molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

, post-translational modification (PTM) is the

covalent A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...

process of changing

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s following

protein biosynthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the produc ...

. PTMs may involve

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

or occur spontaneously. Proteins are created by ribosomes, which translate

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

into polypeptide chains, which may then change to form the mature protein product. PTMs are important components in cell signalling, as for example when prohormones are converted to

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

s. Post-translational modifications can occur on the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

side chain In organic chemistry and biochemistry, a side chain is a substituent, chemical group that is attached to a core part of the molecule called the "main chain" or backbone chain, backbone. The side chain is a hydrocarbon branching element of a mo ...

s or at the protein's C- or N- termini. They can expand the chemical set of the 22

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

by changing an existing

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

or adding a new one such as phosphate.

Phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

is highly effective for controlling the enzyme activity and is the most common change after translation. Many

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

and prokaryotic proteins also have

carbohydrate A carbohydrate () is a biomolecule composed of carbon (C), hydrogen (H), and oxygen (O) atoms. The typical hydrogen-to-oxygen atomic ratio is 2:1, analogous to that of water, and is represented by the empirical formula (where ''m'' and ''n'' ...

molecules attached to them in a process called

glycosylation Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...

, which can promote

protein folding Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...

and improve stability as well as serving regulatory functions. Attachment of

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

molecules, known as lipidation, often targets a protein or part of a protein attached to the

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

. Other forms of post-translational modification consist of cleaving

peptide bond In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...

s, as in processing a propeptide to a mature form or removing the initiator

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other non-essential amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine play ...

residue. The formation of disulfide bonds from

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

residues may also be referred to as a post-translational modification. For instance, the peptide

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

is cut twice after disulfide bonds are formed, and a propeptide is removed from the middle of the chain; the resulting protein consists of two polypeptide chains connected by disulfide bonds. Some types of post-translational modification are consequences of

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

. Carbonylation is one example that targets the modified protein for degradation and can result in the formation of protein aggregates. Specific amino acid modifications can be used as

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

s indicating oxidative damage. PTMs and metal ions play a crucial and reciprocal role in regulating protein function, influencing cellular processes such as signal transduction and gene expression, with dysregulated interactions implicated in diseases like cancer and neurodegenerative disorders. Sites that often undergo post-translational modification are those that have a functional group that can serve as a

nucleophile In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...

in the reaction: the hydroxyl groups of serine,

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form when dissolved in water), a carboxyl group (which is in the deprotonated −COO− ...

, and tyrosine; the

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

forms of

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

, and

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...

; the thiolate

anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

; the carboxylates of aspartate and

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

; and the N- and C-termini. In addition, although the

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

of asparagine is a weak nucleophile, it can serve as an attachment point for

glycan The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate ...

s. Rarer modifications can occur at oxidized

s and at some methylene groups in side chains. Post-translational modification of proteins can be experimentally detected by a variety of techniques, including

mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...

, Eastern blotting, and Western blotting.

PTMs involving addition of functional groups

Addition by an enzyme ''in vivo''

Hydrophobic groups for membrane localization

* myristoylation (a type of acylation), attachment of myristate, a C₁₄ saturated acid * palmitoylation (a type of acylation), attachment of palmitate, a C₁₆ saturated acid * isoprenylation or prenylation, the addition of an isoprenoid group (e.g. farnesol and geranylgeraniol) ** farnesylation ** geranylgeranylation * glypiation, glycosylphosphatidylinositol (GPI) anchor formation via an amide bond to C-terminal tail

Cofactors for enhanced enzymatic activity

* lipoylation (a type of acylation), attachment of a lipoate (C₈) functional group * flavin moiety ( flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD)) may be covalently attached * heme C attachment via

thioether In organic chemistry, a sulfide (British English sulphide) or thioether is an organosulfur functional group with the connectivity as shown on right. Like many other sulfur-containing compounds, Volatile organic compound, volatile sulfides have ...

bonds with

s * phosphopantetheinylation, the addition of a 4'-phosphopantetheinyl moiety from

coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric ac ...

, as in fatty acid, polyketide, non-ribosomal peptide and leucine biosynthesis * retinylidene Schiff base formation

Modifications of translation factors

* diphthamide formation (on a histidine found in eEF2) * ethanolamine phosphoglycerol attachment (on glutamate found in eEF1α) * hypusine formation (on conserved lysine of eIF5A (eukaryotic) and aIF5A (archaeal)) * beta-Lysine addition on a conserved lysine of the elongation factor P (EFP) in most bacteria. EFP is a homolog to eIF5A (eukaryotic) and aIF5A (archaeal) (see above).

