FOX1_CAEEL
ID FOX1_CAEEL Reviewed; 429 AA.
AC Q10572; A0A168HBS9; A0A168HBX9; Q22304;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 3.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Sex determination protein fox-1;
DE AltName: Full=Feminizing locus on X protein 1;
GN Name=fox-1 {ECO:0000312|WormBase:T07D1.4d};
GN ORFNames=T07D1.4 {ECO:0000312|WormBase:T07D1.4d};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=CB1489; TISSUE=Embryo;
RX PubMed=7821230; DOI=10.1242/dev.120.12.3681;
RA Hodgkin J., Zellan J.D., Albertson D.G.;
RT "Identification of a candidate primary sex determination locus, fox-1, on
RT the X chromosome of Caenorhabditis elegans.";
RL Development 120:3681-3689(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, FUNCTION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9927456; DOI=10.1093/genetics/151.2.617;
RA Skipper M., Milne C.A., Hodgkin J.;
RT "Genetic and molecular analysis of fox-1, a numerator element involved in
RT Caenorhabditis elegans primary sex determination.";
RL Genetics 151:617-631(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=9217163; DOI=10.1038/40669;
RA Nicoll M., Akerib C.C., Meyer B.J.;
RT "X-chromosome-counting mechanisms that determine nematode sex.";
RL Nature 388:200-204(1997).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=11303786; DOI=10.1385/jmn:15:3:231;
RA Kiehl T.R., Shibata H., Pulst S.M.;
RT "The ortholog of human ataxin-2 is essential for early embryonic patterning
RT in C. elegans.";
RL J. Mol. Neurosci. 15:231-241(2000).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16139225; DOI=10.1016/j.devcel.2005.06.009;
RA Powell J.R., Jow M.M., Meyer B.J.;
RT "The T-box transcription factor SEA-1 is an autosomal element of the X:A
RT signal that determines C. elegans sex.";
RL Dev. Cell 9:339-349(2005).
RN [7]
RP FUNCTION.
RX PubMed=17060915; DOI=10.1038/nmeth944;
RA Kuroyanagi H., Kobayashi T., Mitani S., Hagiwara M.;
RT "Transgenic alternative-splicing reporters reveal tissue-specific
RT expression profiles and regulation mechanisms in vivo.";
RL Nat. Methods 3:909-915(2006).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17720939; DOI=10.1534/genetics.106.061812;
RA Gladden J.M., Meyer B.J.;
RT "A ONECUT homeodomain protein communicates X chromosome dose to specify
RT Caenorhabditis elegans sexual fate by repressing a sex switch gene.";
RL Genetics 177:1621-1637(2007).
RN [9]
RP FUNCTION, INTERACTION WITH SUP-12, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=17923701; DOI=10.1128/mcb.01508-07;
RA Kuroyanagi H., Ohno G., Mitani S., Hagiwara M.;
RT "The Fox-1 family and SUP-12 coordinately regulate tissue-specific
RT alternative splicing in vivo.";
RL Mol. Cell. Biol. 27:8612-8621(2007).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21471153; DOI=10.1242/dev.057109;
RA Huang X., Zhang H., Zhang H.;
RT "The zinc-finger protein SEA-2 regulates larval developmental timing and
RT adult lifespan in C. elegans.";
RL Development 138:2059-2068(2011).
RN [11]
RP FUNCTION.
RX PubMed=23666922; DOI=10.1101/gad.217026.113;
RA Farboud B., Nix P., Jow M.M., Gladden J.M., Meyer B.J.;
RT "Molecular antagonism between X-chromosome and autosome signals determines
RT nematode sex.";
RL Genes Dev. 27:1159-1178(2013).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 423-LEU--TYR-429.
