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Sp4 trans-acting transcription factor 4 [ Mus musculus (house mouse) ]

Gene ID: 20688, updated on 21-Apr-2024

Summary

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Official Symbol
Sp4provided by MGI
Official Full Name
trans-acting transcription factor 4provided by MGI
Primary source
MGI:MGI:107595
See related
Ensembl:ENSMUSG00000025323 AllianceGenome:MGI:107595
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
HF-1b; HF1-b; 5730497N03Rik
Summary
Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and identical protein binding activity. Acts upstream of or within regulation of heart contraction. Predicted to be located in cytosol and nucleoplasm. Is expressed in several structures, including alimentary system; embryo mesenchyme; genitourinary system; nervous system; and sensory organ. Used to study schizophrenia. Human ortholog(s) of this gene implicated in congenital heart disease and dilated cardiomyopathy. Orthologous to human SP4 (Sp4 transcription factor). [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in whole brain E14.5 (RPKM 2.8), CNS E14 (RPKM 2.6) and 23 other tissues See more
Orthologs
human all
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Genomic context

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Location:
12 F2; 12 63.48 cM
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 12 NC_000078.7 (118195421..118265211, complement)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 12 NC_000078.6 (118231686..118301440, complement)

Chromosome 12 - NC_000078.7Genomic Context describing neighboring genes Neighboring gene 60S acidic ribosomal protein P2 pseudogene Neighboring gene STARR-seq mESC enhancer starr_33427 Neighboring gene cell division cycle associated 7 like Neighboring gene dynein, axonemal, heavy chain 11 Neighboring gene STARR-seq mESC enhancer starr_33429 Neighboring gene STARR-positive B cell enhancer mm9_chr12:119539914-119540215 Neighboring gene STARR-positive B cell enhancer mm9_chr12:119540362-119540663 Neighboring gene CapStarr-seq enhancer MGSCv37_chr12:119611733-119611916 Neighboring gene STARR-seq mESC enhancer starr_33430 Neighboring gene CapStarr-seq enhancer MGSCv37_chr12:119615690-119615886 Neighboring gene Riken cDNA D230030E09 gene Neighboring gene predicted gene, 25577

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Ketamine independently modulated power and phase-coupling of theta oscillations in Sp4 hypomorphic mice. Wang X, et al. PLoS One, 2018. PMID 29513708, Free PMC Article
  2. GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders. Young JW, et al. Neuropsychopharmacology, 2015 Nov. PMID 25907107, Free PMC Article
  3. Transcription factor Sp4 regulates expression of nervous wreck 2 to control NMDAR1 levels and dendrite patterning. Sun X, et al. Dev Neurobiol, 2015 Jan. PMID 25045015, Free PMC Article
  4. Specificity protein 4 (Sp4) regulates the transcription of AMPA receptor subunit GluA2 (Gria2). Priya A, et al. Biochim Biophys Acta, 2014 Jun. PMID 24576410, Free PMC Article
  5. Neuron-specific specificity protein 4 bigenomically regulates the transcription of all mitochondria- and nucleus-encoded cytochrome c oxidase subunit genes in neurons. Johar K, et al. J Neurochem, 2013 Nov. PMID 24032355, Free PMC Article

See all (47) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Although our studies initially focused on the relationship between Sp4, TRPV1 and thermal hyperalgesia, our results more broadly suggest that a larger Sp4-dependent gene network or nociceptive transcriptome exists inclusive of TRPV1, TRPA1 and TRPM8.
    Title: Transcription factor Sp4 is required for hyperalgesic state persistence.
  2. RNAi-mediated depletion of Sp4 and Klf5 decreased Tas1r1 expression, while overexpression of Klf5, but not Sp4, significantly increased Tas1r1 expression in the myoblast cells.
    Title: Krüppel-like factor 5 (Klf5) regulates expression of mouse T1R1 amino acid receptor gene (Tas1r1) in C2C12 myoblast cells.
  3. Sp4 hypomorphic mice had markedly elevated theta power localized frontally and parietally, a more pronounced theta phase progression along the neuraxis, and a stronger frontal-parietal theta coupling. Acute subanesthetic ketamine did not affect theta power in wildtype animals but significantly reduced it in Sp4 hypomorphic mice, nearly completely neutralizing their excessive frontal/parietal theta power.
    Title: Ketamine independently modulated power and phase-coupling of theta oscillations in Sp4 hypomorphic mice.
  4. elucidation of the Sp4 molecular pathway in Sp4 hypomorphic mice may provide novel insights to our understanding of abnormal NMDAR signaling in schizophrenia
    Title: Prolonged Ketamine Effects in Sp4 Hypomorphic Mice: Mimicking Phenotypes of Schizophrenia.
  5. The transcription factor Specificity Protein 4 (SP4) is important for neurodevelopment and is genetically associated with both schizophrenia and bipolar disorder.
    Title: GlyT-1 Inhibition Attenuates Attentional But Not Learning or Motivational Deficits of the Sp4 Hypomorphic Mouse Model Relevant to Psychiatric Disorders.
  6. Results suggest that the Sp4 gene in forebrain GABAergic neurons regulates ketamine-induced hyperlocomotion
    Title: Restoration of Sp4 in Forebrain GABAergic Neurons Rescues Hypersensitivity to Ketamine in Sp4 Hypomorphic Mice.
  7. Sp4 functionally regulated GluN1, GluN2A, and GluN2B, but not GluN2C.
    Title: Specificity protein 4 functionally regulates the transcription of NMDA receptor subunits GluN1, GluN2A, and GluN2B.
  8. neuron-specific Sp4 regulates the expression of all 13 subunits of mitochondrial cytochrome c oxidase(COX) enzyme in primary neurons. Sp4 also regulates mitochondrial transcription factors (TFAM, TFB1M, and TFB2M) and a COX assembly protein SURF-1.
    Title: Neuron-specific specificity protein 4 bigenomically regulates the transcription of all mitochondria- and nucleus-encoded cytochrome c oxidase subunit genes in neurons.
  9. Sp4 hypomorphic mice could therefore serve as a genetic model to investigate impaired NMDA functions resulting from loss-of-function mutations of human SP4 gene in schizophrenia and/or other psychiatric disorders.
    Title: Reduced NMDAR1 expression in the Sp4 hypomorphic mouse may contribute to endophenotypes of human psychiatric disorders.
  10. Dendritic growth and arborization of dentate granule cells was decreased in hippocampal cultures in vitro from SP4 null mutant neonatal mice.
    Title: Impaired postnatal development of hippocampal dentate gyrus in Sp4 null mutant mice.
Submit: New GeneRIF Correction See all GeneRIFs (14)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Targeted (6)  1 citation
  • Endonuclease-mediated (1) 

