:Abstract: This communication will critically evaluate whether the p53/p63/p73 family are potential functional homologs of the Ndt80 rejuvenation factor.
p53 is a transcription factor capable of sensing a wide range of stress signals. Oxidative, osmotic, heat shock and starvation stresses induces p53 transcriptional activity. All p53-family proteins have a role in in genome protection and share tumour-suppressive activity of p53 to some extent [8,10 in (Lunardi et al., 2010); 20308539].
p53-family is a good example of antagonistic pleiotropy for reproduction, tumor suppression and longevity (http://www.ncbi.nlm.nih.gov/pubmed/20457559). The p53 ancestral genes in worms and flies are to ensure germ-line genomic integrity and fidelity of developmental processes which are retained in vertebrates.
CEP-1 sequence is more similar to p63 [Suh et al., 2006]. CEP-1 is able to bind, albeit with lower affinity, to human p53 consensus sites, and structural analysis indiciates that some key features of its DNA binding are conserved [Yuen et al., 2004; Schumacher et al., 2001].
Physiological germline apoptosis is cep-1 independent and it induction does not rely on pro-apoptotic BH3-only protein EGL-1 and therefore differs from other C. elegans apoptosis. CEP-1-dependent apoptosis is induced by a DNA damage or chromosomal integrity checkpoint. RB and E2F transcription factor subunits promote physiological cell death and function downstream of or in parallel to CEP-1 in the DNA damage response.
CEP-1 promotes DNA damage-induced apoptosis and is required for normal meiotic chromosomal segregation. Bloom syndrome protein HLM-6 acts on CEP-1. RAD-5/CLK-2 acts on CEP-1 too. clk-2 mutant is long-lived [Harris et al., 2006; 16951081]. GLD-1 translational represses CEP-1 expression. CEP-1 functions during normal development in absence of stress to repress 331 genes and activate just 28 genes. In response to genotoxic stress 1394 genes are activated and 942 are repressed. CEP-1 and PHG-1 mediate the decreased developmental rate and embryonic viability in clk-2/TEL2 gene, which regulates lifespan and checkpoint responses [Derry et al., 2007; 17186023]. AKT-1 regulates apoptosis dependent on cep-1 [Quevedo et al., 2007; 17276923]. CEP-1 interacts with NOTCH signalling.
GLD-1 binds directly to the cep-1 3’UTR and represses CEP-1 translation. The human homolog of GLD-1 is quaking [Wormbook].
C. elegans AKT-1 and AKT-2 kinases down-regulate CEP-1 [Quevedo et al., 2007 in Wormbook]. Their removal appears to result in evaluation in CEP-1 abundance, posttranscriptional modification, or both.
RNAi or knockout of cep-1 increases lifespan, which is dependent of functional daf-16. hus-1 mutant exhibit increased lifespan. cep-1 knockout did not have increased resistance to heat, oxidative or ultraviolet stress. cep-1 RNAi does not extend the lifespan of sir-2.1 overexpression, neither does it alter dauer formation propensity or nuclear-localization of DAF-16 even under heat-stress [Arum and Johnson, 2007; 17895432].
Many of the genes induced by ionizing radiation are also transcriptional regulated in longevity mutants [Greiss et al., 2008; 18627611].
Transcriptional coactivators previously through to be dedicated to the Notch signalling, called Mastermind-like (MAML)1-3 in mammals and LAG-3/SEL-8 in C. elegans function as transcriptional coactivators of p53 and CEP-1, respectively [Zhao et al., 2007 in Wormbook]. No mutator phenotype was detected in cep-1 mutants [Harris et al., 2006 in Wormbook].
NST-1 nucleostemin interacts with CEP-1 [Kudron and Reinke, 2008; 18725931].
