Reviewed, UniProtKB/Swiss-Prot Q9NWB1 (FOX1A_HUMAN)

Names and origin

Protein names

Recommended name:
    Fox-1 homolog A
Alternative name(s):
    Ataxin-2-binding protein 1
    Hexaribonucleotide-binding protein 1

Gene names

Name:	FOX1
Synonyms:	A2BP, A2BP1, HRNBP1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	397 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Regulates alternative splicing of tissue-specific exons and of differentially spliced exons during erythropoiesis. Ref.6
Subunit structure	Binds to the C-terminal of ATXN2.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity.
Tissue specificity	Predominantly expressed in muscle and brain.
Sequence similarities	Contains 1 RRM (RNA recognition motif) domain.

Ontologies

Keywords
Biological process	mRNA processing mRNA splicing
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	RNA-binding
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	RNA splicing Inferred from electronic annotation. Source: UniProtKB-KW RNA transport Ref.1 Non-traceable author statement. Source: UniProtKB mRNA processing Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell trans-Golgi network Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	RNA binding Ref.1 Non-traceable author statement. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro protein C-terminus binding Ref.1 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATN1	P54259	1	EBI-945906,EBI-945980
ATXN1	P54253	1	EBI-945906,EBI-930964
NUMBL	Q9Y6R0	1	EBI-945906,EBI-945925
PLEKHA5	Q9HAU0	1	EBI-945906,EBI-945934
PSMF1	Q92530	1	EBI-945906,EBI-945916
QKI	Q96PU8	1	EBI-945906,EBI-945792
RBM9	O43251	1	EBI-945906,EBI-746056

Alternative products

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

Isoform 1 (identifier: Q9NWB1-1)

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: Q9NWB1-2)

Also known as: Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MNCEREQLR → MLASQGVLLHPYGVPMIVPAAPYLPGLIQ
     302-310: DGFYGADIY → EPVYGNKLLQ

Isoform 3 (identifier: Q9NWB1-3)

Also known as: 1;

The sequence of this isoform differs from the canonical sequence as follows:
     226-253: GTVLLCQANQEGSSMYSAPSSLVYTSAM → V

Isoform 4 (identifier: Q9NWB1-4)

Also known as: Alpha;

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MNCEREQLR → MLASQGVLLHPYGVPMIVPAAPYLPGLIQ
     302-310: DGFYGADIY → EPVYGNKLLQ
     358-383: Missing.

Isoform 5 (identifier: Q9NWB1-5)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MNCEREQLR → MLASQGVLLHPYGVPMIVPAAPYLPGLIQ
     302-310: DGFYGADIY → EPVYGNKLLQ
     332-397: SYGRVYAADP...RGGYNRFAPY → RNQFVFVAAD...LQPPPTALVP

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 397

397

Fox-1 homolog A

PRO_0000081480

Regions

Domain

117 – 193

77

RRM

Sites

Site

118

1

Interaction with RNA

Site

126

1

Interaction with RNA

Site

127

1

Interaction with RNA

Site

151

1

Interaction with RNA

Site

156

1

Interaction with RNA

Site

160

1

Interaction with RNA

Site

184

1

Interaction with RNA

Site

194

1

Interaction with RNA

Natural variations

Alternative sequence

1 – 9

9

MNCEREQLR → MLASQGVLLHPYGVPMIVPA APYLPGLIQ in isoform 2, isoform 4 and isoform 5.

VSP_030874

Alternative sequence

226 – 253

28

GTVLL…YTSAM → V in isoform 3.

VSP_030875

Alternative sequence

302 – 310

9

DGFYGADIY → EPVYGNKLLQ in isoform 2, isoform 4 and isoform 5.

VSP_030876

Alternative sequence

332 – 397

66

SYGRV…RFAPY → RNQFVFVAADEISCNTSAVT DEFMLPTPTTTHLLQPPPTA LVP in isoform 5.

VSP_030877

Alternative sequence

358 – 383

26

Missing in isoform 4.

