As part of the  inflammatory  response, ATP activates the  P2RX7  receptor, triggering a drop in intracellular  potassium  levels and the formation of  inflammasomes


Microglial  activation in the CNS via purinergic signalling


Clopidogrel  (Plavix), an inhibitor of the  P2Y12  receptor, was formerly the second best-selling drug in the world [ 61 ]


Schematic representation of the Ran cycle


Ran cycle involvement in nucleocytoplasmic transport at the nuclear pore


The postsynaptic  dendrite  (green) and presynaptic neuron (yellow) found in  retrograde neurotransmission.


Feedback loop found in retrograde neurological signaling.


Function of scaffold proteins [ 1 ]


Crystal structure of NpSRII-HtrII complex dimer. SRII is in blue. View is along the membrane, extracellular space is on the top. Only transmembrane helices of HtrII are resolved.


This is a figure shows several different brain imaging scans using [ 18 F]ISO-1 sigma-2 receptor ligands. The scans allow tracking of  tumor  growth and cancer progression over a 10-week period. The figure also includes  MRI  scans for comparison with PET scans.


Src-associated adaptor protein Skap2 with 1u5e code


Simplified representation of major signal transduction pathways in mammals.


3D Medical animation still showing signal transduction.


An overview of integrin-mediated signal transduction, adapted from Hehlgens  et al.  (2007). [ 37 ]


How to read signal transduction diagrams, what does normal arrow and flathead arrow means.


Elements of Signal transduction cascade networking


Occurrence of the term "signal transduction" in  MEDLINE -indexed papers since 1977


Gene Structure :  Chromosome: 1; NC_000001.10 (167778625..167883453, complement)


Crystal Structure of Ste5 Protein


Suppressor of Cytokine Signaling 2


Antigen presentation  stimulates T cells to become either  "cytotoxic" CD8+ cells  or  "helper" CD4+ cells .


T-cell receptor complexed with  MHC I  and  MHC II


Activation of macrophage or B cell by T helper cell


T-cell dependent B-cell activation, showing TH2-cell (left) B-cell (right) and several interaction molecules self-made according to Janeway et al,  Immunologie  (Berlin, 2002)


Antigen presentation stimulates naïve CD8+ and CD4+ T cells to become mature  "cytotoxic" CD8+ cells  and "helper" CD4+ cells respectively .


T h 1/T h 2 Model for helper T cells. An antigen is ingested and processed by an  APC . It presents fragments from it to T cells. The upper, T h 0, is a T helper cell. The fragment is presented to it by  MHC2 . [ 24 ]  IFN-γ,  interferon γ ; TGF-β,  transforming growth factor β ; mø,  macrophage ; IL-2,  interleukin 2 ; IL-4,  interleukin 4


TGF Beta ligand binds to receptor


Type II receptor recruits type I receptor and phosphorylates


Type I receptor phosphorylates R-SMAD


R-SMAD binds coSMAD


R-SMAD-coSMAD complex enters nucleus


Histopathology of thyroid parenchyma with autolytic changes seen at  autopsy , with  thyroid follicular cells  sloughing off into the follicles.


A  Diagram of the process of autophagy, which produces the structures  autophagosomes  (AP), and  autolysosomes  (AL);  B  Electron micrograph of autophagic structures AP and AL in the  fat body  of a  fruit fly  larva;  C  Fluorescently-labeled autophagosomes AP in liver cells of starved mice.


Cartoon of cleavage furrow formation and resolution. (A) depicts a normal cleavage furrow resolution. (B) depicts a cleavage furrow regression leading to a binucleated cell


The binucleated cell above is an oral squamous cell carcinoma, cell line UPCI-SCC-103. A: The cancer cell treated with antibodies against tubulin. B: The same cancer cell stained with DAPI, highlighting the nuclei. C: Both photos superimposed.


Dosage-response curves


Fig. 1  Immunofluorescence patterns of cyclin B and phosphorylated cyclin-dependent kinase1 (Cdk1) in HeLa cells change as they go from G2 to anaphase.


Fig. 2  Irreversible and bistable switch in mitotic exit with control parameter being Sic1 level and order parameter being cell cycle phases.


Fig. 3  Simplified network involving Cdk1-Clb2, APC-Cdh1, Sic1, and Cdc14. Double negative feedback loop, mediated by APC-Cdh1 and Sic1, is required to suppress Cdk1-Clb2 and trigger mitotic exit.


Diagram illustrating the movement of a branch point between two homologous pieces of DNA.  Migration travels to the left and stops when it reaches the end of the homologous region.  The second branch point on the right is free to move in either direction as well.


Open X structure of a Holliday junction.  RuvA binds to the DNA and fits in between the double strands on all four sides.  RuvA also has a domain that fits inside the centre of the junction.


The Holliday junction converts between the open X structure (top) and the stacked X structure (bottom) depending on the Mg 2+  concentration.


Overview of signal transduction pathways involved in  apoptosis


Morphological changes associated with apoptosis


Example events in autophagy


Cell division in prokaryotes ( binary fission ) and eukaryotes ( mitosis  and  meiosis ). The thick lines are chromosomes, and the thin blue lines are fibers pulling on the chromosomes and pushing the ends of the cell apart.


The  cell cycle  in eukaryotes:  I = Interphase, M = Mitosis, G 0  = Gap 0, G 1  = Gap 1, G 2  = Gap 2, S = Synthesis, G 3  = Gap 3.


Divisome and elongasome complexes responsible for peptidoglycan synthesis during lateral cell-wall growth and division. [ 13 ]


The phases (ordered counter-clockwise) of cell division ( mitosis ) and the  cell cycle  in animal cells.


Image of the  mitotic spindle  in a human cell showing  microtubules  in green, chromosomes (DNA) in blue, and kinetochores in red.  [ citation needed ]


Cell division over 42. The cells were directly imaged in the cell culture vessel, using non-invasive  quantitative phase contrast time-lapse microscopy . [ 38 ]


Kurt Michel with his phase-contrast microscope


Cell division, growth & proliferation


Cell division without cell growth during embryonic cleavage


Figure 1:Cell cycle and growth


Cell growth


Chromosomes


Cell division, growth, and proliferation


Stem cell  differentiation into various animal tissue types


Cell-count distribution featuring cellular differentiation for three types of cells (progenitor

 z

 {\displaystyle z}

 , osteoblast

 y

 {\displaystyle y}

 , and chondrocyte

 x

 {\displaystyle x}

 ) exposed to pro-osteoblast stimulus. [ 1 ]


Micrograph  showing  some dedifferentiation , (at left edge of image). + A  differentiated  component, showing  lipoblasts  and increased  vascularity , (right edge of image). +  Fully differentiated   adipose tissue , showing a few blood vessels, (center of image). ( Micrograph  of  liposarcoma  prepared with  H&E stain ).


Diagram exposing several methods used to revert adult somatic cells to  totipotency  or  pluripotency .


Mechanisms of cellular differentiation


An overview of major signal transduction pathways.


Cells subjected to heat shock. Cells in slide 'e' exhibit dysmorphic nuclei as a result of this exposure to stress, however 24 hours later cells largely recovered, as shown in slide 'f'.


Francis Crick's 1958 figure showing various information transfers


Unusual flows of information highlighted in green


In  August Weismann 's  germ plasm  theory, the hereditary material, the germ plasm, is confined to the  gonads . Somatic cells (of the body)  develop afresh  in each generation from the germ plasm. Whatever may happen to those cells does not affect the next generation.


Crossing over occurs between prophase I and metaphase I and is the process where two homologous non-sister chromatids pair up with each other and exchange different segments of genetic material to form two recombinant chromosome sister chromatids. It can also happen during mitotic division, [ 1 ]  which may result in loss of heterozygosity. Crossing over is important for the normal segregation of chromosomes during meiosis. [ 2 ]  Crossing over also accounts for genetic variation, because due to the swapping of genetic material during crossing over, the  chromatids  held together by the  centromere  are no longer identical. So, when the chromosomes go on to meiosis II and separate, some of the daughter cells receive daughter chromosomes with recombined alleles. Due to this genetic recombination, the offspring have a different set of alleles and genes than their parents do. In the diagram, genes B and b are crossed over with each other, making the resulting recombinants after meiosis Ab, AB, ab, and aB.


Thomas Hunt Morgan's illustration of crossing over (1916)


A double crossing over


A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with a homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.


The difference between  gene conversion  and  chromosomal crossover .


Histopathology of a  pheochromocytoma  with coagulative necrosis, displayed at gross pathology (upper left) and light microscopy at low (upper right), medium (lower left) and high magnification (lower right).


A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.


Chloroplasts can be seen travelling around the central vacuole of a cell in  Rhizomnium punctatum


Top: Idealized cytoplasmic flow in hyphae of  Neurospora crassa . Bottom: Actual cytoplasmic flow in hyphae of  Neurospora crassa . Microtubules (red) orient themselves perpendicular to flow as they exit the septal hole, deaccelerating the flow faster than the idealized case preventing the formation of eddies on the downstream side of the septum. Nuclei and other proteins aggregate on the upstream side which maintain the integrity of the septum.


Density-dependent fecundity


Parasite-induced vector mortality


Density-dependence processes (red) in filariasis life cycle


DNA damage in non-replicating cells, if not repaired and accumulated can lead to aging. DNA damage in replicating cells, if not repaired can lead to either apoptosis or to cancer.


Initiation of  DNA demethylation  at a  CpG site . In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides ( CpG sites ), forming  5-methylcytosine -pG, or 5mCpG. Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming  8-hydroxy-2'-deoxyguanosine  (8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site.  The  base excision repair  enzyme  OGG1  targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits  TET1  and TET1 oxidizes the 5mC adjacent to the 8-OHdG.  This initiates demethylation of 5mC. [ 83 ]


DNA damage resulting in multiple broken chromosomes


Structure of the base-excision repair enzyme  uracil-DNA glycosylase  excising a hydrolytically-produced uracil residue from DNA. The uracil residue is shown in yellow.


The main double-strand break repair pathways


DNA ligase, shown above repairing chromosomal damage, is an enzyme that joins broken nucleotides together by catalyzing the formation of an internucleotide  ester  bond between the phosphate backbone and the deoxyribose nucleotides.


DNA repair rate is an important determinant of cell pathology.


Most life span influencing genes affect the rate of DNA damage.


A chart of common DNA damaging agents, examples of lesions they cause in DNA, and pathways used to repair these lesions. Also shown are many of the genes in these pathways, an indication of which genes are epigenetically regulated to have reduced (or increased) expression in various cancers. It also shows genes in the error-prone microhomology-mediated end joining pathway with increased expression in various cancers.


Initiation of  DNA demethylation  at a  CpG site . In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides ( CpG sites ), forming  5-methylcytosine -pG, or 5mCpG. Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming  8-hydroxy-2'-deoxyguanosine  (8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site. The  base excision repair  enzyme  OGG1  targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits  TET1  and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates demethylation of 5mC. [ 132 ]


DNA replication: The  double helix  is 'unzipped' and unwound, then each separated strand (turquoise) acts as a template for replicating a new partner strand (green).  Nucleotides  (bases) are matched to synthesize the new partner strands into two new double helices.


The structure of the DNA  double helix  (type  B-DNA ). The  atoms  in the structure are color-coded by  element  and the detailed structures of two  base pairs  are shown in the bottom right.


DNA polymerases adds nucleotides to the 3′ end of a strand of DNA. [ 21 ]  If a mismatch is accidentally incorporated, the polymerase is inhibited from further extension. Proofreading removes the mismatched nucleotide and extension continues.


