biology

SH2 domain

SH2 domain is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand SH2 domain rather than just read about it. In short: The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains bind to phosphorylated tyrosine residues on other proteins, modifying the function or activity of the SH2-containing protein.

Key takeaways

SH2 domain belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect SH2 domain to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of SH2 domain from memory before moving on to harder problems.

Reference excerpt

The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains bind to phosphorylated tyrosine residues on other proteins, modifying the function or activity of the SH2-containing protein. The SH2 domain may be considered as a prototypical modular protein-protein interaction domain, in that it allows for the transmission of signals controlling a variety of intracellular functions. SH2 domains are especially common in adaptor proteins that aid in the signal transduction of receptor tyrosine kinase pathways.

Structure and interactions SH2 domains contain about 100 amino acid residues and exhibit a central antiparallel β-sheet centered between two α-helices. Binding to phosphotyrosine-containing peptides involves a strictly-conserved Arg residue that pairs with the negatively-charged phosphate on the phosphotyrosine, and a surrounding pocket that recognizes flanking sequences on the target peptide. Compared to other signaling proteins, SH2 domains exhibit only a moderate degree of specificity for their target peptides, due to the relative weakness of the interactions with the flanking sequences. Over 100 human proteins are known to contain SH2 domains. A variety of tyrosine-containing sequences have been found to bind SH2 domains and are conserved across a wide range of organisms, performing similar functions. Binding of a phosphotyrosine-containing protein to an SH2 domain may lead to either activation or inactivation of the SH2-containing protein, depending on the types of interactions formed between the SH2 domain and other domains of the enzyme. Mutations that disrupt the structural stability of the SH2 domain, or that affect the binding of the phosphotyrosine peptide of the target, are involved in a range of diseases including X-linked agammaglobulinemia and severe combined immunodeficiency.

Diversity SH2 domains are not present in yeast and appear at the boundary between protozoa and animalia in organisms such as the social amoeba Dictyostelium discoideum. A detailed bioinformatic examination of SH2 domains of human and mouse reveals 120 SH2 domains contained within 115 proteins encoded by the human genome, representing a rapid rate of evolutionary expansion among the SH2 domains. A large number of SH2 domain structures have been solved and many SH2 proteins have been knocked out in mice.

Applications SH2 domains, and other binding domains, have been used in protein engineering to create protein assemblies. Protein assemblies are formed when several proteins bind to one another to create a larger structure (called a supramolecular assembly). Using molecular biology techniques, fusion proteins of specific enzymes and SH2 domains have been created, which can bind to each other to form protein assemblies. Since SH2 domains require phosphorylation in order for binding to occur, the use of kinase and phosphatase enzymes gives researchers control over whether protein assemblies will form or not. High affinity engineered SH2 domains have been developed and utilized for protein assembly applications. The goal of most protein assembly formation is to increase the efficiency of metabolic pathways via enzymatic co-localization. Other applications of SH2 domain mediated protein assemblies have been in the formation of high density fractal-like structures, which have extensive molecular trapping properties.

Examples Human proteins containing this domain include:

ABL1; ABL2 BCAR3; BLK; BLNK; BMX; BTK CHN2; CISH; CRK; CRKL; CSK DAPP1 FER; FES; FGR; FRK; FYN GRAP; GRAP2; GRB10; GRB14; GRB2; GRB7 HCK; HSH2D INPP5D; INPPL1; ITK; JAK2; LCK; LCP2; LYN MATK; NCK1; NCK2 PIK3R1; PIK3R2; PIK3R3; PLCG1; PLCG2; PTK6; PTPN11; PTPN6; RASA1 SH2B1; SH2B2; SH2B3; SH2D1A; SH2D1B; SH2D2A; SH2D3A; SH2D3C; SH2D4A; SH2D4B; SH2D5; SH2D6; SH3BP2; SHB; SHC1; SHC3; SHC4; SHD; SHE SLA; SLA2 SOCS1; SOCS2; SOCS3; SOCS4; SOCS5; SOCS6; SOCS7 SRC; SRMS STAT1; STAT2; STAT3; STAT4; STAT5A; STAT5B; STAT6 SUPT6H; SYK TEC; TENC1; TNS; TNS1; TNS3; TNS4; TXK VAV1; VAV2; VAV3 YES1; ZAP70

See also Phosphotyrosine-binding domains also bind phosphorylated tyrosines Anthony Pawson, discoverer of the SH2 Domain

References

External links SH2 Domain website created by lab of Dr. Piers Nash

Illustrations

Worked examples

Example 1 — a first encounter with SH2 domain

Start with the simplest possible case. Write down what SH2 domain claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to SH2 domain before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about SH2 domain ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of SH2 domain

In research: SH2 domain appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses SH2 domain in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: SH2 domain is common in secondary-school and first-year university syllabi. It links to neighbouring topics Peripheral membrane proteins, Protein domains, Signal transduction, so understanding it makes those chapters shorter.
In everyday life: Look for SH2 domain outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study SH2 domain in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what SH2 domain means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain SH2 domain out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is SH2 domain in simple terms?

Why does SH2 domain matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study SH2 domain?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on SH2 domain.