id: B5UBC1 gene_symbol: PIKM1-TS product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:39947 label: Oryza sativa Japonica Group description: >- Pikm1-TS (Pikm-1) is the 1,143-residue sensor NLR encoded by the Pikm allele of the Pik blast-resistance locus on rice chromosome 11 (cultivar Tsuyuake). It is an intracellular coiled-coil nucleotide-binding leucine-rich repeat (CC-NB-LRR) immune receptor with an integrated heavy-metal-associated (HMA, RATX1) domain inserted between the N-terminal coiled coil and the NB-ARC domain. Pikm-1 works together with the adjacent, unrelated helper NLR Pikm-2: transgenic rice carrying either gene alone is susceptible, while plants carrying both resist Magnaporthe oryzae strains that deliver matching effectors. The integrated HMA domain directly binds the fungal MAX-family effectors AVR-PikD, AVR-PikE and AVR-PikA (affinity and response D > E > A, nanomolar KD for AVR-PikD), and also AVR-Mgk1, but not the escape variants AVR-PikC and AVR-PikF. Binding specificity at the HMA interface determines recognition specificity, and two HMA residues distinguish the broad Pikm recognition profile from that of the Piks allele. The HMA domain keeps the HMA fold but lacks the cysteines of the metal-binding motif and functions as an effector-binding decoy rather than as a metal-binding module. Effector binding by Pikm-1 initiates effector-triggered immunity, with cell death execution depending on the P-loop and MHD motifs of the helper Pik-2. Sensor and helper alleles are co-adapted, and mismatched pairs can be autoactive. Pikm-1 is widely used as a chassis for engineering new recognition specificities by swapping its HMA domain for other HMA domains or nanobodies. alternative_records: - id: Q2QZF2 relationship: REFERENCE_PROTEOME_CANDIDATE reference_proteome: UP000059680 reviewed_on: '2026-10-19' reason: Retain B5UBC1 as the primary Swiss-Prot accession. The leading hit is reviewed PIK5-NP, with the synonym PIKM1, but only 58.42% global identity and extensive differences. The source cultivars differ, and the reference record describes Nipponbare lacking AVR-Pik recognition. A related resistance-locus representation is plausible, but copy-number, locus and specificity differences prevent an equivalence assertion. evidence: - type: PROTEOME_SEARCH description: MMseqs2 searched 48,896 sequences across UP000059680 at E <= 1e-5 and sensitivity 7.5, returning 384 hits. Every returned sequence was globally aligned using BLOSUM62 with gap-open -10 and extension -0.5. Scores and sequences for all 384 returned candidates are retained, with 10 detailed alignment files. The heuristic search does not establish genomic absence or unique locus identity. supported_by: - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: 'target_sequence_count: 48896' - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: 'candidate_count: 384' - type: SEQUENCE_COMPARISON description: 'Q2QZF2: 697 identities across 1193 global-alignment columns (58.4241% identity including gaps), 378 substitutions and 118 gap columns. Query coverage is 94.0507%; target coverage is 95.5556%. Sequence similarity is interpreted in the manual rationale. Identity over paired residues is 64.8372% (697/1075); gap columns are excluded from this denominator.' supported_by: - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: |- query_length: 1143 target_length: 1125 alignment_columns: 1193 identities: 697 mismatches: 378 gap_columns: 118 identity_percent: 58.4241 query_coverage_percent: 94.0507 target_coverage_percent: 95.5556 - type: PROTEOME_MEMBERSHIP description: The primary accession is outside every searched exact-taxon reference proteome. Current UniProt records place Q2QZF2 in UP000059680 and give it the same taxon as the primary. supported_by: - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: 'primary_in_any_reference_proteome: false' - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: 'alternative_in_reference_proteome: true' - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: 'same_taxon: true' - type: RECORD_HISTORY description: 'Sampled UniSave observations: 