HMEN_DROME
ID HMEN_DROME Reviewed; 552 AA.
AC P02836; P02837; Q0E9C0; Q24356; Q9V601;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 02-FEB-2004, sequence version 2.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Segmentation polarity homeobox protein engrailed;
GN Name=en; ORFNames=CG9015;
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 [GENOMIC DNA / MRNA].
RC TISSUE=Embryo;
RX PubMed=3917855; DOI=10.1016/0092-8674(85)90306-x;
RA Poole S.J., Kauvar L.M., Drees B., Kornberg T.;
RT "The engrailed locus of Drosophila: structural analysis of an embryonic
RT transcript.";
RL Cell 40:37-43(1985).
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.
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].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 443-518.
RX PubMed=2481829; DOI=10.1038/313284a0;
RA Fjose A., McGinnis W., Gehring W.J.;
RT "Isolation of a homoeo box-containing gene from the engrailed region of
RT Drosophila and the spatial distribution of its transcripts.";
RL Nature 313:284-289(1985).
RN [6]
RP CHARACTERIZATION.
RX PubMed=8334991; DOI=10.1002/j.1460-2075.1993.tb05934.x;
RA Han K., Manley J.L.;
RT "Functional domains of the Drosophila Engrailed protein.";
RL EMBO J. 12:2723-2733(1993).
RN [7]
RP PHOSPHORYLATION.
RX PubMed=2899884; DOI=10.1093/nar/16.14.6637;
RA Gay N.J., Poole S.J., Kornberg T.B.;
RT "The Drosophila engrailed protein is phosphorylated by a serine-specific
RT protein kinase.";
RL Nucleic Acids Res. 16:6637-6647(1988).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=3935318; DOI=10.1016/0092-8674(85)90012-1;
RA Dinardo S., Kuner J.M., Theis J., O'Farrell P.H.;
RT "Development of embryonic pattern in D. melanogaster as revealed by
RT accumulation of the nuclear engrailed protein.";
RL Cell 43:59-69(1985).
RN [9]
RP INTERACTION WITH WG AND EN.
RC TISSUE=Embryo;
RX PubMed=1335365; DOI=10.1016/s0092-8674(05)80065-0;
RA Siegfried E., Chou T.B., Perrimon N.;
RT "wingless signaling acts through zeste-white 3, the Drosophila homolog of
RT glycogen synthase kinase-3, to regulate engrailed and establish cell
RT fate.";
RL Cell 71:1167-1179(1992).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 453-512.
RX PubMed=1977522; DOI=10.1016/0092-8674(90)90453-l;
RA Kissinger C.R., Liu B., Martin-Blanco E., Kornberg T.B., Pabo C.O.;
RT "Crystal structure of an engrailed homeodomain-DNA complex at 2.8-A
RT resolution: a framework for understanding homeodomain-DNA interactions.";
RL Cell 63:579-590(1990).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 458-512 OF MUTANT LYS-508.
RX PubMed=9309220; DOI=10.1016/s0969-2126(97)00256-6;
RA Tucker-Kellogg L., Rould M.A., Chambers K.A., Ades S.E., Sauer R.T.,
RA Pabo C.O.;
RT "Engrailed (Gln50-->Lys) homeodomain-DNA complex at 1.9-A resolution:
RT structural basis for enhanced affinity and altered specificity.";
RL Structure 5:1047-1054(1997).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 455-512.
RX PubMed=9813123; DOI=10.1006/jmbi.1998.2147;
RA Fraenkel E., Rould M.A., Chambers K.A., Pabo C.O.;
RT "Engrailed homeodomain-DNA complex at 2.2-A resolution: a detailed view of
RT the interface and comparison with other engrailed structures.";
RL J. Mol. Biol. 284:351-361(1998).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 456-512.
RX PubMed=10889025; DOI=10.1021/bi000071a;
RA Grant R.A., Rould M.A., Klemm J.D., Pabo C.O.;
RT "Exploring the role of glutamine 50 in the homeodomain-DNA interface:
RT crystal structure of engrailed (Gln50 --> Ala) complex at 2.0 A.";
RL Biochemistry 39:8187-8192(2000).
CC -!- FUNCTION: This protein specifies the body segmentation pattern. It is
CC required for the development of the central nervous system.
CC Transcriptional regulator that represses activated promoters. Wg
CC signaling operates by inactivating the SGG repression of EN
CC autoactivation.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:3935318}.
