Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0003735 structural constituent of ribosome	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: This annotation derives from the RPS14 portion of the chimeric gene model. Ribosomal protein S14 is indeed a structural constituent of the mitochondrial ribosome. However, this annotation should apply to the RPS14 protein product from alternative splicing, not to the SDH2 iron-sulfur subunit. Since this UniProt entry is named as SDH2, this annotation is misleading when applied to the combined entry. Reason: Correct for the RPS14 alternative splice product but not for the SDH2 product that this entry primarily represents. The InterPro match to ribosomal uS14 (IPR001209) is real and reflects the RPS14 coding region within the chimeric gene model. Supporting Evidence: PMID:10430921 the two gene transcripts result from a single mRNA precursor by alternative splicing
GO:0008177 succinate dehydrogenase (quinone) activity	IEA GO_REF:0000003	MODIFY	Summary: GO:0008177 represents the overall catalytic activity of the entire SDH complex (Complex II), not the activity of an individual subunit. SDH2 is the iron-sulfur subunit that transfers electrons within the complex but does not independently catalyze the succinate-to-ubiquinone reaction. The SDH2 subunit contributes to this activity as part of the complex. Reason: SDH2 does not independently enable succinate dehydrogenase (quinone) activity — this is a complex-level activity requiring all four SDH subunits (SDH1-4). Per GO annotation guidelines, the qualifier should be contributes_to (not enables) for the complex activity, since SDH2 cannot catalyze the overall reaction alone. The subunit-specific function that SDH2 independently enables is electron transfer activity (GO:0009055). Proposed replacements: electron transfer activity Supporting Evidence: file:9POAL/NCGR_LOCUS67308/NCGR_LOCUS67308-notes.md SDH2 is the iron-sulfur protein (IP) component of mitochondrial Complex II that transfers electrons from succinate to ubiquinone via three iron-sulfur clusters
GO:0009055 electron transfer activity	IEA GO_REF:0000002	ACCEPT	Summary: Electron transfer activity is the core molecular function of the SDH2 iron-sulfur subunit. SDH2 transfers electrons from succinate (received via FAD on SDH1) through its three iron-sulfur clusters ([2Fe-2S], [3Fe-4S], [4Fe-4S]) to ubiquinone at the membrane-embedded SDH3/SDH4 subunits. Reason: This correctly captures the subunit-specific molecular function of SDH2. The iron-sulfur clusters serve as an electron relay chain within Complex II. Supporting Evidence: file:9POAL/NCGR_LOCUS67308/NCGR_LOCUS67308-notes.md SDH2 transfers electrons from succinate to ubiquinone via three iron-sulfur clusters
GO:0016491 oxidoreductase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Oxidoreductase activity is a broad parent term. The more specific electron transfer activity (GO:0009055) already captures the SDH2 function more precisely. Reason: While technically correct as a parent of electron transfer activity, this is too general to be informative. The more specific GO:0009055 is already annotated and is preferable.
GO:0051536 iron-sulfur cluster binding	IEA GO_REF:0000002	ACCEPT	Summary: SDH2 binds three distinct iron-sulfur clusters: [2Fe-2S], [3Fe-4S], and [4Fe-4S]. These are essential cofactors for the electron relay function of the subunit within Complex II. The 2Fe-2S ferredoxin domain (residues 49-141) and 4Fe-4S ferredoxin domain (residues 184-214) are confirmed by PROSITE domain predictions. Reason: Core cofactor binding function of SDH2. The iron-sulfur clusters are essential for electron transfer within the respiratory chain complex.
GO:0051537 2 iron, 2 sulfur cluster binding	IEA GO_REF:0000002	ACCEPT	Summary: SDH2 binds one [2Fe-2S] cluster via the 2Fe-2S ferredoxin domain at residues 49-141. This is a more specific child term of iron-sulfur cluster binding (GO:0051536) and correctly captures one of the three iron-sulfur cluster types bound by SDH2. Reason: SDH2 binds one [2Fe-2S] cluster as confirmed by UniProt cofactor annotation and the 2Fe-2S ferredoxin domain. This is a core cofactor binding function.
GO:0006099 tricarboxylic acid cycle	IEA GO_REF:0000120	ACCEPT	Summary: Complex II (succinate dehydrogenase) is the only enzyme shared between the TCA cycle and the electron transport chain. SDH2 is an essential subunit of this complex. The complex catalyzes the oxidation of succinate to fumarate (TCA cycle step) while simultaneously reducing ubiquinone (respiratory chain function). Reason: SDH2 is directly involved in the TCA cycle as a subunit of succinate dehydrogenase, which catalyzes the succinate-to-fumarate step.
GO:0006412 translation	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: This annotation derives from the RPS14 portion of the chimeric gene model. RPS14 is a mitochondrial ribosomal protein involved in mitochondrial translation. This annotation is correct for the RPS14 alternative splice product but not for the SDH2 protein. Reason: Correct for the RPS14 product from alternative splicing of this locus, but not for SDH2. The InterPro match to ribosomal uS14 reflects the genuine RPS14 coding region in the chimeric gene model. Supporting Evidence: PMID:10430921 the two gene transcripts result from a single mRNA precursor by alternative splicing
GO:0009060 aerobic respiration	IEA GO_REF:0000118	ACCEPT	Summary: Complex II functions in aerobic respiration as part of the mitochondrial electron transport chain. SDH2 is essential for this process, transferring electrons from the TCA cycle intermediate succinate to the respiratory chain via ubiquinone. Reason: SDH2 is directly involved in aerobic respiration through its role in Complex II, which links the TCA cycle to the electron transport chain.
GO:0022904 respiratory electron transport chain	IEA GO_REF:0000118	ACCEPT	Summary: SDH2 is a core component of the respiratory electron transport chain as part of Complex II. It facilitates electron transfer from succinate to ubiquinone, feeding electrons into the downstream respiratory chain (Complex III and Complex IV). Reason: Core biological process for SDH2. The electron transfer function of SDH2 is integral to the respiratory electron transport chain.
GO:0005739 mitochondrion	IEA GO_REF:0000118	ACCEPT	Summary: Both SDH2 and RPS14 products from this locus are targeted to mitochondria. SDH2 is located at the mitochondrial inner membrane as part of Complex II. RPS14 is a component of the mitochondrial ribosome in the matrix. Reason: Correct localization for both alternative splice products of this locus.
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: SDH2 is a peripheral membrane protein on the matrix side of the mitochondrial inner membrane, anchored to the membrane-embedded SDH3/SDH4 subunits. This is the correct subcellular localization for SDH2 function in Complex II. Reason: Correct and well-supported localization for SDH2 as part of the inner membrane-associated Complex II.
GO:0005840 ribosome	IEA GO_REF:0000002	MODIFY	Summary: This annotation derives from the RPS14 portion of the chimeric gene model. RPS14 is a component of the mitochondrial small ribosomal subunit. More specifically, this should be annotated to the mitochondrial small ribosomal subunit (GO:0005763). Reason: The generic "ribosome" term is too broad. The RPS14 product is specifically a component of the mitochondrial small ribosomal subunit. Additionally, this annotation applies to the RPS14 splice product, not to SDH2. Proposed replacements: mitochondrial small ribosomal subunit
GO:0009536 plastid	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: While plants do have a plastidial succinate dehydrogenase, the primary and well-characterized function of SDH2 is mitochondrial. The plastid annotation is based on automated subcellular location prediction and lacks specific experimental evidence for this gene product. Reason: Plastid SDH exists in plants but the evidence for plastid localization of this specific SDH2 is from automated prediction only. The primary function is mitochondrial.
GO:0045273 respiratory chain complex II (succinate dehydrogenase)	IEA GO_REF:0000117	ACCEPT	Summary: SDH2 is the iron-sulfur protein (IP) subunit of respiratory chain complex II. In plants, Complex II is composed of eight subunits: the four classical SDH1-4 subunits plus four plant-specific subunits. SDH2 is essential for the electron relay function within the complex. Reason: Core component annotation. SDH2 is a defining subunit of Complex II. The part_of qualifier is appropriate.

