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General Information
Symbol
Dmel\sima
Species
D. melanogaster
Name
similar
Annotation Symbol
CG45051
Feature Type
FlyBase ID
FBgn0266411
Gene Model Status
Stock Availability
Gene Summary
Functions as a transcriptional regulator of the adaptive response to hypoxia. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. (UniProt, Q24167)
Contribute a Gene Snapshot for this gene.
Also Known As

HIF-1α, HIF-1a, l(3)j11B7, HIF-1, HIF1A

Key Links
Genomic Location
Cytogenetic map
Sequence location
3R:30,058,311..30,121,798 [+]
Recombination map
3-100
RefSeq locus
NT_033777 REGION:30058311..30121798
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Gene Ontology (GO) Annotations (19 terms)
Molecular Function (4 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN001889196
(assigned by GO_Central )
inferred from electronic annotation with InterPro:IPR011598
(assigned by InterPro )
inferred from biological aspect of ancestor with PANTHER:PTN001889196
(assigned by GO_Central )
Biological Process (12 terms)
Terms Based on Experimental Evidence (10 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from mutant phenotype
inferred from mutant phenotype
involved_in oogenesis
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:Vhl; FB:FBgn0041174
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
inferred from sequence or structural similarity with HGNC:4910
inferred from biological aspect of ancestor with PANTHER:PTN000548864
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN000548738
(assigned by GO_Central )
inferred from sequence or structural similarity with HGNC:4910
Cellular Component (3 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (0 terms)
Protein Family (UniProt)
-
Summaries
Gene Group (FlyBase)
BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS -
Basic helix-loop-helix (bHLH) transcription factors are sequence-specific DNA-binding proteins that regulate transcription. They are characterized by a 60 amino acid region comprising a basic DNA binding domain followed by a HLH motif formed from two amphipathic α-helices connected by a loop. bHLH transcription factors form homo- and hetero-dimeric complexes, which bind to a E box consensus sequence. (Adapted from PMID:15186484).
HYPOXIA-INDUCIBLE FACTOR -
Hypoxia-inducible factor (HIF) mediates hypoxia-dependent transcription. It is a heterodimeric basic helix-loop-helix transcription factor complex composed of a constitutively expressed HIF-β subunit and an oxygen-regulated HIF-α subunit. (Adapted from FBrf0190953).
Pathway (FlyBase)
Insulin-like Receptor Signaling Pathway Core Components -
The Insulin-like Receptor (IR) signaling pathway in Drosophila is initiated by the binding of an insulin-like peptides to the Insulin-like receptor (InR). (Adapted from FBrf0232297, FBrf0230017 and FBrf0229989.)
Protein Function (UniProtKB)
Functions as a transcriptional regulator of the adaptive response to hypoxia. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters.
(UniProt, Q24167)
Summary (Interactive Fly)

bHLH-PAS domain transcription factor - a key regulator of responses to hypoxia - mediates mitochondrial retrograde signaling - regulates lifespan extension by inhibiting c-Myc-TFAM signaling and mitochondrial biogenesis

Gene Model and Products
Number of Transcripts
4
Number of Unique Polypeptides
4

Please see the JBrowse view of Dmel\sima 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

Tissue-specific extension of 3' UTRs observed during later stages (FBrf0218523, FBrf0219848); all variants may not be annotated

Gene model reviewed during 5.47

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

Gene model reviewed during 5.53

Gene model includes transcripts encoding non-overlapping portions of the full CDS.

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0344374
6178
1507
FBtr0344375
3543
426
FBtr0344373
4704
869
FBtr0344376
5978
1593
Additional Transcript Data and Comments
Reported size (kB)

6.1 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0310747
165.8
1507
5.01
FBpp0310748
47.6
426
8.53
FBpp0310746
95.4
869
4.37
FBpp0310749
176.3
1593
4.89
Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments
Reported size (kDa)

1505 (aa); 150 (kD observed)

Comments
External Data
Subunit Structure (UniProtKB)

Efficient DNA binding requires dimerization with another bHLH protein. Interacts with Vhl.

