Falcon deep research was attempted and failed with HTTP 402; the configured Perplexity-lite fallback failed with HTTP 401. No provider-named output was retained. The review instead uses the reviewed UniProt P21815 record, QuickGO annotation metadata, the local Reactome record, cached primary publications, and manual literature searches. The synthesis is recorded in IBSP-deep-research-manual.md.
IBSP encodes bone sialoprotein, a highly modified secreted SIBLING-family extracellular-matrix protein. It is abundant among the noncollagenous proteins of bone, binds hydroxyapatite with high affinity, and contains an RGD integrin-binding motif. Human bone-derived and recombinant BSP directly bind hydroxyapatite and support cell attachment PMID:11459848. Native BSP and an internal fragment also inhibit seeded hydroxyapatite crystal growth, showing that mineral binding can influence crystal behavior rather than serving only as passive retention PMID:9258751.
Human developmental localization places BSP in mature osteoblasts, osteocytes, osteoclasts, hypertrophic chondrocytes, and bone matrix, but not immature osteogenic precursors PMID:1818768. Mouse Ibsp knockout produces delayed primary ossification and lower cortical mineral density, supporting conserved involvement in bone formation and mineralization PMID:24816232.
The RGD-containing region binds alpha-V/beta-3 integrin. Peptide substitution or truncation strongly changes osteoblast-like cell attachment PMID:24103036. Direct cell assays show BSP supports alpha-V/beta-3-dependent adhesion and migration of osteoblastoid, endothelial, and tumor cells PMID:10640428. Thus integrin binding, cell adhesion, and positive regulation of cell adhesion are core; positive regulation of cell migration is a justified additional process.
In glioblastoma models, perivascular IBSP also promotes tumor-cell migration and growth PMID:36261010. This is strong context-specific biology but is not used to redefine the skeletal core function.
BSP binds complement factor H after initial attachment to alpha-V/beta-3 and protects tumor cells from complement-mediated lysis PMID:10747989. Negative regulation of complement-dependent cytotoxicity is proposed as a non-core experimental annotation. The generic protein-binding annotation from this paper is replaced with integrin binding; no current GO molecular-function term specifically captures factor H binding.
The PMID:16210410 abstract describes a membrane-enriched proteomic survey during osteoblast differentiation but does not identify IBSP or expose the gene-specific quantitative result. Because the full text was not available and the experimental curator may have seen gene-level evidence absent from the abstract, osteoblast differentiation and membrane are left UNDECIDED rather than removed.
The HuRI interactions with FAM9B and FXYD3 come from binary interaction screening and use the uninformative protein-binding term. They lack an established endogenous mechanism and are marked over-annotated.
The vesicle ISS traces through rat BSP to direct detection in isolated growth-plate matrix vesicles (PMID:18758911). The biology is plausible and conserved, but extracellular vesicle is more informative than the generic vesicle term, so the annotation is modified.
The cellular response to growth factor stimulus transfer ultimately reflects experimentally regulated mouse Ibsp expression. It is kept as non-core because it describes regulation of IBSP expression rather than the direct molecular action of the protein.
| Annotation group | Decision |
|---|---|
| extracellular matrix organization, IBA | ACCEPT |
| bone mineralization, IBA | ACCEPT |
| ossification, IEA | MODIFY to bone mineralization |
| extracellular region, IEA | MODIFY to extracellular matrix |
| cell adhesion, IEA | MODIFY to positive regulation of cell adhesion |
| protein binding, HuRI | MARK_AS_OVER_ANNOTATED |
| non-collagenous component of interstitial matrix | ACCEPT |
| structural molecule activity | MODIFY to integrin binding |
| small molecule binding | MODIFY to hydroxyapatite binding |
| protein binding, factor H/integrin paper | MODIFY to integrin binding |
| osteoblast differentiation, HDA | UNDECIDED |
| membrane, HDA | UNDECIDED |
| integrin binding, IMP | ACCEPT |
| positive regulation of cell adhesion, IMP | ACCEPT |
| extracellular region, ISS | ACCEPT |
| cell adhesion, ISS | ACCEPT |
| extracellular matrix organization, ISS | ACCEPT |
| vesicle, ISS | MODIFY to extracellular vesicle |
| cellular response to growth factor stimulus, ISS | KEEP_AS_NON_CORE |
| extracellular region, Reactome TAS | ACCEPT |