Nucleolus is a major coordinator of cellular stress response by regulating p53. A screen for negative regulators of detoxification genes identified WD40 repeat containing protein WDR-46. WDR-46 is highly conserved with yeast UTP7, which functions in 18S rRNA processing and assembly of the 40S small ribosomal subunit. WDR-46 is also required for rRNA procession and is expressed in the nucleoli of multiple tissues in C. elegans. Mutations or silencing of WDR-46 activates SKN-1 and increase expression of its target genes. Wdr-46 depletion reduces lifespan and stress resistance, which is partially compensated. CEP-1 is partially required for activation of gst-4 when wdr-46 or other ribosome processing genes are silenced but not when translation initiations genes are silenced, indicating that disruptions to nucleolar function can activate SKN-1 which involves cep-1 and is independent of protein translation [Leung et al., 2011].
Deletion, depletion, or inhibition of p53 induces autophagy in human, mouse, and nematode cells. cep-1 mutants exhibit a prolonged lifespan. BEC-1 (Atg6/Beclin-1) did not affect wildtype lifespan, but reduced increased lifespan of cep-1 mutant down to approximately normal levels [Kudron and Reinke, 2008; 18728385].
Some mechanisms that are involved in DNA-damage checkpoint are also involved in germ cell “immortality” [Gartner et al., 2008; 18781708].
CEP-1 ceramid connection [Deng et al., 2008; 18832646].
smg-1 encodes a ser/thr kinase, inactivation extends lifespan which requires daf-18/PTEN and cep-1 and converges of daf-16. Human SMG-1 has also been implicated in p53 signalling [Masse et al., 2008; 18836529].
sir-2.1 genetically acts in parallel to cep-1.
CEP-1 increases or decreases lifespan depending on the level of mitochondrial bioenergetics stress. CEP-1 is required for lifespan extension by mild suppression of mitochondrial function, but also mediates the developmental arrest and life shortening by severe mitochondrial stress. Mild mitochondrial dysfunction induces a protective response in a hormetic-like fashion and extends lifespan. Lifespan extension induced by reduced expression of different mitochondrial proteins involved in electron transport chain functionally requires cep-1. Reducing expression of frataxin induces antioxidant glutathionine-S-transferase via CEP-1 [Ventura et al., 2009; 20172019].
[Figure: p53 dual role.]
CBP-1 (p300/CBP) functions as a cofactor for CEP-1. PRMT-5 forms a complex with both CEP-1 and CBP-1 and methylate the latter. PRMT-5 likely represses CEP-1 transcriptional activity through CBP-1 [Yang et al., 2009; 19521535]. CBP-1 is DR-essential and required for several anti-ageing drugs to prolong lifespan. CBP-1 is induced by bacterial dilution DR regimen.
Nucleolar proteins suppress innate immunity by suppressing CEP-1. NOL-6 a nuclear RNA-associated protein involved in ribosome biogenesis. Mutation or silencing NOL-6 or other nucleolar proteins results in changed resistance against bacterial infections. nul-6 mutation increased expression of CEP-1 regulated genes. Activation of innate immunity by inhibition of nucleolar proteins requires CEP-1 and its transcriptional target SYM-1. CEP-1 plays a role in apoptosis, meiosis and stress resistance [21, 51-54 in (Fuhrman et al., 2009); 19763173].
Expression of exo-3, the apurinic/apyrimidine endonuclease 1 (APE1) ortholog, is reduced by 45% during ageing. Suppression of cep-1, involved in downregulation of exo-3, increased exo-3 expression without an effect on ROS levels, preserved neuronal integrity and increased motility and lifespan. Suppression of trx-1 and trx-2, involved in redox chaperone activity of exo-3, overrides the protective effect of cep-1 RNAi on neuronal integrity neuronal function, mean and maximum lifespan [Schlotterer et al., 2010; 20346071].
HIF-1 upregulates TYR-2 in ASJ sensory neurons. TYR-2 is secreted to antagonize CEP-1 [Sendoel et al., 2010; 20520707]. Genome-wide analysis of germ cell proliferation identifies VRK-1 as a key negative regulator of CEP-1 [Waters et al., 2010; 20599896].
