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.
The preferred accession for this review is B5UBC1. These relationships are manually assessed.
REFERENCE PROTEOME CANDIDATE · Reviewed 2026-10-19
Reference proteome: UP000059680
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.
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.
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
target_sequence_count: 48896
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
candidate_count: 384
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.
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
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
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.
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
primary_in_any_reference_proteome: false
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
alternative_in_reference_proteome: true
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
same_taxon: true
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.
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
entry_date: 09-DEC-2015, entry version 28. proteomes: []
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
entry_date: 11-DEC-2019, entry version 50. proteomes: []
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
entry_date: 27-NOV-2024, entry version 64. proteomes: []
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.
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
value: PIK5-NP
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
value: PIKM1
file:ORYSJ/PIKM1-TS/PIKM1-TS-record-evidence.yaml
Nipponbare doesn't recognize the effector avirulence protein AVR-Pik
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006952 defense response | IEA GO_REF:0000120 | ACCEPT | 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. 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. Supporting Evidence: PMID:18940787 Pikm-specific resistance is conferred by cooperation of Pikm1-TS and Pikm2-TS |
| GO:0043531 ADP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:37199729 suggests that an intact P-loop in Pikp-1 is not essential for Pik-mediated signaling PMID:37199729 This autoactivity requires an intact P-loop and MHD motif in Pikp-2 |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | REMOVE | 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. 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. Supporting Evidence: PMID:26304198 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 file:ORYSJ/PIKM1-TS/PIKM1-TS-deep-research-falcon.md Direct ATP-hydrolysis activity or a metal substrate for this particular full-length protein was not established by the studies reviewed. |
| GO:0051707 response to other organism | IEA GO_REF:0000117 | MODIFY | 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. 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 replacements: defense response to fungus Supporting Evidence: PMID:36656825 Furthermore, Sasa2 transformants expressing AVR-Mgk1 triggered resistance in the rice cultivar Tsuyuake (Pikm). PMID:29988155 Rice plants expressing the Pikm allele resist infection by blast strains expressing any of three AVR-Pik effector variants |
| GO:0140376 innate immune receptor activity | IDA PMID:29988155 Polymorphic residues in rice NLRs expand binding and respons... | NEW | 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. 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. Supporting Evidence: PMID:29988155 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. PMID:22805093 This binding specificity correlates with the recognition specificity between AVR and R genes. PMID:36656825 The integrated HMA domain of Pikm-1 bound AVR-Mgk1 and AVR-PikD, whereas the HMA domain of Piks-1 bound only AVR-Mgk1 PMID:37486356 we observed strong binding of AVR-PikD to the Pikm-1 HMA (equilibrium dissociation constant [KD] = ∼10 nM) |
| GO:0002758 innate immune response-activating signaling pathway | IMP PMID:36656825 Disentangling the complex gene interaction networks between ... | NEW | 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. 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. Supporting Evidence: PMID:18940787 Pikm-specific resistance is conferred by cooperation of Pikm1-TS and Pikm2-TS PMID:36656825 Pik proteins Pikm, Pik*, and Pikp detect and bind AVR-Mgk1 and AVR-PikD via the Pik-1 integrated HMA domain |
Loading supporting content…
Download this section (compressed HTML)Q: 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?
Q: 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.
Q: 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?
Experiment: Determine the subcellular localization of a functional, complementing Pikm-1 fusion in rice cells before and after AVR-Pik recognition.
Experiment: 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.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)