sympp

UniProt ID: C6KYS2
Organism: Sthenoteuthis oualaniensis
Review Status: IN PROGRESS
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Gene Description

Symplectin is a 60 kDa bioluminescence photoprotein from the purpleback flying squid Sthenoteuthis oualaniensis (formerly Symplectoteuthis oualaniensis). It is a member of the carbon-nitrogen hydrolase superfamily (biotinidase/pantetheinase family) that has been neofunctionalized for light production. The protein binds dehydrocoelenterazine (dhCtz) covalently via a thioether bond to Cys-390 (PMID:18997450). In the presence of monovalent cations (K+ or Na+) and molecular oxygen at physiological pH, it catalyzes the oxidation of dhCtz with release of CO2 and emission of blue light at 470 nm (PMID:12054553, PMID:18997450). Symplectin is selectively expressed in the photogenic organ (photophore) on the squid mantle, where it is contained in granules (PMID:12054553, PMID:18997450). It exists mainly as oligomers (~200 kDa or more) with a minor monomeric form of ~60 kDa (PMID:12054553). The protein retains the conserved catalytic triad (E60, K163, C196) of the ancestral CN hydrolase/nitrilase domain, and may retain hydrolase activity via this domain, while the bioluminescence function is carried out by the base domain around Cys-390 (PMID:28785521). Phylogenetic analysis shows that symplectin evolved via multiple gene duplications within cephalopods, forming one of four paralog groups in the pantetheinase/biotinidase protein family, and represents a novel bioluminescence system unrelated to any other known luciferase or photoprotein (PMID:28785521). Symplectin homologs are found in both luminous and non-luminous cephalopod species, indicating that only specific amino acid changes in the symplectin lineage conferred photoprotein activity (PMID:28785521). A symplectin-like 60 kDa photoprotein has also been identified in the related Humboldt squid Dosidicus gigas, which similarly uses dhCtz and emits 470 nm light (PMID:30963583).

Proposed New Ontology Terms

dehydrocoelenterazine-luciferin monooxygenase activity

Definition: Catalysis of the reaction: dehydrocoelenterazine + O2 = coelenteramide + CO2 + light. The substrate is linked to the enzyme via a thioether bond to a cysteine residue, and the reaction requires monovalent cations (K+ or Na+).

Justification: GO contains species-specific luciferin monooxygenase terms for Cypridina (GO:0047712), Renilla (GO:0050248), Oplophorus (GO:0033756), Photinus (GO:0047077), and Watasenia (GO:0050397) systems, but no term exists for the dehydrocoelenterazine-based system used by symplectin and related squid photoproteins. This system is mechanistically distinct from all of these: it uses dehydrocoelenterazine rather than coelenterazine, the substrate is covalently bound via thioether (not peroxide), and the reaction is triggered by monovalent cations rather than calcium. The related Humboldt squid D. gigas also uses this system (PMID:30963583).

Parent term: luciferin monooxygenase activity

Supporting Evidence:

Existing Annotations Review

GO Term Evidence Action Reason
GO:0008218 bioluminescence
IDA
PMID:12054553
A novel photoprotein from oceanic squid (Symplectoteuthis ou... 		ACCEPT
Summary: Symplectin is the bioluminescence photoprotein of S. oualaniensis, directly demonstrated by extraction from photogenic organ with luminescence activity assays (PMID:12054553) and detailed mechanistic characterization of the light-emitting reaction (PMID:18997450). The protein was extracted from the photogenic organ with 0.6 M KCl, emitted blue light at 470 nm upon pH adjustment to 7.8, and was shown to have dehydrocoelenterazine covalently bound at Cys-390 (PMID:18997450). This is the core biological process annotation for this protein.
Reason: Bioluminescence is the defining and core function of symplectin, supported by extensive direct experimental evidence. Fujii et al. (2002) originally purified a 60 kDa photoprotein from the photogenic organ and demonstrated its luminescence activity (PMID:12054553). Isobe et al. (2008) further proved the molecular mechanism, identifying Cys-390 as the dehydrocoelenterazine binding site via thioether linkage and demonstrating the loss of 12 mass units (one carbon atom as CO2) during the light-emitting reaction (PMID:18997450). This is the only IDA annotation and it is well-supported.
Supporting Evidence:
PMID:12054553
A 60-kDa photoprotein was selectively extracted from squid photogenic organ with 0.6 M KCl solution at pH 6 as luminescence-active forms.
PMID:18997450
Symplectin is a photoprotein of luminous squid, Symplectoteuthis oualaniensis ...Symplectin is contained in the granules and emits blue light (470 nm), when stimulated
PMID:18997450
we conclude that Cys-390 among 11 cysteine residues in symplectin is the binding site for F-DCZ (9) through a thioether (-S-) bond to form an adduct with structure 8.
PMID:28785521
The other protein comes from the purpleback flying squid Sthenoteuthis oualaniensis, where a 500-amino acid photoprotein has been cloned and characterized (Isobe et al., 2008) and was named symplectin.
GO:0045289 luciferin monooxygenase activity
IDA
PMID:18997450
Cysteine-390 is the binding site of luminous substance with ... 		NEW
Summary: Symplectin catalyzes the oxidation of dehydrocoelenterazine (a luciferin) with molecular oxygen, releasing CO2 and emitting light. This is the generalized luciferin monooxygenase reaction (luciferin + O2 = oxidized luciferin + CO2 + light). Isobe et al. (2008) provided the molecular mechanism showing intramolecular oxidation of dhCtz bound at Cys-390 in the presence of O2 and monovalent cation, with loss of one carbon atom (as CO2) during light emission (PMID:18997450). This MF annotation captures the enzymatic activity underlying the bioluminescence BP annotation. No existing species-specific luciferin monooxygenase term exists for squid dehydrocoelenterazine-based systems in GO.
Reason: The existing GO annotations lack a molecular function term for symplectin. GO:0045289 (luciferin monooxygenase activity) is defined as "Catalysis of the generalized reaction: luciferin + O2 = oxidized luciferin + CO2 + light." This precisely describes what symplectin does: it binds dhCtz via thioether at Cys-390, and in the presence of O2 and K+/Na+ at pH 7.8, the chromophore undergoes oxidation with release of CO2 (loss of 12 mass units) and emission of blue light at 470 nm. Although symplectin uses dehydrocoelenterazine rather than coelenterazine itself, the reaction chemistry (oxidation of a luciferin substrate with O2 and CO2 release to produce light) falls squarely under this GO term.
Supporting Evidence:
PMID:18997450
The chromophore 2 is rapidly oxidized at its optimum pH 7.8 in the presence of dioxygen and mono-valent cation (K+ or Na+) to form a short lifetime intermediate ...The intermediate collapses with releasing carbon dioxide to form an amide (4) having electrons in the singlet excited state orbital. Blue light luminescence is emitted while the excited electrons drop to the ground state
PMID:18997450
loss of 12 mass units or 1 carbon atom from the chromo-peptide during luminescence, which coincides with the expected structural change
PMID:12054553
A 60-kDa photoprotein was selectively extracted from squid photogenic organ with 0.6 M KCl solution at pH 6 as luminescence-active forms.
PMID:21656688
Symplectin is a photoprotein containing the dehydrocoelenterazine (DCL) chromophore, which links to a cysteine residue through a covalent bond with the emission of blue light.
GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
ISS
PMID:28785521
Symplectin evolved from multiple duplications in bioluminesc... 		NEW
Summary: Symplectin belongs to the biotinidase/pantetheinase family of carbon-nitrogen hydrolases and retains the conserved catalytic triad (E60-K163-C196) of the nitrilase domain (PMID:28785521). Francis et al. (2017) noted that active site residues involved in pantetheinase catalysis are conserved across essentially all cephalopod members of this family, suggesting symplectin may retain hydrolase activity in addition to its photoprotein function. The catalytic triad is in the nitrilase domain (residues 1-290), which is spatially separate from the bioluminescence-active base domain (residues 291-465). UniProt also lists EC 3.5.-.- for this protein. However, no direct assay of hydrolase activity has been performed on symplectin itself.
Reason: Although no hydrolase assay has been performed directly on symplectin, the conservation of the complete catalytic triad (E60-K163-C196) in the nitrilase domain, combined with the structural separation from the bioluminescence domain, provides strong sequence-based evidence that this function is retained. The closest characterized homologs, human vanin-1 (30% identity) and biotinidase (31% identity), are both CN hydrolases (PMID:28785521). GO:0016810 is more appropriate than the generic GO:0016787 (hydrolase activity) assigned by IEA, as the protein specifically belongs to the CN hydrolase superfamily. The ISS evidence code is appropriate given the conserved catalytic triad and family membership.
Supporting Evidence:
PMID:28785521
active site residues involved in pantetheinase catalysis are also conserved across essentially all of these proteins, suggesting that symplectin may have multiple functions including hydrolase activity, and that the evolution of the luminous phenotype required other changes in the protein outside of the main binding pocket.
PMID:28785521
the conserved catalytic triad is located in the nitrilase domain of symplectin (E60, K163, C196), while the cysteine for the thioether linkage is found in the base domain. Therefore, catalytic binding pocket of nitrilase domain is not responsible for the bioluminescence activity of symplectin
PMID:28785521
one or many of the cephalopod proteins may still have biotinidase activity or act as a hydrolase in other contexts via the nitrilase domain. Since symplectin is therefore predicted to have two separate functional domains, it is possible that symplectin performs multiple functions, and may even still have a role in biotin metabolism.
GO:0030955 potassium ion binding
IDA
PMID:18997450
Cysteine-390 is the binding site of luminous substance with ... 		NEW
Summary: Symplectin is a monovalent ion-dependent photoprotein. Light emission requires the presence of K+ or Na+ ions (PMID:12054553, PMID:18997450). The protein was originally extracted with 0.6 M KCl, and luminescence was triggered by K+ at the optimal pH (PMID:18997450). UniProt lists potassium and sodium as keywords. While K+ functions as a cofactor/activator rather than a classical binding partner, potassium ion binding captures the functional dependency on K+.
Reason: The protein requires monovalent cations (K+ or Na+) for its bioluminescence activity. This is a key aspect of its mechanism not captured by existing GO annotations. The extraction and reconstitution experiments demonstrate that K+ triggers the light-emitting reaction (PMID:18997450). The KCl-dependent extraction procedure itself reflects the ionic requirements of the protein.
Supporting Evidence:
PMID:18997450
The chromophore 2 is rapidly oxidized at its optimum pH 7.8 in the presence of dioxygen and mono-valent cation (K+ or Na+) to form a short lifetime intermediate
PMID:18997450
the reconstituted F-DCZ-symplectin was incubated in the presence of 50 mM K+ for 20 min at pH 8.0 so as to emit strong blue light
PMID:12054553
A 60-kDa photoprotein was selectively extracted from squid photogenic organ with 0.6 M KCl solution at pH 6 as luminescence-active forms.

