Q17381 (PHA4_CAEEL) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Caenorhabditis elegans [Reference proteome]

Taxonomic identifier

6239 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Nematoda › Chromadorea › Rhabditida › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis

Protein attributes

Sequence length	506 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Coiled coil
Ligand	DNA-binding
Molecular function	Activator Developmental protein Repressor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 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
Cellular_component	transcription factor complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	DNA 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 protein domain specific binding Inferred from Biological aspect of Ancestor. Source: RefGenome sequence-specific DNA binding Inferred from direct assay Ref.7PubMed 20530643Ref.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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 506	506	Defective pharyngeal development protein 4		PRO_0000294935
Regions
	DNA binding	236 – 330	95	Fork-head
	Coiled coil	38 – 66	29	Potential
Natural variations
	Alternative sequence	1 – 95	95	Missing in isoform c. Ref.5		VSP_052483
	Alternative sequence	1 – 64	64	Missing in isoform b. Ref.5		VSP_052482
Experimental info
	Mutagenesis	158	1	L → F in q400; induces embryonic developmental arrest and lack of a pharynx. Ref.9 Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Isoform a (I) [UniParc]. Last modified November 1, 1996. Version 1. Checksum: B9AF5D1A846F2A5E	FASTA	506	55,427
	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
	Isoform b (II) [UniParc]. Checksum: C7BEF1674EEB5A19	FASTA	442	48,114
	10 20 30 40 50 60 MLPNGTTSGT SDTGNQVPAT SSAASSVDYT AMNAQDYLPT YSNTTLNYQP YQYQTAANGL 70 80 90 100 110 120 LNYNNYSQYA TANQLGSNYI SPANFMQGGG ISPLGFTTGT TGATTAAASV ATSSASAVIG 130 140 150 160 170 180 RSNGRSSSTV AASPADRSYS GVSGGQGQEL TIQEFETVTE KIRRHGTYGQ SKPPYSYISL 190 200 210 220 230 240 ITMAIQKSNS RQLTLSEIYN WIMDLFPYYQ NNQQRWQNSI RHSLSFNDCF VKVARSPDKP 250 260 270 280 290 300 GKGSFWTLHE HCGNMFENGC YLRRQKRFKV KEREPSRKKR NANSQQLHQQ QHIPKMEIKE 310 320 330 340 350 360 EDPTSITTTS SLGAYSLIPQ ISTKKEIKEE LKAVQDATAA AANLGLIDPS GTPSAVNHSQ 370 380 390 400 410 420 PTSVISSVGT LGTTQAQMTL NGQYASPYLY SSDFATILPQ SQNFLNNTLY NTTSSYPGID 430 440 YTNGVYQNTL YSSTNPNSAA NL
	Isoform c (III) [UniParc]. Checksum: 79DAC4026BE69CD3	FASTA	411	45,143
	10 20 30 40 50 60 MNAQDYLPTY SNTTLNYQPY QYQTAANGLL NYNNYSQYAT ANQLGSNYIS PANFMQGGGI 70 80 90 100 110 120 SPLGFTTGTT GATTAAASVA TSSASAVIGR SNGRSSSTVA ASPADRSYSG VSGGQGQELT 130 140 150 160 170 180 IQEFETVTEK IRRHGTYGQS KPPYSYISLI TMAIQKSNSR QLTLSEIYNW IMDLFPYYQN 190 200 210 220 230 240 NQQRWQNSIR HSLSFNDCFV KVARSPDKPG KGSFWTLHEH CGNMFENGCY LRRQKRFKVK 250 260 270 280 290 300 EREPSRKKRN ANSQQLHQQQ HIPKMEIKEE DPTSITTTSS LGAYSLIPQI STKKEIKEEL 310 320 330 340 350 360 KAVQDATAAA ANLGLIDPSG TPSAVNHSQP TSVISSVGTL GTTQAQMTLN GQYASPYLYS 370 380 390 400 410 SDFATILPQS QNFLNNTLYN TTSSYPGIDY TNGVYQNTLY SSTNPNSAAN L

References

	« Hide 'large scale' referencesShow '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.
PIR	T21941.
RefSeq	NP_001041114.1. NM_001047649.2. NP_001041115.1. NM_001047650.2. NP_001041116.1. NM_001047651.3.
3D structure databases
HSSP	HSSP built from PDB template 1D5V based on UniProtKB Q99958.
ProteinModelPortal	Q17381.
SMR	Q17381. Positions 234-334.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-27474N.
IntAct	Q17381. 12 interactions.
MINT	MINT-1038224.
Proteomic databases
PaxDb	Q17381.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	F38A6.1a; F38A6.1a; F38A6.1.
GeneID	180357.
KEGG	cel:CELE_F38A6.1.
UCSC	F38A6.1a. c. elegans.
Organism-specific databases
CTD	180357.
WormBase	F38A6.1a; CE15998; WBGene00004013; pha-4. F38A6.1b; CE40228; WBGene00004013; pha-4. F38A6.1c; CE40229; WBGene00004013; pha-4.
Phylogenomic databases
eggNOG	COG5025.
GeneTree	ENSGT00690000101636.
HOGENOM	HOG000115523.
InParanoid	Q17381.
OMA	PSRKKRN.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR001766. TF_fork_head. IPR018122. TF_fork_head_CS. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00250. Fork_head. 1 hit. [Graphical view]
PRINTS	PR00053. FORKHEAD.
SMART	SM00339. FH. 1 hit. [Graphical view]
PROSITE	PS00657. FORK_HEAD_1. 1 hit. PS00658. FORK_HEAD_2. 1 hit. PS50039. FORK_HEAD_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	909012.

Entry information

Entry name

PHA4_CAEEL

Accession

Primary (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:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Caenorhabditis annotation project