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Q17381

- PHA4_CAEEL

UniProt

Q17381 - PHA4_CAEEL

Protein

Defective pharyngeal development protein 4

Gene

pha-4

Organism
Caenorhabditis elegans
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 128 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    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-3.10 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi236 – 33095Fork-headPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. sequence-specific DNA binding Source: WormBase
    2. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: WormBase

    GO - Biological processi

    1. cell differentiation Source: WormBase
    2. cell fate specification involved in pattern specification Source: WormBase
    3. determination of adult lifespan Source: WormBase
    4. embryonic morphogenesis Source: WormBase
    5. pharynx development Source: WormBase
    6. positive regulation of macroautophagy Source: WormBase
    7. positive regulation of transcription from RNA polymerase II promoter Source: WormBase
    8. positive regulation of translation Source: WormBase
    9. transcription from RNA polymerase II promoter Source: GOC

    Keywords - Molecular functioni

    Activator, Developmental protein, Repressor

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    SignaLinkiQ17381.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Defective pharyngeal development protein 4
    Alternative name(s):
    Ce-fkh-1
    Fork head-HNF-3 homolog
    Gene namesi
    Name:pha-4Imported
    Synonyms:fkh-1Imported
    ORF Names:F38A6.1
    OrganismiCaenorhabditis elegans
    Taxonomic identifieri6239 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
    ProteomesiUP000001940: Chromosome V

    Organism-specific databases

    WormBaseiF38A6.1a; CE15998; WBGene00004013; pha-4.
    F38A6.1b; CE40228; WBGene00004013; pha-4.
    F38A6.1c; CE40229; WBGene00004013; pha-4.

    Subcellular locationi

    Nucleus 3 PublicationsPROSITE-ProRule annotation
    Note: Present in nuclei of all cells of larval and adult pharynx but variable in neuronal nuclei.3 Publications

    GO - Cellular componenti

    1. nucleus Source: WormBase

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    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.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi158 – 1581L → F in q400; induces embryonic developmental arrest and lack of a pharynx. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 506506Defective pharyngeal development protein 4PRO_0000294935Add
    BLAST

    Proteomic databases

    PaxDbiQ17381.

    Expressioni

    Tissue specificityi

    Strongly expressed in the embryonic pharynx, particularly pharyngeal primordium precursor cells. Expression less strong in the embryonic gut.2 Publications

    Developmental stagei

    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.4 Publications

    Interactioni

    Protein-protein interaction databases

    BioGridi45314. 29 interactions.
    DIPiDIP-27474N.
    IntActiQ17381. 74 interactions.
    MINTiMINT-1038224.

    Structurei

    3D structure databases

    ProteinModelPortaliQ17381.
    SMRiQ17381. Positions 234-334.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili38 – 6629Sequence AnalysisAdd
    BLAST

    Sequence similaritiesi

    Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    eggNOGiCOG5025.
    GeneTreeiENSGT00740000115067.
    HOGENOMiHOG000115523.
    InParanoidiQ17381.
    OMAiQKRFKVK.
    OrthoDBiEOG7C8GHD.
    PhylomeDBiQ17381.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    InterProiIPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF00250. Fork_head. 1 hit.
    [Graphical view]
    PRINTSiPR00053. FORKHEAD.
    SMARTiSM00339. FH. 1 hit.
    [Graphical view]
    PROSITEiPS00657. FORK_HEAD_1. 1 hit.
    PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform a1 Publication (identifier: Q17381-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MTSPSSDEDI IDIRVIKEEP ESEPDSEAEP ATTTNSTDSE DSVEQENKKL    50
    LETEKNRKRE QKHKMLPNGT TSGTSDTGNQ VPATSSAASS VDYTAMNAQD 100
    YLPTYSNTTL NYQPYQYQTA ANGLLNYNNY SQYATANQLG SNYISPANFM 150
    QGGGISPLGF TTGTTGATTA AASVATSSAS AVIGRSNGRS SSTVAASPAD 200
    RSYSGVSGGQ GQELTIQEFE TVTEKIRRHG TYGQSKPPYS YISLITMAIQ 250
    KSNSRQLTLS EIYNWIMDLF PYYQNNQQRW QNSIRHSLSF NDCFVKVARS 300
    PDKPGKGSFW TLHEHCGNMF ENGCYLRRQK RFKVKEREPS RKKRNANSQQ 350
    LHQQQHIPKM EIKEEDPTSI TTTSSLGAYS LIPQISTKKE IKEELKAVQD 400
    ATAAAANLGL IDPSGTPSAV NHSQPTSVIS SVGTLGTTQA QMTLNGQYAS 450
    PYLYSSDFAT ILPQSQNFLN NTLYNTTSSY PGIDYTNGVY QNTLYSSTNP 500
    NSAANL 506
    Length:506
    Mass (Da):55,427
    Last modified:November 1, 1996 - v1
    Checksum:iB9AF5D1A846F2A5E
    GO
    Isoform b1 Publication (identifier: Q17381-2) [UniParc]FASTAAdd to Basket

    Also known as: II

    The sequence of this isoform differs from the canonical sequence as follows:
         1-64: Missing.

