FlyBase Gene Report: Dmel\spz

General Information

Symbol

Dmel\spz

Species

D. melanogaster

Name

spatzle

Annotation Symbol

CG6134

Feature Type

protein_coding_gene

FlyBase ID

FBgn0003495

Gene Model Status

Current

Stock Availability

19 publicly available

Gene Summary

spatzle (spz) encodes a secreted protein which, after cleavage by an extracellular serine protease (encoded by ea or SPE), can induce the dimerization of the product of Tl, and the subsequent activation of the Toll pathway. It contributes to function of the Toll signaling cascade, which plays a key role in various developmental and immune processes, notably embryonic dorso-ventral patterning and regulation of antimicrobial peptides. [Date last reviewed: 2019-06-06] (FlyBase Gene Snapshot)

All Summaries

Gene Snapshot
Alliance
Auto summary
Pathway
Gene Group
UniProtKB
Red Book
Interactive Fly

Also Known As

Spaetzle, Spz-1

Key Links

Genomic Location

Cytogenetic map

97E1-97E1

Sequence location

3R:27,064,990..27,070,070 [-]

Recombination map

3-92

RefSeq locus

NT_033777 REGION:27064990..27070070

Sequence

Get Decorated FASTA

Genomic Maps

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Other Genome Views

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

Function

GO Summary Ribbons

Gene Ontology (GO) Annotations (31 terms)

Molecular Function (5 terms)

Terms Based on Experimental Evidence (4 terms)

CV Term

Evidence

References

enables growth factor activity

inferred from mutant phenotype

(Zhu et al., 2008)

enables protein homodimerization activity

inferred from direct assay

(Hoffmann et al., 2008)

enables receptor ligand activity

inferred from direct assay

(Chowdhury et al., 2019, Lewis et al., 2013, Hu et al., 2004, Weber et al., 2003)

enables Toll binding

inferred from physical interaction with FLYBASE:Tl; FB:FBgn0262473

(Parthier et al., 2014, Gangloff et al., 2008, Weber et al., 2007, Weber et al., 2003)

inferred from direct assay

(Chowdhury et al., 2019, Hu et al., 2004)

Terms Based on Predictions or Assertions (3 terms)

CV Term

Evidence

References

enables cytokine activity

traceable author statement

(Underhill, 2003)

enables growth factor activity

inferred from biological aspect of ancestor with PANTHER:PTN002354018

(assigned by GO_Central )

(Gaudet et al., 2011)

enables Toll binding

inferred from biological aspect of ancestor with PANTHER:PTN002354018

(assigned by GO_Central )

(Gaudet et al., 2011)

Biological Process (24 terms)

Terms Based on Experimental Evidence (23 terms)

CV Term

Evidence

References

involved_in antifungal innate immune response

inferred from direct assay

(Weber et al., 2003)

inferred from mutant phenotype

(Tauszig et al., 2000)

involved_in cell competition in a multicellular organism

inferred from mutant phenotype

(Alpar et al., 2018)

involved_in defense response to fungus

inferred from mutant phenotype

(assigned by UniProt )

(Jang et al., 2006)

inferred from mutant phenotype

(Leulier et al., 2006)

involved_in defense response to Gram-negative bacterium

inferred from mutant phenotype

(assigned by UniProt )

(Yamamoto-Hino and Goto, 2016)

involved_in defense response to Gram-positive bacterium

inferred from mutant phenotype

(assigned by UniProt )

(Yamamoto-Hino and Goto, 2016)

inferred from mutant phenotype

(Leulier et al., 2006, Rutschmann et al., 2002)

inferred from direct assay

(Weber et al., 2003)

involved_in dorsal/ventral axis specification

inferred from direct assay

(DeLotto and DeLotto, 1998)

inferred from genetic interaction with FLYBASE:pip; FB:FBgn0003089

(Schneider et al., 1994)

inferred from genetic interaction with FLYBASE:Spn27A; FB:FBgn0028990

(Ligoxygakis et al., 2003)

involved_in dorsal/ventral pattern formation

inferred from direct assay

(Hoffmann et al., 2008)

involved_in innate immune response

inferred from mutant phenotype

(assigned by UniProt )

(Yamamoto-Hino and Goto, 2016)

inferred from direct assay

(Chien et al., 2006)

inferred from mutant phenotype

(Shia et al., 2009, El Chamy et al., 2008)

involved_in larval somatic muscle development

inferred from mutant phenotype

(Halfon and Keshishian, 1998)

involved_in motor neuron axon guidance

inferred from mutant phenotype

(Zhu et al., 2008)

involved_in oocyte dorsal/ventral axis specification

inferred from expression pattern

(assigned by UniProt )

(Morisato and Anderson, 1994)

involved_in positive regulation of antifungal peptide biosynthetic process

inferred from mutant phenotype

(Manfruelli et al., 1999)

involved_in positive regulation of antifungal peptide production

inferred from mutant phenotype

(Lemaitre et al., 1996)

involved_in positive regulation of antimicrobial peptide biosynthetic process

inferred from direct assay

(Hu et al., 2004)

involved_in positive regulation of antimicrobial peptide production

inferred from genetic interaction with UniProtKB:Q9VMU8

(assigned by UniProt )

