FLS2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006898 receptor-mediated endocytosis	IDA PMID:23085733 Spatio-temporal cellular dynamics of the Arabidopsis flagell...	KEEP AS NON CORE	Summary: FLS2 is ligand-dependently internalized after flg22 perception, and activation-state-dependent endosomal sorting is well supported. This describes receptor trafficking and signal attenuation rather than the core receptor activity itself. Reason: The annotation is biologically correct for activated FLS2, but it is a regulated fate of the receptor rather than the main evolved molecular function of the gene product.
GO:0016045 detection of bacterium	IMP PMID:10911994 FLS2: an LRR receptor-like kinase involved in the perception...	ACCEPT	Summary: FLS2 was identified genetically as the receptor-like kinase required for Arabidopsis perception of the bacterial flagellin elicitor. Reason: Detection of bacterial flagellin is central to Q9FL28/FLS2 biology and is supported by mutant and complementation evidence in the original FLS2 study.
GO:0042742 defense response to bacterium	IMP PMID:18158241 Pseudomonas syringae effector AvrPto blocks innate immunity ...	KEEP AS NON CORE	Summary: FLS2-dependent PAMP perception contributes to antibacterial defense, and AvrPto suppresses this immunity by targeting receptor kinases including FLS2. Reason: The antibacterial defense outcome is well supported, but the more precise core process for this gene is pathogen-associated molecular pattern receptor signaling.
GO:0042742 defense response to bacterium	IMP PMID:19095898 Glucosinolate metabolites required for an Arabidopsis innate...	KEEP AS NON CORE	Summary: The paper analyzes flg22-triggered innate immune responses including pathogen-triggered callose and resistance outputs. FLS2 acts upstream of these antibacterial defense responses through flagellin perception. Reason: The annotation is directionally correct, but it captures a broad defense outcome rather than the receptor kinase signaling role that is most informative for FLS2.
GO:0052544 defense response by callose deposition in cell wall	IMP PMID:19095898 Glucosinolate metabolites required for an Arabidopsis innate...	KEEP AS NON CORE	Summary: Flg22-triggered callose deposition is a downstream PAMP-triggered immunity output requiring the FLS2 pathway. Reason: Callose deposition is a valid downstream defense output, but FLS2 is the upstream flagellin receptor rather than a direct callose deposition or cell wall biosynthetic factor.
GO:0140426 pathogen-associated molecular pattern receptor signaling pathway	IMP PMID:20113440 Early signaling through the Arabidopsis pattern recognition ...	ACCEPT	Summary: FLS2-dependent flg22 perception activates early plasma-membrane electrical and calcium-associated signaling through the PAMP receptor pathway. Reason: This is the best existing biological-process term for the core FLS2 role: a cell-surface receptor pathway initiated by bacterial flagellin perception. Supporting Evidence: file:ARATH/FLS2/FLS2-deep-research-falcon.md The Falcon report summarizes Q9FL28/FLS2 as a plasma-membrane flagellin pattern-recognition receptor that activates PAMP-triggered immune signaling.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	MODIFY	Summary: The InterPro kinase-domain mapping is correct but too generic for FLS2, which is a single-pass receptor-like serine/threonine kinase. Reason: A more specific experimentally and domain-supported term exists for this protein. Proposed replacements: transmembrane receptor protein serine/threonine kinase activity
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000003	MODIFY	Summary: FLS2 has serine/threonine protein kinase activity, but the EC-based term omits the receptor and transmembrane context that distinguishes this protein. Reason: The specific receptor protein serine/threonine kinase term is a better fit for an LRR receptor-like kinase. Proposed replacements: transmembrane receptor protein serine/threonine kinase activity
GO:0004675 transmembrane receptor protein serine/threonine kinase activity	ISS PMID:10911994 FLS2: an LRR receptor-like kinase involved in the perception...	ACCEPT	Summary: FLS2 encodes a membrane-spanning LRR receptor-like kinase whose cytoplasmic kinase domain is required for flagellin responses. Reason: This molecular-function term captures the core receptor kinase activity of Q9FL28/FLS2.
GO:0005515 protein binding	IPI DOI:10.1038/s41586-020-2210-3	MARK AS OVER ANNOTATED	Summary: The cited work supports FLS2-BAK1/BIK1 receptor complex context and BIK1 release/internalization, but "protein binding" is too vague to represent the functional role of FLS2. Reason: The interaction evidence is useful mechanistic context, but GO:0005515 does not convey FLS2's receptor kinase or PAMP receptor activity.
GO:0005515 protein binding	IPI PMID:17625569 A flagellin-induced complex of the receptor FLS2 and BAK1 in...	MARK AS OVER ANNOTATED	Summary: The publication shows ligand-dependent FLS2 association with BAK1 during flagellin signaling. Reason: A generic protein binding annotation obscures the specific coreceptor complex formed during PAMP receptor signaling.
GO:0005515 protein binding	IPI PMID:17626179 The receptor-like kinase SERK3/BAK1 is a central regulator o...	MARK AS OVER ANNOTATED	Summary: SERK3/BAK1 rapidly enters an elicitor-dependent complex with FLS2 during flg22-triggered PTI. Reason: The physical interaction is real, but the annotation should not elevate vague protein binding over the specific FLS2-BAK1 receptor signaling event.
GO:0005515 protein binding	IPI PMID:18158241 Pseudomonas syringae effector AvrPto blocks innate immunity ...	MARK AS OVER ANNOTATED	Summary: AvrPto binds Arabidopsis FLS2 and other receptor kinases to block plant immune responses. Reason: Effector binding is mechanistically relevant but not a core molecular function of the plant receptor; GO:0005515 is too broad to be useful.
GO:0005515 protein binding	IPI PMID:19062288 Plant pattern-recognition receptor FLS2 is directed for degr...	MARK AS OVER ANNOTATED	Summary: AvrPtoB associates with FLS2 and promotes ubiquitination/degradation of the receptor as a pathogen virulence mechanism. Reason: This pathogen effector interaction is not the core FLS2 function and is better discussed as immune suppression/turnover context than as generic protein binding.
GO:0005515 protein binding	IPI PMID:20018686 A receptor-like cytoplasmic kinase, BIK1, associates with a ...	MARK AS OVER ANNOTATED	Summary: BIK1 associates with the FLS2/BAK1 receptor complex and is phosphorylated upon flagellin perception. Reason: The interaction supports the signaling complex, but GO:0005515 is under-informative compared with FLS2's PAMP receptor signaling role.
GO:0005515 protein binding	IPI PMID:20404519 Phosphorylation of receptor-like cytoplasmic kinases by bact...	MARK AS OVER ANNOTATED	Summary: The cited report reviews BIK1 and related RLCK association with the flagellin receptor complex downstream of FLS2/BAK1. Reason: This is useful pathway context, but the generic binding term should not be retained as a core functional annotation.
GO:0005515 protein binding	IPI PMID:20413097 Receptor-like cytoplasmic kinases integrate signaling from m...	MARK AS OVER ANNOTATED	Summary: BIK1 and related PBL kinases interact with FLS2 and are rapidly phosphorylated after FLS2 activation. Reason: The evidence supports downstream immune receptor complex signaling, not an informative standalone protein-binding function.
GO:0005515 protein binding	IPI PMID:20472560 Novel functions of Stomatal Cytokinesis-Defective 1 (SCD1) i...	MARK AS OVER ANNOTATED	Summary: SCD1 was implicated in bacterial PAMP response pathways and FLS2-associated immunity context. Reason: The annotation is a low-information interaction-style annotation and is peripheral to the receptor's core flagellin perception and kinase signaling function.
GO:0005515 protein binding	IPI PMID:21499263 Stem-cell-triggered immunity through CLV3p-FLS2 signalling.	MARK AS OVER ANNOTATED	Summary: This paper supports FLS2-mediated signaling by the endogenous CLV3 peptide and shows CLV3p-induced FLS2-BAK1 interaction. Reason: The noncanonical ligand/coreceptor interaction is interesting but should not be represented only as generic protein binding.
GO:0005515 protein binding	IPI PMID:21726371 Physical association of pattern-triggered immunity (PTI) and...	MARK AS OVER ANNOTATED	Summary: FLS2 was reported to physically associate with several ETI immune receptors, suggesting early PTI/ETI receptor proximity. Reason: These interactions are not the defining molecular function of FLS2 and GO:0005515 is too nonspecific for curation.
GO:0005515 protein binding	IPI PMID:22087006 Brassinosteroids inhibit pathogen-associated molecular patte...	MARK AS OVER ANNOTATED	Summary: The study examines FLS2-mediated immune signaling and BAK1-related pathway context during brassinosteroid crosstalk. Reason: Generic protein binding does not capture the specific signaling biology and should not be treated as a core FLS2 annotation.
GO:0005515 protein binding	IPI PMID:23250427 CRT1 is a nuclear-translocated MORC endonuclease that partic...	MARK AS OVER ANNOTATED	Summary: CRT1/MORC1 was reported to interact with FLS2 in immunity-related assays. Reason: This interaction is peripheral regulatory context and is not an informative molecular-function annotation for FLS2.
GO:0005515 protein binding	IPI PMID:23395902 Pseudomonas HopU1 modulates plant immune receptor levels by ...	MARK AS OVER ANNOTATED	Summary: GRP7-associated regulation affects FLS2/EFR transcripts and receptor levels during HopU1-mediated immune suppression. Reason: The evidence concerns regulation of receptor abundance and pathogen effector interference; GO:0005515 is not an informative function for FLS2.
GO:0005515 protein binding	IPI PMID:23532072 BR-SIGNALING KINASE1 physically associates with FLAGELLIN SE...	MARK AS OVER ANNOTATED	Summary: BSK1 physically associates with FLS2 and contributes to a subset of flg22-induced immune responses. Reason: The interaction supports pathway architecture, but generic protein binding is much less informative than receptor kinase/PAMP receptor signaling.
GO:0005515 protein binding	IPI PMID:24114786 Structural basis for flg22-induced activation of the Arabido...	MODIFY	Summary: The structural study directly supports flg22 perception by FLS2 and flg22-induced FLS2-BAK1 immune complex assembly. Reason: For this evidence, the more informative molecular-function annotation is pattern recognition receptor activity, rather than generic protein binding. Proposed replacements: pattern recognition receptor activity
GO:0005515 protein binding	IPI PMID:24629339 The FLS2-associated kinase BIK1 directly phosphorylates the ...	MARK AS OVER ANNOTATED	Summary: The paper places RBOHD downstream of the FLS2-associated kinase BIK1 in ROS and stomatal defense signaling. Reason: The evidence supports pathway wiring downstream of FLS2, but GO:0005515 does not describe FLS2's core activity.
GO:0005515 protein binding	IPI PMID:27208222 Two Redundant Receptor-Like Cytoplasmic Kinases Function Dow...	MARK AS OVER ANNOTATED	Summary: PCRK1 and PCRK2 interact with FLS2 and act downstream of pattern recognition receptors in salicylic-acid biosynthesis activation. Reason: These interactions are useful regulatory context, but they should not be curated as a generic binding function of FLS2.
GO:0005515 protein binding	IPI PMID:27317676 The Arabidopsis Malectin-Like/LRR-RLK IOS1 Is Critical for B...	MARK AS OVER ANNOTATED	Summary: IOS1 associates with FLS2/EFR/CERK1 complexes and promotes FLS2-BAK1 complex formation upon MAMP treatment. Reason: IOS1 binding is a pathway-regulatory interaction; the generic GO:0005515 term is not informative for FLS2 core function.
GO:0005515 protein binding	IPI PMID:29320478 An extracellular network of Arabidopsis leucine-rich repeat ...	MARK AS OVER ANNOTATED	Summary: The extracellular LRR-RK network study provides broad high-throughput interaction context for FLS2 and other receptor kinases. Reason: The interaction network is valuable context, but individual generic protein-binding annotations are too nonspecific and should not define FLS2 function.
GO:0005515 protein binding	IPI PMID:32327536 STRESS INDUCED FACTOR 2 Regulates Arabidopsis Stomatal Immun...	MARK AS OVER ANNOTATED	Summary: SIF2 physically associates with the FLS2-BAK1 PRR complex and links it to SLAC1-dependent stomatal immunity. Reason: This is a specific regulatory interaction in stomatal immunity, but GO:0005515 is too vague for the FLS2 review.
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATP binding is expected for the cytoplasmic protein kinase domain of FLS2. Reason: The annotation is compatible with the kinase domain but is less informative than the receptor protein serine/threonine kinase activity.
GO:0042802 identical protein binding	IPI PMID:29320478 An extracellular network of Arabidopsis leucine-rich repeat ...	MARK AS OVER ANNOTATED	Summary: The extracellular interaction network reported FLS2 self-interaction evidence, but other curated context indicates FLS2's key functional complex is ligand-induced association with BAK1/SERK co-receptors and downstream kinases. Reason: Identical protein binding is not a useful core annotation for FLS2 and should not override the established flg22-induced heteromeric receptor complex model.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	MODIFY	Summary: Rhea supports protein serine phosphorylation chemistry, but FLS2 is a receptor-like serine/threonine kinase and the serine-only term is incomplete. Reason: Replace with the specific receptor serine/threonine kinase activity term that captures both catalytic and membrane receptor context. Proposed replacements: transmembrane receptor protein serine/threonine kinase activity
GO:0007165 signal transduction	IEA GO_REF:0000117	MODIFY	Summary: FLS2 clearly participates in signal transduction, but this ARBA term is far broader than the known flagellin/PAMP receptor pathway. Reason: The specific FLS2 process is pathogen-associated molecular pattern receptor signaling. Proposed replacements: pathogen-associated molecular pattern receptor signaling pathway
GO:0007178 cell surface receptor protein serine/threonine kinase signaling pathway	IEA GO_REF:0000108	MODIFY	Summary: This logically inferred pathway term is directionally correct but still less specific than FLS2's established role in PAMP receptor signaling. Reason: The PAMP receptor signaling term more accurately represents the flagellin-triggered immune pathway. Proposed replacements: pathogen-associated molecular pattern receptor signaling pathway
GO:0071555 cell wall organization	IEA GO_REF:0000117	MODIFY	Summary: FLS2 acts upstream of callose deposition after flg22 perception, but it is not a general cell wall organization factor. Reason: A defense-specific callose deposition term is more accurate than broad cell wall organization. Proposed replacements: defense response by callose deposition in cell wall
GO:0005768 endosome	IDA DOI:10.1038/s41586-020-2210-3	MODIFY	Summary: Ligand-triggered FLS2/BIK1 pathway studies support dynamic endocytic compartment localization, but FLS2 is a single-pass membrane receptor. Reason: Endosome membrane is the more specific cellular-component term for the membrane-embedded receptor after internalization. Proposed replacements: endosome membrane
GO:0005768 endosome	IDA PMID:23085733 Spatio-temporal cellular dynamics of the Arabidopsis flagell...	MODIFY	Summary: Activated FLS2 is sorted into endosomal compartments after flg22 treatment. Reason: Because FLS2 is a transmembrane receptor, endosome membrane is more precise than the whole endosome component. Proposed replacements: endosome membrane
GO:0005886 plasma membrane	IDA DOI:10.1038/s41586-020-2210-3	ACCEPT	Summary: FLS2 is a plasma-membrane receptor in the flagellin-triggered PRR complex. Reason: Plasma membrane localization is essential to FLS2's cell-surface PAMP receptor role.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping to plasma membrane is consistent with direct experimental localization and FLS2 receptor biology. Reason: This location is well supported by independent experimental studies and is central to FLS2 function.
GO:0005886 plasma membrane	ISM GO_REF:0000122	ACCEPT	Summary: Prediction-based plasma membrane localization agrees with the experimentally established cell-surface receptor localization. Reason: Although the evidence code is computational, the asserted location is strongly supported by the overall literature.
GO:0005886 plasma membrane	HDA PMID:17644812 A high content in lipid-modified peripheral proteins and int...	ACCEPT	Summary: Plasma membrane proteomics identified Arabidopsis plasma membrane proteins, including receptor-like kinases, and is consistent with FLS2's cell-surface localization. Reason: The high-throughput annotation is consistent with direct FLS2 localization studies and the receptor's topology.
GO:0005886 plasma membrane	EXP PMID:24923602 Salicylic acid signaling controls the maturation and localiz...	ACCEPT	Summary: Salicylic-acid signaling increases the plasma-membrane pool of FLS2 and BAK1, supporting PM localization of the receptor complex. Reason: Plasma membrane localization is experimentally supported and biologically central for FLS2 ligand perception. Supporting Evidence: PMID:24923602 SA signaling also increases the PM pools of FLAGELLIN SENSING2 (FLS2)
GO:0005886 plasma membrane	EXP PMID:32404997 Ligand-induced monoubiquitination of BIK1 regulates plant im...	ACCEPT	Summary: FLS2-BAK1 receptor complex studies support plasma membrane localization before ligand-triggered downstream BIK1 release and endocytic dynamics. Reason: This is a core cellular location for FLS2-mediated PAMP perception. Supporting Evidence: PMID:32404997 FLS2 is polyubiquitinated and endocytosed 40 min after flg22 perception for signaling attenuation.
GO:0010008 endosome membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular-location mapping places activated/internalized FLS2 at the endosome membrane. Reason: Endosome membrane localization is a supported trafficking state of FLS2, but the primary site of ligand perception is the plasma membrane.
GO:0010008 endosome membrane	EXP PMID:24923602 Salicylic acid signaling controls the maturation and localiz...	KEEP AS NON CORE	Summary: FLS2 membrane pools and trafficking are regulated in defense-related secretory/endosomal contexts. Reason: This is valid supporting localization context, but it is secondary to the plasma membrane PRR role.
GO:0010008 endosome membrane	EXP PMID:32404997 Ligand-induced monoubiquitination of BIK1 regulates plant im...	KEEP AS NON CORE	Summary: Ligand-triggered FLS2 complex signaling is coupled to endocytic dynamics of signaling components. Reason: Endosome membrane localization is relevant to receptor/signaling component turnover but is not the primary core location for PAMP perception.
GO:0012505 endomembrane system	IDA DOI:10.1038/s41586-020-2210-3	MODIFY	Summary: FLS2 pathway components enter endocytic compartments after ligand activation, but "endomembrane system" is too broad for a curated FLS2 location. Reason: Endosome membrane is the more specific and biologically informative term for the activated receptor trafficking state. Proposed replacements: endosome membrane
GO:0016020 membrane	ISS PMID:10911994 FLS2: an LRR receptor-like kinase involved in the perception...	MODIFY	Summary: FLS2 was identified as a membrane receptor-like kinase, but the generic membrane term is underspecified. Reason: Plasma membrane is the experimentally supported and functionally relevant membrane compartment for flagellin perception. Proposed replacements: plasma membrane
GO:0016020 membrane	IDA PMID:16510871 Ligand-induced endocytosis of the pattern recognition recept...	MODIFY	Summary: FLS2-GFP resides at the cell membrane and moves into intracellular vesicles after flg22 stimulation. Reason: The direct localization evidence supports more specific plasma membrane and endosome membrane annotations. Proposed replacements: plasma membrane endosome membrane
GO:0071944 cell periphery	IEA GO_REF:0000117	MODIFY	Summary: ARBA inferred a broad cell-periphery location that is consistent with FLS2 being a cell-surface receptor. Reason: Plasma membrane is the more precise cellular-component term for FLS2. Proposed replacements: plasma membrane

