[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND ALTERNATIVE SPLICING. STRAIN=Bristol N2; DOI=10.1006/dbio.1996.0219; PubMed=8812130 [NCBI, ExPASy, EBI, Israel, Japan] Azzaria M., Goszczynski B., Chung M.A., Kalb J.M., McGhee J.D.; "A fork head/HNF-3 homolog expressed in the pharynx and intestine of the Caenorhabditis elegans embryo."; Dev. Biol. 178:289-303(1996).
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. STRAIN=Bristol N2; DOI=10.1126/science.282.5396.2012; PubMed=9851916 [NCBI, ExPASy, EBI, Israel, Japan] The C. elegans sequencing consortium; "Genome sequence of the nematode C. elegans: a platform for investigating biology."; Science 282:2012-2018(1998).
[3]	FUNCTION. PubMed=7607089 [NCBI, ExPASy, EBI, Israel, Japan] Mango S.E., Lambie E.J., Kimble J.; "The pha-4 gene is required to generate the pharyngeal primordium of Caenorhabditis elegans."; Development 120:3019-3031(1994).
[4]	FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. PubMed=9584117 [NCBI, ExPASy, EBI, Israel, Japan] Kalb J.M., Lau K.K., Goszczynski B., Fukushige T., Moons D., Okkema P.G., McGhee J.D.; "pha-4 is Ce-fkh-1, a fork head/HNF-3alpha,beta,gamma homolog that functions in organogenesis of the C. elegans pharynx."; Development 125:2171-2180(1998).
[5]	FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE. PubMed=9649499 [NCBI, ExPASy, EBI, Israel, Japan] Horner M.A., Quintin S., Domeier M.E., Kimble J., Labouesse M., Mango S.E.; "pha-4, an HNF-3 homolog, specifies pharyngeal organ identity in Caenorhabditis elegans."; Genes Dev. 12:1947-1952(1998).
[6]	FUNCTION. DOI=10.1126/science.1065175; PubMed=11823633 [NCBI, ExPASy, EBI, Israel, Japan] Gaudet J., Mango S.E.; "Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4."; Science 295:821-825(2002).
[7]	FUNCTION. DOI=10.1016/j.ydbio.2003.10.015; PubMed=14738885 [NCBI, ExPASy, EBI, Israel, Japan] Vilimas T., Abraham A., Okkema P.G.; "An early pharyngeal muscle enhancer from the Caenorhabditis elegans ceh-22 gene is targeted by the forkhead factor PHA-4."; Dev. Biol. 266:388-398(2004).
[8]	DEVELOPMENTAL STAGE. DOI=10.1016/j.devcel.2004.12.019; PubMed=15737928 [NCBI, ExPASy, EBI, Israel, Japan] Grosshans H., Johnson T., Reinert K.L., Gerstein M., Slack F.J.; "The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C. elegans."; Dev. Cell 8:321-330(2005).
[9]	FUNCTION, AND MUTAGENESIS OF LEU-158. DOI=10.1002/dvdy.20550; PubMed=16127716 [NCBI, ExPASy, EBI, Israel, Japan] Kaltenbach L.S., Updike D.L., Mango S.E.; "Contribution of the amino and carboxyl termini for PHA-4/FoxA function in Caenorhabditis elegans."; Dev. Dyn. 234:346-354(2005).
[10]	FUNCTION. DOI=10.1371/journal.pgen.0020161; PubMed=17009877 [NCBI, ExPASy, EBI, Israel, Japan] Updike D.L., Mango S.E.; "Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA."; PLoS Genet. 2:1500-1510(2006).
[11]	FUNCTION. DOI=10.1016/j.ydbio.2006.08.023; PubMed=17005176 [NCBI, ExPASy, EBI, Israel, Japan] Smith P.A., Mango S.E.; "Role of T-box gene tbx-2 for anterior foregut muscle development in C. elegans."; Dev. Biol. 302:25-39(2007).
[12]	FUNCTION, AND DEVELOPMENTAL STAGE. DOI=10.1016/j.ydbio.2006.11.042; PubMed=17250823 [NCBI, ExPASy, EBI, Israel, Japan] Kiefer J.C., Smith P.A., Mango S.E.; "PHA-4/FoxA cooperates with TAM-1/TRIM to regulate cell fate restriction in the C. elegans foregut."; Dev. Biol. 303:611-624(2007).
[13]	FUNCTION, AND SUBCELLULAR LOCATION. DOI=10.1038/nature05837; PubMed=17476212 [NCBI, ExPASy, EBI, Israel, Japan] Panowski S.H., Wolff S., Aguilaniu H., Durieux J., Dillin A.; "PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans."; Nature 447:550-555(2007).