(Yamamoto-Hino et al., 2015)

involved_in positive regulation of biosynthetic process of antibacterial peptides active against Gram-positive bacteria

inferred from mutant phenotype

(Shia et al., 2009)

inferred from mutant phenotype

(assigned by UniProt )

(Jang et al., 2006)

acts_upstream_of positive regulation of gene expression

inferred from mutant phenotype

(assigned by UniProt )

(Hanson et al., 2021)

involved_in positive regulation of Toll signaling pathway

inferred from mutant phenotype

(assigned by UniProt )

(Jang et al., 2006)

involved_in regulation of Toll signaling pathway

inferred from mutant phenotype

(assigned by UniProt )

(Yamamoto-Hino and Goto, 2016)

involved_in response to hydrogen peroxide

inferred from direct assay

(Capilla et al., 2017)

involved_in response to tumor cell

inferred from mutant phenotype

(Parisi et al., 2014)

involved_in response to wounding

inferred from expression pattern

(Capilla et al., 2017)

involved_in Toll signaling pathway

inferred from direct assay

(Chowdhury et al., 2019, Lewis et al., 2013, Weber et al., 2003, DeLotto and DeLotto, 1998, Belvin et al., 1995)

inferred from mutant phenotype

(Yamamoto-Hino and Goto, 2016, El Chamy et al., 2008, Weber et al., 2007, Jang et al., 2006, Tauszig et al., 2000, Manfruelli et al., 1999, Lemaitre et al., 1996, Schneider et al., 1994)

inferred from genetic interaction with FLYBASE:Spn27A; FB:FBgn0028990

(Ligoxygakis et al., 2003)

Terms Based on Predictions or Assertions (4 terms)

CV Term

Evidence

References

involved_in central nervous system formation

inferred from biological aspect of ancestor with PANTHER:PTN002354018

(assigned by GO_Central )

(Gaudet et al., 2011)

involved_in innate immune response

inferred from biological aspect of ancestor with PANTHER:PTN002354018

(assigned by GO_Central )

(Gaudet et al., 2011)

involved_in regulation of Toll signaling pathway

inferred from biological aspect of ancestor with PANTHER:PTN002354018

(assigned by GO_Central )

(Gaudet et al., 2011)

involved_in Toll signaling pathway

non-traceable author statement

(assigned by UniProt )

(Morisato and Anderson, 1994)

Cellular Component (2 terms)

Terms Based on Experimental Evidence (2 terms)

CV Term

Evidence

References

located_in extracellular region

inferred from direct assay

(assigned by UniProt )

(Morisato and Anderson, 1994)

located_in extracellular space

inferred from direct assay

(Chowdhury et al., 2019, Ming et al., 2014, Shia et al., 2009, Chang and Morisato, 2002, DeLotto and DeLotto, 1998)

Terms Based on Predictions or Assertions (1 term)

CV Term

Evidence

References

is_active_in extracellular region

inferred from biological aspect of ancestor with PANTHER:PTN002354018

(assigned by GO_Central )

(Gaudet et al., 2011)

Gene Group (FlyBase)

DORSAL GROUP

SPATZLES

Pathway (FlyBase)

Toll-NF-κB Signaling Pathway Core Components

Protein Family (UniProt)

Protein Signatures (InterPro)

Summaries

Gene Snapshot

Gene Group (FlyBase)

DORSAL GROUP -: The Dorsal group genes encode components of the Toll pathway and were initially identified by maternal effect mutations resulting in the dorsalization of the embryo. (Adapted from FBrf0091014 and FBrf0223077).
SPATZLES -: The spatzles are a family of secreted proteins that share a neutrotrophin-like cystine-knot domain. Proteolytically activated, spz binds Tl and activates canonical Toll signaling in embryonic dorsal-ventral patterning and innate immunity. spz, spz5 and NT1 are more closely related to each other and to the vertebrate neurotrophins than other members of the spatzle family and some family members have neutrophin-like activity. (Adpated from FBrf0206302).

Pathway (FlyBase)

Toll-NF-κB Signaling Pathway Core Components -: In Drosophila, the canonical Toll signaling pathway is initiated by the binding of a spatzle ligand to Toll (Tl) or a Toll-like receptor leading to the nuclear localization of the NF-κB (dl or Dif) transcription factor. (Adapted from FBrf0091014 and FBrf0223077).

Protein Function (UniProtKB)

The activated form, spaetzle C-106, acts as a ligand for the Toll receptor (PubMed:12872120). Binding to Toll activates the Toll signaling pathway and induces expression of the antifungal peptide drosomycin (PubMed:8808632). Component of the extracellular signaling pathway that establishes dorsal-ventral polarity in the embryo (PubMed:8124709, PubMed:11212919).

(UniProt, P48607)

Phenotypic Description (Red Book; Lindsley and Zimm 1992)

spz: spaztle

Maternal-effect lethal. Embryos dorsalized, germline dependent. Phenotypic rescue achieved by injection of cytoplasm or poly(A)+RNA from wild-type embryos into young embryos produced by spz females; cytoplasm more effective than RNA (Seifert et al.). Temperature-sensitive period of spz3 extends from oogenesis through fertilization until about the time of pole-cell formation. Strong alleles amorphic by deficiency testing. Pole-cell-transplantation studies indicate that spz acts in germ line and not soma of mother (Seifert et al.).