Overview of the steps in DNA replication


Steps in DNA synthesis


Role of initiators for initiation of DNA replication


Formation of pre-replication complex


Scheme of the replication fork. a: template, b: leading strand, c: lagging strand, d: replication fork, e: primer, f:  Okazaki fragments


Many enzymes are involved in the DNA replication fork.


The assembled human DNA clamp, a  trimer  of the protein  PCNA


E. coli Replisome. Notably, the DNA on lagging strand forms a loop. The exact structure of replisome is not well understood.


The cell cycle of eukaryotic cells


Dam methylates adenine of GATC sites after replication


Replication fork restarts by homologous recombination following replication stress


Epigenetic consequences of nucleosome reassembly defects at stalled replication forks


Dynamin assembled into helical polymers as visualized by negative stain electron microscopy. [ 5 ]


Micrograph  showing emperipolesis in a case of  Rosai-Dorfman disease .  H&E stain .


Endoplasmic-reticulum-associated protein degradation is one of several protein degradation pathways in the ER


Human embryo—length, 2 mm. Dorsal view, with the amnion laid open. X 30.


Key inducers of the epithelial to mesenchymal transition process.


Epithelial to mesenchymal cell transition – loss of cell adhesion leads to constriction and extrusion of newly mesenchymal cell.


Cancer cells enter the bloodstream after undergoing EMT induced by TGF-β released from platelets. Once in the bloodstream, metastatic cancer cells recruit platelets for use as a physical barrier that helps protect these cells from elimination by immune cells. The metastatic cancer cell can use the attached platelets to adhere to P-selectin expressed by activated endothelial cells lining the blood vessel walls. Following adhesion to the endothelium, the metastatic cancer cell exits the bloodstream at the secondary site to begin formation of a new tumor.


Human prostate cancer cells undergoing ferroptosis


Initiation of ferroptosis by inhibition of Xc- system of  GPX4  activity


Induction of neurodegeneration by Ferroptosis


Structures of small molecule inducers of ferroptosis (erastin, IKE, RSL3, ML162)


Mechanism of ML210 prodrug activation (adapted from PMID 32231343) [ 103 ]


Structures of GCL inhibitors (BSO, KOJ-1, KOJ-2)


Structures of FSP1 inhibitors (iFSP1, viFSP1, FSEN1, icFSP1)


A renal biopsy from a patient with  anti-neutrophil cytoplasmic antibody  (ANCA)-associated  glomerulonephritis  reveals a lesion characterized by bright  eosinophilia  on  H&E staining  (yellow arrow, left) and intense red staining with  trichrome  (right), confirming the presence of fibrinoid necrosis. [ note 1 ]


An H&E  micrograph  showing (intensely pink) fibrinoid necrosis (large blood vessel – right of image) in a case of  vasculitis  ( eosinophilic granulomatosis with polyangiitis ).


An  H&E -stained  micrograph  of a rheumatoid nodule reveals its characteristic histological structure, featuring a central core composed of fibrinoid necrosis, and surrounding this core is a layer of  palisading   macrophages  and  epithelioid histiocytes .


A  Bacillus cereus  cell that has undergone filamentation following antibacterial treatment (upper electron micrograph; top right) and regularly sized cells of untreated  B. cereus  (lower electron micrograph)


Domain structure of formin proteins across phyla. [ 1 ]


A model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left. Most recombination events appear to be the SDSA type.


Thomas Hunt Morgan 's illustration of crossing over (1916)


Schematic representation of the s2m RNA secondary structure, with tertiary structural interactions indicated as long range contacts.


The diagram depicts actions taken when a stress is introduced to the cell. Stress will induce HSF-1 and cause proteins to misfold. Molecular chaperones will aid these proteins to fold correctly or if the degree of misfolding is too severe, the protein will be eliminated through the proteasome or autophagy.


Front view of the human enzyme Histone Lysine N-Methyltransferase, H3 lysine-4 specific.


Epigenetic mechanisms


Scanning electron micrograph  of a phagocyte (yellow, right) phagocytosing  anthrax bacilli  (orange, left)


Haeckel's monograph in which the ability of blood cell to ingest particles is first reported


The conserved  secondary structure  of  sok   non-coding RNA  transcript which binds with  hok  mRNA.


Intracellular transport between the  Golgi apparatus  and the  endoplasmic reticulum


How SNARE proteins play a role in intracellular transport


A cytoplasmic dynein motor bound to a microtubule.


A kinesin molecule bound to a microtubule.


How microtubules play a role in intracellular transport


Intraflagellar transport in the cilia of the nematode  C. elegans


A simplified model of intraflagellar transport.


A sheet of cells undergoing invagination


Apical constriction leading to invagination of a monolayer of cells


Formation of the ventral furrow in a  Drosophila  embryo. Cell nuclei (blue), membranes (green), and myosin (red) are stained.


Cartoon of neural tube formation in a mouse embryo, showing the median hinge point and points of tissue buckling along the sides


Invagination of the archenteron during sea urchin gastrulation


Invagination process in an amphioxus


Morphological characteristics of karyolysis and other forms of nuclear destruction.


Apoptosis


In meiosis, the  chromosomes  duplicate (during  interphase ) and  homologous chromosomes  exchange genetic information ( chromosomal crossover ) during the first division, called  meiosis I . The daughter cells divide again in  meiosis II , splitting up  sister chromatids  to form haploid  gametes . Two gametes fuse during  fertilization , forming a diploid cell ( zygote ) with a complete set of paired chromosomes.


Meiosis Prophase I in mice. In Leptotene (L), the axial elements (stained by SYCP3) begin to form. In Zygotene (Z), the transverse elements (SYCP1) and central elements of the synaptonemal complex are partially installed (appearing as yellow as they overlap with SYCP3). In Pachytene (P), it is fully installed except on the sex chromosomes. In Diplotene (D), it disassembles revealing chiasmata. CREST marks the centromeres.


Schematic of the synaptonemal complex at different stages of prophase I and the chromosomes arranged as a linear array of loops.


Diplontic life cycle


Haplontic life cycle.


Overview of chromatides' and chromosomes' distribution within the mitotic and meiotic cycle of a male human cell


Mitotic recombination can result in homozygous expression in a heterozygous individual [ dead link  ]


The Necroptosis Signaling Pathway


Structural changes of cells undergoing necrosis and  apoptosis


Karyolysis  (and  contraction band necrosis ) in  myocardial infarction  (heart attack)


Examples of different levels of nuclear architecture.


The hierarchical structure through which DNA is packaged into chromosomes.


A cartoon representing an enhancer interacting with genes through DNA looping.


The 23 human  chromosome territories  during  prometaphase  in  fibroblast  cells


Micrograph  of an  ameloblastoma  showing characteristic palisading.  H&E stain .


Structure of a rosette in pathology.


Rosettes  are named after the  flower-like architectural ornament . [ 2 ]


Flexner–Wintersteiner rosettes  in  Retinoblastoma .


Micrograph of Homer-Wright pseudorosettes


Palisading in nodular  basal-cell carcinoma .


PARP-1 protein domain breakdown


Overview of phagocytosis


Phagocytosis versus exocytosis


The engulfing of a pathogen by a phagocyte


Scanning electron micrograph  of a phagocyte (yellow, right) phagocytosing  anthrax bacilli  (orange, left)


Trophozoites of  Entamoeba histolytica  with ingested erythrocytes


Phagoptosis occurs when signals on the surface of a (target) cell activate phagocytic receptors on a phagocyte, inducing uptake into a phagosome, where the cell is killed and digested.


Pinocytosis


Certain transcripts contain poison exons that can be incorporated via alternative splicing. Skipping of the poison exon leads to a productive transcript that is translated to protein. Incorporation of the poison exon introduces a premature termination codon into the transcript that leads to degradation of the transcript via nonsense-mediated decay. (PDB: 2N3L)


Prophase is the first step of cell division in mitosis. As it occurs after G2 of interphase, DNA has been already replicated when prophase begins. [ 1 ]


Fluorescence microscope  image of two mouse cell nuclei in prophase (scale bar is 5 μm). [ 2 ]


Arabidopsis thaliana  cell in preprophase, prophase and prometaphase. Preprophase band is present along the cell wall from images 1–3, is fading in image 4, and disappears by image 5. [ 1 ]


Apoptosis


Morphological characteristics of pyknosis and other forms of nuclear destruction


Original caption: [ 7 ]  Histopathological findings of the resected left adrenal gland (September 2009). a Gross appearance of the cut surface of the left adrenal tumor 3 cm in size showed the inferior surface to be necrotic. b−i Microscopic examination of the left adrenal tumor (b, d−f; hematoxylin and eosin staining. c, g−i; chromogranin A staining). Nontumoral adrenal gland in the right lower corner, and well-encapsulated tumor in the remainder of the photograph (b). The tumor had a large area of coagulative necrosis in the center. The necrotic material contained morphologically ghost cells (d, e) and was immunohistochemically markedly positive for chromogranin A (c, g, h). There were numerous hemosiderin-laden macrophages and histiocytes accompanied by vascular proliferation in the region adjacent to the area of necrosis (e, h). The viable region along the periphery of the tumor contained numerous cells undergoing pyknosis (f), and the cytoplasm of the tumor cells was positive for chromogranin A staining (i) [ 7 ]


Apoptotic DNA laddering visualized in  agarose gel . DNA from cells treated with an apoptotic inducing substance (left). A  1 kb   marker  (middle). Untreated cell DNA (right)


Mechanism of clathrin-dependent endocytosis


Endocytosis is triggered when a specific receptor is activated in receptor-mediated endocytosis.


rRNA biogenesis and assembly in prokaryote and eukaryotes. Notably in Eukaryotes 5S rRNA is synthesised by  RNA polymerase III  whereas other eukaryote rRNA molecules are transcribed by  RNA polymerase I .


Elderly  Klamath  woman photographed by  Edward S. Curtis  in 1924


Past and projected age of the human world population through time as of 2021 [ 75 ]


Healthspan-lifespan gap (LHG) [ 75 ]


Healthspan extension relies on the unison of social, clinical and scientific programs or domains of work. [ 75 ]


schematic domain structure of septin polypeptide chain


a) schematic of septin molecule with GTP binding domain to one side and the N and C termini of the polypeptide chain to the other  b) schematic of septin heterohexameric complex (of human septins), where different septins bind to each other via their GTP binding domains or via the N and C termini. Note the symmetry of the complex   c) schematic how septin complexes could align to form septin filaments


Septins in  Saccharomyces cerevisiae   (fluorescent micrograph)  • Green: septins ( AgSEP7- GFP )  • Red: cell outline ( phase contrast )  • Scale bar: 10 μm


Septins in  Ashbya gossypii   (fluorescent micrograph) • Green: septins ( AgSEP7- GFP )  • Red: cell outline ( phase contrast )  • Inlay: 3D reconstruction of a discontinuous septin ring  • Scale bars: 10 μm


Fig. 1. Tyr-Recombinases: Details of the crossover step. Top: Traditional view including strand-exchange followed by branch-migration (proofreading). The mechanism occurs in the framework of a synaptic complex (1) including both DNA sites in parallel orientation. While branch-migration explains the specific homology requirements and the reversibility of the process in a straightforward manner, it cannot be reconciled with the motions recombinase subunits have to undergo in three dimensions. Bottom: Current view. Two simultaneous strand-swaps, each depending on the complementarity of three successive bases at (or close to) the edges of the 8-bp spacer (dashed lines indicate base-pairing). Didactic complications arise from the fact that, in this model, the synaptic complex must accommodate both substrates in an anti-parallel orientation. This synaptic complex (1) arises from the association of two individual recombinase subunits ("protomers"; gray ovals) with the respective target site. Its formation depends on inter-protomer contacts and DNA bending, which in turn define the subunits (green) with an active role during the first crossover reaction. Both representations illustrate only one half of the respective pathway. These parts are separated by a Holliday junction/isomerization step before the product (3) can be released.