Core Functions

Iron-sulfur subunit of mitochondrial Complex II (succinate dehydrogenase) that transfers electrons from succinate to ubiquinone via three iron-sulfur clusters ([2Fe-2S], [3Fe-4S], [4Fe-4S]). This dual-function complex links the TCA cycle (succinate to fumarate oxidation) with the respiratory electron transport chain. SDH2 does not independently catalyze the overall succinate dehydrogenase reaction but contributes to it as the electron relay component within the multi-subunit complex.

Molecular Function:

electron transfer activity

Directly Involved In:

tricarboxylic acid cycle respiratory electron transport chain

Cellular Locations:

mitochondrial inner membrane

In Complex:

respiratory chain complex II (succinate dehydrogenase)

Supporting Evidence:

PMID:10417711
Transferred rps14 was found integrated between both exons of a gene encoding the iron-sulphur subunit of the respiratory complex II (sdh2)

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms.

GO_REF:0000003

Gene Ontology annotation based on EC number mapping.

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping.

GO_REF:0000117

Gene Ontology annotation by ARBA (Association-Rule-Based Annotator).

GO_REF:0000118

Gene Ontology annotation by TreeGrafter.

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods.

PMID:10430921

A single nuclear transcript encoding mitochondrial RPS14 and SDHB of rice is processed by alternative splicing: common use of the same mitochondrial targeting signal for different proteins.