    Show »
    Length:442
    Mass (Da):48,114
    Checksum:iC7BEF1674EEB5A19
    GO
    Isoform c1 Publication (identifier: Q17381-3) [UniParc]FASTAAdd to Basket

    Also known as: III

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

    Show »
    Length:411
    Mass (Da):45,143
    Checksum:i79DAC4026BE69CD3
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 9595Missing in isoform c. 1 PublicationVSP_052483Add
    BLAST
    Alternative sequencei1 – 6464Missing in isoform b. 1 PublicationVSP_052482Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U51163 Genomic DNA. Translation: AAA96319.1.
    Z92833 Genomic DNA. Translation: CAB07378.1.
    Z92833 Genomic DNA. Translation: CAK12559.1.
    Z92833 Genomic DNA. Translation: CAK12560.1.
    PIRiT21941.
    RefSeqiNP_001041114.1. NM_001047649.2. [Q17381-1]
    NP_001041115.1. NM_001047650.2. [Q17381-2]
    NP_001041116.1. NM_001047651.3. [Q17381-3]
    UniGeneiCel.17389.

    Genome annotation databases

    EnsemblMetazoaiF38A6.1a; F38A6.1a; WBGene00004013. [Q17381-1]
    GeneIDi180357.
    KEGGicel:CELE_F38A6.1.
    UCSCiF38A6.1a. c. elegans. [Q17381-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U51163 Genomic DNA. Translation: AAA96319.1 .
    Z92833 Genomic DNA. Translation: CAB07378.1 .
    Z92833 Genomic DNA. Translation: CAK12559.1 .
    Z92833 Genomic DNA. Translation: CAK12560.1 .
    PIRi T21941.
    RefSeqi NP_001041114.1. NM_001047649.2. [Q17381-1 ]
    NP_001041115.1. NM_001047650.2. [Q17381-2 ]
    NP_001041116.1. NM_001047651.3. [Q17381-3 ]
    UniGenei Cel.17389.

    3D structure databases

    ProteinModelPortali Q17381.
    SMRi Q17381. Positions 234-334.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 45314. 29 interactions.
    DIPi DIP-27474N.
    IntActi Q17381. 74 interactions.
    MINTi MINT-1038224.

    Proteomic databases

    PaxDbi Q17381.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    EnsemblMetazoai F38A6.1a ; F38A6.1a ; WBGene00004013 . [Q17381-1 ]
    GeneIDi 180357.
    KEGGi cel:CELE_F38A6.1.
    UCSCi F38A6.1a. c. elegans. [Q17381-1 ]

    Organism-specific databases

    CTDi 180357.
    WormBasei F38A6.1a ; CE15998 ; WBGene00004013 ; pha-4.
    F38A6.1b ; CE40228 ; WBGene00004013 ; pha-4.
    F38A6.1c ; CE40229 ; WBGene00004013 ; pha-4.

    Phylogenomic databases

    eggNOGi COG5025.
    GeneTreei ENSGT00740000115067.
    HOGENOMi HOG000115523.
    InParanoidi Q17381.
    OMAi QKRFKVK.
    OrthoDBi EOG7C8GHD.
    PhylomeDBi Q17381.

    Enzyme and pathway databases

    SignaLinki Q17381.

    Miscellaneous databases

    NextBioi 909012.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF00250. Fork_head. 1 hit.
    [Graphical view ]
    PRINTSi PR00053. FORKHEAD.
    SMARTi SM00339. FH. 1 hit.
    [Graphical view ]
    PROSITEi PS00657. FORK_HEAD_1. 1 hit.
    PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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 N2Imported.
    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.

    Entry informationi

    Entry nameiPHA4_CAEEL
    AccessioniPrimary (citable) accession number: Q17381
    Secondary accession number(s): Q1HAZ5, Q1HAZ6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 10, 2007
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 128 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programCaenorhabditis annotation project

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Caenorhabditis elegans
      Caenorhabditis elegans: entries, gene names and cross-references to WormBase
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3