VSP_030878

Experimental info

Mutagenesis

120

1

H → A: Reduces RNA-binding affinity 160-fold. Ref.7

Mutagenesis

126

1

F → A, I or R: Reduces RNA-binding affinity 1500-fold. Ref.7

Mutagenesis

126

1

F → H or W: Reduces RNA-binding affinity 15-fold. Ref.7

Mutagenesis

126

1

F → Y: No effect on RNA-binding. Ref.7

Mutagenesis

158

1

F → A: Reduces RNA-binding affinity 700-fold. Ref.7

Mutagenesis

160

1

F → A: Reduces RNA-binding affinity 30'000-fold. Ref.7

Sequence conflict

92

1

T → A in BAA91472. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

397

Helix Strand Turn

Details...

Beta strand

118 – 123

6

Helix

130 – 136

7

Helix

137 – 139

3

Beta strand

146 – 148

3

Beta strand

158 – 162

5

Helix

167 – 176

10

Beta strand

187 – 190

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 5, 2008. Version 2. Checksum: EA96AA7B6E144D80	FASTA	397	42,784
	10 20 30 40 50 60 MNCEREQLRG NQEAAAAPDT MAQPYASAQF APPQNGIPAE YTAPHPHPAP EYTGQTTVPE 70 80 90 100 110 120 HTLNLYPPAQ THSEQSPADT SAQTVSGTAT QTDDAAPTDG QPQTQPSENT ENKSQPKRLH 130 140 150 160 170 180 VSNIPFRFRD PDLRQMFGQF GKILDVEIIF NERGSKGFGF VTFENSADAD RAREKLHGTV 190 200 210 220 230 240 VEGRKIEVNN ATARVMTNKK TVNPYTNGWK LNPVVGAVYS PEFYAGTVLL CQANQEGSSM 250 260 270 280 290 300 YSAPSSLVYT SAMPGFPYPA ATAAAAYRGA HLRGRGRTVY NTFRAAAPPP PIPAYGGVVY 310 320 330 340 350 360 QDGFYGADIY GGYAAYRYAQ PTPATAAAYS DSYGRVYAAD PYHHALAPAP TYGVGAMNAF 370 380 390 APLTDAKTRS HADDVGLVLS SLQASIYRGG YNRFAPY
	Isoform 2 (Gamma). Checksum: 47D6FC140F75D01A	FASTA	418	44,793
	10 20 30 40 50 60 MLASQGVLLH PYGVPMIVPA APYLPGLIQG NQEAAAAPDT MAQPYASAQF APPQNGIPAE 70 80 90 100 110 120 YTAPHPHPAP EYTGQTTVPE HTLNLYPPAQ THSEQSPADT SAQTVSGTAT QTDDAAPTDG 130 140 150 160 170 180 QPQTQPSENT ENKSQPKRLH VSNIPFRFRD PDLRQMFGQF GKILDVEIIF NERGSKGFGF 190 200 210 220 230 240 VTFENSADAD RAREKLHGTV VEGRKIEVNN ATARVMTNKK TVNPYTNGWK LNPVVGAVYS 250 260 270 280 290 300 PEFYAGTVLL CQANQEGSSM YSAPSSLVYT SAMPGFPYPA ATAAAAYRGA HLRGRGRTVY 310 320 330 340 350 360 NTFRAAAPPP PIPAYGGVVY QEPVYGNKLL QGGYAAYRYA QPTPATAAAY SDSYGRVYAA 370 380 390 400 410 DPYHHALAPA PTYGVGAMNA FAPLTDAKTR SHADDVGLVL SSLQASIYRG GYNRFAPY
	Isoform 3 (1). Checksum: 26DBC3263B7E5EA9	FASTA	370	40,005
	10 20 30 40 50 60 MNCEREQLRG NQEAAAAPDT MAQPYASAQF APPQNGIPAE YTAPHPHPAP EYTGQTTVPE 70 80 90 100 110 120 HTLNLYPPAQ THSEQSPADT SAQTVSGTAT QTDDAAPTDG QPQTQPSENT ENKSQPKRLH 130 140 150 160 170 180 VSNIPFRFRD PDLRQMFGQF GKILDVEIIF NERGSKGFGF VTFENSADAD RAREKLHGTV 190 200 210 220 230 240 VEGRKIEVNN ATARVMTNKK TVNPYTNGWK LNPVVGAVYS PEFYAVPGFP YPAATAAAAY 250 260 270 280 290 300 RGAHLRGRGR TVYNTFRAAA PPPPIPAYGG VVYQDGFYGA DIYGGYAAYR YAQPTPATAA 310 320 330 340 350 360 AYSDSYGRVY AADPYHHALA PAPTYGVGAM NAFAPLTDAK TRSHADDVGL VLSSLQASIY 370 RGGYNRFAPY
	Isoform 4 (Alpha). Checksum: 68F8CEFE2FC6D674	FASTA	392	42,084
	10 20 30 40 50 60 MLASQGVLLH PYGVPMIVPA APYLPGLIQG NQEAAAAPDT MAQPYASAQF APPQNGIPAE 70 80 90 100 110 120 YTAPHPHPAP EYTGQTTVPE HTLNLYPPAQ THSEQSPADT SAQTVSGTAT QTDDAAPTDG 130 140 150 160 170 180 QPQTQPSENT ENKSQPKRLH VSNIPFRFRD PDLRQMFGQF GKILDVEIIF NERGSKGFGF 190 200 210 220 230 240 VTFENSADAD RAREKLHGTV VEGRKIEVNN ATARVMTNKK TVNPYTNGWK LNPVVGAVYS 250 260 270 280 290 300 PEFYAGTVLL CQANQEGSSM YSAPSSLVYT SAMPGFPYPA ATAAAAYRGA HLRGRGRTVY 310 320 330 340 350 360 NTFRAAAPPP PIPAYGGVVY QEPVYGNKLL QGGYAAYRYA QPTPATAAAY SDSYGRVYAA 370 380 390 DPYHHALAPA PTYGVGAMAS IYRGGYNRFA PY