In rice, rps14 was transferred from the mitochondrial genome to the nuclear sdh2 locus, producing alternatively spliced transcripts for SDH2 and a chimeric SDH2-RPS14 precursor

"the two gene transcripts result from a single mRNA precursor by alternative splicing"

PMID:10417711

Transfer of rps14 from the mitochondrion to the nucleus in maize implied integration within a gene encoding the iron-sulphur subunit of succinate dehydrogenase and expression by alternative splicing.

The same SDH2-RPS14 fusion arrangement exists in maize, confirming it is a grass-wide phenomenon

"Transferred rps14 was found integrated between both exons of a gene encoding the iron-sulphur subunit of the respiratory complex II (sdh2)"

PMID:10799306

The nuclear-encoded SDH2-RPS14 precursor is proteolytically processed between SDH2 and RPS14 to generate maize mitochondrial RPS14.

The SDH2-RPS14 chimeric precursor is imported into mitochondria and proteolytically processed to yield mature RPS14

"the chimeric precursor undergoes proteolytical processing between SDH2 and RPS14. This processing generates RPS14, which is found assembled into mitochondrial ribosomes"

PMID:16842621

Pervasive survival of expressed mitochondrial rps14 pseudogenes in grasses and their relatives for 80 million years following three functional transfers to the nucleus.

rps14 pseudogenes are pervasive across grasses, documenting the lineage-specific endosymbiotic gene transfer

file:9POAL/NCGR_LOCUS67308/NCGR_LOCUS67308-notes.md

NCGR_LOCUS67308 review notes

Suggested Experiments

Experiment: RT-PCR or RNA-seq analysis of the NCGR_LOCUS67308 locus in Miscanthus lutarioriparius to confirm alternative splicing produces separate SDH2 and RPS14 transcripts, as demonstrated in rice and maize.

Experiment: Subcellular fractionation and immunoblotting to confirm SDH2 localization to mitochondrial inner membrane and determine whether any SDH2 is present in plastids.

Deep Research

Falcon

(NCGR_LOCUS67308-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 23 citations 2026-04-22T22:56:16.476386

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 NCGR_LOCUS67308 (UniProt A0A811SRM7) in Miscanthus lutarioriparius

Executive summary

The gene NCGR_LOCUS67308 (UniProt: A0A811SRM7) is described in the provided UniProt record as “succinate dehydrogenase [ubiquinone] iron–sulfur subunit, mitochondrial” (EC 1.3.5.1) from Miscanthus lutarioriparius, but the same record also states it “belongs to the universal ribosomal protein uS14 family,” which conflicts with the expected biology of an SDH iron–sulfur subunit. Because no accession- or locus-specific primary literature for Miscanthus lutarioriparius was retrieved in the tool-based searches, this report provides a conservative functional annotation grounded in: (i) authoritative Complex II reviews (2023–2024 prioritized), and (ii) plant experimental evidence from a closely related angiosperm (maize) in which the iron–sulfur SDH subunit gene is explicitly identified and quantified under stress. The weight of evidence supports annotating A0A811SRM7 as an SDHB/SDH2-like Fe–S electron-transfer subunit of mitochondrial Complex II (succinate dehydrogenase), with expected mitochondrial inner-membrane association through Complex II. (iverson2023anevolvingview pages 1-2, bouillaud2023inhibitionofsuccinate pages 3-5, fedorin2022effectofsalt pages 2-5)

1) Target verification (critical identity checks)

What was verified using tools:
* Literature searches for “A0A811SRM7”, “NCGR_LOCUS67308”, and “Miscanthus lutarioriparius succinate dehydrogenase SDHB” returned no directly matching papers in the retrieved corpus, so the symbol is effectively literature-limited/ambiguous at the species level within this environment.
* The functional interpretation therefore must rely on the supplied UniProt description plus conserved SDH/Complex II evidence.

Internal inconsistency to flag:
* SDHB proteins are Fe–S electron-transfer subunits of Complex II (succinate dehydrogenase), whereas uS14 is a small ribosomal protein family. The conserved Complex II literature consistently defines SDHB as the iron–sulfur (Ip) subunit with Fe–S clusters mediating electron transfer between the FAD active site (SDHA) and quinone site (SDHC/SDHD). (iverson2023anevolvingview pages 1-2)
* Given this, the UniProt note “uS14 family” should be treated as a probable misannotation in the provided record unless independently validated by sequence/domain analysis (not available via the current tools). This report does not switch to researching ribosomal uS14, in compliance with the user’s constraints.