Core Functions

FLS2 enables extracellular pattern-recognition receptor activity for bacterial flagellin-derived flg22 at the plant plasma membrane, leading to ligand-induced BAK1/SERK co-receptor recruitment and activation of pattern-triggered immunity.

Molecular Function:

pattern recognition receptor activity

Directly Involved In:

detection of bacterium pathogen-associated molecular pattern receptor signaling pathway

Cellular Locations:

plasma membrane

Supporting Evidence:

PMID:10911994
The FLS2 gene is ubiquitously expressed and encodes a putative receptor kinase.
PMID:24114786
Flagellin perception in Arabidopsis is through recognition of its highly conserved N-terminal epitope

The cytoplasmic kinase domain of FLS2 functions as a transmembrane receptor protein serine/threonine kinase in the activated immune receptor complex, coordinating phosphorylation-dependent signaling through BIK1/PBL kinases and downstream calcium, ROS, MAPK, transcriptional, stomatal, and callose defense outputs.

Molecular Function:

transmembrane receptor protein serine/threonine kinase activity

Directly Involved In:

pathogen-associated molecular pattern receptor signaling pathway

Cellular Locations:

plasma membrane endosome membrane

Supporting Evidence:

PMID:17625569
FLS2 and BAK1 form a complex
PMID:20018686
BIK1 associates with FLS2 and BAK1 in vivo and in vitro.
file:interpro/panther/PTHR48056/PTHR48056-entries.csv
Q9FL28,LRR receptor-like serine/threonine-protein kinase FLS2,protein,3702,Arabidopsis thaliana,Arabidopsis thaliana (Mouse-ear cress),FLS2,1173,PTHR48056:SF83,LRR RECEPTOR-LIKE SERINE_THREONINE-PROTEIN KINASE FLS2,True

References

UniProtKB:Q9FL28

UniProtKB reviewed entry for Arabidopsis FLS2/At5g46330

file:ARATH/FLS2/FLS2-deep-research-falcon.md

Falcon deep research report for Arabidopsis FLS2/Q9FL28

PANTHER:PTHR48056

Plant LRR receptor-like serine/threonine-protein kinases PANTHER family

FLS2/Q9FL28 is assigned to the FLS2-specific PTHR48056:SF83 subfamily.

