Nomenclature of Phycobilin lyases and related proteins

• All phycobilin lyases and related proteins This list allows users to retrieve any sequence from any organism included in the database by its locus tag/orf id or Genbank number when available.
• S/U clan The X-ray structure of one member of this phycobilin lyase group was determined at 2.8 Å resolution : CpcSIII of Thermosynechococcus elongatus BP1 (Kuzin et al., 2007; Kupka et al., 2009; Schluchter el al., 2010; Protein Data Bank ID: 3BDR). It is structurally related to the calyx-shaped lipocalin family (InterPro IPR002345). It possesses a 8-stranded anti-parallel, β-barrel structure with an α-helix. Searches using Phyre2 show that all members of the S/U clan have the same fold.
• S/U clan - Phycobilin lyases Members of this group encompass characterized phycobilin lyases as well as enzymes that are uncharacterized so far.
• CpcS family Two members of the CpcS family were biochemically characterized: Nostoc sp. PCC7120 CpcS-III and Synechococcus sp. PCC 7002 CpcS-I. Both bind a PCB at Cys-82 (consensus numbering) of alpha and beta-allophycocyanin (ApcA, B, D, F), beta-phycocyanin (CpcB/RpcB and beta-phycoerythrocyanin (PecB) in vivo (Zhao et al., 2007a,b). In vitro, CpcS can also catalyze the attachment of PEB to Cys-84 of alpha and beta-PEI (CpeA-B) and is thus is a nearly universal lyase with respect to apoproteins but is highly specific of this binding site.
• CpcS-I subfamily Classification proposed by Shen et al. (2008) and Schluchter et al. (2010). CpcS-I forms a heterodimer with CpcU-I in Synechococcus sp. PCC 7002 (Saunée et al., 2008; Shen et al., 2008). All strains containing a CpcS-I homolog also possess a CpcU-I homolog, except PCC7335 (see phyletic profiles).
• CpcS-II subfamily Classification proposed by Shen et al. (2008) and Schluchter et al. (2010). This subfamily contain only marine Synechococcus/Cyanobium. Co-occurrence with CpcU-II in phyletic profiles suggests that CpcS-II form an heterodimer with CpcU-II .
• CpcS-III subfamily Classification proposed by Shen et al. (2008) and Schluchter et al. (2010). None of the strains possessing the cpcS-III gene, including all PEC-containing strains, contains a cpcU gene (see phyletic profiles). The X-ray structure of CpcS-III from Thermosynechococcus elongatus BP1 (tll1699) is available (PDB database ID: 3BDR) and was crystallized as a homodimer. CpcS-III was erroneously called CpeS1 by Zhao et al. (2007a) and Tu et al. (2008).
• CpcU family CpcU proteins form heterodimers with some CpcS types
• CpcU-I subfamily CpcU-I forms a heterodimer with CpcS-I, as shown in Synechococcus sp. PCC7002 (Saunée et al, 2008; Shen et al, 2008).
• CpcU-II subfamily Present only in marine Synechococcus and Cyanobium spp.). Not formely characterized yet but likely forms a heterodimer with CpcS-II. Indeed, CpcU-II sequences are most closely related to CpcU-I and they have the same phyletic profile as CpsS-II.
• CpeS family Two members of this family were characterized biochemically : the "CpeS Pro HL" of Prochlorococcus marinus MED4 (Wiethaus et al 2010) and the CpeS-I of Fremyella diplosiphon Fd33/UTEX481/PCC7601 (Biswas et al., 2011).
• CpeS-I subfamily The CpeS-I from Fremyella diplosiphon strain UTEX481 was characterized as a PEB:Cys-80 beta-PE lyase (Biswas et al., 2011). This subfamily contains all PE-containing cyanobacteria outside the marine Synechococcus/Prochlorococcus branch
• CpeS-II subfamily This subfamily contains all marine picocyanobacteria, except Prochlorococcus HL ecotypes the derived CpeS sequence of which was classified in a different subfamily (CpeS ProHL).
• CpeS-ProHL subfamily This subfamily contains only the sequences of Prochlorococcus marinus HL ecotypes. CpeS sequence is the sole phycobilin lyase present in these genomes and was biochemically characterized in strain MED4 as a PEB:Cys-82 beta-PEIII (PpeB) lyase (Wiethaus et al., 2010). PpeB is also the sole PBP present in this (and other Prochlorococcus HL) strain.
