BST1 Protein

BST1 Protein

Overview

BST1 protein (Bone Marrow Stromal Cell Antigen 1, also known as CD157 or ADP-ribosyl cyclase 2) is a GPI-anchored cell surface enzyme encoded by the [BST1](/genes/bst1) gene. BST1 catalyzes the synthesis of cyclic ADP-ribose (cADPR) from NAD+, regulating intracellular calcium signaling. BST1 is expressed on immune cells, bone marrow stromal cells, and within the central nervous system. Genome-wide association studies have identified BST1 as a significant risk locus for [Parkinson's disease](/diseases/parkinsons-disease), with risk variants potentially affecting microglial immune function and calcium homeostasis in the brain.

BST1 Protein

Overview

BST1 protein (Bone Marrow Stromal Cell Antigen 1, also known as CD157 or ADP-ribosyl cyclase 2) is a GPI-anchored cell surface enzyme encoded by the [BST1](/genes/bst1) gene. BST1 catalyzes the synthesis of cyclic ADP-ribose (cADPR) from NAD+, regulating intracellular calcium signaling. BST1 is expressed on immune cells, bone marrow stromal cells, and within the central nervous system. Genome-wide association studies have identified BST1 as a significant risk locus for [Parkinson's disease](/diseases/parkinsons-disease), with risk variants potentially affecting microglial immune function and calcium homeostasis in the brain.

<div class="infobox infobox-protein"> [@satake2009]
<div class="infobox-header">BST1 Protein</div> [@hirata1994]
<table> [@saad2011]
<tr><td class="infobox-label">Protein Name</td><td>ADP-ribosyl cyclase 2 (CD157)</td></tr> [@malavasi2008]
<tr><td class="infobox-label">Gene</td><td>[BST1](/genes/bst1)</td></tr>
<tr><td class="infobox-label">UniProt ID</td><td>[Q10588](https://www.uniprot.org/uniprot/Q10588)</td></tr>
<tr><td class="infobox-label">PDB IDs</td><td>[1ISF](https://www.rcsb.org/structure/1ISF)</td></tr>
<tr><td class="infobox-label">Molecular Weight</td><td>33.9 kDa</td></tr>
<tr><td class="infobox-label">Subcellular Localization</td><td>Cell surface (GPI-anchored), lipid rafts</td></tr>
<tr><td class="infobox-label">Protein Family</td><td>ADP-ribosyl cyclase family (CD38/BST1)</td></tr>
<tr><td class="infobox-label">Associated Diseases</td><td>[Parkinson's disease](/diseases/parkinsons-disease)</td></tr>
</table>
</div>

Structure

Domain Architecture

• Signal peptide (residues 1-26)
• Extracellular catalytic domain (residues 27-283): Contains the NAD+-binding cleft and ADP-ribosyl cyclase catalytic site; structurally homologous to [CD38](/genes/cd38) (~33% sequence identity)
• GPI-anchor signal (residues 284-318): Cleaved and replaced by the GPI anchor for cell surface attachment

Catalytic Site

• Key catalytic residues: Glu148 (catalytic glutamate), Trp171, Asp155
• NAD+ binding: NAD+ enters the active site cleft; BST1 cleaves the nicotinamide-ribose bond and cyclizes ADP-ribose to form cADPR
• Compared to CD38: BST1 has weaker cyclase activity but stronger NADase (hydrolase) activity, producing ADPR as the major product

GPI Anchor and Lipid Raft Association

• The GPI anchor tethers BST1 to the outer leaflet of the plasma membrane
• BST1 partitions into cholesterol-rich lipid raft microdomains
• Lipid raft localization is important for signal transduction and receptor clustering
• BST1 can be released from the cell surface by GPI-specific phospholipase C or shed by metalloproteinases

Normal Function

NAD+ Metabolism and Calcium Signaling

• cADPR activates ryanodine receptors on the ER, releasing intracellular Ca2+
• This NAD+-calcium signaling axis regulates cell activation, proliferation, and chemotaxis
• BST1 also generates ADPR, which activates TRPM2 calcium channels
• In [neurons](/entities/neurons), cADPR/ADPR signaling modulates synaptic transmission and plasticity

Immune Cell Functions

• Neutrophil migration: BST1 functions as a receptor for growth factor-primed neutrophil transendothelial migration
• Pre-B cell growth: BST1 was originally identified as a stromal cell factor supporting pre-B lymphocyte growth
• Monocyte/macrophage activation: BST1 engagement promotes inflammatory cytokine production

Brain Functions

• Expressed in [microglia](/cell-types/microglia), [astrocytes](/cell-types/astrocytes), and neurons at low-moderate levels
• Microglial BST1 regulates calcium-dependent phagocytosis and inflammatory responses
• Neuronal BST1 contributes to calcium homeostasis and synaptic function
• NAD+ metabolism through BST1 intersects with [SIRT1](/genes/sirt1)/[SIRT2](/genes/sirt2) sirtuin-dependent neuroprotection pathways

Role in Disease

Parkinson's Disease

• Lead SNP: rs4698412 (4p15.32, p < 5×10−8 in combined Asian and European populations)
• Risk mechanism: Risk alleles are associated with altered BST1 expression, potentially affecting microglial calcium signaling and NAD+ metabolism
• Microglial inflammation: Dysregulated BST1 activity may enhance microglial inflammatory responses through cADPR-mediated calcium mobilization
• NAD+ depletion: Excessive BST1 NADase activity could deplete neuronal NAD+ pools, impairing sirtuin-dependent mitochondrial quality control and [PINK1](/genes/pink1)/[Parkin](/genes/prkn) pathway function
• Dopaminergic vulnerability: Calcium dysregulation through BST1/TRPM2 signaling may increase susceptibility of [substantia nigra dopaminergic neurons](/cell-types/substantia-nigra-dopaminergic-neurons), which already have elevated calcium demands
• Immune-mediated neurodegeneration: BST1 risk variants may shift microglial phenotype toward pro-inflammatory activation, accelerating [α-synuclein](/proteins/alpha-synuclein)-driven neurodegeneration

Connection to CD38 and NAD+ Biology

• BST1 and its paralog [CD38](/genes/cd38) are the major NADases in mammals
• CD38 expression increases with age and inflammation, depleting NAD+ pools
• BST1 may similarly contribute to age-related NAD+ decline in the brain
• NAD+ supplementation strategies (NMN, NR) may counteract BST1/CD38-mediated NAD+ depletion

Therapeutic Targeting

• BST1 inhibitors: Small molecules targeting the catalytic site could preserve NAD+ pools and reduce cADPR-mediated inflammatory calcium signaling
• NAD+ supplementation: Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) restore NAD+ pools depleted by BST1/CD38
• CD38/BST1 dual inhibitors: 78c and apigenin inhibit both CD38 and BST1 NADase activity
• Anti-BST1 antibodies: Potential for modulating microglial inflammatory responses

See Also

• [BST1 Gene](/genes/bst1)
• [CD38](/genes/cd38) — paralog NADase
• [SIRT1](/genes/sirt1) / [SIRT2](/genes/sirt2) — NAD+-dependent deacetylases
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)

External Links

• [UniProt: Q10588](https://www.uniprot.org/uniprot/Q10588)
• [PDB: 1ISF](https://www.rcsb.org/structure/1ISF)
• [GeneCards: BST1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=BST1)

References