"Q9FL28,LRR receptor-like serine/threonine-protein kinase FLS2,protein,3702,Arabidopsis thaliana,Arabidopsis thaliana (Mouse-ear cress),FLS2,1173,PTHR48056:SF83,LRR RECEPTOR-LIKE SERINE_THREONINE-PROTEIN KINASE FLS2,True"

file:interpro/panther/PTHR48056/PTHR48056-entries.csv

PANTHER PTHR48056 entries including Arabidopsis FLS2

Arabidopsis FLS2 is assigned to PTHR48056:SF83, the FLS2-specific LRR receptor-like Ser/Thr kinase subfamily.

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000003

Gene Ontology annotation based on Enzyme Commission mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000116

Automatic Gene Ontology annotation based on Rhea mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000122

AtSubP analysis

PMID:10911994

FLS2: an LRR receptor-like kinase involved in the perception of the bacterial elicitor flagellin in Arabidopsis.

PMID:16510871

Ligand-induced endocytosis of the pattern recognition receptor FLS2 in Arabidopsis.

PMID:17625569

A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant defence.

PMID:17626179

The receptor-like kinase SERK3/BAK1 is a central regulator of innate immunity in plants.

PMID:17644812

A high content in lipid-modified peripheral proteins and integral receptor kinases features in the arabidopsis plasma membrane proteome.

PMID:18158241

Pseudomonas syringae effector AvrPto blocks innate immunity by targeting receptor kinases.

PMID:19062288

Plant pattern-recognition receptor FLS2 is directed for degradation by the bacterial ubiquitin ligase AvrPtoB.

PMID:19095898

Glucosinolate metabolites required for an Arabidopsis innate immune response.

PMID:20018686

A receptor-like cytoplasmic kinase, BIK1, associates with a flagellin receptor complex to initiate plant innate immunity.

PMID:20113440

Early signaling through the Arabidopsis pattern recognition receptors FLS2 and EFR involves Ca-associated opening of plasma membrane anion channels.

PMID:20404519

Phosphorylation of receptor-like cytoplasmic kinases by bacterial flagellin.

PMID:20413097

Receptor-like cytoplasmic kinases integrate signaling from multiple plant immune receptors and are targeted by a Pseudomonas syringae effector.

PMID:20472560

Novel functions of Stomatal Cytokinesis-Defective 1 (SCD1) in innate immune responses against bacteria.

PMID:21499263

Stem-cell-triggered immunity through CLV3p-FLS2 signalling.

PMID:21726371

Physical association of pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) immune receptors in Arabidopsis.

PMID:22087006

Brassinosteroids inhibit pathogen-associated molecular pattern-triggered immune signaling independent of the receptor kinase BAK1.

PMID:23085733

Spatio-temporal cellular dynamics of the Arabidopsis flagellin receptor reveal activation status-dependent endosomal sorting.

PMID:23250427

CRT1 is a nuclear-translocated MORC endonuclease that participates in multiple levels of plant immunity.

PMID:23395902

Pseudomonas HopU1 modulates plant immune receptor levels by blocking the interaction of their mRNAs with GRP7.

PMID:23532072

BR-SIGNALING KINASE1 physically associates with FLAGELLIN SENSING2 and regulates plant innate immunity in Arabidopsis.

PMID:24114786

Structural basis for flg22-induced activation of the Arabidopsis FLS2-BAK1 immune complex.

PMID:24629339

The FLS2-associated kinase BIK1 directly phosphorylates the NADPH oxidase RbohD to control plant immunity.

PMID:24923602

Salicylic acid signaling controls the maturation and localization of the arabidopsis defense protein ACCELERATED CELL DEATH6.

PMID:27208222

Two Redundant Receptor-Like Cytoplasmic Kinases Function Downstream of Pattern Recognition Receptors to Regulate Activation of SA Biosynthesis.

PMID:27317676

The Arabidopsis Malectin-Like/LRR-RLK IOS1 Is Critical for BAK1-Dependent and BAK1-Independent Pattern-Triggered Immunity.

PMID:29320478

An extracellular network of Arabidopsis leucine-rich repeat receptor kinases.

PMID:32327536

STRESS INDUCED FACTOR 2 Regulates Arabidopsis Stomatal Immunity through Phosphorylation of the Anion Channel SLAC1.

PMID:32404997

Ligand-induced monoubiquitination of BIK1 regulates plant immunity.

DOI:10.1038/s41586-020-2210-3

Ligand-induced monoubiquitination of BIK1 regulates plant immunity.

DOI retained because GOA uses this identifier for four source annotations

"PMID:32404997 is the same publication, but validation requires the GOA original reference IDs to remain unchanged."

Suggested Experiments

Experiment: Compare endogenous-locus FLS2 variants defective in flg22 binding, kinase-catalytic activity, BAK1 recruitment, or endocytic sorting for restoration of calcium influx, ROS burst, MAPK activation, callose deposition, bacterial resistance, and receptor turnover in fls2 null plants.

Hypothesis: FLS2 ligand binding, kinase activity, and endocytosis make separable contributions to early PTI signaling and later receptor attenuation.

Type: structure-function genetics

Deep Research

Falcon

(FLS2-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 24 citations 2026-05-05T07:21:02.424033

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Functional Annotation of FLS2 (UniProt Q9FL28) in Arabidopsis thaliana

0) Target verification (mandatory)

The literature evidence matches the UniProt target (Q9FL28) as Arabidopsis thaliana FLAGELLIN-SENSING 2 (FLS2): a plasma membrane (PM)–localized leucine-rich repeat receptor-like kinase (LRR-RLK) that recognizes bacterial flagellin (flg22), recruits the co-receptor BAK1, and signals through the receptor-like cytoplasmic kinase BIK1 to trigger pattern-triggered immunity (PTI). This domain architecture and biological role align with the UniProt description (extracellular LRRs + TM + intracellular Ser/Thr kinase). (wang2023modificationsoftwo pages 1-4, lee2024reprogrammingofflagellin pages 1-2, bai2023bik1proteinhomeostasis pages 1-2)

1) Key concepts and current understanding

1.1 Definitions and core concepts

Pattern recognition receptor (PRR) / MAMP receptor: Cell-surface receptor that detects conserved microbial molecules (microbe-/pathogen-associated molecular patterns; MAMPs/PAMPs) and activates PTI. FLS2 is a prototypical PRR in plants. (wang2023modificationsoftwo pages 1-4, zhang2024unlockingnaturesdefense pages 1-2)

Ligand (MAMP) for FLS2: The canonical ligand is flg22, an immunogenic 22–amino-acid peptide epitope derived from bacterial flagellin. (wang2023modificationsoftwo pages 1-4, wan2017comparativeanalysisof pages 10-14)

Co-receptor: Many LRR-RKs require a SERK-family co-receptor. For Arabidopsis FLS2, the co-receptor is BAK1 (SERK3), which associates with FLS2 upon ligand perception to initiate signaling. (wang2023modificationsoftwo pages 1-4, bai2023bik1proteinhomeostasis pages 1-2)

1.2 Molecular function and reaction type (kinase activity)

FLS2 is a receptor Ser/Thr protein kinase whose molecular function is to transduce an extracellular bacterial flagellin-derived peptide signal into intracellular phosphorylation cascades. Its role is not to catalyze small-molecule metabolism but to catalyze protein phosphorylation in receptor complex activation and downstream signal propagation (autophosphorylation/transphosphorylation within receptor complexes are described as early events). (wang2023modificationsoftwo pages 1-4)

1.3 Ligand specificity and receptor complex formation

Ligand binding site and structural principle: Structural/functional synthesis places flg22 binding on the concave surface of the FLS2 LRR domain (reported as LRR3–LRR16 in a summarized structural description). (wan2017comparativeanalysisof pages 10-14)

Complex assembly kinetics: flg22 induces association of FLS2 with BAK1 very rapidly (reported as detectable in <15 seconds). (wan2017comparativeanalysisof pages 10-14)

Core signaling complex: Upon activation, FLS2 associates with BAK1 and forms a complex that includes BIK1. Early events include sequential auto- and trans-phosphorylation in the heterotrimer and mono-ubiquitination of BIK1, leading to BIK1 release and downstream signaling. (wang2023modificationsoftwo pages 1-4)

1.4 Downstream signaling outputs (cellular and physiological)

Across sources, FLS2 activation triggers hallmark PTI outputs: ROS burst, Ca2+ influx/ion channel activation, MAP kinase activation, transcriptional reprogramming of defense genes, stomatal closure, callose deposition, and prolonged outputs including seedling growth inhibition (a growth–defense tradeoff phenotype). (lee2024reprogrammingofflagellin pages 1-2, zhao2024structuralandbiochemical pages 1-2, wan2017comparativeanalysisof pages 10-14)

A key mechanistic node is BIK1, which becomes hyper-phosphorylated upon PAMP perception and directly phosphorylates multiple effectors, including:
- RbohD (NADPH oxidase) → ROS burst
- OSCA1.3 (Ca2+-permeable channel) and CNGC2/CNGC4 (cyclic nucleotide-gated channels) → Ca2+ entry and stomatal immunity
(bai2023bik1proteinhomeostasis pages 1-2)

2) Subcellular localization and trafficking/turnover

2.1 Localization

FLS2 is described as a plasma membrane–localized LRR-RLK. (wang2023modificationsoftwo pages 1-4, zhao2024structuralandbiochemical pages 1-2)

2.2 Endocytosis and receptor abundance control

FLS2 abundance and signaling duration are regulated by both ubiquitin-mediated turnover and endomembrane trafficking:

1) Proteasome-associated attenuation: In the presence of flagellin/flg22, BAK1 phosphorylates E3 ligases PUB12/PUB13, which then interact with and ubiquitinate FLS2 to attenuate signaling by promoting degradation via the ubiquitin–26S proteasome route (as described in the mechanistic summary). (wang2023modificationsoftwo pages 1-4)

2) Clathrin-dependent endocytosis and vacuolar routing: Activated FLS2 is internalized by clathrin-dependent endocytosis and traffics through TGN/early endosome (TGN/EE), intermediate compartments, and late endosome/multivesicular body (LE/MVB)/PVC before putative vacuolar breakdown. Dynamin-related proteins DRP2B and DRP1A contribute to endocytosis and regulate PM abundance of FLS2; ESCRT-I subunits VPS28-2 and VPS37-1 contribute to sorting activated FLS2 into MVB lumen for degradation. (wang2023modificationsoftwo pages 1-4)

3) Recent developments and latest research (prioritizing 2023–2024)

