FB2025_01 , released February 20, 2025
Gene: Dmel\Npc2a
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General Information
Symbol
Dmel\Npc2a
Species
D. melanogaster
Name
Niemann-Pick type C-2a
Annotation Symbol
CG7291
Feature Type
protein_coding_gene
FlyBase ID
FBgn0031381
Gene Model Status
Current
Stock Availability
14 publicly available
Gene Summary
Niemann-Pick type C-2a (Npc2a) encodes a protein involved in regulating sterol homeostasis and hydroxyecdysone biosynthesis. It also plays a role in the immune signaling via interaction with bacterial lipopolysaccharides, lipid A, peptidoglycan and lipoteichoic acid. [Date last reviewed: 2021-01-21] (FlyBase Gene Snapshot)
All Summaries
Also Known As

NPC2, Niemann-Pick Type C-2

Key Links
Genomic Location
Cytogenetic map
22B8-22B8
Sequence location
Recombination map
2-3
RefSeq locus
NT_033779 REGION:1988290..1988940
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 (14 terms)
Molecular Function (7 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
enables lipid antigen binding
inferred from direct assay
(Shi et al., 2012)
enables lipopolysaccharide binding
inferred from direct assay
(Shi et al., 2012)
enables lipoteichoic acid binding
inferred from direct assay
(Shi et al., 2012)
enables peptidoglycan binding
inferred from direct assay
(Shi et al., 2012)
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
enables cholesterol binding
inferred from sequence or structural similarity with UniProtKB:P61916
(Gene Ontology Curators, 2002-)
enables cholesterol transfer activity
inferred from sequence or structural similarity with UniProtKB:P61916
(Gene Ontology Curators, 2002-)
enables sterol binding
inferred from electronic annotation with InterPro:IPR039670
(InterPro Project Members, 2004-)
inferred from biological aspect of ancestor with PANTHER:PTN000139325
(GO Reference Genome Project, 2011-)
inferred from sequence or structural similarity with HGNC:14537
(Huang et al., 2007)
Biological Process (6 terms)
Terms Based on Experimental Evidence (5 terms)
CV Term
Evidence
References
acts_upstream_of ecdysteroid biosynthetic process
inferred from genetic interaction with FLYBASE:Npc2b; FB:FBgn0038198
(Huang et al., 2007)
involved_in positive regulation of defense response to bacterium
inferred from expression pattern
(Shi et al., 2012)
involved_in sterol homeostasis
inferred from mutant phenotype
(Huang et al., 2007)
involved_in sterol transport
inferred from mutant phenotype
(Huang et al., 2007)
involved_in synaptic target recognition
inferred from mutant phenotype
(Kurusu et al., 2008)
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
involved_in intracellular cholesterol transport
inferred from sequence or structural similarity with UniProtKB:P61916
(Gene Ontology Curators, 2002-)
inferred from electronic annotation with InterPro:IPR033916
(InterPro Project Members, 2004-)
involved_in sterol transport
inferred from biological aspect of ancestor with PANTHER:PTN000139325
(GO Reference Genome Project, 2011-)
Cellular Component (1 term)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
located_in extracellular space
inferred from direct assay
(Shi et al., 2012)
Terms Based on Predictions or Assertions (0 terms)
Gene Group (FlyBase)
Protein Family (UniProt)
Belongs to the NPC2 family. (Q9VQ62)
Protein Signatures (InterPro)
Summaries
Gene Snapshot
Niemann-Pick type C-2a (Npc2a) encodes a protein involved in regulating sterol homeostasis and hydroxyecdysone biosynthesis. It also plays a role in the immune signaling via interaction with bacterial lipopolysaccharides, lipid A, peptidoglycan and lipoteichoic acid. [Date last reviewed: 2021-01-21]
Gene Group (FlyBase)
MD-2-RELATED LIPID-RECOGNITION PROTEINS -
Myeloid differentiation factor-2-related lipid-recognition (ML) domain-containing proteins are a broadly classed as lipid-binding proteins and have been implicated in processes such as lipid metabolism and innate immunity. (Adapted from FBrf0218672.)
Protein Function (UniProtKB)
Functions redundantly with Npc2b in regulating sterol homeostasis and ecdysteroid biosynthesis, probably by controlling the availability of sterol substrate.
(UniProt, Q9VQ62)
Summary (Interactive Fly)

lysosomal cholesterol-binding protein that functions redundantly with npc2b in regulating sterol homeostasis and ecdysteroid biosynthesis