Summary (Interactive Fly)

secreted - ligand for Toll - the Easter protease is likely to be the direct proteolytic activator of Spätzle

Interactive Fly

Gene Model and Products

Number of Transcripts

Number of Unique Polypeptides

Please see the JBrowse view of Dmel\spz 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

Structure New Section

Protein 3D structure (Predicted by AlphaFold) (AlphaFold entry P48607)

If you don't see the viewer to the right, refresh your browser.

Model Confidence:

Very high (pLDDT > 90)
Confident (90 > pLDDT > 70)
Low (70 > pLDDT > 50)
Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Comments on Gene Model

Alternative transcripts labeled with isoform names according to (FBrf0134774)

Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.

Gene model reviewed during 5.46

Sequence Ontology: Class of Gene

nuclear_gene

protein_coding_gene

Transcript Data

Annotated Transcripts

Name

FlyBase ID

RefSeq ID

Length (nt)

Assoc. CDS (aa)

spz-RA

FBtr0085137

NM_079802

2128

326

spz-RB

FBtr0085138

NM_170312

2050

300

spz-RC

FBtr0085139

NM_170315

1909

253

spz-RD

FBtr0085140

NM_170316

1969

273

spz-RI

FBtr0085145

NM_170309

1831

227

spz-RJ

FBtr0085146

NM_170313

1882

244

spz-RK

FBtr0112834

NM_001104472

2118

290

spz-RL

FBtr0114372

NM_001144644

2058

270

Additional Transcript Data and Comments

Reported size (kB)

2.3, 2.1, 1.9 (longest cDNA)

(Morisato and Anderson, 1994)

Comments

External Data

Crossreferences

Polypeptide Data

Annotated Polypeptides

Name

FlyBase ID

Predicted MW (kDa)

Length (aa)

Theoretical pI

UniProt

RefSeq ID

GenBank

spz-PA

FBpp0084507

37.4

326

6.59

FBpp0084508

34.3

300

7.21

FBpp0084509

29.0

253

6.03

NP_733194

AAN14394

spz-PD

FBpp0084510

30.9

273

7.42

NP_733195

AAN14395

spz-PI

FBpp0084515

25.9

227

6.97

NP_733188

AAN14388

spz-PJ

FBpp0084516

28.0

244

6.35

FBpp0111747

33.0

290

6.85

FBpp0112921

31.0

270

7.21

A1Z0H7

NP_001138116

ACL83572

Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments

Reported size (kDa)

326, 253 (aa); 38, 29 (kD predicted); 23 (kD)

(Morisato and Anderson, 1994)

24 (kD)

(Schneider et al., 1994)

Comments

External Data

Subunit Structure (UniProtKB)

Homodimer; disulfide-linked (PubMed:12872120, PubMed:9533958). In the presence of Tl, crystal structures show one Tl molecule bound to a spaetzle C-106 homodimer (PubMed:24733933, PubMed:24282309). However, the active complex probably consists of two Tl molecules bound to a spaetzle C-106 homodimer (PubMed:24282309, PubMed:24733933). This is supported by in vitro experiments which also show binding of the spaetzle C-106 dimer to 2 Tl receptors (PubMed:12872120). Ligand binding induces conformational changes in the extracellular domain of Tl (PubMed:24282309). This may enable a secondary homodimerization interface at the C-terminus of the Tl extracellular domain (PubMed:24282309).

(UniProt, P48607)

Post Translational Modification

During embryonic development, easter cleaves the signal peptide and also generates the C-terminal 12 kDa active fragment, C-106 (except for isoform 8.24 and isoform 11.27 as they do not contain the cleavage site) (PubMed:9533958). During the immune response, cleaved in the same manner by SPE (PubMed:16399077).

Extracellular forms of isoform 8.19 and isoform 11.7 are glycosylated.

(UniProt, P48607)

Crossreferences

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

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\spz using the Feature Mapper tool.

External Data

Crossreferences

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

spz_1

Linkouts

Expression Data

Expression Summary Ribbons

Colored tiles in ribbon indicate that the Fly Cell Atlas project found the gene expressed in that cell type. Darker colors mean that more cells of that cell type express the gene:

low

high

Colorless tiles indicate that there is no scRNAseq data for the gene in that cell type.

Colored tiles in ribbon indicate that expression data (RNA and/or protein) has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.

Colored tiles in the ribbon indicate the average RNA expression level of the gene at the indicated stages:

low

high

as determined by RNA-seq (RPKM) using whole organism samples modENCODE, Brown et al., 2014. 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

embryonic stage

A1-7 segment border muscle cell

(Zhu et al., 2008)

A1-7 lateral transverse muscle cell

(Zhu et al., 2008)

embryonic stage 1 -- 3

organism

Comment: maternally deposited

(Fisher et al., 2012)

embryonic stage 13

ventral midline of embryo

(Zhu et al., 2008)

embryonic stage 13 -- 16

embryonic foregut

(Fisher et al., 2012)

embryonic rectum

(Fisher et al., 2012)

northern blot

Stage

Tissue/Position (including subcellular localization)

Reference

embryonic stage 1 -- 4

Comment: reference states 0-2 hr AEL

(Morisato and Anderson, 1994)

oogenesis & adult stage | female

ovary

(Morisato and Anderson, 1994)

Additional Descriptive Data

spz transcripts are detected in RNA from ovaries and early embryos. In embryos, spz transcripts are rare and disappear within 2 hours after egg laying.