Comments

FUNCTION: Acts as a transcription factor required for formation of the pharyngeal primordium. Binds to the consensus sequence 5'-T[AG]TT[TG][AG][TC]-3' with variations of the sequence affecting onset of target gene expression. Activates a wide array of pharyngeal genes including ceh-22 and myo-2 and represses ectodermal genes lin-26 and elt-3, ensuring pharyngeal cell fate. Required for recruitment of htz-1 to a subset of pharyngeal promoters to ensure gene activation and also acts synergistically with tbx-2 in pharyngeal development. Acts in the regulation of diet-restriction-mediated longevity by increasing expression of sod-1, sod-2, sod-4 and sod-5 but not sod-3.
INTERACTION:
Q18937:-; NbExp=1; IntAct=EBI-321384, EBI-315080;
Q8ITV6:-; NbExp=1; IntAct=EBI-321384, EBI-319717;
Q9U1X3:-; NbExp=1; IntAct=EBI-321384, EBI-315967;
Q22030:asd-1; NbExp=1; IntAct=EBI-321384, EBI-312085;
O01530:asp-6; NbExp=1; IntAct=EBI-321384, EBI-316691;
Q21361:atf-2; NbExp=1; IntAct=EBI-321384, EBI-317743;
Q23158:atn-1; NbExp=1; IntAct=EBI-321384, EBI-314014;
Q9U1S2:brp-1; NbExp=1; IntAct=EBI-321384, EBI-313822;
Q10572:fox-1; NbExp=1; IntAct=EBI-321384, EBI-317821;
P91820:lst-1; NbExp=1; IntAct=EBI-321384, EBI-313618;
P92004:tag-260; NbExp=1; IntAct=EBI-321384, EBI-316398;
O16936:tam-1; NbExp=1; IntAct=EBI-321384, EBI-319647;
SUBCELLULAR LOCATION: Nucleus. Note=Present in nuclei of all cells of larval and adult pharynx but variable in neuronal nuclei.

ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing.

Name	a
Synonyms	I
Isoform ID	Q17381-1
This is the isoform sequence displayed in this entry.

Name	b
Synonyms	II
Isoform ID	Q17381-2
Features which should be applied to build the isoform sequence: VSP_052482.

Name	c
Synonyms	III
Isoform ID	Q17381-3
Features which should be applied to build the isoform sequence: VSP_052483.

TISSUE SPECIFICITY: Strongly expressed in the embryonic pharynx, particularly pharyngeal primordium precursor cells. Expression less strong in the embryonic gut.
DEVELOPMENTAL STAGE: Expression first seen at the 8E cell stage in the embryonic gut. After hatching, expression is almost diminished in the pharynx and gut. Expressed in L3/L4 larvae in cells of the developing gonad. At the 8-12E stage, expression is seen for the first time in the rectal precursors. Intestinal expression is down-regulated during the larval to adult transition.
MISCELLANEOUS: Worms lacking pha-4 are unable to form the pharyngeal primordium with the pharyngeal precursor cells, ABaraapapaa and ABaraapppaa showing arrested development prior to terminal cell division. Some mutants exhibit malformed rectal tissues and fail to undergo proper embryonic elongation.
SIMILARITY: Contains 1 fork-head DNA-binding domain.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U51163; AAA96319.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Z92833; CAB07378.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Z92833; CAK12559.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Z92833; CAK12560.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

T21941; T21941.

NP_001041114.1; -.

3D structure databases

HSSP

Q99958; 1D5V. [HSSP ENTRY / PDB]

ModBase

Q17381.

Protein-protein interaction databases

DIP

DIP:27474N; -.

IntAct

Q17381; -.

Organism-specific databases

WormBase

WBGene00004013; pha-4.

