sima similar [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: simaprovided by FlyBase
Official Full Name: similarprovided by FlyBase
Primary source: FLYBASE:FBgn0266411
Locus tag: Dmel_CG45051
See related: AllianceGenome:FB:FBgn0266411
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: 7951; bHLHe56; CG31031; CG45051; CG7951; dHIF-1alpha; dHIF-alpha; Dmel\CG45051; DMU43090; hif; HIF alpha; HIF-1; Hif-1A; HIF-1a; HIF-1alpha; HIF-alpha/sima; HIF1; HIF1A; Hif1alpha; HIF1alpha; Hifalpha; HIFalpha; l(3)j11B7; Sima; SIMA
Old locus tag: Dmel_CG31031; Dmel_CG7951
Summary: Enables DNA-binding transcription activator activity, RNA polymerase II-specific. Involved in several processes, including insulin receptor signaling pathway; positive regulation of catabolic process; and positive regulation of macromolecule biosynthetic process. Located in cytosol and nucleus. Part of RNA polymerase II transcription regulator complex. Is expressed in embryonic/larval crystal cell and organism. Human ortholog(s) of this gene implicated in several diseases, including artery disease (multiple); carcinoma (multiple); diabetic retinopathy; polycythemia (multiple); and type 2 diabetes mellitus. Orthologous to several human genes including EPAS1 (endothelial PAS domain protein 1) and HIF3A (hypoxia inducible factor 3 subunit alpha). [provided by Alliance of Genome Resources, Nov 2024]
Orthologs: all
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Genomic context

Location:: 99D3-99D7; 3-100 cM

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	3R	NT_033777.3 (30058311..30121798)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	3R	NT_033777.2 (25884033..25947520)

Chromosome 3R - NT_033777.3 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sima, a Drosophila homolog of HIF-1alpha, in fat body tissue inhibits larval body growth by inducing Tribbles gene expression.
Title: Sima, a Drosophila homolog of HIF-1α, in fat body tissue inhibits larval body growth by inducing Tribbles gene expression.
Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis.
Title: Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis.
In the mutant for Trh smaller synaptic boutons form clusters named satellite boutons appear at larval neuromuscular junctions, which is induced by the reduction of internal oxygen levels due to defective tracheal branches. Sima is critical in mediating hypoxia-induced satellite bouton formation. Sima upregulates the level of the Wg signal in glia, leading to reorganized microtubule structures within presynaptic sites.
Title: Glial response to hypoxia in mutants of NPAS1/3 homolog Trachealess through Wg signaling to modulate synaptic bouton organization.
most HIF1A targets require either TIP60, the CDK8-Mediator complex, or both as coactivators for full expression in hypoxia.
Title: The TIP60 Complex Is a Conserved Coactivator of HIF1A.
Musashi is a novel regulator of HIF that inhibits responses to hypoxia specifically when oxygen is available.
Title: Musashi mediates translational repression of the Drosophila hypoxia inducible factor.
miR-190 is a novel regulator of the hypoxia response that represses the oxygen sensor Fatiga, leading to HIFalpha stabilization and enhancement of hypoxic responses.
Title: miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga.
These results indicate that HIF-1alpha is required to restrain the NF-kappaB response, and thus prevents excessive and damaging pro-inflammatory responses.
Title: HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals.
HSF binds to nmnat promoter and induces NMNAT expression under heat shock. In contrast, under hypoxia, HIF1alpha up-regulates NMNAT indirectly through the induction of HSF
Title: Nicotinamide mononucleotide adenylyltransferase is a stress response protein regulated by the heat shock factor/hypoxia-inducible factor 1alpha pathway.
crystal cells express elevated levels of Sima protein orthologous to Hif-alpha; in these cells, Sima activates Notch receptor signaling by a ligand-independent mechanism that promotes hemocyte survival during hematopoietic development and hypoxic stress
Title: Interaction between Notch and Hif-alpha in development and survival of Drosophila blood cells.
fgaB but not fgaA is induced in hypoxia, in a Sima-dependent manner, through a HIF-Responsive Element localized in the first intron of fgaA
Title: Oxygen sensing in Drosophila: multiple isoforms of the prolyl hydroxylase fatiga have different capacity to regulate HIFalpha/Sima.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Pathways from PubChem

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

mobile_element

Loc: 30076282-30076339 mobile_element_type = transposon:INE-1{}3492
Loc: 30084908-30086313 mobile_element_type = transposon:H{}1456

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cellular response to hypoxia	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to hypoxia	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to hypoxia	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to hypoxia	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cellular response to insulin stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in oogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glycolytic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of macroautophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in trachea development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in trachea development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of RNA polymerase II transcription regulator complex	IMP Inferred from Mutant Phenotype more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: uncharacterized protein

NP_001138129.1

similar, isoform B

NP_001263100.1

similar, isoform C

NP_001287599.1

similar, isoform D

NP_524584.2

similar, isoform A

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NT_033777.3 Reference assembly

Range

30058311..30121798

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_079845.4 → NP_524584.2 uncharacterized protein Dmel_CG45051 [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_524584.2

Status: REVIEWED

UniProtKB/Swiss-Prot

Q24167, Q9VAA5

UniProtKB/TrEMBL

B9ER22

Related

FBpp0310747

Conserved Domains (4) summary

cd00083
Location:70 → 123

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:318 → 419

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam00989
Location:170 → 306

PAS; PAS fold

pfam08447
Location:331 → 416

PAS_3; PAS fold
NM_001144657.3 → NP_001138129.1 uncharacterized protein Dmel_CG45051 [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001138129.1

Status: REVIEWED

UniProtKB/TrEMBL

B7Z0S3, Q8MQV4

Conserved Domains (4) summary

cd00083
Location:70 → 123

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:318 → 419

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam00989
Location:170 → 306

PAS; PAS fold

pfam08447
Location:331 → 416

PAS_3; PAS fold
NM_001300670.1 → NP_001287599.1 uncharacterized protein Dmel_CG45051 [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001287599.1

Status: REVIEWED

UniProtKB/TrEMBL

A0A0B4LIX2, B9ER22

Conserved Domains (4) summary

cd00083
Location:156 → 209

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...

cd00130
Location:404 → 505

PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...

pfam00989
Location:256 → 392

PAS; PAS fold

pfam08447
Location:417 → 502

PAS_3; PAS fold
NM_001276171.1 → NP_001263100.1 uncharacterized protein Dmel_CG45051 [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001263100.1

Status: REVIEWED

UniProtKB/TrEMBL

A0A0B4KHI3