Signal-Seeker™: Protein Modification  Background Information

 

tech support

Introduction

The mammalian proteome has been estimated to contain multiple millions of unique proteoforms. This level of complexity is derived from a relatively simple genome (approx. 25,000 genes), a transcriptome which increases the potential protein footprint to 100,000, and protein post-translational modifications (PTMs) which account for the vast increase in proteome complexity and an almost limitless potential for functional diversity. This information suggests that nearly all proteins will be modified by multiple PTMs. For any given protein, a variety of PTM proteoforms offer a way to facilitate rapid cellular changes by altering the structure and function of the protein. 

In many cases PTMs have been shown to work in concert to orchestrate a specific protein function and recent studies have suggested that both cooperative and negative PTM crosstalk is a pervasive and fundamental cell regulatory mechanism.

Importantly for human health and disease, misregulation of PTMs has been implicated in the progression of diseases like cancer, heart failure, neurologic, and metabolic diseases.

See the table below for information about key, regulatory protein modifications, or go to ModPred (also found in our resources link) to see if your target protein may potentially be modified.

 

PTM

Established Function

Novel Function

Signal Transduction

Target Amino Acid(s)

PTM Crosstalk

Modifiers

Acetylation

epigenetic and metabloic regulation

protein stability, localization, synthesis

Yes

K

Yes

HAT, HDAC

Methylation

epigenetic regulation

protein: protein interaction, signal transduction

Yes

R,K

Yes

methyltransferase,

demethylase

N-linked Glycosylation

protein folding, structure, and stability

cell adhesion, trafficking of glycoproteins

Yes

N

Yes

glycosyltransferase,

glycoside hydrolase

O-linked Glycosylation

protein folding, structure, and stability

may compete with phosphorylatin for S,T binding

Yes

S,T

Yes

glycosyltransferase,

glycoside hydrolase

Phosphorylation

signal transduction

protein:protein interaction, precursor to degradation, epigentics

Yes

Y, S, T

Yes

Kinase, phosphatase

Palmitoylation

membrane protein association

subcellular trafficking of proteins, protein:protein interaction, stability

dynamic reversible modification

C, S, T

Yes

palmitoyl protein thioesterases

SUMOylation

nuclear protein localization, transcriptional activity

protein stability, response to stress, cell cycle 

Yes

K

Yes

SAE, ubc9, SENP

Ubiquitination

proteasomal targeting - degradation

protein localization, activity, protein:protein interaction

Yes

K

Yes

Ub Ligase, DUB

a 


Additional Links:

Overview of PTM Detection Techniques and Methods

General PTM IP Protocol

a 


Cytoskeleton is committed to providing the most comprehensive reagents that allow highly sensitive and specific detection of endogenous protein modifications. Signal-Seeker™ kits use affinity beads to isolate and enrich modified proteins from any given cell or tissue lysate. Quality affinity reagents are key to allowing enrichment of often very transient and low level modified species, the affinity beads developed by our scientist are highly optimized to maximie the probability of identifying key regulatory modifications of even the rarest species.

Advantages

• Unparalleled sensitivity due to optimized kit reagents

• Discover and publish novel regulatory mechanisms

• Confirm transfection & proteomic results with endogenous data

• Examine protein modification crosstalk