stx2A

Gene Description

Shiga toxin 2A subunit (Stx2A) is the catalytic A chain of the AB5 Shiga toxin holotoxin produced by EHEC O157:H7. It is an rRNA N-glycosylase (EC 3.2.2.22) that depurinates a specific adenine in the sarcin-ricin loop of 28S rRNA, thereby inactivating ribosomes and halting protein synthesis. This ribosome-inactivating protein (RIP) activity leads to cell death and is the primary mechanism by which Shiga toxin causes hemolytic uremic syndrome (HUS). Stx2A represents a TRUE TOXIN with direct cytotoxic activity, in contrast to type III effectors like NleB1 that modulate signaling without direct cytotoxicity.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0035821 modulation of process of another organism	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Correct but overly broad. Stx2A modulates host translation by inactivating ribosomes, which falls under this term. The more specific terms (rRNA N-glycosylase, negative regulation of translation) are more informative.
GO:0016787 hydrolase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Correct parent term. rRNA N-glycosylases hydrolyze the N-glycosidic bond between adenine and ribose in rRNA. This is appropriately captured by the more specific child term GO:0030598.
GO:0017148 negative regulation of translation	IEA GO_REF:0000120	ACCEPT	Summary: Correct and core biological process. Stx2A inhibits translation by depurinating the sarcin-ricin loop of 28S rRNA, blocking elongation factor-dependent GTPase activity and halting ribosome function. This is the mechanism of toxicity.
GO:0030598 rRNA N-glycosylase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core molecular function. Stx2A is an rRNA N-glycosylase (EC 3.2.2.22) that removes adenine A4324 from the sarcin-ricin loop of 28S rRNA. This is the defining enzymatic activity of ribosome-inactivating proteins (RIPs). Cryo-EM (2023) and X-ray structures (2024) confirm the mechanism and P-stalk recruitment interface.
GO:0090729 toxin activity	IEA GO_REF:0000043	ACCEPT	Summary: LEGITIMATE toxin annotation. Unlike type III effectors (e.g., NleB1) that modulate signaling, Stx2A is a TRUE TOXIN with direct cytotoxic activity. It inactivates ribosomes, halts protein synthesis, and causes cell death. This is the defining virulence factor of EHEC O157:H7 and causes hemolytic uremic syndrome (HUS) in humans. The GO definition of toxin activity requiring initiating pathogenesis leading to an abnormal, generally detrimental state is clearly met by Stx2A.

Core Functions

Stx2A is an rRNA N-glycosylase (EC 3.2.2.22) that removes adenine A4324 from the sarcin-ricin loop of 28S rRNA. This is the core enzymatic activity of ribosome-inactivating proteins (RIPs). The enzyme is recruited to ribosomes via interaction with the P-stalk pentamer.

Molecular Function:

rRNA N-glycosylase activity

Directly Involved In:

negative regulation of translation

Stx2A is a TRUE TOXIN with direct cytotoxic activity. Unlike type III effectors that modulate signaling, Stx2A directly inactivates ribosomes, halts protein synthesis, and causes cell death. This is the defining virulence factor of EHEC O157:H7 and causes hemolytic uremic syndrome (HUS) in humans.

Molecular Function:

toxin activity

Gene Description

Existing Annotations Review

Core Functions

Stx2A is an rRNA N-glycosylase (EC 3.2.2.22) that removes adenine A4324 from the sarcin-ricin loop of 28S rRNA. This is the core enzymatic activity of ribosome-inactivating proteins (RIPs). The enzyme is recruited to ribosomes via interaction with the P-stalk pentamer.

Stx2A is a TRUE TOXIN with direct cytotoxic activity. Unlike type III effectors that modulate signaling, Stx2A directly inactivates ribosomes, halts protein synthesis, and causes cell death. This is the defining virulence factor of EHEC O157:H7 and causes hemolytic uremic syndrome (HUS) in humans.

References

Deep Research

Falcon

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