Q8BIF2 (RFOX3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RNA binding protein fox-1 homolog 3

Alternative name(s):
Fox-1 homolog C
Hexaribonucleotide-binding protein 3
Short name=Fox-3
Neuronal nuclei
Short name=NeuN

Gene names

Name:	Rbfox3
Synonyms:	D11Bwg0517e, Hrnbp3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	374 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	RNA-binding protein that regulates alternative splicing events. Regulates alternative splicing of RBFOX2 to enhance the production of mRNA species that are targeted for nonsense-mediated decay (NMD). Ref.1 Ref.6
Subcellular location	Nucleus Ref.1 Ref.6 Ref.7 Ref.8. Cytoplasm Ref.1 Ref.6 Ref.7 Ref.8. Isoform 1: Nucleus Ref.1 Ref.6 Ref.7 Ref.8. Isoform 4: Cytoplasm Ref.1 Ref.6 Ref.7 Ref.8. Isoform 5: Nucleus Ref.1 Ref.6 Ref.7 Ref.8.
Tissue specificity	Widely expressed in brain, regions including cerebral cortex, hippocampus, thalamus, caudate/putamen, cerebellum, as well as in the spinal cord (at protein level). Not expressed in all neuronal cells within a region, in cerebellum, expression is absent in Purkinje cells (at protein level). Expressed in the retina in the ganglion cells and some cells in the inner nuclear layer, but absent from the photoreceptor cells and most cells in the inner nuclear layer (at protein level). Ref.1 Ref.6 Ref.7 Ref.8
Developmental stage	In the neural tube, expressed as early as embryonic day 9.5 (E9.5) and expression is confined to the nervous system. By embryonic day 12.5, can be found in the developing ventral horns and is also detected in the developing dorsal horns as well as in the dorsal root ganglion. Not detected in the ventricular zone, roof plate, floor plate or marginal zone (developing white matter). It is expressed from embryonic stage to adulthood. Ref.7
Induction	By retinoic acid. Expression is up-regulated in P19 cells during neural differentiation upon retinoic acid treatment (at the protein level). Ref.1 Ref.6
Post-translational modification	Phosphorylated Probable. Ref.8
Sequence similarities	Contains 1 RRM (RNA recognition motif) domain.
Caution	Initial characterization was derived from usage of a monoclonal antibody (A60) directed to an unknown protein called NeuN (Ref.8 and Ref.7), but later identified as RBFOX3 (Ref.6).

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW regulation of RNA splicing Inferred from electronic annotation. Source: InterPro regulation of alternative mRNA splicing, via spliceosome Inferred from direct assay Ref.6. Source: MGI
Cellular_component	cytoplasm Inferred from direct assay Ref.6. Source: MGI neuronal cell body Inferred from direct assay PubMed 15964665PubMed 20418887PubMed 20578039. Source: MGI nucleus Inferred from direct assay Ref.7PubMed 15148382PubMed 17301088PubMed 21172456Ref.6. Source: MGI
Molecular_function	DNA binding Inferred from direct assay Ref.7. Source: MGI RNA binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HIF1A	Q16665	2	EBI-4567146,EBI-447269	From a different organism.
Hif1a	Q61221	2	EBI-4567146,EBI-298954

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8BIF2-1)

Also known as: Fox3v1; Fox-3-L;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8BIF2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     361-374: Missing.

Isoform 3 (identifier: Q8BIF2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     139-169: Missing.
     361-374: Missing.

Isoform 4 (identifier: Q8BIF2-4)

Also known as: Fox3v3;

The sequence of this isoform differs from the canonical sequence as follows:
     253-299: Missing.
     361-374: Missing.