3.1 2023: BIK1 homeostasis controls signaling amplitude downstream of FLS2

A 2023 Nature Communications study describes how BIK1 protein abundance and activation state are tuned by competing ubiquitin ligases. RGLG1/RGLG2 preferentially associate with hypo-phosphorylated BIK1 and promote its association with BAK1, while PUB25/PUB26 are known to promote BIK1 degradation; these interactions help maintain BIK1 homeostasis and thereby influence immune signaling downstream of PRRs such as FLS2. (bai2023bik1proteinhomeostasis pages 1-2)

3.2 2023: ESCRT-targeting E3 ligase circuit stabilizes FLS2 abundance

A 2023 bioRxiv mechanistic study proposes that E3 ligase XBAT35.2 associates with the FLS2/BAK1/BIK1 complex and ubiquitinates ESCRT-I subunits VPS37-1 (K48-linked chains) and VPS28-2 (K63-linked chains), reducing FLS2 vacuolar breakdown and thereby stabilizing FLS2 to enhance immunity. This work extends the mechanistic picture from “FLS2 is endocytosed” to “specific ubiquitin-regulated ESCRT steps modulate how much receptor is degraded.” (wang2023modificationsoftwo pages 1-4)

3.3 2024: Reprogramming FLS2 with biased/surrogate small-molecule ligands

A 2024 Nature Communications paper conducted a large-scale reverse chemical screen against the FLS2 extracellular domain to test whether an LRR-RK can process structurally distinct ligands. Out of 22,618 compounds, 84 interacted with FLS2ECD. Two synthetic small molecules were prioritized:
- Maya2 (FIC44): binds FLS2ECD with Kd = 8.56 ± 3.07 µM and induces the defense reporter FRK1 in an FLS2-dependent manner.
- FIC04: weaker binding (Kd = 93.91 ± 19.51 µM) and minimal FRK1 induction.
The study interprets these as biased (surrogate) ligands that weakly activate FLS2 and drive antibacterial responses through gene-expression programs distinct from canonical flg22 signaling—an explicit translational entry point for chemical modulation of PRR outputs. (lee2024reprogrammingofflagellin pages 1-2, lee2024reprogrammingofflagellin media 139d0501)

3.4 2024: Updated structural/biochemical understanding of FLS2-like kinase activation (comparative insight)

A 2024 Plant Communications study in rice provides a mechanistic structural framework relevant to FLS2-type receptors more generally: OsFLS2 kinase-domain structures (kinase-dead mutant) were solved with ATP/ADP at 1.98 Å and 2.09 Å resolution and indicate that an active-like conformation can occur without phosphorylation but with weak basal autophosphorylation. The work further shows reciprocal phosphorylation between OsFLS2 and a SERK co-receptor (OsSERK2), leading to rapid phosphorylation of downstream RLCKs. While this is rice, the paper explicitly frames Arabidopsis FLS2–BAK1 complex formation as the canonical paradigm and provides a 2024 “activation logic” that informs how FLS2-family kinase domains can be structurally poised for activation by SERKs. (zhao2024structuralandbiochemical pages 1-2)

4) Current applications and real-world implementations

4.1 Chemical immune modulation (2024)

The surrogate-ligand discovery for FLS2 supports the concept of chemical elicitors that target PRRs directly, not by mimicking microbial peptides but by binding the receptor ectodomain and eliciting a tuned/biased output (e.g., antibacterial restriction with distinct transcriptional programs). Quantitative support includes the size of the screen and measured binding affinities (Kd) for Maya2 and FIC04. (lee2024reprogrammingofflagellin pages 1-2, lee2024reprogrammingofflagellin media 139d0501)

4.2 PRR transfer, natural variation, and deployment considerations (2024)

A 2024 review of PTI natural variation emphasizes that FLS2 is broadly conserved but that species-specific differences (ligand recognition strength, co-receptor/kinase-domain contributions to complex formation) impact translational deployment strategies. It highlights that OsFLS2 can complement Arabidopsis fls2 mutants (functional transfer/complementation) and notes naturally occurring loss-of-function variation affecting flg22-induced ROS in some crop germplasm (example: maize lines with LRR deletions lacking flg22-triggered ROS burst). These observations motivate receptor transfer/engineering while cautioning that co-receptor compatibility and ligand processing can be limiting factors. (hudson2024naturalvariationin pages 2-4)

4.3 Receptor engineering for expanded flagellin perception (preprint with 2024 DOI)

A bioRxiv preprint (posted with DOI dated 2024-09-09) describes a structure-guided workflow to engineer FLS2 homologs with expanded perception of polymorphic flg22 epitopes. It explicitly positions rational receptor engineering and PRR transfer as tools to enhance disease resistance, describing modeling thresholds (e.g., AlphaFold3 ipTM threshold 0.83 for best prediction accuracy) and public deposition of plasmids/data to accelerate downstream engineering efforts. (li2025unlockingexpandedflagellin pages 11-14)

5) Expert opinions and synthesis from authoritative sources

A 2024 MPMI distinguished review frames PM-localized receptor kinases/proteins (including LRR-RKs such as FLS2) as “border controls” that monitor invaders and initiate PTI, while also emphasizing immune homeostasis and the increasingly interconnected relationship between PTI and ETI in contemporary thinking. This is consistent with mechanistic studies showing that receptor abundance/turnover and output tuning are integral to preventing detrimental overactivation. (zhang2024unlockingnaturesdefense pages 1-2, wang2023modificationsoftwo pages 1-4)

6) Key statistics and data points (recent and/or mechanistically precise)

flg22 length: 22 amino acids. (wang2023modificationsoftwo pages 1-4)
FLS2–BAK1 association after flg22: detectable in <15 s (kinetic description in summarized mechanistic account). (wan2017comparativeanalysisof pages 10-14)
2024 chemical screen size: 22,618 compounds, 84 FLS2ECD interactors. (lee2024reprogrammingofflagellin pages 1-2)
Surrogate ligand binding affinities (MST): Maya2 Kd = 8.56 ± 3.07 µM; FIC04 Kd = 93.91 ± 19.51 µM. (lee2024reprogrammingofflagellin pages 1-2, lee2024reprogrammingofflagellin media 139d0501)
Rice FLS2-family kinase structural resolutions: 1.98 Å and 2.09 Å (ATP/ADP-bound). (zhao2024structuralandbiochemical pages 1-2)

Evidence-backed summary tables

Category	Details	Key sources
Identity/Type	Arabidopsis thaliana FLS2 (UniProt Q9FL28) matches the well-characterized FLAGELLIN-SENSING 2 receptor: a plasma-membrane localized leucine-rich repeat receptor-like serine/threonine kinase (LRR-RLK) with an extracellular LRR domain, a single transmembrane helix, and an intracellular kinase domain. The evidence consistently identifies it as the canonical bacterial flagellin receptor in Arabidopsis.	(wang2023modificationsoftwo pages 1-4, lee2024reprogrammingofflagellin pages 1-2, zhao2024structuralandbiochemical pages 1-2)
Ligand specificity	FLS2 recognizes bacterial flagellin, especially the immunogenic 22-amino-acid peptide flg22; structural evidence places flg22 binding on the concave surface of the FLS2 LRR region. A 2024 study further showed that FLS2 can also be weakly activated by surrogate small molecules (for example Maya2), indicating some signaling flexibility beyond the canonical peptide ligand.	(wang2023modificationsoftwo pages 1-4, wan2017comparativeanalysisof pages 10-14, lee2024reprogrammingofflagellin pages 1-2, lee2024reprogrammingofflagellin media 139d0501)
Coreceptor/complex	Upon flg22 perception, FLS2 rapidly associates with the co-receptor BAK1 at the plasma membrane and forms an activated signaling complex that also includes the RLCK BIK1. This complex undergoes sequential auto- and trans-phosphorylation, and ligand perception promotes BIK1 release for downstream signaling.	(wang2023modificationsoftwo pages 1-4, bai2023bik1proteinhomeostasis pages 1-2, wan2017comparativeanalysisof pages 10-14)
Immediate downstream kinases	BIK1 is the principal immediate downstream cytoplasmic kinase highlighted in the evidence. After activation, BIK1 becomes hyper-phosphorylated and phosphorylates targets including RbohD, OSCA1.3, and CNGC2/CNGC4, linking the FLS2 complex to ROS production, Ca2+ influx, and stomatal immunity.	(bai2023bik1proteinhomeostasis pages 1-2, lee2024reprogrammingofflagellin pages 1-2)
Early outputs	Canonical FLS2 signaling induces ROS/ROI production, ion-channel activation and Ca2+ entry, MAPK activation, defense gene transcription, stomatal closure, callose deposition, and prolonged seedling growth inhibition. These responses define FLS2 as a pattern-recognition receptor that initiates pattern-triggered immunity against bacterial pathogens.	(lee2024reprogrammingofflagellin pages 1-2, wan2017comparativeanalysisof pages 10-14, zhao2024structuralandbiochemical pages 1-2)
Trafficking/turnover regulators	FLS2 abundance is tightly controlled by ubiquitination and endomembrane trafficking. PUB12/PUB13 ubiquitinate FLS2 after BAK1-dependent phosphorylation to promote proteasome-associated attenuation, while activated FLS2 undergoes clathrin-dependent endocytosis through TGN/EE to LE/MVB/PVC and likely vacuolar degradation; DRP2B, DRP1A, VPS28-2, and VPS37-1 contribute to these steps.	(wang2023modificationsoftwo pages 1-4)
2023-2024 developments/applications	Recent mechanistic advances include identification of XBAT35.2 as a positive regulator that stabilizes FLS2 by targeting ESCRT-I subunits VPS37-1 and VPS28-2, thereby limiting receptor vacuolar breakdown. In 2024, a reverse chemical screen of 22,618 compounds discovered biased surrogate ligands for FLS2, showing that receptor outputs can be chemically reprogrammed and suggesting translational opportunities for immune modulation and receptor engineering.	(wang2023modificationsoftwo pages 1-4, lee2024reprogrammingofflagellin pages 1-2)
Key quantitative data	Supported quantitative points include: flg22 is a 22-aa peptide; ligand-induced FLS2-BAK1 association can occur in less than 15 s; the 2024 chemical screen tested 22,618 compounds and identified 84 FLS2ECD interactors; Maya2 bound FLS2ECD with Kd = 8.56 ± 3.07 µM, whereas FIC04 showed weaker binding with Kd = 93.91 ± 19.51 µM. In one construct-based assay series, flg22 was tested at 10 nM and Maya ligands at 1, 10, and 100 µM.	(wan2017comparativeanalysisof pages 10-14, lee2024reprogrammingofflagellin pages 1-2, lee2024reprogrammingofflagellin media 139d0501, lee2024reprogrammingofflagellin pages 6-7)

Table: This table summarizes the verified identity, molecular function, signaling role, localization, trafficking, and recent mechanistic advances for Arabidopsis thaliana FLS2 (UniProt Q9FL28). It is useful as a compact evidence-backed reference for building the full research report.