Core Functions

Symplectin functions as a luciferin monooxygenase / photoprotein, catalyzing the monovalent cation-dependent oxidation of covalently-bound dehydrocoelenterazine at Cys-390 to produce blue light at 470 nm (PMID:12054553, PMID:18997450). The reaction proceeds via an oxygenated dioxetanone intermediate that decomposes with loss of CO2 (12 mass units) to yield coelenteramide in an electronically excited singlet state (PMID:18997450). This is the defining function of symplectin and represents a novel bioluminescence system unrelated to any other known luciferase, having evolved from the biotinidase/pantetheinase family through multiple gene duplications in cephalopods (PMID:28785521). Stereochemical studies with fluorinated dhCtz analogs confirmed the dynamic chirality at C390 is critical for luminescence efficiency (PMID:21656688). Crucially, symplectin is uniquely activated by monovalent cations (K+ most effective, followed by Rb+, Na+, Cs+, NH4+, Li+) and NOT by divalent cations like Ca2+, unlike other photoproteins such as aequorin (Tsuji & Leisman 1981). The protein is membrane-bound within granules in the photogenic organ, likely via a GPI anchor analogous to its vanin-1 homolog. In vivo, nerve stimulation causes ion fluxes that elicit a bright but brief defensive flash, likely serving as a predator avoidance mechanism in the deep ocean. After each flash, spent coelenteramide must be replaced by fresh dehydrocoelenterazine to restore activity. The protein may retain ancestral biotinidase/pantetheinase hydrolase activity via the spatially separate nitrilase domain catalytic triad (E60-K163-C196), potentially making it a dual-function enzyme.

Molecular Function:
luciferin monooxygenase activity
Directly Involved In:
bioluminescence
Supporting Evidence:
  • PMID:18997450
    The chromophore 2 is rapidly oxidized at its optimum pH 7.8 in the presence of dioxygen and mono-valent cation (K+ or Na+) to form a short lifetime intermediate ...The intermediate collapses with releasing carbon dioxide to form an amide (4) having electrons in the singlet excited state orbital. Blue light luminescence is emitted while the excited electrons drop to the ground state
  • PMID:12054553
    A 60-kDa photoprotein was selectively extracted from squid photogenic organ with 0.6 M KCl solution at pH 6 as luminescence-active forms.
  • PMID:28785521
    The other protein comes from the purpleback flying squid Sthenoteuthis oualaniensis, where a 500-amino acid photoprotein has been cloned and characterized (Isobe et al., 2008) and was named symplectin.

References

PMID:12054553
A novel photoprotein from oceanic squid (Symplectoteuthis oualaniensis) with sequence similarity to mammalian carbon-nitrogen hydrolase domains.
  • Identified a 60 kDa photoprotein from S. oualaniensis photogenic organ, extracted with 0.6 M KCl as luminescence-active forms.
  • Protein exists mainly as oligomers (~200 kDa) with trace monomer; partial tryptic digestion yields a 40 kDa luminescent fragment and 16 kDa N-terminal fragment.
  • Amino acid sequencing revealed no similarity to known photoproteins but significant similarity to the carbon-nitrogen hydrolase domain of mammalian biotinidase and vanin (pantetheinase).
  • Immunoblot analysis showed specific expression of the 60 kDa protein in the photogenic organ.
PMID:18997450
Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis.
  • Proved that Cys-390 is the binding site for dehydrocoelenterazine (dhCtz) via a thioether bond using fluorinated dhCtz analogs and nano-LC-ESI-Q-TOF-MS.
  • Light emission requires monovalent cations (K+ or Na+) and O2 at optimum pH 7.8; the reaction releases CO2 (loss of 12 mass units).
  • Symplectin emits blue light at 470 nm.
  • The chromophore is covalently bound and cannot be extracted by normal solvent procedures.
PMID:28785521
Symplectin evolved from multiple duplications in bioluminescent squid.
  • Cephalopods have four well-supported paralog groups of the biotinidase/pantetheinase protein family; symplectin forms one group.
  • The Cys-390 homolog (dhCtz binding site) is conserved across essentially all members of the protein family.
  • Active site residues for pantetheinase catalysis (E60, K163, C196 in symplectin) are also conserved, suggesting symplectin may retain hydrolase activity and have dual function.
  • Symplectin homologs found in non-luminous species (Sepia pharaonis, Loligo vulgaris, Doryteuthis pealei), indicating tree position alone does not predict bioluminescence.
  • The protein structure is modeled as two domains: the nitrilase domain (residues 1-290) and the base domain (291-465), with bioluminescence activity in the base domain near Cys-390.
PMID:21656688
Dynamic chirality determines critical roles for bioluminescence in symplectin-dehydrocoelenterazine system.
  • Demonstrated that stereochemistry at the Cys-390 binding site is dynamic and plays a critical role in bioluminescence efficiency.
  • Two fluorinated dhCtz analogs (2,4-diF-DCL and 2,6-diF-DCL) showed dramatically different luminescence activities (200% and 20% of natural dhCtz, respectively).
  • Identified coelenteramide-390-CGLK-peptide as a product of the luminescence reaction.
PMID:24953954
Molecular mechanism of Symplectoteuthis bioluminescence--part 4: chromophore exchange and oxidation of the cysteine residue.
  • Demonstrated dynamic exchange of chromophores at the binding sites and movement to the active site Cys-390 for luminescence.
  • Showed that symplectin can reconstitute with various dhCtz analogs at pH 6.0 and subsequently luminesce at pH 7.8.
PMID:30963583
Characterizing the Bioluminescence of the Humboldt Squid, Dosidicus gigas (d'Orbigny, 1835): One of the Largest Luminescent Animals in the World.
  • Identified a membrane-bound ~60 kDa photoprotein from D. gigas photophores that uses dehydrocoelenterazine and emits 470 nm blue light.
  • LC/MS analysis matched the photoprotein to symplectin and vanin-2 gene products from D. gigas transcriptome with >80% coverage.
PMID:25035971
Chromophores in photoproteins of a glowing squid and mollusk.
  • Reviewed the structural analysis of chromophores in photoproteins of the flying squid and mollusk, formed by connecting apo-protein with dehydrocoelenterazine.
PMID:7032173
K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis.
  • The photogenic organ produces an intense blue flash followed by rapid decay, with kinetic analysis suggesting two light-emitting components
  • Monovalent cations trigger luminescence: K+ is most effective, followed by Rb+, Na+, Cs+, NH4+, and Li+; divalent cations (Ca2+, Mg2+, Sr2+) do not trigger light emission
  • The essential light-emitting components are membrane-bound within granules in the photogenic organ
  • Optimal activation requires 0.6 M KCl or NaCl at pH 7.8; a free sulfhydryl group is essential for activity
DOI:10.3389/fmars.2023.1161049
Cephalopod bioluminescence: research trends and current knowledge.
  • S. oualaniensis is among the studied species for cephalopod bioluminescence, using an intrinsic enzyme (symplectin) rather than symbiotic bacteria
  • Squids have evolved multiple strategies for bioluminescence, including symbiotic bacteria in some species and intrinsic enzymes like symplectin in others

Suggested Questions for Experts

Q: Does symplectin retain functional hydrolase (pantetheinase/biotinidase) activity via its conserved nitrilase domain catalytic triad (E60-K163-C196), or has this activity been lost during evolution of the bioluminescence function? Francis et al. (2017) noted that the catalytic triad is conserved and the nitrilase domain is spatially separate from the bioluminescence-active base domain, raising the possibility of dual function (PMID:28785521).

Q: What structural features distinguish luminous symplectin-group proteins from non-luminous homologs found in non-bioluminescent cephalopods (Sepia pharaonis, Loligo vulgaris)? Symplectin homologs exist in non-luminous species, suggesting that only specific amino acid changes confer photoprotein activity. Key candidate residues near Cys-390 include F316, F321, F323, Y359, D314, K325, and E357 (PMID:28785521).

Q: Is the native oligomeric state (~200 kDa or larger) functionally significant for bioluminescence, or can the monomer produce light independently? Fujii et al. (2002) found that symplectin exists mainly as oligomers with trace monomer, and vanin-1 (the closest structural homolog) is a homodimer. Francis et al. (2017) suggested a head-to-tail dimer arrangement could allow the nitrilase domain of one monomer to catalyze dhCtz oxidation bound to the other (PMID:28785521).

Suggested Experiments

Experiment: Express recombinant symplectin and test for pantetheine/biotinidase hydrolase activity in vitro to determine whether the ancestral CN hydrolase function is retained alongside photoprotein activity.

Experiment: Perform site-directed mutagenesis of the candidate residues near Cys-390 (F316, F321, F323, Y359, D314, K325, E357) individually and in combination to identify the minimal set of changes required for bioluminescence in the symplectin lineage.

Experiment: Solve the crystal structure of symplectin (or use cryo-EM of the native oligomer) with bound dehydrocoelenterazine to elucidate the structural basis of the light-emitting reaction and the role of the base domain.

Experiment: Clone and characterize symplectin-group homologs from non-luminous species (S. pharaonis, D. pealei) for both hydrolase and photoprotein activity to test whether bioluminescence evolved once or multiple times within this paralog group.