Fig. 2. Ser-Recombinases: The (essentially irreversible) subunit-rotation pathway. Contrary to Tyr-recombinases, the four participating DNA strands are cut in synchrony at points staggered by only 2 bp (leaving little room for proofreading). Subunit-rotation (180°) permits the exchange of strands while covalently linked to the protein partner. The intermediate exposure of double-strand breaks bears risks of triggering illegitimate recombination and thereby secondary reactions. Here, the synaptic complex arises from the association of pre-formed recombinase dimers with the respective target sites (CTD/NTD, C-/N-terminal domain). Like for Tyr-recombinases, each site contains two arms, each accommodating one protomer. As both arms are structured slightly differently, the subunits become conformationally tuned and thereby prepared for their respective role in the  recombination cycle. Contrary to members of the Tyr-class the recombination pathway converts two different substrate sites (attP and attB) to site-hybrids  (attL and attR) . This explains the irreversible nature of this particular recombination pathway, which can only be overcome by auxiliary "recombination directionality factors" (RDFs).


Fig. 3A. Reversible insertion and excision by the Cre-lox system.


Fig. 3B. Inversion by the Cre-lox system.


Cell growth, division & proliferation


Regulation of transcription in mammals . An active enhancer regulatory region of DNA is enabled to interact with the  promoter  DNA region of its target  gene  by the formation of a chromosome loop. This can initiate  messenger RNA  (mRNA) synthesis by  RNA polymerase II  (RNAP II) bound to the promoter at the transcription start site of the gene. The loop is stabilized by one architectural protein anchored to the enhancer and one anchored to the promoter and these proteins are joined to form a dimer (red zigzags). Specific regulatory  transcription factors  bind to DNA sequence motifs on the enhancer. General transcription factors bind to the promoter. When a transcription factor is activated by a signal (here indicated as  phosphorylation  shown by a small red star on a transcription factor on the enhancer) the enhancer is activated and can now activate its target promoter. The active enhancer is transcribed on each strand of DNA in opposite directions by bound RNAP IIs. Mediator (a complex consisting of about 26 proteins in an interacting structure) communicates regulatory signals from the enhancer DNA-bound transcription factors to the promoter.


This shows where the methyl group is added when 5-methylcytosine is formed


Schematic  karyogram  of a human, showing an overview of the  human genome  on  G banding , wherein the lighter regions are generally more transcriptionally active, whereas darker regions are more inactive, including  non-coding DNA . Further information:  Karyotype


Simple diagram of transcription elongation


Image showing RNA polymerase interacting with different factors and DNA during transcription, especially CTD (C Terminal Domain)


The Image shows how CTD is carrying protein for further changes in the RNA


Electron micrograph  of transcription of ribosomal RNA. The forming  ribosomal RNA  strands are visible as branches from the main DNA strand. [ citation needed ]


Scheme of  reverse transcription


Overview of eukaryotic  messenger RNA  (mRNA) translation


Translation of mRNA and ribosomal  protein synthesis


Initiation and elongation stages of translation involving RNA  nucleobases , the ribosome,  transfer RNA , and  amino acids


The three phases of translation: (1) in initiation, the small ribosomal subunit binds to the RNA strand and the initiator tRNA–amino acid complex binds to the start codon, culminating in attachment of the large subunit; (2) elongation occurs as a cycle, in which codons are sequentially recognized by charged tRNAs, followed by peptide bond formation with transfer of the polypeptide between tRNAs within the ribosome and finally translocation of the ribosome to the next codon; (3) termination, when a stop codon is reached, a release factor binds and the  polypeptide  is released (note that labels for translocation and peptide bond formation are reversed in this image)


A ribosome translating a protein that is secreted into the  endoplasmic reticulum  (tRNAs colored dark blue)


Tertiary structure of tRNA ( CCA tail  in yellow,  Acceptor stem  in purple,  Variable loop  in orange,  D arm  in red,  Anticodon arm  in blue with  Anticodon  in black,  T arm  in green)


Figure M0. Basic and the simplest model  M0  of protein synthesis.  Here, * M – amount of mRNA with translation initiation site not occupied by assembling ribosome, * F – amount of mRNA with translation initiation site occupied by assembling ribosome, * R – amount of ribosomes sitting on mRNA synthesizing proteins, * P – amount of synthesized proteins. [ 23 ]


Figure M1'. The extended model of protein synthesis  M1  with explicit presentation of 40S, 60S and initiation factors (IF) binding. [ 23 ]


5' TL elements regulate translation initiation.


A simplified diagram of the processes involved in protein folding. The polypeptide is translated from its ribosome directly into the ER, where it is glycosylated and guided through modification steps to reach its desired conformation. It is then transported from the ER to the Golgi apparatus for final modifications. Where misfolding proteins continually breach quality control, chaperones including Grp78 facilitate its removal from the ER through retrotranslocation, where it is broken down by the ubiquitin-proteasome pathway as part of the ERAD system.


A simplified diagram of the initiation of the UPR by prolonged and overwhelming protein misfolding. Grp78 recruitment to chaperone the misfolded proteins results in Grp78 dissociation from its conformational binding state of the transmembrane receptor proteins PERK, IRE1 and ATF6. Dissociation results in receptor homodimerisation and oligomerisation to an active state. The activated cytosolic domain of PERK phosphorylates the eIF2alpha, inhibiting translation and resulting in cell cycle arrest. The activated cytosolic domain of IRE1 cleaves the 26bp intron from its substrate  XBP1 , facilitating its translation to form the transcription factor  XBP1 . Activated ATF6 translocates to the Golgi, cleaved by proteases to form an active 50kDa fragment (ATF6 p50). ATF6 p50 and  XBP1  bind ERSE promoters in the nucleus to produce upregulation of the proteins involved in the unfolded protein response.


Figure showing part of the female colony of  Halecium beanii , from an 1873 article by  George James Allman [ 6 ]


Q J Microsc Sci  cover with  Company of Biologists


A Russian edition of the journal


Structured Digital Abstract logo


NIH-3T3 fibroblasts in  cell culture .


Differentiated adipocytes in a 3T3-L1 cell line stained with  Oil Red O


A549 cells under  DIC microscopy , from a 3-4 days old culture, showing an abundance of intercellular connections, including possible  cytonemes ,  filopodia  and other epithelial bridges. (These cells have endocytosed 25x73 nm  colloidal gold  nanorods.)


Intercalary located akinete of  Dolichospermum smithii


Terminally located akinete of  Gloeotrichia


Schematic representation of a  protein electrophoresis  gel


Labelled diagram of ciliate with highlighted cytoproct (anal pore)


Anatomical diagram of a  cydippid comb jelly .


Bathocyroe fosteri  with anal pore.


Actions of the major  digestive hormones  secreted by APUD cells


Reproduction of Radiococcus and Tetracoccus by forming 4 autospores within a single cell


Trypanochloris can form more than 128 autospores from a single cell. [ 6 ]


Differential interference contrast microscopy  image of  Pseudokirchneriella subcapitata  cells dividing in two, four, and eight-autospore formation. [ 7 ]


Birbeck granules


The fluorescent staining of yeast with calcofluor-white. The cell walls fluoresce to a vivid blue color.


The cross section of an Eagle Fern shows the bright green and bright blue fluorescence seen with CFW.


Catabolite Activator Protein (blue) bound to a piece of DNA (red).


A  ribosome  is a  biological machine  that utilizes  protein dynamics  on  nanoscales  to  translate  RNA into proteins


This illustration shows where the cisternae can be found on the Golgi apparatus. As well as the location of the cis and trans Golgi network.


Cells without (left) and with (right) Detention Centers


Monod's original results on Diauxie. Time in hours is plotted on the horizontal axis. Optical density (equivalent to cell concentration) is plotted on the vertical axis.


Bottle of DMEM cell culture medium


Figure 1:  A) Architecture of the common C-terminal and N-terminal domains; B) The crystal structure of mouse EHD2 dimer. The top monomer is colored to match the domain architecture depicted in (A) [ 2 ]


Figure 2:  Proposed model of EHD facilitated endocytosis [ 6 ]


Encapsulin-capsid components are shown in purple. Cargo proteins are shown in teal. Non-cargo accessory components are shown in grey. Dotted lines show optional operon components.


Different types of  plastid


Ex vivo  brainstem: (A)  coronal  view displaying the anterior portion of the tissue sample, (B)  sagittal  view displaying the left-hand side of the tissue sample [ 1 ]


Gonadotropic Cell with FSH Granule


Signaling Pathway in Gonadotropic Cell Initiated by GnRH Binding to GnRHR


Endocrine System with FSH and LH Produced by Gonadotropic Cells in Anterior Pituitary


Figure 1. Diagram of Notch Signaling Pathway for Hairless Gene in Drosophila


Figure 2. Hand-drawn Image Showing the Differing Phenotypes Between the Wild Type ("wt") and Hairless ("H") Drosophila.


The p53 protein, shown interacting with a strand of  DNA , is overexpressed in HT-29 cells.


Illustrations of intracrine, paracrine, autocrine and endocrine


Micrograph of hyaline cartilage containing isogenous groups.


Cartoon representation of hyaline cartilage with isogenous groups.


Schematic drawing of  Cafeteria roenbergensis  ( Heterokonta :  Bicosoecida ) with two unequal (heterokont) flagella: an anterior straminipilous (with tubular tripartite mastigonemes) and a posterior smooth


A chrysomonad ( Heterokonta :  Chrysophyceae ) under  TEM , with a smooth flagellum (1) and a long flagellum covered with mastigonemes (3)


Two cryptomonads ( Cryptophyceae ) under  SEM . Mastigonemes not visible.


Hematopoiesis: MEP differentiates into megakaryocytes and erythrocytes.


Megakaryopoiesis: Megakaryocyte actively forming platelets.


Cell wall  and middle lamella (top)


Placement of middle lamella in plant-tissue  (highly diagrammatic)


Scanning electron micrograph of a nanoknife. An individual carbon nanotube is being stretched between two tungsten needles. The triangular tip is an atomic force cantilever,  measuring the knife's breaking point.( NIST )


Process by which NSP2 phosphorylation leads to the hyper-phosphorylation of NSP5. This eventually leads to the formation of viroplasms. This image was created using BioRender.


Properties of common prostate cancer cell lines


Actin (Phalloidin) and Nuclei (DAPI) staining


PC3 cell cultured in plastic plate


The purple mesh represents pericentriolar material (PCM)


Chemical structure of  sn -1-stearoyl-2-arachidonoyl phosphatidylinositol (3,4)-bisphosphate


Animation of plithotaxis in action


Lactotropic Cells (in blue)


Promegakaryocyte


Comparison of monoblast, promonocyte and monocyte.


Different plastids


Figure 1.  Map of the R1 Plasmid isolated by Katherine E. L. Cox and Joel F. Schildbach.