(UniProt, Q24167)
Domain

The oxygen-dependent degradation (ODD) domain is required for cytoplasmic localization in normoxia.

(UniProt, Q24167)
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\sima 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
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
organism | ubiquitous

Comment: maternally deposited

Additional Descriptive Data

sima is expressed in most or all cells in the embryo from the blastoderm stage to the end of embryogenesis.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\sima in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
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
EMBL-EBI Single Cell Expression Atlas
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 29 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 17 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of sima
Transgenic constructs containing regulatory region of sima
Aberrations (Deficiencies and Duplications) ( 1 )
Inferred from experimentation ( 1 )
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
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v8.0)
Homo sapiens (Human) (8)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
9 of 15
Yes
Yes
2  
8 of 15
No
Yes
7 of 15
No
Yes
3 of 15
No
No
3 of 15
No
No
3 of 15
No
No
2 of 15
No
No
1 of 15
No
No
1  
Model Organism Orthologs (via DIOPT v8.0)
Mus musculus (laboratory mouse) (7)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
9 of 15
Yes
Yes
8 of 15
No
Yes
7 of 15
No
Yes
3 of 15
No
No
3 of 15
No
No
2 of 15
No
No
2 of 15
No
No
Rattus norvegicus (Norway rat) (9)
8 of 13
Yes
Yes
5 of 13
No
Yes
5 of 13
No
Yes
3 of 13
No
No
2 of 13
No
No
2 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
Xenopus tropicalis (Western clawed frog) (5)
5 of 12
Yes
Yes
5 of 12
Yes
Yes
3 of 12
No
No
3 of 12
No
No
2 of 12
No
No
Danio rerio (Zebrafish) (11)
9 of 15
Yes
Yes
8 of 15
No
Yes
8 of 15
No
Yes
7 of 15
No
Yes
6 of 15
No
Yes
6 of 15
No
Yes
3 of 15
No
No
2 of 15
No
Yes
2 of 15
No
No
2 of 15
No
No
2 of 15
No
No
Caenorhabditis elegans (Nematode, roundworm) (2)
7 of 15
Yes
Yes
4 of 15
No
No
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) ( EOG0919012V )
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
Drosophila persimilis
Drosophila willistoni
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG09150184 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( None identified )
No non-Dipteran orthologies identified
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( None identified )
No non-Insect Arthropod orthologies identified
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G0486 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v8.0)
Drosophila melanogaster (Fruit fly) (3)
4 of 10
3 of 10
2 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 ( 1 )
Human Ortholog
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
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.
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
Show neighbor-neighbor interactions:
Select Layout:
Legend:
Protein
RNA
Selected Interactor(s)
Interactions Browser

Please see the Physical Interaction reports below for full details
protein-protein
Physical Interaction
Assay
References
RNA-protein
Physical Interaction
Assay
References
Summary of Genetic Interactions
esyN Network Diagram
esyN Network Key:
Suppression
Enhancement

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
External Data
Subunit Structure (UniProtKB)
Efficient DNA binding requires dimerization with another bHLH protein. Interacts with Vhl.
(UniProt, Q24167 )
Linkouts
DroID - A comprehensive database of gene and protein interactions.
MIST (protein-protein) - An integrated Molecular Interaction Database
Pathways
Signaling Pathways (FlyBase)
Insulin-like Receptor Signaling Pathway Core Components -
The Insulin-like Receptor (IR) signaling pathway in Drosophila is initiated by the binding of an insulin-like peptides to the Insulin-like receptor (InR). (Adapted from FBrf0232297, FBrf0230017 and FBrf0229989.)
Metabolic Pathways
External Data
Linkouts
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
Genomic Location and Detailed Mapping Data
Chromosome (arm)
3R
Recombination map
3-100
Cytogenetic map
Sequence location
3R:30,058,311..30,121,798 [+]
FlyBase Computed Cytological Location
Cytogenetic map
Evidence for location
99D4-99D4
Limits computationally determined from genome sequence between P{PZ}ncd05884 and P{lacW}l(3)s2500s2500
Experimentally Determined Cytological Location
Cytogenetic map
Notes
References
99E1-99E2
(determined by in situ hybridisation)
99D6-99D9
(determined by in situ hybridisation)
Experimentally Determined Recombination Data
Left of (cM)
Right of (cM)
Notes
Stocks and Reagents
Stocks (22)
Genomic Clones (42)
cDNA Clones (80)
 

