FlyBase Gene Report: Dmel\tok

General Information

Symbol

Dmel\tok

Species

D. melanogaster

Name

tolkin

Annotation Symbol

CG6863

Feature Type

protein_coding_gene

FlyBase ID

FBgn0004885

Gene Model Status

Current

Stock Availability

18 publicly available

Gene Snapshot

tolkin (tok) encodes a Zinc metallopeptidase with similar substrate specificity to the product of tld, which is its paralog. It cleaves the product of sog as well as the prodomains of several TGF-beta ligands. [Date last reviewed: 2019-03-14]

Other Summaries

Alliance
Auto summary
Pathway
Gene Group
Interactive Fly

Also Known As

tlr, tolloid-related 1, tldr-1, tolloid-related, tlr-1

Key Links

Genomic Location

Cytogenetic map

96A18-96A19

Sequence location

3R:24,719,697..24,749,125 [+]

Recombination map

3-85

RefSeq locus

NT_033777 REGION:24719697..24749125

Sequence

Get Decorated FASTA

Genomic Maps

JBrowse GBrowse

Help me choose

Other Genome Views

The following external sites may use different assemblies or annotations than FlyBase.

Function

GO Summary Ribbons

Gene Ontology (GO) Annotations (11 terms)

Molecular Function (3 terms)

Terms Based on Experimental Evidence (1 term)

CV Term

Evidence

References

enables metalloendopeptidase activity

inferred from direct assay

(Serpe and O'Connor, 2006)

Terms Based on Predictions or Assertions (2 terms)

CV Term

Evidence

References

enables calcium ion binding

inferred from electronic annotation with InterPro:IPR001881, InterPro:IPR018097

(assigned by InterPro )

(FlyBase Curators et al., 2004-)

enables zinc ion binding

inferred from electronic annotation with InterPro:IPR006026

(assigned by InterPro )

(FlyBase Curators et al., 2004-)

Biological Process (7 terms)

Terms Based on Experimental Evidence (7 terms)

CV Term

Evidence

References

involved_in axon guidance

inferred from mutant phenotype

(Serpe and O'Connor, 2006)

involved_in defasciculation of motor neuron axon

inferred from mutant phenotype

(Meyer and Aberle, 2006)

involved_in imaginal disc-derived wing vein morphogenesis

inferred from mutant phenotype

(Serpe et al., 2005)

involved_in motor neuron axon guidance

inferred from mutant phenotype

(Meyer and Aberle, 2006)

involved_in positive regulation of activin receptor signaling pathway

inferred from direct assay

(Serpe and O'Connor, 2006)

involved_in positive regulation of BMP signaling pathway

inferred from genetic interaction with FLYBASE:sog; FB:FBgn0003463, FLYBASE:tsg; FB:FBgn0003865

(Peluso et al., 2011)

involved_in protein processing

inferred from direct assay

(Serpe and O'Connor, 2006)

Terms Based on Predictions or Assertions (0 terms)

Cellular Component (1 term)

Terms Based on Experimental Evidence (1 term)

CV Term

Evidence

References

located_in extracellular space

inferred from direct assay

(Serpe and O'Connor, 2006)

Terms Based on Predictions or Assertions (0 terms)

Gene Group (FlyBase)

ASTACINS

Pathway (FlyBase)

Positive Regulators of Activin Signaling Pathway

Positive Regulators of BMP Signaling Pathway

Protein Family (UniProt)

Protein Signatures (InterPro)

Summaries

Pathway (FlyBase)

Positive Regulators of Activin Signaling Pathway -: Positive regulators of activin signaling up-regulate the pathway, ultimately resulting in the increased nuclear activity of the Smox/Med transcription factor complex.
Positive Regulators of BMP Signaling Pathway -: Positive regulators of Bone Morphogenetic Protein (BMP) signaling up-regulate the pathway, ultimately resulting in the increased nuclear activity of the Mad/Med transcription factor complex.

Gene Group (FlyBase)

ASTACINS -: Astacins belong to MEROPS family M12, subfamily A, and also to the group of peptidases known as the "metzincins", due to a conserved methionine C-terminal to the zinc ligands. They are multi-domain metallopeptidases with manifold functions in metabolism. They are either secreted or membrane-anchored. (Adapted from FBrf0239469 and PMID:23092796.)

Summary (Interactive Fly)

BMP-1 homolog - a Zinc metallopeptidase with similar substrate specificity to tolloid, which is its paralog. Tok cleaves the Decapentaplegic inhibitor Short gastrulation as well as the prodomains of several TGF-beta ligands

Interactive Fly

Gene Model and Products

Number of Transcripts

Number of Unique Polypeptides

Please see the JBrowse view of Dmel\tok for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)

Isoform displayed:

Pfam protein domains

InterPro name

classification

start

end

Protein Domains (via SMART)

Isoform displayed:

SMART protein domains

InterPro name

classification

start

end

Comments on Gene Model

Low-frequency RNA-Seq exon junction(s) not annotated.

