HNF4_DROME
ID HNF4_DROME Reviewed; 704 AA.
AC P49866; A8DYX8; C5WLN3; Q8IGG2; Q8IPF2; Q9VLI7; Q9VLI8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Transcription factor HNF-4 homolog;
DE Short=dHNF4;
DE AltName: Full=Nuclear receptor subfamily 2 group A member 4;
GN Name=Hnf4; Synonyms=NR2A4; ORFNames=CG9310;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, SUBUNIT, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Ovary;
RX PubMed=8440243; DOI=10.1002/j.1460-2075.1993.tb05685.x;
RA Zhong W., Sladek F.M., Darnell J.E. Jr.;
RT "The expression pattern of a Drosophila homolog to the mouse transcription
RT factor HNF-4 suggests a determinative role in gut formation.";
RL EMBO J. 12:537-544(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B).
RC STRAIN=Berkeley; TISSUE=Embryo, and Head;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley;
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.;
RL Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=19254568; DOI=10.1016/j.cmet.2009.01.009;
RA Palanker L., Tennessen J.M., Lam G., Thummel C.S.;
RT "Drosophila HNF4 regulates lipid mobilization and beta-oxidation.";
RL Cell Metab. 9:228-239(2009).
CC -!- FUNCTION: Transcriptionally controlled transcription factor. Important
CC for the differentiation of various specialized cell types that arise
CC from both endoderm and mesoderm. May have a role in early gut
CC formation. Plays an essential role in lipid catabolism, regulating
CC lipid mobilization and beta-oxidation in response to nutrient
CC deprivation. {ECO:0000269|PubMed:19254568, ECO:0000269|PubMed:8440243}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:8440243}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:19254568}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A;
CC IsoId=P49866-1; Sequence=Displayed;
CC Name=D;
CC IsoId=P49866-2; Sequence=VSP_054577;
CC Name=B;
CC IsoId=P49866-3; Sequence=VSP_054578;
CC -!- TISSUE SPECIFICITY: In third instar larvae, expressed at high levels in
CC midgut and attached gastric caeca, fat body, Malpighian tubules and
CC oenocytes, and at lower levels in proventriculus, salivary glands,
CC epidermis, brain and ring gland. Not detected in imaginal disks and the
CC median neurosecretory cells that produce insulin-like peptides (at
CC protein level). In developing embryos, expressed in mid-gut, fat bodies
CC and the distal region of Malpighian tubules.
CC {ECO:0000269|PubMed:19254568, ECO:0000269|PubMed:8440243}.
CC -!- DISRUPTION PHENOTYPE: Under normal culture conditions, the flies
CC progress through development until they die during or shortly after
CC adult eclosion. Under low density culture conditions, many flies
CC survive and develop into morphologically normal adults. The mutant
CC flies are, however, very sensitive to starvation, displaying inability
CC to efficiently mobilize stored lipid in the midgut and fat body,
CC increased levels of long-chain fatty acids and triglycerides, and
CC premature death. {ECO:0000269|PubMed:19254568}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB09592.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAN71555.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=ACS68165.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U70874; AAB09592.1; ALT_INIT; mRNA.
DR EMBL; AE014134; AAF52702.2; -; Genomic_DNA.
DR EMBL; AE014134; AAF52703.2; -; Genomic_DNA.
DR EMBL; AE014134; AAN10680.1; -; Genomic_DNA.
DR EMBL; AE014134; ABV53653.1; -; Genomic_DNA.
DR EMBL; BT001800; AAN71555.1; ALT_INIT; mRNA.
DR EMBL; BT003533; AAO39537.1; -; mRNA.
DR EMBL; BT088848; ACS68165.1; ALT_INIT; mRNA.
DR PIR; S36218; S36218.
DR RefSeq; NP_001097126.1; NM_001103656.3. [P49866-2]
DR RefSeq; NP_476887.2; NM_057539.5. [P49866-1]
DR RefSeq; NP_723413.1; NM_164833.2. [P49866-3]
DR RefSeq; NP_723414.2; NM_164834.2. [P49866-1]
DR AlphaFoldDB; P49866; -.
DR SMR; P49866; -.
DR BioGRID; 69122; 12.
DR DIP; DIP-19209N; -.
DR IntAct; P49866; 4.
DR STRING; 7227.FBpp0079350; -.
DR PaxDb; P49866; -.
DR PRIDE; P49866; -.
DR DNASU; 44544; -.
DR EnsemblMetazoa; FBtr0079747; FBpp0079349; FBgn0004914. [P49866-1]
DR EnsemblMetazoa; FBtr0079748; FBpp0079350; FBgn0004914. [P49866-3]
DR EnsemblMetazoa; FBtr0112846; FBpp0111759; FBgn0004914. [P49866-2]
DR EnsemblMetazoa; FBtr0336633; FBpp0307616; FBgn0004914. [P49866-1]
DR GeneID; 44544; -.