Isoform 5 (identifier: Q8BIF2-5)

Also known as: Fox3v2; Fox-3-S;

The sequence of this isoform differs from the canonical sequence as follows:
     253-299: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 374	374	RNA binding protein fox-1 homolog 3		PRO_0000349208
Regions
	Domain	99 – 175	77	RRM
	Compositional bias	4 – 58	55	Pro-rich
	Compositional bias	242 – 295	54	Pro-rich
Sites
	Site	100	1	Interaction with RNA By similarity
	Site	108	1	Interaction with RNA By similarity
	Site	109	1	Interaction with RNA By similarity
	Site	133	1	Interaction with RNA By similarity
	Site	138	1	Interaction with RNA By similarity
	Site	142	1	Interaction with RNA By similarity
	Site	166	1	Interaction with RNA By similarity
	Site	176	1	Interaction with RNA By similarity
Natural variations
	Alternative sequence	139 – 169	31	Missing in isoform 3.		VSP_035219
	Alternative sequence	253 – 299	47	Missing in isoform 4 and isoform 5.		VSP_043949
	Alternative sequence	361 – 374	14	Missing in isoform 2, isoform 3 and isoform 4.		VSP_035220
Experimental info
	Sequence conflict	266	1	A → V in BAC37531. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Fox3v1) (Fox-3-L) [UniParc]. Last modified September 2, 2008. Version 2. Checksum: AC1454ADBCD2B810	FASTA	374	40,610
	10 20 30 40 50 60 MAQPYPPAQY PPPPQNGIPA EYAPPPPHPT QDYSGQTPVP PEHGMTLYTP AQTHPEQPGT 70 80 90 100 110 120 EASTQPIAGT QTVPQADEAA QTDNQQLHPS DPTEKQQPKR LHVSNIPFRF RDPDLRQMFG 130 140 150 160 170 180 QFGKILDVEI IFNERGSKGF GFVTFETSSD ADRAREKLNG TIVEGRKIEV NNATARVMTN 190 200 210 220 230 240 KKPGNPYANG WKLNPVVGTV YGPEFYAVTS FPYPTTGTAV AYRGAHLRGR GRAVYNTFRA 250 260 270 280 290 300 APPPPPIPTY GAALEQTLVK MPVPWAGLAP CPLPPQQTPE PAYPTSPAFP PLSCPFASRV 310 320 330 340 350 360 VYQDGFYGAE IYGGYAAYRY AQPAAATAAA YSDSYGRVYA AADPYHHTIG PTATYSIGTM 370 ASLCRGGYSR FTPY
	Isoform 2 [UniParc]. Checksum: 789CC518B9F6CC92	FASTA	360	39,051
	10 20 30 40 50 60 MAQPYPPAQY PPPPQNGIPA EYAPPPPHPT QDYSGQTPVP PEHGMTLYTP AQTHPEQPGT 70 80 90 100 110 120 EASTQPIAGT QTVPQADEAA QTDNQQLHPS DPTEKQQPKR LHVSNIPFRF RDPDLRQMFG 130 140 150 160 170 180 QFGKILDVEI IFNERGSKGF GFVTFETSSD ADRAREKLNG TIVEGRKIEV NNATARVMTN 190 200 210 220 230 240 KKPGNPYANG WKLNPVVGTV YGPEFYAVTS FPYPTTGTAV AYRGAHLRGR GRAVYNTFRA 250 260 270 280 290 300 APPPPPIPTY GAALEQTLVK MPVPWAGLAP CPLPPQQTPE PAYPTSPAFP PLSCPFASRV 310 320 330 340 350 360 VYQDGFYGAE IYGGYAAYRY AQPAAATAAA YSDSYGRVYA AADPYHHTIG PTATYSIGTM
	Isoform 3 [UniParc]. Checksum: BB7BA1021A5216D6	FASTA	329	35,638
	10 20 30 40 50 60 MAQPYPPAQY PPPPQNGIPA EYAPPPPHPT QDYSGQTPVP PEHGMTLYTP AQTHPEQPGT 70 80 90 100 110 120 EASTQPIAGT QTVPQADEAA QTDNQQLHPS DPTEKQQPKR LHVSNIPFRF RDPDLRQMFG 130 140 150 160 170 180 QFGKILDVEI IFNERGSKVN NATARVMTNK KPGNPYANGW KLNPVVGTVY GPEFYAVTSF 190 200 210 220 230 240 PYPTTGTAVA YRGAHLRGRG RAVYNTFRAA PPPPPIPTYG AALEQTLVKM PVPWAGLAPC 250 260 270 280 290 300 PLPPQQTPEP AYPTSPAFPP LSCPFASRVV YQDGFYGAEI YGGYAAYRYA QPAAATAAAY 310 320 SDSYGRVYAA ADPYHHTIGP TATYSIGTM
