Protein / target
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1
Protein at a glance
Biological role
NAD+ nucleosidase activity, cyclic ADP-ribose generating
Primary system
Immune system
Strongest disease association
Parkinson disease
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
2 approved · 2 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Multifunctional transmembrane glycoprotein able to exert enzymatic activities and also to mobilize calcium, to transduce signals, to adhere to hyaluronan and to other ligands. Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosphate, NAADP(+), from 2'-phospho-cADPR and nicotinic acid, as well as from NADP(+) and nicotinic acid. At both pH 5.0 and pH 7.4 preferentially transforms 2'-phospho-cADPR into NAADP(+), while preferentially cleaving NADP(+) to cADPR and ADPRP rather than into NADDP(+) (PubMed:16690024). Has cADPR hydrolase activity (PubMed:7961800, PubMed:8253715). Functions also as a receptor that binds the ligand CD31 on endothelial cells, promoting lymphocyte activation, proliferation, and migration across the endothelial barrier (PubMed:9551996). Involved in the regulation of crucial dendritic cell functions acquired at the mature stage, such as CCL21-driven migration, survival, and Th1-polarizing activity (PubMed:16293598). In lamina propria T lymphocytes, CD38/CD31 cognate interactions initiate a multistep signaling pathway resulting in activation of LCK anf LAT, followed by cytokine release (PubMed:11259373)
Subcellular location
Domains and Gene Ontology detail (36)Hide
Gene Ontology
- Cbasolateral plasma membrane
- Ccell surface
- Cextracellular exosome
- Cmembrane
- Cnuclear membrane
- Cplasma membrane
- Fidentical protein binding
- FNAD+ nucleosidase activity, cyclic ADP-ribose generating
- Fphosphorus-oxygen lyase activity
- Fsignaling receptor activity
- Ftransferase activity
- Papoptotic signaling pathway
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Immune signalling
- ·Multifunctional transmembrane glycoprotein able to exert enzymatic activities and also t…
- ·B cell receptor signaling pathway
- ·positive regulation of B cell proliferation
- ·response to interleukin-1
Metabolic enzyme activity
- ·transferase activity
- ·nicotinate metabolic process
Transcriptional regulation
- ·negative regulation of DNA-templated transcription
- ·positive regulation of DNA-templated transcription
Apoptosis & cell death
- ·negative regulation of apoptotic process
Muscle contraction
- ·artery smooth muscle contraction
View underlying pathways (1)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Lymphocyte differentiation antigen CD38 inhibitor
Appears in clinical studies involving plasma cell myeloma, neoplasm, smoldering plasma cell myeloma, smoldering plasma cell myeloma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,023 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 4 total
plasma cell myeloma · neoplasm · plasma cell myeloma
plasma cell myeloma · Proteinuria · kidney disorder
plasma cell myeloma · neoplasm · smoldering plasma cell myeloma
autoimmune thrombocytopenic purpura · myasthenia gravis · autoimmune thrombocytopenic purpura
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Related literature
Papers indexed under “ADP-ribosyl Cyclase 1” — a subject heading that covers this protein without being specific to it. Shown as context; not counted as this protein's own research activity.
Europe PMC literature, reached through a MeSH descriptor linked to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- Industry developmentEHA: J&J sharpens myeloma edge as Talvey, Darzalex Faspro combo proves its worth in earlier disease stage
- New publicationBortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial.
- New publicationMaintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial.
- New publicationDaratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study.
- Safety communication
Drug Safety Update: Daratumumab (Darzalex▼): risk of reactivation of hepatitis B virus
- New publicationBortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study.
- New publicationTargeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy.
- Accelerated approval granted
Accelerated approval: Darzalex (EMA)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.