DR KEGG; dme:Dmel_CG9310; -.
DR UCSC; CG9310-RA; d. melanogaster.
DR UCSC; CG9310-RB; d. melanogaster.
DR UCSC; CG9310-RD; d. melanogaster.
DR CTD; 44544; -.
DR FlyBase; FBgn0004914; Hnf4.
DR VEuPathDB; VectorBase:FBgn0004914; -.
DR eggNOG; KOG4215; Eukaryota.
DR GeneTree; ENSGT00940000167734; -.
DR InParanoid; P49866; -.
DR Reactome; R-DME-383280; Nuclear Receptor transcription pathway.
DR SignaLink; P49866; -.
DR BioGRID-ORCS; 44544; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 44544; -.
DR PRO; PR:P49866; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0004914; Expressed in thoracico-abdominal ganglion (Drosophila) and 41 other tissues.
DR ExpressionAtlas; P49866; baseline and differential.
DR Genevisible; P49866; DM.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0003707; F:nuclear steroid receptor activity; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IMP:FlyBase.
DR GO; GO:0042593; P:glucose homeostasis; IMP:FlyBase.
DR GO; GO:0016042; P:lipid catabolic process; IDA:FlyBase.
DR GO; GO:0034440; P:lipid oxidation; IDA:FlyBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:FlyBase.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR000003; Retinoid-X_rcpt/HNF4.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00545; RETINOIDXR.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Lipid degradation; Lipid metabolism;
KW Metal-binding; Nucleus; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..704
FT /note="Transcription factor HNF-4 homolog"
FT /id="PRO_0000053565"
FT DOMAIN 232..470
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 139..214
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 142..162
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 178..197
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 93..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 474..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 563..624
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 684..704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 478..516
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 563..600
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..32
FT /note="MMKHPQDLSVTDDQQLMKVNKVEKMEQELHDP -> MVRKSGRVKISSRDRV
FT AVGNILLRGKVGGGRVAVAAAEEAEAGRRRRRRDSSASRTASSD (in isoform
FT B)"
FT /evidence="ECO:0000303|Ref.4, ECO:0000303|Ref.5"
FT /id="VSP_054578"
FT VAR_SEQ 1..32
FT /note="MMKHPQDLSVTDDQQLMKVNKVEKMEQELHDP -> MYASMLPSLLNMKTEN
FT LTSSSYDDAFLLEENLLHIM (in isoform D)"
FT /evidence="ECO:0000305"
FT /id="VSP_054577"
FT CONFLICT 113
FT /note="N -> Y (in Ref. 1; AAB09592)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="S -> N (in Ref. 1; AAB09592)"
FT /evidence="ECO:0000305"
FT CONFLICT 159
FT /note="C -> F (in Ref. 4; AAN71555)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 704 AA; 76388 MW; 5868280AFE7A00CC CRC64;
MMKHPQDLSV TDDQQLMKVN KVEKMEQELH DPESESHIMH ADALASAYPA ASQPHSPIGL
ALSPNGGGLG LSNSSNQSSE NFALCNGNGN AGSAGGGSAS SGSNNNNSMF SPNNNLSGSG
SGTNSSQQQL QQQQQQQSPT VCAICGDRAT GKHYGASSCD GCKGFFRRSV RKNHQYTCRF
ARNCVVDKDK RNQCRYCRLR KCFKAGMKKE AVQNERDRIS CRRTSNDDPD PGNGLSVISL
VKAENESRQS KAGAAMEPNI NEDLSNKQFA SINDVCESMK QQLLTLVEWA KQIPAFNELQ
LDDQVALLRA HAGEHLLLGL SRRSMHLKDV LLLSNNCVIT RHCPDPLVSP NLDISRIGAR
IIDELVTVMK DVGIDDTEFA CIKALVFFDP NAKGLNEPHR IKSLRHQILN NLEDYISDRQ
YESRGRFGEI LLILPVLQSI TWQMIEQIQF AKIFGVAHID SLLQEMLLGG ELADNPLPLS
PPNQSNDYQS PTHTGNMEGG NQVNSSLDSL ATSGGPGSHS LDLEVQHIQA LIEANSADDS
FRAYAASTAA AAAAAVSSSS SAPASVAPAS ISPPLNSPKS QHQHQQHATH QQQQESSYLD
MPVKHYNGSR SGPLPTQHSP QRMHPYQRAV ASPVEVSSGG GGLGLRNPAD ITLNEYNRSE
GSSAEELLRR TPLKIRAPEM LTAPAGYGTE PCRMTLKQEP ETGY