	Isoform 4 (Fox3v3) [UniParc]. Checksum: 664AB23CC03D9B7A	FASTA	313	34,068
	10 20 30 40 50 60 MAQPYPPAQY PPPPQNGIPA EYAPPPPHPT QDYSGQTPVP PEHGMTLYTP AQTHPEQPGT 70 80 90 100 110 120 EASTQPIAGT QTVPQADEAA QTDNQQLHPS DPTEKQQPKR LHVSNIPFRF RDPDLRQMFG 130 140 150 160 170 180 QFGKILDVEI IFNERGSKGF GFVTFETSSD ADRAREKLNG TIVEGRKIEV NNATARVMTN 190 200 210 220 230 240 KKPGNPYANG WKLNPVVGTV YGPEFYAVTS FPYPTTGTAV AYRGAHLRGR GRAVYNTFRA 250 260 270 280 290 300 APPPPPIPTY GAVVYQDGFY GAEIYGGYAA YRYAQPAAAT AAAYSDSYGR VYAAADPYHH 310 TIGPTATYSI GTM
	Isoform 5 (Fox3v2) (Fox-3-S) [UniParc]. Checksum: 2952868AD8C8E39A	FASTA	327	35,628
	10 20 30 40 50 60 MAQPYPPAQY PPPPQNGIPA EYAPPPPHPT QDYSGQTPVP PEHGMTLYTP AQTHPEQPGT 70 80 90 100 110 120 EASTQPIAGT QTVPQADEAA QTDNQQLHPS DPTEKQQPKR LHVSNIPFRF RDPDLRQMFG 130 140 150 160 170 180 QFGKILDVEI IFNERGSKGF GFVTFETSSD ADRAREKLNG TIVEGRKIEV NNATARVMTN 190 200 210 220 230 240 KKPGNPYANG WKLNPVVGTV YGPEFYAVTS FPYPTTGTAV AYRGAHLRGR GRAVYNTFRA 250 260 270 280 290 300 APPPPPIPTY GAVVYQDGFY GAEIYGGYAA YRYAQPAAAT AAAYSDSYGR VYAAADPYHH 310 320 TIGPTATYSI GTMASLCRGG YSRFTPY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of neuronal nuclei (NeuN) as Fox-3, a new member of the Fox-1 gene family of splicing factors." Kim K.K., Adelstein R.S., Kawamoto S. J. Biol. Chem. 284:31052-31061(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 5), PROTEIN SEQUENCE OF 139-153; 156-166 AND 320-360, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION BY RETINOIC ACID. Tissue: Brain.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Diencephalon and Head.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[4]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Eye.
[6]	"NeuN/Rbfox3 nuclear and cytoplasmic isoforms differentially regulate alternative splicing and nonsense-mediated decay of Rbfox2." Dredge B.K., Jensen K.B. PLoS ONE 6:E21585-E21585(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 102-135; 139-153; 192-201; 239-250 AND 319-337, FUNCTION, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, INDUCTION BY RETINOIC ACID, MASS SPECTROMETRY (ISOFORMS 1; 4 AND 5).
[7]	"NeuN, a neuronal specific nuclear protein in vertebrates." Mullen R.J., Buck C.R., Smith A.M. Development 116:201-211(1992) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[8]	"Characterization of the neuronal marker NeuN as a multiply phosphorylated antigen with discrete subcellular localization." Lind D., Franken S., Kappler J., Jankowski J., Schilling K. J. Neurosci. Res. 79:295-302(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION.