CC -!- DEVELOPMENTAL STAGE: Expression initiates prior to the ninth embryonic
CC nuclear division cycle within 1.5 hours after fertilization. By the
CC cellular blastoderm stage (the 14th nuclear division cycle) is
CC localized into 14 stripes, 1-2 cells wide, spaced along the anterior-
CC posterior axis of the embryo.
CC -!- PTM: Phosphorylated. Phosphorylation may directly or allosterically
CC modify its function. {ECO:0000269|PubMed:2899884}.
CC -!- SIMILARITY: Belongs to the engrailed homeobox family. {ECO:0000305}.
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DR EMBL; M10017; AAA65478.1; -; mRNA.
DR EMBL; K03055; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; K03056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AE013599; AAF58639.1; -; Genomic_DNA.
DR EMBL; AY069448; AAL39593.1; -; mRNA.
DR EMBL; X01765; CAA25906.1; -; Genomic_DNA.
DR PIR; A90862; WJFFEN.
DR RefSeq; NP_523700.2; NM_078976.4.
DR RefSeq; NP_725059.1; NM_165841.2.
DR PDB; 1DU0; X-ray; 2.00 A; A/B=456-512.
DR PDB; 1ENH; X-ray; 2.10 A; A=456-509.
DR PDB; 1HDD; X-ray; 2.80 A; C/D=453-512.
DR PDB; 1P7I; X-ray; 2.10 A; A/B/C/D=454-512.
DR PDB; 1P7J; X-ray; 2.10 A; A/B/C/D=454-512.
DR PDB; 1ZTR; NMR; -; A=453-512.
DR PDB; 2HDD; X-ray; 1.90 A; A/B=454-512.
DR PDB; 2HOS; X-ray; 1.90 A; A/B=453-513.
DR PDB; 2HOT; X-ray; 2.19 A; A/B=453-513.
DR PDB; 2JWT; NMR; -; A=453-512.
DR PDB; 2P81; NMR; -; A=469-512.
DR PDB; 3HDD; X-ray; 2.20 A; A/B=454-513.
DR PDB; 6FVC; NMR; -; A=454-512.
DR PDB; 6M3D; X-ray; 1.60 A; C=453-512.
DR PDBsum; 1DU0; -.
DR PDBsum; 1ENH; -.
DR PDBsum; 1HDD; -.
DR PDBsum; 1P7I; -.
DR PDBsum; 1P7J; -.
DR PDBsum; 1ZTR; -.
DR PDBsum; 2HDD; -.
DR PDBsum; 2HOS; -.
DR PDBsum; 2HOT; -.
DR PDBsum; 2JWT; -.
DR PDBsum; 2P81; -.
DR PDBsum; 3HDD; -.
DR PDBsum; 6FVC; -.
DR PDBsum; 6M3D; -.
DR AlphaFoldDB; P02836; -.
DR BMRB; P02836; -.
DR SMR; P02836; -.
DR BioGRID; 62028; 29.
DR ELM; P02836; -.
DR IntAct; P02836; 6.
DR STRING; 7227.FBpp0087197; -.
DR iPTMnet; P02836; -.
DR PaxDb; P02836; -.
DR DNASU; 36240; -.
DR EnsemblMetazoa; FBtr0088095; FBpp0087197; FBgn0000577.
DR EnsemblMetazoa; FBtr0088096; FBpp0087198; FBgn0000577.
DR GeneID; 36240; -.
DR KEGG; dme:Dmel_CG9015; -.
DR CTD; 36240; -.
DR FlyBase; FBgn0000577; en.
DR VEuPathDB; VectorBase:FBgn0000577; -.
DR eggNOG; KOG0493; Eukaryota.
DR GeneTree; ENSGT00940000167868; -.
DR HOGENOM; CLU_485085_0_0_1; -.
DR InParanoid; P02836; -.
DR OMA; FHNQTHT; -.
DR OrthoDB; 858478at2759; -.
DR PhylomeDB; P02836; -.
DR SignaLink; P02836; -.
DR BioGRID-ORCS; 36240; 0 hits in 3 CRISPR screens.
DR EvolutionaryTrace; P02836; -.
DR GenomeRNAi; 36240; -.
DR PRO; PR:P02836; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0000577; Expressed in head epidermis primordium (Drosophila) and 57 other tissues.
DR ExpressionAtlas; P02836; baseline and differential.
DR Genevisible; P02836; DM.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:FlyBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:FlyBase.
DR GO; GO:0007487; P:analia development; TAS:FlyBase.
DR GO; GO:0035288; P:anterior head segmentation; TAS:FlyBase.
DR GO; GO:0048099; P:anterior/posterior lineage restriction, imaginal disc; TAS:FlyBase.