9-1-1 complex and PI3K-related protein ATR (sensor of DNA damage) are recruited to chromatin in presence of unrepaired meiotic DSBs in both females and males germlines. Checkpoint kinase CH-1 is phosphorylated and CEP-1 induces expression fo BH3-only pro-apoptic protein in germlines and of both sexes under activating conditions, Core cell death machinery is expressed in female and male germlines, but CED-3 caspase is not activated in male germline. Recombination checkpoint function in male germ cells to promote repair of meiotic recombination intermediates, thereby improving the fidelity of chromosome transmission in absence of apoptosis [Jaramillo-Lambert et al., 2010; 20970339].
gld-1/Notch mutations dramatically shortened lifespan due to germ cell tumour growth. Long lifespans of daf-2 mutants were not shortened at all by gld-1 mutations, as double mutations lived just as long as long-lived worms with just daf-2 mutation. This was attributed to decreased cell division and increased DAF-16/p53-dependent apoptosis specifically in the tumors. DR or inhibition of respiration did not affect apoptosis but reduced tumor cell divisions. None of these longevity mutations affected mitosis in normal germlines [ http://www.worldhealth.net/news/longevity_genes_fight_cancer_at_its_sour/].
Reduced insulin signalling (daf-2) [7,8 in (Pinkston et al., 2006)], DR (eat-2) [9 in (Pinkston et al., 2006)], disrupted respiratory chain components (isp-1) [10 in (Pinkston et al., 2006)] or ubiquinone production (clk-1) [11 in (Pinkston et al., 2006)] affect distinct pathways [3,4,9 in (Pinkston et al., 2006)], although they may converge on common downstream processes [Pinkston et al., 2006].
[Figure: Germcell signaling]
MAPK kinase signalling controls CEP-1-dependent apoptosis by several distinct pathways that converge on CEP-1 [Rutkowski et al., 2011; 21901106].
CEP-1 transcriptional stress response genes are mainly expressed in somatic tissues. Many genes evoked by ionizing radiation are transcriptional regulated in longevity mutants [Greiss et al., 2008; http://www.biomedcentral.com/1471-2164/9/334].
Genome-wide distribution of 19 histone modifications, one histone variant and eight chromatin-associated proteins in embryos and L3 larvae.
Dmp53 is dispensable for normal development [ 20308539]. Repression of fruit fly p53 increases survival. In Drosophila manipulating p53 function has developmental stage-, sex and stress-specific effects on lifespan. Mutating endogenous p53 had a sex-specific effect on lifespan [Waskar et al., 2009; 20157574].
In females flies, high levels of p53 function results in lifespan reduction, as expression of a DNp53 in extends lifespan, and hypmorphic and amorphic mutations of endogenous p53 result in lifespan extension and moderate stress resistance. In males however, it was the opposite, because increased p53 levels in adults results in longer lifespan. During larval development, moderate overexpression of p53 increased lifespan in both males and females.
Reduction in p53 function in adult neurons specifically had a beneficial effect on longevity. Lifespans of flies that have reduced p53 function in adult neuronal cells cannot be further extended by DR [9 in (Hur and Walker, 2009)]. dSir3 directly deacetylates p53, which inhibits its function as a transcriptional activator [11 in (Hur and Walker, 2009)]. A consequence of lowered p53 activity in adults neuron is the reduction of Drosophila insulin-like peptide 2 dIL2 [12 in (Hur and Walker, 2009)].
NF-Y transcriptional upregulates Dmp53 [21044877].
Dmp53 regulates neuronal stem cells self-renewal [Ouyang et al., 2011].
Loss of Dmp53 results in a reduced lifespan [Lee et al., 2003] and in mice overproduction of a short isoform of p53 accelerates ageing [Maier et al., 2004].
Daxx-like protein interacts with Dmp53 and affects longevity [Bodai et al., 2007].