2) Key concepts and definitions (current understanding)

2.1 Succinate dehydrogenase (SDH; mitochondrial Complex II)

Definition and role:
* Mitochondrial Complex II (succinate dehydrogenase; SDH) is a heterotetrameric, membrane-associated enzyme that links the TCA cycle with the electron transport chain. Canonically it comprises SDHA, SDHB, SDHC, SDHD. (iverson2023anevolvingview pages 1-2, bouillaud2023inhibitionofsuccinate pages 3-5)

Catalyzed reaction and electron acceptor:
* SDH catalyzes oxidation of succinate to fumarate, releasing 2H+ and 2e−:
HOOC-CH2-CH2-COOH → HOOC-CH=CH-COOH + 2H+ + 2e− (bouillaud2023inhibitionofsuccinate pages 3-5)
* The electron acceptor is a membrane quinone (coenzyme Q), reduced as:
Q + 2e− + 2H+ → QH2 (bouillaud2023inhibitionofsuccinate pages 3-5)
* Complex II is emphasized as a redox enzyme that does not pump protons (unlike complexes I, III, IV). (bouillaud2023inhibitionofsuccinate pages 3-5)

2.2 SDHB (iron–sulfur subunit; “Ip” subunit)

Core definition:
* In the 2023 JBC review, SDHB is defined as the iron–sulfur (Ip) subunit that houses three Fe–S clusters and mediates electron transfer between SDHA’s FAD site and the membrane quinone site (SDHC/SDHD). (iverson2023anevolvingview pages 1-2)

Cofactors and electron pathway:
* Reviews describe Complex II cofactors including FAD and multiple Fe–S clusters (2Fe-2S, 3Fe-4S, 4Fe-4S) as part of the electron-transfer chain within the enzyme. (iverson2023anevolvingview pages 2-4)

3) Functional annotation for NCGR_LOCUS67308 / A0A811SRM7 (inferred)

3.1 Primary molecular function

Most likely function:
* The gene product is best annotated as the SDHB/SDH2-like Fe–S electron-transfer subunit of succinate dehydrogenase (Complex II), supporting electron transfer from succinate oxidation (via SDHA/FAD) toward quinone reduction in the mitochondrial inner membrane. (iverson2023anevolvingview pages 1-2, bouillaud2023inhibitionofsuccinate pages 3-5)

Substrate specificity:
* Complex II’s substrate is succinate (oxidized to fumarate); the electron acceptor is ubiquinone (Q). (bouillaud2023inhibitionofsuccinate pages 3-5)

3.2 Cellular and subcellular localization

Complex II is an enzymatic assembly inserted in the mitochondrial inner membrane, with SDHA/SDHB forming a catalytic “SDH side” and SDHC/SDHD comprising the membrane “complex II side” that reduces the quinone pool. (bouillaud2023inhibitionofsuccinate pages 3-5)
A schematic of subunits and cofactors (FAD, FeS, quinone) and how assays intercept electrons is shown in Bouillaud 2023 (Figure 4). (bouillaud2023inhibitionofsuccinate media e6ec7f85)

4) Pathway context and biological processes

4.1 Respiration and energy metabolism

SDH/Complex II provides an entry point of electrons to the respiratory chain through quinone, directly connecting carbon metabolism with electron transport. (bouillaud2023inhibitionofsuccinate pages 3-5)

4.2 Succinate as a signaling/metabolic hub (broader context)

Although much of the mechanistic signaling literature is from animals/microbes, the 2023 JBC review argues that Complex II is a key controller of cellular succinate levels and that succinate can act as a signaling metabolite influencing cell fate through multiple routes, including inhibition of α-ketoglutarate–dependent enzymes (e.g., prolyl hydroxylases and demethylases). (iverson2023anevolvingview pages 1-2, iverson2023anevolvingview pages 10-11)

5) Recent developments (prioritizing 2023–2024 sources)

5.1 Noncanonical Complex II assemblies and megacomplex biology (2023)

Iverson et al. (JBC, 2023-06) describes an “evolving view” in which Complex II can exist in noncanonical/alternative assemblies, including SDHA-containing lower-mass species (“Complex II-low”) associated with altered signaling, and highlights that most canonical mammalian respirasomes lack Complex II, with exceptions reported in specific organisms. (iverson2023anevolvingview pages 7-8, iverson2023anevolvingview pages 5-7)
The same review notes substantial diversity: at least 14 unique Complex II enzymes spanning multiple evolutionary subclasses with differences in architecture and membrane/cofactor features—relevant when inferring function from distant homologs. (iverson2023anevolvingview pages 5-7)

5.2 Complex II within broader mitochondrial redox-cofactor frameworks (2024)

A 2024 review reiterates that respiratory chain complexes transfer electrons via redox cofactors including flavins and iron–sulfur clusters, and frames SDH subunit A (FAD) transferring electrons to Fe–S centers in subunit B, with ubiquinone handled by SDHC/SDHD. (ragab2024comprehensiveoverviewof pages 1-3)

6) Current applications and real-world implementations

6.1 Functional assays used in research and annotation

SDH activity is commonly assayed by succinate-driven reduction of artificial acceptors such as DCPIP or tetrazolium salts, often using intermediates such as decylubiquinone or PMS; malonate is used to validate SDH specificity. (bouillaud2023inhibitionofsuccinate pages 5-7)
A schematic depiction of these assays and cofactors is provided in Bouillaud 2023 (Figure 4). (bouillaud2023inhibitionofsuccinate media e6ec7f85)