Gene model reviewed during 5.49

Sequence Ontology: Class of Gene

nuclear_gene

protein_coding_gene

Transcript Data

Annotated Transcripts

Name

FlyBase ID

RefSeq ID

Length (nt)

Assoc. CDS (aa)

tok-RA

FBtr0084690

NM_057531

5368

1464

tok-RB

FBtr0084689

NM_170168

5247

1464

tok-RC

FBtr0339252

NM_001300581

5364

1464

Additional Transcript Data and Comments

Reported size (kB)

5.5 (northern blot)

(Finelli et al., 1995)

5.4 (northern blot)

(Nguyen et al., 1994)

Comments

External Data

Crossreferences

Polypeptide Data

Annotated Polypeptides

Name

FlyBase ID

Predicted MW (kDa)

Length (aa)

Theoretical pI

RefSeq ID

GenBank

tok-PA

FBpp0084069

165.2

1464

6.26

NP_476879

AAF56328

tok-PB

FBpp0084068

165.2

1464

6.26

NP_733035

AAN14017

tok-PC

FBpp0308359

165.2

1464

6.26

NP_001287510

AHN57509

Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

1464 aa isoforms: tok-PA, tok-PB, tok-PC

Additional Polypeptide Data and Comments

Reported size (kDa)

1464 (aa)

(Finelli et al., 1995)

1464 (aa); 165 (kD predicted)

(Nguyen et al., 1994)

Comments

External Data

Crossreferences

InterPro - A database of protein families, domains and functional sites

MEROPS - An information resource for peptidases (also termed proteases, proteinases and proteolytic enzymes) and the proteins that inhibit them.

Linkouts

Sequences Consistent with the Gene Model

Nucleotide / Polypeptide Records

UniProt

Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\tok using the Feature Mapper tool.

External Data

Crossreferences

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

tok_1
tok_2

Linkouts

Expression Data

Expression Summary Ribbons

Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.

For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.

Transcript Expression

in situ

Stage

Tissue/Position (including subcellular localization)

Reference

third instar larval stage

larval outer optic anlage

(Finelli et al., 1995)

embryonic stage 14 -- 17

corpus allatum primordium

(Finelli et al., 1995, Nguyen et al., 1994)

embryonic stage 10 -- 11

embryonic optic lobe primordium

(Nguyen et al., 1994)

embryonic stage 4 -- 6

dorsal ectoderm anlage

Comment: anlage in statu nascendi

(Fisher et al., 2012)

embryonic stage 7 -- 8

amnioserosa anlage

(Fisher et al., 2012)

dorsal ectoderm

(Fisher et al., 2012)

embryonic stage 9 -- 10

amnioserosa

(Fisher et al., 2012)

embryonic stage 13 -- 16

embryonic/larval corpus allatum

(Fisher et al., 2012)

larval midline neuron

(Kearney et al., 2004)

embryonic stage 9 -- 12

midline primordium

(Kearney et al., 2004)

northern blot

Stage

Tissue/Position (including subcellular localization)

Reference

embryonic stage 17

central nervous system | restricted

(Nguyen et al., 1994)

sensillum basiconicum

(Nguyen et al., 1994)

embryonic/larval proventriculus

(Nguyen et al., 1994)

third instar larval stage

morphogenetic furrow | anterior to

(Finelli et al., 1995, Nguyen et al., 1994)

eye-antennal disc

(Finelli et al., 1995, Nguyen et al., 1994)

embryonic/larval brain

(Finelli et al., 1995)

imaginal disc

(Finelli et al., 1995, Nguyen et al., 1994)

embryonic/larval optic lobe

(Nguyen et al., 1994)

embryonic stage

peripheral nervous system | restricted

(Nguyen et al., 1994)

embryonic/larval pharynx

(Nguyen et al., 1994)

amnioproctodeal invagination

(Nguyen et al., 1994)

mesectoderm | vicinity of

(Finelli et al., 1995)

stomodeal invagination

(Nguyen et al., 1994)

larval stage

embryonic/larval corpus allatum

(Nguyen et al., 1994)

blastoderm stage

organism | dorsal

(Finelli et al., 1995)

embryonic stage 12 -- 17

somatic mesoderm

(Nguyen et al., 1994)

visceral mesoderm

(Nguyen et al., 1994)

embryonic stage 14 -- 17

central nervous system | restricted

(Finelli et al., 1995)

embryonic stage 10

peripheral nervous system precursor cluster

(Nguyen et al., 1994)

embryonic stage 5

organism | dorsal

(Nguyen et al., 1994)

embryonic stage -- adult stage

(Finelli et al., 1995, Nguyen et al., 1994)

Additional Descriptive Data

tok transcripts are expressed throughout development. They are first detected by in situ hybridization in the dorsal part of the blastoderm embryo. During germ band extension, tok is exressed near the mesectoderm. During stage 10, three faint lateral spots are observed in the thoracic segments. During dorsal closure, expression is seen in cells that will form the corpus allatum of the ring gland. Expression is also observed in a few cells in the CNS, a few of which were tentatively identified as RP neurons or just lateral to them. In later embryos, expression is observed in many large ventral cells in the nerve cord. In the larval brain, tok is expressed in distinct rings in both hemispheres, one of which corresponds to the outer proliferation center. tok stains most imaginal discs in their entirety with some areas staining more intensely than others. In the eye imaginal disc, the staining is located anterior to the morphogenetic furrow. A comparison of the expression patterns of tok, tld, and dpp is made.