Of 41 mammalian orthologs 37 bound to one or more p53-family members. Dmp53 interacts with itself. The Dmp53 interactome has a significant overrepresentation of genes associated with gametogenesis. Among the Dmp53 interactors were mitochondrial proteins. GTPBP4, which interacts with p53 is a nucleolar protein involved in 60S ribosome biogenesis. Most orthologs of in vitro Dmp53 interactors bound efficiently to TAp73α, which may have implication for p53 phylogenesis [6,12,15; 20308539].
Loss of Dmp53 results in a reduced lifespan while in mice overproduction of a short isoform of p53 accelerates ageing [7,11 in (Bodai et al., 2007)].
The process of meiotic recombination instigates programmed activation of p53 in the germ line. Like its mammalian counterpart, it coordinates stress responses and promotes genome stability [8-12 in (Lu et al., 2010)]. Transient p53 expression was observed in germ line precursor of all females. The pulse of p53 activity occurs in oocyte precursors. p53 was also transiently activated in early spermatocytes. It appeared to peak between the leptotene and zygotene stages and disappeared after the early pacheytene stage. A defining step in sexual reproduction, meiosis, signals a programmed burst of p53 activation. Activity is stimulated by Spo11 action in Drosophila female (recombination does not occur in males) and in mice. The activation in flies requires the kinase chk2. Flies lacking p53 are viable and fertile, thus it does not exert essential functions needed for gametogenesis or proper chromosome segregation (Lu et al., 2010). Might p53 function be to rejuvenate cells?
Even slight constitutive hyper-activation of p53 results in premature ageing phenotypes in rodents [6,7 in (Hur and Walker, 2009)]. Adult mice that express a hypermorphic truncated p53 allele display a dramatic reduction in incidence of cancer, but had an shortened lifespan and exhibit many hallmarks of early ageing [7 in (Hur and Walker, 2009)]. Increasing p53 function using a hypermorphic p53 allele speeds up ageing in mature animals by depleting stem cell pools [6 in (Hur and Walker, 2009)]. p63 is important in stem cells. Ectopical increased p53 might interrupt p63 functions.
p53 has been argued to mediate the effect of DR, via its interconnection with AMPK, IIS, SIRT1 and TOR1. p53 negatively regulates the insulin/IGF-1 and TOR signaling via its target genes (PTEN, AMPK, Sestrin 1/2, TSC2) and the activation of autophagy [Tucci, 2012; 22983298].
Optimal p63 DNA-binding conesus motif consists of a CA(T)TG core and a AT-rich 5’ and 3’ flanking sequence [Ortt and Sinha, 2006]. The determined consensus sequence is 5'-RRRC(A/G)(A/T)GYYYRRRC(A/T)(C/T)GYYY-3' [Perez et al., 2007]. p63 interacts with SATB2 [Chung et al., 2011; 21965674]. p53/63/p73-family transcriptional suppress IGF1-R [Werner, 2011; 21963847]. This resource claims to provide expression data of every single p53/63/73 family member isoform [Sbisa et al., 2007]).
REDD1 is a developmentally regulated transcriptional target of p63 and p53, which links p63 to the regulation of reactive oxygene species [Ellisen et al., 2002].
iASPP is an inhibitor of senescence. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is able to prevent premature cellular senescence in mouse embryonic fibroblasts. iASPP bound p63 and inhibits the transcriptional activity of both TAp63α and ΔNp63α in vitro and influenced expression of p63-regulated genes (such as loricrin and involucrin) in vivo [Notari et al., 2011; 21930934].
A novel p63 transcript (GTAp63) is specifically expressed in healthy human testes and germ cell precursors of human testes but not in testicular cancer cells. ERV-9 regulatory region to contribute to the maintenance of male germ line stability [Liu and Eiden, 2011; 21994760].