(Morisato and Anderson, 1994)

Marker for

Subcellular Localization

CV Term

Polypeptide Expression

immunolocalization

Stage

Tissue/Position (including subcellular localization)

Reference

larval stage

lamellocyte | faint

(Paddibhatla et al., 2010)

embryonic/larval plasmatocyte

(Paddibhatla et al., 2010)

Additional Descriptive Data

spz protein is secreted into the perivitelline space.

(Morisato and Anderson, 1994)

Marker for

Subcellular Localization

CV Term

Evidence

References

located_in extracellular region

inferred from direct assay

(assigned by UniProt )

(Morisato and Anderson, 1994)

located_in extracellular space

inferred from direct assay

(Chowdhury et al., 2019, Ming et al., 2014, Shia et al., 2009, Chang and Morisato, 2002, DeLotto and DeLotto, 1998)

Expression Deduced from Reporters

High-Throughput Expression Data

Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\spz 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\spz

View exonic expression by tissue for Dmel\spz

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

FBgn0003495

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

43256/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0003495

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0003495

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0003495

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

CG6134

Flygut - An atlas of the Drosophila adult midgut

FBgn0003495

Images

FlyExpress - Embryonic expression images (BDGP data)

Show all FlyExpress processed images for Dmel\spz

Stages(s) 1-3
Stages(s) 13-16

FlyBase Wiki

Image Based Resources

Alleles, Insertions, Transgenic Constructs, and Aberrations

Classical and Insertion Alleles ( 33 )

For All Classical and Insertion Alleles Show

Other relevant insertions

Transgenic Constructs ( 24 )

For All Alleles Carried on Transgenic Constructs Show

Transgenic constructs containing/affecting coding region of spz

Transgenic constructs containing regulatory region of spz

Aberrations (Deficiencies and Duplications) ( 7 )

Inferred from experimentation ( 7 )

Gene disrupted in

Df(3R)Bd

(Morisato and Anderson, 1994)

Df(3R)Tl-D

(Morisato and Anderson, 1994)

Df(3R)Tl-I

(Morisato and Anderson, 1994)

Df(3R)Tl-X

(Tearle and Nusslein-Volhard, 1987)

Gene not disrupted in

Df(3R)D605

(Hecht and Anderson, 1993, Tearle and Nusslein-Volhard, 1987)

Df(3R)R38.3

(Hecht and Anderson, 1993)

Df(3R)ro80b

(Tearle and Nusslein-Volhard, 1987)

Inferred from location ( 0 )

Alleles Representing Disease-Implicated Variants

Phenotypes

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

Lethality

Allele

lethal | dominant | maternal effect

spz^D1

lethal | maternal effect

spz¹

lethal | maternal effect | recessive

lethal - all die during embryonic stage | germline clone | non-rescuable maternal effect | recessive

lethal - all die during embryonic stage | maternal effect | recessive

partially lethal

spz²

partially lethal - majority die | recessive

spz^Δ8-1

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

spz^GD570

viable, with Scer\GAL4^Mef2.PR

spz^GD570

viable, with Scer\GAL4^pnr-MD237

spz^GD570

Other Phenotypes

Allele

abnormal immune response

abnormal immune response | adult stage

spz⁴

abnormal immune response | adult stage, with Scer\GAL4^r4

spz^KK112908

abnormal immune response | adult stage, with Scer\GAL4^yolk

spz^KK112908

abnormal immune response | conditional

spz⁴

abnormal immune response | recessive

spz²⁰

abnormal locomotor rhythm

spz²

abnormal neuroanatomy

spz²

increased mortality | adult stage | conditional

spz⁴

increased mortality | conditional

spz⁴

radiation sensitive

spz⁴

short lived | conditional

spz⁴

some die during embryonic stage | non-rescuable maternal effect | recessive

some die during embryonic stage | recessive | maternal effect | recessive

visible | adult stage | conditional

spz⁴

Phenotype manifest in

Allele

embryo | maternal effect, with Scer\GAL4^VP16.nos.UTR

spz^UASp.mGFP6

embryo | ventral

spz^unspecified

embryonic/first instar larval cuticle, with Df(3R)Bd

spz⁴

embryonic/first instar larval cuticle (with Df(3R)Bd)

spz⁴

embryonic/first instar larval cuticle | dorsal | maternal effect

embryonic/first instar larval cuticle | lateral | maternal effect

embryonic/first instar larval cuticle | maternal effect, with Scer\GAL4^VP16.otu

spz^UASp.Tag:HA

embryonic/first instar larval cuticle | maternal effect | ventral

embryonic/larval fat body, with Scer\GAL4^Cg.PA

spz^act.UAS

embryonic/larval fat body, with Scer\GAL4^Hml.PG

spz^act.UAS

embryonic/larval fat body, with Scer\GAL4^Lsp2.PH

spz^act.UAS

embryonic/larval hemocoel, with Scer\GAL4^Cg.PA

spz^act.UAS

embryonic/larval hemocoel, with Scer\GAL4^Hml.PG

spz^act.UAS

embryonic/larval hemocoel, with Scer\GAL4^Lsp2.PH

spz^act.UAS

embryonic/larval somatic muscle cell

ventral furrow | ectopic, with Df(3R)Bd

spz⁴

ventral furrow | ectopic (with Df(3R)Bd)

spz⁴

ventral furrow | increased number, with Df(3R)Bd

spz⁴

ventral furrow | increased number (with Df(3R)Bd)

spz⁴

wing | conditional

spz⁴

Orthologs

Downloads

Download All DIOPT Orthologs

Human Orthologs (via DIOPT v8.0)

Homo sapiens (Human) (0)

No records found.