(Finelli et al., 1995)

tok transcripts are expressed throughout development with the highest levels in larvae and pupae. By in situ hybridization, they are first detected on the dorsal surface of late cellular blastoderm embryos. In early stages of germ band extension, they are detected in the anterior and posterior midgut invaginations and later in the visceral mesoderm and pharynx. At stage 10, expression is observed in patches of thoracic cells thought to be proneural clusters and later strong expression is observed in thoracic PNS cells. At stage 10-11, transient expression is observed in optic lobe precursor cells. During dorsal closure, cells that will form the corpus allatum express tok. At stage 17, tok expression is observed in the CNS, in thoracic clusters thought to be the basiconical sensillum and in the proventriculus. In third instar larvae, tok is expressed in all imaginal discs and in the proliferative regions of the optic lobes. In the eye discs, strong tok expression is only found anterior to the morphogenetic furrow. Complex patterns of staining are seen in the other discs. Expression also continues in the corpus allatum of the ring gland. With the exception of the ring gland, the pattern of tok is very similar to that of tld in larval tissues but tld is expressed at a significantly lower level.

(Nguyen et al., 1994)

Marker for

Subcellular Localization

CV Term

Polypeptide Expression

Additional Descriptive Data

Marker for

Subcellular Localization

CV Term

Evidence

References

located_in extracellular space

inferred from direct assay

(Serpe and O'Connor, 2006)

Expression Deduced from Reporters

High-Throughput Expression Data

Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\tok in GBrowse 2

RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region

View exonic expression by developmental stage for Dmel\tok

View exonic expression by tissue for Dmel\tok

Bulk Downloads

RNA-Seq RPKM values for all genes

Reference

See Gelbart and Emmert, 2013 for analysis details and data files for all genes.

Developmental Proteome: Life Cycle

Developmental Proteome: Embryogenesis

External Data and Images

Linkouts

BDGP expression data - Patterns of gene expression in Drosophila embryogenesis

FBgn0004885

FLIGHT - Cell culture data for RNAi and other high-throughput technologies

FBgn0004885

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

CG6863-RB

Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns

CG6863

Flygut - An atlas of the Drosophila adult midgut

FBgn0004885

Images

FlyExpress - Embryonic expression images (BDGP data)

Show all FlyExpress processed images for Dmel\tok

Stages(s) 4-6
Stages(s) 7-8
Stages(s) 13-16

FlyBase Wiki

Image Based Resources

Alleles, Insertions, and Transgenic Constructs

Classical and Insertion Alleles ( 31 )

For All Classical and Insertion Alleles Show

Other relevant insertions

Transgenic Constructs ( 8 )

For All Alleles Carried on Transgenic Constructs Show

Transgenic constructs containing/affecting coding region of tok

Transgenic constructs containing regulatory region of tok

Deletions and Duplications ( 4 )

Not disrupted in

Df(3R)96B

(Bloomington Drosophila Stock Center, 1998.6.2)

Disrupted in

Df(3R)BSC520

(Christensen et al., 2008.4.15)

Df(3R)tld-γ1

(Finelli et al., 1995)

Tp(3;2)slo3

(Nguyen et al., 1994)

Phenotypes

For more details about a specific phenotype click on the relevant allele symbol.

Lethality

Allele

lethal

lethal, with Scer\GAL4^Mef2.PR

tok^GD245

lethal | larval stage (with tok^E1)

tok^Δ2-41

lethal | larval stage (with tok^Δ2-41)

tok^E1

lethal | pupal stage (with tok^E1)

tok^Δ2-41

lethal | pupal stage (with tok^Δ2-41)

tok^E1

lethal - all die before end of larval stage

tok^Δ2-41

lethal - all die before end of larval stage (with Df(3R)tld-γ1)

tok^E1

lethal - all die before end of larval stage (with tok^E1)

tok^Δ2-41

lethal - all die before end of larval stage (with tok^Δ2-41)

tok^E1

lethal - all die before end of larval stage | recessive

viable

viable, with Dcr-2^UAS.cDa, Scer\GAL4^elav.PLu

tok^GD245

viable, with Scer\GAL4^pnr-MD237

tok^GD245

viable, with Scer\GAL4^tin.CΔ4

tok^GD245

Sterility

Allele

fertile

tok^EY00956

Other Phenotypes

Allele

developmental rate defective

tok^Δ2-41

neuroanatomy defective (with tok^D427)

tok^K788

neuroanatomy defective (with tok^K788)

tok^D427

neuroanatomy defective | embryonic stage

tok^Δ2-41

neuroanatomy defective | embryonic stage (with Df(3R)tld-γ1)

tok^E1

neuroanatomy defective | embryonic stage (with tok^E1)

tok^Δ2-41

neuroanatomy defective | embryonic stage (with tok^Δ2-41)

tok^E1

neuroanatomy defective | larval stage

tok^Δ2-41

neuroanatomy defective | larval stage (with Df(3R)tld-γ1)

tok^E1

neuroanatomy defective | larval stage (with tok^E1)

tok^Δ2-41

neuroanatomy defective | larval stage (with tok^Δ2-41)

tok^E1

some die during larval stage

tok^Δ2-41

some die during larval stage (with Df(3R)tld-γ1)

