TLD_DROME
ID TLD_DROME Reviewed; 1067 AA.
AC P25723; Q9VC46;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Dorsal-ventral patterning protein tolloid;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=tld; ORFNames=CG6868;
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].
RC STRAIN=Canton-S;
RX PubMed=1840509; DOI=10.1016/0092-8674(91)90522-z;
RA Shimell M.J., Ferguson E.L., Childs S.R., O'Connor M.B.;
RT "The Drosophila dorsal-ventral patterning gene tolloid is related to human
RT bone morphogenetic protein 1.";
RL Cell 67:469-481(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=7600963; DOI=10.1242/dev.120.4.861;
RA Finelli A.L., Bossie C.A., Xie T., Padgett R.W.;
RT "Mutational analysis of the Drosophila tolloid gene, a human BMP-1
RT homolog.";
RL Development 120:861-870(1994).
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.
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).
CC -!- FUNCTION: Required for normal dorsal development. TLD may interact
CC physically with DPP-C protein.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01211};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU01211};
CC -!- MISCELLANEOUS: Mutations in TLD lead to a partial transformation of
CC dorsal ectoderm into ventral ectoderm.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA28491.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAC46482.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; M76976; AAA28491.1; ALT_INIT; mRNA.
DR EMBL; U04239; AAC46482.1; ALT_INIT; Unassigned_DNA.
DR EMBL; AE014297; AAF56329.2; -; Genomic_DNA.
DR PIR; A39288; A39288.
DR RefSeq; NP_524487.2; NM_079763.4.
DR AlphaFoldDB; P25723; -.
DR SMR; P25723; -.
DR BioGRID; 67870; 7.
DR DIP; DIP-22889N; -.
DR IntAct; P25723; 1.
DR STRING; 7227.FBpp0084070; -.
DR MEROPS; M12.010; -.
DR GlyGen; P25723; 8 sites.
DR PaxDb; P25723; -.
DR EnsemblMetazoa; FBtr0084691; FBpp0084070; FBgn0003719.
DR GeneID; 42945; -.
DR KEGG; dme:Dmel_CG6868; -.
DR UCSC; CG6868-RA; d. melanogaster.
DR CTD; 42945; -.
DR FlyBase; FBgn0003719; tld.
DR VEuPathDB; VectorBase:FBgn0003719; -.
DR eggNOG; KOG3714; Eukaryota.
DR HOGENOM; CLU_005140_0_0_1; -.
DR InParanoid; P25723; -.
DR OMA; WTKQTVG; -.
DR OrthoDB; 170905at2759; -.
DR PhylomeDB; P25723; -.
DR BRENDA; 3.4.24.19; 1994.
DR Reactome; R-DME-2243919; Crosslinking of collagen fibrils.
DR SignaLink; P25723; -.
DR BioGRID-ORCS; 42945; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 42945; -.
DR PRO; PR:P25723; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0003719; Expressed in ectoderm and 44 other tissues.
DR ExpressionAtlas; P25723; baseline and differential.
DR Genevisible; P25723; DM.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005518; F:collagen binding; IDA:FlyBase.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007378; P:amnioserosa formation; IMP:FlyBase.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IBA:GO_Central.
DR GO; GO:0008586; P:imaginal disc-derived wing vein morphogenesis; IMP:FlyBase.
DR GO; GO:0007313; P:maternal specification of dorsal/ventral axis, oocyte, soma encoded; IMP:FlyBase.
DR GO; GO:0032927; P:positive regulation of activin receptor signaling pathway; IDA:FlyBase.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IDA:FlyBase.
DR GO; GO:0016485; P:protein processing; IDA:FlyBase.
DR GO; GO:0006508; P:proteolysis; IDA:FlyBase.
DR GO; GO:0045464; P:R8 cell fate specification; IMP:FlyBase.
DR CDD; cd00041; CUB; 5.
DR CDD; cd04281; ZnMc_BMP1_TLD; 1.
DR Gene3D; 2.60.120.290; -; 5.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR015446; BMP_1/tolloid-like.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001506; Peptidase_M12A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR InterPro; IPR034036; ZnMP_TLD/BMP1.
DR Pfam; PF01400; Astacin; 1.
DR Pfam; PF00431; CUB; 5.
DR Pfam; PF07645; EGF_CA; 1.
DR PIRSF; PIRSF001199; BMP_1/tolloid-like; 1.
DR PRINTS; PR00480; ASTACIN.
DR SMART; SM00042; CUB; 5.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF49854; SSF49854; 5.
DR PROSITE; PS51864; ASTACIN; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 2.
DR PROSITE; PS01180; CUB; 5.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01187; EGF_CA; 2.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Calcium; Cleavage on pair of basic residues; Developmental protein;
KW Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Repeat; Signal; Zinc;
KW Zymogen.
