FB2026_03 , released September 17, 2026
Gene: Dmel\SIFa
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General Information
Symbol
Dmel\SIFa
Species
D. melanogaster
Name
SIFamide
Annotation Symbol
CG33527
Feature Type
protein_coding_gene
FlyBase ID
FBgn0053527
Gene Model Status
Current
Stock Availability
10 publicly available
Gene Summary
SIFamide (SIFa) encodes a neuropeptide conserved across many insects and other arthropods, produced by only a few neurons that project widely throughout the nervous system. By binding to its receptor SIFaR, it functions in a signaling pathway related to vertebrate GnIH, helping to align internal states with behavior. SIFa plays key roles in regulating feeding, sleep, and reproductive strategies, ensuring that energy is conserved or invested appropriately. [Date last reviewed: 2025-09-18] (FlyBase Gene Snapshot)
All Summaries
Also Known As

IFa, Neb-LFamide, Drm-IFa

Key Links
Genomic Location
Cytogenetic map
60D5-60D5
Sequence location
Recombination map
2-107
RefSeq locus
NT_033778 REGION:24577566..24578143
Sequence
Get Decorated FASTA
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
NCBI
UCSC
Ensembl
PopFly
Function
Gene Ontology (GO) Annotations (11 terms)
Molecular Function (4 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
enables neuropeptide hormone activity
inferred from mutant phenotype
(Zhang et al., 2025)
enables neuropeptide receptor binding
inferred from physical interaction with FLYBASE:SIFaR; FB:FBgn0038880
(Jorgensen et al., 2006)
enables receptor ligand activity
inferred from physical interaction with FLYBASE:SIFaR; FB:FBgn0038880
(Jorgensen et al., 2006)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
enables hormone activity
non-traceable author statement
(Hewes and Taghert, 2001)
Biological Process (6 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
involved_in male mating behavior
inferred from mutant phenotype
(Zhang et al., 2025)
involved_in mating behavior, sex discrimination
inferred from mutant phenotype
(Sellami and Veenstra, 2015)
inferred from mutant phenotype
(Zhang et al., 2025, Terhzaz et al., 2007)
involved_in negative regulation of female receptivity
inferred from mutant phenotype
(Terhzaz et al., 2007)
involved_in neuropeptide signaling pathway
inferred from mutant phenotype
(Zhang et al., 2025)
inferred from direct assay
(Jorgensen et al., 2006)
involved_in positive regulation of circadian sleep/wake cycle, sleep
inferred from mutant phenotype
(Park et al., 2014)
involved_in regulation of circadian rhythm
inferred from mutant phenotype
(Bai et al., 2018)
Terms Based on Predictions or Assertions (0 terms)
Cellular Component (1 term)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
located_in extracellular region
inferred by curator from GO:0048018,GO:0071855
(Jorgensen et al., 2006)
Gene Group / Complex (FlyBase)
Protein Family (UniProt)
Belongs to the FARP (FMRFamide related peptide) family. (Q6IGX9)
Protein Signatures (InterPro)
Summaries
Gene Snapshot
SIFamide (SIFa) encodes a neuropeptide conserved across many insects and other arthropods, produced by only a few neurons that project widely throughout the nervous system. By binding to its receptor SIFaR, it functions in a signaling pathway related to vertebrate GnIH, helping to align internal states with behavior. SIFa plays key roles in regulating feeding, sleep, and reproductive strategies, ensuring that energy is conserved or invested appropriately. [Date last reviewed: 2025-09-18]
Gene Group / Complex (FlyBase)
NEUROPEPTIDES -
Neuropeptides are secreted into the extracellular space where they interact with cell surface receptors (usually G protein coupled receptors). They are extremely diverse, acting as neurotransmitters, neuromodulators, hormones or growth factors. (Adapted from FBrf0211443 and PMID:27813667).
Protein Function (UniProtKB)
Ligand for the neuropeptide SIFamide receptor (PubMed:16378592). Modulates sexual behavior by negatively regulating female receptivity to male courtship and by playing a role in male sex discrimination (PubMed:17126293, PubMed:26469541). Also involved in promoting sleep (PubMed:24658384).
(UniProt, Q6IGX9)
Summary (Interactive Fly)

hormone, regulation of feeding behavior and sexual behavior, brain

Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\SIFa 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
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry Q6IGX9)

