Details for: IBSP

Gene ID: 3381

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: IBSP

Ensembl ID: ENSG00000029559

Description: integrin binding sialoprotein

Cell Significance Landscape

Associated with

Significant Cells

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

  • chondrocyte CL0000138
    CSI 2.29
    rCSI 3.64%
    PRS 95.28
  • macrophage CL0000235
    CSI 1.74
    rCSI 3.16%
    PRS 96.45

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • 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 Integrin Binding Sialoprotein ([IBSP](/details-gene/3381)), also known as Bone Sialoprotein II, is a key protein component of the extracellular matrix (ECM), primarily associated with mineralized tissues. It plays a fundamental role in processes such as bone mineralization, osteoblast differentiation, and cell adhesion through its ability to bind integrins. The gene is located on chromosome 4q22.1 and its dysfunction is associated with certain bone-related pathologies ([147563](https://omim.org/entry/147563)). Expression data indicates its highest significance in structural cells like [chondrocytes](/details-cell/CL0000138) and, notably, also in immune cells such as [macrophages](/details-cell/CL0000235), suggesting a broader role in tissue remodeling and potentially immune regulation beyond its classical function in bone biology. ## Cellular Roles and Expression Landscape The expression profile of [IBSP](/details-gene/3381) highlights its specialized function in specific cell lineages. **Overall**, the gene shows the highest significance in [chondrocytes](/details-cell/CL0000138) (CSI: 2.29), which is consistent with its established role in cartilage and endochondral ossification ([Link](https://doi.org/10.1007/bf02555854)). Its function as a critical component of the mineralized matrix is well-documented ([Link](https://doi.org/10.1016/s0021-9258(18)47991-4)). Interestingly, [IBSP](/details-gene/3381) also demonstrates high significance in [macrophages](/details-cell/CL0000235) (CSI: 1.74). This suggests a potential role for [IBSP](/details-gene/3381) in modulating macrophage function, such as adhesion, migration, or polarization, particularly in the context of tissue injury, repair, and inflammation where macrophages interact extensively with a dynamically changing ECM. Recent research has implicated [IBSP](/details-gene/3381) in mediating tumor cell migration within the glioblastoma perivascular niche, a process often involving tumor-associated macrophages, further supporting its role in cell migration outside of bone homeostasis ([Link](https://doi.org/10.1016/j.celrep.2022.111511)). ## Pathways and Molecular Function The functions of [IBSP](/details-gene/3381) are primarily centered on extracellular matrix dynamics and cell-matrix interactions. As an extracellular protein ([GO:0005576](https://www.ebi.ac.uk/QuickGO/term/GO:0005576)), it is a core constituent of the ECM ([R-HSA-1474244](https://reactome.org/content/detail/R-HSA-1474244)). Its molecular activities are dominated by its capacity for 'Integrin binding' ([GO:0005178](https://www.ebi.ac.uk/QuickGO/term/GO:0005178)), which facilitates 'Cell adhesion' ([GO:0007155](https://www.ebi.ac.uk/QuickGO/term/GO:0007155)) and interaction with integrin complexes on the cell surface ([R-HSA-216083](https://reactome.org/content/detail/R-HSA-216083)). This interaction is crucial for processes like osteoblast differentiation ([GO:0001649](https://www.ebi.ac.uk/QuickGO/term/GO:0001649)) and bone mineralization ([GO:0030282](https://www.ebi.ac.uk/QuickGO/term/GO:0030282)), where [IBSP](/details-gene/3381) helps anchor cells to the matrix and organize mineral deposition ([Link](https://doi.org/10.1074/jbc.m105689200)). The activation of integrin αVβ3, for example, has been shown to regulate cell adhesion and migration specifically to [IBSP](/details-gene/3381) ([Link](https://doi.org/10.1006/excr.1999.4765)). ## Research Directions The dual significance of [IBSP](/details-gene/3381) in both structural ([chondrocytes](/details-cell/CL0000138)) and immune ([macrophages](/details-cell/CL0000235)) cells suggests it may act as a communication bridge between tissue structure and immune surveillance. This opens several avenues for future research. **Testable Hypotheses:** 1. [IBSP](/details-gene/3381) produced in the tumor microenvironment acts as a key chemoattractant and adhesion substrate for [macrophages](/details-cell/CL0000235), promoting their recruitment and retention, which in turn facilitates tumor progression and invasion. 2. In degenerative joint diseases like osteoarthritis, altered cleavage or expression of [IBSP](/details-gene/3381) within the cartilage matrix disrupts normal [chondrocyte](/details-cell/CL0000138) adhesion and signaling, contributing to cartilage degradation. **Proposed Experiment:** To test the first hypothesis, a co-culture experiment could be designed. Glioblastoma cells with CRISPR-Cas9-mediated knockout of [IBSP](/details-gene/3381) could be cultured alongside wild-type glioblastoma cells. Human monocyte-derived [macrophages](/details-cell/CL0000235) could then be introduced into the system. Using live-cell imaging and transwell migration assays, one could directly quantify macrophage migration towards and adhesion to [IBSP](/details-gene/3381)-producing versus [IBSP](/details-gene/3381)-deficient tumor cells. Furthermore, RNA-sequencing of the co-cultured [macrophages](/details-cell/CL0000235) would reveal if interaction with [IBSP](/details-gene/3381) alters their polarization state (e.g., towards a pro-tumoral M2 phenotype). **Therapeutic Potential:** As an extracellular, secreted protein involved in cell adhesion and migration, [IBSP](/details-gene/3381) presents a promising therapeutic target, particularly in oncology. Its role in mediating tumor cell migration suggests that targeting it could inhibit metastasis ([Link](https://doi.org/10.1016/j.celrep.2022.111511)). A therapeutic strategy would likely involve **inhibition**. This could be achieved using monoclonal antibodies that block the integrin-binding domain of [IBSP](/details-gene/3381), thereby preventing cancer cells and associated immune cells from using it as a scaffold for invasion. Such a targeted approach may offer specificity and reduce off-target effects compared to conventional chemotherapy.