6.2 Chemical inhibition as a probe of function

Hydrophilic substrate analogs (e.g., malonate, oxaloacetate, 3-nitropropionic acid/NPA) inhibit the “SDH side” (SDHA), whereas inhibitors such as TTFA, atpenin, and SDHI pesticides disrupt electron transfer near the quinone side. (bouillaud2023inhibitionofsuccinate pages 5-7)

7) Relevant quantitative data and statistics (recent studies)

7.1 Kinetic/assay parameters from a 2023 review

Reported SDH apparent Km for succinate ranges from 0.5–3 mM. (bouillaud2023inhibitionofsuccinate pages 5-7)
For biochemical assays aimed at Vmax, ~20 mM succinate is recommended; maximal succinate-driven mitochondrial oxygen consumption in isolated liver mitochondria is reported at ~5–20 mM succinate. (bouillaud2023inhibitionofsuccinate pages 5-7)

7.2 Plant stress-linked regulation dataset (maize; publication date 2022-12-23, volume year 2023)

In maize leaves exposed to salt stress (150 mM NaCl):
* Ssadh1 (SSADH; GABA shunt) transcripts peak at ~4.5× at 3 h, coinciding with promoter methylation decrease (from ~75% to ~50%). (fedorin2022effectofsalt pages 2-5)
* SSADH activity increases ~3×, peaking at 6 h. (fedorin2022effectofsalt pages 2-5)
* SDH activity becomes ~2× higher by 24 h, with mitochondrial succinate oxidation increasing ~40%. (fedorin2022effectofsalt pages 2-5)
* The SDH iron–sulfur subunit gene Sdh2-3 (SDHB) shows ~2–3× expression increase at 12–24 h, and its promoter methylation decreases from ~75% to 50% starting at 6 h and remaining reduced through 24 h. (fedorin2022effectofsalt pages 2-5)
These data support that plant SDHB-like genes can be transcriptionally and epigenetically regulated during salinity stress, consistent with a role in stress-associated succinate oxidation (“salt respiration”), but they are not Miscanthus-specific. (fedorin2022effectofsalt pages 1-2, fedorin2022effectofsalt pages 2-5)

8) Expert opinion and synthesis (authoritative sources)

The 2023 JBC review positions Complex II as more than a static respiratory enzyme, emphasizing its roles in succinate control, signaling, and dynamic assembly into alternative species, which is important when interpreting SDHB-like genes in non-model plants where direct experiments are lacking. (iverson2023anevolvingview pages 1-2, iverson2023anevolvingview pages 7-8)
The 2023 IJMS review emphasizes the conceptual separation of an “SDH side” and “Complex II side,” helping interpret how mutations/inhibitors and Fe–S subunits affect either succinate oxidation chemistry or quinone reduction/electron transfer. (bouillaud2023inhibitionofsuccinate pages 5-7)

9) Practical functional annotation statement (recommended)

Recommended annotation for NCGR_LOCUS67308 / A0A811SRM7 (with caveat):
Probable succinate dehydrogenase [ubiquinone] iron–sulfur subunit (SDHB/SDH2-like), a mitochondrial inner-membrane-associated respiratory-chain component of Complex II; mediates Fe–S-dependent electron transfer from SDHA-bound FAD (succinate oxidation) to the membrane quinone pool (ubiquinone reduction), thereby linking the TCA cycle to oxidative phosphorylation. (iverson2023anevolvingview pages 1-2, bouillaud2023inhibitionofsuccinate pages 3-5, bouillaud2023inhibitionofsuccinate media e6ec7f85)