• CpeU family Not biochemically characterized yet. Given its gene environment, it is possibly a PEI:PEB lyase, but the cysteinyl residue it chromophorylates is unknown yet. In marine Synechococcus, it may also act on the corresponding site of PEII, at least in low PUB strains.
• CpeU-I subfamily includes PE-containing cyanobacteria other than marine Synechococcus. Most sequences have multiple possible start codons.
• CpeU-II subfamily includes all PE-containing strains marine Synechococcus (subcluster 5)
• S/U clan related proteins These proteins are related to characterized or probable phycobilin lyases but may have other metabolic functions.
• CpcS homologs family Unknown function. Present only in some PC- or PE-containing cyanobacteria but absent from marine picocyanobacteria.
• CpcV family Unknown function. A CpcV mutant had no discernable phenotype in Synechococcus sp. PCC 7002 (Shen et al., 2008)
• T clan The structure of CpcT of Nostoc sp. PCC7120 and its complex with phycocyanobilin was resolved at 1.95 and 2.50 Å resolution (Protein Data Bank ID: 4O4O), respectively. CpcT forms a dimer and adopts a calyx-shaped β-barrel fold (Zhou et al., 2014). The structure of the CpeT of the cyanophage P-HM1 was resolved at 1.8 Å (Protein Data Bank ID: 5HI8; Gasper et al., 2017).
• T clan - Phycobilin lyases
• CpcT family Characterized in Synechococcus sp. PCC 7002 and Nostoc sp. PCC7120 to attach a PCB at Cys-153 of beta-PC (Shen et al., 2006; Zhao et al., 2007a,b). Nostoc sp. PCC 7120 CpcT also attaches PCB to Cys 155 of PecB (i.e. beta-PEC; Zhao et al., 2007a,b). Crystal structures of CpcT from Nostoc sp. PCC7120 and its complex with phycocyanobilin, have been obtained at 1.95 and 2.50 Å resolution, respectively (Zhou et al. 2014). CpcT forms a dimer and adopts a calyx-shaped beta-barrel fold.
• CpeT family CpeT from the Prochlorococcus marinus MED4 cyanophage P-HM1 was biochemically characterized and its structure resolved at 1.8-Å (Protein Data Bank ID: 5HI8). It attaches a PEB at Cys-155 of beta-PEI (Gasper et al. 2017) and perhaps at the corresponding position in beta-PEII of marine Synechococcus cyanobacteria.
• RpcT family Gene name proposed by Six et al. (2007). This enzyme is not formerly biochemically characterized yet but indirect evidence suggests that it attaches a PEB at Cys-153 of beta-PC (Blot et al. 2009). RpcT is a paralog of CpcT and they are located in different positions of the PBS rod region of marine Synechococcus spp. (Six et al. 2007). Interestingly, RS9916 possesses both RpcT and CpcT.
• T clan related proteins
• T homologs family Members of the T clan, but function unknown. Called T homologs by Schluchter et al. (2010) and CpcT2 by Zhao et al. (2007).
• E/F clan The crystal structure of the heterodimer of CpcE-I/F-I from Nostoc sp. PCC7120 was determined at a 1.89-Å resolution (Zhao et al., 2017; Protein Data Bank ID: 5N3U). Both subunits are twisted, crescent-shaped α-solenoid structures. CpcE has 15 and CpcF 10 helices. The inner (concave) layer of CpcE and the outer (convex) layer of CpcF form a cavity into which the PCB can fit (Zhao et al., 2017).
• E/F clan: subclan 1 All members of E/F subclan 1 form heteroduplexes or are fusion proteins (RpcG).
• E/F subclan 1 - Phycobilin lyases All members of this subclan form heterodimers (E/F or Y/Z). CpcE/F are found in C-PC-containing strains (which has PCB chromophores at all binding sites) and RpcE/F in strains possessing R-PC (Ong and Glazer 1987, Six et al., 2007). CpcE/F and RpcE/F are mutually exclusive. CpeY/Z are present only in PE-containing strains.
• CpcE/RpcE family
• CpcE-I subfamily Forms a heterodimer with CpcF-I. The CpcE-I/CpcF-I complex attaches a PCB at cys-84 of alpha-PC (Fairchild et al., 1992; Swanson et al. 1992; Bhalerao et al. 1994; . The crystal structure of the heterodimer of CpcE-I/F-I
  from Nostoc sp. PCC7120 was determined at 1.89-Å resolution (Zhao et al., 2017).
• CpcE-II subfamily Likely forms a heterodimer with CpcF-II. This subfamily is present only in marine Synechococcus and Cyanobium.
