellular and Molecular Life Sciences. 66 (24): 3895–907. doi:10.1007/s00018-009-0120-5. PMC 2777236. PMID 19688295.
9. Carreira-Rosario, Arnaldo; et al. (7 March 2016). "Repression of Pumilio Protein Expression by Rbfox1 Promotes Germ Cell Differentiation". Dev. Cell. 36 (5): 562–571. doi:10.1016/j.devcel.2016.02.010. PMC 4785839. PMID 26954550.
10. Lee JA, Damianov A, Lin CH, Fontes M, Parikshak NN, Anderson ES, Geschwind DH, Black DL, Martin KC (2016). "Cytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes". Neuron. 89 (1): 113–28. doi:10.1016/j.neuron.2015.11.025. PMC 4858412. PMID 26687839.
11. Park, Chungoo; Choi, Sunkyung; Kim, Yong-Eun; Lee, Siyeo; Park, Su-Hyung; Adelstein, Robert S.; Kawamoto, Sachiyo; Kim, Kee K. (2017-09-11). "Stress Granules Contain Rbfox2 with Cell Cycle-related mRNAs". Scientific Reports. 7 (1): 11211. Bibcode:2017NatSR...711211P. doi:10.1038/s41598-017-11651-w. ISSN 2045-2322. PMC 5593835. PMID 28894257.
12. Jain, Saumya; Wheeler, Joshua R.; Walters, Robert W.; Agrawal, Anurag; Barsic, Anthony; Parker, Roy (2016-01-28). "ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure". Cell. 164 (3): 487–498. doi:10.1016/j.cell.2015.12.038. ISSN 1097-4172. PMC 4733397. PMID 26777405.

Further reading

• Gallagher TL, Arribere JA, Geurts PA, Exner CR, McDonald KL, Dill KK, Marr HL, Adkar SS, Garnett AT, Amacher SL, Conboy JG (November 2011). "Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions". Developmental Biology. 359 (2): 251–61. doi:10.1016/j.ydbio.2011.08.025. PMC 3521583. PMID 21925157.
• Shibata H, Huynh DP, Pulst SM (May 2000). "A novel protein with RNA-binding motifs interacts with ataxin-2". Human Molecular Genetics. 9 (9): 1303–13. doi:10.1093/hmg/9.9.1303. PMID 10814712.
• Kiehl TR, Shibata H, Vo T, Huynh DP, Pulst SM (August 2001). "Identification and expression of a mouse ortholog of A2BP1". Mammalian Genome. 12 (8): 595–601. doi:10.1007/s00335-001-2056-4. PMID 11471052.
• Underwood JG, Boutz PL, Dougherty JD, Stoilov P, Black DL (November 2005). "Homologues of the Caenorhabditis elegans Fox-1 protein are neuronal splicing regulators in mammals". Molecular and Cellular Biology. 25 (22): 10005–16. doi:10.1128/MCB.25.22.10005-10016.2005. PMC 1280273. PMID 16260614.
• Auweter SD, Fasan R, Reymond L, Underwood JG, Black DL, Pitsch S, Allain FH (January 2006). "Molecular basis of RNA recognition by the human alternative splicing factor Fox-1". The EMBO Journal. 25 (1): 163–73. doi:10.1038/sj.emboj.7600918. PMC 1356361. PMID 16362037.
• Ponthier JL, Schluepen C, Chen W, Lersch RA, Gee SL, Hou VC, Lo AJ, Short SA, Chasis JA, Winkelmann JC, Conboy JG (May 2006). "Fox-2 splicing factor binds to a conserved intron motif to promote inclusion of protein 4.1R alternative exon 16". The Journal of Biological Chemistry. 281 (18): 12468–74. doi:10.1074/jbc.M511556200. PMID 16537540.
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
• Zhou HL, Baraniak AP, Lou H (February 2007). "Role for Fox-1/Fox-2 in mediating the neuronal pathway of calcitonin/calcitonin gene-related peptide alternative RNA processing". Molecular and Cellular Biology. 27 (3): 830–41. doi:10.1128/MCB.01015-06. PMC 1800674. PMID 17101796.