09-DEC-2015, entry version 28.: no Proteomes cross-reference; 11-DEC-2019, entry version 50.: no Proteomes cross-reference; 27-NOV-2024, entry version 64.: no Proteomes cross-reference. These dated observations do not establish uninterrupted membership/absence, the exact change date, or UniProt''s motivation.' supported_by: - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: |- entry_date: 09-DEC-2015, entry version 28. proteomes: [] - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: |- entry_date: 11-DEC-2019, entry version 50. proteomes: [] - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: |- entry_date: 27-NOV-2024, entry version 64. proteomes: [] - type: CURATION_CONTEXT description: The reference record names PIK5-NP with synonym PIKM1 and describes the lack of AVR-Pik recognition in Nipponbare. This supports a candidate at the related resistance locus, not equivalent resistance specificity. supported_by: - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: 'value: PIK5-NP' - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: 'value: PIKM1' - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml supporting_text: Nipponbare doesn't recognize the effector avirulence protein AVR-Pik existing_annotations: - term: id: GO:0006952 label: defense response evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: involved_in supporting_entities: - ARBA:ARBA00026315 - InterPro:IPR044974 review: summary: >- Combined automated annotation (ARBA plus the plant disease resistance protein family IPR044974). Pikm-1 is a resistance protein required, with Pikm-2, for blast resistance. action: ACCEPT reason: >- General but correct. Pikm-1 is the effector receptor of the Pikm pair and genetic complementation shows it is required for Pikm-specific blast resistance. Treatment matches the RGA5 review, where the same InterPro mapping was accepted. The more specific process terms are captured by the MODIFY and NEW entries below. supported_by: - reference_id: PMID:18940787 supporting_text: Pikm-specific resistance is conferred by cooperation of Pikm1-TS and Pikm2-TS - term: id: GO:0043531 label: ADP binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables supporting_entities: - InterPro:IPR002182 review: summary: >- InterPro2GO mapping from the NB-ARC domain. Pikm-1 has an NB-ARC domain with an intact P-loop (GGGKTT), so ADP binding in the resting state is plausible, but nucleotide binding has not been measured for Pikm-1. action: KEEP_AS_NON_CORE reason: >- Plausible from domain architecture, as resting NLR NB-ARC domains bind ADP. However, in the closely related Pikp allele the sensor P-loop is not essential for Pik signaling, whereas the helper Pik-2 P-loop and MHD motifs are required. Nucleotide binding is therefore not what defines the sensor function of Pikm-1. Consistent with the RGA5 review. supported_by: - reference_id: PMID:37199729 supporting_text: suggests that an intact P-loop in Pikp-1 is not essential for Pik-mediated signaling - reference_id: PMID:37199729 supporting_text: This autoactivity requires an intact P-loop and MHD motif in Pikp-2 - term: id: GO:0046872 label: metal ion binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables supporting_entities: - InterPro:IPR006121 review: summary: >- InterPro2GO mapping from the HMA domain (IPR006121). The Pik-1 integrated HMA domains lack the conserved cysteines of the MxCxxC metal-binding motif. In the Pikm-1 sequence the beta1-alpha1 loop reads PMVDDKS and the whole HMA region (residues 186-264) contains no cysteine. The Pikp-HMA crystal structure contains no metal. action: REMOVE reason: >- The domain-to-GO mapping assumes a canonical metal-binding HMA. The Pikm-1 HMA is a degenerate, effector-binding decoy, no metal binding has been shown, and the motif residues needed for it are absent. Same decision as for the RGA5 integrated HMA. supported_by: - reference_id: PMID:26304198 supporting_text: these Cys residues are not conserved in Pik-1 HMA domains, including Pikp-1. Hence, the Pikp-HMA structure does not contain a metal ion - reference_id: file:ORYSJ/PIKM1-TS/PIKM1-TS-deep-research-falcon.md