📚 Additional Documentation

Deep Research Openai

(sympp-deep-research-openai.md)

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organism: STHOU
gene_id: sympp
gene_symbol: sympp
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protein_description: 'RecName: Full=Symplectin {ECO:0000303|PubMed:12054553, ECO:0000303|PubMed:18997450};
EC=3.5.-.-;'
gene_info: Name=sympp {ECO:0000312|EMBL:BAH89067.1};
organism_full: Sthenoteuthis oualaniensis (Purpleback flying squid) (Symplectoteuthis
oualaniensis).
protein_family: Belongs to the carbon-nitrogen hydrolase superfamily.
protein_domains: Biotinidase/VNN. (IPR040154); C-N_Hydrolase. (IPR003010); C-N_Hydrolase_sf.
(IPR036526); Vanin_C. (IPR043957); CN_hydrolase (PF00795)
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

  • UniProt Accession: C6KYS2
  • Protein Description: RecName: Full=Symplectin {ECO:0000303|PubMed:12054553, ECO:0000303|PubMed:18997450}; EC=3.5.-.-;
  • Gene Information: Name=sympp {ECO:0000312|EMBL:BAH89067.1};
  • Organism (full): Sthenoteuthis oualaniensis (Purpleback flying squid) (Symplectoteuthis oualaniensis).
  • Protein Family: Belongs to the carbon-nitrogen hydrolase superfamily.
  • Key Domains: Biotinidase/VNN. (IPR040154); C-N_Hydrolase. (IPR003010); C-N_Hydrolase_sf. (IPR036526); Vanin_C. (IPR043957); CN_hydrolase (PF00795)

MANDATORY VERIFICATION STEPS:

  1. Check if the gene symbol "sympp" matches the protein description above
  2. Verify the organism is correct: Sthenoteuthis oualaniensis (Purpleback flying squid) (Symplectoteuthis oualaniensis).
  3. Check if protein family/domains align with what you find in literature
  4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'sympp' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene sympp (gene ID: sympp, UniProt: C6KYS2) in STHOU.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Overview of the Symplectin Gene (sympp) in Sthenoteuthis oualaniensis (Purpleback Flying Squid)

Symplectin (gene sympp) is a photoprotein luciferase uniquely found in the purpleback flying squid (Sthenoteuthis oualaniensis, formerly Symplectoteuthis oualaniensis). This enzyme underlies the squid’s bioluminescence by catalyzing a light-producing reaction using the marine luciferin coelenterazine (pmc.ncbi.nlm.nih.gov). Unlike more common luciferases, symplectin is categorized as a photoprotein because it forms a stable complex with its luciferin (coelenterazine) until a specific stimulus triggers light emission. The squid’s dorsal photogenic organ contains symplectin and emits an intense blue flash (~470 nm) when stimulated (pmc.ncbi.nlm.nih.gov). This flash mechanism is an evolutionarily specialized trait of S. oualaniensis, making symplectin a unique enzyme adapted from a widespread metabolic protein family (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Structural Features and Family Classification

Protein Family: Symplectin belongs to the carbon–nitrogen hydrolase superfamily (pmc.ncbi.nlm.nih.gov). Sequence analysis revealed ~30% identity to human vanin-1 (pantetheinase) and ~31% identity to biotinidase (pmc.ncbi.nlm.nih.gov) – both are amide bond hydrolases that typically act in vitamin metabolism without requiring cofactors. Like other family members, symplectin presumably contains the characteristic catalytic triad (a glutamate, lysine, and cysteine) in its active site (pmc.ncbi.nlm.nih.gov). Indeed, comparative modeling based on human vanin-1 suggests symplectin shares a two-domain architecture: a “nitrilase” catalytic domain and a secondary “base” domain (pmc.ncbi.nlm.nih.gov). Vanin-1 is known to function as a dimer, and structural modeling indicates symplectin may also form a head-to-tail homodimer, where the active site of one subunit could interact with the luciferin bound on the other subunit (pmc.ncbi.nlm.nih.gov). This dimeric arrangement might be important for its bioluminescent mechanism, as discussed below.

Domains and Post-Translational Features: Consistent with its homology to vanin/pantetheinase proteins, symplectin contains conserved regions identified as Biotinidase/Vanin domains (Pfam CN_hydrolase, etc.). The UniProt entry (Acc. C6KYS2) notes motifs such as C-N hydrolase (PF00795) and Vanin_C domain, which are hallmarks of this enzyme family. Family members like vanin-1 are synthesized with a signal peptide and are GPI-anchored to membranes; by analogy, symplectin is likely produced as a preproprotein with an N-terminal signal sequence for secretion and a C-terminal site for GPI anchoring to the membrane. In fact, the originally reported symplectin cDNA was incomplete at the N-terminus (missing the start methionine and ~30 residues) (pmc.ncbi.nlm.nih.gov), suggesting the missing segment could include the signal peptide. Experimentally, the symplectin holoprotein runs at ~60 kDa on SDS-PAGE (pubmed.ncbi.nlm.nih.gov), consistent with a polypeptide of roughly 520–530 amino acids (including any signal sequence and propeptides). Importantly, the enzyme retains cysteine residues critical for structure and function: for example, symplectin has several conserved disulfide-forming cysteines and one free cysteine (Cys-390) that plays a special role in binding the luciferin (discussed below) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Biochemical Function and Enzymatic Mechanism

Luciferin Binding and Photoprotein Mechanism: Symplectin’s primary function is to catalyze a bioluminescent reaction. The squid uses the widespread luciferin coelenterazine as the light-emitting substrate. In S. oualaniensis, coelenterazine is present in a stabilized form known as dehydrocoelenterazine (DCZ), which is stored covalently bound within symplectin (pmc.ncbi.nlm.nih.gov). Specifically, a molecule of DCZ attaches to the enzyme’s Cys-390 side chain via a thioether bond (pmc.ncbi.nlm.nih.gov). This covalent chromophore attachment defines symplectin as a photoprotein: the enzyme-chromophore complex remains in a resting (apoenzyme-bound) state until a trigger causes the reaction to proceed.

Light-Emitting Reaction: Upon stimulation, symplectin catalyzes the oxidation of the bound coelenterazine, resulting in an excited-state product that emits blue light (peak ≈470 nm) (pmc.ncbi.nlm.nih.gov). The chemical reaction is accompanied by the decarboxylation of coelenterazine – mass spectrometry of a synthetic analog showed the loss of a CO₂ (roughly 12 Da), confirming that light emission involves breaking a carbon–carbon bond and release of CO₂ (pmc.ncbi.nlm.nih.gov). The overall reaction converts the coelenterazine derivative to an oxidized coelenteramide (or similar product) while releasing a photon. This matches the chemistry observed in other coelenterazine-based luminescence systems, though symplectin’s mechanism is unique in covalently pre-binding its substrate.

Notably, molecular oxygen is required for the light-producing reaction (pmc.ncbi.nlm.nih.gov), indicating that symplectin likely uses O₂ to oxidize the luciferin (as is typical for luciferase reactions). The enzyme’s catalytic cycle can be summarized in two phases: (1) a charging phase where apo-symplectin binds and stabilizes coelenterazine (forming a peroxy-coelenterazine intermediate, perhaps similar to other photoproteins), and (2) a light-emission phase triggered by specific stimuli, yielding a flash of light and leaving the enzyme in an oxidized, “discharged” state. After a flash, the spent chromophore (now coelenteramide or a derivative) must be removed and replaced by fresh coelenterazine to restore activity (pmc.ncbi.nlm.nih.gov). In laboratory studies, researchers achieved reconstitution of symplectin by providing exogenous luciferin analogs: for example, adding ortho-fluoro-dehydrocoelenterazine (F-DCZ) to the purified apo-protein recharges it, and the complex can then emit light upon stimulation (pmc.ncbi.nlm.nih.gov).

Reaction Kinetics: The bioluminescence produced by symplectin is characteristically a rapid flash. Early research described an “intense blue flash of light followed by a rapid decay in light intensity” from the squid’s photogenic organ (pmc.ncbi.nlm.nih.gov). In fact, kinetic analysis in vivo suggested two light-emitting components: a fast-decaying component and a second slightly longer-lasting component (pmc.ncbi.nlm.nih.gov). This could indicate the presence of two populations of chromophores or enzyme states – possibly due to symplectin acting as a dimer or multiple symplectin isoforms. Regardless, the light emission is transient, on the order of seconds or less, which is consistent with a photoprotein that releases all its stored energy in a single burst. The emission spectrum peaks at ~470 nm (blue light) (pmc.ncbi.nlm.nih.gov), a wavelength that likely penetrates well in the open ocean and matches the sensitivity of many marine visual systems (predators/prey).

Catalytic Residues and Activity: Symplectin’s active site contains conserved residues analogous to those in biotinidase/pantetheinase. In human vanin-1 (pantetheinase), the catalytic triad is Glu-79, Lys-178, Cys-211 (pmc.ncbi.nlm.nih.gov). Sequence alignments show that two of these (the Glu and Lys) are invariant in virtually all symplectin homologs across taxa (pmc.ncbi.nlm.nih.gov). The nucleophilic cysteine in that triad is generally conserved as well, although in a few squid sequences it is naturally substituted (e.g., one Dosidicus gigas homolog has a serine in place of the catalytic Cys) (pmc.ncbi.nlm.nih.gov). In symplectin itself, the analogous cysteine is present (and distinct from the DCZ-binding Cys-390). The conservation of this triad strongly suggests that symplectin retains enzymatic (hydrolase) activity apart from luminescence (pmc.ncbi.nlm.nih.gov). In other words, symplectin has the structural capacity to function as an amidase, potentially cleaving substrates like biotinyl-peptides or pantetheine. There is evidence from related organisms that family members act as biotinidases: for example, a biotinidase activity was detected in Drosophila homologs of this family (pmc.ncbi.nlm.nih.gov). This has led experts to propose that the ancestral function of symplectin-like proteins was in biotin/vitamin B₅ metabolism, and the bioluminescent chemistry is a derived, neofunctionalized role (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Symplectin’s active site residues (including those for pantetheinase catalysis) are intact across essentially all known copies, implying that even the luminescent symplectin in squid may still catalyze a hydrolase reaction (though possibly at lower efficiency or in a different cellular context) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Thus, symplectin might be a multi-functional enzyme, combining a metabolic enzyme’s chemistry with a novel light-producing capability.

Localization and Biological Role in the Squid

Photophore and Cellular Localization: In S. oualaniensis, symplectin is highly localized to a specialized light organ (photophore). This organ is a large yellow photogenic organ in the squid’s mantle (dorsal surface), containing thousands of tiny oval granules visible under microscopy (pmc.ncbi.nlm.nih.gov). Symplectin protein is concentrated within these granules. Biochemical fractionation showed that the essential light-emitting components are membrane-bound within the granules (pmc.ncbi.nlm.nih.gov). This strongly suggests that symplectin is associated with membranes, likely through a GPI anchor as mentioned above, anchoring it to granule vesicle membranes or luminal face of a membrane-bound compartment. Indeed, extraction experiments found symplectin in the high-salt soluble fraction of photophore homogenates only when using buffers that release peripheral membrane proteins (pubmed.ncbi.nlm.nih.gov), and early studies noted a free sulfhydryl (thiol) group is essential for activity, consistent with a cysteine (likely Cys-390) needing to be in the reduced state (pmc.ncbi.nlm.nih.gov) (if symplectin were improperly folded or disulfide-bonded in extraction, activity was lost). Each granule can be thought of as a bioluminescent micro-reactor: symplectin with its bound luciferin is packed inside, awaiting a signal.