If you don't see a structure in the viewer, 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.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Gene model reviewed during 5.52

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
SIFa-RB
FBtr0305055
NM_001259567
526
72
Additional Transcript Data and Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
SIFa-PB
FBpp0293592
7.9
72
8.21
Q6IGX9
NP_001246496
AFH08249
Polypeptides with Identical Sequences

There is only one protein coding transcript and one polypeptide associated with this gene

Additional Polypeptide Data and Comments
Reported size (kDa)
Comments

Small SIFa-derived neuropeptides identified by 2D capillary LC/ESI-MS/MS: AYRKPPFNGSIF-amide.

(Baggerman et al., 2005)
External Data
Crossreferences
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

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

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.57

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
third instar larval stage
larval SIFamide cell of pars intercerebralis
(Terhzaz et al., 2007)
adult stage
adult SIFamide cell of pars intercerebralis
(Terhzaz et al., 2007)
microinjection
Stage
Tissue/Position (including subcellular localization)
Reference
adult stage
adult insulin secreting cell of pars intercerebralis
(Cavanaugh et al., 2014)
Additional Descriptive Data

Expression of SIFa was established via single cell RNA sequencing of ScerGAL4Kurs58 or ScerGAL4c767 positive pars intercerebralis neurons. Expression was found in two out of five tested cells.

(Cavanaugh et al., 2014)
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
third instar larval stage
larval insulin secreting cell of pars intercerebralis | subset
(Sellami et al., 2012)
larval SIFamide cell of pars intercerebralis
(Terhzaz et al., 2007)
wandering third instar larval stage
larval ring gland projection neuron
(Verleyen et al., 2004)
adult stage
adult brain | restricted
(Kahsai and Winther, 2011, Carlsson et al., 2010)
adult pars intercerebralis
(Kahsai and Winther, 2011, Carlsson et al., 2010)
adult antennal lobe glomerulus | subset
(Carlsson et al., 2010)
fan-shaped body | dorsal
(Kahsai and Winther, 2011)
fan-shaped body | faint | ventral
(Kahsai and Winther, 2011)
fan-shaped body | central | faint
(Kahsai and Winther, 2011)
ellipsoid body
(Kahsai and Winther, 2011)
protocerebral bridge
(Kahsai and Winther, 2011)
adult insulin secreting cell of pars intercerebralis
(Verleyen et al., 2004)
adult pars intercerebralis | restricted
(Cavanaugh et al., 2014)
adult SIFamide cell of pars intercerebralis
(Martelli et al., 2017, Terhzaz et al., 2007)
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
wandering third instar larval stage
larval central nervous system
(Baggerman et al., 2005)
Additional Descriptive Data

Expression of SIFa protein is found in a subset of four ScerGAL4Kurs58 positive pars intercerebralis neurons.

(Cavanaugh et al., 2014)

SIFa colocalizes with larval dorsomedial ScerGAL4ATP7.PB expressing larval dorsomedial neurosecretory cells.

(Sellami et al., 2012)

SIFa protein is detected in layer 5 of the fan-shaped body, as well as faintly in the central and ventral layers.

(Kahsai and Winther, 2011)

SIFa protein is expressed in 4 cells in the pars intercerebralis that extend processes throughout most of the brain neuropils, except for the mushroom body stalks, lobes and calyces. The processes that innervate the antennal lobe arborise in most glomeruli. In addition, 3 pairs of cell bodies are detected in the dorsolateral protocerebrum. The cells labelled in the pars intercerebralis by SIFa also express ScerGAL4IFa.PT.

(Carlsson et al., 2010)

Ifa protein is expressed in two pairs of neurons in the pars intercerebralis, that project into the ventral nerve cord. These cells also have numerous Ifa varicosities in adult flies.