• RpcE subfamily Likely forms a heterodimer with RpcF. The activity of the RpcE/F complex was not formerly characterized but it is thought to attach a PEB at cys-84 of alpha-PC-II in most PE-containing marine Synechococcus spp. RpcE and RpcF are closely related to CpcE and CpcF, respectively.
• CpcF/RpcF family
• CpcF-I subfamily Forms a heterodimer with CpcE-I. The CpcE-I/CpcF-I complex attaches a PCB at cys-84 of alpha-PC. The crystal structure of the heterodimer of CpcE-I/F-I
  from Nostoc sp. PCC7120 was determined at 1.89-Å resolution (Zhao et al., 2017).
• CpcF-II subfamily Likely forms a heterodimer with CpcE-II. This subfamily is present only in marine Synechococcus and Cyanobium.
• RpcF subfamily Likely forms a heterodimer with RpcE. The activity of the RpcE/F complex was not formerly characterized but it is thought to attach a PEB at cys-84 of alpha-PC-II in most PE-containing marine Synechococcus spp. RpcE and RpcF are closely related to CpcE and CpcF, respectively.
• CpeY family CpeY is a lyase involved in the attachment of PEB at Cys-82 alpha-PE (CpeA). Its activity is enhanced by CpeZ. CpeY alone, but not CpeZ can ligate PEB to CpeA, but with a reduced yield than CpeY and CpeZ together (Biswas et al., 2011)
• CpeZ family CpeZ enhances the activity of CpeY. CpeYZ is involved in the attachment of PEB at Cys-82 alpha-PE (CpeA). CpeY alone, but not CpeZ can ligate PEB to CpeA, but with a reduced yield than CpeY and CpeZ together (Biswas et al., 2011). More recently Kronfel et al. (2019) showed that CpeZ acts as a chaperone-like protein, assisting in the folding/stability of PE subunits, allowing bilin lyases such as CpeY and CpeS to attach PEB to their PE subunit.
• E/F subclan 1 - Phycobilin lyases-isomerases This group gathers PecE/F, a PCB lyase isomerase found only in PEC-containing strains (Zhao et al., 2000, 2002, 2005; Storf et al., 2001) and RpcG, a fusion PEB lyase-isomerase found only in some PEII-containing marine strains (Synechococcus and Crocosphaera; Blot et al. 2009). In vitro, both PecE/F and RpcG can bind PCB and PEB on alpha-84 PC or PEI (Blot et al., 2009).
• PecE family Forms a heterodimer with PecF. The PecE/F complex attaches a PCB and isomerises it to PVB at Cys-84 of alpha-PEC.
• PecF family Forms a heterodimer with PecE. The PecE/F complex attaches a PCB and isomerises it to PVB at Cys-84 of alpha-PEC.
• RpcG family Fusion protein with C-term and N-term parts showing similarity to PecE and PecF but different function in vivo: RpcG attaches a PEB and isomerises it to PUB at cys-84 of alpha-PC. Found only in some marine cyanobacteria.
• E/F clan: subclan 2 Two phycobilin lyase-isomerases were characterized in the E/F subclan 2: MpeZ by Shukla et al.(2012) and MpeU but only partially by Mahmoud et al. (2017) . They do not seem to form heteroduplexes and so members of this group might be monomers or homodimers. This group also contains several enzymes which have been characterized but are not phycobilin lyases (IaiH, NblB, etc.).
• E/F subclan 2 - Phycobilin lyases and lyases-isomerases
• CpeF family Also called MpeX in Prochlorococcus marinus SS120 (Hess et al.,1999) and MpeV in marine Synechococcus spp. (Wilbanks et al., 1993, Six et al., 2007). In the latter group, it is found both in strains with a low PUB:PEB ratio and in type IV chromatic adapters, which also have MpeU. CpeF is the bilin lyase that ligates the doubly linked phycoerythrobilin on
  β- phycoerythrin in Fremyella diplosiphon (Kronfel et al. 2019).
• MpeU family Present only in PEII-containing marine Synechococcus. It is found both in strains with a high PUB:PEB ratio and in type IV chromatic adapters (Six et al., 2007; Mahmoud et al., 2017). Interruption of mpeU caused a reduction in PUB content, impaired phycobilisome assembly and reduced growth rate more strongly in blue than green light.(Mahmoud et al.2017). MpeU.is therefore important for adaptation of Synechococcus spp. to blue light.