	Isoform 5 (Beta). Checksum: 2299F9127AA1DE39	FASTA	395	42,402
	10 20 30 40 50 60 MLASQGVLLH PYGVPMIVPA APYLPGLIQG NQEAAAAPDT MAQPYASAQF APPQNGIPAE 70 80 90 100 110 120 YTAPHPHPAP EYTGQTTVPE HTLNLYPPAQ THSEQSPADT SAQTVSGTAT QTDDAAPTDG 130 140 150 160 170 180 QPQTQPSENT ENKSQPKRLH VSNIPFRFRD PDLRQMFGQF GKILDVEIIF NERGSKGFGF 190 200 210 220 230 240 VTFENSADAD RAREKLHGTV VEGRKIEVNN ATARVMTNKK TVNPYTNGWK LNPVVGAVYS 250 260 270 280 290 300 PEFYAGTVLL CQANQEGSSM YSAPSSLVYT SAMPGFPYPA ATAAAAYRGA HLRGRGRTVY 310 320 330 340 350 360 NTFRAAAPPP PIPAYGGVVY QEPVYGNKLL QGGYAAYRYA QPTPATAAAY SDRNQFVFVA 370 380 390 ADEISCNTSA VTDEFMLPTP TTTHLLQPPP TALVP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel protein with RNA-binding motifs interacts with ataxin-2." Shibata H., Huynh D.P., Pulst S.-M. Hum. Mol. Genet. 9:1303-1313(2000) [PubMed: 10814712] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Molecular cloning and chromosomal localization of a human brain, heart and skeletal muscle specific RNA binding protein gene homologous to fox-1 in Caenorhabditis elegans." Chen W., Chu Z.-L., Blough R.I., Liu L., Hoppes B., Winkelmann J.C. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 2; 4 AND 5).
[3]	"An alternative splicing of a novel protein with RNA-binding motifs interacts with ataxin-2." Yu L., Guo J., She X. Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
[6]	"Fox-2 splicing factor binds to a conserved intron motif to promote inclusion of protein 4.1R alternative exon 16." Ponthier J.L., Schluepen C., Chen W., Lersch R.A., Gee S.L., Hou V.C., Lo A.J., Short S.A., Chasis J.A., Winkelmann J.C., Conboy J.G. J. Biol. Chem. 281:12468-12474(2006) [PubMed: 16537540] [Abstract] Cited for: FUNCTION.
[7]	"Molecular basis of RNA recognition by the human alternative splicing factor Fox-1." Auweter S.D., Fasan R., Reymond L., Underwood J.G., Black D.L., Pitsch S., Allain F.H.-T. EMBO J. 25:163-173(2006) [PubMed: 16362037] [Abstract] Cited for: STRUCTURE BY NMR OF 109-196 IN COMPLEX WITH RNA, MUTAGENESIS OF HIS-120; PHE-126; PHE-158 AND PHE-160.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF107203 mRNA. Translation: AAF78291.1. Different initiation.
AF229057 mRNA. Translation: AAL71904.1.
AF094849 mRNA. Translation: AAL83405.1.
AF109106 mRNA. Translation: AAL83406.1.
AF109120 , AF109107, AF109108, AF109109, AF109110, AF109111, AF109112, AF109113, AF109114, AF109115, AF109116, AF109117, AF109118, AF109119 Genomic DNA. Translation: AAL83407.1.
AF109120 , AF109107, AF109108, AF109109, AF109110, AF109111, AF109112, AF109113, AF109114, AF109115, AF109116, AF109117, AF109119 Genomic DNA. Translation: AAL83408.1.
AF109120 , AF109107, AF109108, AF109109, AF109110, AF109111, AF109112, AF109113, AF109114, AF109115, AF109116, AF109117, AF109119 Genomic DNA. Translation: AAL83409.1.
AF448859 mRNA. Translation: AAP41925.1.
AK001027 mRNA. Translation: BAA91472.1.
BC113691 mRNA. Translation: AAI13692.1.