tok^E1

some die during larval stage (with tok^E1)

tok^Δ2-41

some die during larval stage (with tok^Δ2-41)

tok^E1

some die during larval stage | recessive

visible, with Scer\GAL4^how-24B

tok^{UAS.cSa.Tag:HA}

Phenotype manifest in

Allele

A1-7 ventral longitudinal muscle 1

tok^Δ2-41

A1-7 ventral longitudinal muscle 1 (with Df(3R)tld-γ1)

tok^E1

A1-7 ventral longitudinal muscle 1 (with tok^E1)

tok^Δ2-41

A1-7 ventral longitudinal muscle 1 (with tok^Δ2-41)

tok^E1

abdominal segmental nerve

tok^Δ2-41

abdominal segmental nerve (with Df(3R)tld-γ1)

tok^E1

abdominal segmental nerve (with tok^E1)

tok^Δ2-41

abdominal segmental nerve (with tok^Δ2-41)

tok^E1

anterior crossvein

tok^Δ2-41

crossvein (with tok^E1)

tok^Δ2-41

crossvein (with tok^Δ2-41)

tok^E1

embryonic/larval brain

embryonic/larval neuromuscular junction

tok^Δ2-41

embryonic/larval neuromuscular junction (with Df(3R)tld-γ1)

tok^E1

embryonic/larval neuromuscular junction (with tok^E1)

tok^Δ2-41

embryonic/larval neuromuscular junction (with tok^Δ2-41)

tok^E1

imaginal disc | larval stage

intersegmental nerve

tok^Δ2-41

intersegmental nerve (with Df(3R)tld-γ1)

tok^E1

intersegmental nerve (with tok^D427)

tok^K788

intersegmental nerve (with tok^E1)

tok^Δ2-41

intersegmental nerve (with tok^K788)

tok^D427

intersegmental nerve (with tok^Δ2-41)

tok^E1

intersegmental nerve | embryonic stage (with tok^D427)

tok^K788

intersegmental nerve | embryonic stage (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal dorsal acute muscle 1 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal dorsal acute muscle 1 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal dorsal acute muscle 2 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal dorsal acute muscle 2 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal dorsal oblique muscle 1 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal dorsal oblique muscle 1 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal dorsal oblique muscle 2 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal dorsal oblique muscle 2 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal lateral transverse muscle 1 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal lateral transverse muscle 1 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal lateral transverse muscle 2 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal lateral transverse muscle 2 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal lateral transverse muscle 3 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal lateral transverse muscle 3 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal lateral transverse muscle 4 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal lateral transverse muscle 4 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral acute muscle 1 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral acute muscle 1 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral acute muscle 2 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral acute muscle 2 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral acute muscle 3 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral acute muscle 3 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral longitudinal muscle 1 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral longitudinal muscle 1 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral longitudinal muscle 2 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral longitudinal muscle 2 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral longitudinal muscle 3 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral longitudinal muscle 3 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral longitudinal muscle 4 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral longitudinal muscle 4 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral oblique muscle 4 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral oblique muscle 4 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral oblique muscle 5 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral oblique muscle 5 (with tok^K788)

tok^D427

larval neuromuscular junction & abdominal ventral oblique muscle 6 (with tok^D427)

tok^K788

larval neuromuscular junction & abdominal ventral oblique muscle 6 (with tok^K788)

tok^D427

longitudinal connective (with tok^E1)

tok^Δ2-41

longitudinal connective (with tok^Δ2-41)

tok^E1

posterior crossvein

tok^Δ2-41

presumptive embryonic/larval central nervous system (with tok^D427)

tok^K788

presumptive embryonic/larval central nervous system (with tok^K788)

tok^D427

segmental nerve (with tok^D427)

tok^K788

segmental nerve (with tok^K788)

tok^D427

segmental nerve | embryonic stage (with tok^D427)

tok^K788

segmental nerve | embryonic stage (with tok^K788)

tok^D427

wing, with Scer\GAL4^how-24B

tok^{UAS.cSa.Tag:HA}

Orthologs

Downloads

Download All DIOPT Orthologs

Download All OrthoDB Orthologs

Human Orthologs (via DIOPT v8.0)

Homo sapiens (Human) (14)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Hsap\BMP1

11 of 15

Yes

Hsap\TLL1

11 of 15

Yes

Hsap\TLL2

10 of 15

Yes

Hsap\ASTL

1 of 15

Hsap\C1S

1 of 15

Hsap\CDCP2

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Yes

Hsap\TMPRSS6

1 of 15

Hsap\TMPRSS15

1 of 15

Yes

Hsap\TNFAIP6

1 of 15

Yes

Model Organism Orthologs (via DIOPT v8.0)

Mus musculus (laboratory mouse) (14)

Species\Gene Symbol

Score

Best Score

Best Reverse Score

Source

Alignment

Complementation?

Transgene?