Smaller chemical groups

* acylation, e.g. ''O''-acylation (

esters In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...

), ''N''-acylation ( amides), ''S''-acylation ( thioesters) ** acetylation, the addition of an

acetyl In organic chemistry, an acetyl group is a functional group denoted by the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, an acetyl grou ...

group, either at the

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the amin ...

of the protein or at

residues. The reverse is called deacetylation. ** formylation *

alkylation Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting al ...

, the addition of an

alkyl In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl group is derived from a cy ...

group, e.g. methyl, ethyl ** methylation the addition of a methyl group, usually at

residues. The reverse is called

demethylation Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen at ...

. * amidation at C-terminus. Formed by oxidative dissociation of a C-terminal Gly residue. *

bond formation **

addition *** arginylation, a

tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

-mediation addition *** polyglutamylation, covalent linkage of

glutamic acid Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α- amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can ...

residues to the N-terminus of tubulin and some other proteins. (See tubulin polyglutamylase) *** polyglycylation, covalent linkage of one to more than 40

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

residues to the tubulin C-terminal tail * butyrylation * gamma-carboxylation dependent on

Vitamin K Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-translational modification, post-synthesis modification of certain proteins ...

, the addition of a glycosyl group to either

, asparagine,

, hydroxylysine, serine,

, tyrosine, or

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

resulting in a glycoprotein. Distinct from

glycation Glycation (non-enzymatic glycosylation) is the covalent bond, covalent attachment of a sugar to a protein, lipid or nucleic acid molecule. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is th ...

, which is regarded as a nonenzymatic attachment of sugars. ** ''O''-GlcNAc, addition of ''N''-acetylglucosamine to serine or threonine residues in a β-glycosidic linkage ** polysialylation, addition of polysialic acid (PSA) to neural cell adhesion molecule (NCAM) * malonylation * hydroxylation: addition of an oxygen atom to the side-chain of a Pro or Lys residue * iodination: addition of an iodine atom to the aromatic ring of a tyrosine residue (e.g. in thyroglobulin) * nucleotide addition such as ADP-ribosylation * phosphate ester (''O''-linked) or phosphoramidate (''N''-linked) formation **

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

, the addition of a

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

group, usually to serine,

, and tyrosine (''O''-linked), or

(''N''-linked) ** adenylylation, the addition of an adenylyl moiety, usually to tyrosine (''O''-linked), or

and

(''N''-linked) ** uridylylation, the addition of an uridylyl-group (i.e.

uridine monophosphate Uridine monophosphate (UMP), also known as 5′-uridylic acid ( conjugate base uridylate), is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside uridine. UMP consists of the phosphate group, th ...

(UMP)), usually to tyrosine * propionylation * pyroglutamate formation * ''S''-glutathionylation * ''S''-nitrosylation * ''S''-sulfenylation (''aka'' ''S''-sulphenylation), reversible covalent addition of one oxygen atom to the thiol group of a

residue * ''S''-sulfinylation, normally irreversible covalent addition of two oxygen atoms to the thiol group of a

residue * ''S''-sulfonylation, normally irreversible covalent addition of three oxygen atoms to the thiol group of a

residue, resulting in the formation of a cysteic acid residue * succinylation addition of a succinyl group to

* sulfation, the addition of a sulfate group to a tyrosine.

Non-enzymatic modifications ''in vivo''

Examples of non-enzymatic PTMs are glycation, glycoxidation, nitrosylation, oxidation, succination, and lipoxidation. *

, the addition of a sugar molecule to a protein without the controlling action of an enzyme. * carbamylation the addition of Isocyanic acid to a protein's N-terminus or the side-chain of Lys. * carbonylation the addition of carbon monoxide to other organic/inorganic compounds. * spontaneous isopeptide bond formation, as found in many surface proteins of

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain ...

Non-enzymatic additions ''in vitro''

* biotinylation: covalent attachment of a biotin moiety using a biotinylation reagent, typically for the purpose of labeling a protein. * carbamylation: the addition of isocyanic acid to a protein's N-terminus or the side-chain of Lys or Cys residues, typically resulting from exposure to urea solutions. * oxidation: addition of one or more oxygen atoms to a susceptible side-chain, principally of Met, Trp, His or Cys residues. Formation of

disulfide In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inorg ...

bonds between Cys residues. * pegylation: covalent attachment of

polyethylene glycol Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular wei ...

(PEG) using a pegylation reagent, typically to the N-terminus or the side-chains of Lys residues. Pegylation is used to improve the efficacy of protein pharmaceuticals.