RBL (Rat Basophilic Leukaemia) Cell Line


Tissue culture flasks


"Gallus ex Persia", illustration from the  Ornithologiae Tomus Alter  of  Ulisse Aldrovandi , 1600


Illustration from the  Geflügel-Album  of  Jean Bungartz , 1885


Septins in  Saccharomyces cerevisiae   (fluorescent micrograph)  • Green: septins ( AgSEP7- GFP )  • Red: cell outline ( phase contrast )  • Scale bar: 10 μm


Cross section of the  epithelium  of a  seminiferous tubule  showing various stages of spermatocyte development


Scheme showing analogies in the process of maturation of the ovum and the development of the spermatids (young spermatozoa).


A spinner


Prickle Cells Drawing - Artist: Sandy G Phillips-Long


Histologic image showing a section of epidermis. Stratum spinosum labeled slightly below center.


An image of the spleen in the human body. Also shows the red and white pulp regions.


Synapsis during Meiosis. The circled area is the part where synapsis occurs, where the two chromatids meet before crossing over


Skeletal muscle , with terminal cisterna labeled near bottom.


Pictures G-N show the tip links connecting the stereocilia.


Transmission electron micrograph  depicting tonofilaments, labeled tf, running longitudinally within the dorsal epidermal cells of the  girdle  of a  chiton


Touton giant cells in a  juvenile xanthogranuloma .  H&E stain .


Illustration of a transition: each of the 4 nucleotide changes between purines or between pyrimidines (in blue). The 8 other changes are  transversions  (in red).


Formation of Traube cells. Crystals of  potassium ferrocyanide  are put into a solution of  copper sulfate  (left). The interaction between them forms a film of  potassium ferrocyanide  at the vessel wall (right). The film is slowly filled with water inside it, like a membrane of a plant cell.


Blue coloured elastic fibers


Schematic representation of structural classes of protein according to the  CATH  classification scheme. [ 1 ]


The human genome, categorized by function of each gene product, given both as number of genes and as percentage of all genes. [ 7 ]


The human genome, categorized by the predicted  subcellular location  distribution of each gene product. [ 8 ]


A representation of the 3D structure of the protein  myoglobin  showing turquoise  α-helices . This protein was the first to have its structure solved by  X-ray crystallography . Toward the right-center among the coils, a  prosthetic group  called a  heme group  (shown in gray) with a bound oxygen molecule (red).


polypeptide


John Kendrew  with model of myoglobin in progress


Chemical structure of the peptide bond (bottom) and the three-dimensional structure of a peptide bond between an  alanine  and an adjacent amino acid (top/inset). The bond itself is made of the  CHON  elements.


Resonance  structures of the  peptide bond  that links individual amino acids to form a protein  polymer


A ribosome produces a protein using mRNA as template


The  DNA  sequence of a gene  encodes  the amino acid sequence of a protein


Peptide Synthesis


The crystal structure of the  chaperonin , a huge protein complex. A single protein subunit is highlighted. Chaperonins assist protein folding.


Three possible representations of the three-dimensional structure of the protein  triose phosphate isomerase .  Left : All-atom representation colored by atom type.  Middle:  Simplified representation illustrating the backbone conformation, colored by secondary structure.  Right : Solvent-accessible surface representation colored by residue type (acidic residues red, basic residues blue, polar residues green, nonpolar residues white).


Molecular surface of several proteins showing their comparative sizes. From left to right are:  immunoglobulin G  (IgG, an  antibody ),  hemoglobin ,  insulin  (a hormone),  adenylate kinase  (an enzyme), and  glutamine synthetase  (an enzyme).


Protein domains vs. motifs . Protein domains (such as the  EVH1 domain ) are functional units within proteins that fold into defined 3D structures. Motifs are usually short sequences with specific functions but without a stable 3D structure. Many motifs are binding sites for other proteins (such as the red and green bars shown here in the context of a  VASP  protein). [ 55 ]


The enzyme  hexokinase  is shown as a conventional ball-and-stick molecular model. To scale in the top right-hand corner are two of its substrates,  ATP  and  glucose .


Ribbon diagram  of a mouse antibody against  cholera  that binds a  carbohydrate  antigen


Protein Structure


Proteins in various  cellular compartments  and structures tagged with  green fluorescent protein  (here, white)


Constituent amino-acids can be analyzed to predict secondary, tertiary and quaternary protein structure, in this case hemoglobin containing  heme  units


Hydrolysis of protein.  X = HCl and heat for industrial proteolysis.  X = protease for biological proteolysis


Allosteric regulation of an enzyme


A –  Active site  B – Allosteric site  C –  Substrate  D –  Inhibitor  E –  Enzyme This is a diagram of allosteric regulation of an enzyme.


Amino  Acids


The anaphase-promoting complex (APC) is a large protein complex containing 11–13 subunits, including a RING subunit (Apc11) and a cullin (Apc2). APC activity requires association with activator subunits (Cdc20 or Cdh1) that contribute to substrate binding.


M–Cdk activity promotes the events of early mitosis, resulting in the metaphase alignment of sister chromatids on the spindle. M–Cdk activity also promotes the activation of APCCdc20, which triggers anaphase and mitotic exit by stimulating the destruction of regulatory proteins, such as securin and cyclins, that govern these events. By promoting cyclin destruction and thus Cdk inactivation, APCCdc20 also triggers activation of APCCdh1, thereby ensuring continued APC activity in G 1 .


A timeline of key ancient protein analysis since the 1950s.


Structure of AcrIIA4 obtained with the UCSF Chimera software, [ 12 ]  where its PDB file was uploaded. [ 13 ]  Different colours were assigned to the four different secondary structures found in this protein: blue for β-strands, red for α-helices, orange for the 3 10  helix, and grey for loops. Originally, the PDB file contains the 20 lowest energy sequences (and thus, the most stable ones) superposed, one of which was randomly selected to create the figure. [ 14 ]


Phage-phage cooperation:  First phage infections may be unable to hamper the CRISPR immunity, but phage-phage cooperations increasingly boost Acr production and host immunosuppression, which produces an increase on the vulnerability of the host cell to reinfection, and finally allows a successful infection and spreading of a second phage.   Based on a representation found in the 17th reference.   [ 17 ]


Diagram showing type I-F CRISPR-Cas system, as well as inhibition mechanisms of three type I-F anti-CRISPRs. Type I-F CRISPR complex is made of 60 crRNA nucleotides and nine Cas proteins (the protein type is specified by the numbers 5,8,7,6). AcrF1 goes to Cas7f, preventing target DNA access to the crRNA guide. AcrF2 interacts both with Cas8f and Cas7f, difficulting target DNA access to the binding pocket. Finally, AcrF3 forms a  homodimer , interacting with Cas3 by preventing its contact with the Cascade complex.  Based on a representation from a review found in the references below.   [ 21 ]


Phage therapy  could be used against antibiotic resistance, as bacteriophages can kill bacteria, and cure an infection.


Phage therapy is a good alternative to the use of antibiotics, but some bacteria have CRISPR-Cas systems. Nevertheless, if phages had Acr proteins, they would inhibit the CRISPR-Cas immune system and infect the cell. At the end of the phage reproduction cycle, which takes place inside bacteria, new phages would be released, provoking the cell lysis.


Fig. 1  There is no structure resolved for Cdh1 of  Saccharomyces cerevisiae . There is a model based on template pdb2ovq, which shows the  SCF(Fbw7)  ubiquitin ligase complex. Fbw7 is also a WD repeat protein like Cdh1. (The model for Cdh1 can be found on the webpage of  SWISS-MODEL Repository , [ 7 ] [ 8 ]  see the external link at the end of this page)


This is a representation of a cartoon that showcases myoglobin and apomyoglobin. It also shows individual helices with A to H labeling. It is also showcasing the removal of a heme group from myoglobin to show apomyoglobin instead.


This is a picture of an Apomyoglobin structure. It specifically shows cross-linking in glycated W7FW17F apomyoglobin.


Overview of signal transduction pathways involved with  apoptosis .


Schematic illustration of the four known conserved domains in four members of the PIKKs family [ 13 ]


ATM-mediated two-step response to DNA double strand breaks. In the rapid response activated ATM phosphorylates effector kinase CHK2 which phosphorylates CDC25A, targeting it for ubiquitination and degradation. Therefore, phosphorylated CDK2-Cyclin accumulates and progression through the cell cycle is blocked. In the delayed response ATM phosphorylates the inhibitor of p53, MDM2, and p53, which is also phosphorylated by Chk2. The resulting activation and stabilization of p53 leads to an increased expression of Cdk inhibitor p21, which further helps to keep Cdk activity low and to maintain long-term cell cycle arrest. [ 15 ]


Caffeine  is an ATM inhibitor with low activity


AZD0156  is a highly active ATM inhibitor from AstraZeneca


Schematic of copper homeostasis  cell biology


ATOX1 copper coordination


Model of ligand exchange copper transfer from Atx1 to Ccc2


Human Embryonic Stem Cells


BLNK’s function and interaction shown in a schematic of BCR signaling pathways. BCR antigen recognition activates  Src family kinases , including the  SYK  and  BTK   tyrosine kinases . Syk then phosphorylates BLNK, which can recruit downstream signaling molecules such as  Grb2 ,  PLCG2 ,  Vav  and  Nck .


Sequence of BZW2 is shown with positions of spacing information, charge clusters, and repeats.


BZW2 structure from Phyre2 colored from N-terminus (red) to C-terminus (blue).


Schematic of the post-translational modification locations on the BZW2 protein.


A phylogenetic tree illustrates the BZW2 sequence relationships between orthologs.


BZW2 corrected divergence over million years diverged from humans,


Schematic representation of MHC class I


Caspase-8 (as surface) cleavage of Bid (as ribbon) (visualization by  Kosi Gramatikoff )


Crystal structure of B-phycoerythrin, a type of phycobiliprotein


Chemical structure of a phycocyanobilin molecule (characterised by tetrapyrrole rings); the bilin chromophore of the phycocyanin biliprotein


A phycobilisome made up by stacks of phycobiliprotein subunits attached together.


The large white butterfly ( Pieris brassicae ), from which the biliprotein known as 'bilin-binding protein' was extracted.


Biotin Carboxyl Carrier Protein


anterior cervical discectomy and fusion


Sequence relationships among mammalian bone morphogenetic proteins (mouse/human). Modified after Ducy & Karsenty 2000 [ 24 ]


BSM can be derived from any bovine source.


The structure of mucin is shown and includes a core protein with O-linked glycans.


BSM adsorbs to surfaces with the chains extending outward from the adsorption site.


Conceptual Translation of C1orf167 showcasing the conserved Domain of Unknown Function that begins at the break between exon 13 and exon 14.


Schematic Illustration of predicted post-translational modifications for C1orf167 made using the Dog 2.0  [ 19 ]  The DUF at locations 954-1418 is labeled


Multiple Sequence Alignment of Strict Orthologs for C1orf167. Beginning of the conserved DUF region at the break between exon 13 and 14 is shown. [ 33 ]


Dot matrix analysis of uncharacterized protein C2orf16 isoform 2. The P-S-E-R-S-H-H-S repeat sequence is visualized via the darker area of the matrix from amino acid 1500–1984, and a half P-S-E-R-S-H-H-S repeat sequence is seen as a band near amino acid 1200.


C2orf16 Isoform 2 predicted 3D structure showing the three major domains of the protein. Domain 3 contains the P-S-E-R-S-H-H-S repeat sequence.


P-S-E-R-S-H-H-S Repeat Sequence Logo


Chromosomal location of C2orf74. Image made using NCBI Genome Decorator Page [ 1 ]


Antibody staining results from The Human Protein Atlas. [ 17 ]  Immunocytochemical antibody staining results are listed as showing localization to the centrosome (Green, frame A). Other examples of the same antibody staining as well as immunohistochemical results show strong presence of this gene in the cytoplasm. (Green, frame B. Dark brown, frame C).