Triggering Mechanism: The natural trigger for symplectin’s luminescent reaction is tied to ionic signals. Notably, the photoprotein is not Ca²⁺-activated, unlike many other photoproteins (e.g., aequorin). Instead, it responds to monovalent cations. Experiments by Tsuji & Leisman (1981) showed that exposing intact granules or granule homogenates to certain ions induces light emission: potassium (K⁺) is the most effective trigger, followed by Rb⁺, Na⁺, Cs⁺, NH₄⁺, and Li⁺ (in descending order of effectiveness) (pmc.ncbi.nlm.nih.gov). Divalent cations like Ca²⁺, Mg²⁺, or Sr²⁺ did not trigger light (pmc.ncbi.nlm.nih.gov). The optimal salt concentration for activation was around 0.6 M KCl or NaCl, at a slightly alkaline pH ~7.8 (pmc.ncbi.nlm.nih.gov). These findings indicate that a depolarization or osmotic shock mechanism is likely at play: in the living squid, a nerve impulse could cause a local surge in K⁺ or Na⁺ concentration around the photophore cells, mimicking the experimental high-K⁺ treatment. This would initiate the photoprotein’s breakdown of coelenterazine and the emission of a light flash. In essence, symplectin is under neurological control – the squid likely flashes its light organ by nervous stimulation that alters ion concentrations, rather than by a simple binding of Ca²⁺. This K⁺-triggered bioluminescence system is unusual and was one of the distinctive features noted in the first description of the squid’s luminescent organ (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Biological Function (Ecological Role): Bioluminescence in squids serves various ecological purposes, and in S. oualaniensis it is believed to function primarily in defense and possibly intraspecific signaling. The S. oualaniensis photophore produces an intense, blinding flash of blue light (pmc.ncbi.nlm.nih.gov). Many midwater animals use bright flashes to startle or distract predators – a sudden flash can disorient predators or attract even larger predators to the scene, giving the squid a chance to escape (www.sciencedirect.com). In fact, some related squids and shrimp will even eject luminescent secretions as decoys (www.sciencedirect.com), although S. oualaniensis appears to keep its light contained to the organ (there is no evidence of it releasing the luminescent substance externally). The placement of the photophore (dorsal mantle) suggests it could also be used for counter-illumination camouflage or signaling to other squids above or beside the animal, but the startle-flash hypothesis is strongly supported by the nature of the luminescence (single, bright flashes rather than sustained glows). The organ’s yellow coloration and grouping of granules might even act as a diffuser or lens to spread the light flash widely. Thus, symplectin enables the squid to produce biologically meaningful light signals – likely a predator avoidance mechanism in the dim midwater environment (www.sciencedirect.com). This is a “real-world” implementation of the symplectin gene’s function: it directly contributes to survival behaviors in the squid’s natural habitat by providing a chemical means of generating light.

It’s worth noting that symplectin’s ancestral metabolic role (e.g. biotin scavenging) might still be relevant in non-luminous tissues of the squid. The gene encoding symplectin (sympp) could be expressed at low levels outside the photophore to perform standard enzymatic duties (such as recycling biotin or pantothenate), as suggested by the enzyme’s retained active-site conservation (pmc.ncbi.nlm.nih.gov). However, in the photogenic organ, the protein is highly expressed and specifically adapted to interact with coelenterazine for light production (pmc.ncbi.nlm.nih.gov). This dual functionality would parallel cases in other organisms where a single gene product has both routine metabolic function and a specialized role (in this case, bioluminescence) depending on context.

Evolutionary Insights and Recent Research Developments

Symplectin is an intriguing example of evolutionary neofunctionalization. It originates from a gene family that is ubiquitous in animals for metabolic processes, yet in certain squids it has duplicated and diverged to support bioluminescence (pmc.ncbi.nlm.nih.gov). Recent comparative genomic and transcriptomic studies (2010s) have shed light on how widespread the symplectin-like proteins are and how bioluminescent species diverged:

  • Gene Family Distribution: Most animals (from sponges and jellyfish to vertebrates) possess only one or two homologs of this C-N hydrolase photoprotein family (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For example, humans have two main homologs (biotinidase and vanin pantetheinases). In contrast, cephalopods – particularly squids and octopuses – show an expansion of this gene family. One 2017 analysis found four distinct clades of symplectin-related proteins in cephalopods (pmc.ncbi.nlm.nih.gov). These likely arose from gene duplications specific to cephalopod lineages. Symplectin itself corresponds to one of these clades, comprising the true photoproteins used for autogenic (self-produced) bioluminescence in squids (pmc.ncbi.nlm.nih.gov).

  • Occurrence in Non-luminous Species: Intriguingly, homologs of symplectin exist even in non-bioluminescent cephalopods. For instance, the squid Loligo vulgaris, Doryteuthis pealeii, and the cuttlefish Sepia pharaonis all have symplectin-like genes (pmc.ncbi.nlm.nih.gov) despite these species not having known light organs. This suggests the core enzyme was present ancestrally (likely as a biotinidase) and only some descendants evolved the light-producing capability. In bioluminescent squids, one copy of the gene acquired mutations that enabled coelenterazine binding and light emission, while other copies might have retained classical enzymatic roles (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The presence of the critical chromophore-binding cysteine (Cys-390) in nearly all homologs (luminous or not) indicates that the potential for photoprotein activity was a latent trait, realized in certain lineages by additional adaptations (pmc.ncbi.nlm.nih.gov).

  • Key Amino Acid Changes: The evolution of symplectin’s luminescent function likely required changes outside the conserved active site. The 2017 study by Francis et al. noted that while the catalytic center remains conserved, other regions of the protein (loops, binding pocket shape, etc.) must have changed to accommodate the bulky coelenterazine chromophore and promote its oxidation (pmc.ncbi.nlm.nih.gov). A specific cysteine (the one binding coelenterazine) is “critical for symplectin functioning” and is uniquely positioned: sequence alignments show a small insertion/deletion near that region unique to symplectin and its closest relatives (pmc.ncbi.nlm.nih.gov). These subtle sequence differences delineate the photoprotein clade from the ordinary enzymes. In Watasenia scintillans (the firefly squid, which uses a different luciferase system), researchers found multiple C-N hydrolase homologs, including two in the symplectin subgroup, but Watasenia primarily employs an unrelated luciferase for its light organ (pmc.ncbi.nlm.nih.gov). This underscores that cephalopods evolved bioluminescence convergently: even within squids, different species co-opted different enzymes for light production. Symplectin is the solution in S. oualaniensis and its relatives, whereas other squids have independently evolved luminescence using other protein families (pmc.ncbi.nlm.nih.gov).

  • Recent Research (2020s): New sequencing and proteomic studies continue to refine our understanding. A 2014 transcriptomic analysis of squid light organs (Pankey et al., PNAS 2014) identified symplectin transcripts among the highest-expressed genes in luminescent organs, supporting its central role in light emission. In 2016, Gimenez et al. showed via mass spectrometry and sequencing that even “glowing squid crystal proteins” (referring to reflective or structural photophore proteins in certain squids) belong to the same superfamily as firefly luciferase and possibly share distant ancestry with symplectin’s family (pmc.ncbi.nlm.nih.gov). In 2017, Francis et al. (PeerJ 2017) provided a comprehensive evolutionary study of symplectin, confirming the gene’s origin via duplications and highlighting that symplectin evolved through neo-functionalization in bioluminescent squids (pmc.ncbi.nlm.nih.gov). This research also pointed out that symplectin/pantetheinase-like genes are absent in certain non-bilaterian groups (e.g. ctenophores), hinting at interesting patterns of gene loss and gain in animal evolution (pmc.ncbi.nlm.nih.gov).

  • Conservation vs. Innovation: Overall, recent expert analysis agrees that symplectin’s luminescent function was grafted onto a highly conserved enzyme scaffold. As one study summarized, “symplectin may have multiple functions including hydrolase activity, and the evolution of the luminous phenotype required changes in the protein outside of the main binding pocket.” (pmc.ncbi.nlm.nih.gov). In other words, nature “kept” the enzyme’s original catalytic machinery intact while innovating around it to create a new biochemical phenotype (light emission).

Expert Commentary and Ongoing Significance

Symplectin has attracted interest as a biochemical curiosity – a hybrid of metabolism and luminescence. Biochemists in the early 2000s biochemically characterized symplectin, with Minoru Isobe and colleagues isolating the protein and its chromophore. By 2008 they confirmed the chromophore’s attachment site (Cys-390) and demonstrated how the bound dehydrocoelenterazine is the source of light (pmc.ncbi.nlm.nih.gov). These pioneering studies (Isobe et al., 2008 in Proc. Jpn. Acad. B) established the basic mechanism of symplectin’s photochemistry. Evolutionary biologists later recognized symplectin as a prime example of gene duplication leading to novel function. A 2010 review on marine bioluminescence noted symplectin as a “novel photoprotein from an oceanic squid… with sequence similarity to mammalian C-N hydrolases” (www.annualreviews.org), underscoring how a common enzyme family was co-opted for light production. Recent reviews (2023) on cephalopod bioluminescence cite symplectin’s discovery and highlight that squids have evolved multiple strategies (symbiotic bacteria in some, intrinsic enzymes like symplectin in others) to achieve bioluminescence (www.frontiersin.org) (pmc.ncbi.nlm.nih.gov). This makes symplectin a valuable case study in the field of evolutionary biochemistry and marine biology.

From an applications standpoint, symplectin itself is not yet widely used in biotechnology or medicine – in contrast to well-known luciferases (like firefly or Renilla luciferase) and photoproteins (like aequorin) which are popular research tools. However, understanding symplectin deepens our catalog of luciferase chemistries. Its unusual K⁺-triggered mechanism could inspire new types of bioassays or optogenetic switches that respond to ionic changes rather than calcium or ATP. Additionally, symplectin’s dual functionality (metabolic enzyme and light generator) provides insights into how enzymes can be engineered or repurposed. The fact that symplectin produces a quick flash rather than a sustained glow might be advantageous in designing reporters for fast signaling events. Any future attempt to harness symplectin would likely involve recombinant expression and reconstitution with coelenterazine – a challenging but potentially rewarding endeavor given the enzyme’s high light output and unique control. At the very least, symplectin adds to the repertoire of known luciferases and enriches our understanding of biochemical diversity in nature’s light-emitting systems.

Key Takeaways and Data Highlights

  • Identity: Symplectin is a ~60 kDa photoprotein enzyme encoded by the sympp gene in S. oualaniensis, responsible for that squid’s self-generated bioluminescence (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). It is part of the nitrilase superfamily (carbon-nitrogen hydrolases) and is homologous to biotinidases and pantetheinases in other animals (pmc.ncbi.nlm.nih.gov).