Genular Protein ID: 1703682246

Symbol: SIAL_HUMAN

Name: Bone sialoprotein II

UniProtKB Accession Codes:

P21815

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DisProt 1 EMBL 9 Ensembl 1 GO 12 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SIGNOR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 2404984

Title: Human bone sialoprotein. Deduced protein sequence and chromosomal localization.

PubMed ID: 2404984

DOI: 10.1016/s0021-9258(19)39982-x

PubMed ID: 8406493

Title: The human bone sialoprotein gene (IBSP): genomic localization and characterization.

PubMed ID: 8406493

DOI: 10.1006/geno.1993.1340

PubMed ID: 8061918

Title: Characterization of the human bone sialoprotein (BSP) gene and its promoter sequence.

PubMed ID: 8061918

DOI: 10.1016/0945-053x(94)90027-2

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 3597437

Title: Purification and partial characterization of small proteoglycans I and II, bone sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone.

PubMed ID: 3597437

DOI: 10.1016/s0021-9258(18)47991-4

PubMed ID: 11459848

Title: Structural characterization of human recombinant and bone-derived bone sialoprotein. Functional implications for cell attachment and hydroxyapatite binding.

PubMed ID: 11459848

DOI: 10.1074/jbc.m105689200

PubMed ID: 1818768

Title: Expression of bone sialoprotein (BSP) in developing human tissues.

PubMed ID: 1818768

DOI: 10.1007/bf02555854

PubMed ID: 10640428

Title: Activation of integrin alpha(V)beta(3) regulates cell adhesion and migration to bone sialoprotein.

PubMed ID: 10640428

DOI: 10.1006/excr.1999.4765

PubMed ID: 11669636

Title: Posttranslational modifications to human bone sialoprotein determined by mass spectrometry.

PubMed ID: 11669636

DOI: 10.1021/bi010887r

PubMed ID: 24103036

Title: Structure-activity relationship of human bone sialoprotein peptides.

PubMed ID: 24103036

DOI: 10.1111/eos.12081

PubMed ID: 36261010

Title: A molecular interactome of the glioblastoma perivascular niche reveals integrin binding sialoprotein as a mediator of tumor cell migration.

PubMed ID: 36261010

DOI: 10.1016/j.celrep.2022.111511

Sequence Information:

  • Length: 317
  • Mass: 35148
  • Checksum: 736CB6B8C3716FE7
  • Sequence:
    • MKTALILLSI LGMACAFSMK NLHRRVKIED SEENGVFKYR PRYYLYKHAY FYPHLKRFPV 
QGSSDSSEEN GDDSSEEEEE EEETSNEGEN NEESNEDEDS EAENTTLSAT TLGYGEDATP 
GTGYTGLAAI QLPKKAGDIT NKATKEKESD EEEEEEEEGN ENEESEAEVD ENEQGINGTS 
TNSTEAENGN GSSGGDNGEE GEEESVTGAN AEDTTETGRQ GKGTSKTTTS PNGGFEPTTP 
PQVYRTTSPP FGKTTTVEYE GEYEYTGANE YDNGYEIYES ENGEPRGDNY RAYEDEYSYF 
KGQGYDGYDG QNYYHHQ