supporting_text: Direct ATP-hydrolysis activity or a metal substrate for this particular full-length protein was not established by the studies reviewed. - term: id: GO:0051707 label: response to other organism evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in supporting_entities: - ARBA:ARBA00029118 review: summary: >- ARBA transfer of a very broad response term. Pikm-1 takes part in defense against the rice blast fungus M. oryzae, as the receptor that binds its effectors. action: MODIFY reason: >- Correct but uninformative. The documented native role of Pikm-1 is defense against a fungus: transgenic rice carrying Pikm1-TS and Pikm2-TS resists M. oryzae, and fungal strains expressing AVR-Mgk1 trigger resistance in Tsuyuake (Pikm) rice. Pikm-1 does part of the work of this defense response, since it is the receptor that perceives the fungal effectors (not only a gene whose loss gives a phenotype). GO:0050832 defense response to fungus is therefore proposed. Engineered recognition of non-fungal targets (nanobody fusions) is not native and does not justify broader terms. proposed_replacement_terms: - id: GO:0050832 label: defense response to fungus supported_by: - reference_id: PMID:36656825 supporting_text: Furthermore, Sasa2 transformants expressing AVR-Mgk1 triggered resistance in the rice cultivar Tsuyuake (Pikm). - reference_id: PMID:29988155 supporting_text: Rice plants expressing the Pikm allele resist infection by blast strains expressing any of three AVR-Pik effector variants - term: id: GO:0140376 label: innate immune receptor activity evidence_type: IDA original_reference_id: PMID:29988155 qualifier: enables review: summary: >- Pikm-1 directly binds the M. oryzae effectors AVR-PikD, AVR-PikE, AVR-PikA and AVR-Mgk1 through its integrated HMA domain (Y2H, co-IP, SPR, crystal structures of the Pikm-HMA complexes), and this binding determines recognition and resistance. action: NEW reason: >- This is the core molecular function of Pikm-1 and is absent from GOA. The ligand is a pathogen effector perceived directly; binding specificity matches recognition specificity across Pik and AVR-Pik alleles, and HMA residues that weaken binding weaken the response. The same term is annotated experimentally to the comparable HMA-integrated sensor RGA5. It belongs on the sensor Pikm-1, not on the helper Pikm-2. additional_reference_ids: - PMID:22805093 - PMID:36656825 - PMID:37486356 supported_by: - reference_id: PMID:29988155 supporting_text: Unlike Pikp, the integrated heavy metal-associated (HMA) domain of Pikm binds with high affinity to each of the three recognized effector variants, and variation at binding interfaces between effectors and Pikp-HMA or Pikm-HMA domains encodes specificity. - reference_id: PMID:22805093 supporting_text: This binding specificity correlates with the recognition specificity between AVR and R genes. - reference_id: PMID:36656825 supporting_text: The integrated HMA domain of Pikm-1 bound AVR-Mgk1 and AVR-PikD, whereas the HMA domain of Piks-1 bound only AVR-Mgk1 - reference_id: PMID:37486356 supporting_text: we observed strong binding of AVR-PikD to the Pikm-1 HMA (equilibrium dissociation constant [KD] = ∼10 nM) - term: id: GO:0002758 label: innate immune response-activating signaling pathway evidence_type: IMP original_reference_id: PMID:36656825 qualifier: involved_in review: summary: >- As the receptor that binds the effector ligand, Pikm-1 starts the effector-triggered immune signaling that, through the helper Pikm-2, leads to cell death and resistance. action: NEW reason: >- Participation test: the term is defined as signals generated by a ligand binding to its receptor, and Pikm-1 is that receptor, so it performs the first step of the pathway rather than being merely required for it. Comparator check: the HMA-integrated sensor RGA5 (IDA) and Arabidopsis RPS4 carry GO:0002758; plant NLR signaling is not annotated to GO:0035872, so that term is not used. Cell death execution (plant-type hypersensitive response) is not proposed for the sensor, because it depends on the helper Pik-2 P-loop and MHD