FT SIGNAL 1..36
FT /evidence="ECO:0000255"
FT PROPEP 37..136
FT /evidence="ECO:0000255"
FT /id="PRO_0000028903"
FT CHAIN 137..1067
FT /note="Dorsal-ventral patterning protein tolloid"
FT /id="PRO_0000028904"
FT DOMAIN 136..338
FT /note="Peptidase M12A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DOMAIN 340..477
FT /note="CUB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 478..591
FT /note="CUB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 591..631
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 634..753
FT /note="CUB 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 753..793
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 797..909
FT /note="CUB 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 910..1026
FT /note="CUB 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT MOTIF 245..247
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 325..327
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT ACT_SITE 232
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 231
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 235
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT CARBOHYD 176
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 543
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 644
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 677
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 791
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 864
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 918
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 179..337
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 201..223
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 203..204
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT DISULFID 340..390
FT /evidence="ECO:0000250"
FT DISULFID 417..439
FT /evidence="ECO:0000250"
FT DISULFID 478..505
FT /evidence="ECO:0000250"
FT DISULFID 532..554
FT /evidence="ECO:0000250"
FT DISULFID 595..606
FT /evidence="ECO:0000250"
FT DISULFID 602..615
FT /evidence="ECO:0000250"
FT DISULFID 617..630
FT /evidence="ECO:0000250"
FT DISULFID 634..662
FT /evidence="ECO:0000250"
FT DISULFID 693..716
FT /evidence="ECO:0000250"
FT DISULFID 757..768
FT /evidence="ECO:0000250"
FT DISULFID 764..777
FT /evidence="ECO:0000250"
FT DISULFID 779..792
FT /evidence="ECO:0000250"
FT DISULFID 797..823
FT /evidence="ECO:0000250"
FT DISULFID 850..872
FT /evidence="ECO:0000250"
FT DISULFID 910..940
FT /evidence="ECO:0000250"
FT DISULFID 967..989
FT /evidence="ECO:0000250"
SQ SEQUENCE 1067 AA; 121780 MW; 6375871E9F2B54C2 CRC64;
MKGMRLMPMK MKAKLVVLSV GALWMMMFFL VDYAEGRRLS QLPESECDFD FKEQPEDFFG
ILDSSLVPPK EPKDDIYQLK TTRQHSGRRR KQSHKSQNKA ALRLPPPFLW TDDAVDVLQH
SHSPTLNGQP IQRRRRAVTV RKERTWDYGV IPYEIDTIFS GAHKALFKQA MRHWENFTCI
KFVERDPNLH ANYIYFTVKN CGCCSFLGKN GNGRQPISIG RNCEKFGIII HELGHTIGFH
HEHARGDRDK HIVINKGNIM RGQEYNFDVL SPEEVDLPLL PYDLNSIMHY AKNSFSKSPY
LDTITPIGIP PGTHLELGQR KRLSRGDIVQ ANLLYKCASC GRTYQQNSGH IVSPHFIYSG
NGVLSEFEGS GDAGEDPSAE SEFDASLTNC EWRITATNGE KVILHLQQLH LMSSDDCTQD
YLEIRDGYWH KSPLVRRICG NVSGEVITTQ TSRMLLNYVN RNAAKGYRGF KARFEVVCGG
DLKLTKDQSI DSPNYPMDYM PDKECVWRIT APDNHQVALK FQSFELEKHD GCAYDFVEIR
DGNHSDSRLI GRFCGDKLPP NIKTRSNQMY IRFVSDSSVQ KLGFSAALML DVDECKFTDH
GCQHLCINTL GSYQCGCRAG YELQANGKTC EDACGGVVDA TKSNGSLYSP SYPDVYPNSK
QCVWEVVAPP NHAVFLNFSH FDLEGTRFHY TKCNYDYLII YSKMRDNRLK KIGIYCGHEL
PPVVNSEQSI LRLEFYSDRT VQRSGFVAKF VIDVDECSMN NGGCQHRCRN TFGSYQCSCR
NGYTLAENGH NCTETRCKFE ITTSYGVLQS PNYPEDYPRN IYCYWHFQTV LGHRIQLTFH
DFEVESHQEC IYDYVAIYDG RSENSSTLGI YCGGREPYAV IASTNEMFMV LATDAGLQRK
GFKATFVSEC GGYLRATNHS QTFYSHPRYG SRPYKRNMYC DWRIQADPES SVKIRFLHFE
IEYSERCDYD YLEITEEGYS MNTIHGRFCG KHKPPIIISN SDTLLLRFQT DESNSLRGFA
ISFMAVDPPE DSVGEDFDAV TPFPGYLKSM YSSETGSDHL LPPSRLI