IPI

IPI00152050.
IPI00164146.
IPI00170678.
IPI00170712.
IPI00385553.

RefSeq

NP_001135805.1.
NP_001135806.1.
NP_061193.2.
NP_665898.1.
NP_665899.1.
NP_665900.1.

UniGene

Hs.459842

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ERR	NMR	-	A	109-196	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9NWB1. 23 interactions.

STRING

Q9NWB1.

Genome annotation databases

Ensembl

ENST00000340209; ENSP00000344196; ENSG00000078328; Homo sapiens. [Genome view]

GeneID

54715.

KEGG

hsa:54715.

UCSC

uc002cys.1. human.
uc002cyt.1. human.
uc002cyw.1. human.
uc002cyx.1. human.
uc002cyy.1. human.

Organism-specific databases

CTD

54715.

GeneCards

GC16P006009.

MIM

605104. gene.

Phylogenomic databases

HOVERGEN

Q9NWB1.

OMA

QEATAPP.

Gene expression databases

ArrayExpress

Q9NWB1.

Bgee

Q9NWB1.

Genevestigator

Q9NWB1.

GermOnline

ENSG00000078328. Homo sapiens.

Family and domain databases

InterPro

IPR012677. a_b_plait_nuc_bd.
IPR017325. RNA-bd_9/Ataxin-2-bd.
IPR000504. RRM_RNP1.
[Graphical view]

Gene3D

G3DSA:3.30.70.330. a_b_plait_nuc_bd. 1 hit.

Pfam

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 Resources

NextBio

57277.

SOURCE

Search...

Entry information

Entry name

FOX1A_HUMAN

Accession

Primary (citable) accession number: Q9NWB1
Secondary accession number(s): Q7Z7I7 , Q8TAE3, Q8TAF2, Q8WYB2, Q9NS20

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	February 5, 2008
Last modified:	December 15, 2009
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.