(Verleyen et al., 2004)
Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\SIFa in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
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
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Flygut - An atlas of the Drosophila adult midgut
Images
FlyBase Wiki
Image Based Resources
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 7 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 11 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of SIFa
Transgenic constructs containing regulatory region of SIFa
Aberrations (Deficiencies and Duplications) ( 0 )
Inferred from experimentation ( 0 )
Inferred from location ( 8 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
Orthologs
Downloads
Download All DIOPT Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
Domainoid
eggNOG
Hieranoid
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (0)
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
Domainoid
eggNOG
Hieranoid
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (0)
Mus musculus (laboratory mouse) (0)
Xenopus tropicalis (Western clawed frog) (0)
Danio rerio (Zebrafish) (0)
Caenorhabditis elegans (Nematode, roundworm) (0)
Anopheles gambiae (African malaria mosquito) (1)
Agam\IFA
8 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (0)
Saccharomyces cerevisiae (Brewer's yeast) (0)
Schizosaccharomyces pombe (Fission yeast) (0)
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:SIFa. Refer to their site for version information.
Paralogs
Downloads
Download All DIOPT Paralogs
Paralogs (via DIOPT v9.1)
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 3 )
    Allele
    Disease
    Evidence
    References
    SIFa1
    model of  tauopathy
    CEA
    (Bai et al., 2018)
    SIFa2
    model of  tauopathy
    CEA
    (Bai et al., 2018)
    SIFa3
    model of  tauopathy
    CEA
    (Bai et al., 2018)
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Disease Associations of Human Orthologs (via DIOPT v9.1 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
    Interaction Browsers
    View in FlyBase Interactions Browser   View in MIST tool (external link)
    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    SIFa - SIFaR
    phenotype-based detection assay, inferred by author
    (Jorgensen et al., 2006)
    Summary of Genetic Interactions
    Interaction Browsers
    View in FlyBase Interactions Browser   View in MIST tool (external link)
    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    SIFa
    enhanceable
    Nf1
    (Bai et al., 2018)
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    TrpA1
    suppressible
    SIFa
    (Martelli et al., 2017)
    External Data
    Linkouts
    DroID - A comprehensive database of gene and protein interactions.
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    FlyBase
    External Links
    External Data
    Linkouts
    Class of Gene
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    2R
    Recombination map
    2-107
    Cytogenetic map
    60D5-60D5
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    60D5-60D5
    Limits computationally determined from genome sequence between P{lacW}Nurf-38k16102 and P{lacW}Mmp1k04809
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    60D5-60D6
    (Terhzaz, 2001.5.4)
    Experimentally Determined Recombination Data
    Location

    2-107

    (FlyBase, 2016)

    2-111.0

    (Comeron et al., 2012)
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (10)
    Genomic Clones (16)
     

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

    cDNA Clones (3)
     

    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 JBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequenced
    BDGP DGC clones
      Other clones
      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.

      cDNA Clones, End Sequenced (ESTs)
      BDGP DGC clones
        Other clones
          RNAi and Array Information
          Linkouts
          DRSC - Results frm RNAi screens
          Antibody Information
          Laboratory Generated Antibodies
           

          polyclonal

          (Song et al., 2025, Verleyen et al., 2004)
          Commercially Available Antibodies
           
          Cell Line Information
          Publicly Available Cell Lines
           
            Other Stable Cell Lines
             
              Other Comments
              Relationship to Other Genes
              Source for database merge of
              Additional comments

              Release 4.1 annotation CG33527 corresponds to the 3' part of release 2 annotation CG4681 (which was deleted in the release 3 version of CG4681). Release 4.1 annotation CG33527 corresponds to IFa.

              (FlyBase Genome Annotators, 2005)

              The 3' part of release 2 annotation CG4681 (which was deleted in the release 3 version of CG4681) corresponds to part of a separate gene - IFa.

              (FlyBase, 1996-)
              Nomenclature History
              Source for database identify of

              Source for identity of: SIFa IFa

              (FlyBase, 2009-)
              Nomenclature comments

              Changed from 'IFa' to 'SIFa' to reflect usage in the literature and match nomenclature of the receptor ('SIFaR').