Mmus\Bmp1

11 of 15

Yes

Mmus\Tll1

10 of 15

Yes

Mmus\Tll2

10 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Yes

Mmus\Tmprss15

1 of 15

Mmus\Tnfaip6

1 of 15

Yes

Rattus norvegicus (Norway rat) (12)

Rnor\Tll2

9 of 13

Yes

8 of 13

5 of 13

1 of 13

1 of 13

1 of 13

Yes

1 of 13

1 of 13

1 of 13

1 of 13

Yes

Rnor\Pcolce

1 of 13

Yes

Rnor\Tnfaip6

1 of 13

Yes

Xenopus tropicalis (Western clawed frog) (17)

Xtro\bmp1

5 of 12

Yes

Xtro\tll1

3 of 12

Xtro\tll1

3 of 12

Yes

Xtro\tll2

3 of 12

Xtro\tll2

2 of 12

Yes

Xtro\accs

1 of 12

Xtro\cubn

1 of 12

Xtro\cuzd1.2

1 of 12

Yes

Xtro\LOC100489456

1 of 12

Xtro\LOC100492324

1 of 12

Xtro\LOC101733252

1 of 12

Yes

Xtro\mep1a

1 of 12

Xtro\mep1b

1 of 12

Xtro\pcolce2

1 of 12

Yes

Xtro\pcolce

1 of 12

Yes

Xtro\tnfaip6

1 of 12

Yes

Xtro\uvs.2

1 of 12

Danio rerio (Zebrafish) (23)

Drer\tll1

11 of 15

Yes

Drer\bmp1a

10 of 15

Yes

6 of 15

2 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Yes

Drer\cuzd1.2

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Yes

Drer\pcolce2b

1 of 15

Yes

Drer\pcolcea

1 of 15

Yes

Drer\pcolceb

1 of 15

Yes

Drer\si:ch73-40a17.3

1 of 15

Drer\tnfaip6

1 of 15

Yes

Caenorhabditis elegans (Nematode, roundworm) (42)

Cele\nas-39

12 of 15

Yes

Cele\hch-1

2 of 15

Yes

2 of 15

2 of 15

2 of 15

2 of 15

2 of 15

2 of 15

2 of 15

2 of 15

2 of 15

2 of 15

2 of 15

2 of 15

Yes

2 of 15

2 of 15

2 of 15

2 of 15

2 of 15

Yes

Cele\Y19D10A.6

2 of 15

Cele\dpy-31

1 of 15

Cele\F38B2.3

1 of 15

Yes

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

1 of 15

Arabidopsis thaliana (thale-cress) (0)

No records found.

Saccharomyces cerevisiae (Brewer's yeast) (0)

No records found.

Schizosaccharomyces pombe (Fission yeast) (0)

No records found.

Ortholog(s) in Drosophila Species (via OrthoDB v9.1) ( EOG091900LX )

Organism

Common Name

Gene

AAA Syntenic Ortholog

Multiple Dmel Genes in this Orthologous Group

Drosophila suzukii

Spotted wing Drosophila

Drosophila simulans

Drosophila sechellia

Drosophila erecta

Drosophila yakuba

Drosophila ananassae

Drosophila pseudoobscura pseudoobscura

Dpse\GA19912

Drosophila persimilis

Dper\GL13621

Drosophila willistoni

Dwil\GK14033

Drosophila virilis

Dvir\GJ23651

Drosophila mojavensis

Dmoj\GI24022

Drosophila grimshawi

Dgri\GH18445

Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG091500JT )

Organism

Common Name

Gene

Multiple Dmel Genes in this Orthologous Group

Musca domestica

House fly

Mdoa\17019914

Glossina morsitans

Tsetse fly

Gmor\GMOY002622

Lucilia cuprina

Australian sheep blowfly

Lcup\FF38_06122

Mayetiola destructor

Hessian fly

Mdes\Mdes001641

Aedes aegypti

Yellow fever mosquito

Aaeg\AAEL013239

Aedes aegypti

Yellow fever mosquito

Aaeg\AAEL001566

Anopheles darlingi

American malaria mosquito

Adar\ADAC004786

Anopheles gambiae

Malaria mosquito

Agam\AGAP003702

Culex quinquefasciatus

Southern house mosquito

Cqui\CPIJ011508

Culex quinquefasciatus

Southern house mosquito

Cqui\CPIJ012475

Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W012C )