Birds eye view of the coding region of the C2orf74 gene and the promoters in the region. Red boxes represent C2orf74 exons while blue arrows represent promoter regions.


Predicted 3D structure of the human 3'UTR. Stem-loops have been colored red, yellow, green, cyan, blue, purple, and magenta. Potential mi-RNA binding sites are labelled in light pink, and polyadenylation sites are labelled in orange.


Figure 4: Rate of evolution comparison between C2orf74, Cytochrome C, and Fibrinogen Alpha. C2orf74 appears to evolve even faster than Fibrinogen alpha, which serves as a standard for rapidly evolving genes.


Left: Microarray data from NCBI GEO showing decreased level of C2orf74 expression in  colorectal cancer  cells regardless of whether they were positive or negative for  CD133  (a proposed biomarker for cancer.), but not in other types of cancerous cells such as carcinoma associated fibroblasts. Right: Microarray data from NCBI GEO showing decreased level of C2orf74 expression in  colorectal adenomas , but not in normal  mucosa . Note that adenomas are benign tumors that arise from normal mucosa, making the difference in C2orf74 expression relevant.


Predicted tertiary structure of c7orf26 with leucine zipper elements highlighted in red, and dileucine components highlighted in green.


Location of c7orf26 on chromosome 7


Diagram depicting the expression of c7orf26 in tissues throughout the body.


Phylogenetic Tree of nearest orthologs of c7orf26


Location of C9orf25 on the - strand of Chromosome 9


Speed of evolution of C9orf25 in some orthologs compared to evolution of  Cytochrome C  and  Fibrinogen [ 16 ]


Secondary structure of the FAM219A gene


Expression and amount of C9orf25 present in prostate cells  [ 22 ]


A graph depicting the rate of divergence for the human gene C9orf85 in comparison to Homo sapiens Cytochrome C and Fibrinogen Alpha Chain.


Multiple sequence alignment of C9orf85 showcasing the most significant & conserved cysteines.


Conceptual translation of human C11orf91 gene/protein.


Tertiary Structure of human C11orf91 protein. Created with AlphaFold Protein Structure Database. [ 8 ]


Corrected Sequence Divergence vs. Median Date of Divergence graph for human C11orf91,  Fibrinogen Alpha , and  Cytochrome C .


Cytogenetic band: 12q23.2 [ 6 ]


Tertiary structure  for C12orf42 protein. [ 7 ]


This protein cartoon illustrates the location of, the domain DUF4607 and two nuclear localization sequences.


Illustrates the translocation that occurred that led to a deletion in chromosome 12. Where chromosome 12q23 cross-fused with TRDREC and TRAJ61 segment. This interfered with C12orf42 gene. [ 19 ]


Diagram of C16orf78 protein with ubiquitination sites marked in red and phosphorylation sites marked in gray. [ 8 ]


Phyre2 generated model of C16orf78 rendered in  Chimera .


Expression of C16orf78 across multiple human tissues [ 16 ]


In situ hybridization data of C17orf53 in the hypothalamus (top) and the mesencephalon (bottom).


The table above denotes common orthologs of C17orf53


C17orf53 phylogenetic tree of its orthologs


The secondary structure of c17orf53


The predicted tertiary structure of C17orf53


Protein interactions of c17orf53


NCBI GEO Expression Profile for C18orf63


Amino acid composition of the average protein (left) and Amino acid composition of C18orf63 (right)


Partial 3D structure for C18orf63


Motifs and Domains for C18orf63


Rate of evolution for C18orf63 when compared to betaglobin, fibrinogen alpha, and cytochrome c


C19orf38  location on chromosome 19, gene neighborhood, and gene overview.


HIDE1 protein three-dimensional structure. [ 10 ]


Human Protein HIDE1 domain, motif, and post translational modification diagram.


Table of C19orf38 transcript orthologs and related properties.   Data is organized by median date of divergence (MYA), and then sequence identity to  Homo sapien  (Hsa) protein. [ 18 ] [ 19 ]


human  C19orf38  unrooted evolutionary tree .


Gene Neighborhood of C19orf67


Splice Variants for C19orf67. [ 7 ]


Predicted Post-Translational Modifications and Domains of UPF0575 C19orf67.


Abundance of C19orf67 found throughout the body in humans relative to abundances of other human proteins


This conceptual translation of c22orf23 includes post-translational modifications indicated on the right, start codon in green, stop codon in red, exon-exon junctions in blue, polyadenylation tail in orange, and highly conserved amino acids in purple.


Predicted secondary structure of C22orf23. 53% of the sequence is predicted as disordered and cannot be predicted with confidence. It has a coverage modeled of 28% with a 42.9% confidence. The image was created using Phyre2. [ 14 ]


[ 8 ]   Upon activation of Toll signaling by Gram-positive and Gram-negative bacteria infection, Cactin in the cytosol binds to Cactus and mediates the release of Dif and Dorsal from Cactus, allowing their translocation into the nucleus and activation of AMP genes.


Figure 1 : Evolutionary lineage of vertebrate  CNN1 .


Figure 2. Structural and functional domains of calponin.  The linear structural map summarized primarily from studies of chicken calponin 1 illustrates the structural and functional domains of calponin. The CH domain, two actin-binding sites, three repeating sequence motifs, and the C-terminal variable region are outlined. The CH domain overlaps with the ERK signaling binding region. Amino acid sequences of the two actin-binding sites in the three isoforms and the three repeating motifs of calponin 1 are shown in the insets. The regulatory phosphorylation sites Ser 175  and Thr 184  are located in the second actin-binding site that overlaps with the first repeating motif. Potentially phosphorylatable serine residues corresponding to Ser 175  are conserved in repeats 2 and 3, while a Thr 184  equivalent is conserved in repeat 2. Different from calponin 1 and calponin 3, calponin 2 has a potentially phosphorylatable additional serine at position 177.


Figure 1:  Evolutionary lineage of vertebrate calponin 2 deduced from alignment of amino acid sequences.


Figure 2. Proteins interacting with calponin.  Calponin binds actin filaments through two actin-binding sites (ABS1 and ABS2), tropomyosin via the N-terminal CH domain, and gelsolin via the region of actin-binding sites. Calponin interacts with microtubules through the region including the actin-binding sites and the repeating motifs and with desmin through the region from N-terminal domain to the end of actin-binding sites. The segment of amino acids 144-182 in calponin interacts with myosin.  In the presence of Ca 2+ ,  calmodulin  and  S100  bind calponin at the region of actin-binding sites and reverse calponin’s inhibition of myosin MgATPase. An N-terminal 22-kDa fragment of calponin interacts with phosphatidylserine and phosphatidylinositol. *The interaction between calponin and  caldesmon  is controversial.


Figure 1.  Evolutionary lineage of vertebrate calponin 3 isoforms deduced from alignment of amino acid sequences.


Carboxypeptidase A , from bovine pancreas


Figure 1. CPA Active Site


Figure 2.  CPA-Catalyzed proteolysis promoted by coordinated water molecule.


This is the predicted structure of CARD11 produced by AlphaFold. The different colored regions reflect the confidence that a particular residue is in that location, with dark blue being the most confident and orange indicating the least confidence.


Figure 1. Interaction network and domain structure scheme of Cass4.  SH3 domain (SH3) preceded by a short region with no defined functional elements; SH2-binding site motifs, which when tyrosine-phosphorylated allow interaction with SH2-domain containing proteins; serine-rich region encompassing 4-helices and a second highly conserved four-helix bundle that has been recognized as functionally and structurally similar to a focal adhesion targeting [FAT] domain. .


Predicted tertiary structure ( I-TASSER )


GEO Profile of CCDC92 expression in humans. The blue dots indicate the percentile at which the protein was expressed in that tissue compared with all other proteins.


Adjusted amino acid changes per 100 (m) against millions of years since the species diverged from humans determines how quickly the protein changes. Fibrinogen and Cytochrome C are given as a reference.


GEO Profile of GDS4006. Observes the effect of a histone deacetylase inhibitor and a hypomethylating agent on CCDC92 levels.


GEO profile of CCDC92 for experiment GDS3049. Observes expression levels in the presence and absence of a tyrosine kinase inhibitor (Imantinib)


CCDC113 expression in human tissues. [ 18 ]


The red line shows the CCDC138 locus on chromosome 2q12.3.


CCDC138 multiple sequence alignment showing conserved regions.


CCDC138 rooted phylogeny tree


Pairwise sequence alignment comparing isoforms 1 and 2 of the CCDC138 protein.


CCDC138 secondary structure as predicted by PELE


Chain A, crystal analysis structure of Clpb


Promoter region of CCDC138 with labeled transcription factor binding sites


Microarray-assessed tissue expression patterns shown in GEO profile.


Transcript variants of CCDC138


The location of  CCDC180  on human chromosome 9 within locus 9q22.33 is marked with a line.


Here are shown the major domains present within the protein CCDC180: Domains of Unknown Function 4455 and 4456, two coiled-coil domains, and a glutamic acid rich domain.


A model of CCDC180 secondary and tertiary structure predicted by the University of Michigan I-TASSER server [ 6 ]


Translation of the mRNA and protein sequence for the human protein CCDC180, including domains, secondary structure, exon splice sites, and post-translation modification sites


GEO Profile for the expression of the human protein CCDC180 in normal tissues [ 13 ]


The amino acid changes per 100 (m) in a selection of orthologs of CCDC180 versus time of divergence of the species from human in millions of years. This is compared to Cytochrom C and Fibrinogen to indicate the relatively high speed of evolution of the CCDC180 protein.


Front (top) and side (bottom) views of the structure (PDB:  1rzr [ 1 ] ) of CcpA (green and red) in complex with co-regulator Hpr-Ser46-P (blue) and target (operator) DNA sequence (gold).  CcpA binds DNA as a homodimer (green and red monomer chains) in the N-terminal region of the protein.  Binding is modulated allosterically by binding of Hpr-Ser46-P (blue) and small molecule ligands (not shown).


Chromosome location of CDV3 from  NCBI Gene . [ 7 ]


Conceptual translation of the longest CDV3 isoform annotated with CDV3's predicted secondary structure and conserved amino acids.


Predicted CDV3 3D structure from I-TASSER.


HPA RNA-seq Normal Tissue Expression from NCBI Gene entry on CDV3.


Tissue-specific circular RNA induction during human fetal development from NCBI Gene entry on CDV3.


RNA sequencing of total RNA from 20 human tissues from NCBI Gene entry on CDV3.


Illumina bodyMap2 transcriptome from NCBI Gene entry on CDV3.


A conceptual translation showing predicted sites of CDV3 protein regulation.


Phylogenetic tree of species with CDV3 orthologs using Phylogeny.fr


Fig. 1  The figure shows a sketch of how the SCF complex functions, and what the role of Cdc4 is within this structure (-> adaptor function).


cIAP1 structure


Micrograph  of a  paraganglioma  stained with chromogranin-A  immunostain .


Schematic representation of a circular permutation in two proteins. The first protein (outer circle) has the sequence a-b-c. After the permutation the second protein (inner circle) has the sequence c-a-b. The letters N and C indicate the location of the amino- and carboxy-termini of the protein sequences and how their positions change relative to each other.