General gene information

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Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables DNA binding ISO
Inferred from Sequence Orthology
more info
  
enables DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
enables DNA-binding transcription factor activity ISO
Inferred from Sequence Orthology
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 cis-regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables identical protein binding ISO
Inferred from Sequence Orthology
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables sequence-specific DNA binding ISO
Inferred from Sequence Orthology
more info
  
Process Evidence Code Pubs
acts_upstream_of_or_within regulation of heart contraction 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
  
acts_upstream_of_or_within_positive_effect regulation of transcription by RNA polymerase II ISO
Inferred from Sequence Orthology
more info
  
Component Evidence Code Pubs
located_in cytosol ISO
Inferred from Sequence Orthology
more info
  
located_in nucleoplasm ISO
Inferred from Sequence Orthology
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
transcription factor Sp4

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)

  1. NM_001166385.2 → NP_001159857.2  transcription factor Sp4 isoform 2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This difference results in a shorter isoform (2) compared to isoform 1.
    Source sequence(s)
    AC163032, AC163034, BC076630, BY070406
    Consensus CDS
    CCDS88413.1
    UniProtKB/TrEMBL
    K4DI62, Q6DFV2
    Related
    ENSMUSP00000026367.11, ENSMUST00000026367.11
    Conserved Domains (4) summary
    sd00017
    Location:645 → 667
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam00096
    Location:703 → 725
    zf-C2H2; Zinc finger, C2H2 type
    cd22536
    Location:30 → 644
    SP4_N; N-terminal domain of transcription factor Specificity Protein (SP) 4
    pfam13465
    Location:689 → 712
    zf-H2C2_2; Zinc-finger double domain

  2. NM_009239.4 → NP_033265.4  transcription factor Sp4 isoform 1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC163032, AC163034, BC076630, BY070406
    Consensus CDS
    CCDS36579.1
    UniProtKB/Swiss-Prot
    E9QNI3, Q62445
    UniProtKB/TrEMBL
    A0A1Y7VJR5
    Related
    ENSMUSP00000152603.2, ENSMUST00000222314.2
    Conserved Domains (4) summary
    COG5048
    Location:660 → 731
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:647 → 669
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam00096
    Location:705 → 727
    zf-C2H2; Zinc finger, C2H2 type
    pfam13465
    Location:691 → 714
    zf-H2C2_2; Zinc-finger double domain

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

  1. NC_000078.7 Reference GRCm39 C57BL/6J

    Range
    118195421..118265211 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017315007.3 → XP_017170496.1  transcription factor Sp4 isoform X1

    UniProtKB/Swiss-Prot
    E9QNI3, Q62445
    Conserved Domains (3) summary
    sd00017
    Location:632 → 654
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam00096
    Location:690 → 712
    zf-C2H2; Zinc finger, C2H2 type
    pfam13465
    Location:676 → 699
    zf-H2C2_2; Zinc-finger double domain

  2. XM_036157278.1 → XP_036013171.1  transcription factor Sp4 isoform X2

    UniProtKB/Swiss-Prot
    E9QNI3, Q62445
    Conserved Domains (4) summary
    sd00017
    Location:588 → 610
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam00096
    Location:646 → 668
    zf-C2H2; Zinc finger, C2H2 type
    pfam13465
    Location:632 → 655
    zf-H2C2_2; Zinc-finger double domain
    cd22536
    Location:30 → 587
    SP4_N; N-terminal domain of transcription factor Specificity Protein (SP) 4

  3. XM_036157279.1 → XP_036013172.1  transcription factor Sp4 isoform X3

    Conserved Domains (5) summary
    COG5048
    Location:349 → 420
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:336 → 358
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam00096
    Location:334 → 358
    zf-C2H2; Zinc finger, C2H2 type
    pfam13465
    Location:380 → 403
    zf-H2C2_2; Zinc-finger double domain
    cl41773
    Location:1 → 335
    SP1-4_N; N-terminal domain of transcription factor Specificity Proteins (SP) 1-4
Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q62445.2 GenPept UniProtKB/Swiss-Prot:Q62445

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