SP3 Sp3 transcription factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: SP3provided by HGNC
Official Full Name: Sp3 transcription factorprovided by HGNC
Primary source: HGNC:HGNC:11208
See related: Ensembl:ENSG00000172845 MIM:601804; AllianceGenome:HGNC:11208
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: SPR2
Summary: This gene belongs to a family of Sp1 related genes that encode transcription factors that regulate transcription by binding to consensus GC- and GT-box regulatory elements in target genes. This protein contains a zinc finger DNA-binding domain and several transactivation domains, and has been reported to function as a bifunctional transcription factor that either stimulates or represses the transcription of numerous genes. Transcript variants encoding different isoforms have been described for this gene, and one has been reported to initiate translation from a non-AUG (AUA) start codon. Additional isoforms, resulting from the use of alternate downstream translation initiation sites, have also been noted. A related pseudogene has been identified on chromosome 13. [provided by RefSeq, Feb 2010]
Expression: Ubiquitous expression in bone marrow (RPKM 21.0), thyroid (RPKM 19.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q31.1

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (173900775..173965702, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (174387111..174452024, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (174765503..174830430, complement)

Chromosome 2 - NC_000002.12 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
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?

Specificity protein 1/3 regulate T-cell acute lymphoblastic leukemia cell proliferation and apoptosis through beta-catenin by acting as targets of miR-495-3p.
Title: Specificity protein 1/3 regulate T-cell acute lymphoblastic leukemia cell proliferation and apoptosis through β-catenin by acting as targets of miR-495-3p.
SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells.
Title: SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells.
Caspase-Mediated Cleavage of the Transcription Factor Sp3: Possible Relevance to Cancer and the Lytic Cycle of Kaposi's Sarcoma-Associated Herpesvirus.
Title: Caspase-Mediated Cleavage of the Transcription Factor Sp3: Possible Relevance to Cancer and the Lytic Cycle of Kaposi's Sarcoma-Associated Herpesvirus.
A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear beta-catenin levels.
Title: A novel Lnc408 maintains breast cancer stem cell stemness by recruiting SP3 to suppress CBY1 transcription and increasing nuclear β-catenin levels.
SP3 is associated with migration, invasion, and Akt/PKB signalling in MDA-MB-231 breast cancer cells.
Title: SP3 is associated with migration, invasion, and Akt/PKB signalling in MDA-MB-231 breast cancer cells.
Sp3 Transcription Factor Cooperates with the Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein To Synergistically Activate Specific Viral and Cellular Gene Promoters.
Title: Sp3 Transcription Factor Cooperates with the Kaposi's Sarcoma-Associated Herpesvirus ORF50 Protein To Synergistically Activate Specific Viral and Cellular Gene Promoters.
The authors identified that human papillomavirus type 8 E7 protein exerts control over cellular gene expression through Sp1/3 binding motifs, which may contribute to the virus-mediated keratinocyte transformation and subsequent fibronectin-dependent invasion.
Title: HPV8 activates cellular gene expression mainly through Sp1/3 binding sites.
These findings suggest that the transcription of the b4GalT3 gene is regulated by differential DNA binding of Sp3 and Sp1 in neuroblastoma and lung cancer. The increased expression of b4GalT3 in neuroblastoma may be ascribed to the enhanced expression of Sp3, which is observed for various cancers.
Title: Transcription of human β4-galactosyltransferase 3 is regulated by differential DNA binding of Sp1/Sp3 in SH-SY5Y human neuroblastoma and A549 human lung cancer cell lines.
expression of the nearby cyclindependent kinase inhibitor 1C (CDKN1C) gene was revealed to be upregulated after SP3 knockdown in cells that possessed non-risk alleles. This suggests that CDKN1C is potentially one of the functional targets of SNP rs163184, which modulates the binding activity of the locus for Sp3 and Lsd1/Kdm1a
Title: A type 2 diabetes-associated SNP in KCNQ1 (rs163184) modulates the binding activity of the locus for Sp3 and Lsd1/Kdm1a, potentially affecting CDKN1C expression.
Sp1, Sp3 and Sp4 are non-oncogene addiction (NOA) genes and are attractive drug targets for individual and combined cancer chemotherapies.
Title: Specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 are non-oncogene addiction genes in cancer cells.

Submit: New GeneRIF Correction See all GeneRIFs (145)

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
A genome-wide association study of chronic otitis media with effusion and recurrent otitis media identifies a novel susceptibility locus on chromosome 2. EBI GWAS Catalog EBI GWAS CatalogPubMed
Chromosome 2q31.1 associates with ESRD in women with type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Pol	gag-pol	Transcription factors Oct-1, Oct-2, PU.1, Sp1, and Sp3 are recruited to the HS7 regulatory site in the pol coding region, suggesting that Oct-1, Oct-2, PU.1, Sp1, and Sp3 indirectly interact with HIV-1 Pol	PubMed
Tat	tat	HIV-1 Tat downregulates SOD2 expression by interacting with Sp1 and Sp3 to increase the Sp3-containing complexes on the basal SOD2 promoter	PubMed
	tat	In hepatic cells, HIV-1 Tat expression upregulates Sp1 and Sp3, which play different roles in regulating MnSOD transcription (overexpression of Sp1 stimulates, while overexpression of Sp3 represses transcriptional activity)	PubMed
	tat	Sp3 represses basal expression from the HIV-1 LTR promoter, and overexpression of Sp3 inhibits HIV-1 Tat-mediated transactivation of the HIV-1 LTR promoter	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH65817 (e-PCR)
- UniSTS:24064

RH68948 (e-PCR)
- UniSTS:15361

RH65732 (e-PCR)
- UniSTS:59168

SHGC-81056 (e-PCR)
- UniSTS:103573

PMC305603P1 (e-PCR)
- UniSTS:272552

SP3_2024 (e-PCR)
- UniSTS:471770

PMC169877P1 (e-PCR)
- UniSTS:271610

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
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 DNA-binding transcription repressor activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in definitive hemopoiesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic camera-type eye morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic placenta development	IEA Inferred from Electronic Annotation more info
involved_in embryonic process involved in female pregnancy	IEA Inferred from Electronic Annotation more info
involved_in embryonic skeletal system development	IEA Inferred from Electronic Annotation more info
involved_in enucleate erythrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in granulocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in liver development	IEA Inferred from Electronic Annotation more info
involved_in lung development	IEA Inferred from Electronic Annotation more info
involved_in megakaryocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in monocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in myeloid progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in natural killer cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in ossification	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction 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	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in trophectodermal cell differentiation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in PML body	IEA Inferred from Electronic Annotation more info
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IC Inferred by Curator more info	PubMed
part_of protein-DNA complex	ISS Inferred from Sequence or Structural Similarity more info	PubMed
part_of transcription repressor complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: transcription factor Sp3

Names: GC-binding transcription factor Sp3; specificity protein 3

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_029153.2 RefSeqGene

Range

5329..69927

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001017371.5 → NP_001017371.3 transcription factor Sp3 isoform 2

See identical proteins and their annotated locations for NP_001017371.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) is missing exons 1 and 2 found in transcript variant 1, and has a different 5' end. It initiates translation from a non-AUG (AUA) start site, and encodes an isoform (2) with a shorter N-terminus compared to isoform 1. Alternative translation initiation from downstream, in-frame AUG start codons produces shorter isoforms.

Source sequence(s)

AB209334, AC093399, AC106900, AY070137, BQ010796, M97191

Consensus CDS

CCDS46452.1

UniProtKB/TrEMBL

H0Y6K5

Related

ENSP00000406140.3, ENST00000418194.7

Conserved Domains (4) summary

COG5048
Location:568 → 650

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:555 → 577

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:613 → 635

zf-C2H2; Zinc finger, C2H2 type

pfam13465
Location:599 → 622

zf-H2C2_2; Zinc-finger double domain
NM_001172712.1 → NP_001166183.1 transcription factor Sp3 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1. Alternative translation initiation from downstream, in-frame start codons produces shorter isoforms.

Source sequence(s)

AB209334, AY441957, BC143928, BQ010796, M97191

UniProtKB/TrEMBL

B7ZLN9

Related

ENSP00000413665.1, ENST00000416195.1

Conserved Domains (4) summary

COG5048
Location:633 → 715

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:620 → 642

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:678 → 700

zf-C2H2; Zinc finger, C2H2 type

pfam13465
Location:664 → 687

zf-H2C2_2; Zinc-finger double domain
NM_003111.5 → NP_003102.1 transcription factor Sp3 isoform 1

See identical proteins and their annotated locations for NP_003102.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). Alternative translation initiation from downstream, in-frame start codons produces shorter isoforms.

Source sequence(s)

AC016737, AC093399, AC106900

Consensus CDS

CCDS2254.1

UniProtKB/Swiss-Prot

A0AVL9, B4E2B7, Q02447, Q69B26, Q69B27, Q8TD56, Q8WWU4, Q9BQR1

UniProtKB/TrEMBL

B7ZLN9

Related

ENSP00000310301.6, ENST00000310015.12

Conserved Domains (4) summary

COG5048
Location:636 → 718

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:623 → 645

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:681 → 703

zf-C2H2; Zinc finger, C2H2 type

pfam13465
Location:667 → 690

zf-H2C2_2; Zinc-finger double domain