Source (first author, year)	Publication date (month/year if known)	Venue	Key finding related to FLS2	Quantitative/statistical details	URL/DOI	Evidence citation ids
Bai, 2023	Aug 2023	Nature Communications	Defined a 2023 regulatory layer downstream of Arabidopsis FLS2 in which BIK1 homeostasis is maintained by interplay among ubiquitin ligases; BIK1 acts immediately downstream of FLS2/BAK1 and phosphorylates RbohD, OSCA1.3, and CNGC2/4 to drive ROS, Ca2+ influx, and stomatal immunity.	Peer-reviewed study; excerpt notes RGLG1/2 preferentially bind hypo-phosphorylated BIK1 and positively regulate immune signaling, while PUB25 mediates RGLG2 degradation.	https://doi.org/10.1038/s41467-023-40364-0	(bai2023bik1proteinhomeostasis pages 1-2)
Wang, 2023	Aug 2023	bioRxiv	Identified XBAT35.2 as a positive regulator of FLS2 abundance: it associates with FLS2/BAK1/BIK1 and ubiquitinates ESCRT-I subunits VPS37-1 and VPS28-2, limiting FLS2 vacuolar breakdown and stabilizing receptor-mediated immunity.	flg22 recognized as a 22-aa peptide; FLS2–BAK1 association described as instantaneous; XBAT35.2 adds K48-linked chains to VPS37-1 and K63-linked chains to VPS28-2.	https://doi.org/10.1101/2023.08.10.552820	(wang2023modificationsoftwo pages 1-4)
Zhang, 2024	Feb 2024	Molecular Plant-Microbe Interactions	Review synthesizing recent PRR knowledge and positioning FLS2 as a plasma-membrane RK sentinel for MAMP perception and PTI, useful for interpreting FLS2 in the broader receptor-network and immune-homeostasis context.	Review article; no new FLS2-specific quantitative measurements in excerpt.	https://doi.org/10.1094/MPMI-10-23-0177-HH	(zhang2024unlockingnaturesdefense pages 1-2)
Zhao, 2024	Mar 2024	Plant Communications	Structural/biochemical work in rice provided a recent mechanistic model relevant to Arabidopsis FLS2: FLS2-type kinase domains can adopt an active conformation with weak basal autophosphorylation, while SERK co-receptors drive reciprocal phosphorylation and rapid RLCK phosphorylation.	OsFLS2 kinase-dead structures solved at 1.98 Å and 2.09 Å; enhanced OsFLS2–OsSERK2 interaction in presence of flg22; identifies recent mechanistic framework for FLS2-like activation.	https://doi.org/10.1016/j.xplc.2023.100785	(zhao2024structuralandbiochemical pages 1-2)
Hudson, 2024	Mar 2024	Molecular Plant Pathology	Review on natural PTI variation highlighting translational implications for FLS2 transfer/engineering: FLS2 is broadly conserved but ligand recognition and co-receptor requirements differ across species, affecting deployment strategies.	Notes OsFLS2 can complement Arabidopsis fls2 mutants; reports natural loss-of-function examples such as maize lines lacking flg22-triggered ROS burst due to LRR deletions; emphasizes species-specific ligand responses.	https://doi.org/10.1111/mpp.13445	(hudson2024naturalvariationin pages 2-4)
Lee, 2024	Nov 2024	Nature Communications	Discovered biased chemical ligands for Arabidopsis FLS2, showing that FLS2 can be weakly activated by noncanonical small molecules to induce antibacterial responses with unusual gene-expression outputs; a direct translational route toward chemical immune modulation.	Screened 22,618 compounds, found 84 FLS2ECD interactors; Maya2 bound FLS2ECD with Kd = 8.56 ± 3.07 µM; FIC04 with Kd = 93.91 ± 19.51 µM; flg22 tested at 10 nM and Maya ligands at 1, 10, 100 µM in follow-up assays.	https://doi.org/10.1038/s41467-024-54271-5	(lee2024reprogrammingofflagellin pages 1-2, lee2024reprogrammingofflagellin pages 6-7, lee2024reprogrammingofflagellin media 139d0501)
Li, 2025	Sep 2025 (preprint; DOI dated 2024-09-09)	bioRxiv	Presented a rational receptor-engineering workflow to expand flagellin perception by modifying FLS2 homologs; supports translational use of engineered or transferred FLS2 variants for broader pathogen recognition.	Structural modeling retained complexes with ipTM > 0.8; AF3 ipTM threshold 0.83 gave highest prediction accuracy; residues within 5 Å of ligand/co-receptor were selected for engineering; public plasmids/data deposited.	https://doi.org/10.1101/2024.09.09.612155	(li2025unlockingexpandedflagellin pages 1-4, li2025unlockingexpandedflagellin pages 11-14)

Table: This table summarizes 2023–2024 advances and closely related 2025 preprint developments with a 2024 DOI relevant to Arabidopsis FLS2, emphasizing mechanistic discoveries and translational applications such as receptor engineering and chemical elicitation.

Notes on evidence scope and limitations

Some foundational structural claims for Arabidopsis FLS2 (e.g., precise residues mediating flg22/BAK1 interfaces) are referenced by the recent sources but are not fully reproduced in the retrieved excerpts; the report therefore emphasizes claims explicitly stated in the extracted text and avoids adding unquoted residue-level details. (wan2017comparativeanalysisof pages 10-14, wang2023modificationsoftwo pages 1-4)
The rice structural study informs conserved activation mechanisms for FLS2-family receptors but is not direct experimental evidence on Arabidopsis Q9FL28 kinase-domain structure; it is presented as comparative mechanistic insight. (zhao2024structuralandbiochemical pages 1-2)

References

(wang2023modificationsoftwo pages 1-4): Chaofeng Wang, Yi Zhang, Bangjun Zhou, Pooja Raj Verma, Sadia Hamera, and Lirong Zeng. Modifications of two escrt-i subunits with distinct ubiquitin chains regulate plant immunity. bioRxiv, Aug 2023. URL: https://doi.org/10.1101/2023.08.10.552820, doi:10.1101/2023.08.10.552820. This article has 0 citations.
(lee2024reprogrammingofflagellin pages 1-2): Du-Hwa Lee, Ho-Seok Lee, Min-Soo Choi, Katarzyna Parys, Kaori L. Honda, Y. Kondoh, Jung-Min Lee, Natalie Edelbacher, Geon-Young Heo, Balaji Enugutti, Hiroyuki Osada, Ken Shirasu, and Youssef Belkhadir. Reprogramming of flagellin receptor responses with surrogate ligands. Nature Communications, Nov 2024. URL: https://doi.org/10.1038/s41467-024-54271-5, doi:10.1038/s41467-024-54271-5. This article has 8 citations and is from a highest quality peer-reviewed journal.
(bai2023bik1proteinhomeostasis pages 1-2): Jiaojiao Bai, Yuanyuan Zhou, Jianhang Sun, Kexin Chen, Yufang Han, Ranran Wang, Yanmin Zou, Mingshuo Du, and Dongping Lu. Bik1 protein homeostasis is maintained by the interplay of different ubiquitin ligases in immune signaling. Nature Communications, Aug 2023. URL: https://doi.org/10.1038/s41467-023-40364-0, doi:10.1038/s41467-023-40364-0. This article has 32 citations and is from a highest quality peer-reviewed journal.
(zhang2024unlockingnaturesdefense pages 1-2): Chao Zhang, Yingpeng Xie, Ping He, and Libo Shan. Unlocking nature's defense: plant pattern recognition receptors as guardians against pathogenic threats. Molecular plant-microbe interactions : MPMI, 37:MPMI10230177HH, Feb 2024. URL: https://doi.org/10.1094/mpmi-10-23-0177-hh, doi:10.1094/mpmi-10-23-0177-hh. This article has 47 citations.
(wan2017comparativeanalysisof pages 10-14): Wei-Lin Wan. Comparative analysis of signaling pathways triggered by different pattern-recognition receptor-types. ArXiv, Dec 2017. URL: https://doi.org/10.15496/publikation-20566, doi:10.15496/publikation-20566. This article has 0 citations.
(zhao2024structuralandbiochemical pages 1-2): Qiaoqiao Zhao, Jinlin Bao, Huailong Li, Wei Hu, Yanqiong Kong, Yifeng Zhong, Qiang Fu, Guolyu Xu, Fenmei Liu, Xi Jiao, Jian Jin, and Zhenhua Ming. Structural and biochemical basis of fls2-mediated signal activation and transduction in rice. Plant Communications, 5:100785, Mar 2024. URL: https://doi.org/10.1016/j.xplc.2023.100785, doi:10.1016/j.xplc.2023.100785. This article has 28 citations and is from a peer-reviewed journal.
(lee2024reprogrammingofflagellin media 139d0501): Du-Hwa Lee, Ho-Seok Lee, Min-Soo Choi, Katarzyna Parys, Kaori L. Honda, Y. Kondoh, Jung-Min Lee, Natalie Edelbacher, Geon-Young Heo, Balaji Enugutti, Hiroyuki Osada, Ken Shirasu, and Youssef Belkhadir. Reprogramming of flagellin receptor responses with surrogate ligands. Nature Communications, Nov 2024. URL: https://doi.org/10.1038/s41467-024-54271-5, doi:10.1038/s41467-024-54271-5. This article has 8 citations and is from a highest quality peer-reviewed journal.
(hudson2024naturalvariationin pages 2-4): Asher Hudson, Alexander Mullens, Sarah Hind, Tiffany Jamann, and Peter Balint‐Kurti. Natural variation in the pattern‐triggered immunity response in plants: investigations, implications and applications. Molecular Plant Pathology, Mar 2024. URL: https://doi.org/10.1111/mpp.13445, doi:10.1111/mpp.13445. This article has 25 citations and is from a peer-reviewed journal.
(li2025unlockingexpandedflagellin pages 11-14): Tianrun Li, Esteban Jarquin Bolanos, Danielle Stevens, Hanxu Sha, Daniil M Prigozhin, and Gitta Coaker. Unlocking expanded flagellin perception through rational receptor engineering. bioRxiv, Sep 2025. URL: https://doi.org/10.1101/2024.09.09.612155, doi:10.1101/2024.09.09.612155. This article has 25 citations.
(lee2024reprogrammingofflagellin pages 6-7): Du-Hwa Lee, Ho-Seok Lee, Min-Soo Choi, Katarzyna Parys, Kaori L. Honda, Y. Kondoh, Jung-Min Lee, Natalie Edelbacher, Geon-Young Heo, Balaji Enugutti, Hiroyuki Osada, Ken Shirasu, and Youssef Belkhadir. Reprogramming of flagellin receptor responses with surrogate ligands. Nature Communications, Nov 2024. URL: https://doi.org/10.1038/s41467-024-54271-5, doi:10.1038/s41467-024-54271-5. This article has 8 citations and is from a highest quality peer-reviewed journal.
(li2025unlockingexpandedflagellin pages 1-4): Tianrun Li, Esteban Jarquin Bolanos, Danielle Stevens, Hanxu Sha, Daniil M Prigozhin, and Gitta Coaker. Unlocking expanded flagellin perception through rational receptor engineering. bioRxiv, Sep 2025. URL: https://doi.org/10.1101/2024.09.09.612155, doi:10.1101/2024.09.09.612155. This article has 25 citations.