Two proteins that are related by a circular permutation.  Concanavalin A  (left), from the Protein Data Bank ( PDB :  3cna ), and peanut  lectin  (right), from  PDB :  2pel , which is homologous to favin. The termini of the proteins are highlighted by blue and green spheres, and the sequence of residues is indicated by the gradient from blue (N-terminus) to green (C-terminus). The 3D fold of the two proteins is highly similar; however, the N- and C- termini are located on different positions of the protein. [ 1 ]


The permutation by duplication mechanism for producing a circular permutation. First, a gene 1-2-3 is duplicated to form 1-2-3-1-2-3. Next, a start codon is introduced before the first domain 2 and a stop codon after the second domain 1, removing redundant sections and resulting in a circularly permuted gene 2-3-1.


Suggested relationship between saposin and swaposin. They could have evolved from a similar gene. [ 7 ]  Both consist of four alpha helices with the order of helices being permuted relative to each other.


The fission and fusion mechanism of circular permutation. Two separate genes arise (potentially from the fission of a single gene). If the genes fuse together in different orders in two orthologues, a circular permutation occurs.


Transhydrogenases in various organisms can be found in three different domain arrangements. In  cattle , the three domains are arranged sequentially. In the bacteria  E. coli ,  Rb. capsulatus , and  R. rubrum , the transhydrogenase consists of two or three subunits. Finally, transhydrogenase from the protist  E. tenella  consists of a single subunit that is circularly permuted relative to cattle transhydrogenase. [ 20 ]


Mechanism of clathrin-mediated endocytosis.


The activator, thyroid hormone receptor (TR), is bound to a corepressor preventing transcription of the target gene. The binding of a ligand hormone causes the corepressor to dissociate and a coactivator is recruited. The activator bound coactivator recruits RNA polymerase and other transcription machinery that then begins transcribing the target gene.


Histone acetyltransferase (HAT) removes the acetyl group from acetyl-CoA and transfers it the N-terminal tail of chromatin histones. In the reverse reaction, histone deacetylase (HDAC) removes the acetyl group from the histone tails and binds it to coenzyme A to form acetyl-CoA.


N-terminal acetyltransferase (NAT) transfers the acetyl group from acetyl coenzyme A (Ac-CoA) to the N-terminal amino group of a polypeptide.


Diagram of cohesin showing its four constituent protein subunits


Models of SMC and cohesin structure


Crystal structure of mouse coronin-1. [ 6 ]


SARS-CoV-2  main proteinase  dimer  with the  catalytic dyad  ( H41 ;  C145 ) in complex with protease inhibitor chemical 11a ( PDB :  6LZE )


The original crowdsourced design of the fragment merge (TRY-UNI-714a760b-6)


Some of the international participants in COVID Moonshot.


The image shows the exact location of CXorf49 on the minus strand of the X chromosome.


Image of the protein with the domain of unknown function.


This phylogenetic tree made with CRUSTALW on SDSC Biology Workbench [ 6 ]   shows how CXorf49 in Human (Hsa), Chimpanzee(Ptro), Malayan flying lemur(Gava), Sheep (Ovari), Pacific walrus(Ord), Aardvark(Oafaf), Chinese tree shrew (Tuchi) and House mouse(Mmus) has diverged over time.


Tertiary structure of human cyclin A (lacking the amino-terminal 170 amino acids), showing the central core of two five-helix bundles, with additional helices at the amino terminus (black) and carboxyl terminus (grey). The yellow region in helix 1 is the MRAIL sequence or hydrophobic patch, which contributes to the recognition of some substrates. (PDB 1fin)


Expression of human cyclins through the  cell cycle .


Expression of human cyclins through the  cell cycle


Expression of cyclins through the  cell cycle .


Role of CDK4, cyklin D, Rb and E2F in cell cycle regulation


Crystal Structure of the human Cdk1 homolog, Cdk2


Fig. 1  The diagram shows the role of Cdk1 in progression through the  S. cerevisiae  cell cycle. Cln3-Cdk1 leads to Cln1,2-Cdk1 activity, eventually resulting in Clb5,6-Cdk1 activity and then Clb1-4-Cdk1 activity. [ 5 ]


Cdk2 (blue) and its binding partner, cyclin A (red). [ 13 ]


Cdk2 (blue) and its binding partner cyclin E (orange). [ 15 ]


Graphical abstract of CDK2  [ 29 ]


Overview of signal transduction pathways involved in  apoptosis .


Cdk5 functions


Cdk5 is a transitional state to the overexposure to drugs as cocaine. It can be explained by the increased expression of Cdk5 in NA, PFC and VTA only when it comes to frequent cocaine doses significantly close in time


Cdk5 forms a complex with p25, which results in nerve cells apoptosis and neuroinflammation.


Quantum dynamics of a Davydov soliton with

 χ
 =
 35

 {\displaystyle \chi =35}

  pN generated by an initial Gaussian step distribution of amide I energy over 3 peptide groups at the N-end of a single α-helix spine composed of 40 peptide groups (extending along the  x -axis) during a period of 125 picoseconds. Quantum probabilities

 |

 a

 n

 |

 2

 {\displaystyle |a_{n}|^{2}}

  of amide I excitation are plotted in blue along the  z -axis. Phonon lattice displacement differences

 b

 n

 −

 b

 n
 −
 1

 {\displaystyle b_{n}-b_{n-1}}

  (measured in picometers) are plotted in red along the  y -axis. The soliton is formed by self-trapping of the amide I energy by the induced lattice distortion. [ 1 ] [ 2 ]


DSP is found in the teeth


Crystal structure of human Desmocollin-1 ectodomain, PDB 5IRY [ 1 ] [ 2 ]


Annotated features of TMEM261 protein including topology and important sites for phosphorylation and Myristoylation as well DUF4536 and transmembrane helical domains.


Some proteins found to interact with TMEM261


Tissue expression of TMEM261 showing tissue enriched gene (TEG) expression  [ 27 ]


Doublecortin expression in the rat  dentate gyrus , 21st postnatal day. Oomen et al., 2009. [ 6 ]


Double layer hippocampus seen in Doublecortin knock out mice (right panels) compared to the normal hippocampus in wild type mice (left panels). Figure extracted from the work of the laboratory of  Fiona Francis


An animation of the structure of the dark state of dronpa protein


On-cis (green) and Off-trans (yellow) states of the chromophore. Nearby residues that move are also shown. Clockwise from the top: Arg66, Val157, Ser142, Cys-Tyr-Gly chromophore.


Figure 1.  Scheme, representing major proteins interacting with EFS through highly conserved motifs.


Left:  protoporphyrin IX . Right: modified form of heme cofactor released from peroxidase by protease digestion under nonreducing conditions. [ 9 ]


Active site of eosinophil peroxidase in the resting (reduced) state. Pictured: Proximal histidine-asparagine interaction (bottom); distal histidine and bound water (top). In the oxidized form, the oxyferryl radical takes the place of the bound solvent molecule, and the halide substrate binds alongside that. Not pictured: other bound solvent water molecules. Refer to PDB crystal structures or  refs. [ 11 ]  and. [ 9 ]


ERICH2 gene location as depicted by the National Center for Biotechnology Information (NCBI).


Cartoon of the ERICH2 protein. The green box represents the PHA03247 domain, the orange box represents the amidation site, the blue box represents the cAMP- and cGMP- dependent protein kinase binding site. The gray box labels P represents an area rich in Proline, while the gray box label conserved is that in which is conserved throughout distant orthologs. the gray tags represent phosphorylation sites, and the red flags represents sites of glutamate amino acids. The green lines on the top of the cartoon represent the Pat4 nuclear localization signals while the gray brackets represent the Pat7 localization signals.


Conceptual Translation of ERICH2. Intron-exon boundaries are highlighted in yellow. The PHA03247 domain is highlight it light gray. The acetylation site is in orange font. The amidation site is in light blue font. The c-AMP and c-GMP dependent protein kinase phosphorylation site is highlighted teal. Phosphorylation sites are in pink text. The most conserved region in distant orthologs is highlighted green. The beta strand structure is represented by a black arrow. The alpha helix structure is represented by a purple arrow.


A  fluoroscopy  of human cells, from the CACO-2 cell line of  colorectal cancer , showing the presence of the ERICH2 antibody, as well as highlighted microtubules and DNA. The figure shows the location of the ERICH2 protein, mainly in the nucleoli fibrillar center and vesicles. [ 13 ]


Heme in chlorocruorin, the source of its unique green color.


The image displays the structure of eRF1 alone with key annotations of significant sites. [ 16 ]


Hydrolysis of ester bond to release nascent protein [ 37 ]


Mechanistic steps of Nonsense Mediated Decay pathway [ 38 ]


Extrinsic apoptosis pathway:  The Fas receptor (FasR) is stimulated by Fas ligand (FasL), recruiting FADD to the FasR via an interaction between the death domains (DD) of both molecules. Procaspase 8 is recruited to FADD and interacts via the death effector domains (DED) of both molecules. This results in the cleavage and activation of procaspase 8, forming caspase 8, which goes on to cleave and activate other caspases such as procaspase 3 to initiate the caspase cascade which leads to cell death.


Regulation of FADD by MKRN1:  MKRN1 ubiquitinylates FADD targeting it for degradation by the 26S proteosome. As it is degraded, FADD can no longer bind to the Fas receptor (Fas R) to induce apoptosis.


Human Chromosome 5


Tertiary Structure of the human FAM13B protein from AlphaFold


Annotated FAM13B protein, made from The CUCKOO Workgroup


Annotated post-translational modification sites on human FAM13B protein, made from The CUCKOO Workgroup


Multiple sequence alignment of a conserved area of the FAM13B protein


Structure of FAM63B protein showing the domain of unknown function, bipartite tryptophan binding motif, hydrophobic stretchm, and KDEL signal.


Predicted protein structure of FAM63B as determined by iTASSER.


The phylogenetic tree from TimeTree shows a time calibration for the evolution of FAM63B among humans (Has), prairie voles (Moc), polar bears (Uma), Western clawed frogs (Xtr), and Western Indian Ocean coelacanth (Latimeria chalumnae, Lch). The fish is the most diverged, followed by the amphibian, and the mammals, especially humans, are the least diverged. This is as expected in accordance with the evolutionary history of organisms on Earth, and FAM63B shows no great exception to the rule.


FAM71E2 gene


5' UTR folding FAM71E2


3' UTR folding FAM71E2


Visualization of domains and motifs on the FAM71E2 gene


Secondary structure of FAM71E2


Metaphase II stage oocytes matured in vivo


Estrogen receptor alpha-silenced MCF7 breast cancer cells.


Neural transcription factor SOX11 depletion effect on mantle cell lymphoma cell line


Evolution chart FAM71E2


FAM89A located downstream of the ARV1 gene.


Immunofluorescent staining of RH-30 cell line reveals FAM89A localization to Golgi apparatus, vesicles, and nucleoplasm (shown in green). [ 24 ]


Schematic diagram of FAM89A 184 amino acid (aa) length protein with annotations of the leucine-rich adaptor protein (LURAP) domain and the post-translational modifications.


Pairwise sequence alignment of FAM89A to its paralog, FAM89A, reveals an unidentified conserved region containing experimentally verified FAM89B phosphorylation site.


Relative divergence of FAM89A reveals FAM89A's rapid rate of mutation accumulation relative to fibrinogen, a gene that is evolving rapidly, and cytochrome c, a gene that is evolving slowly.


Genomic region of 3' UTR of gene FAM151A


FAM151A Expression in HPA RNA-seq normal tissues [ 9 ]


Antibody staining of FAM151A in human kidney tissue


FAM151A tertiary structure as predicted by AlphaFold2


Shannon information content  of amino acid residues for 20 aligned FAM151A sequences.


