Sim2 single-minded family bHLH transcription factor 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Sim2provided by MGI
Official Full Name: single-minded family bHLH transcription factor 2provided by MGI
Primary source: MGI:MGI:98307
See related: Ensembl:ENSMUSG00000062713 AllianceGenome:MGI:98307
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: bHLHe15
Summary: Enables DNA binding activity and protein heterodimerization activity. Acts upstream of or within embryonic pattern specification; lung development; and negative regulation of transcription by RNA polymerase II. Located in nucleus. Is expressed in several structures, including branchial arch; future brain; genitourinary system; limb; and musculoskeletal system. Orthologous to human SIM2 (SIM bHLH transcription factor 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in kidney adult (RPKM 3.3), limb E14.5 (RPKM 2.0) and 5 other tissues See more
Orthologs: human all
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Genomic context

Location:: 16 C4; 16 55.05 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	16	NC_000082.7 (93885963..93927891)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	16	NC_000082.6 (94085104..94127032)

Chromosome 16 - NC_000082.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Ethanol induced Sim2 expression in cerebral cortices of P7 Mice via the PKA pathway.
Title: Ethanol Activation of PKA Mediates Single-Minded 2 Expression in Neuronal Cells.
Study provides evidence that SIM2 binds a specific set of enhancer elements thus explaining how SIM2 can regulate its gene network in neuronal features.
Title: HSA21 Single-Minded 2 (Sim2) Binding Sites Co-Localize with Super-Enhancers and Pioneer Transcription Factors in Pluripotent Mouse ES Cells.
Our results establish that SIM2 is a crucial regulator in controlling expression of intestinal AMPs
Title: SIM2 maintains innate host defense of the small intestine.
Sim2 prevents entry into the myogenic program by repressing MyoD transcription during limb embryonic myogenesis.
Title: Sim2 prevents entry into the myogenic program by repressing MyoD transcription during limb embryonic myogenesis.
mammary gland involution is disrupted in Sim2s overexpression and STAT3-mediated signaling and other pathways involved in the acute phase response are inhibited
Title: Singleminded-2s (Sim2s) promotes delayed involution of the mouse mammary gland through suppression of Stat3 and NFκB.
Sim2s is required for establishing and maintaining mammary gland differentiation.
Title: The bHLH/PAS transcription factor singleminded 2s promotes mammary gland lactogenic differentiation.
chick and mouse Sim2 gene expression is enhanced in limb ventral muscle masses versus dorsal ventral muscle masses
Title: Sim1 and Sim2 expression during chick and mouse limb development.
Sim2 play an role in the pathogenesis of Down syndrome by inhibiting neurite growth and cell differentiation.
Title: [Effect of Sim2 gene on the differentiation of PC12 cells].
Ha-Ras transformation of MCF10A cells leads to repression of Singleminded-2s through NOTCH and C/EBPbeta.
Title: Ha-Ras transformation of MCF10A cells leads to repression of Singleminded-2s through NOTCH and C/EBPbeta.
SIM2s is the first protein shown to bind and repress the SLUG promoter. SIM2s is a key regulator of mammary-ductal development. Loss of SIM2s is associated with an invasive, epithelial-msesnchymal-transition-like phenotype.
Title: Loss of singleminded-2s in the mouse mammary gland induces an epithelial-mesenchymal transition associated with up-regulation of slug and matrix metalloprotease 2.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (4) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D16Mit119 (e-PCR), detects polymorphism
- UniSTS:127747

Sim2 (e-PCR), detects polymorphism
- UniSTS:259140

Sim2 (e-PCR), detects polymorphism
- UniSTS:259656

U40576 (e-PCR)
- UniSTS:163580

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity	IEA Inferred from Electronic Annotation more info
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 binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryonic pattern specification	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lung development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within nervous system development	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in nuclear body	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: single-minded homolog 2

Names: SIM transcription factor; mSIM; single-minded 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_011377.2 → NP_035507.2 single-minded homolog 2

See identical proteins and their annotated locations for NP_035507.2

Status: VALIDATED

Source sequence(s)

CU207273, D63383, U42554

Consensus CDS

CCDS37406.1

UniProtKB/Swiss-Prot

O35391, Q61046, Q61079, Q61904

Related

ENSMUSP00000072043.8, ENSMUST00000072182.9

Conserved Domains (6) summary

smart00091
Location:79 → 140

PAS; PAS domain

cd00083
Location:2 → 52

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:229 → 328

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:79 → 141

PAS; PAS fold

pfam06621
Location:359 → 650

SIM_C; Single-minded protein C-terminus

pfam08447
Location:243 → 329

PAS_3; PAS fold

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000082.7 Reference GRCm39 C57BL/6J

Range

93885963..93927891

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006522966.4 → XP_006523029.1 single-minded homolog 2 isoform X1

Conserved Domains (4) summary

smart00091
Location:83 → 144

PAS; PAS domain

pfam06621
Location:363 → 654

SIM_C; Single-minded protein C-terminus

pfam08447
Location:247 → 333

PAS_3; PAS fold

cl00081
Location:1 → 78

bHLH_SF; basic Helix Loop Helix (bHLH) domain superfamily
XM_017316897.2 → XP_017172386.1 single-minded homolog 2 isoform X2

Conserved Domains (4) summary

smart00091
Location:83 → 144

PAS; PAS domain

pfam06621
Location:363 → 545

SIM_C; Single-minded protein C-terminus

pfam08447
Location:247 → 333

PAS_3; PAS fold

cl00081
Location:1 → 78

bHLH_SF; basic Helix Loop Helix (bHLH) domain superfamily
XM_006522967.5 → XP_006523030.1 single-minded homolog 2 isoform X3

See identical proteins and their annotated locations for XP_006523030.1

Conserved Domains (3) summary

cd00130
Location:1 → 57

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 ...

pfam06621
Location:258 → 549

SIM_C; Single-minded protein C-terminus

pfam08447
Location:142 → 228

PAS_3; PAS fold
XM_006522968.4 → XP_006523031.1 single-minded homolog 2 isoform X3

See identical proteins and their annotated locations for XP_006523031.1

Conserved Domains (3) summary

cd00130
Location:1 → 57

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 ...

pfam06621
Location:258 → 549

SIM_C; Single-minded protein C-terminus

pfam08447
Location:142 → 228

PAS_3; PAS fold