SIM2 single-minded homolog 2 (Drosophila) [Homo sapiens] - Gene

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Summary

Official Symbol: SIM2provided by HGNC
Official Full Name: single-minded homolog 2 (Drosophila)provided by HGNC
Primary source: HGNC:10883
See related: Ensembl:ENSG00000159263; HPRD:02935; MIM:600892; Vega:OTTHUMG00000086637
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SIM; bHLHe15; HMC13F06; HMC29C01; MGC119447
Summary: SIM1 and SIM2 genes are Drosophila single-minded (sim) gene homologs. The Drosophila sim gene encodes a transcription factor that is a master regulator of fruit fly neurogenesis. SIM2 maps within the so-called Down syndrome chromosomal region. Based on the mapping position, its potential function as transcriptional repressor and similarity to Drosophila sim, it is proposed that SIM2 may contribute to some specific Down syndrome phenotypes [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 21q22.13

Sequence :: Chromosome: 21; NC_000021.8 (38071991..38122510)

See SIM2 in Epigenomics, MapViewer

Chromosome 21 - NC_000021.8 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

These results suggest an involvement of SIM2 in key traits of prostate tumor cell biology.
Title: The role of the transcription factor SIM2 in prostate cancer.
Significantly lower frequency of SIM2 C-G haplotype (rs2073601-rs2073416) was noticed in individuals with Down syndrome (P value =0.01669) and their fathers (P value=0.01185)
Title: Exploratory investigation on functional significance of ETS2 and SIM2 genes in Down syndrome.
Genetic variants of SIM2 gene may not be associated with the susceptibility to congenital scoliosis and different clinical phenotypes of CS in Chinese Han population.
Title: [Association study of SIM2 gene polymorphisms with susceptibility to congenital scoliosis in a Chinese Han population].
The SIM2 is expressed in prostate cancer(PCa) and that anti-SIM2 antibodies are detectable in PCa patients' sera implicate SIM2 as a PCa-associated antigen that is a suitable potential target for PCa immunotherapy.
Title: Identification of the transcription factor single-minded homologue 2 as a potential biomarker and immunotherapy target in prostate cancer.
SIM2s' functional interference with HIF1alpha activities on BNIP3 may indicate a novel role for SIM2s in promoting tumourigenesis.
Title: The HIF1alpha-inducible pro-cell death gene BNIP3 is a novel target of SIM2s repression through cross-talk on the hypoxia response element.
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.
Knockdown of SIM2s in MCF-7 breast cancer cells contributed to an epithelial-mesenchymal transition associated with increased MMP2 and slug levels.
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.
provide a direct link between SIM2-s and differentiation, and may provide a model to identify SIM2-s targets
Title: Inhibition of Single Minded 2 gene expression mediates tumor-selective apoptosis and differentiation in human colon cancer cells.
SIM1 and SIM2 have a novel nuclear localization signal
Title: A novel nuclear localization signal in the human single-minded proteins SIM1 and SIM2.
Potential role of SIM2 in central nervous system development. SIM2 overexpression could participate in pathogenesis of mental retardation in Down syndrome.
Title: Spatial and temporal localization during embryonic and fetal human development of the transcription factor SIM2 in brain regions altered in Down syndrome.

Submit: New GeneRIF Correction See all (15)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
Q14190	P27540	ARNT	HPRD	PubMed
Q14190	O60260	PARK2	HPRD	PubMed
BioGRID:112384	BioGRID:117348	ARIH1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112384	BioGRID:106898	ARNT	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:112384	BioGRID:115244	ARNT2	BioGRID	PubMed	Two-hybrid
	NC_000007.11	EPO	BIND	PubMed	SIM2 interacts with the hypoxia-inducible enhancer of the EPO gene. This interaction was modeled on a demonstrated interaction between mouse SIM2 and the human EPO enhancer.
BioGRID:112384	BioGRID:111105	PARK2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112384	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
DNA binding	IEA Inferred from Electronic Annotation more info
protein heterodimerization activity	IEA Inferred from Electronic Annotation more info
sequence-specific DNA binding transcription factor activity	IEA Inferred from Electronic Annotation more info
signal transducer activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cell differentiation	IEA Inferred from Electronic Annotation more info
embryonic pattern specification	IEA Inferred from Electronic Annotation more info
lung development	IEA Inferred from Electronic Annotation more info
multicellular organismal development	IEA Inferred from Electronic Annotation more info
negative regulation of transcription from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
nervous system development	IEA Inferred from Electronic Annotation more info
regulation of transcription, DNA-dependent	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
NOT nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: single-minded homolog 2

Names: single-minded homolog 2; transcription factor SIM2; single-minded homolog 2, short isoform; class E basic helix-loop-helix protein 15

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NCBI Reference Sequences (RefSeq)

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.

Genomic

NG_029519.1 RefSeqGene

Range

5001..55520

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005069.3 → NP_005060.1 single-minded homolog 2 long isoform

Status: REVIEWED

Description

Transcript Variant: Unlike the SIM2s protein, the long isoform does not include the sequence encoded by intron 10.

Source sequence(s)

AI625864, BC110444, U80456

Consensus CDS

CCDS13646.1

UniProtKB/Swiss-Prot

Q14190

Related

ENSP00000290399, OTTHUMP00000109043, ENST00000290399, OTTHUMT00000194692

Conserved Domains (4) summary

cd00083
Location:2 – 52
Blast Score: 115

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
Blast Score: 155

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:358 – 609
Blast Score: 591

SIM_C; Single-minded protein C-terminus

pfam08447
Location:243 – 329
Blast Score: 181

PAS_3; PAS fold
NM_009586.2 → NP_033664.2 single-minded homolog 2 short isoform

Status: REVIEWED

Description

Transcript Variant: The SIM2s protein includes an altered C-terminus encoded by part of intron 10.

Source sequence(s)

BC110444, U80457

Consensus CDS

CCDS46647.1

UniProtKB/Swiss-Prot

Q14190

Related

ENSP00000404176, ENST00000430056

Conserved Domains (4) summary

cd00083
Location:2 – 52
Blast Score: 117

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
Blast Score: 156

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:358 – 525
Blast Score: 530

SIM_C; Single-minded protein C-terminus

pfam08447
Location:243 – 329
Blast Score: 183

PAS_3; PAS fold

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000021.8 Reference GRCh37.p5 Primary Assembly

Range

38071991..38122510

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000153.1 Alternate HuRef

Range

23547929..23598327

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB003185.1	BAA21489.1
		BAA21490.1
genomic	AP000697.1	BAA89433.1
genomic	CH471079.2	EAX09737.1
		EAX09738.1
genomic	D44444.1	BAA07906.1
genomic	D44445.1	BAA07907.1
genomic	D44446.1	BAA07908.1
genomic	D44447.1	BAA07909.1
genomic	D44448.1	BAA07910.1
genomic	D70838.1	BAA11108.1
genomic	D85922.1	BAA12919.1
mRNA	AI625864.1	None
mRNA	AJ001858.1	CAA05055.1
mRNA	AJ001859.1	None
mRNA	BC110444.2	AAI10445.1
mRNA	U80456.1	AAB62396.1
mRNA	U80457.1	AAB62397.1
mRNA	X83514.1	None
mRNA	X83515.1	None
mRNA	X84790.1	CAA59261.1