ΔNp63 is involved in multiple functions during skin development and in adult stem/progenitor cell regulation. TAp63 is a guardian of oocyte integrity and its endogenous expression is barely detectable in embryos and adult (except in oocytes). TAp63 is mainly expressed in ooxytes and induced in response to cellular stress [4] including wound healing [10]. TAp63 controls skin homeostasis by maintaining dermal and epidermal progenitor/stem cell pool and protecting them from senescence, DNA damage and genomic instability. TAp63 acts also in cell-nonautonous manner on adjancent cells. SKPs and endogenous dermal precursours, from which they derive, originate from neural crest. Skin-derived precursors (SKPs) in TAp63-/- mice exhibit rapid signs of premature ageing, senescence, DNA damage and genomic instability [35]. Tap63 deficiency in dermal stem cell compartment of the hair follicle is correlated with cellular senescence and hair loss. Such a senescence process associated with hair loss is also observed in normal ageing of wild type mice. p63 is regulated by miRNAs [19], but can also regulate miRNAs [20,21] and Dicer [21]. TAp63 isoform regulates senescence and suppresses tumorigenesis [23]. TAp63 is cirtical for skin homeostasis, maintaining epidermal and dermal stem cells in a healthy and functional state with intact genomes. Depletion of adult stem cells may be a major cuase of tissue ageing [47].
ChIP-seq and ChIP-on-chip analysis on somatic epithelial cells identified p63-target genes [17,58 in (Paris et al., 2011); http://www.nature.com/cdd/journal/vaop/ncurrent/full/cdd2011181a.html].
A cohort of miRNA including miR-138, -181a, -181b and -130b increased in expression with serial passages, miR-138m -181a an -181b, but not miR-130b overexpression was sufficient to induce senescence. Sirt1 is a direct target of miR-138m -181a and -181b, whereas ΔNp63 expression was inhibited by miR-130b. ΔNp63 inhibits miR-138, -181a, -181b and -130b expression by binding directly to p63-responseive elements located in close proximity. Changes in miRNA expression by modulating the levels of regulatory proteins like p63 and Sirt1 strongly contributes to induction of senescence [Cervo et al., 2012].
TAp63-/- mice are obese and diabetic through improper regulation of SIRT1 and AMPKα.
Both TAp73-/- and TAp63+/- mice display increased senescence and reduced lifespan. Absence of either TAp73 or TAp63 led to accelerated senescence in MEFs, with several microRNA targets being p63 targets. Ras-induced senescence was abrogated in TAp63-/- MEFs. Upon overexpression ΔNp63 promoted growth by regulating c-rel. β-catenin activates ΔNp63 [Kadakia et al., 2012].
Dmp53 interactions are very well conserved in mammals [Lunardi et al., 2010]. Dmp53 interactome is enriched for Zn, Chromatin remodeler (acetyltransferases such as Gcn5), transcription factors (e.g. HOX), heat shock factors, and respiration as well as reproductive terms.
TP63 is the founding ancestor of the p53-family members and it displays homology to the rejuvenation transcription factor Ndt80 [Figure: Evolutionary conservation of rejuvenation factors]. Ndt80 and TAp63Δ are to 21% (75/706) identical and to 32% (147/706) similar on the global level [Table: Global Alignment (Needlemann-Wunsch) of p63-family members], while exhibiting 23% (139/615) identity and 40% (243/615) similarity in a local alignment [Table: Local Alignment (Smith-Waterman) of p63-family members].
.. figure:: https://s3.amazonaws.com/DRessential/Evolutionary_conservation_of_rejuvenation_factors_a.png :width: 1200
**Figure: Evolutionary conservation of rejuvenation factors.**
TP63 is the founding ancestor of the p53/p63/p73-family members and it displays homology to the rejuvenation transcription factor Ndt80 [Figure: Multiple sequence alignment of Ndt80 with all p63 family members in worm, fly and humans]. Yeast NDT80 encodes a single gene product, C. elegans CEP-1 has two isoforms, D. melanogaster Dmp53 encodes three isoforms. In mammals, there are three different paralogs p53, p63 and p73 with p63 beeing the ancestor. p63 has two different transcriptional initiation sites generating proteins containing (TA) or lacking (DeltaN) an acidic transactivation domain. Alternative C-terminal splicing creates three splice variants (alpha, beta or gamma). These results in a minimum of six p63 isoforms at various levels of relative expression.