Model Organism Orthologs (via DIOPT v8.0)

Mus musculus (laboratory mouse) (0)

No records found.

Rattus norvegicus (Norway rat) (0)

No records found.

Xenopus tropicalis (Western clawed frog) (0)

No records found.

Danio rerio (Zebrafish) (0)

No records found.

Caenorhabditis elegans (Nematode, roundworm) (0)

No records found.

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.

Other Organism Orthologs (via OrthoDB)

Paralogs

Downloads

Download All DIOPT Paralogs

Paralogs (via DIOPT v8.0)

Drosophila melanogaster (Fruit fly) (5)

Gene Symbol

Score

Source

Alignment

2 of 10

NT1

1 of 10

spz3

1 of 10

spz4

1 of 10

spz6

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 ( 0 )

Human Ortholog

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 4 )

Allele

Disease

Interaction

References

spz⁴

ameliorates hematologic cancer

modeled by lwr^4-3, lwr⁵

(Paddibhatla et al., 2010)

spz^act.UAS

exacerbates carcinoma

modeled by Ras85D^V12.UAS, l(2)gl⁴

(Mishra-Gorur et al., 2019)

spz^KK112908

exacerbates cancer

modeled by dlg1^A40.2

(Parisi et al., 2014)

spz^HM05024

ameliorates neurodegenerative disease

modeled by Zzzz\CTG^{rCUG.99.UAS.Tag:MYC,Tag:FLAG}, Zzzz\CAG^{99.UAS.Tag:MYC,Tag:FLAG}

(Samaraweera et al., 2013)

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?

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

spz

detection by mass spectrometry, molecular sieving, molecular weight estimation by staining, affinity chromatography technology, western blot, comigration in non denaturing gel electrophoresis, anti tag coimmunoprecipitation, anti tag western blot, x-ray crystallography, phenotype-based detection assay, fluorescence microscopy, inferred by author

(Haskel-Ittah et al., 2012, Arnot et al., 2010, Hoffmann et al., 2008, Hu et al., 2004, Weber et al., 2003, DeLotto and DeLotto, 1998)

spz - Toll-7

anti tag coimmunoprecipitation, anti tag western blot

(Chowdhury et al., 2019)

spz - ea

enzymatic study, molecular weight estimation by staining, western blot, inferred by author, anti tag western blot

(Ursel et al., 2013, Hashimoto et al., 2003, Dissing et al., 2001)

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

Rel|spz

suppressible

BaraA1

(Hanson et al., 2021)

spz

suppressible

cact

(Belvin et al., 1995)

spz

suppressible

cic

(Goff et al., 2001)

enhanceable

(Zhu et al., 2008)

enhanceable

(Zhu et al., 2008)

enhanceable

(Cho et al., 2010)

enhanceable

(De Gregorio et al., 2002)

enhanceable

(Zhu et al., 2008)

enhanceable

(Nonaka et al., 2018)

spz

enhanceable

(Zhu et al., 2008)

spz

suppressible

(McIlroy et al., 2013)

enhanceable

(Riede, 1996)

suppressible

(McIlroy et al., 2013)

spz

suppressible

Toll-7

(McIlroy et al., 2013)

Starting gene(s)

Interaction type

Interacting gene(s)

Reference

cact

enhanceable

spz

(Wakabayashi-Ito et al., 2001)

dlg1

enhanceable

spz

(Parisi et al., 2014)

suppressible

(Morisato, 2001)

suppressible

(Liu et al., 2015)

suppressible

(Green et al., 2000)

enhanceable

(Zhu et al., 2008)

suppressible

(Zhu et al., 2008)

enhanceable

(De Gregorio et al., 2002)

Spn27A

suppressible

spz

(Hashimoto et al., 2003)

enhanceable

(Zhu et al., 2008)

enhanceable

(Zhu et al., 2008)

enhanceable

(Zhu et al., 2008)

enhanceable

(Riede, 1996)

enhanceable

(Riede, 1996)

External Data

Subunit Structure (UniProtKB)

(UniProt, P48607 )

Linkouts

BioGRID - A database of protein and genetic interactions.

68145

DroID - A comprehensive database of gene and protein interactions.

FBgn0003495

MIST (genetic) - An integrated Molecular Interaction Database

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

Pathways

Signaling Pathways (FlyBase)

Toll-NF-κB Signaling Pathway Core Components -: In Drosophila, the canonical Toll signaling pathway is initiated by the binding of a spatzle ligand to Toll (Tl) or a Toll-like receptor leading to the nuclear localization of the NF-κB (dl or Dif) transcription factor. (Adapted from FBrf0091014 and FBrf0223077).