Citations

wang2023modificationsoftwo pages 1-4
wan2017comparativeanalysisof pages 10-14
zhao2024structuralandbiochemical pages 1-2
hudson2024naturalvariationin pages 2-4
li2025unlockingexpandedflagellin pages 11-14
lee2024reprogrammingofflagellin pages 1-2
zhang2024unlockingnaturesdefense pages 1-2
lee2024reprogrammingofflagellin pages 6-7
li2025unlockingexpandedflagellin pages 1-4
https://doi.org/10.1038/s41467-023-40364-0
https://doi.org/10.1101/2023.08.10.552820
https://doi.org/10.1094/MPMI-10-23-0177-HH
https://doi.org/10.1016/j.xplc.2023.100785
https://doi.org/10.1111/mpp.13445
https://doi.org/10.1038/s41467-024-54271-5
https://doi.org/10.1101/2024.09.09.612155
https://doi.org/10.1101/2023.08.10.552820,
https://doi.org/10.1038/s41467-024-54271-5,
https://doi.org/10.1038/s41467-023-40364-0,
https://doi.org/10.1094/mpmi-10-23-0177-hh,
https://doi.org/10.15496/publikation-20566,
https://doi.org/10.1016/j.xplc.2023.100785,
https://doi.org/10.1111/mpp.13445,
https://doi.org/10.1101/2024.09.09.612155,