Synthesis table

Annotation aspect	Best-supported statement	Evidence type	Key citations with year + DOI URL
Identity	Direct Miscanthus-specific literature for NCGR_LOCUS67308 / UniProt A0A811SRM7 was not found in the retrieved corpus. Based on the UniProt description and conserved Complex II biology, the protein is best annotated as a mitochondrial succinate dehydrogenase iron-sulfur subunit (SDHB/SDH2-like); the supplied note calling it a uS14 ribosomal family protein is inconsistent with SDHB-like Fe-S/Complex II annotations and should be treated cautiously.	Inference/orthology + review	Iverson 2023, J Biol Chem, https://doi.org/10.1016/j.jbc.2023.104761 (iverson2023anevolvingview pages 1-2, iverson2023anevolvingview pages 2-4); Bouillaud 2023, Int J Mol Sci, https://doi.org/10.3390/ijms24044045 (bouillaud2023inhibitionofsuccinate pages 3-5)
Reaction	Succinate dehydrogenase/Complex II catalyzes succinate → fumarate + 2H+ + 2e-, coupled to quinone (Q) reduction to quinol (QH2); Complex II is a redox enzyme that links the TCA cycle to the respiratory chain and does not directly pump protons.	Review	Bouillaud 2023, Int J Mol Sci, https://doi.org/10.3390/ijms24044045 (bouillaud2023inhibitionofsuccinate pages 3-5); Iverson 2023, J Biol Chem, https://doi.org/10.1016/j.jbc.2023.104761 (iverson2023anevolvingview pages 1-2, iverson2023anevolvingview pages 2-4)
Subunits	Canonical mitochondrial Complex II is a 4-subunit complex (SDHA, SDHB, SDHC, SDHD). SDHA and SDHB form the matrix-facing catalytic/hydrophilic arm; SDHC/SDHD form the membrane anchor/quinone-binding region.	Review + background	Iverson 2023, J Biol Chem, https://doi.org/10.1016/j.jbc.2023.104761 (iverson2023anevolvingview pages 1-2); Ragab 2024, Genes Nutr, https://doi.org/10.1186/s12263-024-00740-x (ragab2024comprehensiveoverviewof pages 1-3); Bouillaud 2023, Int J Mol Sci, https://doi.org/10.3390/ijms24044045 (bouillaud2023inhibitionofsuccinate pages 3-5)
Cofactors/domains	SDHB is the iron-sulfur subunit that relays electrons from SDHA-bound FAD toward quinone. Conserved Complex II literature supports three Fe-S clusters in SDHB ([2Fe-2S], [4Fe-4S], [3Fe-4S] / equivalent orderings reported by source context) and Fe-S-dependent electron transfer, consistent with the UniProt Fe-S domain calls.	Inference/orthology + review	Iverson 2023, J Biol Chem, https://doi.org/10.1016/j.jbc.2023.104761 (iverson2023anevolvingview pages 2-4, iverson2023anevolvingview pages 1-2); Miklovicova 2025 background excerpt (miklovicova2025mitochondrialrespiratorycomplex pages 22-26); Bouillaud 2023, Int J Mol Sci, https://doi.org/10.3390/ijms24044045 (bouillaud2023inhibitionofsuccinate pages 5-7)
Localization	Best-supported localization is the mitochondrial inner membrane Complex II, with the SDHB polypeptide in the matrix-facing catalytic arm associated with membrane subunits that pass electrons to the ubiquinone pool.	Inference/orthology + review	Bouillaud 2023, Int J Mol Sci, https://doi.org/10.3390/ijms24044045 (bouillaud2023inhibitionofsuccinate pages 3-5, bouillaud2023inhibitionofsuccinate pages 5-7); Ragab 2024, Genes Nutr, https://doi.org/10.1186/s12263-024-00740-x (ragab2024comprehensiveoverviewof pages 1-3); Iverson 2023, J Biol Chem, https://doi.org/10.1016/j.jbc.2023.104761 (iverson2023anevolvingview pages 1-2)
Pathways	The gene product most likely functions in mitochondrial respiration/oxidative phosphorylation and the TCA cycle, serving as the electron-transfer link from succinate oxidation to the ubiquinone pool. In plants, SDH also interfaces functionally with succinate metabolism supplied by the GABA shunt under stress.	Inference/orthology + direct plant experiment (other species)	Fedorin 2022/2023, Plants, https://doi.org/10.3390/plants12010068 (fedorin2022effectofsalt pages 1-2, fedorin2022effectofsalt pages 2-5); Bouillaud 2023, Int J Mol Sci, https://doi.org/10.3390/ijms24044045 (bouillaud2023inhibitionofsuccinate pages 3-5); Iverson 2023, J Biol Chem, https://doi.org/10.1016/j.jbc.2023.104761 (iverson2023anevolvingview pages 1-2)
Regulation/stress links	In maize leaves under 150 mM NaCl, Sdh2-3 (SDHB) expression increased about 2-3-fold at 12-24 h, promoter methylation decreased from about 75% to 50% from 6 h onward, SDH activity became ~2-fold higher by 24 h, and mitochondrial succinate oxidation increased by about 40%. This supports stress-responsive regulation of plant SDHB-like genes, but the evidence is not Miscanthus-specific.	Direct experiment in orthologous plant system	Fedorin 2022/2023, Plants, https://doi.org/10.3390/plants12010068 (fedorin2022effectofsalt pages 2-5, fedorin2022effectofsalt pages 1-2)
Assays/inhibitors	SDH activity is measured using succinate-dependent reduction assays (e.g., DCPIP, tetrazolium salts, decylubiquinone/PMS intermediates) or succinate-supported mitochondrial respiration. Malonate, NPA, oxaloacetate inhibit the SDH/SDHA side; TTFA, atpenin, and SDHIs inhibit electron transfer near the quinone side. Reported Km for succinate is ~0.5-3 mM, with ~20 mM succinate often used for Vmax assays.	Review	Bouillaud 2023, Int J Mol Sci, https://doi.org/10.3390/ijms24044045 (bouillaud2023inhibitionofsuccinate pages 5-7)
Recent developments	Recent work emphasizes Complex II as not only a respiratory enzyme but also a signaling hub: succinate accumulation, ROS coupling, noncanonical/low-mass assemblies, and occasional megacomplex participation have emerged as active topics. The 2023 JBC review notes at least 14 unique Complex II enzymes across evolutionary subclasses and highlights altered signaling associated with Complex II-low species. These findings inform annotation context but do not directly validate Miscanthus NCGR_LOCUS67308.	Review + background	Iverson 2023, J Biol Chem, https://doi.org/10.1016/j.jbc.2023.104761 (iverson2023anevolvingview pages 5-7, iverson2023anevolvingview pages 7-8, iverson2023anevolvingview pages 2-4, iverson2023anevolvingview pages 10-11); Miklovicova 2025 background excerpt (miklovicova2025mitochondrialrespiratorycomplex pages 22-26)