RX PubMed=23468662; DOI=10.1371/journal.pgen.1003337;
RA Kuroyanagi H., Watanabe Y., Hagiwara M.;
RT "CELF family RNA-binding protein UNC-75 regulates two sets of mutually
RT exclusive exons of the unc-32 gene in neuron-specific manners in
RT Caenorhabditis elegans.";
RL PLoS Genet. 9:e1003337-e1003337(2013).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=33372658; DOI=10.7554/elife.62963;
RA Farboud B., Novak C.S., Nicoll M., Quiogue A., Meyer B.J.;
RT "Dose-dependent action of the RNA binding protein FOX-1 to relay X-
RT chromosome number and determine C. elegans sex.";
RL Elife 9:0-0(2020).
CC -!- FUNCTION: RNA-binding protein that regulates tissue-specific
CC alternative splicing events by binding to 5'-UGCAUG-3' and 5'-GCACG-3'
CC elements (PubMed:17060915, PubMed:17923701, PubMed:23468662,
CC PubMed:33372658). Also binds to poly(A), poly(G), poly(C), or poly(U)
CC stretches of RNA (PubMed:9927456). Plays a role in the sex
CC determination pathway and X chromosome dosage compensation, and
CC together with sex-1 is involved in making the distinction between one
CC and two X-chromosomes (PubMed:7821230, PubMed:21471153,
CC PubMed:23666922, PubMed:9217163, PubMed:9927456, PubMed:16139225,
CC PubMed:17720939, PubMed:33372658). Binds to 5'-GCAUG-3' and 5'-GCACG-3'
CC elements in intron 6 of the pre-mRNA of the sex-determining factor xol-
CC 1 to promote its alternative splicing and together with sex-1
CC negatively regulates the expression of xol-1 to promote hermaphrodite
CC development (PubMed:9217163, PubMed:33372658). Negatively regulates the
CC expression of the active isoform of xol-1 (isoform b) by promoting
CC intron 6 retention and the deletion of exon 7 coding sequences in
CC hermaphrodite embryos (PubMed:33372658). Furthermore, binding to the
CC pre-mRNA of xol-1 can also direct the use of an alternative 3' splice
CC site enabling the xol-1 transcript to be trans-spliced to unrelated
CC genes on chromosome 2, which also leads to xol-1 exon 7 deletion
CC (PubMed:33372658). Does not seem to regulate the retention of introns 1
CC to 5 of xol-1 pre-mRNA (PubMed:33372658). Plays a role in the
CC association of the dosage compensation complex proteins dpy-27 and sdc-
CC 3 with the hermaphrodite X chromosomes (PubMed:16139225,
CC PubMed:17720939). Binds to 5'-UGCAUG-3' elements in intron 7 of the
CC pre-mRNA of unc-32 to promote its alternative splicing in neuronal
CC tissues (PubMed:23468662). Binds to 5'-UGCAUG-3' elements in intron 4
CC of the pre-mRNA of egl-15 to promote its alternative splicing in body
CC wall muscle tissues (PubMed:17060915). Promotes binding of RNA-binding
CC protein sup-12 to target RNA (PubMed:17923701). Plays a role in male
CC mating behavior (PubMed:9927456). {ECO:0000269|PubMed:16139225,
CC ECO:0000269|PubMed:17060915, ECO:0000269|PubMed:17720939,
CC ECO:0000269|PubMed:17923701, ECO:0000269|PubMed:21471153,
CC ECO:0000269|PubMed:23468662, ECO:0000269|PubMed:23666922,
CC ECO:0000269|PubMed:33372658, ECO:0000269|PubMed:7821230,
CC ECO:0000269|PubMed:9217163, ECO:0000269|PubMed:9927456}.