📄 View Raw YAML

id: Q9FL28
gene_symbol: FLS2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:3702
  label: Arabidopsis thaliana
description: >-
  Arabidopsis FLS2 (At5g46330; UniProt Q9FL28) is the FLAGELLIN-SENSING 2
  leucine-rich repeat receptor-like serine/threonine kinase, not the unrelated
  flavonol synthase accession sometimes sharing the FLS2 symbol. FLS2 is a
  plasma-membrane pattern-recognition receptor that detects bacterial flagellin,
  especially the flg22 epitope, recruits SERK-family co-receptors such as
  BAK1/SERK3 and receptor-like cytoplasmic kinases including BIK1/PBL proteins,
  and initiates pattern-triggered immunity. Ligand perception drives receptor
  complex phosphorylation, calcium/anion channel and ROS signaling, MAP kinase
  activation, defense gene expression, callose deposition, stomatal defense, and
  regulated receptor endocytosis/turnover.
references:
- id: UniProtKB:Q9FL28
  title: UniProtKB reviewed entry for Arabidopsis FLS2/At5g46330
  findings: []
- id: file:ARATH/FLS2/FLS2-deep-research-falcon.md
  title: Falcon deep research report for Arabidopsis FLS2/Q9FL28
  findings: []
- id: PANTHER:PTHR48056
  title: Plant LRR receptor-like serine/threonine-protein kinases PANTHER family
  findings:
  - statement: FLS2/Q9FL28 is assigned to the FLS2-specific PTHR48056:SF83 subfamily.
    supporting_text: >-
      Q9FL28,LRR receptor-like serine/threonine-protein kinase FLS2,protein,3702,Arabidopsis
      thaliana,Arabidopsis thaliana (Mouse-ear cress),FLS2,1173,PTHR48056:SF83,LRR
      RECEPTOR-LIKE SERINE_THREONINE-PROTEIN KINASE FLS2,True
- id: file:interpro/panther/PTHR48056/PTHR48056-entries.csv
  title: PANTHER PTHR48056 entries including Arabidopsis FLS2
  findings:
  - statement: >-
      Arabidopsis FLS2 is assigned to PTHR48056:SF83, the FLS2-specific LRR receptor-like
      Ser/Thr kinase subfamily.
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology
    links
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000122
  title: AtSubP analysis
  findings: []
- id: PMID:10911994
  title: 'FLS2: an LRR receptor-like kinase involved in the perception of the bacterial
    elicitor flagellin in Arabidopsis.'
  findings: []
- id: PMID:16510871
  title: Ligand-induced endocytosis of the pattern recognition receptor FLS2 in Arabidopsis.
  findings: []
- id: PMID:17625569
  title: A flagellin-induced complex of the receptor FLS2 and BAK1 initiates plant
    defence.
  findings: []
- id: PMID:17626179
  title: The receptor-like kinase SERK3/BAK1 is a central regulator of innate immunity
    in plants.
  findings: []
- id: PMID:17644812
  title: A high content in lipid-modified peripheral proteins and integral receptor
    kinases features in the arabidopsis plasma membrane proteome.
  findings: []
- id: PMID:18158241
  title: Pseudomonas syringae effector AvrPto blocks innate immunity by targeting
    receptor kinases.
  findings: []
- id: PMID:19062288
  title: Plant pattern-recognition receptor FLS2 is directed for degradation by the
    bacterial ubiquitin ligase AvrPtoB.
  findings: []
- id: PMID:19095898
  title: Glucosinolate metabolites required for an Arabidopsis innate immune response.
  findings: []
- id: PMID:20018686
  title: A receptor-like cytoplasmic kinase, BIK1, associates with a flagellin receptor
    complex to initiate plant innate immunity.
  findings: []
- id: PMID:20113440
  title: Early signaling through the Arabidopsis pattern recognition receptors FLS2
    and EFR involves Ca-associated opening of plasma membrane anion channels.
  findings: []
- id: PMID:20404519
  title: Phosphorylation of receptor-like cytoplasmic kinases by bacterial flagellin.
  findings: []
- id: PMID:20413097
  title: Receptor-like cytoplasmic kinases integrate signaling from multiple plant
    immune receptors and are targeted by a Pseudomonas syringae effector.
  findings: []
- id: PMID:20472560
  title: Novel functions of Stomatal Cytokinesis-Defective 1 (SCD1) in innate immune
    responses against bacteria.
  findings: []
- id: PMID:21499263
  title: Stem-cell-triggered immunity through CLV3p-FLS2 signalling.
  findings: []
- id: PMID:21726371
  title: Physical association of pattern-triggered immunity (PTI) and effector-triggered
    immunity (ETI) immune receptors in Arabidopsis.
  findings: []
- id: PMID:22087006
  title: Brassinosteroids inhibit pathogen-associated molecular pattern-triggered
    immune signaling independent of the receptor kinase BAK1.
  findings: []
- id: PMID:23085733
  title: Spatio-temporal cellular dynamics of the Arabidopsis flagellin receptor reveal
    activation status-dependent endosomal sorting.
  findings: []
- id: PMID:23250427
  title: CRT1 is a nuclear-translocated MORC endonuclease that participates in multiple
    levels of plant immunity.
  findings: []
- id: PMID:23395902
  title: Pseudomonas HopU1 modulates plant immune receptor levels by blocking the
    interaction of their mRNAs with GRP7.
  findings: []
- id: PMID:23532072
  title: BR-SIGNALING KINASE1 physically associates with FLAGELLIN SENSING2 and regulates
    plant innate immunity in Arabidopsis.
  findings: []
- id: PMID:24114786
  title: Structural basis for flg22-induced activation of the Arabidopsis FLS2-BAK1
    immune complex.
  findings: []
- id: PMID:24629339
  title: The FLS2-associated kinase BIK1 directly phosphorylates the NADPH oxidase
    RbohD to control plant immunity.
  findings: []
- id: PMID:24923602
  title: Salicylic acid signaling controls the maturation and localization of the
    arabidopsis defense protein ACCELERATED CELL DEATH6.
  findings: []
- id: PMID:27208222
  title: Two Redundant Receptor-Like Cytoplasmic Kinases Function Downstream of Pattern
    Recognition Receptors to Regulate Activation of SA Biosynthesis.
  findings: []
- id: PMID:27317676
  title: The Arabidopsis Malectin-Like/LRR-RLK IOS1 Is Critical for BAK1-Dependent
    and BAK1-Independent Pattern-Triggered Immunity.
  findings: []
- id: PMID:29320478
  title: An extracellular network of Arabidopsis leucine-rich repeat receptor kinases.
  findings: []
- id: PMID:32327536
  title: STRESS INDUCED FACTOR 2 Regulates Arabidopsis Stomatal Immunity through Phosphorylation
    of the Anion Channel SLAC1.
  findings: []
- id: PMID:32404997
  title: Ligand-induced monoubiquitination of BIK1 regulates plant immunity.
  findings: []
- id: DOI:10.1038/s41586-020-2210-3
  title: Ligand-induced monoubiquitination of BIK1 regulates plant immunity.
  findings:
  - statement: DOI retained because GOA uses this identifier for four source annotations
    supporting_text: PMID:32404997 is the same publication, but validation requires the GOA original reference IDs to remain unchanged.
existing_annotations:
- term:
    id: GO:0006898
    label: receptor-mediated endocytosis
  evidence_type: IDA
  original_reference_id: PMID:23085733
  review:
    summary: >-
      FLS2 is ligand-dependently internalized after flg22 perception, and
      activation-state-dependent endosomal sorting is well supported. This
      describes receptor trafficking and signal attenuation rather than the core
      receptor activity itself.
    action: KEEP_AS_NON_CORE
    reason: >-
      The annotation is biologically correct for activated FLS2, but it is a
      regulated fate of the receptor rather than the main evolved molecular
      function of the gene product.
- term:
    id: GO:0016045
    label: detection of bacterium
  evidence_type: IMP
  original_reference_id: PMID:10911994
  review:
    summary: >-
      FLS2 was identified genetically as the receptor-like kinase required for
      Arabidopsis perception of the bacterial flagellin elicitor.
    action: ACCEPT
    reason: >-
      Detection of bacterial flagellin is central to Q9FL28/FLS2 biology and is
      supported by mutant and complementation evidence in the original FLS2
      study.
- term:
    id: GO:0042742
    label: defense response to bacterium
  evidence_type: IMP
  original_reference_id: PMID:18158241
  review:
    summary: >-
      FLS2-dependent PAMP perception contributes to antibacterial defense, and
      AvrPto suppresses this immunity by targeting receptor kinases including
      FLS2.
    action: KEEP_AS_NON_CORE
    reason: >-
      The antibacterial defense outcome is well supported, but the more precise
      core process for this gene is pathogen-associated molecular pattern
      receptor signaling.
- term:
    id: GO:0042742
    label: defense response to bacterium
  evidence_type: IMP
  original_reference_id: PMID:19095898
  review:
    summary: >-
      The paper analyzes flg22-triggered innate immune responses including
      pathogen-triggered callose and resistance outputs. FLS2 acts upstream of
      these antibacterial defense responses through flagellin perception.
    action: KEEP_AS_NON_CORE
    reason: >-
      The annotation is directionally correct, but it captures a broad defense
      outcome rather than the receptor kinase signaling role that is most
      informative for FLS2.
- term:
    id: GO:0052544
    label: defense response by callose deposition in cell wall
  evidence_type: IMP
  original_reference_id: PMID:19095898
  review:
    summary: >-
      Flg22-triggered callose deposition is a downstream PAMP-triggered immunity
      output requiring the FLS2 pathway.
    action: KEEP_AS_NON_CORE
    reason: >-
      Callose deposition is a valid downstream defense output, but FLS2 is the
      upstream flagellin receptor rather than a direct callose deposition or cell
      wall biosynthetic factor.
- term:
    id: GO:0140426
    label: pathogen-associated molecular pattern receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:20113440
  review:
    summary: >-
      FLS2-dependent flg22 perception activates early plasma-membrane electrical
      and calcium-associated signaling through the PAMP receptor pathway.
    action: ACCEPT
    reason: >-
      This is the best existing biological-process term for the core FLS2 role:
      a cell-surface receptor pathway initiated by bacterial flagellin
      perception.
    supported_by:
    - reference_id: file:ARATH/FLS2/FLS2-deep-research-falcon.md
      supporting_text: >-
        The Falcon report summarizes Q9FL28/FLS2 as a plasma-membrane
        flagellin pattern-recognition receptor that activates PAMP-triggered
        immune signaling.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      The InterPro kinase-domain mapping is correct but too generic for FLS2,
      which is a single-pass receptor-like serine/threonine kinase.
    action: MODIFY
    reason: >-
      A more specific experimentally and domain-supported term exists for this
      protein.
    proposed_replacement_terms:
    - id: GO:0004675
      label: transmembrane receptor protein serine/threonine kinase activity
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  review:
    summary: >-
      FLS2 has serine/threonine protein kinase activity, but the EC-based term
      omits the receptor and transmembrane context that distinguishes this
      protein.
    action: MODIFY
    reason: >-
      The specific receptor protein serine/threonine kinase term is a better fit
      for an LRR receptor-like kinase.
    proposed_replacement_terms:
    - id: GO:0004675
      label: transmembrane receptor protein serine/threonine kinase activity
- term:
    id: GO:0004675
    label: transmembrane receptor protein serine/threonine kinase activity
  evidence_type: ISS
  original_reference_id: PMID:10911994
  review:
    summary: >-
      FLS2 encodes a membrane-spanning LRR receptor-like kinase whose cytoplasmic
      kinase domain is required for flagellin responses.
    action: ACCEPT
    reason: >-
      This molecular-function term captures the core receptor kinase activity of
      Q9FL28/FLS2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: DOI:10.1038/s41586-020-2210-3
  review:
    summary: >-
      The cited work supports FLS2-BAK1/BIK1 receptor complex context and BIK1
      release/internalization, but "protein binding" is too vague to represent
      the functional role of FLS2.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction evidence is useful mechanistic context, but GO:0005515
      does not convey FLS2's receptor kinase or PAMP receptor activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17625569
  review:
    summary: >-
      The publication shows ligand-dependent FLS2 association with BAK1 during
      flagellin signaling.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      A generic protein binding annotation obscures the specific coreceptor
      complex formed during PAMP receptor signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17626179
  review:
    summary: >-
      SERK3/BAK1 rapidly enters an elicitor-dependent complex with FLS2 during
      flg22-triggered PTI.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The physical interaction is real, but the annotation should not elevate
      vague protein binding over the specific FLS2-BAK1 receptor signaling
      event.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18158241
  review:
    summary: >-
      AvrPto binds Arabidopsis FLS2 and other receptor kinases to block plant
      immune responses.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Effector binding is mechanistically relevant but not a core molecular
      function of the plant receptor; GO:0005515 is too broad to be useful.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19062288
  review:
    summary: >-
      AvrPtoB associates with FLS2 and promotes ubiquitination/degradation of the
      receptor as a pathogen virulence mechanism.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This pathogen effector interaction is not the core FLS2 function and is
      better discussed as immune suppression/turnover context than as generic
      protein binding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20018686
  review:
    summary: >-
      BIK1 associates with the FLS2/BAK1 receptor complex and is phosphorylated
      upon flagellin perception.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction supports the signaling complex, but GO:0005515 is
      under-informative compared with FLS2's PAMP receptor signaling role.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20404519
  review:
    summary: >-
      The cited report reviews BIK1 and related RLCK association with the
      flagellin receptor complex downstream of FLS2/BAK1.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is useful pathway context, but the generic binding term should not be
      retained as a core functional annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20413097
  review:
    summary: >-
      BIK1 and related PBL kinases interact with FLS2 and are rapidly
      phosphorylated after FLS2 activation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The evidence supports downstream immune receptor complex signaling, not an
      informative standalone protein-binding function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20472560
  review:
    summary: >-
      SCD1 was implicated in bacterial PAMP response pathways and FLS2-associated
      immunity context.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The annotation is a low-information interaction-style annotation and is
      peripheral to the receptor's core flagellin perception and kinase
      signaling function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21499263
  review:
    summary: >-
      This paper supports FLS2-mediated signaling by the endogenous CLV3 peptide
      and shows CLV3p-induced FLS2-BAK1 interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The noncanonical ligand/coreceptor interaction is interesting but should
      not be represented only as generic protein binding.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21726371
  review:
    summary: >-
      FLS2 was reported to physically associate with several ETI immune
      receptors, suggesting early PTI/ETI receptor proximity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      These interactions are not the defining molecular function of FLS2 and
      GO:0005515 is too nonspecific for curation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22087006
  review:
    summary: >-
      The study examines FLS2-mediated immune signaling and BAK1-related pathway
      context during brassinosteroid crosstalk.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Generic protein binding does not capture the specific signaling biology
      and should not be treated as a core FLS2 annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23250427
  review:
    summary: >-
      CRT1/MORC1 was reported to interact with FLS2 in immunity-related assays.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This interaction is peripheral regulatory context and is not an
      informative molecular-function annotation for FLS2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23395902
  review:
    summary: >-
      GRP7-associated regulation affects FLS2/EFR transcripts and receptor
      levels during HopU1-mediated immune suppression.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The evidence concerns regulation of receptor abundance and pathogen
      effector interference; GO:0005515 is not an informative function for FLS2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23532072
  review:
    summary: >-
      BSK1 physically associates with FLS2 and contributes to a subset of
      flg22-induced immune responses.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction supports pathway architecture, but generic protein binding
      is much less informative than receptor kinase/PAMP receptor signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24114786
  review:
    summary: >-
      The structural study directly supports flg22 perception by FLS2 and
      flg22-induced FLS2-BAK1 immune complex assembly.
    action: MODIFY
    reason: >-
      For this evidence, the more informative molecular-function annotation is
      pattern recognition receptor activity, rather than generic protein
      binding.
    proposed_replacement_terms:
    - id: GO:0038187
      label: pattern recognition receptor activity
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24629339
  review:
    summary: >-
      The paper places RBOHD downstream of the FLS2-associated kinase BIK1 in
      ROS and stomatal defense signaling.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The evidence supports pathway wiring downstream of FLS2, but GO:0005515
      does not describe FLS2's core activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27208222
  review:
    summary: >-
      PCRK1 and PCRK2 interact with FLS2 and act downstream of pattern
      recognition receptors in salicylic-acid biosynthesis activation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      These interactions are useful regulatory context, but they should not be
      curated as a generic binding function of FLS2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27317676
  review:
    summary: >-
      IOS1 associates with FLS2/EFR/CERK1 complexes and promotes FLS2-BAK1
      complex formation upon MAMP treatment.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      IOS1 binding is a pathway-regulatory interaction; the generic GO:0005515
      term is not informative for FLS2 core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29320478
  review:
    summary: >-
      The extracellular LRR-RK network study provides broad high-throughput
      interaction context for FLS2 and other receptor kinases.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction network is valuable context, but individual generic
      protein-binding annotations are too nonspecific and should not define FLS2
      function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32327536
  review:
    summary: >-
      SIF2 physically associates with the FLS2-BAK1 PRR complex and links it to
      SLAC1-dependent stomatal immunity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This is a specific regulatory interaction in stomatal immunity, but
      GO:0005515 is too vague for the FLS2 review.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      ATP binding is expected for the cytoplasmic protein kinase domain of FLS2.
    action: KEEP_AS_NON_CORE
    reason: >-
      The annotation is compatible with the kinase domain but is less
      informative than the receptor protein serine/threonine kinase activity.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:29320478
  review:
    summary: >-
      The extracellular interaction network reported FLS2 self-interaction
      evidence, but other curated context indicates FLS2's key functional
      complex is ligand-induced association with BAK1/SERK co-receptors and
      downstream kinases.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Identical protein binding is not a useful core annotation for FLS2 and
      should not override the established flg22-induced heteromeric receptor
      complex model.
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    summary: >-
      Rhea supports protein serine phosphorylation chemistry, but FLS2 is a
      receptor-like serine/threonine kinase and the serine-only term is
      incomplete.
    action: MODIFY
    reason: >-
      Replace with the specific receptor serine/threonine kinase activity term
      that captures both catalytic and membrane receptor context.
    proposed_replacement_terms:
    - id: GO:0004675
      label: transmembrane receptor protein serine/threonine kinase activity
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      FLS2 clearly participates in signal transduction, but this ARBA term is
      far broader than the known flagellin/PAMP receptor pathway.
    action: MODIFY
    reason: >-
      The specific FLS2 process is pathogen-associated molecular pattern
      receptor signaling.
    proposed_replacement_terms:
    - id: GO:0140426
      label: pathogen-associated molecular pattern receptor signaling pathway
- term:
    id: GO:0007178
    label: cell surface receptor protein serine/threonine kinase signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: >-
      This logically inferred pathway term is directionally correct but still
      less specific than FLS2's established role in PAMP receptor signaling.
    action: MODIFY
    reason: >-
      The PAMP receptor signaling term more accurately represents the
      flagellin-triggered immune pathway.
    proposed_replacement_terms:
    - id: GO:0140426
      label: pathogen-associated molecular pattern receptor signaling pathway
- term:
    id: GO:0071555
    label: cell wall organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      FLS2 acts upstream of callose deposition after flg22 perception, but it is
      not a general cell wall organization factor.
    action: MODIFY
    reason: >-
      A defense-specific callose deposition term is more accurate than broad
      cell wall organization.
    proposed_replacement_terms:
    - id: GO:0052544
      label: defense response by callose deposition in cell wall
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: DOI:10.1038/s41586-020-2210-3
  review:
    summary: >-
      Ligand-triggered FLS2/BIK1 pathway studies support dynamic endocytic
      compartment localization, but FLS2 is a single-pass membrane receptor.
    action: MODIFY
    reason: >-
      Endosome membrane is the more specific cellular-component term for the
      membrane-embedded receptor after internalization.
    proposed_replacement_terms:
    - id: GO:0010008
      label: endosome membrane
- term:
    id: GO:0005768
    label: endosome
  evidence_type: IDA
  original_reference_id: PMID:23085733
  review:
    summary: >-
      Activated FLS2 is sorted into endosomal compartments after flg22 treatment.
    action: MODIFY
    reason: >-
      Because FLS2 is a transmembrane receptor, endosome membrane is more
      precise than the whole endosome component.
    proposed_replacement_terms:
    - id: GO:0010008
      label: endosome membrane
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: DOI:10.1038/s41586-020-2210-3
  review:
    summary: >-
      FLS2 is a plasma-membrane receptor in the flagellin-triggered PRR complex.
    action: ACCEPT
    reason: >-
      Plasma membrane localization is essential to FLS2's cell-surface PAMP
      receptor role.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      UniProt subcellular-location mapping to plasma membrane is consistent with
      direct experimental localization and FLS2 receptor biology.
    action: ACCEPT
    reason: >-
      This location is well supported by independent experimental studies and is
      central to FLS2 function.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISM
  original_reference_id: GO_REF:0000122
  review:
    summary: >-
      Prediction-based plasma membrane localization agrees with the experimentally
      established cell-surface receptor localization.
    action: ACCEPT
    reason: >-
      Although the evidence code is computational, the asserted location is
      strongly supported by the overall literature.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: HDA
  original_reference_id: PMID:17644812
  review:
    summary: >-
      Plasma membrane proteomics identified Arabidopsis plasma membrane proteins,
      including receptor-like kinases, and is consistent with FLS2's cell-surface
      localization.
    action: ACCEPT
    reason: >-
      The high-throughput annotation is consistent with direct FLS2 localization
      studies and the receptor's topology.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:24923602
  review:
    summary: >-
      Salicylic-acid signaling increases the plasma-membrane pool of FLS2 and
      BAK1, supporting PM localization of the receptor complex.
    action: ACCEPT
    reason: >-
      Plasma membrane localization is experimentally supported and biologically
      central for FLS2 ligand perception.
    supported_by:
    - reference_id: PMID:24923602
      supporting_text: SA signaling also increases the PM pools of FLAGELLIN SENSING2 (FLS2)
      reference_section_type: ABSTRACT
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:32404997
  review:
    summary: >-
      FLS2-BAK1 receptor complex studies support plasma membrane localization
      before ligand-triggered downstream BIK1 release and endocytic dynamics.
    action: ACCEPT
    reason: >-
      This is a core cellular location for FLS2-mediated PAMP perception.
    supported_by:
    - reference_id: PMID:32404997
      supporting_text: FLS2 is polyubiquitinated and endocytosed 40 min after flg22 perception for signaling attenuation.
      reference_section_type: RESULTS
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      UniProt subcellular-location mapping places activated/internalized FLS2 at
      the endosome membrane.
    action: KEEP_AS_NON_CORE
    reason: >-
      Endosome membrane localization is a supported trafficking state of FLS2,
      but the primary site of ligand perception is the plasma membrane.
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: EXP
  original_reference_id: PMID:24923602
  review:
    summary: >-
      FLS2 membrane pools and trafficking are regulated in defense-related
      secretory/endosomal contexts.
    action: KEEP_AS_NON_CORE
    reason: >-
      This is valid supporting localization context, but it is secondary to the
      plasma membrane PRR role.
- term:
    id: GO:0010008
    label: endosome membrane
  evidence_type: EXP
  original_reference_id: PMID:32404997
  review:
    summary: >-
      Ligand-triggered FLS2 complex signaling is coupled to endocytic dynamics of
      signaling components.
    action: KEEP_AS_NON_CORE
    reason: >-
      Endosome membrane localization is relevant to receptor/signaling component
      turnover but is not the primary core location for PAMP perception.
- term:
    id: GO:0012505
    label: endomembrane system
  evidence_type: IDA
  original_reference_id: DOI:10.1038/s41586-020-2210-3
  review:
    summary: >-
      FLS2 pathway components enter endocytic compartments after ligand
      activation, but "endomembrane system" is too broad for a curated FLS2
      location.
    action: MODIFY
    reason: >-
      Endosome membrane is the more specific and biologically informative term
      for the activated receptor trafficking state.
    proposed_replacement_terms:
    - id: GO:0010008
      label: endosome membrane
- term:
    id: GO:0016020
    label: membrane
  evidence_type: ISS
  original_reference_id: PMID:10911994
  review:
    summary: >-
      FLS2 was identified as a membrane receptor-like kinase, but the generic
      membrane term is underspecified.
    action: MODIFY
    reason: >-
      Plasma membrane is the experimentally supported and functionally relevant
      membrane compartment for flagellin perception.
    proposed_replacement_terms:
    - id: GO:0005886
      label: plasma membrane
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:16510871
  review:
    summary: >-
      FLS2-GFP resides at the cell membrane and moves into intracellular vesicles
      after flg22 stimulation.
    action: MODIFY
    reason: >-
      The direct localization evidence supports more specific plasma membrane
      and endosome membrane annotations.
    proposed_replacement_terms:
    - id: GO:0005886
      label: plasma membrane
    - id: GO:0010008
      label: endosome membrane
- term:
    id: GO:0071944
    label: cell periphery
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      ARBA inferred a broad cell-periphery location that is consistent with FLS2
      being a cell-surface receptor.
    action: MODIFY
    reason: >-
      Plasma membrane is the more precise cellular-component term for FLS2.
    proposed_replacement_terms:
    - id: GO:0005886
      label: plasma membrane
core_functions:
- description: >-
    FLS2 enables extracellular pattern-recognition receptor activity for
    bacterial flagellin-derived flg22 at the plant plasma membrane, leading to
    ligand-induced BAK1/SERK co-receptor recruitment and activation of
    pattern-triggered immunity.
  molecular_function:
    id: GO:0038187
    label: pattern recognition receptor activity
  directly_involved_in:
  - id: GO:0016045
    label: detection of bacterium
  - id: GO:0140426
    label: pathogen-associated molecular pattern receptor signaling pathway
  locations:
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: PMID:10911994
    supporting_text: The FLS2 gene is ubiquitously expressed and encodes a putative receptor kinase.
    reference_section_type: ABSTRACT
  - reference_id: PMID:24114786
    supporting_text: Flagellin perception in Arabidopsis is through recognition of its highly conserved N-terminal epitope
    reference_section_type: ABSTRACT
- description: >-
    The cytoplasmic kinase domain of FLS2 functions as a transmembrane receptor
    protein serine/threonine kinase in the activated immune receptor complex,
    coordinating phosphorylation-dependent signaling through BIK1/PBL kinases
    and downstream calcium, ROS, MAPK, transcriptional, stomatal, and callose
    defense outputs.
  molecular_function:
    id: GO:0004675
    label: transmembrane receptor protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0140426
    label: pathogen-associated molecular pattern receptor signaling pathway
  locations:
  - id: GO:0005886
    label: plasma membrane
  - id: GO:0010008
    label: endosome membrane
  supported_by:
  - reference_id: PMID:17625569
    supporting_text: FLS2 and BAK1 form a complex
    reference_section_type: ABSTRACT
  - reference_id: PMID:20018686
    supporting_text: BIK1 associates with FLS2 and BAK1 in vivo and in vitro.
    reference_section_type: ABSTRACT
  - reference_id: file:interpro/panther/PTHR48056/PTHR48056-entries.csv
    supporting_text: >-
      Q9FL28,LRR receptor-like serine/threonine-protein kinase FLS2,protein,3702,Arabidopsis
      thaliana,Arabidopsis thaliana (Mouse-ear cress),FLS2,1173,PTHR48056:SF83,LRR
      RECEPTOR-LIKE SERINE_THREONINE-PROTEIN KINASE FLS2,True
proposed_new_terms: []
suggested_questions:
- question: >-
    Should GO add or use a ligand-specific "bacterial flagellin receptor
    activity" child of pattern recognition receptor activity for FLS2-like
    receptors, or is GO:0038187 intentionally the desired granularity?
- question: >-
    Should CLV3p-FLS2 signaling be curated as a noncanonical FLS2 function for
    Arabidopsis stem-cell immunity, or treated only as context for the canonical
    flagellin receptor pathway?
suggested_experiments:
- experiment_type: structure-function genetics
  hypothesis: >-
    FLS2 ligand binding, kinase activity, and endocytosis make separable
    contributions to early PTI signaling and later receptor attenuation.
  description: >-
    Compare endogenous-locus FLS2 variants defective in flg22 binding,
    kinase-catalytic activity, BAK1 recruitment, or endocytic sorting for
    restoration of calcium influx, ROS burst, MAPK activation, callose
    deposition, bacterial resistance, and receptor turnover in fls2 null plants.