The process of meiotic recombination instigates programmed activation of Dmp53 in the germ line. Double-stranded breaks in DNA generated by the topoisomerase Spo11 provoked functional Dmp53 activity. Given the function of Dmp53 in meiosis it suggests that tumor-suppressive fucntions may have been co-opted form primordial activities linked to recombination.
p53/p63/p73-family members coordinate stress responses and promote genome stability [17310982; 14729967; 10860994; 12935877; 12672954].
Organisms lacking NDT80 and Dmp53 are viable and fertile. Mice lacking all p63 isoforms die at birth and exhibit severe developmental abnormalities.
p53-family members in fly and mammals are like NDT80 transiently induced during gametogenesis. Appeared to peak between the leptonene and dzygotene stages and disappears after early pachytene stage. A defining step in sexual reproduction, meiosis, signals a programmed burst of p53-family activation. Activity is stimulated by the action of Spo11 in Drosophila females (rembination does not occur in males) and in mice. Activation in flies requires kinase chk2 (which also has roles later in oogenesis) [12361566].
p53/p63/p73 regulate the miRNA processing complex [Liu et al., 2012].
hTERT promoter is strongly repressed by p53/p63/p73 family members. p53-mediates repression occurred through p53-dependent transcription inhibition of c-Myc or through E-box/E2F pathways, respectively. p63TAα-mediated repression occurred through Sp1, p63TAγ-mediated repression occurred through E2F signalling. P73α and p73β-mediated repression occurred through NF-YB2 [Yao et al., 2012].
Protein sequences were retrieved from UniProt, Muscle was used for creating a multiple sequence alignment which was utilized for Jalview and alignment coloured with Clustalx. The global and local alignments between two amino acid sequences were determined with the Needleman-Wunsch [5420325] and Smith-Waterman [Smith and Waterman, 1981] algorithm, respectively.
.. Blast Zbtb16 and make a multiple alignment, maybe with Ndt80. Compare recognition sequences. Zbtb16 is homologus to Zap1 and Azf1.
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Multiple sequence alignment via the Needleman-Wunsch algorithm of the members of the p63-family with Ndt80. Protein Ndt80 CEP-1a CEP-1b Dmp53a Dmp53b Dmp53g TAp63a TAp63b TAp63g DNp63a DNp63b DNp63g Ndt80 100 20 32 29 32 29 32 31 31 32 31 30 CEP-1a 18 100 31 26 23 26 20 22 24 21 23 26 CEP-1b 24 31 100 30 32 30 31 34 32 35 32 31 Dmp53a 23 22 24 100 77 100 28 34 36 27 37 39 Dmp53b 22 21 22 77 100 77 29 32 37 29 33 33 Dmp53g 23 22 24 100 77 100 28 34 36 27 37 39 TAp63a 21 18 21 22 21 22 100 82 70 86 68 56 TAp63b 23 19 22 24 19 24 82 100 84 68 83 67 TAp63g 24 21 23 25 23 25 70 84 100 56 67 80 DNp63a 22 18 22 20 19 20 86 67 55 100 79 65 DNp63b 24 19 21 23 18 23 67 83 66 79 100 81 DNp63g 24 21 22 24 22 24 55 66 80 65 80 100
