EAST_DROME
ID EAST_DROME Reviewed; 392 AA.
AC P13582; Q9VF90;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2003, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Serine protease easter;
DE EC=3.4.21.-;
DE Flags: Precursor;
GN Name=ea; ORFNames=CG4920;
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].
RX PubMed=2492450; DOI=10.1016/0092-8674(89)90242-0;
RA Chasan R., Anderson K.V.;
RT "The role of easter, an apparent serine protease, in organizing the dorsal-
RT ventral pattern of the Drosophila embryo.";
RL Cell 56:391-400(1989).
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;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J.W., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.A.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P.W., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J.M., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K.H., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND CLEAVAGE EVENTS.
RX PubMed=9477324; DOI=10.1242/dev.125.7.1261;
RA Misra S., Hecht P., Maeda R., Anderson K.V.;
RT "Positive and negative regulation of Easter, a member of the serine
RT protease family that controls dorsal-ventral patterning in the Drosophila
RT embryo.";
RL Development 125:1261-1267(1998).
RN [6]
RP CLEAVAGE OF SPAETZLE.
RX PubMed=9533958; DOI=10.1016/s0925-4773(98)00024-0;
RA DeLotto Y., DeLotto R.;
RT "Proteolytic processing of the Drosophila Spatzle protein by easter
RT generates a dimeric NGF-like molecule with ventralising activity.";
RL Mech. Dev. 72:141-148(1998).
RN [7]
RP FUNCTION, AND MUTAGENESIS.
RX PubMed=2107028; DOI=10.1016/0092-8674(90)90100-s;
RA Jin Y., Anderson K.V.;
RT "Dominant and recessive alleles of the Drosophila easter gene are point
RT mutations at conserved sites in the serine protease catalytic domain.";
RL Cell 60:873-881(1990).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF GLU-193; SER-338 AND PRO-373.
RX PubMed=12493753; DOI=10.1074/jbc.m211820200;
RA Rose T., LeMosy E.K., Cantwell A.M., Banerjee-Roy D., Skeath J.B.,
RA Di Cera E.;
RT "Three-dimensional models of proteases involved in patterning of the
RT Drosophila Embryo. Crucial role of predicted cation binding sites.";
RL J. Biol. Chem. 278:11320-11330(2003).
CC -!- FUNCTION: Component of the extracellular signaling pathway that
CC establishes the dorsal-ventral pathway of the embryo (PubMed:9477324,
CC PubMed:2107028, PubMed:12493753). Three proteases; ndl, gd and snk
CC process easter to create active easter (PubMed:9477324). Active easter
CC defines cell identities along the dorsal-ventral continuum by
CC activating the spz ligand for the Tl receptor in the ventral region of
CC the embryo (PubMed:9477324). {ECO:0000269|PubMed:12493753,
CC ECO:0000269|PubMed:2107028, ECO:0000269|PubMed:9477324}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9477324}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:9477324}.
CC -!- DOMAIN: The clip domain consists of 35-55 residues which are 'knitted'
CC together usually by 3 conserved disulfide bonds forming a clip-like
CC compact structure. {ECO:0000255|PROSITE-ProRule:PRU01236}.
CC -!- PTM: Activation peptide and active catalytic domain are associated by a
CC disulfide bond. Processed easter is present in extremely low amounts in
CC the early embryo as it is rapidly converted into a high molecular mass
CC complex, which may contain a protease inhibitor. Zymogen activation is
CC also controlled by a negative feedback loop from Dorsal.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. CLIP subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01236}.
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DR EMBL; J03154; AAA28496.1; -; mRNA.
DR EMBL; AE014297; AAF55170.1; -; Genomic_DNA.
DR EMBL; BT009978; AAQ22447.1; -; mRNA.
DR PIR; A30100; A30100.
DR RefSeq; NP_524362.2; NM_079638.3.
DR AlphaFoldDB; P13582; -.
DR SMR; P13582; -.
DR BioGRID; 66921; 14.
DR DIP; DIP-18843N; -.
DR IntAct; P13582; 1.
DR STRING; 7227.FBpp0082539; -.
DR MEROPS; S01.201; -.
DR PaxDb; P13582; -.
DR DNASU; 41858; -.
DR EnsemblMetazoa; FBtr0083083; FBpp0082539; FBgn0000533.
DR GeneID; 41858; -.
DR KEGG; dme:Dmel_CG4920; -.
DR UCSC; CG4920-RA; d. melanogaster.
DR CTD; 41858; -.
DR FlyBase; FBgn0000533; ea.
DR VEuPathDB; VectorBase:FBgn0000533; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000173909; -.
DR InParanoid; P13582; -.
DR PhylomeDB; P13582; -.
DR Reactome; R-DME-209442; Formation of the trans-membrane 'signalling complex'.
DR BioGRID-ORCS; 41858; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 41858; -.
DR PRO; PR:P13582; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0000533; Expressed in mouthpart and 16 other tissues.
DR ExpressionAtlas; P13582; baseline and differential.
DR Genevisible; P13582; DM.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0098595; C:perivitelline space; IDA:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:FlyBase.
DR GO; GO:0009950; P:dorsal/ventral axis specification; IMP:FlyBase.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IMP:UniProtKB.
DR GO; GO:0007311; P:maternal specification of dorsal/ventral axis, oocyte, germ-line encoded; TAS:FlyBase.
DR GO; GO:0045752; P:positive regulation of Toll signaling pathway; IDA:FlyBase.
DR GO; GO:0006508; P:proteolysis; IDA:FlyBase.
DR GO; GO:0007370; P:ventral furrow formation; IMP:UniProtKB.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 3.30.1640.30; -; 1.
DR InterPro; IPR022700; CLIP.