Gene Description

Existing Annotations Review

Core Functions

FLS2 enables extracellular pattern-recognition receptor activity for bacterial flagellin-derived flg22 at the plant plasma membrane, leading to ligand-induced BAK1/SERK co-receptor recruitment and activation of pattern-triggered immunity.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Functional Annotation of FLS2 (UniProt Q9FL28) in Arabidopsis thaliana

0) Target verification (mandatory)

1) Key concepts and current understanding

1.1 Definitions and core concepts

1.2 Molecular function and reaction type (kinase activity)

1.3 Ligand specificity and receptor complex formation

1.4 Downstream signaling outputs (cellular and physiological)

2) Subcellular localization and trafficking/turnover

2.1 Localization

2.2 Endocytosis and receptor abundance control

3) Recent developments and latest research (prioritizing 2023–2024)

3.1 2023: BIK1 homeostasis controls signaling amplitude downstream of FLS2

3.2 2023: ESCRT-targeting E3 ligase circuit stabilizes FLS2 abundance

3.3 2024: Reprogramming FLS2 with biased/surrogate small-molecule ligands

3.4 2024: Updated structural/biochemical understanding of FLS2-like kinase activation (comparative insight)

4) Current applications and real-world implementations

4.1 Chemical immune modulation (2024)

4.2 PRR transfer, natural variation, and deployment considerations (2024)

4.3 Receptor engineering for expanded flagellin perception (preprint with 2024 DOI)

5) Expert opinions and synthesis from authoritative sources

6) Key statistics and data points (recent and/or mechanistically precise)

Evidence-backed summary tables

Notes on evidence scope and limitations

Citations

📄 View Raw YAML