Organism

Common Name

Gene

Multiple Dmel Genes in this Orthologous Group

Bombyx mori

Silkmoth

Bmor\BGIBMGA002519

Bombyx mori

Silkmoth

Bmor\BGIBMGA001394

Bombyx mori

Silkmoth

Bmor\BGIBMGA005594

Bombyx mori

Silkmoth

Bmor\BGIBMGA002518

Danaus plexippus

Monarch butterfly

Dple\DPOGS214690-PA

Danaus plexippus

Monarch butterfly

Dple\DPOGS206492-PA

Heliconius melpomene

Postman butterfly

Hmel\HMEL011886

Heliconius melpomene

Postman butterfly

Hmel\HMEL005204

Apis florea

Little honeybee

Aflo\2230624036

Apis mellifera

Western honey bee

Amel\GB52106

Bombus impatiens

Common eastern bumble bee

Bimp\BIMP19157

Bombus terrestris

Buff-tailed bumblebee

Bter\15213060

Linepithema humile

Argentine ant

Lhum\LH21745

Linepithema humile

Argentine ant

Lhum\LH25746

Megachile rotundata

Alfalfa leafcutting bee

Mrot\MROTU:0009bf

Nasonia vitripennis

Parasitic wasp

Nvit\Nasvi2EG003413

Nasonia vitripennis

Parasitic wasp

Nvit\Nasvi2EG003818

Dendroctonus ponderosae

Mountain pine beetle

Dpod\YQE_11228

Tribolium castaneum

Red flour beetle

Tcas\GLEAN_07734-OG241

Tribolium castaneum

Red flour beetle

Tcas\TC034615

Pediculus humanus

Human body louse

Phum\PHUM570110

Rhodnius prolixus

Kissing bug

Rpro\bmp1

Rhodnius prolixus

Kissing bug

Rpro\RPRC006385

Rhodnius prolixus

Kissing bug

Rpro\RPRC006482

Cimex lectularius

Bed bug

Clec\CLEC006600

Cimex lectularius

Bed bug

Clec\CLEC013627

Cimex lectularius

Bed bug

Clec\CLEC013626

Acyrthosiphon pisum

Pea aphid

Apim\ACYPI006588

Acyrthosiphon pisum

Pea aphid

Apim\ACYPI007969

Acyrthosiphon pisum

Pea aphid

Apim\ACYPI001899

Acyrthosiphon pisum

Pea aphid

Apim\ACYPI082479

Acyrthosiphon pisum

Pea aphid

Apim\ACYPI007955

Zootermopsis nevadensis

Nevada dampwood termite

Znev\Znev_03518

Zootermopsis nevadensis

Nevada dampwood termite

Znev\Znev_12714

Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X010N )

Organism

Common Name

Gene

Multiple Dmel Genes in this Orthologous Group

Strigamia maritima

European centipede

Smar\SMAR012846

Ixodes scapularis

Black-legged tick

Isca\ISCW016865

Ixodes scapularis

Black-legged tick

Isca\ISCW016868

Ixodes scapularis

Black-legged tick

Isca\ISCW016869

Stegodyphus mimosarum

African social velvet spider

Smim\KFM59925.1

Stegodyphus mimosarum

African social velvet spider

Smim\KFM65057.1

Stegodyphus mimosarum

African social velvet spider

Smim\KFM78109.1

Stegodyphus mimosarum

African social velvet spider

Smim\KFM78314.1

Stegodyphus mimosarum

African social velvet spider

Smim\KFM78107.1

Tetranychus urticae

Two-spotted spider mite

Turt\tetur08g04030

Tetranychus urticae

Two-spotted spider mite

Turt\tetur08g04040

Tetranychus urticae

Two-spotted spider mite

Turt\tetur43g00260

Tetranychus urticae

Two-spotted spider mite

Turt\tetur20g02880

Tetranychus urticae

Two-spotted spider mite

Turt\tetur08g04020

Tetranychus urticae

Two-spotted spider mite

Turt\tetur08g03860

Tetranychus urticae

Two-spotted spider mite

Turt\tetur08g04050

Daphnia pulex

Water flea

Dpux\DAPPUDRAFT_204203

Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G009U )

Organism

Common Name

Gene

Multiple Dmel Genes in this Orthologous Group

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-AnL11_1

Strongylocentrotus purpuratus

Purple sea urchin

Spur\SPU_004115gn

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Astp

Strongylocentrotus purpuratus

Purple sea urchin

Spur\SPU_007393gn

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Bmp1/TldL2

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-AnL7_1

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Astacin5

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Tll1L_1

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Bmp1/TldL1

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Cubnr_3

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Astacin7

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Astacin8

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Astacin4

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-AspLm

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-An

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Tll1_2

Strongylocentrotus purpuratus

Purple sea urchin

Spur\Sp-Cubn2

Ciona intestinalis

Vase tunicate

Cint\LOC100185524

Ciona intestinalis

Vase tunicate

Cint\LOC100175061

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000008374

Ciona intestinalis

Vase tunicate

Cint\tolloid

Ciona intestinalis

Vase tunicate

Cint\LOC100186632

Ciona intestinalis

Vase tunicate

Cint\LOC100175318

Ciona intestinalis

Vase tunicate

Cint\LOC100176208

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000022631

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000019889

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000019778

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000024060

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000017130

Ciona intestinalis

Vase tunicate

Cint\LOC100182127

Ciona intestinalis

Vase tunicate

Cint\LOC100176496

Ciona intestinalis

Vase tunicate

Cint\LOC100181769

Ciona intestinalis

Vase tunicate

Cint\ENSCING00000021949

Ciona intestinalis

Vase tunicate

Cint\LOC100184704

Gallus gallus

Domestic chicken

Ggal\MEP1B

Gallus gallus

Domestic chicken

Ggal\TLL2

Gallus gallus

Domestic chicken

Ggal\CUBN

Gallus gallus

Domestic chicken

Ggal\MEP1A

Gallus gallus

Domestic chicken

Ggal\TLL1

Paralogs

Downloads

Download All DIOPT Paralogs

Paralogs (via DIOPT v8.0)

Drosophila melanogaster (Fruit fly) (20)