              (FlyBase, 2009-)
              Etymology
              Synonyms and Secondary IDs (15)
              Reported As
              Symbol Synonym
              CG33527
              (Mao et al., 2024, Meadows, 2018.10.31, Perkins et al., 2009, Yew et al., 2009, Wegener and Gorbashov, 2008)
              Drm-IFa
              (Mertens et al., 2002, vanden Broeck, 2001)
              Drm-SIFa
              (Nassel, 2002)
              IFAMIDE
              (Baggerman et al., 2005)
              IFa
              (Crocker et al., 2016, Kahsai and Winther, 2011, Wegener and Gorbashov, 2008, Santos et al., 2007)
              Neb-LFamide
              (Verleyen et al., 2004)
              SIF
              (Nässel and Wu, 2021)
              SIFR
              (Park et al., 2014)
              SIFa
              (Kubrak et al., 2026, Ryu et al., 2026, Zhang and Kim, 2026, Ahmad et al., 2025, Asahina and Zelikowsky, 2025, Nässel, 2025, Nässel, 2025, Song et al., 2025, Zhang et al., 2025, Mahishi et al., 2024, Chen et al., 2023, Dvořáček et al., 2022, Nässel and Wu, 2022, Nässel and Zandawala, 2022, Huang et al., 2021, Nässel, 2021, Schoberleitner et al., 2021, Shafer and Keene, 2021, Zhang et al., 2021, King and Sehgal, 2020, Nässel and Zandawala, 2020, Neamtu et al., 2020, Deng et al., 2019, Dreyer et al., 2019, Lin et al., 2019, Nässel et al., 2019, Rao and Deng, 2019.10.23, Croset et al., 2018, Donlea et al., 2018, Sayin et al., 2018, Transgenic RNAi Project members, 2017-, Ou et al., 2016, Huang et al., 2015, Lee et al., 2015, Cao et al., 2014, Cavanaugh et al., 2014, Shang et al., 2013, Kahsai and Winther, 2011, Nässel and Winther, 2010, Park et al., 2008)
              SIFamide
              (Lee and Wu, 2020, Artiushin and Sehgal, 2017, Sellami and Veenstra, 2015, Veenstra, 2009, Veenstra et al., 2008, Terhzaz et al., 2007, Jorgensen et al., 2006)
              Name Synonyms
              AYRKPPFNGSLFamide
              (Verleyen et al., 2004)
              IFamide
              Neb-LFamide
              (Verleyen et al., 2004)
              SIFamide
              (Shafer, 2025, Bajar et al., 2022, Nässel et al., 2019, Ly et al., 2018, Martelli et al., 2017, Caers et al., 2012, Kahsai and Winther, 2011, Carlsson et al., 2010, Nässel and Winther, 2010, Yew et al., 2009, Johnson et al., 2008, Park et al., 2008, Hewes and Taghert, 2001)
              SIfamide
              (Lee et al., 2014)
              neuropeptide AYRKPPFNGSIFamide
              (Terhzaz et al., 2007)
              neuropeptide IFamide
              (Baggerman et al., 2005)
              Secondary FlyBase IDs
              • FBgn0035029
              • FBgn0064238
              Datasets (0)
              Study focus (0)
              Experimental Role
              Project
              Project Type
              Title
              Study result (0)
              Result
              Result Type
              Title
              External Crossreferences and Linkouts ( 27 )
              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.
              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.
              UniProt/Swiss-Prot - Manually annotated and reviewed 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.
              BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
              DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
              EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
              FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
              FlyMine - An integrated database for Drosophila genomics
              InterPro - A database of protein families, domains and functional sites
              KEGG Genes - Molecular building blocks of life in the genomic space.
              MARRVEL_MODEL - MARRVEL (model organism gene)
              Linkouts
              Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
              DroID - A comprehensive database of gene and protein interactions.
              DRSC - Results frm RNAi screens
              Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
              FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
              FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
              Flygut - An atlas of the Drosophila adult midgut
              iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
              Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
              References (98)