motifs. additional_reference_ids: - PMID:18940787 supported_by: - reference_id: PMID:18940787 supporting_text: Pikm-specific resistance is conferred by cooperation of Pikm1-TS and Pikm2-TS - reference_id: PMID:36656825 supporting_text: Pik proteins Pikm, Pik*, and Pikp detect and bind AVR-Mgk1 and AVR-PikD via the Pik-1 integrated HMA domain core_functions: - description: >- Intracellular sensor NLR. Its integrated HMA decoy domain, located between the coiled coil and the NB-ARC domain, directly binds the M. oryzae MAX effectors AVR-PikD, AVR-PikE, AVR-PikA and AVR-Mgk1. Effector binding is the recognition event that starts effector-triggered immunity executed with the helper NLR Pikm-2. molecular_function: id: GO:0140376 label: innate immune receptor activity directly_involved_in: - id: GO:0002758 label: innate immune response-activating signaling pathway - id: GO:0050832 label: defense response to fungus supported_by: - reference_id: PMID:29988155 supporting_text: Unlike Pikp, the integrated heavy metal-associated (HMA) domain of Pikm binds with high affinity to each of the three recognized effector variants - reference_id: PMID:36656825 supporting_text: The integrated HMA domain of Pikm-1 bound AVR-Mgk1 and AVR-PikD, whereas the HMA domain of Piks-1 bound only AVR-Mgk1 - reference_id: PMID:18940787 supporting_text: Pikm-specific resistance is conferred by cooperation of Pikm1-TS and Pikm2-TS suggested_questions: - question: >- In RGA5/RGA4 the sensor represses an autoactive executor, which supports a molecular function inhibitor activity annotation on RGA5. Is there evidence that Pikm-1 likewise restrains Pikm-2 in the resting state (e.g. autoactivity of Pikm-1 HMA chimeras or of the Pikp-1/Pikm-2 mismatch), or does the Pik pair act cooperatively so that no inhibitor term applies? - question: >- Where does Pikm-1 act in rice cells? Localization of native or functional tagged Pikm-1 in rice has not been reported, so no cellular component can be assigned with confidence. - question: >- The UniProt function text describes recognition as indirect, but the Pikm-1 HMA domain binds AVR-Pik effectors directly. Should the free-text function be corrected? suggested_experiments: - description: >- Determine the subcellular localization of a functional, complementing Pikm-1 fusion in rice cells before and after AVR-Pik recognition. - description: >- Cryo-EM structure of full-length Pikm-1/Pikm-2 with and without AVR-PikD to establish how effector binding to the HMA domain activates the helper and whether a resistosome-like complex forms. references: - id: file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml title: Compact archived record and sequence evidence for B5UBC1 - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:18940787 title: Two adjacent nucleotide-binding site-leucine-rich repeat class genes are required to confer Pikm-specific rice blast resistance. findings: [] - id: PMID:22805093 title: Arms race co-evolution of Magnaporthe oryzae AVR-Pik and rice Pik genes driven by their physical interactions. findings: [] - id: PMID:29988155 title: Polymorphic residues in rice NLRs expand binding and response to effectors of the blast pathogen. findings: [] - id: PMID:26304198 title: Structural basis of pathogen recognition by an integrated HMA domain in a plant NLR immune receptor. findings: [] - id: PMID:36656825 title: Disentangling the complex gene interaction networks between rice and the blast fungus identifies a new pathogen effector. findings: [] - id: PMID:37199729 title: Effector target-guided engineering of an integrated domain expands the disease resistance profile of a rice NLR immune receptor. findings: [] - id: PMID:38968126 title: Bioengineering a plant NLR immune receptor with a robust binding interface toward a conserved fungal pathogen effector. findings: [] - id: PMID:37486356 title: Allelic compatibility in plant immune receptors facilitates engineering of new effector recognition specificities. findings: [] - id: file:ORYSJ/PIKM1-TS/PIKM1-TS-deep-research-falcon.md title: Falcon (Edison Scientific) deep research report for PIKM1-TS findings: []