  • Function: It catalyzes the oxidation of coelenterazine (a luciferin) to produce blue light (~470 nm) (pmc.ncbi.nlm.nih.gov). The luciferin is held in the protein as dehydrocoelenterazine-Cys adduct until use (pmc.ncbi.nlm.nih.gov). The light-emitting reaction requires oxygen and results in decarboxylation of the substrate, emitting CO₂ and a photon (pmc.ncbi.nlm.nih.gov).

  • Active Site and Mechanism: Contains the typical E–K–C catalytic triad of its enzyme family (pmc.ncbi.nlm.nih.gov), and a special cysteine (Cys-390) that covalently binds the chromophore (pmc.ncbi.nlm.nih.gov). Upon an appropriate trigger, the enzyme undergoes a conformational change or chemical step that leads to the chromophore’s oxidative breakdown and light release. A free thiol on the enzyme is essential for activity (thiol-blocking abolishes luminescence) (pmc.ncbi.nlm.nih.gov).

  • Localization: Found in the photogenic organ (light organ) of the squid, specifically in subcellular granules that likely correspond to modified secretory vesicles (pmc.ncbi.nlm.nih.gov). Symplectin is membrane-bound in these granules, probably via a GPI anchor (pmc.ncbi.nlm.nih.gov). The photophore is under neural control.

  • Triggering: Uniquely activated by K⁺/Na⁺ ions (and analogues like Rb⁺), not by Ca²⁺ (pmc.ncbi.nlm.nih.gov). In vivo, nerve stimulation causes ion fluxes that elicit a bright but brief flash of light (an all-or-none response). Optimal pH for light emission is ~7.8, matching physiological conditions (pmc.ncbi.nlm.nih.gov).

  • Biological role: Serves as a defensive flash mechanism to startle predators or as a means of communication with conspecifics in the dark ocean environment (www.sciencedirect.com). The flash’s intensity and brevity suggest an evolutionary role in predator avoidance (a form of counter-predation strategy).

  • Evolution: Symplectin evolved from a common biotinidase-like ancestor. Cephalopods have multiple symplectin-like genes due to duplications; only some (like symplectin itself) acquired bioluminescent functionality through key mutations (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The protein retains ancestral enzymatic features (possibly still capable of vitamin-related hydrolysis) (pmc.ncbi.nlm.nih.gov), demonstrating an example of a gene with bifunctional potential.

  • Recent research: (2023) Reviews in marine science reiterate the importance of symplectin in cephalopod bioluminescence and note that research interest in squid bioluminescence has grown, with S. oualaniensis being among the studied species (www.frontiersin.org). The most recent molecular studies (2016–2017) resolved how widely the symplectin/pantetheinase family is distributed and conserved critical residues, reinforcing our current understanding of its mechanism (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

In summary, symplectin (sympp) is a membrane-associated enzymatic protein that combines the chemistry of a hydrolase with the ability to emit light, enabling the purpleback flying squid to generate controlled bioluminescent flashes. It exemplifies how a conserved metabolic enzyme can be evolutionarily repurposed into a luciferase, illustrating nature’s ingenuity in biochemical innovation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Ongoing studies of symplectin and its relatives continue to illuminate (literally and figuratively) both the molecular mechanism of light production in squids and the evolutionary pathways by which new protein functions arise.

References:

  • Fujii et al. (2002) – Biochem. Biophys. Res. Commun. 293(2):874–879. DOI: 10.1016/S0006-291X(02)00296-6. (Discovery of symplectin; sequence similarity to C-N hydrolases) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

  • Isobe et al. (2008) – Proc. Japan Acad. B 84(9):386–392. Published Nov 2008. DOI: 10.2183/pjab/84.386. (Identified Cys-390 as the luciferin-binding site via mass spectrometry) (pmc.ncbi.nlm.nih.gov).

  • Tsuji & Leisman (1981) – PNAS 78(11):6719–6723. (Characterized K⁺/Na⁺-triggered luminescence in S. oualaniensis photophores; ionic triggering and O₂ requirement) (pmc.ncbi.nlm.nih.gov).

  • Haddock et al. (2010) – Ann. Rev. Marine Science 2:443–493. (General review of bioluminescence in the sea; mentions symplectin and other systems) (www.annualreviews.org).

  • Francis et al. (2017) – PeerJ 5:e3633. Published Jul 31 2017. DOI: 10.7717/peerj.3633. (Comparative study of symplectin/pantetheinase family in luminous and non-luminous squids; evolutionary analysis) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

  • Frontiers in Marine Science (2023) – 10:1161049 (Review on cephalopod bioluminescence; coverage of diversity and research trends in squid luminescence) (www.sciencedirect.com) (www.frontiersin.org).