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

Please see the JBrowse view of Dmel\Npc2a 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 Q9VQ62)

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 5.40

Gene model reviewed during 5.47

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
Npc2a-RA
FBtr0077816
NM_134793
651
148
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
Npc2a-PA
FBpp0077492
16.0
148
4.95
Q9VQ62
NP_608637
AAF51319
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
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\Npc2a 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).

-0.18

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
embryonic stage
organism | ubiquitous
(Huang et al., 2007)
embryonic stage 13 -- 17
embryonic/larval salivary gland | intense
(Huang et al., 2007)
embryonic/larval midgut | intense
(Huang et al., 2007)
larval ventral nerve cord | intense
(Huang et al., 2007)
third instar larval stage
larval brain
(Huang et al., 2007)
Additional Descriptive Data

Npc2a transcript is maternally deposited, and is uniformly distributed in early embryos. It is ubiquitously expressed at all embryonic stages. Higher levels of Npc2a transcript are expressed in many embryonic tissues, including in the midgut, salivary glands, and ventral nerve cord. High levels of Npc2a transcript are also observed in the larval brain lobes.

(Huang et al., 2007)
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
day 7 of adulthood -- day 49 of adulthood
adult heart
(Cammarato et al., 2011)
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in extracellular space
inferred from direct assay
(Shi et al., 2012)
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Npc2a 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
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
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyBase Wiki
Image Based Resources
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 8 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 9 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Npc2a
Transgenic constructs containing regulatory region of Npc2a
Aberrations (Deficiencies and Duplications) ( 2 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
viable
viable, with Dcr-2UAS.cDa, Scer\GAL4elav.PLu
viable, with Scer\GAL4Mef2.PR
viable, with Scer\GAL4pnr-MD237
viable, with Scer\GAL4tin.CΔ4
Sterility
Allele
fertile
Other Phenotypes
Allele
short lived
Phenotype manifest in
Allele
Malpighian tubule
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) (1)
Hsap\NPC2
14 of 14
Yes
Yes
1  
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) (1)
Rnor\Npc2
14 of 14
Yes
Yes
Mus musculus (laboratory mouse) (1)
Mmus\Npc2
13 of 14
Yes
Yes
Xenopus tropicalis (Western clawed frog) (3)
Xtro\npc2
2 of 13
Yes
Yes
Xtro\fabp7
1 of 13
No
Yes
Xtro\odam
1 of 13
No
Yes
Danio rerio (Zebrafish) (3)
Drer\npc2.1
14 of 14
Yes
Yes
Drer\npc2.2
14 of 14
Yes
Yes
Drer\si:ch73-138n13.1
1 of 14
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (1)
Cele\heh-1
9 of 14
Yes
Yes
Anopheles gambiae (African malaria mosquito) (14)
Agam\AgaP_AGAP002848
4 of 12
Yes
Yes
Agam\AgaP_AGAP001956
3 of 12
No
No
Agam\AgaP_AGAP002804
3 of 12
No
No
Agam\AgaP_AGAP002847
3 of 12
No
No
Agam\AgaP_AGAP002849
3 of 12
No
No
Agam\AgaP_AGAP002850
3 of 12
No
No
Agam\AgaP_AGAP002851
3 of 12
No
No
Agam\AgaP_AGAP002857
3 of 12
No
No
Agam\AgaP_AGAP007197
3 of 12
No
No
Agam\AgaP_AGAP013106
3 of 12
No
No
Agam\AgaP_AGAP013388
3 of 12
No
No
Agam\AgaP_AGAP002852
2 of 12
No
No
Agam\AgaP_AGAP007415
2 of 12
No
No
Agam\AgaP_AGAP012352
1 of 12
No
No
Arabidopsis thaliana (thale-cress) (9)
Atha\AT1G45015
1 of 13
Yes
Yes
Atha\AT2G16005
1 of 13
Yes
Yes
Atha\AT2G26370
1 of 13
Yes
Yes
Atha\AT3G11780
1 of 13
Yes
Yes
Atha\AT3G44100
1 of 13
Yes
Yes
Atha\AT5G06480
1 of 13
Yes
Yes
Atha\AT5G23820
1 of 13
Yes
Yes
Atha\AT5G23830
1 of 13
Yes
Yes
Atha\AT5G23840
1 of 13
Yes
Yes
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:Npc2a. Refer to their site for version information.
Paralogs
Downloads
Download All DIOPT Paralogs
Paralogs (via DIOPT v9.1)
Gene Symbol
Score
Source
Compara
Domainoid
eggNOG
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Drosophila melanogaster (Fruit fly) (7)
Npc2b
6 of 13
Npc2c
5 of 13
Npc2d
5 of 13
Npc2e
5 of 13
Npc2f
3 of 13
Npc2g
3 of 13
Npc2h
3 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Allele
Disease
Evidence
References
Npc2aunspecified
model of  Niemann-Pick disease
CEA with Npc2bunspecified
(Huang et al., 2007)
Potential Models Based on Orthology ( 1 )
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?
NPC2; NPC intracellular cholesterol transporter 2
14 of 14
601015
 
