SIM2 SIM bHLH transcription factor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SIM2provided by HGNC
Official Full Name: SIM bHLH transcription factor 2provided by HGNC
Primary source: HGNC:HGNC:10883
See related: Ensembl:ENSG00000159263 MIM:600892; AllianceGenome:HGNC:10883
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
Summary: This gene represents a homolog of the Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of neurogenesis. The encoded protein is ubiquitinated by RING-IBR-RING-type E3 ubiquitin ligases, including the parkin RBR E3 ubiquitin protein ligase. This gene maps within the so-called Down syndrome chromosomal region, and is thus thought to contribute to some specific Down syndrome phenotypes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]
Expression: Biased expression in kidney (RPKM 5.4), esophagus (RPKM 4.7) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 21q22.13

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	21	NC_000021.9 (36699115..36749917)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	21	NC_060945.1 (35081302..35132110)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	21	NC_000021.8 (38071415..38122218)

Chromosome 21 - NC_000021.9 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: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Characterization of functionally deficient SIM2 variants found in patients with neurological phenotypes.
Title: Characterization of functionally deficient SIM2 variants found in patients with neurological phenotypes.
Long noncoding RNA CASC15 facilitates esophageal squamous cell carcinoma tumorigenesis via decreasing SIM2 stability via FTOmediated demethylation.
Title: Long non‑coding RNA CASC15 facilitates esophageal squamous cell carcinoma tumorigenesis via decreasing SIM2 stability via FTO‑mediated demethylation.
CD24 and CK4 are upregulated by SIM2, and are predictive biomarkers for chemoradiotherapy and surgery in esophageal cancer.
Title: CD24 and CK4 are upregulated by SIM2, and are predictive biomarkers for chemoradiotherapy and surgery in esophageal cancer.
these results show a role for SIM2s in the resolution of replication stress and further characterize the necessity of SIM2s for effective RAD51 loading in response to DNA damage or stress, ultimately promoting genomic integrity and thus preventing the accumulation of cancer-promoting mutations.
Title: Loss of SIM2s inhibits RAD51 binding and leads to unresolved replication stress.
These findings support a role for SIM2s in the prevention of breast cancer progression through its ability to repress PTGS2 expression via modulating the NFkappaB signaling pathway.
Title: Cross-talk between SIM2s and NFκB regulates cyclooxygenase 2 expression in breast cancer.
attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma
Title: SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma.
SIM2s interacts with ATM and is stabilized through ATM-dependent phosphorylation in response to IR.
Title: ATM-dependent activation of SIM2s regulates homologous recombination and epithelial-mesenchymal transition.
TMEM75 functions as an oncogene relying on activation of SIM2 in colorectal cancer.
Title: Long noncoding RNA TMEM75 promotes colorectal cancer progression by activation of SIM2.
SIM2 increases CRT sensitivity through tumor differentiation by cooperation with ARNT.
Title: Multiple roles of single-minded 2 in esophageal squamous cell carcinoma and its clinical implications.
Two genes, OR51E2 and SIM2, and two miRNAs, miR-200c and miR-200b, showed significant association with prostate cancer.
Title: Circulating mRNAs and miRNAs as candidate markers for the diagnosis and prognosis of prostate cancer.

Submit: New GeneRIF Correction See all GeneRIFs (32)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S275 (e-PCR)
- UniSTS:147992

SHGC-52065 (e-PCR)
- UniSTS:81957

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

G34611 (e-PCR)
- UniSTS:39753

SHGC-87636 (e-PCR)
- UniSTS:54124

D21S395 (e-PCR)
- UniSTS:147864

D21S396 (e-PCR)
- UniSTS:147865

SHGC-51958 (e-PCR)
- UniSTS:69274

PMC153629P1 (e-PCR)
- UniSTS:271265

D21S1841 (e-PCR)
- UniSTS:41702

D5S1597E (e-PCR)
- UniSTS:151019

D21S1726E (e-PCR)
- UniSTS:150781

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	TAS Traceable Author Statement more info	PubMed
enables DNA-binding transcription factor activity	TAS Traceable Author Statement more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment 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 heterodimerization activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in embryonic pattern specification	IEA Inferred from Electronic Annotation more info
involved_in lung development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in nervous system development	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 chromatin	ISA Inferred from Sequence Alignment more info
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: single-minded homolog 2

Names: class E basic helix-loop-helix protein 15; single-minded family bHLH transcription factor 2; transcription factor SIM2

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.

Genomic

NG_029519.2 RefSeqGene

Range

5002..55804

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005069.6 → NP_005060.1 single-minded homolog 2 long isoform

See identical proteins and their annotated locations for NP_005060.1

Status: REVIEWED

Description

Transcript Variant: This variant (SIM2) represents the longer transcript and encodes the longer isoform (long).

Source sequence(s)

AP000697, BC052313, BC110444, BM848475, U80456

Consensus CDS

CCDS13646.1

UniProtKB/Swiss-Prot

O60766, Q14190, Q15470, Q15471, Q15472, Q15473, Q16532, Q2TBD8

Related

ENSP00000290399.6, ENST00000290399.11

Conserved Domains (6) summary

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 → 159

PAS; PAS fold

pfam06621
Location:359 → 660

SIM_C; Single-minded protein C-terminus

pfam08447
Location:243 → 329

PAS_3; PAS fold

pfam15830
Location:578 → 653

DUF4712; Domain of unknown function (DUF4712)
NM_009586.5 → NP_033664.2 single-minded homolog 2 short isoform

See identical proteins and their annotated locations for NP_033664.2

Status: REVIEWED

Description

Transcript Variant: This variant (SIM2s) contains alternate 3' exon structure, and it thus differs in the 3' coding region and 3' UTR, compared to variant SIM2. The encoded isoform (short) has a distinct C-terminus and is shorter than isoform long.

Source sequence(s)

AP000697, BC052313, BC110444, BM848475, U80457

UniProtKB/TrEMBL

H7BZX8

Related

ENST00000481185.1

Conserved Domains (4) summary

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:88 → 158

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:359 → 523

SIM_C; Single-minded protein C-terminus

pfam08447
Location:243 → 329

PAS_3; PAS fold

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000021.9 Reference GRCh38.p14 Primary Assembly

Range

36699115..36749917

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047440953.1 → XP_047296909.1 single-minded homolog 2 isoform X3
XM_017028442.3 → XP_016883931.1 single-minded homolog 2 isoform X2

Conserved Domains (3) summary

smart00091
Location:79 → 140

PAS; PAS domain

pfam08447
Location:243 → 326

PAS_3; PAS fold

cd19739
Location:1 → 74

bHLH-PAS_SIM2; basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain found in single-minded homolog 2 (SIM2) and similar proteins
XM_047440952.1 → XP_047296908.1 single-minded homolog 2 isoform X1
XM_011529694.2 → XP_011527996.1 single-minded homolog 2 isoform X1

Conserved Domains (4) summary

cd00130
Location:128 → 227

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 → 559

SIM_C; Single-minded protein C-terminus

pfam08447
Location:142 → 228

PAS_3; PAS fold

pfam15830
Location:477 → 552

DUF4712; Domain of unknown function (DUF4712)