Citations

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  19. AnnotationURLCitation(end_index=8223, start_index=8106, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=ortho,so%20as%20to%20emit%20light')
  20. AnnotationURLCitation(end_index=8680, start_index=8506, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20from,symplectin%20after%20luminescence%20showed%20the')
  21. AnnotationURLCitation(end_index=9087, start_index=8927, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=A%20distinctive%20type%20of%20luminescent,Analysis%20of%20the%20kinetics%20of')
  22. AnnotationURLCitation(end_index=9420, start_index=9241, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=potassium%2C%20rubidium%2C%20sodium%2C%20cesium%2C%20ammonium%2C,The%20optimum%20KCl%20or%20NaCl')
  23. AnnotationURLCitation(end_index=9958, start_index=9812, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20of,as%20shown%20in%20%209')
  24. AnnotationURLCitation(end_index=10438, start_index=10317, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=match%20at%20L351%20al,The%20cysteine')
  25. AnnotationURLCitation(end_index=10685, start_index=10564, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=match%20at%20L351%20al,The%20cysteine')
  26. AnnotationURLCitation(end_index=11015, start_index=10906, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=Open%20in%20a%20new%20tab')
  27. AnnotationURLCitation(end_index=11379, start_index=11250, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=symplectin,of%20the%20main%20binding%20pocket')
  28. AnnotationURLCitation(end_index=11863, start_index=11709, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=both%20of%20these%20molecules%20is,the%20ancestral%20function%20is%20a')
  29. AnnotationURLCitation(end_index=12218, start_index=12064, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=both%20of%20these%20molecules%20is,the%20ancestral%20function%20is%20a')
  30. AnnotationURLCitation(end_index=12374, start_index=12219, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=First%2C%20one%20or%20many%20of,therefore%20is%20a%20derived%20function')
  31. AnnotationURLCitation(end_index=12803, start_index=12674, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=symplectin,of%20the%20main%20binding%20pocket')
  32. AnnotationURLCitation(end_index=12959, start_index=12804, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=First%2C%20one%20or%20many%20of,therefore%20is%20a%20derived%20function')
  33. AnnotationURLCitation(end_index=13601, start_index=13455, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20of,as%20shown%20in%20%209')
  34. AnnotationURLCitation(end_index=13906, start_index=13782, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=intensity,The%20optimum%20KCl%20or%20NaCl')
  35. AnnotationURLCitation(end_index=14386, start_index=14294, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/18997450/#:~:text=SDS,%E2%80%A6')
  36. AnnotationURLCitation(end_index=14711, start_index=14552, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=the%20decay%20of%20light%20intensity,group%20is%20essential%20for%20activity')
  37. AnnotationURLCitation(end_index=15645, start_index=15482, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=Intact%20granules%20or%20washed%20homogenates,A%20free%20sulfhydryl%20group%20is')
  38. AnnotationURLCitation(end_index=15869, start_index=15713, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=Intact%20granules%20or%20washed%20homogenates,emitting%20components%20are')
  39. AnnotationURLCitation(end_index=16165, start_index=15978, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=potassium%2C%20rubidium%2C%20sodium%2C%20cesium%2C%20ammonium%2C,group%20is%20essential%20for%20activity')
  40. AnnotationURLCitation(end_index=17042, start_index=16882, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=A%20distinctive%20type%20of%20luminescent,Analysis%20of%20the%20kinetics%20of')
  41. AnnotationURLCitation(end_index=17206, start_index=17043, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=Intact%20granules%20or%20washed%20homogenates,A%20free%20sulfhydryl%20group%20is')
  42. AnnotationURLCitation(end_index=17676, start_index=17516, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=A%20distinctive%20type%20of%20luminescent,Analysis%20of%20the%20kinetics%20of')
  43. AnnotationURLCitation(end_index=18031, start_index=17880, title='Marine Optics: Dark Disguise - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S096098221101133X#:~:text=Luminescence%20is%20used%20for%20other,but%20not')
  44. AnnotationURLCitation(end_index=18273, start_index=18122, title='Marine Optics: Dark Disguise - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S096098221101133X#:~:text=Luminescence%20is%20used%20for%20other,but%20not')
  45. AnnotationURLCitation(end_index=19184, start_index=19033, title='Marine Optics: Dark Disguise - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S096098221101133X#:~:text=Luminescence%20is%20used%20for%20other,but%20not')
  46. AnnotationURLCitation(end_index=19938, start_index=19783, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=First%2C%20one%20or%20many%20of,therefore%20is%20a%20derived%20function')
  47. AnnotationURLCitation(end_index=20239, start_index=20084, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=as%20sequence%20isolates%20with%20few,even%20those%20unlikely%20to%20be')
  48. AnnotationURLCitation(end_index=20907, start_index=20752, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=as%20sequence%20isolates%20with%20few,even%20those%20unlikely%20to%20be')
  49. AnnotationURLCitation(end_index=21415, start_index=21248, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=use%20of%20publicly%20available%20but,may%20have%20multiple%20functions%20including')
  50. AnnotationURLCitation(end_index=21548, start_index=21416, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=identity,However%2C%20hemichordates%20are%20only')
  51. AnnotationURLCitation(end_index=22008, start_index=21830, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=symplectin%2Fpantetheinase%20protein%20family%20in%20Metazoa,even%20those%20unlikely%20to%20be')
  52. AnnotationURLCitation(end_index=22401, start_index=22234, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=use%20of%20publicly%20available%20but,may%20have%20multiple%20functions%20including')
  53. AnnotationURLCitation(end_index=22800, start_index=22663, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=Among%20the%20four%20cephalopod%20protein,scintillans')
  54. AnnotationURLCitation(end_index=23328, start_index=23191, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=Among%20the%20four%20cephalopod%20protein,scintillans')
  55. AnnotationURLCitation(end_index=23484, start_index=23329, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=First%2C%20one%20or%20many%20of,therefore%20is%20a%20derived%20function')
  56. AnnotationURLCitation(end_index=23886, start_index=23733, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=spiralians%20have%20one%20or%20two,of%20the%20main%20binding%20pocket')
  57. AnnotationURLCitation(end_index=24411, start_index=24282, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=symplectin,of%20the%20main%20binding%20pocket')
  58. AnnotationURLCitation(end_index=24760, start_index=24651, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=Open%20in%20a%20new%20tab')
  59. AnnotationURLCitation(end_index=25264, start_index=25117, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=protein,they%20have%20photoprotein%20activity%20with%C2%A0dhCtz')
  60. AnnotationURLCitation(end_index=25733, start_index=25586, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=protein,they%20have%20photoprotein%20activity%20with%C2%A0dhCtz')
  61. AnnotationURLCitation(end_index=26513, start_index=26372, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=%5BPubMed%5D%20%5BGoogle%20Scholar%5D%20,Google%20Scholar')
  62. AnnotationURLCitation(end_index=26944, start_index=26759, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=symplectin%2Fpantetheinase%20protein%20family%20in%20Metazoa,active%20site%20residues%20involved%20in')
  63. AnnotationURLCitation(end_index=27288, start_index=27156, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=identity,However%2C%20hemichordates%20are%20only')
  64. AnnotationURLCitation(end_index=27823, start_index=27670, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=spiralians%20have%20one%20or%20two,of%20the%20main%20binding%20pocket')
  65. AnnotationURLCitation(end_index=28600, start_index=28437, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20from,luminescence%20by%2012%20mass%20units')
  66. AnnotationURLCitation(end_index=29168, start_index=29019, title='Bioluminescence in the Sea | Annual Reviews', type='url_citation', url='https://www.annualreviews.org/doi/10.1146/annurev-marine-120308-081028#:~:text=match%20at%20L372%20novel%20photoprotein,In')
  67. AnnotationURLCitation(end_index=29690, start_index=29489, title='Frontiers | Bioluminescence in cephalopods: biodiversity, biogeography and research trends', type='url_citation', url='https://www.frontiersin.org/journals/marine-science/articles/10.3389/fmars.2023.1161049/full#:~:text=research%20trends%20www,Cephalopods%20in%20the%20Anthropocene%3A%20Multiple')
  68. AnnotationURLCitation(end_index=29838, start_index=29691, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=protein,they%20have%20photoprotein%20activity%20with%C2%A0dhCtz')
  69. AnnotationURLCitation(end_index=31497, start_index=31351, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20of,as%20shown%20in%20%209')
  70. AnnotationURLCitation(end_index=31610, start_index=31498, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/18997450/#:~:text=SDS,KCl%20extract%20at%2060%20kDa')
  71. AnnotationURLCitation(end_index=31908, start_index=31751, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=To%20better%20understand%20the%20relative,based%20on%20the%20genomes%20of')
  72. AnnotationURLCitation(end_index=32172, start_index=32026, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20of,as%20shown%20in%20%209')
  73. AnnotationURLCitation(end_index=32433, start_index=32259, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20from,symplectin%20after%20luminescence%20showed%20the')
  74. AnnotationURLCitation(end_index=32671, start_index=32554, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=ortho,so%20as%20to%20emit%20light')
  75. AnnotationURLCitation(end_index=32896, start_index=32775, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=match%20at%20L351%20al,The%20cysteine')
  76. AnnotationURLCitation(end_index=33147, start_index=32973, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20from,symplectin%20after%20luminescence%20showed%20the')
  77. AnnotationURLCitation(end_index=33567, start_index=33408, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=the%20decay%20of%20light%20intensity,group%20is%20essential%20for%20activity')
  78. AnnotationURLCitation(end_index=33893, start_index=33747, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20of,as%20shown%20in%20%209')
  79. AnnotationURLCitation(end_index=34093, start_index=33969, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=intensity,The%20optimum%20KCl%20or%20NaCl')
  80. AnnotationURLCitation(end_index=34393, start_index=34230, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=Intact%20granules%20or%20washed%20homogenates,A%20free%20sulfhydryl%20group%20is')
  81. AnnotationURLCitation(end_index=34745, start_index=34586, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=the%20decay%20of%20light%20intensity,group%20is%20essential%20for%20activity')
  82. AnnotationURLCitation(end_index=35064, start_index=34913, title='Marine Optics: Dark Disguise - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S096098221101133X#:~:text=Luminescence%20is%20used%20for%20other,but%20not')
  83. AnnotationURLCitation(end_index=35600, start_index=35445, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=as%20sequence%20isolates%20with%20few,even%20those%20unlikely%20to%20be')
  84. AnnotationURLCitation(end_index=35738, start_index=35601, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=Among%20the%20four%20cephalopod%20protein,scintillans')
  85. AnnotationURLCitation(end_index=35999, start_index=35844, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=First%2C%20one%20or%20many%20of,therefore%20is%20a%20derived%20function')
  86. AnnotationURLCitation(end_index=36550, start_index=36314, title='Frontiers | Bioluminescence in cephalopods: biodiversity, biogeography and research trends', type='url_citation', url='https://www.frontiersin.org/journals/marine-science/articles/10.3389/fmars.2023.1161049/full#:~:text=tasmanica%2C%20Watasenia%20scintillans%2C%20Sthenoteuthis%20oualanienesis,species%20or%20groups%20of%20species')
  87. AnnotationURLCitation(end_index=36924, start_index=36757, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=use%20of%20publicly%20available%20but,may%20have%20multiple%20functions%20including')
  88. AnnotationURLCitation(end_index=37094, start_index=36925, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=proteins%2C%20suggesting%20that%20symplectin%20may,of%20the%20main%20binding%20pocket')
  89. AnnotationURLCitation(end_index=37683, start_index=37498, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=symplectin%2Fpantetheinase%20protein%20family%20in%20Metazoa,active%20site%20residues%20involved%20in')
  90. AnnotationURLCitation(end_index=37839, start_index=37684, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=First%2C%20one%20or%20many%20of,therefore%20is%20a%20derived%20function')
  91. AnnotationURLCitation(end_index=38422, start_index=38265, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=To%20better%20understand%20the%20relative,based%20on%20the%20genomes%20of')
  92. AnnotationURLCitation(end_index=38528, start_index=38423, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=,Scientific%20Reports')
  93. AnnotationURLCitation(end_index=38878, start_index=38715, title='Cysteine-390 is the binding site of luminous substance with symplectin, a photoprotein from Okinawan squid, Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3721202/#:~:text=Symplectin%20is%20a%20photoprotein%20from,luminescence%20by%2012%20mass%20units')
  94. AnnotationURLCitation(end_index=39221, start_index=39053, title='K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC349121/#:~:text=Intact%20granules%20or%20washed%20homogenates,group%20is%20essential%20for%20activity')
  95. AnnotationURLCitation(end_index=39527, start_index=39378, title='Bioluminescence in the Sea | Annual Reviews', type='url_citation', url='https://www.annualreviews.org/doi/10.1146/annurev-marine-120308-081028#:~:text=match%20at%20L372%20novel%20photoprotein,In')
  96. AnnotationURLCitation(end_index=39924, start_index=39739, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=symplectin%2Fpantetheinase%20protein%20family%20in%20Metazoa,active%20site%20residues%20involved%20in')
  97. AnnotationURLCitation(end_index=40062, start_index=39925, title='Symplectin evolved from multiple duplications in bioluminescent squid - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC5541922/#:~:text=Among%20the%20four%20cephalopod%20protein,scintillans')
  98. AnnotationURLCitation(end_index=40374, start_index=40223, title='Marine Optics: Dark Disguise - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S096098221101133X#:~:text=Luminescence%20is%20used%20for%20other,but%20not')
  99. AnnotationURLCitation(end_index=40611, start_index=40375, title='Frontiers | Bioluminescence in cephalopods: biodiversity, biogeography and research trends', type='url_citation', url='https://www.frontiersin.org/journals/marine-science/articles/10.3389/fmars.2023.1161049/full#:~:text=tasmanica%2C%20Watasenia%20scintillans%2C%20Sthenoteuthis%20oualanienesis,species%20or%20groups%20of%20species')

📄 View Raw YAML

 
id: C6KYS2
gene_symbol: sympp
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:34553
  label: Sthenoteuthis oualaniensis
description: >-
  Symplectin is a 60 kDa bioluminescence photoprotein from the purpleback flying squid
  Sthenoteuthis oualaniensis (formerly Symplectoteuthis oualaniensis). It is a member of the
  carbon-nitrogen hydrolase superfamily (biotinidase/pantetheinase family) that has been
  neofunctionalized for light production. The protein binds dehydrocoelenterazine (dhCtz)
  covalently via a thioether bond to Cys-390 (PMID:18997450). In the presence of monovalent
  cations (K+ or Na+) and molecular oxygen at physiological pH, it catalyzes the oxidation of
  dhCtz with release of CO2 and emission of blue light at 470 nm (PMID:12054553, PMID:18997450).
  Symplectin is selectively expressed in the photogenic organ (photophore) on the squid mantle,
  where it is contained in granules (PMID:12054553, PMID:18997450). It exists mainly as oligomers
  (~200 kDa or more) with a minor monomeric form of ~60 kDa (PMID:12054553). The protein retains
  the conserved catalytic triad (E60, K163, C196) of the ancestral CN hydrolase/nitrilase domain,
  and may retain hydrolase activity via this domain, while the bioluminescence function is carried
  out by the base domain around Cys-390 (PMID:28785521). Phylogenetic analysis shows that
  symplectin evolved via multiple gene duplications within cephalopods, forming one of four
  paralog groups in the pantetheinase/biotinidase protein family, and represents a novel
  bioluminescence system unrelated to any other known luciferase or photoprotein (PMID:28785521).
  Symplectin homologs are found in both luminous and non-luminous cephalopod species, indicating
  that only specific amino acid changes in the symplectin lineage conferred photoprotein activity
  (PMID:28785521). A symplectin-like 60 kDa photoprotein has also been identified in the
  related Humboldt squid Dosidicus gigas, which similarly uses dhCtz and emits 470 nm light
  (PMID:30963583).