Conjugation with other proteins or peptides

* ubiquitination, the

linkage to the protein ubiquitin. * SUMOylation, the covalent linkage to the

SUMO protein In molecular biology, SUMO (Small Ubiquitin-like Modifier) proteins are a Protein family, family of small proteins that are covalent bond, covalently attached to and detached from other proteins in cell (biology), cells to modify their function. T ...

(small ubiquitin-related modifier) * neddylation, the covalent linkage to the Nedd protein * ISGylation, the covalent linkage to the ISG15 protein (interferon-stimulated gene 15) * pupylation, the covalent linkage to the prokaryotic ubiquitin-like protein

Chemical modification of amino acids

* citrullination, or deimination, the conversion of

citrulline The organic compound citrulline is an α-amino acid. Its name is derived from '' citrullus'', the Latin word for watermelon. Although named and described by gastroenterologists since the late 19th century, it was first isolated from watermelon in ...

* deamidation, the conversion of glutamine to

or asparagine to

aspartic acid Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protei ...

* eliminylation, the conversion to an alkene by beta-elimination of phosphothreonine and phosphoserine, or

dehydration In physiology, dehydration is a lack of total body water that disrupts metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of water. Mild deh ...

and serine

Structural changes

* disulfide bridges, the covalent linkage of two

amino acids * lysine-cysteine bridges, the covalent linkage of 1 lysine and 1 or 2 cystine residues via an oxygen atom (NOS and SONOS bridges) * proteolytic cleavage, cleavage of a protein at a peptide bond * isoaspartate formation, via the cyclisation of asparagine or aspartic acid amino-acid residues * racemization ** of serine by protein-serine epimerase ** of

alanine Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group sid ...

in dermorphin, a frog

opioid peptide Opioid peptides or opiate peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these p ...

** of

in deltorphin, also a frog opioid peptide *

protein splicing Protein splicing is an intramolecular reaction of a particular protein in which an internal protein segment (called an intein) is removed from a precursor protein with a ligation of C-terminal and N-terminal external proteins (called exteins) o ...

, self-catalytic removal of inteins analogous to mRNA processing

Statistics

Common PTMs by frequency

In 2011, statistics of each post-translational modification experimentally and putatively detected have been compiled using proteome-wide information from the Swiss-Prot database. The 10 most common experimentally found modifications were as follows:

Common PTMs by residue

Some common post-translational modifications to specific amino-acid residues are shown below. Modifications occur on the side-chain unless indicated otherwise.

Databases and tools

Protein sequences contain sequence motifs that are recognized by modifying enzymes, and which can be documented or predicted in PTM databases. With the large number of different modifications being discovered, there is a need to document this sort of information in databases. PTM information can be collected through experimental means or predicted from high-quality, manually curated data. Numerous databases have been created, often with a focus on certain taxonomic groups (e.g. human proteins) or other features.

List of resources

PhosphoSitePlus
– A database of comprehensive information and tools for the study of mammalian protein post-translational modification * ProteomeScout – A database of proteins and post-translational modifications experimentally * Human Protein Reference Database – A database for different modifications and understand different proteins, their class, and function/process related to disease causing proteins * PROSITE – A database of Consensus patterns for many types of PTM's including sites * RESID – A database consisting of a collection of annotations and structures for PTMs.
iPTMnet
– A database that integrates PTM information from several knowledgbases and text mining results. * dbPTM – A database that shows different PTM's and information regarding their chemical components/structures and a frequency for amino acid modified site
Uniprot
has PTM information although that may be less comprehensive than in more specialized databases. Image for Wiki 1

The ''O''-GlcNAc Database
- A curated database for protein O-GlcNAcylation and referencing more than 14 000 protein entries and 10 000 ''O''-GlcNAc sites.

Tools

List of software for visualization of proteins and their PTMs * PyMOL – introduce a set of common PTM's into protein models * AWESOME – Interactive tool to see the role of single nucleotide polymorphisms to PTM's * Chimera – Interactive Database to visualize molecules

Case examples

* Cleavage and formation of disulfide bridges during the production of

* PTM of histones as regulation of transcription: RNA polymerase control by chromatin structure * PTM of

RNA polymerase II RNA polymerase II (RNAP II and Pol II) is a Protein complex, multiprotein complex that Transcription (biology), transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNA pol ...

as regulation of transcription * Cleavage of polypeptide chains as crucial for lectin specificity * Influence of Ni(II) in the Acetylation of Histones H4 Protein

References

External links

Controlled vocabulary of post-translational modifications
in Uniprot
List of posttranslational modifications in ExPASy

Browse SCOP domains by PTM
— from the dcGO database
Overview and description of commonly used post-translational modification detection techniques
{{DEFAULTSORT:Posttranslational Modification Gene expression Protein structure Protein biosynthesis Cell biology