DR InterPro; IPR038565; CLIP_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF12032; CLIP; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00680; CLIP; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS51888; CLIP; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Calcium; Developmental protein; Disulfide bond; Hydrolase; Metal-binding;
KW Protease; Reference proteome; Secreted; Serine protease; Signal; Zymogen.
FT SIGNAL 1..19
FT /evidence="ECO:0000305"
FT PROPEP 20..127
FT /note="Activation peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000028133"
FT CHAIN 128..392
FT /note="Serine protease easter"
FT /id="PRO_0000028134"
FT DOMAIN 36..89
FT /note="Clip"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DOMAIN 128..391
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 173
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 240
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 338
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT BINDING 195
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q9GRW0"
FT BINDING 198
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT BINDING 201
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O97366"
FT DISULFID 37..88
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 47..78
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 53..89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01236"
FT DISULFID 120..260
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT DISULFID 158..174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 202..212
FT /evidence="ECO:0000250|UniProtKB:Q9VB68"
FT DISULFID 307..324
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 334..367
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT MUTAGEN 131
FT /note="G->E: In EA 20N; results in extreme lateralized
FT embryonic pattern where the most dorsal pattern elements
FT (e.g. dorsal cuticles) and the most ventral pattern element
FT (mesoderm) are absent."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 172
FT /note="S->L: In EA 111; results in temperature-sensitive
FT defects in dorsoventral patterning."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 193
FT /note="E->A,K: Probable loss of calcium binding which might
FT affect catalytic activity. Results in defective
FT dorsoventral patterning showing a complete dorsalization in
FT which there is no ventral furrow or headfold, cells at the
FT posterior do not migrate, and multiple symmetric folds
FT appear along the anterior-posterior axis of the embryo."
FT /evidence="ECO:0000269|PubMed:12493753"
FT MUTAGEN 283
FT /note="G->S: In EA 84B; results in weakly ventralized
FT embryos with ventral denticle bands that are approximately
FT normal in width and the filzkorper have the normal tubular
FT morphology."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 324
FT /note="C->Y: In EA 818; results in temperature-sensitive
FT defects in dorsoventral patterning."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 325
FT /note="A->V: In EA 83I and EA 4102; results in ventralized
FT embryos."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 335
FT /note="R->C: In EA 125.3; results in ventralized embryos."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 335
FT /note="R->Q: In EA QGDS; results in lateralised embryos."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 336
FT /note="G->S: In EA 12A; results in weakly ventralized
FT embryos with ventral denticle bands that are approximately
FT normal in width and the filzkorper have the normal tubular
FT morphology."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 338
FT /note="S->A: Loss of catalytic activity results in
FT defective dorsoventral patterning characterized by a
FT complete dorsalization in which there is no ventral furrow
FT or headfold, cells at the posterior do not migrate, and
FT multiple symmetric folds appear along the anterior-
FT posterior axis of the embryo."
FT /evidence="ECO:0000269|PubMed:12493753,
FT ECO:0000269|PubMed:2107028"
FT MUTAGEN 339
FT /note="G->R: In EA 1; results in completely dorsalized
FT embryos."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 360
FT /note="V->M: In EA 5.13; results in extreme lateralized
FT embryonic pattern where the most dorsal pattern elements
FT (e.g. dorsal cuticle) and the most ventral pattern element
FT (mesoderm) are absent."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 363
FT /note="G->E: In EA 8; results in completely dorsalized
FT embryos."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 371
FT /note="G->R: In EA 161.13; results in weakly ventralized
FT embryos with ventral denticle bands that are approximately
FT normal in width and the filzkorper have the normal tubular
FT morphology."
FT /evidence="ECO:0000269|PubMed:2107028"
FT MUTAGEN 373
FT /note="P->I,Y: Probable loss of catalytic activity results
FT in partially defective dorsoventral patterning; during
FT gastrulation, shows defective ventralization; in late
FT embryogenesis results in moderately dorsalized embryos
FT presenting defective lateral filzkorper, head skeleton and
FT ventral denticles."
FT /evidence="ECO:0000269|PubMed:12493753"
FT MUTAGEN 373
FT /note="P->S: In EA 5022; probable loss of catalytic
FT activity results in partially defective dorsoventral
FT patterning; in gastrulation, shows an intermediate
FT ventralization with the headfold prominent on the dorsal
FT side and some anteriorward displacement of posterior cells
FT along the dorsal site; in late embryogenesis, shows partial
FT filzkorper and head skeleton, as well as ventral denticles
FT erroneously in dorsal position."
FT /evidence="ECO:0000269|PubMed:12493753,
FT ECO:0000269|PubMed:2107028"
FT CONFLICT 302
FT /note="S -> F (in Ref. 2; AAF55170/AAQ22447)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 392 AA; 43065 MW; 1309C41E6FC176B6 CRC64;
MLKPSIICLF LGILAKSSAG QFYFPNEAAQ VPNYGRCITP NRERALCIHL EDCKYLYGLL
TTTPLRDTDR LYLSRSQCGY TNGKVLICCP DRYRESSSET TPPPKPNVTS NSLLPLPGQC
GNILSNRIYG GMKTKIDEFP WMALIEYTKS QGKKGHHCGG SLISTRYVIT ASHCVNGKAL
PTDWRLSGVR LGEWDTNTNP DCEVDVRGMK DCAPPHLDVP VERTIPHPDY IPASKNQVND
IALLRLAQQV EYTDFVRPIC LPLDVNLRSA TFDGITMDVA GWGKTEQLSA SNLKLKAAVE
GSRMDECQNV YSSQDILLED TQMCAGGKEG VDSCRGDSGG PLIGLDTNKV NTYYFLAGVV
SFGPTPCGLA GWPGVYTLVG KYVDWIQNTI ES
