P25723 (TLD_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Dorsal-ventral patterning protein tolloid
EC=3.4.24.-

Gene names

Name:	tld
ORF Names:	CG6868

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	1067 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Required for normal dorsal development. TLD may interact physically with DPP-C protein.
Miscellaneous	Mutations in TLD lead to a partial transformation of dorsal ectoderm into ventral ectoderm.
Sequence similarities	Belongs to the peptidase M12A family. Contains 5 CUB domains. Contains 2 EGF-like domains.
Sequence caution	The sequence AAA28491.1 differs from that shown. Reason: Erroneous initiation. The sequence AAC46482.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Domain	EGF-like domain Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Developmental protein Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	amnioserosa formation Non-traceable author statement PubMed 11532914. Source: FlyBase imaginal disc-derived wing vein morphogenesis Inferred from mutant phenotype PubMed 15872004. Source: FlyBase maternal specification of dorsal/ventral axis, oocyte, soma encoded Inferred from mutant phenotype PubMed 16781701. Source: FlyBase negative regulation of gene expression Inferred from direct assay PubMed 16780828. Source: FlyBase positive regulation of BMP signaling pathway Traceable author statement PubMed 11290316. Source: FlyBase protein processing Inferred from direct assay PubMed 17119021. Source: FlyBase proteolysis Non-traceable author statement PubMed 9712300. Source: FlyBase regulation of transforming growth factor beta receptor signaling pathway Traceable author statement PubMed 11700289. Source: FlyBase terminal region determination Inferred from genetic interaction PubMed 1905816. Source: FlyBase torso signaling pathway Inferred from genetic interaction PubMed 1905816. Source: FlyBase
Cellular_component	extracellular region Non-traceable author statement PubMed 9712300. Source: FlyBase
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro metalloendopeptidase activity Non-traceable author statement PubMed 11290316PubMed 11700289. Source: FlyBase zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 36	36	Potential
	Propeptide	37 – 136	100	Potential		PRO_0000028903
	Chain	137 – 1067	931	Dorsal-ventral patterning protein tolloid		PRO_0000028904
Regions
	Domain	340 – 477	138	CUB 1
	Domain	478 – 591	114	CUB 2
	Domain	591 – 631	41	EGF-like 1; calcium-binding Potential
	Domain	634 – 753	120	CUB 3
	Domain	753 – 793	41	EGF-like 2; calcium-binding Potential
	Domain	797 – 909	113	CUB 4
	Domain	910 – 1026	117	CUB 5
	Region	137 – 339	203	Metalloprotease
	Motif	245 – 247	3	Cell attachment site Potential
	Motif	325 – 327	3	Cell attachment site Potential
Sites
	Active site	232	1	By similarity
	Metal binding	231	1	Zinc; catalytic By similarity
	Metal binding	235	1	Zinc; catalytic By similarity
	Metal binding	241	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	176	1	N-linked (GlcNAc...) Potential
	Glycosylation	441	1	N-linked (GlcNAc...) Potential
	Glycosylation	543	1	N-linked (GlcNAc...) Potential
	Glycosylation	644	1	N-linked (GlcNAc...) Potential
	Glycosylation	677	1	N-linked (GlcNAc...) Potential
	Glycosylation	791	1	N-linked (GlcNAc...) Potential
	Glycosylation	864	1	N-linked (GlcNAc...) Potential
	Glycosylation	918	1	N-linked (GlcNAc...) Potential
	Disulfide bond	340 ↔ 390		By similarity
	Disulfide bond	417 ↔ 439		By similarity
	Disulfide bond	478 ↔ 505		By similarity
	Disulfide bond	532 ↔ 554		By similarity
	Disulfide bond	595 ↔ 606		By similarity
	Disulfide bond	602 ↔ 615		By similarity
	Disulfide bond	617 ↔ 630		By similarity
	Disulfide bond	634 ↔ 662		By similarity
	Disulfide bond	693 ↔ 716		By similarity
	Disulfide bond	757 ↔ 768		By similarity
	Disulfide bond	764 ↔ 777		By similarity
	Disulfide bond	779 ↔ 792		By similarity
	Disulfide bond	797 ↔ 823		By similarity
	Disulfide bond	850 ↔ 872		By similarity
	Disulfide bond	910 ↔ 940		By similarity
	Disulfide bond	967 ↔ 989		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P25723 [UniParc]. Last modified August 16, 2004. Version 2. Checksum: 6375871E9F2B54C2	FASTA	1,067	121,780
