ADA17_DROME
ID ADA17_DROME Reviewed; 732 AA.
AC Q9VAC5; Q868A7; Q8IMJ9; Q95RZ4;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=ADAM 17-like protease;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=Tace; ORFNames=CG7908;
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).
RC TISSUE=Embryo;
RA Wei S., Brew K.;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Head;
RA Sapir A., Tsruya R., Shilo B.-Z.;
RT "Asymmetric notch signaling depends on constitutive cleavage of delta.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 2-732 (ISOFORM B).
RC STRAIN=Berkeley; TISSUE=Embryo, and Head;
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 (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P78536};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P78536};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=Q9VAC5-1; Sequence=Displayed;
CC Name=B;
CC IsoId=Q9VAC5-2; Sequence=VSP_037658, VSP_037659;
CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC dissociation of the cysteine from the zinc ion upon the activation-
CC peptide release activates the enzyme.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO24939.1; Type=Miscellaneous discrepancy; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR EMBL; AY212802; AAO53296.1; -; mRNA.
DR EMBL; AY525768; AAS48650.1; -; mRNA.
DR EMBL; AE014297; AAN14205.3; -; Genomic_DNA.
DR EMBL; AE014297; AAF56986.2; -; Genomic_DNA.
DR EMBL; AY061030; AAL28578.1; -; mRNA.
DR EMBL; BT003184; AAO24939.1; ALT_SEQ; mRNA.
DR RefSeq; NP_651759.4; NM_143502.4. [Q9VAC5-2]
DR RefSeq; NP_733334.1; NM_170455.3. [Q9VAC5-1]
DR AlphaFoldDB; Q9VAC5; -.
DR SMR; Q9VAC5; -.
DR BioGRID; 68414; 2.
DR STRING; 7227.FBpp0084917; -.
DR MEROPS; M12.217; -.
DR GlyGen; Q9VAC5; 4 sites.
DR PaxDb; Q9VAC5; -.
DR PRIDE; Q9VAC5; -.
DR EnsemblMetazoa; FBtr0085550; FBpp0084916; FBgn0039734. [Q9VAC5-2]
DR EnsemblMetazoa; FBtr0085551; FBpp0084917; FBgn0039734. [Q9VAC5-1]
DR GeneID; 43558; -.
DR KEGG; dme:Dmel_CG7908; -.
DR UCSC; CG7908-RA; d. melanogaster. [Q9VAC5-1]
DR CTD; 43558; -.
DR FlyBase; FBgn0039734; Tace.
DR VEuPathDB; VectorBase:FBgn0039734; -.
DR eggNOG; KOG3658; Eukaryota.
DR GeneTree; ENSGT00940000155443; -.
DR HOGENOM; CLU_004602_2_0_1; -.
DR InParanoid; Q9VAC5; -.
DR OMA; FYHGRVF; -.
DR PhylomeDB; Q9VAC5; -.
DR SignaLink; Q9VAC5; -.
DR BioGRID-ORCS; 43558; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 43558; -.
DR PRO; PR:Q9VAC5; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039734; Expressed in second segment of antenna (Drosophila) and 8 other tissues.
DR ExpressionAtlas; Q9VAC5; baseline and differential.
DR Genevisible; Q9VAC5; DM.
DR GO; GO:0016021; C:integral component of membrane; ISS:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:FlyBase.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:FlyBase.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IMP:FlyBase.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IMP:FlyBase.
DR GO; GO:0007220; P:Notch receptor processing; IMP:FlyBase.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:FlyBase.
DR GO; GO:0010942; P:positive regulation of cell death; IGI:FlyBase.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IDA:FlyBase.
DR CDD; cd14246; ADAM17_MPD; 1.
DR CDD; cd04270; ZnMc_TACE_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR034025; ADAM10_ADAM17.