The structure of the FcεRI receptor


Summary of IgE/FcεRI receptor mediated downward signal cascade


Chromosome 4


Schematic structures of dysferlin, myoferlin, and otoferlin; three ferlin proteins that are associated with human diseases. Lack of functional dysferlin can cause a group of muscular dystrophies knows as dysferlinopathies. Myoferlin is highly expressed in several types of cancer, and mutations in otoferlin can cause deafness.


Superposition of dysferlin FerA structural model obtained by Robetta and  ab initio  bead model obtained by experimental Small Angel X-Ray Scattering experiments.


Topologies of ferlin domains. Labels A-F indicate:  A: ferlin topology containing all seven C2 domains; B: (-)C2DE; C: (-)C2A; D: (-)C2A, (-)C2DE; E: (-)C2A, (-)C2DE, (-)FerB; F: (-)C2A, (-)C2 D, (-)C2E, (-)C2DE,(-)C2F. Different C2 domains are also labeled as C2A-C2F. In other studies, C2DE, C2E, and C2F are denoted as C2E, C2F, and C2G. In this figure, C2, DysF, and transmembrane are an amalgamation of SMART results, and FerA, FerB and FerI are an amalgamation of PFAM results.


Structure of the forkhead-associated domain


Predicted structure of FHAD1 using RaptorX software


Expression profile for FHAD1 from Human Protein Atlas


5' UTR stem loops


3' UTR stem loops


Rate of evolution


Phylogenetic tree for FHAD1


3-D structure of flavodoxin protein


(RCF-1) Trigonal form of recombinant oxidized long chain flavodoxin in Anabaena/Nostoc sp. The active site is characterized by a FMN (flavin mono-nucleotide) cofactor highlighted in magenta. SO4 residue highlighted in yellow. As with most flavodoxins, the residues near the binding site are large and hydrophobic.


Reversible binding between FAST and a fluorogene


splitFAST, a split fluorescent reporter


Formyl functional group is shown in blue.


Cycle for  methanogenesis , showing initial formylation of methanofuran [ 11 ]


Methionyl tRNAfMet transformylase complexed with initiator formylmethionyl tRNA fMet . Rendered from PDB 2FMT.


The chemical synthesis of  N -formylmethionine is catalyzed by the enzyme methionyl-tRNA formyltransferase.


Active site of PurN GAR transformylased in a complex with the folate based inhibitor 5-deaza-5,6,7,8-tetrahydrofolate (5dTHF). The α-amino group of GAR (Pink) is located in a position which would attack a N10-formate group on the folate based inhibitor (yellow). Asn 106, His 108, and Asp 144 are colored green. Rendered from PDB 1CDE.


Mechanism of PurN GAR transformylase


Reaction catalyzed by PurT GAR transformylase


1M9N Active site of AICAR transformylase. Lys267 (cyan), His268 (purple), AICAR (green). Rendered from PDB 1M9N.


Mechanism catalyzed by AICAR transformylase


Formylation is a post-translational modification which occurs on lysine residues.


Formylation of lysine can compete with acetylation as a post-translational modification.


Formyl phosphate is a proposed product of oxidative DNA damage.


Chemical structure of lometrexol


The universal structure of antibody includes the constant regions part of the fragment crystallizable(Fc) region of the antibody (shown in dark blue). It also includes the fragment antigen binding which is composed of one heavy and one light chain (shown as L for light and H for heavy). Each heavy and light chain is composed of one variable region and one constant region (shown as V or C). The variable regions are composed of 7 amino acid segments; three of which are hypervariable regions or CDR (yellow) and four of which are FR(shown in green for heavy chains and pink for light chains).


Figure 1:Overview over the functions of GCN2. (GCN1/GCN20=GCN1p/GCN20p binding site; PsiKD = unknown function; KD = Kinase Domain; HisRS = histidyl-tRNA synthetase) Adapted from [ 5 ]


GFAP  immunostaining  in a glial neoplasm ( anaplastic astrocytoma )


GFAP  immunostaining  of an astrocyte in cell culture in red and counterstained for  vimentin  in green. GFAP and vimentin colocalize in cytoplasmic  intermediate filaments , so the astrocyte appears yellow. Nuclear DNA is stained blue with  DAPI . Antibodies, cell preparation and image generated by  EnCor Biotechnology Inc.


The skeleton of a bamboo coral; the darker joints are gorgonin nodes


Guanosine diphosphate


Guanosine triphosphate


G proteins have an inherent GTPase hydrolytic activity that is slow. However, in the presence of GAP, this hydrolytic activity is fast.


GAP works to open the G protein for nucleophilic attack by water and induce a GDP-like charge distribution.


Normally, G proteins are regulated by GAP, which results in controlled cell division.


Without GAP, G proteins are constitutively on because of their slow hydrolytic activity and GEFs constantly replacing GDP with GTP. This results in unregulated cell division and the formation of tumors.


G proteins without hydrolytic activity cannot hydrolyze bound GTP. GAPs cannot activate a nonfunctional enzyme, and the G protein is constitutively active, resulting in unregulated cell division and the formation of tumors.


Dehulled hemp seeds (food) containing about 10g of hemp protein per 30g serving


A package of unflavored hemp protein


Hfq protein with a bound sRNA.


Structure of the ring-finger domain of ICP0


Schematic representation of the assembly of the core histones into the nucleosome


Histone heterooctamer (H3,H4,H2A,H2B) + DNA fragment, Frog


Steps in nucleosome assembly


Basic units of chromatin structure


Histone tails and their function in chromatin formation


Schematic representation of histone modifications. Based on Rodriguez-Paredes and Esteller, Nature, 2011


The crystal structure of the nucleosome core particle consisting of   H2A  ,   H2B  ,   H3   and   H4   core histones, and DNA. The view is from the top through the superhelical axis.


Histone acetylation alters chromatin structure.  Shown in this illustration, the dynamic state of histone acetylation/deacetylation regulated by HAT and HDAC enzymes. Acetylation of histones alters accessibility of chromatin and allows DNA binding proteins to interact with exposed sites to activate gene transcription and downstream cellular functions.


A diagram showing where H1 can be found in the nucleosome


The crystal structure of the  nucleosome  core particle consisting of  H2A ,   H2B ,  H3  and   H4   core histones, and DNA. The view is from the top through the superhelical axis.


Structure of the H2AFJ protein


Basic units of  chromatin  structure


The nucleosome assembles when DNA wraps around the histone octamer, two H2A-H2B dimers bound to an H3-H4 tetramer.


DNA  is wrapped around  histones  to form  nucleosomes . Nucleosomes are shown as " beads on a string " with the distinction between  euchromatin  and  heterochromatin .


The basic units of  chromatin  structure.


The dynamic state of histone acetylation/deacetylation regulated by  HAT  and  HDAC  enzymes; acetylation of histones alters accessibility of chromatin.


A  phosphoryl group  is shown in blue.


An  O-GlcNAcylated   threonine  residue. The  GlcNAc  moiety is shown in red while the modified threonine is shown in black.


An  adenosine diphosphate ribose  group.


The amino acid  arginine  (left) is converted to  citrulline  (right) via the process of  citrullination .


Proline  trans-cis isomerization  by a  PPIase  enzyme.


Predicted 3D structure of the HSH2D protein


Structure of hydramacin-1


A hydra (size: several millimetres)


IGHM dimer, Human


Inner nuclear membrane proteins structure. Amino-termini (N) and carboxy-termini (C) are indicated in red. Adapted from Holmer and Worman (2001) [ 1 ]


A) Full length protein sequence of Arabidopsis. B) 3D structures of ILK repeats. C) N-terminal is blue C-terminal is red. Shows the succession of secondary elements. D) Amino acid sequence of ILK.


The invasin-mediated uptake into mammalian cells involves a clustering model. Multivalent invasin induces integrin clustering by simultaneously binding to multiple integrin heterodimers. This process, dependent on ligand binding and β1-integrin multimerization, leads to the association of various cell signaling molecules, triggering the involvement of additional signaling and cytoskeletal proteins. [ 12 ]


Immunoglobulin M (IgM)  pentameric  antibody molecule (consisting of five base units). 1: Base unit.  2:  Heavy chains . 3:  Light chains . 4:  J chain . 5: Intermolecular disulfide bonds.


Schematic of immunoglobulin A  dimer  showing  H-chain  (blue),  L-chain  (red),  J-chain  (magenta)  and  secretory component  (yellow).


Tight junctions are formed from action of different JAM proteins working in conjunction. Many of these JAM proteins will be localized in these junctions.


Molecular surface model of K-Casein [ 2 ]


In red/blue Phe105-Met106 bond of κ- casein [ 2 ]


Fluorescein isothiocyanate


Syntenic  gene organization of  keratin  and keratin-associated proteins on  human chromosome 17  and mouse chromosome 11. Based on Wu & Irwin (2018). [ 1 ]


Ki-67  immunostaining  of a  brain tumour  with a high proliferative rate


Chromosomal neighborhood of gene KIAA0232


Graphic alignment of KIAA0232 and DUF4603 from NCBI BLAST


This is a conceptual Translation of the gene KIAA0408.


Ideogram of human chromosome 2 showing the location of KIAA2012  (Image generated using BioRender) .


Human KIAA2012 promoter sequence. In red are common SNPs, highlighted in yellow is the conserved RFX1-6 transcription factor binding site, and the bolded letters show the transcription start site.


Schematic of KIAA2012 with annotations showing the Glutamine (E) and Glutamic Acid (Q) rich regions, DUF 4670, and the mixed charge cluster (MCC).  (Made using IBS Online Drawing Tool) .


Predicted folding pattern and 3-D structure of KIAA2012.  (Image generated by I-Tasser Online Tool) .


Predicted KIAA2012 secondary structure with a 91.2% confidence level.  (Image generated by Phyre 2.0)


Unrooted phylogenetic tree of the KIAA2012 orthologs found in Table 1.  Mammals (yellow), reptiles (red), amphibians (green), and fish (blue) are circled to differentiate between them, and images of each species are provided next to the three-letter code


The bioluminescent fish  Parapriacanthus ransonneti , which obtains its luciferase protein from its diet, rather than encoding it within its own genome


The rotating view of a smoothed chain of a knotted protein (PDB ID: 1xd3)


Four knot types identified in proteins: the 3 1  knot (upper left), the 4 1  knot (upper right), the 5 2  knots (lower left) and the 6 1  knot (lower right). These images were produced by KnotPlot. [ 5 ]  Note that the 3 1  knot has in fact two distinct forms: left-handed and right-handed. What is shown here is a right-handed 3 1  knot.


(A) A protein is an open chain. (B) To create a closed loop, we pick a point at an infinite distance, and connect it to the N and C termini, thus the whole topological structure becomes a closed loop.


A possible slipknot in a protein. If the terminus is cut from the red line (1), a trefoil knot is created (2).


Compound #40 (Amato 2011)


The tricopper site found in many laccases; note that each  copper  center is bound to the  imidazole  sidechains of  histidines  (color code: copper is brown,  nitrogen  is blue).


Leaf protein concentrate (Leafu) made from  stinging nettles


Lateral hemagglutinine


An  oligosaccharide  (shown in grey) bound in the binding site of a plant lectin ( Griffonia simplicifolia  isolectin IV in complex with the Lewis b  blood group  determinant); only a part of the oligosaccharide (central, in grey) is shown for clarity.


Lectin  histochemistry  of fish muscles infected by a  myxozoan


Leucoagglutinin is a toxic  phytohemagglutinin  found in raw  Vicia faba  (fava bean).