Metabolic Pathways

External Data

Linkouts

KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.

Toll and Imd signaling pathway

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

Genomic Location and Detailed Mapping Data

Chromosome (arm)

Recombination map

3-92

Cytogenetic map

97E1-97E1

Sequence location

3R:27,064,990..27,070,070 [-]

FlyBase Computed Cytological Location

Cytogenetic map

Evidence for location

97E1-97E1

Limits computationally determined from genome sequence between P{PZ}sda⁰³⁸⁸⁴ and P{PZ}btz^rL203

Experimentally Determined Cytological Location

Cytogenetic map

Notes

References

Experimentally Determined Recombination Data

Location

3-92

(FlyBase, 2016, Riede, 1996, Tearle and Nusslein-Volhard, 1987)

3-89.3

(Comeron et al., 2012)

Left of (cM)

Right of (cM)

Notes

Stocks and Reagents

Stocks (19)

Aberrations including deletions of this gene Aberrations including duplications of this gene

Bloomington

3115

spz² ca¹/TM1

28538

y¹ v¹; P{TRiP.HM05024}attP2

58499

y¹ v¹; P{TRiP.HMJ22258}attP40

66923

y¹ v¹; P{TRiP.HMS05389}attP40

34313

y¹ w^*; Mi{MIC}spz^MI02318

51092

y¹ w^*; Mi{MIC}spz^MI08633

3287

ru¹ st¹ ea¹⁴ spz³ ca¹/TM1

14442

y¹ w^67c23; ry⁵⁰⁶ P{SUPor-P}spz^KG05402

Kyoto

106855

spz² ca¹/TM1

106958

ru¹ st¹ ea¹⁴ spz³ ca¹/TM1

VDRC

v105017

P{KK112908}VIE-260B

v7571

w¹¹¹⁸; P{GD570}v7571/TM3

More stocks available...

Genomic Clones (21)

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

cDNA Clones (117)

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

FI05217

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.

FBgn0003495

cDNA Clones, End Sequenced (ESTs)

BDGP DGC clones

Other clones

RNAi and Array Information

Linkouts

DRSC - Results frm RNAi screens

FBgn0003495

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

43256

Antibody Information

Laboratory Generated Antibodies

Commercially Available Antibodies

Other Information

Relationship to Other Genes

Source for database identify of

Source for database merge of

Additional comments

A dorsalising activity for the heterologous ea, spz and Tl proteins in UV-ventralised Xenopus embryos is demonstrated: spz rescues axis structures in UV-ventralised Xenopus embryos. The activity is inhibited by co-injection of a dominant cact variant.

(Armstrong et al., 1998)

Other Comments

Gene expression is increased in response to the presence of two copies of Scer\GAL4^hs.PB.

(Liu and Lehmann, 2008)

NT1 amd spz are expressed in the embryonic lateral muscles in a complementary pattern, suggesting that they may aid targeting by different axonal projections and promote the survival of distinct subsets of neurons.

(Zhu et al., 2008)

The mature, processed, form of the spz gene product binds to the Tl ectodomain with high affinity and with a stoichiometry of one spz dimer to two Tl receptors. The spz pro-domain sequence acts to prevent interaction of the spz cytokine and its receptor Tl.

(Weber et al., 2003)

A linear activation cascade spz-Tl-cact-dl/Dif leads to the induction of the Drs gene in larval fat body cells.

(Manfruelli et al., 1999)

ea can directly cleave spz at a unique position, the spz carboxy-terminal fragment generated has the biological and biochemical properties of the polarising activity of spz, it exists as a disulfide-linked dimer and appears to share structural similarities with the nerve growth factor and the neurotrophin family of growth factor ligands.

(DeLotto and DeLotto, 1998)

spz is required for muscle development in the embryo.

(Halfon and Keshishian, 1998)

The embryonic regulatory pathway, comprising the gene products between spz and cact (Tl, tub and pll) but not the genes acting upstream or downstream (ea and dl), is involved in the induction of the Drs gene in adults. Mutations that affect the synthesis of antimicrobial peptides dramatically lower the resistance of flies to infection.

(Lemaitre et al., 1996)

Does not belong to the proliferative class of genes involved in Malignant Brain Tumor (MBT) syndrome.

(Riede, 1996)

Mutations in spz, tld and yeti cooperatively induce brain tumor formation in the Malignant Brain Tumor strain.

(Riede, 1996)

The secreted spz product must be activated by proteolytic cleavage, and localized proteolytic processing of the spz protein determines where the receptor, Tl, is active.

(Morisato and Anderson, 1994)

The spz product acts immediately upstream of Tl in dorso-ventral pattern formation in the embryo, and may encode the ligand that activates Tl.

(Morisato and Anderson, 1994)

spz is the soluble extracellular factor (polarising activity) that induces ventral structures when injected into the extracellular space of embryos.Proteolytic processing of spz product generates a polarised form of spz which defines embryonic dorsal ventral polarity by activation of Tl on the ventral side of the embryo.

(Schneider et al., 1994)

Double mutant combinations of spz with ea alleles demonstrate that spatial regulation of ea activity by localized zymogen activation is a key initial event in defining the polarity of the dorsal-ventral embryonic pattern.