[9]	"Autoregulation of Fox protein expression to produce dominant negative splicing factors." Damianov A., Black D.L. RNA 16:405-416(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	FJ958310 mRNA. Translation: ACY91937.1. FJ958311 mRNA. Translation: ACY91938.1. AK079086 mRNA. Translation: BAC37531.1. AK160816 mRNA. Translation: BAE36031.1. AL591514 Genomic DNA. No translation available. AL591544 Genomic DNA. No translation available. AL591075 Genomic DNA. Translation: CAM15761.1. AL591075 Genomic DNA. Translation: CAM15760.1. AL591075 Genomic DNA. Translation: CAM15762.1. AL591075 Genomic DNA. Translation: CAX16099.1. AL591075 Genomic DNA. Translation: CAX16100.1. CH466558 Genomic DNA. Translation: EDL34674.1. BC054403 mRNA. Translation: AAH54403.1.
IPI	IPI00222115. IPI00408241. IPI00648836. IPI00720112. IPI00894965.
RefSeq	NP_001020102.2. NM_001024931.2. NP_001034256.1. NM_001039167.1. NP_001034257.1. NM_001039168.1.
UniGene	Mm.341103.
3D structure databases
ProteinModelPortal	Q8BIF2.
SMR	Q8BIF2. Positions 95-178.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8BIF2. 2 interactions.
MINT	MINT-4110740.
Proteomic databases
PaxDb	Q8BIF2.
PRIDE	Q8BIF2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000017576; ENSMUSP00000017576; ENSMUSG00000025576. ENSMUST00000069343; ENSMUSP00000069598; ENSMUSG00000025576. ENSMUST00000103023; ENSMUSP00000099312; ENSMUSG00000025576. ENSMUST00000106278; ENSMUSP00000101885; ENSMUSG00000025576. ENSMUST00000117731; ENSMUSP00000113636; ENSMUSG00000025576. ENSMUST00000120061; ENSMUSP00000113987; ENSMUSG00000025576.
GeneID	52897.
KEGG	mmu:52897.
UCSC	uc007mpl.1. mouse. uc007mpm.1. mouse. uc007mpn.1. mouse. uc007mpp.1. mouse.
Organism-specific databases
CTD	146713.
MGI	MGI:106368. Rbfox3.
Phylogenomic databases
eggNOG	NOG258617.
GeneTree	ENSGT00390000013767.
HOVERGEN	HBG000044.
InParanoid	Q8BIF2.
KO	K14946.
OMA	LQASLCR.
Gene expression databases
ArrayExpress	Q8BIF2.
Bgee	Q8BIF2.
Genevestigator	Q8BIF2.
Family and domain databases
Gene3D	3.30.70.330. 1 hit.
InterPro	IPR025670. Fox-1_C_dom. IPR012677. Nucleotide-bd_a/b_plait. IPR017325. RNA-bd_Fox-1. IPR000504. RRM_dom. [Graphical view]
Pfam	PF12414. Fox-1_C. 2 hits. PF00076. RRM_1. 1 hit. [Graphical view]
PIRSF	PIRSF037932. Ataxin_2_bd_A2BP. 1 hit.
SMART	SM00360. RRM. 1 hit. [Graphical view]
PROSITE	PS50102. RRM. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	309687.
SOURCE	Search...

Entry information

Entry name

RFOX3_MOUSE

Accession

Primary (citable) accession number: Q8BIF2
Secondary accession number(s): A2A4W7 , A2A4W8, B7ZC12, B7ZC13, D1GI07, Q3TUE0, Q7TQI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 2, 2008
Last sequence update:	September 2, 2008
Last modified:	May 29, 2013
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program