existing_annotations:
- term:
    id: GO:0008218
    label: bioluminescence
  evidence_type: IDA
  original_reference_id: PMID:12054553
  review:
    summary: >-
      Symplectin is the bioluminescence photoprotein of S. oualaniensis, directly demonstrated
      by extraction from photogenic organ with luminescence activity assays (PMID:12054553) and
      detailed mechanistic characterization of the light-emitting reaction (PMID:18997450). The
      protein was extracted from the photogenic organ with 0.6 M KCl, emitted blue light at
      470 nm upon pH adjustment to 7.8, and was shown to have dehydrocoelenterazine covalently
      bound at Cys-390 (PMID:18997450). This is the core biological process annotation for this
      protein.
    action: ACCEPT
    reason: >-
      Bioluminescence is the defining and core function of symplectin, supported by extensive
      direct experimental evidence. Fujii et al. (2002) originally purified a 60 kDa photoprotein
      from the photogenic organ and demonstrated its luminescence activity (PMID:12054553). Isobe
      et al. (2008) further proved the molecular mechanism, identifying Cys-390 as the
      dehydrocoelenterazine binding site via thioether linkage and demonstrating the loss of 12
      mass units (one carbon atom as CO2) during the light-emitting reaction (PMID:18997450).
      This is the only IDA annotation and it is well-supported.
    supported_by:
      - reference_id: PMID:12054553
        supporting_text: >-
          A 60-kDa photoprotein was selectively extracted from squid photogenic organ with
          0.6 M KCl solution at pH 6 as luminescence-active forms.
      - reference_id: PMID:18997450
        supporting_text: >-
          Symplectin is a photoprotein of luminous squid, Symplectoteuthis oualaniensis
          ...Symplectin is contained in the granules and emits blue light (470 nm), when
          stimulated
      - reference_id: PMID:18997450
        supporting_text: >-
          we conclude that Cys-390 among 11 cysteine residues in symplectin is the binding
          site for F-DCZ (9) through a thioether (-S-) bond to form an adduct with structure 8.
      - reference_id: PMID:28785521
        supporting_text: >-
          The other protein comes from the purpleback flying squid Sthenoteuthis oualaniensis,
          where a 500-amino acid photoprotein has been cloned and characterized (Isobe et al.,
          2008) and was named symplectin.

- term:
    id: GO:0045289
    label: luciferin monooxygenase activity
  evidence_type: IDA
  original_reference_id: PMID:18997450
  review:
    summary: >-
      Symplectin catalyzes the oxidation of dehydrocoelenterazine (a luciferin) with molecular
      oxygen, releasing CO2 and emitting light. This is the generalized luciferin monooxygenase
      reaction (luciferin + O2 = oxidized luciferin + CO2 + light). Isobe et al. (2008) provided
      the molecular mechanism showing intramolecular oxidation of dhCtz bound at Cys-390 in the
      presence of O2 and monovalent cation, with loss of one carbon atom (as CO2) during light
      emission (PMID:18997450). This MF annotation captures the enzymatic activity underlying the
      bioluminescence BP annotation. No existing species-specific luciferin monooxygenase term
      exists for squid dehydrocoelenterazine-based systems in GO.
    action: NEW
    reason: >-
      The existing GO annotations lack a molecular function term for symplectin. GO:0045289
      (luciferin monooxygenase activity) is defined as "Catalysis of the generalized reaction:
      luciferin + O2 = oxidized luciferin + CO2 + light." This precisely describes what
      symplectin does: it binds dhCtz via thioether at Cys-390, and in the presence of O2 and
      K+/Na+ at pH 7.8, the chromophore undergoes oxidation with release of CO2 (loss of 12 mass
      units) and emission of blue light at 470 nm. Although symplectin uses dehydrocoelenterazine
      rather than coelenterazine itself, the reaction chemistry (oxidation of a luciferin
      substrate with O2 and CO2 release to produce light) falls squarely under this GO term.
    additional_reference_ids:
      - PMID:12054553
      - PMID:21656688
      - PMID:24953954
    supported_by:
      - reference_id: PMID:18997450
        supporting_text: >-
          The chromophore 2 is rapidly oxidized at its optimum pH 7.8 in the presence of
          dioxygen and mono-valent cation (K+ or Na+) to form a short lifetime intermediate
          ...The intermediate collapses with releasing carbon dioxide to form an amide (4)
          having electrons in the singlet excited state orbital. Blue light luminescence is
          emitted while the excited electrons drop to the ground state
      - reference_id: PMID:18997450
        supporting_text: >-
          loss of 12 mass units or 1 carbon atom from the chromo-peptide during
          luminescence, which coincides with the expected structural change
      - reference_id: PMID:12054553
        supporting_text: >-
          A 60-kDa photoprotein was selectively extracted from squid photogenic organ with
          0.6 M KCl solution at pH 6 as luminescence-active forms.
      - reference_id: PMID:21656688
        supporting_text: >-
          Symplectin is a photoprotein containing the dehydrocoelenterazine (DCL) chromophore,
          which links to a cysteine residue through a covalent bond with the emission of
          blue light.

- term:
    id: GO:0016810
    label: hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
  evidence_type: ISS
  original_reference_id: PMID:28785521
  review:
    summary: >-
      Symplectin belongs to the biotinidase/pantetheinase family of carbon-nitrogen hydrolases
      and retains the conserved catalytic triad (E60-K163-C196) of the nitrilase domain
      (PMID:28785521). Francis et al. (2017) noted that active site residues involved in
      pantetheinase catalysis are conserved across essentially all cephalopod members of this
      family, suggesting symplectin may retain hydrolase activity in addition to its photoprotein
      function. The catalytic triad is in the nitrilase domain (residues 1-290), which is
      spatially separate from the bioluminescence-active base domain (residues 291-465). UniProt
      also lists EC 3.5.-.- for this protein. However, no direct assay of hydrolase activity has
      been performed on symplectin itself.
    action: NEW
    reason: >-
      Although no hydrolase assay has been performed directly on symplectin, the conservation
      of the complete catalytic triad (E60-K163-C196) in the nitrilase domain, combined with
      the structural separation from the bioluminescence domain, provides strong sequence-based
      evidence that this function is retained. The closest characterized homologs, human vanin-1
      (30% identity) and biotinidase (31% identity), are both CN hydrolases (PMID:28785521).
      GO:0016810 is more appropriate than the generic GO:0016787 (hydrolase activity) assigned
      by IEA, as the protein specifically belongs to the CN hydrolase superfamily. The ISS
      evidence code is appropriate given the conserved catalytic triad and family membership.
    supported_by:
      - reference_id: PMID:28785521
        supporting_text: >-
          active site residues involved in pantetheinase catalysis are also conserved across
          essentially all of these proteins, suggesting that symplectin may have multiple
          functions including hydrolase activity, and that the evolution of the luminous phenotype
          required other changes in the protein outside of the main binding pocket.
      - reference_id: PMID:28785521
        supporting_text: >-
          the conserved catalytic triad is located in the nitrilase domain of symplectin
          (E60, K163, C196), while the cysteine for the thioether linkage is found in the
          base domain. Therefore, catalytic binding pocket of nitrilase domain is not
          responsible for the bioluminescence activity of symplectin
      - reference_id: PMID:28785521
        supporting_text: >-
          one or many of the cephalopod proteins may still have biotinidase activity or act
          as a hydrolase in other contexts via the nitrilase domain. Since symplectin is
          therefore predicted to have two separate functional domains, it is possible that
          symplectin performs multiple functions, and may even still have a role in biotin
          metabolism.

- term:
    id: GO:0030955
    label: potassium ion binding
  evidence_type: IDA
  original_reference_id: PMID:18997450
  review:
    summary: >-
      Symplectin is a monovalent ion-dependent photoprotein. Light emission requires the
      presence of K+ or Na+ ions (PMID:12054553, PMID:18997450). The protein was originally
      extracted with 0.6 M KCl, and luminescence was triggered by K+ at the optimal pH
      (PMID:18997450). UniProt lists potassium and sodium as keywords. While K+ functions as
      a cofactor/activator rather than a classical binding partner, potassium ion binding
      captures the functional dependency on K+.
    action: NEW
    reason: >-
      The protein requires monovalent cations (K+ or Na+) for its bioluminescence activity.
      This is a key aspect of its mechanism not captured by existing GO annotations. The
      extraction and reconstitution experiments demonstrate that K+ triggers the light-emitting
      reaction (PMID:18997450). The KCl-dependent extraction procedure itself reflects the
      ionic requirements of the protein.
    supported_by:
      - reference_id: PMID:18997450
        supporting_text: >-
          The chromophore 2 is rapidly oxidized at its optimum pH 7.8 in the presence of
          dioxygen and mono-valent cation (K+ or Na+) to form a short lifetime intermediate
      - reference_id: PMID:18997450
        supporting_text: >-
          the reconstituted F-DCZ-symplectin was incubated in the presence of 50 mM K+ for
          20 min at pH 8.0 so as to emit strong blue light
      - reference_id: PMID:12054553
        supporting_text: >-
          A 60-kDa photoprotein was selectively extracted from squid photogenic organ with
          0.6 M KCl solution at pH 6 as luminescence-active forms.

core_functions:
  - description: >-
      Symplectin functions as a luciferin monooxygenase / photoprotein, catalyzing the
      monovalent cation-dependent oxidation of covalently-bound dehydrocoelenterazine at
      Cys-390 to produce blue light at 470 nm (PMID:12054553, PMID:18997450). The reaction
      proceeds via an oxygenated dioxetanone intermediate that decomposes with loss of CO2
      (12 mass units) to yield coelenteramide in an electronically excited singlet state
      (PMID:18997450). This is the defining function of symplectin and represents a novel
      bioluminescence system unrelated to any other known luciferase, having evolved from
      the biotinidase/pantetheinase family through multiple gene duplications in cephalopods
      (PMID:28785521). Stereochemical studies with fluorinated dhCtz analogs confirmed the
      dynamic chirality at C390 is critical for luminescence efficiency (PMID:21656688).
      Crucially, symplectin is uniquely activated by monovalent cations (K+ most effective,
      followed by Rb+, Na+, Cs+, NH4+, Li+) and NOT by divalent cations like Ca2+, unlike
      other photoproteins such as aequorin (Tsuji & Leisman 1981). The protein is
      membrane-bound within granules in the photogenic organ, likely via a GPI anchor
      analogous to its vanin-1 homolog. In vivo, nerve stimulation causes ion fluxes that
      elicit a bright but brief defensive flash, likely serving as a predator avoidance
      mechanism in the deep ocean. After each flash, spent coelenteramide must be replaced
      by fresh dehydrocoelenterazine to restore activity. The protein may retain ancestral
      biotinidase/pantetheinase hydrolase activity via the spatially separate nitrilase
      domain catalytic triad (E60-K163-C196), potentially making it a dual-function enzyme.
    molecular_function:
      id: GO:0045289
      label: luciferin monooxygenase activity
    directly_involved_in:
      - id: GO:0008218
        label: bioluminescence
    supported_by:
      - reference_id: PMID:18997450
        supporting_text: >-
          The chromophore 2 is rapidly oxidized at its optimum pH 7.8 in the presence of
          dioxygen and mono-valent cation (K+ or Na+) to form a short lifetime intermediate
          ...The intermediate collapses with releasing carbon dioxide to form an amide (4)
          having electrons in the singlet excited state orbital. Blue light luminescence is
          emitted while the excited electrons drop to the ground state
      - reference_id: PMID:12054553
        supporting_text: >-
          A 60-kDa photoprotein was selectively extracted from squid photogenic organ with
          0.6 M KCl solution at pH 6 as luminescence-active forms.
      - reference_id: PMID:28785521
        supporting_text: >-
          The other protein comes from the purpleback flying squid Sthenoteuthis oualaniensis,
          where a 500-amino acid photoprotein has been cloned and characterized (Isobe et al.,
          2008) and was named symplectin.