LRRIQ1 chromosome location


Using the leucine-rich repeat Query sequence of the LRRIQ1 protein, the Phyre2 program was utilized to make a figure outlining the predicted secondary structure based on its similarity to template leucine rich motifs.


Schematic illustration made using DOG software showing the domain of unknown function (DUF4641) as well as the location of secondary structures such as alpha helices, and post-translation modifications such as SUMO sites.


Displays the modeled secondary structures of LOC101059915 with the red indicating alpha helices, and the yellow indicating possible beta sheets.


Shows the unrooted branching of select orthologs for LOC10105519.


Cytogenic location of LOC101928193 at 9q34.2. [ 3 ]  The gene is on the positive strand and is located from base pairs 133,189,767 to 133,192,979.


LOC101928193 amino acid composition. [ 12 ]  This is a glycine, valine, and serine rich protein. It is also methionine, asparagine, aspartic acid, glutamic acid, and lysine poor.


LOC101928193 predicted secondary structure. [ 13 ]  The orange c's indicate predicted coils and the red e's indicate predicted beta sheets.


LOC101928193 predicted tertiary structure.  Image coloured by rainbow N → C terminus. [ 14 ]


LOC101928193 conceptual translation with post-translational modifications and motifs.


The Mean RPKM Values of 27 Different Human Tissues From RNA-Sequencing of LOC101928193. [ 4 ]  The protein is most highly expressed in the thyroid, ovaries, skin, and testes.


LOC101928193 promoter and isoforms. [ 4 ] [ 21 ]  There is one promoter and three isoforms.


LOC101928193 5' UTR stem loops near AUG. [ 22 ]


LOC101928193 Unrooted Phylogenetic Tree.  Color coded by taxonomic group: Mammals (orange), amphibians (green), fish (blue), mollusks (yellow), cnidarians (teal), fungi (lime green), and bacteria (purple). [ 25 ]


LOC101929193 rate of evolution in comparison to cytochrome c and fibrinogen. [ 3 ] [ 26 ]


LOC101928193 conserved coding domain found from a multiple sequence alignment of orthologs. [ 27 ]  A  sequence logo  provides a richer and more precise description of, for example, a  binding site , than would a  consensus sequence .


The best model generated by  I-TASSER [ 21 ]  for LRRIQ3. The 3 leucine-rich repeats are shown in red, salmon, and magenta respectively. The IQ calmodulin-binding domain is shown in green.


A representation of the domains, motif, and post-translational modification sites of LRRIQ3, generated using DOG 2.0. [ 24 ]


Diagram of  LUZP2  modification sites. The green bar is the area of the leucine zipper region.


Predicted structure of LUZP2 using I-TASSER [ 10 ]


Protein abundance values of  LUZP2  in various tissues in H. sapiens according to PaxDb. Abundance in parts per million. Relative protein abundance histogram from PaxDb.  LUZP2  is shown the red bin. [ 11 ]


Evolutionary rate of  LUZP2  compared to  Fibrinogen alpha  and  Cytochrome c .


Mad1 function in SAC. Mad1 homodimer in unattached kinetochores is bound to two c-Mad2 and forms a catalytic receptor for cytozolic o-Mad2. Complex Mad1-cMadD2-oMad2 catalyzes conformational change of inactive oMad2 to the active c-Mad2 form. C-Mad2 then binds to Cdc20 and mediates APC/C inhibition and mitotic arrest.


Crystal structure, dimer of Mad1-Mad2 complex, yellow and red=Mad1 monomers, palegreen= Mad2 monomers


The Maturation of mRNA


Figure 1: The Inhibitor Cystine Knot motif is shown. A compact disulfide-bond core with the following three pairs: Cys3-Cys17, Cys10-Cys21, and Cys16-Cys32.


Figure 2: MCa has a dipole moment with a basic-rich surface including the residues Lys19, Lys20, Lys22, Arg23, Arg24, and Arg3 without any acidic residue. The opposite surface contains four acidic residues Asp2, Glu12, Asp15, and Glu29.


Overview of signal transduction pathways involved in  apoptosis


A protein structure model of human mesothelin and the binding sites of MUC16 (CA125) and antibodies [ 16 ]


The structure of the C-terminal DUF1608 domain of the Methanosarcinales S-layer Tile Protein MA0829. A, the C-terminal DUF1608 domain of MA0829 with domain I colored red, domain II in blue, and the connector subdomain in yellow. B, the crystallographic dimer of the MA0829 CTR. C, a trimer of crystallographic CTR homodimers. Ammonium citrate ligands from the crystallization solution bound at intermolecular interfaces are shown in space filling representation. D, the hexagonal tiles formed from trimeric CTR homodimer assemblies. The primary, asymmetric, and trimer pores are indicated. E, a cutaway side view of the model of the MSTP S-layer (the representation in D is rotated 90° from the viewer). The position of the primary pore is indicated by arrowheads. Adapted from  [ 10 ]


PDB 2z0d EBI


MIF4GD is located on human chromosome 17q25.1 (second white band from bottom).


Schematic drawing of MIF4GD protein. MIF4G domain and predicted low complexity domains are shown, as well as predicted phosphorylation sites (red), and other post-translational modification sites, including acetylation and OGlcNAc sites (gray).


The predicted tertiary structure of MIF4GD by I-TASSER program. [ 14 ]  The MIF4G domain is colored gray, the N-terminus is located on the left in purple, and the C-terminus is on the right colored in red.


Conceptual Translation of MIF4GD mRNA and resulting protein. The MIF4G domain is highlighted in yellow, and a low complexity domain is highlighted in light purple. Predicted RNA-binding protein binding sites are highlighted in green, predicted miRNA binding sites are highlighted in pink, and predicted stem-loops are highlighted in blue. Conserved amino acids are bolded and/or underlined.


An unrooted phylogenetic tree of 19 MIF4GD orthologs, showing the divergence from the human MIF4GD protein (annotated with black arrow). Mammals are annotated with orange box, chordates by a red circle, and arthropods are within green oval. [ 40 ] [ 41 ] [ 42 ] [ 43 ] [ 44 ] [ 45 ] [ 46 ] [ 47 ]


Chromosome 14 diagram with MIPOL1 gene locus marked in red [ 9 ]


Gene neighborhood of MIPOL1


Fig.1. MIPOL1 domain diagram generated using Prosite MyDomains. [ 14 ]  The two coiled-coil domains are highlighted in blue. The green line indicates the Nuclear localization signal. Some important phosphorylation sites have been highlighted in red. Studies have shown that phosphorylation is an important modification for controlling nucleus-cytoplasm shuttling, and may therefore play an important role in sub-cellular localization of this protein (by modifying the  NLS  or  NES ) [ 15 ]  O-GlcNACylation site has been highlighted in grey.


Fig.2.Multiple Sequence Alignment of MIPOL1 Orthologs showing conservation of Bipartite Nuclear Localization Signal in Mammalian orthologs (Hsa is human, Lve is Lipotes vexillifer (dolphin), and Mja is Manis javanica (Pangolin)


Fig.3. Annotated conceptual translation of MIPOL1 isoform 1 showing the most important features. The underlined parts represent the coiled-coil domains. Bolded amino acids are highly conserved even in orthologs as distant as Cnidarians. Other bracketed regions show conserved protein family regions identified such as COG1196 and COG 4372. Exon boundaries are highlighted in blue. Bipartite nuclear localization signal is highlighted in blue. Parts of the protein absent in other isoforms have been highlighted.


Fig.4.Tertiary structure of MIPOL1 generated using I-TASSER: [ 25 ]  Blue represents the N-terminus, Red represents the C-terminus


Fig.5. Plot of number of amino acid changes per 100 amino acids as a function of date of divergence for MIPOL1, cytochrome c and Fibrinogen alpha


Schematic demonstrating  mitochondrial   fatty acid   beta-oxidation  and effects of  long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, LCHAD deficiency


Proteins that function as morpheeins are illustrated using a dice analogy where one dice can morph into two different shapes, cubic and tetrahedral. The illustrated assemblies apply a rule that the dice face with one spot must contact the dice face with four spots. To satisfy the rule for each dice in an assembly, the cubic dice can only form a tetramer and the tetrahedral dice can only assemble to a pentamer. This is analogous to two different conformations (morpheein forms) of a protein subunit each dictating assembly to a different oligomer. All dice in one assembly must be of the same shape before assembly. Thus, for example, the tetramer must come apart, and its component dice must change shape to a pyramid before they can participate in assembly into a pentamer.


A protein with 3 functional domains


Mothers against decapentaplegic homolog 2 , one of the nine homologues of mothers against decapentaplegic


APC/C structure indicating where the linear motifs from substrates bind.


Location of the  MT-ATP8  gene in the human mitochondrial genome.  MT-ATP8  is one of the two ATP synthase mitochondrial genes (red boxes).


The 46-nucleotide overlap in the reading frames of the human mitochondrial genes  MT-ATP8  and  MT-ATP6 . For each nucleotide triplet (square brackets), the corresponding amino acid is given (one-letter code), either in the +1 frame for  MT-ATP8  (in red) or in the +3 frame for  MT-ATP6  (in blue).


Location of the  MT-ND1  gene in the human mitochondrial genome.  MT-ND1  is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).


Location of the  MT-ND2  gene in the human mitochondrial genome.  MT-ND2  is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).


Location of the  MT-ND3  gene in the human mitochondrial genome.  MT-ND3  is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).


Location of the  MT-ND4  gene in the human mitochondrial genome.  MT-ND4  is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).


Location of the  MT-ND4L  gene in the human mitochondrial genome.  MT-ND4L  is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).


Location of the  MT-ND5  gene in the human mitochondrial genome.  MT-ND5  is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).


Location of the  MT-ND6  gene on the L strand of the human mitochondrial genome.  MT-ND6  is one of the seven NADH dehydrogenase mitochondrial genes (yellow boxes).


Tumor metastasis initiated by interactions between MUC16 and  mesothelin .


Interaction of MUC16 (CA125) and mesothelin [ 21 ]


Serum  protein electrophoresis  showing a paraprotein (spike/peak in the gamma zone) in a patient with  multiple myeloma .


Detailed representation of the M-band region of the sarcomere. [ 1 ]  Myomesin is bound to myosin at its N-terminal. Obscurin connects the myomesin dimers and binds to the C-terminal of titin. It is thought that the myomesin-titin interaction is vital for the execution of the mechanical functions of the  Ser/Thr kinase  domain of titin. [ 2 ]


Sarcomere and M-band structure. [ 3 ]  (a) electron micrograph of mouse heart muscle sarcomere. (b) diagram of sarcomere layout from (a). Myosin thick filaments are blue, thin actin filaments are orange, Z-discs are black, and the M-band is grey/white. (c) schematic of M-band composition of M-lines. (d) M-band hexagonal lattice based on electron microscopy sections. Blue circles represent myosin, pink circles represent linking filaments, and black lines are the positions of the linking material.


Domains of myomesin family. [ 3 ]  Binding partners are shown in purple. (a) myomesin 1: EH-sequence, S and H splicing variant are shown in green. (b) myomesin 2: has a noticeably smaller N-terminal than myomesin 1. (c) myomesin 3: shorter than myomesin 2.


A  tetrapeptide  (example:  Val - Gly - Ser - Ala ) with  green  highlighted N-terminal α-amino acid (example: L- valine ) and  blue  marked C-terminal α-amino acid (example: L- alanine ). This tetrapeptide could be encoded by the mRNA sequence 5'- GUU   GGU   AGU   GCU -3'.


Main symptoms of neurofibromatosis type I [ 28 ]