• MpeW family This group includes sequences of putative PEII:PEB lyases-isomerases that are related to MpeY and MpeZ, but sufficiently different to form another family (Humily et al., 2013). Sequence related to MpeY and MpeZ and more distantly to CpeY (Humily et al., 2013). The mpeW gene is specific of one of the two groups of marine Synechococcus able to chromatically acclimate (CA4-B) and is located in a genomic subregion of the large phycobilisome rod region specifically involved in CA4.
• MpeY family Gene present in the "PEII subregion" of the "phycobilisome rod gene region" of all PEII-containing marine Synechococcus strains (Six et al. 2007). This includes WH7803 which has a single PUB, most likely located either at Cys-75 of MpeA or Cys-50/61 of MpeB (Ong & Glazer 1991). MpeY is related to MpeZ and MpeW and more distantly to CpeY. We predict that MpeY is a PEII:PEB lyase-isomerase though its exact specificity remains to be defined.
• MpeZ family Biochemically characterized as a Cys-83 alpha-PEII:PEB lyase isomerase in Synechococcus sp. RS9916 (Shukla et al., 2012). Likely does not form an heterodimer. Sequence related to MpeY and MpeW and more distantly to CpeY (Humily et al., 2013). The mpeZ gene is specific of one of the two groups of marine Synechococcus able to chromatically acclimate (CA4-A) and is generally located outside the main phycobilisome rod region (Six et al., 2007; Humily et al., 2013).
• E/F subclan 2 - Related proteins Members of this group usually have PBS lyase HEAT repeats domains or at least Armadillo-type folds. Most of them are uncharacterized yet and there is no evidence that they are bona fide phycobilin lyases, though they are clearly related to the latter.
• IaiH family Forms a complex with IscA which is involved in iron-sulfur cluster formation in cyanobacteria (Morimoto et al. 2003)
• L8106_11777 homologs family Homologs of the L8106_11777 protein in CCY9616. Some similarity with CpeF and MpeU.
• L8106_16949 homologs family Homologs of the L8106_16949 protein in CCY9616.
  Some similarity with MpeU and CpeF.
• L8106_22089 homologs family Homologs of the L8106_22089 protein in CCY9616.
  Some similarity with CpeZ and iaiH.
• MC7420_3535 homologs family Maybe a fusion protein. Its C-terminus shows similarity with MpeU
• MC7420_4701 homologs family All members of this family possess several PBS lyase HEAT-like repeat domains and a C-term dual specificity phosphatase, catalytic domain.
• NblB/CotB superfamily This group gathers enzymes that either have been biochemically characterized and have another function than phycobilin lyases or are still uncharacterized. All share structural motifs with (and possibly have a similar enzymatic activity as) phycobilin lyases.
• CotB family Described in Balabas et al. (2003) as being involved in the activation of green light-induced genes during complementary chromatic adaptation, but given its presence in strains with a variety of pigmentation, it most likely has another yet-to-be determined function.
• CotB homologs 1 family Members of this family contain an Armadillo-like helical fold. This family is found in all marine Synechococcus as well as some freshwater species.
• CotB homologs 2 family Unknown function. Sequence containing 6 PBS lyase HEAT-like repeats domains.
• NblB family NblB has a role in PBS degradation (together with NblA and NblC). A Synechococcus sp. PCC7942 nblB-less mutant was shown to lack the ability to degrade its phycobilisomes during either sulfur or nitrogen limitation and exhibited an increased ratio of phycocyanin to chlorophyll during nutrient-replete growth (Dolganov and Grossman, 1999). NblB is absent from marine picocyanobacteria. Recently Hu et al. (2019) showed that together with NblA, NblB can 1) interfere with chromophorylation as well as chromophore-detachment of phycobiliprotein; 2) promote dissociation of whole phycobilisomes, cores and, in particular, allophycocyanin trimers. 3) While NblA and NblB do not interact with each other, both interact with lyases, apo- and holo-biliproteins; 4) They promote synergistically the lyase-catalyzed chromophorylation of the β-subunit of the major rod component, C-phycocyanin. 5) They modulate lyase-catalyzed and lyase-independent chromophore transfers among biliproteins, with the core protein, ApcF, the rod protein, CpcA, and sensory biliproteins (phytochromes, cyanobacteriochromes) acting as potential traps. Altogether NblA/B can cooperate with the lyases in remodeling the phycobilisomes.
• Unknown PEB lyase-isomerase PUB chromophores are found at Cys-50/61 of beta-PEI and beta-PEII, Cys-140 of alpha-PEI and PEII and Cys-75 of alpha-PEII in some marine Synechococcus spp. strains with no obvious candidate lyase-isomerase identified for this function so far.