WormPep

F38A6.1a; CE15998. [WormPep / WorfDB]
F38A6.1b; CE40228. [WormPep / WorfDB]
F38A6.1c; CE40229. [WormPep / WorfDB]

Gene expression databases

ArrayExpress

Q17381; -.

Ontologies

GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0009792;	Biological process: embryonic development ending in birth or egg hatching (inferred from mutant phenotype from WormBase).
GO:0040011;	Biological process: locomotion (inferred from mutant phenotype from WormBase).
GO:0002119;	Biological process: nematode larval development (inferred from mutant phenotype from WormBase).
GO:0040010;	Biological process: positive regulation of growth rate (inferred from mutant phenotype from WormBase).
GO:0000003;	Biological process: reproduction (inferred from mutant phenotype from WormBase).
QuickGo view.

Family and domain databases

InterPro

IPR001766; TF_Fork_head.
IPR011991; Wing_hlx_DNA_bd.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 1.

PANTHER

PTHR11829; Fork_box_protein; 1.

Pfam

PF00250; Fork_head; 1.
Pfam graphical view of domain structure.

PRINTS

PR00053; FORKHEAD.

ProDom

PD000425; TF_Fork_head; 1.
[Domain structure / List of seq. sharing at least 1 domain]

SMART

SM00339; FH; 1.
SMART graphical view of domain structure.

PROSITE

PS00657; FORK_HEAD_1; 1.
PS00658; FORK_HEAD_2; 1.
PS50039; FORK_HEAD_3; 1.
PROSITE graphical view of domain structure (profiles).

BLOCKS

Q17381.

Genome annotation databases

Ensembl

F38A6.1; Caenorhabditis elegans. [Contig view]

GeneID

180357; -.

KEGG

cel:F38A6.1; -.

NMPDR

fig|6239.3.peg.22156; -.

Other

ProtoNet

Q17381.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Activator; Alternative splicing; Coiled coil; Complete proteome; Developmental protein; DNA-binding; Nucleus; Repressor; Transcription; Transcription regulation.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 506`	`506`	`Defective pharyngeal development protein 4.`	`PRO_0000294935`
`DNA_BIND`	`236 330`	`95`	`Fork-head.`
`COILED`	`38 66`	`29`	`Potential.`
`VAR_SEQ`	`1 95`		`Missing (in isoform c).`	`VSP_052483`
`VAR_SEQ`	`1 64`		`Missing (in isoform b).`	`VSP_052482`
`MUTAGEN`	`158 158`		`L->F: In q400; induces embryonic developmental arrest and lack of a pharynx.`

Sequence information

Length: 506 AA [This is the length of the unprocessed precursor]

Molecular weight: 55427 Da [This is the MW of the unprocessed precursor]

CRC64: B9AF5D1A846F2A5E [This is a checksum on the sequence]

        10         20         30         40         50         60 
MTSPSSDEDI IDIRVIKEEP ESEPDSEAEP ATTTNSTDSE DSVEQENKKL LETEKNRKRE 

        70         80         90        100        110        120 
QKHKMLPNGT TSGTSDTGNQ VPATSSAASS VDYTAMNAQD YLPTYSNTTL NYQPYQYQTA 

       130        140        150        160        170        180 
ANGLLNYNNY SQYATANQLG SNYISPANFM QGGGISPLGF TTGTTGATTA AASVATSSAS 

       190        200        210        220        230        240 
AVIGRSNGRS SSTVAASPAD RSYSGVSGGQ GQELTIQEFE TVTEKIRRHG TYGQSKPPYS 

       250        260        270        280        290        300 
YISLITMAIQ KSNSRQLTLS EIYNWIMDLF PYYQNNQQRW QNSIRHSLSF NDCFVKVARS 

       310        320        330        340        350        360 
PDKPGKGSFW TLHEHCGNMF ENGCYLRRQK RFKVKEREPS RKKRNANSQQ LHQQQHIPKM 

       370        380        390        400        410        420 
EIKEEDPTSI TTTSSLGAYS LIPQISTKKE IKEELKAVQD ATAAAANLGL IDPSGTPSAV 

       430        440        450        460        470        480 
NHSQPTSVIS SVGTLGTTQA QMTLNGQYAS PYLYSSDFAT ILPQSQNFLN NTLYNTTSSY 

       490        500 
PGIDYTNGVY QNTLYSSTNP NSAANL

Q17381 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools