Details for: SP5

Gene ID: 389058

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SP5

Ensembl ID: ENSG00000204335

Description: Sp5 transcription factor

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Bone morphogenesis
    (GO:0060349)
  • Cellular response to organic cyclic compound
    (GO:0071407)
  • Chromatin
    (GO:0000785)
  • Dna-binding transcription factor activity, rna polymerase ii-specific
    (GO:0000981)
  • Dna-binding transcription repressor activity, rna polymerase ii-specific
    (GO:0001227)
  • Metal ion binding
    (GO:0046872)
  • Negative regulation of transcription by rna polymerase ii
    (GO:0000122)
  • Nucleus
    (GO:0005634)
  • Post-anal tail morphogenesis
    (GO:0036342)
  • Regulation of transcription by rna polymerase ii
    (GO:0006357)
  • Rna polymerase ii cis-regulatory region sequence-specific dna binding
    (GO:0000978)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • conventional dendritic cell CL0000990
    CSI 30.75
    rCSI 25.67%
    PRS 96.62
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 23.92
    rCSI 28.98%
    PRS 92.78
  • regulatory T cell CL0000815
    CSI 17.75
    rCSI 20.58%
    PRS 96.36
  • helper T cell CL0000912
    CSI 17.06
    rCSI 24.12%
    PRS 97.42
  • neural crest cell CL0011012
    CSI 9.65
    rCSI 7.63%
    PRS 99.22
  • basal cell of epidermis CL0002187
    CSI 9.48
    rCSI 16.81%
    PRS 89.95
  • interneuron CL0000099
    CSI 7.84
    rCSI 15.74%
    PRS 98.59
  • chondrocyte CL0000138
    CSI 7.66
    rCSI 12.18%
    PRS 98.49
  • innate lymphoid cell CL0001065
    CSI 6.43
    rCSI 13.28%
    PRS 97.23
  • cytotoxic T cell CL0000910
    CSI 5.78
    rCSI 33.13%
    PRS 97.61
  • skin fibroblast CL0002620
    CSI 3.86
    rCSI 3.33%
    PRS 99.28
  • melanocyte of skin CL1000458
    CSI 3.24
    rCSI 4.42%
    PRS 91.42
  • stem cell CL0000034
    CSI 3.14
    rCSI 3.03%
    PRS 99.31
  • suprabasal keratinocyte CL4033013
    CSI 1.41
    rCSI 2.3%
    PRS 91.95

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SP5](/details-gene/389058) is a protein-coding gene located on chromosome 2q31.1 that encodes the Sp5 transcription factor. As a member of the Sp/KLF family of transcription factors, it plays a fundamental role in regulating gene expression by binding to DNA. Functionally, [SP5](/details-gene/389058) is implicated in the negative regulation of transcription and developmental processes such as bone morphogenesis. Expression data highlights its significant role within the immune system, where it shows the highest significance in [conventional dendritic cell](/details-cell/CL0000990) and various T lymphocyte subsets, including [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) and [regulatory T cell](/details-cell/CL0000815). Its expression in non-immune cells like [neural crest cell](/details-cell/CL0011012) and [chondrocyte](/details-cell/CL0000138) suggests it has pleiotropic functions spanning both immunity and development. ## Cellular Roles and Expression Landscape The expression profile of [SP5](/details-gene/389058) indicates a predominant role in the hematopoietic system, particularly within adaptive and innate immunity. **Overall**, the gene exhibits its highest significance in professional antigen-presenting cells, with [conventional dendritic cell](/details-cell/CL0000990) (CSI: 30.75) being the top-ranked cell type. This suggests a potential function in the initiation and shaping of adaptive immune responses. Furthermore, [SP5](/details-gene/389058) is a significant marker across multiple T lymphocyte lineages, underscoring its importance in T cell biology. It is highly significant in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 23.92), as well as key CD4+ subsets such as [regulatory T cell](/details-cell/CL0000815) (CSI: 17.75) and [helper T cell](/details-cell/CL0000912) (CSI: 17.06). Its presence in both cytotoxic and regulatory arms of the T cell compartment points towards a complex role in modulating immune effector functions and maintaining tolerance. Its significance extends to [innate lymphoid cell](/details-cell/CL0001065) and [cytotoxic T cell](/details-cell/CL0000910), reinforcing its broad involvement in immune surveillance. Beyond the immune system, [SP5](/details-gene/389058) also shows notable significance in several developmental and structural cell types. These include [neural crest cell](/details-cell/CL0011012) (CSI: 9.65), [basal cell of epidermis](/details-cell/CL0002187) (CSI: 9.48), and [chondrocyte](/details-cell/CL0000138) (CSI: 7.66). This diverse expression pattern is consistent with a role in cellular differentiation and tissue maintenance across multiple germ layers. ## Pathways and Molecular Function Functionally, [SP5](/details-gene/389058) operates as a DNA-binding transcription factor. Gene Ontology annotations confirm its molecular activities, including [Dna-binding transcription factor activity, rna polymerase ii-specific](/details-ontology/GO:0000981) and specifically [Dna-binding transcription repressor activity, rna polymerase ii-specific](/details-ontology/GO:0001227). Its localization to the [Nucleus](/details-ontology/GO:0005634) and its association with [Chromatin](/details-ontology/GO:0000785) are consistent with this role. The biological processes associated with [SP5](/details-gene/389058) reflect its involvement in transcriptional control and development. It is annotated in the [Regulation of transcription by rna polymerase ii](/details-ontology/GO:0006357) and more specifically its negative regulation ([GO:0000122](https://www.ebi.ac.uk/QuickGO/term/GO:0000122)). This repressor activity may be central to its function in guiding cell fate decisions. Its role in developmental pathways is highlighted by its association with [Bone morphogenesis](/details-ontology/GO:0060349) and [Post-anal tail morphogenesis](/details-ontology/GO:0036342), which aligns with its observed significance in [chondrocyte](/details-cell/CL0000138). Research has also explored the evolutionary context of domains within the related Sp protein family ([Link](https://doi.org/10.1007/s00018-019-03251-w)). ## Research Directions The available data highlights [SP5](/details-gene/389058) as a transcription factor with a dual role in immunity and development, presenting several avenues for future investigation. **Proposed Testable Hypotheses:** 1. Given its high significance in both [regulatory T cell](/details-cell/CL0000815) and various effector T cell subsets, [SP5](/details-gene/389058) may function as a master regulator that balances immune activation and tolerance by controlling the transcriptional programs that define distinct T cell fates. 2. Based on its high expression in [conventional dendritic cell](/details-cell/CL0000990), [SP5](/details-gene/389058) likely regulates the expression of key genes involved in antigen presentation (e.g., MHC molecules) and co-stimulation, thereby controlling the potency of T cell activation. 3. The gene's role in [Bone morphogenesis](/details-ontology/GO:0060349) and its expression in [chondrocyte](/details-cell/CL0000138) suggest that [SP5](/details-gene/389058) is essential for cartilage development and skeletal patterning, and its dysregulation could contribute to congenital skeletal disorders. **Suggested Experimental Approach:** To test the role of [SP5](/details-gene/389058) in T cell fate determination (Hypothesis 1), a compelling approach would be to utilize CRISPR-Cas9 to knock out the gene in primary human naive CD4+ T cells. These modified cells could then be cultured under polarizing conditions for Th1, Th2, Th17, and induced regulatory T cell (iTreg) lineages. The differentiation efficiency and functional phenotype could be assessed using flow cytometry for key lineage-defining transcription factors (e.g., T-bet, GATA3, RORγt, FOXP3) and cytokine production. Single-cell RNA-sequencing (scRNA-seq) of these populations would provide a high-resolution map of the downstream transcriptional networks controlled by [SP5](/details-gene/389058) in each lineage. **Therapeutic Potential:** As a nuclear transcription factor, [SP5](/details-gene/389058) is a challenging direct drug target using conventional small molecules. However, its crucial role in immune regulation, particularly in [regulatory T cell](/details-cell/CL0000815), suggests that modulating its activity could have therapeutic implications for autoimmune diseases or cancer immunotherapy. If its dysregulation contributes to disease, indirect strategies targeting its upstream signaling pathways or downstream effector genes might be viable. Furthermore, should [SP5](/details-gene/389058) be identified as an aberrantly expressed dependency in certain cancers, it could become a candidate for novel therapeutic modalities such as proteolysis-targeting chimeras (PROTACs), which are capable of inducing the degradation of intracellular proteins.

Genular Protein ID: 2873163673

Symbol: SP5_HUMAN

Name: Transcription factor Sp5

UniProtKB Accession Codes:

Q6BEB4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 31375868

Title: The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs.

PubMed ID: 31375868

DOI: 10.1007/s00018-019-03251-w

Sequence Information:

  • Length: 398
  • Mass: 41964
  • Checksum: BC2C27EE3ED499FA
  • Sequence:
    • MAAVAVLRND SLQAFLQDRT PSASPDLGKH SPLALLAATC SRIGQPGAAA PPDFLQVPYD 
PALGSPSRLF HPWTADMPAH SPGALPPPHP SLGLTPQKTH LQPSFGAAHE LPLTPPADPS 
YPYEFSPVKM LPSSMAALPA SCAPAYVPYA AQAALPPGYS NLLPPPPPPP PPPTCRQLSP 
NPAPDDLPWW SIPQAGAGPG ASGVPGSGLS GACAGAPHAP RFPASAAAAA AAAAALQRGL 
VLGPSDFAQY QSQIAALLQT KAPLAATARR CRRCRCPNCQ AAGGAPEAEP GKKKQHVCHV 
PGCGKVYGKT SHLKAHLRWH TGERPFVCNW LFCGKSFTRS DELQRHLRTH TGEKRFACPE 
CGKRFMRSDH LAKHVKTHQN KKLKVAEAGV KREDARDL