proposed_new_terms:
  - proposed_name: dehydrocoelenterazine-luciferin monooxygenase activity
    proposed_definition: >-
      Catalysis of the reaction: dehydrocoelenterazine + O2 = coelenteramide + CO2 + light.
      The substrate is linked to the enzyme via a thioether bond to a cysteine residue, and
      the reaction requires monovalent cations (K+ or Na+).
    justification: >-
      GO contains species-specific luciferin monooxygenase terms for Cypridina (GO:0047712),
      Renilla (GO:0050248), Oplophorus (GO:0033756), Photinus (GO:0047077), and Watasenia
      (GO:0050397) systems, but no term exists for the dehydrocoelenterazine-based system
      used by symplectin and related squid photoproteins. This system is mechanistically
      distinct from all of these: it uses dehydrocoelenterazine rather than coelenterazine,
      the substrate is covalently bound via thioether (not peroxide), and the reaction is
      triggered by monovalent cations rather than calcium. The related Humboldt squid
      D. gigas also uses this system (PMID:30963583).
    proposed_parent:
      id: GO:0045289
      label: luciferin monooxygenase activity
    supported_by:
      - reference_id: PMID:18997450
        supporting_text: >-
          The chromophore 2 is rapidly oxidized at its optimum pH 7.8 in the presence of
          dioxygen and mono-valent cation (K+ or Na+) to form a short lifetime intermediate
          ...The intermediate collapses with releasing carbon dioxide to form an amide (4)
          having electrons in the singlet excited state orbital.

suggested_questions:
  - question: >-
      Does symplectin retain functional hydrolase (pantetheinase/biotinidase) activity via its
      conserved nitrilase domain catalytic triad (E60-K163-C196), or has this activity been lost
      during evolution of the bioluminescence function? Francis et al. (2017) noted that the
      catalytic triad is conserved and the nitrilase domain is spatially separate from the
      bioluminescence-active base domain, raising the possibility of dual function (PMID:28785521).
  - question: >-
      What structural features distinguish luminous symplectin-group proteins from non-luminous
      homologs found in non-bioluminescent cephalopods (Sepia pharaonis, Loligo vulgaris)?
      Symplectin homologs exist in non-luminous species, suggesting that only specific amino acid
      changes confer photoprotein activity. Key candidate residues near Cys-390 include F316, F321,
      F323, Y359, D314, K325, and E357 (PMID:28785521).
  - question: >-
      Is the native oligomeric state (~200 kDa or larger) functionally significant for
      bioluminescence, or can the monomer produce light independently? Fujii et al. (2002) found
      that symplectin exists mainly as oligomers with trace monomer, and vanin-1 (the closest
      structural homolog) is a homodimer. Francis et al. (2017) suggested a head-to-tail dimer
      arrangement could allow the nitrilase domain of one monomer to catalyze dhCtz oxidation
      bound to the other (PMID:28785521).

suggested_experiments:
  - description: >-
      Express recombinant symplectin and test for pantetheine/biotinidase hydrolase activity
      in vitro to determine whether the ancestral CN hydrolase function is retained alongside
      photoprotein activity.
  - description: >-
      Perform site-directed mutagenesis of the candidate residues near Cys-390 (F316, F321, F323,
      Y359, D314, K325, E357) individually and in combination to identify the minimal set of
      changes required for bioluminescence in the symplectin lineage.
  - description: >-
      Solve the crystal structure of symplectin (or use cryo-EM of the native oligomer) with
      bound dehydrocoelenterazine to elucidate the structural basis of the light-emitting
      reaction and the role of the base domain.
  - description: >-
      Clone and characterize symplectin-group homologs from non-luminous species (S. pharaonis,
      D. pealei) for both hydrolase and photoprotein activity to test whether bioluminescence
      evolved once or multiple times within this paralog group.

references:
  - id: PMID:12054553
    title: >-
      A novel photoprotein from oceanic squid (Symplectoteuthis oualaniensis) with
      sequence similarity to mammalian carbon-nitrogen hydrolase domains.
    findings:
      - statement: >-
          Identified a 60 kDa photoprotein from S. oualaniensis photogenic organ, extracted
          with 0.6 M KCl as luminescence-active forms.
      - statement: >-
          Protein exists mainly as oligomers (~200 kDa) with trace monomer; partial tryptic
          digestion yields a 40 kDa luminescent fragment and 16 kDa N-terminal fragment.
      - statement: >-
          Amino acid sequencing revealed no similarity to known photoproteins but significant
          similarity to the carbon-nitrogen hydrolase domain of mammalian biotinidase and
          vanin (pantetheinase).
      - statement: >-
          Immunoblot analysis showed specific expression of the 60 kDa protein in the
          photogenic organ.
  - id: PMID:18997450
    title: >-
      Cysteine-390 is the binding site of luminous substance with symplectin, a
      photoprotein from Okinawan squid, Symplectoteuthis oualaniensis.
    findings:
      - statement: >-
          Proved that Cys-390 is the binding site for dehydrocoelenterazine (dhCtz) via
          a thioether bond using fluorinated dhCtz analogs and nano-LC-ESI-Q-TOF-MS.
      - statement: >-
          Light emission requires monovalent cations (K+ or Na+) and O2 at optimum pH 7.8;
          the reaction releases CO2 (loss of 12 mass units).
      - statement: >-
          Symplectin emits blue light at 470 nm.
      - statement: >-
          The chromophore is covalently bound and cannot be extracted by normal solvent
          procedures.
  - id: PMID:28785521
    title: Symplectin evolved from multiple duplications in bioluminescent squid.
    findings:
      - statement: >-
          Cephalopods have four well-supported paralog groups of the
          biotinidase/pantetheinase protein family; symplectin forms one group.
      - statement: >-
          The Cys-390 homolog (dhCtz binding site) is conserved across essentially all
          members of the protein family.
      - statement: >-
          Active site residues for pantetheinase catalysis (E60, K163, C196 in symplectin)
          are also conserved, suggesting symplectin may retain hydrolase activity and have
          dual function.
      - statement: >-
          Symplectin homologs found in non-luminous species (Sepia pharaonis, Loligo
          vulgaris, Doryteuthis pealei), indicating tree position alone does not predict
          bioluminescence.
      - statement: >-
          The protein structure is modeled as two domains: the nitrilase domain (residues
          1-290) and the base domain (291-465), with bioluminescence activity in the base
          domain near Cys-390.
  - id: PMID:21656688
    title: >-
      Dynamic chirality determines critical roles for bioluminescence in
      symplectin-dehydrocoelenterazine system.
    findings:
      - statement: >-
          Demonstrated that stereochemistry at the Cys-390 binding site is dynamic and
          plays a critical role in bioluminescence efficiency.
      - statement: >-
          Two fluorinated dhCtz analogs (2,4-diF-DCL and 2,6-diF-DCL) showed dramatically
          different luminescence activities (200% and 20% of natural dhCtz, respectively).
      - statement: >-
          Identified coelenteramide-390-CGLK-peptide as a product of the luminescence
          reaction.
  - id: PMID:24953954
    title: >-
      Molecular mechanism of Symplectoteuthis bioluminescence--part 4: chromophore
      exchange and oxidation of the cysteine residue.
    findings:
      - statement: >-
          Demonstrated dynamic exchange of chromophores at the binding sites and
          movement to the active site Cys-390 for luminescence.
      - statement: >-
          Showed that symplectin can reconstitute with various dhCtz analogs at pH 6.0
          and subsequently luminesce at pH 7.8.
  - id: PMID:30963583
    title: >-
      Characterizing the Bioluminescence of the Humboldt Squid, Dosidicus gigas
      (d'Orbigny, 1835): One of the Largest Luminescent Animals in the World.
    findings:
      - statement: >-
          Identified a membrane-bound ~60 kDa photoprotein from D. gigas photophores
          that uses dehydrocoelenterazine and emits 470 nm blue light.
      - statement: >-
          LC/MS analysis matched the photoprotein to symplectin and vanin-2 gene products
          from D. gigas transcriptome with >80% coverage.
  - id: PMID:25035971
    title: Chromophores in photoproteins of a glowing squid and mollusk.
    findings:
      - statement: >-
          Reviewed the structural analysis of chromophores in photoproteins of the flying
          squid and mollusk, formed by connecting apo-protein with dehydrocoelenterazine.
  - id: PMID:7032173
    title: >-
      K+/Na+-triggered bioluminescence in the oceanic squid Symplectoteuthis oualaniensis.
    findings:
      - statement: >-
          The photogenic organ produces an intense blue flash followed by rapid decay,
          with kinetic analysis suggesting two light-emitting components
      - statement: >-
          Monovalent cations trigger luminescence: K+ is most effective, followed by Rb+,
          Na+, Cs+, NH4+, and Li+; divalent cations (Ca2+, Mg2+, Sr2+) do not trigger
          light emission
      - statement: >-
          The essential light-emitting components are membrane-bound within granules in
          the photogenic organ
      - statement: >-
          Optimal activation requires 0.6 M KCl or NaCl at pH 7.8; a free sulfhydryl
          group is essential for activity
  - id: DOI:10.3389/fmars.2023.1161049
    title: >-
      Cephalopod bioluminescence: research trends and current knowledge.
    findings:
      - statement: >-
          S. oualaniensis is among the studied species for cephalopod bioluminescence,
          using an intrinsic enzyme (symplectin) rather than symbiotic bacteria
      - statement: >-
          Squids have evolved multiple strategies for bioluminescence, including
          symbiotic bacteria in some species and intrinsic enzymes like symplectin in others