DR InterPro; IPR032029; ADAM17_MPD.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR Pfam; PF16698; ADAM17_MPD; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cleavage on pair of basic residues; Disulfide bond;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Signal; Transmembrane; Transmembrane helix;
KW Zinc; Zymogen.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT PROPEP 29..211
FT /evidence="ECO:0000250"
FT /id="PRO_0000029094"
FT CHAIN 212..732
FT /note="ADAM 17-like protease"
FT /id="PRO_0000029095"
FT TOPO_DOM 212..662
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 663..683
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 684..732
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 223..467
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 468..559
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT REGION 196..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 598..662
FT /note="Crambin-like"
FT MOTIF 181..188
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 400
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 399
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P78536"
FT BINDING 403
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P78536"
FT BINDING 409
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P78536"
FT CARBOHYD 100
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 263
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 492
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 604
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 225..328
FT /evidence="ECO:0000250|UniProtKB:P78536"
FT DISULFID 360..462
FT /evidence="ECO:0000250|UniProtKB:P78536"
FT DISULFID 416..446
FT /evidence="ECO:0000250|UniProtKB:P78536"
FT DISULFID 530..551
FT /evidence="ECO:0000250"
FT DISULFID 569..578
FT /evidence="ECO:0000250"
FT DISULFID 574..586
FT /evidence="ECO:0000250"
FT DISULFID 588..595
FT /evidence="ECO:0000250"
FT VAR_SEQ 252..262
FT /note="ISLIDRVHKIY -> VSFLKNPRSII (in isoform B)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_037658"
FT VAR_SEQ 263..732
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|Ref.5"
FT /id="VSP_037659"
FT CONFLICT 208
FT /note="R -> K (in Ref. 2; AAS48650)"
FT /evidence="ECO:0000305"
FT CONFLICT 428..431
FT /note="MYTY -> IHT (in Ref. 2; AAS48650)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="R -> A (in Ref. 2; AAS48650)"
FT /evidence="ECO:0000305"
FT CONFLICT 463
FT /note="F -> L (in Ref. 5; AAL28578)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="S -> F (in Ref. 2; AAS48650)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 732 AA; 83081 MW; 0E96E7B30F973A0B CRC64;
MFTKCISCCG LAIISVFFAC LFVENCAALQ KTLRHYEIFH KDDVVHRVVK RGAKHSTNPF
NTIKEVEFTT LGKNFRLILH PHRDVLHSKF RAYAVDADGN ETVVHMDHDS FYSGRVFGEL
ESSVRAHIED GTMTMSIHLP EETYHIEPSW RHLPEAKKDT MVAYKASDVK VHKNEAGATP
KTCGYIKEGL ELEDKEHGDT LDNELHTREK RQSDQYEYTP TKTRCPLLLV ADYRFFQEMG
GGNTKTTINY LISLIDRVHK IYNDTVWQDR SDQEGFKGMG FVIKKIVVHS EPTRLRGGEA
HYNMIREKWD VRNLLEVFSR EYSHKDFCLA HLFTDLKFEG GILGLAYVGS PRRNSVGGIC
TPEYFKNGYT LYLNSGLSSS RNHYGQRVIT READLVTAHE FGHNWGSEHD PDIPECSPSA
SQGGSFLMYT YSVSGYDVNN KKFSPCSLRS IRKVLQAKSG RCFSEPEESF CGNLRVEGDE
QCDAGLLGTE DNDSCCDKNC KLRRNQGAMC SDKNSPCCQN CQFMASGMKC REAQYATCEQ
EARCTGAHAE CPKSPAMADG TTCQERGQCR NGKCVPYCET QGLQSCMCDI IADACKRCCR
MSINETCFPV EPPDVLPDGT PCITGFCNKG VCEKTIQDVV ERFWDIIEEI NVAKTLRFLK
DNIVMAVVLV TAVFWIPISC VISYFDRKKL RHEMKLIEWS QKLDLIHPSD ERRRVIHIRV
PRQKISVARA CN