CC -!- SUBUNIT: Interacts with sup-12. {ECO:0000269|PubMed:17923701}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23468662,
CC ECO:0000269|PubMed:9217163, ECO:0000305|PubMed:33372658}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=d {ECO:0000312|WormBase:T07D1.4d};
CC IsoId=Q10572-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:T07D1.4a};
CC IsoId=Q10572-2; Sequence=VSP_060630;
CC Name=b {ECO:0000312|WormBase:T07D1.4b};
CC IsoId=Q10572-3; Sequence=VSP_060629;
CC -!- TISSUE SPECIFICITY: In males and hermaphrodites expressed in a subset
CC of cells in the head and tail (PubMed:9927456). Expressed in the
CC pharynx, intestine and in muscles from the vulva and body wall.
CC {ECO:0000269|PubMed:17923701, ECO:0000269|PubMed:9927456}.
CC -!- DEVELOPMENTAL STAGE: Expressed in males and hermaphrodites throughout
CC development (PubMed:17923701, PubMed:9927456). Expressed in early
CC embryos before morphogenesis (PubMed:17923701). In hermaphrodite
CC embryos, first expressed at the 8-16 cell stage of development with
CC expression peaking by the 100-cell stage (PubMed:9217163). Not
CC expressed at the 550-cell stage of embryogenesis (PubMed:9217163).
CC {ECO:0000269|PubMed:17923701, ECO:0000269|PubMed:9217163,
CC ECO:0000269|PubMed:9927456}.
CC -!- DISRUPTION PHENOTYPE: Males and hermaphrodites are viable and there is
CC no change in brood size (PubMed:9217163, PubMed:17720939,
CC PubMed:33372658). In a sex-1(y263) mutant background or a sex-1 RNAi
CC mutant background, males are viable, but hermaphrodites have highly
CC reduced viability due to failure of the dosage compensation complex to
CC assemble on X chromosomes, and the surviving animals show a reduction
CC in brood size (PubMed:17720939, PubMed:16139225, PubMed:33372658).
CC RNAi-mediated knockdown results in a 63% reduction in the number of
CC eggs produced (PubMed:11303786). RNAi-mediated knockdown together with
CC sex-1 results in hermaphrodite embryonic lethality (PubMed:21471153).
CC This hermaphrodite-specific lethality is suppressed in a sea-2 bp283
CC mutant or sea-1 gk799 mutant background (PubMed:21471153).
CC {ECO:0000269|PubMed:11303786, ECO:0000269|PubMed:16139225,
CC ECO:0000269|PubMed:17720939, ECO:0000269|PubMed:21471153,
CC ECO:0000269|PubMed:33372658, ECO:0000269|PubMed:9217163}.
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DR EMBL; U14946; AAA67723.1; -; mRNA.
DR EMBL; BX284606; CCD67194.1; -; Genomic_DNA.
DR EMBL; BX284606; SAP35625.1; -; Genomic_DNA.
DR EMBL; BX284606; SAP35629.1; -; Genomic_DNA.
DR PIR; T16825; T16825.
DR RefSeq; NP_001317738.1; NM_001330895.1. [Q10572-2]
DR RefSeq; NP_001317857.1; NM_001330894.1. [Q10572-1]
DR RefSeq; NP_001317861.1; NM_001330896.1. [Q10572-3]
DR AlphaFoldDB; Q10572; -.
DR BioGRID; 45493; 3.
DR IntAct; Q10572; 2.
DR STRING; 6239.T07D1.4; -.
DR EPD; Q10572; -.
DR PaxDb; Q10572; -.
DR PeptideAtlas; Q10572; -.
DR EnsemblMetazoa; T07D1.4a.1; T07D1.4a.1; WBGene00001484. [Q10572-2]
DR EnsemblMetazoa; T07D1.4a.2; T07D1.4a.2; WBGene00001484. [Q10572-2]
DR EnsemblMetazoa; T07D1.4a.3; T07D1.4a.3; WBGene00001484. [Q10572-2]
DR EnsemblMetazoa; T07D1.4a.4; T07D1.4a.4; WBGene00001484. [Q10572-2]
DR EnsemblMetazoa; T07D1.4b.1; T07D1.4b.1; WBGene00001484. [Q10572-3]
DR EnsemblMetazoa; T07D1.4d.1; T07D1.4d.1; WBGene00001484. [Q10572-1]
DR GeneID; 180549; -.
