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Q17381 (PHA4_CAEEL) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Defective pharyngeal development protein 4
Alternative name(s):
Ce-fkh-1
Fork head-HNF-3 homolog
Gene names
Name:pha-4
Synonyms:fkh-1
ORF Names:F38A6.1
OrganismCaenorhabditis elegans [Reference proteome]
Taxonomic identifier6239 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis

Protein attributes

Sequence length506 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Subcellular location

Nucleus. Note: Present in nuclei of all cells of larval and adult pharynx but variable in neuronal nuclei. Ref.4 Ref.5 Ref.6 Ref.13

Tissue specificity

Strongly expressed in the embryonic pharynx, particularly pharyngeal primordium precursor cells. Expression less strong in the embryonic gut. Ref.1 Ref.4 Ref.5 Ref.6

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. Ref.1 Ref.5 Ref.8 Ref.12

Disruption phenotype

Worms 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. Ref.3

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from mutant phenotype Ref.12. Source: WormBase

cell fate specification involved in pattern specification

Inferred from mutant phenotype Ref.12. Source: WormBase

determination of adult lifespan

Inferred from genetic interaction PubMed 18804378PubMed 21906946. Source: WormBase

embryonic morphogenesis

Inferred from mutant phenotype Ref.3. Source: WormBase

negative regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

pharynx development

Inferred from mutant phenotype Ref.3. Source: WormBase

positive regulation of macroautophagy

Inferred from mutant phenotype PubMed 21906946. Source: WormBase

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 21906946Ref.4. Source: WormBase

positive regulation of translation

Inferred from mutant phenotype PubMed 18804378. Source: WormBase

regulation of sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

tissue development

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription from RNA polymerase II promoter

Inferred from mutant phenotype Ref.4. Source: GOC

   Cellular_componentnucleus

Inferred from direct assay Ref.13Ref.4. Source: WormBase

transcription factor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionDNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

double-stranded DNA binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

sequence-specific DNA binding

Inferred from direct assay Ref.7PubMed 20530643Ref.4. Source: WormBase

sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from mutant phenotype Ref.4. Source: WormBase

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform a Ref.5 (identifier: Q17381-1)

Also known as: I;

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 b Ref.5 (identifier: Q17381-2)

Also known as: II;

The sequence of this isoform differs from the canonical sequence as follows:
     1-64: Missing.
Isoform c Ref.5 (identifier: Q17381-3)

Also known as: III;

The sequence of this isoform differs from the canonical sequence as follows:
     1-95: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 506506Defective pharyngeal development protein 4
PRO_0000294935

Regions

DNA binding236 – 33095Fork-head
Coiled coil38 – 6629 Potential

Natural variations

Alternative sequence1 – 9595Missing in isoform c. Ref.5
VSP_052483
Alternative sequence1 – 6464Missing in isoform b. Ref.5
VSP_052482

Experimental info

Mutagenesis1581L → F in q400; induces embryonic developmental arrest and lack of a pharynx. Ref.9 Ref.10

Sequences

Sequence LengthMass (Da)Tools
Isoform a (I) [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: B9AF5D1A846F2A5E

FASTA50655,427
        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 

« Hide

Isoform b (II) [UniParc].

Checksum: C7BEF1674EEB5A19
Show »

FASTA44248,114
Isoform c (III) [UniParc].

Checksum: 79DAC4026BE69CD3
Show »