(Chasan et al., 1992)

Pole-cell-transplantation studies indicate that spz acts in germ line and not soma of mother.

(Seifert et al., 1987)

Origin and Etymology

Discoverer

Etymology

Identification

External Crossreferences and Linkouts ( 130 )

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.

43256

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/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.

P48607

UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information

P48607

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

Other crossreferences

AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.

P48607

BDGP expression data - Patterns of gene expression in Drosophila embryogenesis

FBgn0003495

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

FBgn0003495

DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species

43256/tissue=All

EMBL-EBI Single Cell Expression Atlas - Single cell expression across species

FBgn0003495

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

spz_1

FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array

FBgn0003495

FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data

FBgn0003495

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

CG6134

Flygut - An atlas of the Drosophila adult midgut

FBgn0003495

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

102173

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

43256

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

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

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

Dmel_CG6134

MARRVEL_MODEL - MARRVEL (model organism gene)

43256

modMine - A data warehouse for the modENCODE project

FBgn0003495

Linkouts

BioGRID - A database of protein and genetic interactions.

68145

DroID - A comprehensive database of gene and protein interactions.

FBgn0003495

DRSC - Results frm RNAi screens

FBgn0003495

FlyCyc Genes - Genes from a BioCyc PGDB for Dmel

FBGN0003495

FlyMine - An integrated database for Drosophila genomics

FBgn0003495

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

Interactive Fly

KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.

Toll and Imd signaling pathway

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 (16)

Reported As

Symbol Synonym

CG6134

(Palu and Thummel, 2016, Hosono et al., 2015, Liu et al., 2015, Buendia et al., 2012, Ni et al., 2010.12.1, Keleman et al., 2009.8.5, Perkins et al., 2009, Wang and Zhu, 2009, Hernandez-Romano et al., 2008, De Gregorio et al., 2002, De Gregorio et al., 2001, Parker et al., 2001)

CT19282

(Parker et al., 2001)

SPZ

(Galenza and Foley, 2019, Ferrandon, 2013, Cronin et al., 2009, Kuranaga and Miura, 2007)

Spatzle

(Marques-Reis and Moreno, 2021, Nagai et al., 2021, Sciambra and Chtarbanova, 2021)

Spz

(Evans et al., 2022, Takeuchi et al., 2022, Dillard et al., 2021, Morata, 2021, Ozakman and Eleftherianos, 2021, Alameh et al., 2020, Baker, 2020, Kanda and Igaki, 2020, Kosakamoto et al., 2020, Luo et al., 2020, Morata and Calleja, 2020, Schloop et al., 2020, Sanuki et al., 2019, Anthoney et al., 2018, Issa et al., 2018, Troha et al., 2018, Kashio et al., 2017, Clavería and Torres, 2016, Katzenberger et al., 2016, Yamamoto-Hino and Goto, 2016, Liu et al., 2015, Shaukat et al., 2015, Vlisidou and Wood, 2015, Wu et al., 2015, Zhan et al., 2015, Engel et al., 2014, Kurata, 2014, Zhou et al., 2014, Bangi, 2013, Kemp et al., 2013, Mbodj et al., 2013, Shilo et al., 2013, Yamamoto-Hino and Goto, 2013, Kounatidis and Ligoxygakis, 2012, Lim and Thiery, 2012, Hidalgo et al., 2011, Lynch and Roth, 2011, Reichhart et al., 2011, Valanne et al., 2011, Kurata, 2010, Valanne et al., 2010, Ahmad et al., 2009, Buchon et al., 2009, Obbard et al., 2009, Gangloff et al., 2008, Hoffmann et al., 2008, Waterhouse et al., 2007, Chen, 2006, Parker and Weber, 2006.12.3, Bischoff et al., 2004, Parker et al., 2001)

Spz-1

(Lu et al., 2020, Chowdhury et al., 2019)

Spz1

(Wang and Zhu, 2009)