.. In violate (left bottom) is percentage identity and in purple (right top) the percentage similarity
Multiple sequence alignment via the Smith-Waterman algorithm of the members of the p63-family with Ndt80. Protein Ndt80 CEP-1a CEP-1b Dmp53a Dmp53b Dmp53g TAp63a TAp63b TAp63g DNp63a DNp63b DNp63g Ndt80 100 39 39 40 43 40 40 42 41 40 43 42 CEP-1a 26 100 100 42 44 42 42 42 42 43 43 43 CEP-1b 24 100 100 45 45 45 41 41 42 41 41 41 Dmp53a 24 24 24 100 100 100 46 46 47 46 46 46 Dmp53b 21 24 23 99 100 100 46 46 46 47 47 47 Dmp53g 24 24 24 100 99 100 46 46 47 46 46 46 TAp63a 23 28 23 25 25 25 100 100 98 100 100 97 TAp63b 22 28 23 25 25 25 100 100 98 100 100 97 TAp63g 23 28 24 26 26 26 97 97 100 97 97 100 DNp63a 23 28 22 25 25 25 100 100 96 100 100 97 DNp63b 22 28 22 25 25 25 100 100 96 100 100 97 DNp63g 23 28 23 26 26 26 96 96 100 96 96 100
.. In violate (left bottom) is percentage identity and in purple (right top) the percentage similarity
Multiple sequence alignment via the Needlemann Wunsch algorithm of Zbtb16 and Psq protein. Protein ZBTB16b ZBTB16a Psq L Psq I Psq H Psq K Psq J Psq E Psq D Psq G Psq F Psq A Psq C Psq B ZBTB16b 100 82 34 34 35 34 34 35 35 35 35 31 30 30 ZBTB16a 82 100 34 32 32 32 32 32 32 32 32 27 27 27 Psq L 23 22 100 34 34 34 34 34 34 34 34 48 48 48 Psq I 19 21 22 100 99 100 100 99 99 99 99 58 60 60 Psq H 19 21 23 99 100 99 99 100 100 100 100 59 61 61 Psq K 19 21 22 100 99 100 100 99 99 99 99 58 60 60 Psq J 19 21 22 100 99 100 100 99 99 99 99 58 60 60 Psq E 19 21 23 99 100 99 99 100 100 100 100 59 61 61 Psq D 19 21 23 99 100 99 99 100 100 100 100 59 61 61 Psq G 19 21 23 99 100 99 99 100 100 100 100 59 61 61 Psq F 19 21 23 99 100 99 99 100 100 100 100 59 61 61 Psq A 22 21 48 58 59 58 58 59 59 59 59 100 98 98 Psq C 22 21 47 60 61 60 60 61 61 61 61 98 100 100 Psq B 22 21 47 60 61 60 60 61 61 61 61 98 100 100
Multiple sequence alignment via the Smith Waterman algorithm of Zbtb16 and Psq protein. Protein ZBTB16b ZBTB16a Psq L Psq I Psq H Psq K Psq J Psq E Psq D Psq G Psq F Psq A Psq C Psq B ZBTB16b 100 82 45 41 41 41 41 41 41 41 41 41 41 41 ZBTB16a 82 100 42 40 40 40 40 40 40 40 40 42 42 42 Psq L 24 22 100 42 42 42 42 42 42 42 42 90 90 90 Psq I 19 21 24 100 100 100 100 100 100 100 100 97 100 100 Psq H 19 21 24 100 100 100 100 100 100 100 100 97 100 100 Psq K 19 21 24 100 100 100 100 100 100 100 100 97 100 100 Psq J 19 21 24 100 100 100 100 100 100 100 100 97 100 100 Psq E 19 21 24 100 100 100 100 100 100 100 100 97 100 100 Psq D 19 21 24 100 100 100 100 100 100 100 100 97 100 100 Psq G 19 21 24 100 100 100 100 100 100 100 100 97 100 100 Psq F 19 21 24 100 100 100 100 100 100 100 100 97 100 100 Psq A 22 21 87 97 97 97 97 97 97 97 97 100 98 98 Psq C 22 21 87 100 100 100 100 100 100 100 100 98 100 100 Psq B 22 21 87 100 100 100 100 100 100 100 100 98 100 100