Gene Symbol

Score

Source

Alignment

tld

7 of 10

3 of 10

3 of 10

2 of 10

2 of 10

2 of 10

2 of 10

2 of 10

2 of 10

2 of 10

2 of 10

2 of 10

2 of 10

2 of 10

2 of 10

1 of 10

1 of 10

1 of 10

1 of 10

1 of 10

Human Disease Associations

FlyBase Human Disease Model Reports

Disease Model Summary Ribbon

Disease Ontology (DO) Annotations

Models Based on Experimental Evidence ( 0 )

Allele

Disease

Evidence

References

Potential Models Based on Orthology ( 2 )

Human Ortholog

Disease

Evidence

References

TLL1; tolloid like 1

model of atrial heart septal defect 6

IEA

(FlyBase, 2019-)

BMP1; bone morphogenetic protein 1

model of osteogenesis imperfecta type 13

IEA

(FlyBase, 2019-)

Modifiers Based on Experimental Evidence ( 0 )

Allele

Disease

Interaction

References

Disease Associations of Human Orthologs (via DIOPT v8.0 and OMIM)

Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.

Homo sapiens (Human)

Gene name

Score

OMIM

OMIM Phenotype

DO term

Complementation?

Transgene?

BMP1; bone morphogenetic protein 1

11 of 15

112264

OSTEOGENESIS IMPERFECTA, TYPE XIII; OI13

osteogenesis imperfecta type 13

TLL1; tolloid like 1

11 of 15

606742

ATRIAL SEPTAL DEFECT 6; ASD6

atrial heart septal defect 6

TLL2; tolloid like 2

10 of 15

606743

Functional Complementation Data

Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.

Interactions

Summary of Physical Interactions

esyN Network Diagram

Interactions Browser

View in Interactions Browser

Please see the Physical Interaction reports below for full details

protein-protein

Physical Interaction

Assay

References

tok - Actβ

inferred by author, enzymatic study, western blot

(Serpe and O'Connor, 2006)

tok - daw

inferred by author, enzymatic study, western blot

(Serpe and O'Connor, 2006)

tok - myo

inferred by author, enzymatic study, western blot

(Serpe and O'Connor, 2006)

Summary of Genetic Interactions

esyN Network Diagram

esyN Network Key:

Suppression

Enhancement

View in Interactions Browser

Please look at the allele data for full details of the genetic interactions

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

tok

suppressible

sog

(Serpe et al., 2005)

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

daw

enhanceable

tok

(Serpe and O'Connor, 2006)

Paics

suppressible

tok

(Schleede and Blair, 2015)

sog

enhanceable

tok

(Peluso et al., 2011, Araujo et al., 2003)

sog|tsg

suppressible

tok

(Peluso et al., 2011, Serpe et al., 2005)

tld

enhanceable

tok

(Serpe et al., 2005)

External Data

Linkouts

DroID - A comprehensive database of gene and protein interactions.

FBgn0004885

InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.

42944

MIST (genetic) - An integrated Molecular Interaction Database

MIST (protein-protein) - An integrated Molecular Interaction Database

Pathways

Signaling Pathways (FlyBase)

Positive Regulators of Activin Signaling Pathway -: Positive regulators of activin signaling up-regulate the pathway, ultimately resulting in the increased nuclear activity of the Smox/Med transcription factor complex.
Positive Regulators of BMP Signaling Pathway -: Positive regulators of Bone Morphogenetic Protein (BMP) signaling up-regulate the pathway, ultimately resulting in the increased nuclear activity of the Mad/Med transcription factor complex.

Metabolic Pathways

External Data

Linkouts

Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.

Genomic Location and Detailed Mapping Data

Chromosome (arm)

Recombination map

3-85

Cytogenetic map

96A18-96A19

Sequence location

3R:24,719,697..24,749,125 [+]

FlyBase Computed Cytological Location

Cytogenetic map

Evidence for location

96A18-96A19

Limits computationally determined from genome sequence between P{PZ}crb⁰⁷²⁰⁷&P{PZ}BRWD3⁰⁵⁸⁴² and P{EP}CycB3^EP3127

Experimentally Determined Cytological Location

Cytogenetic map

Notes

References

96A-96A

(O'Connor, 1994.7.26)

Experimentally Determined Recombination Data

Location

3-85

(FlyBase, 2016)

3-84.5

(Comeron et al., 2012)

(O'Connor, 1994.7.26)

Left of (cM)

Right of (cM)

Notes

Stocks and Reagents

Stocks (18)

Bloomington

10922

P{wG3-4}tok^G3, ry⁵⁰⁶

42371

y¹ w^*; Mi{MIC}tok^MI06118

20105

y¹ w^67c23; P{EPgy2}tok^EY00956

4569

cn¹; tok³/TM3, Sb¹ Ser¹

33224

w^*; P{ID.GAL80}tok^E17.1/TM6B, Tb¹

4586

st¹ e¹ tok¹/TM3, Sb¹ Ser¹

Kyoto

125047

w¹¹¹⁸; P{RS5}tok^5-HA-1069

125434

w¹¹¹⁸; P{RS5}tok^5-HA-1856

107808

st¹ e¹ tok¹/TM3, Sb¹

107800

cn¹; tok³ / TM3, Sb¹ Ser¹

VDRC

v110432

P{KK101665}VIE-260B

v2656

w¹¹¹⁸; P{GD245}v2656

More stocks available...