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
Other Interaction Browsers
Summary of Genetic Interactions
esyN Network Diagram
Show/hide secondary interactors 
(data from AllianceMine provided by esyN)
esyN Network Key:
Suppression
Enhancement
Other 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
Starting gene(s)
Interaction type
Interacting gene(s)
Reference
chb
suppressible
Npc2a
(Lowery et al., 2010)
External Data
Linkouts
BioGRID - A database of protein and genetic interactions.
DroID - A comprehensive database of gene and protein interactions.
Pathways
Signaling Pathways (FlyBase)
Metabolic Pathways
FlyBase
External Links
External Data
Linkouts
KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
Class of Gene
Genomic Location and Detailed Mapping Data
Chromosome (arm)
2L
Recombination map
2-3
Cytogenetic map
22B8-22B8
Sequence location
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
22B8-22B8
Limits computationally determined from genome sequence between P{lacW}CG17646k11021 and P{EP}EP366
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
Experimentally Determined Recombination Data
Location

2-3

(FlyBase, 2016)

2-3.7

(Comeron et al., 2012)
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (14)
Genomic Clones (21)
cDNA Clones (167)
 

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
 
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

      Source for merge of: NPC2 BEST:GH08376

      (Rana, 2004.7.8)

      Source for merge of: CG7291 BcDNA:RH53228

      (FlyBase, 1996-)

      Source for merge of: CG7291 BcDNA:GH22047

      (FlyBase, 1996-)
      Additional comments

      The Npc2a gene may have been derived from the Npc2b gene by retroposition.

      (Pan and Zhang, 2009)

      Source for merge of CG7291 BcDNA:RH53228 was a shared cDNA ( date:030728 ).

      (FlyBase, 1996-)

      Source for merge of CG7291 BcDNA:GH22047 was a shared cDNA ( date:030728 ).

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

      Source for identity of: NPC2 CG7291

      (Huang and Scott, 2004)

      Source for identity of: Npc2a NPC2

      (Huang et al., 2007)
      Nomenclature comments
      Etymology
      Synonyms and Secondary IDs (13)
      Datasets (0)
      Study focus (0)
      Experimental Role
      Project
      Project Type
      Title
      Study result (0)
      Result
      Result Type
      Title
      External Crossreferences and Linkouts ( 40 )
      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.
      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
      BioGRID - A database of protein and genetic interactions.
      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
      Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
      Flygut - An atlas of the Drosophila adult midgut
      FlyMet - A comprehensive tissue-specific metabolomics resource for Drosophila.
      iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
      Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
      KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
      Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
      References (61)