	10 20 30 40 50 60 MKGMRLMPMK MKAKLVVLSV GALWMMMFFL VDYAEGRRLS QLPESECDFD FKEQPEDFFG 70 80 90 100 110 120 ILDSSLVPPK EPKDDIYQLK TTRQHSGRRR KQSHKSQNKA ALRLPPPFLW TDDAVDVLQH 130 140 150 160 170 180 SHSPTLNGQP IQRRRRAVTV RKERTWDYGV IPYEIDTIFS GAHKALFKQA MRHWENFTCI 190 200 210 220 230 240 KFVERDPNLH ANYIYFTVKN CGCCSFLGKN GNGRQPISIG RNCEKFGIII HELGHTIGFH 250 260 270 280 290 300 HEHARGDRDK HIVINKGNIM RGQEYNFDVL SPEEVDLPLL PYDLNSIMHY AKNSFSKSPY 310 320 330 340 350 360 LDTITPIGIP PGTHLELGQR KRLSRGDIVQ ANLLYKCASC GRTYQQNSGH IVSPHFIYSG 370 380 390 400 410 420 NGVLSEFEGS GDAGEDPSAE SEFDASLTNC EWRITATNGE KVILHLQQLH LMSSDDCTQD 430 440 450 460 470 480 YLEIRDGYWH KSPLVRRICG NVSGEVITTQ TSRMLLNYVN RNAAKGYRGF KARFEVVCGG 490 500 510 520 530 540 DLKLTKDQSI DSPNYPMDYM PDKECVWRIT APDNHQVALK FQSFELEKHD GCAYDFVEIR 550 560 570 580 590 600 DGNHSDSRLI GRFCGDKLPP NIKTRSNQMY IRFVSDSSVQ KLGFSAALML DVDECKFTDH 610 620 630 640 650 660 GCQHLCINTL GSYQCGCRAG YELQANGKTC EDACGGVVDA TKSNGSLYSP SYPDVYPNSK 670 680 690 700 710 720 QCVWEVVAPP NHAVFLNFSH FDLEGTRFHY TKCNYDYLII YSKMRDNRLK KIGIYCGHEL 730 740 750 760 770 780 PPVVNSEQSI LRLEFYSDRT VQRSGFVAKF VIDVDECSMN NGGCQHRCRN TFGSYQCSCR 790 800 810 820 830 840 NGYTLAENGH NCTETRCKFE ITTSYGVLQS PNYPEDYPRN IYCYWHFQTV LGHRIQLTFH 850 860 870 880 890 900 DFEVESHQEC IYDYVAIYDG RSENSSTLGI YCGGREPYAV IASTNEMFMV LATDAGLQRK 910 920 930 940 950 960 GFKATFVSEC GGYLRATNHS QTFYSHPRYG SRPYKRNMYC DWRIQADPES SVKIRFLHFE 970 980 990 1000 1010 1020 IEYSERCDYD YLEITEEGYS MNTIHGRFCG KHKPPIIISN SDTLLLRFQT DESNSLRGFA 1030 1040 1050 1060 ISFMAVDPPE DSVGEDFDAV TPFPGYLKSM YSSETGSDHL LPPSRLI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Drosophila dorsal-ventral patterning gene tolloid is related to human bone morphogenetic protein 1." Shimell M.J., Ferguson E.L., Childs S.R., O'Connor M.B. Cell 67:469-481(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Canton-S.
[2]	"Mutational analysis of the Drosophila tolloid gene, a human BMP-1 homolog." Finelli A.L., Bossie C.A., Xie T., Padgett R.W. Development 120:861-870(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[3]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[4]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M76976 mRNA. Translation: AAA28491.1. Different initiation. U04239 Unassigned DNA. Translation: AAC46482.1. Different initiation. AE014297 Genomic DNA. Translation: AAF56329.2.
PIR	A39288.
RefSeq	NP_524487.2. NM_079763.3.
3D structure databases
ProteinModelPortal	P25723.
SMR	P25723. Positions 137-1065.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-22889N.
IntAct	P25723. 1 interaction.
MINT	MINT-1022959.
Protein family/group databases
MEROPS	M12.010.
Proteomic databases
PaxDb	P25723.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0084691; FBpp0084070; FBgn0003719.
GeneID	42945.
KEGG	dme:Dmel_CG6868.
UCSC	CG6868-RA. d. melanogaster.
Organism-specific databases
CTD	42945.
FlyBase	FBgn0003719. tld.
Phylogenomic databases
eggNOG	NOG87014.
GeneTree	ENSGT00700000104171.
InParanoid	P25723.
KO	K13045.
OMA	ETDCSYD.
OrthoDB	EOG4VT4C2.
PhylomeDB	P25723.
Gene expression databases
Bgee	P25723.
GermOnline	CG6868. Drosophila melanogaster.
Family and domain databases
Gene3D	2.60.120.290. 5 hits. 3.40.390.10. 1 hit.
InterPro	IPR015446. BMP_1/tolloid-like. IPR000859. CUB_dom. IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR018097. EGF_Ca-bd_CS. IPR024079. MetalloPept_cat_dom. IPR001506. Peptidase_M12A. IPR006026. Peptidase_Metallo. [Graphical view]
Pfam	PF01400. Astacin. 1 hit. PF00431. CUB. 5 hits. PF07645. EGF_CA. 2 hits. [Graphical view]
PIRSF	PIRSF001199. BMP_1/tolloid-like. 1 hit.
PRINTS	PR00480. ASTACIN.
SMART	SM00042. CUB. 5 hits. SM00179. EGF_CA. 2 hits. SM00235. ZnMc. 1 hit. [Graphical view]
SUPFAM	SSF49854. CUB. 5 hits.
PROSITE	PS00010. ASX_HYDROXYL. 2 hits. PS01180. CUB. 5 hits. PS00022. EGF_1. False negative. PS01186. EGF_2. 2 hits. PS50026. EGF_3. 2 hits. PS01187. EGF_CA. 2 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	42945.
NextBio	831452.

Entry information

Entry name

TLD_DROME

Accession

Primary (citable) accession number: P25723
Secondary accession number(s): Q9VC46

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	August 16, 2004
Last modified:	May 1, 2013
This is version 131 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project