DR KEGG; cel:CELE_T07D1.4; -.
DR UCSC; T07D1.4.2; c. elegans. [Q10572-1]
DR CTD; 180549; -.
DR WormBase; T07D1.4a; CE51693; WBGene00001484; fox-1. [Q10572-2]
DR WormBase; T07D1.4b; CE51620; WBGene00001484; fox-1. [Q10572-3]
DR WormBase; T07D1.4d; CE51563; WBGene00001484; fox-1. [Q10572-1]
DR eggNOG; KOG0125; Eukaryota.
DR GeneTree; ENSGT00940000168999; -.
DR HOGENOM; CLU_662647_0_0_1; -.
DR InParanoid; Q10572; -.
DR OrthoDB; 871288at2759; -.
DR PRO; PR:Q10572; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00001484; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR ExpressionAtlas; Q10572; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:0008143; F:poly(A) binding; IDA:WormBase.
DR GO; GO:0034046; F:poly(G) binding; IDA:WormBase.
DR GO; GO:0008266; F:poly(U) RNA binding; IDA:WormBase.
DR GO; GO:0097157; F:pre-mRNA intronic binding; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0042464; P:dosage compensation by hypoactivation of X chromosome; IMP:UniProtKB.
DR GO; GO:0000366; P:intergenic mRNA trans splicing; IDA:UniProtKB.
DR GO; GO:0007617; P:mating behavior; IMP:WormBase.
DR GO; GO:0016071; P:mRNA metabolic process; IMP:WormBase.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0007538; P:primary sex determination; IMP:UniProtKB.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IMP:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007548; P:sex differentiation; IEA:UniProtKB-KW.
DR CDD; cd12407; RRM_FOX1_like; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR034237; FOX1_RRM.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Differentiation; Nucleus; Reference proteome;
KW RNA-binding; Sexual differentiation; Transcription;
KW Transcription regulation.
FT CHAIN 1..429
FT /note="Sex determination protein fox-1"
FT /id="PRO_0000081589"
FT DOMAIN 183..259
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 156..188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 156..177
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_060629"
FT VAR_SEQ 1..30
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_060630"
FT MUTAGEN 423..429
FT /note="Missing: Disrupts nuclear localization."
FT /evidence="ECO:0000269|PubMed:23468662"
FT CONFLICT 127
FT /note="Q -> R (in Ref. 1; AAA67723)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="A -> P (in Ref. 1; AAA67723)"
FT /evidence="ECO:0000305"
FT CONFLICT 366
FT /note="Q -> L (in Ref. 1; AAA67723)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 429 AA; 45515 MW; F08407ED8E2DCDBD CRC64;
MAELIEEVST ATHASLNACD PIVVNSEALP MQALYQLSAT GAQQQNQQIP IGLSNSLLYQ
QLAAHQQIAA QQHQQQLAVS AAHQTQNNIM LATSAPSLIN HMENSTDGKV KDDPNSDYDL
QLSIQQQLAA AAQAAQMGQT QIGPQIVGQQ GQPVVATTAG STNGSAAVTQ PDPSTSSGPD
GPKRLHVSNI PFRFRDPDLK TMFEKFGVVS DVEIIFNERG SKGFGFVTME RPQDAERARQ
ELHGSMIEGR KIEVNCATAR VHSKKVKPTG GILDQMNPLM AQSALAAQAQ MNRALLLRSP
LVAQSLLGRG AALIPGMQQP AFQLQAALAG NPLAQLQGQP LLFNAAALQT NALQQSAFGM
DPAAVQAALL ANEQARFQLA AAAAQGRIPS SGNASAFGEQ YLSNALATAS LPSYQMNPAL
RTLNRFTPY