Genomic Clones (25)

Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

cDNA Clones (41)

Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

cDNA clones, fully sequenced

BDGP DGC clones

Other clones

DPiM_GH23184

Drosophila Genomics Resource Center cDNA clones

For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

FBgn0004885

cDNA Clones, End Sequenced (ESTs)

BDGP DGC clones

Other clones

RNAi and Array Information

Linkouts

DRSC - Results frm RNAi screens

FBgn0004885

GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents

42944

Antibody Information

Laboratory Generated Antibodies

Commercially Available Antibodies

Other Information

Relationship to Other Genes

Source for database identify of

Source for identity of: tok CG6863

(Kodira, 1999.11)

Source for database merge of

Additional comments

Other Comments

Located 700bp 5' to tld.

(Finelli et al., 1995, Finelli et al., 1995)

Point mutations and deletions in tok indicate it is vital during larval and pupal stages. Escapers of heteroallelic combinations have wing defects in which the posterior crossvein is missing. tok is expressed throughout embryogenesis in patterns that overlap and diverge from tld and dpp.

(Finelli et al., 1995)

tok is necessary for the proper development of the brain and imaginal discs and is involved in the specification of cell fates in the wing.

(Finelli et al., 1995)

The tld gene is the result of an ancient duplication that gave rise to the tld and tok genes, tok lies about 600bp 5' to tld. tok, like tld, is expressed throughout development and is mutatable to a lethal phenotype during larval stages.

(Finelli et al., 1994)

tok has been isolated, sequenced, expression pattern and mutant phenotype studied. tok is required for proper larval and pupal development. tok and tld arose by an ancient gene duplication event and each has subsequently evolved stage specific functions so they are no longer functionally equivalent.

(Nguyen et al., 1994)

Origin and Etymology

Discoverer

Etymology

Identification

External Crossreferences and Linkouts ( 134 )

Sequence Crossreferences

NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.

42944

GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.

GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.

RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.

UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information

Other crossreferences

BDGP expression data - Patterns of gene expression in Drosophila embryogenesis

FBgn0004885

Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones

FBgn0004885

Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.

tok_1
tok_2

Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns

CG6863

Flygut - An atlas of the Drosophila adult midgut

FBgn0004885

GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents

42944

iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)

TC034615

InterPro - A database of protein families, domains and functional sites

KEGG Genes - Molecular building blocks of life in the genomic space.

Dmel_CG6863

MEROPS - An information resource for peptidases (also termed proteases, proteinases and proteolytic enzymes) and the proteins that inhibit them.

modMine - A data warehouse for the modENCODE project

FBgn0004885

Linkouts

DPiM - Drosophila Protein interaction map

FBgn0004885

DroID - A comprehensive database of gene and protein interactions.

FBgn0004885

DRSC - Results frm RNAi screens

FBgn0004885

FLIGHT - Cell culture data for RNAi and other high-throughput technologies

FBgn0004885

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

CG6863-RB

FlyCyc Genes - Genes from a BioCyc PGDB for Dmel

FBGN0004885

FlyMine - An integrated database for Drosophila genomics

FBgn0004885

Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution

Interactive Fly

InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.

42944

MIST (genetic) - An integrated Molecular Interaction Database

MIST (protein-protein) - An integrated Molecular Interaction Database

Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.

Synonyms and Secondary IDs (20)

Reported As

Symbol Synonym

CG6863

(Hosono et al., 2015, Keleman et al., 2009.8.5, Perkins et al., 2009, Carrera et al., 2008)

CT21251

(Hynes and Zhao, 2000)

TLR

(Yadav et al., 2016)

TOK

(Banyai and Patthy, 2004)

Tlr

(Raftery and Umulis, 2012, Serpe et al., 2008, Whitman and Raftery, 2005)

Tlr-1

(Marques, 2005)

Tok

(Ashe, 2002)

tldr-1

(O'Connor, 1994.7.26, Padgett et al., 1992)

tldr1

tlr

(Schleede and Blair, 2015, Peluso et al., 2011, Jensen et al., 2009, O'Connor et al., 2006, Serpe and O'Connor, 2006, Serpe and O'Connor, 2005, Serpe et al., 2005, Araujo et al., 2003, Serpe and O'Connor, 2002)

tlr-1

(Aberle and Meyer, 2005, Nguyen et al., 1994)

tlr1

(Meyer and Aberle, 2006)

Name Synonyms

Tolkin

(Meyer et al., 2011, Araujo et al., 2005, Gim et al., 2001)

Tolloid-related

(Peluso et al., 2011)

piranha

(Meyer and Aberle, 2006)

tld-related-1

(Nguyen et al., 1994)

tolkin

(Upadhyay et al., 2017, Salzer et al., 2010, Anderson et al., 2006, Araujo et al., 2006, Carneiro et al., 2006, Finelli, 1995.8.23)

tolloid-related

(Serpe and O'Connor, 2006, Serpe and O'Connor, 2002)

tolloid-related 1

(Meyer and Aberle, 2006, Padgett et al., 1992)

Secondary FlyBase IDs

Datasets (0)

Study focus (0)

Experimental Role

Project

Project Type

Title

References (104)

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