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
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)
RNAi and Array Information
Linkouts
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
Antibody Information
Laboratory Generated Antibodies
 

polyclonal

Commercially Available Antibodies
 
Other Information
Relationship to Other Genes
Source for database identify of
Source for database merge of

Source for merge of: sima l(3)j11B7

Source for merge of: sima CG31031

Additional comments

Annotations CG7951 and CG31031 merged as CG45051 in release 5.53 of the genome annotation; merge based primarily on RNA-Seq junction and coverage data.

Other Comments

New annotation (CG31031) in release 3 of the genome annotation.

Isolated from a genomic library using a fragment containing the sim basic helix-loop-helix region as a probe, under reduced stringency conditions.

sima has been cloned and sequenced.

Origin and Etymology
Discoverer
Etymology
Identification
External Crossreferences and Linkouts ( 74 )
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 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/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
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
Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
EMBL-EBI Single Cell Expression Atlas
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
KEGG Genes - Molecular building blocks of life in the genomic space.
MARRVEL_MODEL
Linkouts
DroID - A comprehensive database of gene and protein interactions.
Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
MIST (protein-protein) - An integrated Molecular Interaction Database
Synonyms and Secondary IDs (28)
Reported As
Symbol Synonym
sima
(Baker et al., 2021, Millet-Boureima et al., 2021, Zhang et al., 2021, Barretto et al., 2020, Li et al., 2020, Nakajima et al., 2020, Perez-Gomez et al., 2020, Banerjee et al., 2019, Best, 2019, Chen et al., 2019, Hall et al., 2019, Meltzer et al., 2019, Nicholson et al., 2019, Shokri et al., 2019, Texada et al., 2019, Wong et al., 2019, Ariss et al., 2018, Sakakibara et al., 2018, Fochler et al., 2017, Lin et al., 2017, Misra et al., 2017, Transgenic RNAi Project members, 2017-, De Lella Ezcurra et al., 2016, Perez-Perri et al., 2016, Schwartz et al., 2016, Vinayagam et al., 2016, Bandarra et al., 2015, Cagin et al., 2015, Dong et al., 2015, Gene Disruption Project members, 2015-, Palmer and Deng, 2015, Wang et al., 2015, Zarndt et al., 2015, Ashwal-Fluss et al., 2014, Bandarra et al., 2014, Gersten et al., 2014, Wong et al., 2014, Bonke et al., 2013, Chow et al., 2013, Lőw et al., 2013, Mandilaras et al., 2013, Mortimer and Moberg, 2013, Schertel et al., 2013, Spokony and White, 2013.5.10, Zhou and Haddad, 2013, Chakrabarti et al., 2012, Gurudatta et al., 2012, Kim et al., 2012, Rodriguez et al., 2012, Spokony, 2012.12.12, Ali et al., 2011, Guest et al., 2011, Harrison and Haddad, 2011, Mukherjee et al., 2011, van Uden et al., 2011, Acevedo et al., 2010, Doronkin et al., 2010, Hsouna et al., 2010, Lunardi et al., 2010, Mortimer and Moberg, 2009, Qian and Bodmer, 2009, Vigne et al., 2009, Centanin et al., 2008, Khokhar et al., 2008, Vigne and Frelin, 2008, Arquier et al., 2006, Baird et al., 2006, Centanin et al., 2005, Dekanty et al., 2005, FlyBase, 1992-)
Secondary FlyBase IDs
  • FBgn0015542
  • FBgn0011432
  • FBgn0051031
Datasets (0)
Study focus (0)
Experimental Role
Project
Project Type
Title
References (205)