DR GO; GO:0007411; P:axon guidance; IMP:FlyBase.
DR GO; GO:0007386; P:compartment pattern specification; TAS:FlyBase.
DR GO; GO:0035224; P:genital disc anterior/posterior pattern formation; IEP:FlyBase.
DR GO; GO:0035215; P:genital disc development; IMP:FlyBase.
DR GO; GO:0008406; P:gonad development; IMP:FlyBase.
DR GO; GO:0007474; P:imaginal disc-derived wing vein specification; IMP:FlyBase.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:FlyBase.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:FlyBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:FlyBase.
DR GO; GO:0007400; P:neuroblast fate determination; IGI:FlyBase.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:FlyBase.
DR GO; GO:0007388; P:posterior compartment specification; TAS:FlyBase.
DR GO; GO:0035289; P:posterior head segmentation; TAS:FlyBase.
DR GO; GO:0010468; P:regulation of gene expression; IMP:FlyBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007367; P:segment polarity determination; TAS:FlyBase.
DR GO; GO:0035277; P:spiracle morphogenesis, open tracheal system; IMP:FlyBase.
DR GO; GO:0035290; P:trunk segmentation; TAS:FlyBase.
DR GO; GO:0007418; P:ventral midline development; IMP:FlyBase.
DR GO; GO:0048100; P:wing disc anterior/posterior pattern formation; TAS:FlyBase.
DR GO; GO:0007472; P:wing disc morphogenesis; IMP:FlyBase.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR019549; Homeobox-engrailed_C-terminal.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR000747; Homeobox_engrailed.
DR InterPro; IPR020479; Homeobox_metazoa.
DR InterPro; IPR019737; Homoebox-engrailed_CS.
DR InterPro; IPR000047; HTH_motif.
DR Pfam; PF10525; Engrail_1_C_sig; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00026; ENGRAILED.
DR PRINTS; PR00024; HOMEOBOX.
DR PRINTS; PR00031; HTHREPRESSR.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00033; ENGRAILED; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor;
KW Segmentation polarity protein; Transcription; Transcription regulation.
FT CHAIN 1..552
FT /note="Segmentation polarity homeobox protein engrailed"
FT /id="PRO_0000196077"
FT DNA_BIND 454..513
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 93..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 309..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 433..460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 135..149
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 309..381
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 404..418
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 436..460
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 508
FT /note="K->Q: Reduced specificity and affinity for DNA."
FT CONFLICT 195
FT /note="M -> I (in Ref. 1; AAA65478)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="S -> N (in Ref. 1; AAA65478)"
FT /evidence="ECO:0000305"
FT CONFLICT 486
FT /note="Q -> E (in Ref. 5; CAA25906)"
FT /evidence="ECO:0000305"
FT TURN 453..455
FT /evidence="ECO:0007829|PDB:2JWT"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:1ZTR"
FT HELIX 463..475
FT /evidence="ECO:0007829|PDB:6M3D"
FT HELIX 481..491
FT /evidence="ECO:0007829|PDB:6M3D"
FT HELIX 495..512
FT /evidence="ECO:0007829|PDB:6M3D"
SQ SEQUENCE 552 AA; 59411 MW; 92A94C14AA85C527 CRC64;
MALEDRCSPQ SAPSPITLQM QHLHHQQQQQ QQQQQQMQHL HQLQQLQQLH QQQLAAGVFH
HPAMAFDAAA AAAAAAAAAA AHAHAAALQQ RLSGSGSPAS CSTPASSTPL TIKEEESDSV
IGDMSFHNQT HTTNEEEEAE EDDDIDVDVD DTSAGGRLPP PAHQQQSTAK PSLAFSISNI
LSDRFGDVQK PGKSMENQAS IFRPFEASRS QTATPSAFTR VDLLEFSRQQ QAAAAAATAA
MMLERANFLN CFNPAAYPRI HEEIVQSRLR RSAANAVIPP PMSSKMSDAN PEKSALGSLC
KAVSQIGQPA APTMTQPPLS SSASSLASPP PASNASTISS TSSVATSSSS SSSGCSSAAS
SLNSSPSSRL GASGSGVNAS SPQPQPIPPP SAVSRDSGME SSDDTRSETG STTTEGGKNE
MWPAWVYCTR YSDRPSSGPR YRRPKQPKDK TNDEKRPRTA FSSEQLARLK REFNENRYLT
ERRRQQLSSE LGLNEAQIKI WFQNKRAKIK KSTGSKNPLA LQLMAQGLYN HTTVPLTKEE
EELEMRMNGQ IP