mel(3)7

spz

(Bahuguna et al., 2022, Kubrak et al., 2022, Peng et al., 2022, Hanson et al., 2021, Kanoh et al., 2021, Li and Hidalgo, 2021, Marra et al., 2021, Ramond et al., 2021, Snigdha et al., 2021, Iwashita et al., 2020, Krautz et al., 2020, Statzer and Ewald, 2020, Asri et al., 2019, Banerjee et al., 2019, Belmonte et al., 2019, Hanson et al., 2019, Mishra-Gorur et al., 2019, Panettieri et al., 2019, Parvy et al., 2019, Rahimi et al., 2019, Sanchez Bosch et al., 2019, Troha and Buchon, 2019, Troha et al., 2019, Alpar et al., 2018, Shahrestani et al., 2018, Yu et al., 2018, Del Signore et al., 2017, Dostálová et al., 2017, Duneau et al., 2017, Keesey et al., 2017, Kenmoku et al., 2017, Louradour et al., 2017, Patrnogic and Leclerc, 2017, Romero-Pozuelo et al., 2017, Transgenic RNAi Project members, 2017-, Guillou et al., 2016, Iatsenko et al., 2016, Kučerová et al., 2016, Lamiable et al., 2016, Liu et al., 2016, Mistry et al., 2016, Morris et al., 2016, Rahimi et al., 2016, Sandler and Stathopoulos, 2016, Troutwine et al., 2016, Hsu et al., 2015, Kanoh et al., 2015, Neyen and Lemaitre, 2015, Sudmeier et al., 2015, Ward et al., 2015, Xia et al., 2015, Xiao et al., 2015, Yamamoto-Hino et al., 2015, Binggeli et al., 2014, Carvalho et al., 2014, Chambers et al., 2014, Ferreira et al., 2014, Zhou et al., 2014, Clark et al., 2013, Kari et al., 2013, Katzenberger et al., 2013, McIlroy et al., 2013, Nelson et al., 2013, Quintin et al., 2013, Rancès et al., 2013, Samaraweera et al., 2013, Sutcliffe et al., 2013, Buendia et al., 2012, Cho et al., 2012, Haskel-Ittah et al., 2012, Kounatidis and Ligoxygakis, 2012, Lemaitre et al., 2012, Nam et al., 2012, Akhouayri et al., 2011, Bou Aoun et al., 2011, Fullaondo et al., 2011, Glittenberg et al., 2011, Glittenberg et al., 2011, Marcu et al., 2011, Narbonne-Reveau et al., 2011, Zaidman-Rémy et al., 2011, Zhao et al., 2011, Becker et al., 2010, Chen et al., 2010, Cho et al., 2010, Hill-Burns and Clark, 2010, Huang et al., 2010, Matskevich et al., 2010, Paddibhatla et al., 2010, Ahmad et al., 2009, Buchon et al., 2009, Buchon et al., 2009, Charroux and Royet, 2009, Geuking et al., 2009, Seugnet et al., 2009, Shia et al., 2009, Bushati et al., 2008, El Chamy et al., 2008, Gordon et al., 2008, Hoffmann et al., 2008, Jin et al., 2008, Jones et al., 2008, Kwon et al., 2008, Linder et al., 2008, Liu and Lehmann, 2008, Ratnaparkhi et al., 2008, Stramer et al., 2008, Tan et al., 2008, Tang et al., 2008, Vonkavaara et al., 2008, Xi et al., 2008, Zhu et al., 2008, Bidla et al., 2007, Hallem et al., 2007, Hueber et al., 2007, Taylor and Kimbrell, 2007, Wu et al., 2007, Brun et al., 2006, Chen et al., 2006, Chien et al., 2006, Kambris et al., 2006, Kambris et al., 2006, Leclerc et al., 2006, Mulinari et al., 2006, Ryu et al., 2006, Scherfer et al., 2006, Senger et al., 2006, Tang et al., 2006, Zaidman-Remy et al., 2006, Castillejo-Lopez and Häcker, 2005, Zhou et al., 2005, Dionne et al., 2003, Lau et al., 2003, Leulier et al., 2003, Leulier et al., 2003, Ligoxygakis et al., 2002, Rutschmann et al., 2002, Tauszig-Delamasure et al., 2002, DeLotto, 2001, Rutschmann et al., 2000, Lindsley and Zimm, 1992)

Name Synonyms

Protein spaetzle precursor

(Hernandez-Romano et al., 2008)

Spatzle

(Irizarry and Stathopoulos, 2021, Lima et al., 2021, Rosendo Machado et al., 2021, Schneider and Imler, 2021, Arora and Ligoxygakis, 2020, Martin, 2020, Nie et al., 2018, Mussabekova et al., 2017, Di Gregorio et al., 2016, Vanha-Aho et al., 2016, Kwong et al., 2015, Yamamoto-Hino et al., 2015, Zhan et al., 2015, Lindsay and Wasserman, 2014, Xu and Cherry, 2014, Arvanitis et al., 2013, Bangi, 2013, Gendrin et al., 2013, Müller et al., 2013, Stelter et al., 2013, Ursel et al., 2013, Haskel-Ittah et al., 2012, Igboin et al., 2012, Vanha-Aho et al., 2012, Akhouayri et al., 2011, Griffin et al., 2011, Hidalgo et al., 2011, Arnot et al., 2010, Sabin et al., 2010, Stein et al., 2010, Valanne et al., 2010, Buchon et al., 2009, Wang and Zhu, 2009, El Chamy et al., 2008, Hoffmann et al., 2008, Kleino et al., 2008, Tang et al., 2008, Xi et al., 2008, Zhu et al., 2008, Tanji et al., 2007, Weber et al., 2007, Mulinari et al., 2006, Senger et al., 2006, Gangloff and Gay, 2004, Roxstrom-Lindquist et al., 2004, Parker et al., 2001)

Spaztle

(Kingsolver et al., 2013)

spaetzle

(Fink et al., 2016, Becker et al., 2010, Ahmad et al., 2009, Ratnaparkhi et al., 2008, Taylor and Kimbrell, 2007, Brun et al., 2006, Leclerc et al., 2006, Scherfer et al., 2006, Castillejo-Lopez and Häcker, 2005, De Gregorio et al., 2002, Irving et al., 2001, Lemaitre, 2000.12.20, Ulevitch, 1999)

spazle

(Matskevich et al., 2010)

spaztle

(Lindsley and Zimm, 1992)

Secondary FlyBase IDs

Datasets (0)

Study focus (0)

Experimental Role

Project

Project Type

Title

Study result (0)

Result

Result Type

Title

References (522)

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