FASTA41145,143

References

« Hide 'large scale' references
[1]"A fork head/HNF-3 homolog expressed in the pharynx and intestine of the Caenorhabditis elegans embryo."
Azzaria M., Goszczynski B., Chung M.A., Kalb J.M., McGhee J.D.
Dev. Biol. 178:289-303(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, ALTERNATIVE SPLICING.
Strain: Bristol N2.
[2]"Genome sequence of the nematode C. elegans: a platform for investigating biology."
The C. elegans sequencing consortium
Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Bristol N2.
[3]"The pha-4 gene is required to generate the pharyngeal primordium of Caenorhabditis elegans."
Mango S.E., Lambie E.J., Kimble J.
Development 120:3019-3031(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[4]"pha-4 is Ce-fkh-1, a fork head/HNF-3alpha,beta,gamma homolog that functions in organogenesis of the C. elegans pharynx."
Kalb J.M., Lau K.K., Goszczynski B., Fukushige T., Moons D., Okkema P.G., McGhee J.D.
Development 125:2171-2180(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]"pha-4, an HNF-3 homolog, specifies pharyngeal organ identity in Caenorhabditis elegans."
Horner M.A., Quintin S., Domeier M.E., Kimble J., Labouesse M., Mango S.E.
Genes Dev. 12:1947-1952(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[6]"Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4."
Gaudet J., Mango S.E.
Science 295:821-825(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"An early pharyngeal muscle enhancer from the Caenorhabditis elegans ceh-22 gene is targeted by the forkhead factor PHA-4."
Vilimas T., Abraham A., Okkema P.G.
Dev. Biol. 266:388-398(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"The temporal patterning microRNA let-7 regulates several transcription factors at the larval to adult transition in C. elegans."
Grosshans H., Johnson T., Reinert K.L., Gerstein M., Slack F.J.
Dev. Cell 8:321-330(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[9]"Contribution of the amino and carboxyl termini for PHA-4/FoxA function in Caenorhabditis elegans."
Kaltenbach L.S., Updike D.L., Mango S.E.
Dev. Dyn. 234:346-354(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LEU-158.
[10]"Temporal regulation of foregut development by HTZ-1/H2A.Z and PHA-4/FoxA."
Updike D.L., Mango S.E.
PLoS Genet. 2:1500-1510(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Role of T-box gene tbx-2 for anterior foregut muscle development in C. elegans."
Smith P.A., Mango S.E.
Dev. Biol. 302:25-39(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"PHA-4/FoxA cooperates with TAM-1/TRIM to regulate cell fate restriction in the C. elegans foregut."
Kiefer J.C., Smith P.A., Mango S.E.
Dev. Biol. 303:611-624(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[13]"PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans."
Panowski S.H., Wolff S., Aguilaniu H., Durieux J., Dillin A.
Nature 447:550-555(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U51163 Genomic DNA. Translation: AAA96319.1.
Z92833 Genomic DNA. Translation: CAB07378.1.
Z92833 Genomic DNA. Translation: CAK12559.1.
Z92833 Genomic DNA. Translation: CAK12560.1.
PIRT21941.
RefSeqNP_001041114.1. NM_001047649.2.
NP_001041115.1. NM_001047650.2.
NP_001041116.1. NM_001047651.3.
UniGeneCel.17389.

3D structure databases

ProteinModelPortalQ17381.
SMRQ17381. Positions 234-334.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid45314. 29 interactions.
DIPDIP-27474N.
IntActQ17381. 74 interactions.
MINTMINT-1038224.

Proteomic databases

PaxDbQ17381.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaF38A6.1a; F38A6.1a; F38A6.1. [Q17381-1]
GeneID180357.
KEGGcel:CELE_F38A6.1.
UCSCF38A6.1a. c. elegans. [Q17381-1]

Organism-specific databases

CTD180357.
WormBaseF38A6.1a; CE15998; WBGene00004013; pha-4.
F38A6.1b; CE40228; WBGene00004013; pha-4.
F38A6.1c; CE40229; WBGene00004013; pha-4.

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000115523.
InParanoidQ17381.
OMAQKRFKVK.
OrthoDBEOG7C8GHD.
PhylomeDBQ17381.

Enzyme and pathway databases

SignaLinkQ17381.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00657. FORK_HEAD_1. 1 hit.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio909012.

Entry information

Entry namePHA4_CAEEL
AccessionPrimary (citable) accession number: Q17381
Secondary accession number(s): Q1HAZ5, Q1HAZ6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 10, 2007
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

Caenorhabditis elegans

Caenorhabditis elegans: entries, gene names and cross-references to WormBase