Table: This table summarizes the best-supported functional annotation for UniProt A0A811SRM7 / NCGR_LOCUS67308 in Miscanthus lutarioriparius, while clearly separating direct evidence from inference based on conserved plant and eukaryotic Complex II biology. It is useful for reporting the likely SDHB-like role, localization, pathway context, and current evidence limitations.

Key figure (visual evidence)

A schematic of Complex II subunits and redox cofactors (FAD, FeS, quinone), and how common activity assays intercept electrons, was extracted from Bouillaud 2023 (Figure 4). (bouillaud2023inhibitionofsuccinate media e6ec7f85)

Source URLs and publication dates (where available in retrieved texts)

Iverson TM, Singh PK, Cecchini G. An evolving view of complex II—noncanonical complexes, megacomplexes, respiration, signaling, and beyond. Journal of Biological Chemistry. 2023-06. https://doi.org/10.1016/j.jbc.2023.104761 (iverson2023anevolvingview pages 1-2)
Bouillaud F. Inhibition of Succinate Dehydrogenase by Pesticides (SDHIs) and Energy Metabolism. International Journal of Molecular Sciences. 2023-02. https://doi.org/10.3390/ijms24044045 (bouillaud2023inhibitionofsuccinate pages 3-5)
Fedorin DN, Eprintsev AT, Florez Caro OJ, Igamberdiev AU. Effect of Salt Stress on the Activity, Expression, and Promoter Methylation of Succinate Dehydrogenase and Succinic Semialdehyde Dehydrogenase in Maize Leaves. Plants. Published 2022-12-23 (journal volume labeled 2023 in PDF header). https://doi.org/10.3390/plants12010068 (fedorin2022effectofsalt pages 1-2)
Ragab EM, Khamis AA, El Gamal DM, Mohamed TM. Comprehensive overview of how to fade into succinate dehydrogenase dysregulation in cancer cells by naringenin-loaded chitosan nanoparticles. Genes & Nutrition. 2024-05. https://doi.org/10.1186/s12263-024-00740-x (ragab2024comprehensiveoverviewof pages 1-3)

Limitations

No direct experimental publications specifically linking NCGR_LOCUS67308 or UniProt A0A811SRM7 to phenotype, expression, localization, or enzymatic activity in Miscanthus lutarioriparius were retrieved. Therefore, Miscanthus-specific statements are restricted to the provided UniProt identity, while mechanistic and quantitative statements derive from conserved SDH/Complex II literature and a maize ortholog study. (iverson2023anevolvingview pages 1-2, fedorin2022effectofsalt pages 2-5)

References

(iverson2023anevolvingview pages 1-2): T.M. Iverson, Prashant K. Singh, and Gary Cecchini. An evolving view of complex ii—noncanonical complexes, megacomplexes, respiration, signaling, and beyond. Journal of Biological Chemistry, 299:104761, Jun 2023. URL: https://doi.org/10.1016/j.jbc.2023.104761, doi:10.1016/j.jbc.2023.104761. This article has 57 citations and is from a domain leading peer-reviewed journal.
(bouillaud2023inhibitionofsuccinate pages 3-5): Frederic Bouillaud. Inhibition of succinate dehydrogenase by pesticides (sdhis) and energy metabolism. International Journal of Molecular Sciences, 24:4045, Feb 2023. URL: https://doi.org/10.3390/ijms24044045, doi:10.3390/ijms24044045. This article has 57 citations.
(fedorin2022effectofsalt pages 2-5): Dmitry N. Fedorin, Alexander T. Eprintsev, Orlando J. Florez Caro, and Abir U. Igamberdiev. Effect of salt stress on the activity, expression, and promoter methylation of succinate dehydrogenase and succinic semialdehyde dehydrogenase in maize (zea mays l.) leaves. Plants, 12:68, Dec 2022. URL: https://doi.org/10.3390/plants12010068, doi:10.3390/plants12010068. This article has 17 citations.
(iverson2023anevolvingview pages 2-4): T.M. Iverson, Prashant K. Singh, and Gary Cecchini. An evolving view of complex ii—noncanonical complexes, megacomplexes, respiration, signaling, and beyond. Journal of Biological Chemistry, 299:104761, Jun 2023. URL: https://doi.org/10.1016/j.jbc.2023.104761, doi:10.1016/j.jbc.2023.104761. This article has 57 citations and is from a domain leading peer-reviewed journal.
(bouillaud2023inhibitionofsuccinate media e6ec7f85): Frederic Bouillaud. Inhibition of succinate dehydrogenase by pesticides (sdhis) and energy metabolism. International Journal of Molecular Sciences, 24:4045, Feb 2023. URL: https://doi.org/10.3390/ijms24044045, doi:10.3390/ijms24044045. This article has 57 citations.
(iverson2023anevolvingview pages 10-11): T.M. Iverson, Prashant K. Singh, and Gary Cecchini. An evolving view of complex ii—noncanonical complexes, megacomplexes, respiration, signaling, and beyond. Journal of Biological Chemistry, 299:104761, Jun 2023. URL: https://doi.org/10.1016/j.jbc.2023.104761, doi:10.1016/j.jbc.2023.104761. This article has 57 citations and is from a domain leading peer-reviewed journal.
(iverson2023anevolvingview pages 7-8): T.M. Iverson, Prashant K. Singh, and Gary Cecchini. An evolving view of complex ii—noncanonical complexes, megacomplexes, respiration, signaling, and beyond. Journal of Biological Chemistry, 299:104761, Jun 2023. URL: https://doi.org/10.1016/j.jbc.2023.104761, doi:10.1016/j.jbc.2023.104761. This article has 57 citations and is from a domain leading peer-reviewed journal.
(iverson2023anevolvingview pages 5-7): T.M. Iverson, Prashant K. Singh, and Gary Cecchini. An evolving view of complex ii—noncanonical complexes, megacomplexes, respiration, signaling, and beyond. Journal of Biological Chemistry, 299:104761, Jun 2023. URL: https://doi.org/10.1016/j.jbc.2023.104761, doi:10.1016/j.jbc.2023.104761. This article has 57 citations and is from a domain leading peer-reviewed journal.
(ragab2024comprehensiveoverviewof pages 1-3): Eman M. Ragab, Abeer A. Khamis, Doaa M. El Gamal, and Tarek M. Mohamed. Comprehensive overview of how to fade into succinate dehydrogenase dysregulation in cancer cells by naringenin-loaded chitosan nanoparticles. Genes & Nutrition, May 2024. URL: https://doi.org/10.1186/s12263-024-00740-x, doi:10.1186/s12263-024-00740-x. This article has 1 citations and is from a peer-reviewed journal.
(bouillaud2023inhibitionofsuccinate pages 5-7): Frederic Bouillaud. Inhibition of succinate dehydrogenase by pesticides (sdhis) and energy metabolism. International Journal of Molecular Sciences, 24:4045, Feb 2023. URL: https://doi.org/10.3390/ijms24044045, doi:10.3390/ijms24044045. This article has 57 citations.
(fedorin2022effectofsalt pages 1-2): Dmitry N. Fedorin, Alexander T. Eprintsev, Orlando J. Florez Caro, and Abir U. Igamberdiev. Effect of salt stress on the activity, expression, and promoter methylation of succinate dehydrogenase and succinic semialdehyde dehydrogenase in maize (zea mays l.) leaves. Plants, 12:68, Dec 2022. URL: https://doi.org/10.3390/plants12010068, doi:10.3390/plants12010068. This article has 17 citations.
(miklovicova2025mitochondrialrespiratorycomplex pages 22-26): S Miklovičová. Mitochondrial respiratory complex ii and its function in cancer. Unknown journal, 2025.

Citations

iverson2023anevolvingview pages 1-2
bouillaud2023inhibitionofsuccinate pages 3-5
iverson2023anevolvingview pages 2-4
iverson2023anevolvingview pages 5-7
ragab2024comprehensiveoverviewof pages 1-3
bouillaud2023inhibitionofsuccinate pages 5-7
fedorin2022effectofsalt pages 2-5
miklovicova2025mitochondrialrespiratorycomplex pages 22-26
fedorin2022effectofsalt pages 1-2
iverson2023anevolvingview pages 10-11
iverson2023anevolvingview pages 7-8
ubiquinone
2Fe-2S
4Fe-4S
3Fe-4S
https://doi.org/10.1016/j.jbc.2023.104761
https://doi.org/10.3390/ijms24044045
https://doi.org/10.1186/s12263-024-00740-x
https://doi.org/10.3390/plants12010068
https://doi.org/10.1016/j.jbc.2023.104761,
https://doi.org/10.3390/ijms24044045,
https://doi.org/10.3390/plants12010068,
https://doi.org/10.1186/s12263-024-00740-x,

📚 Additional Documentation

Notes

(NCGR_LOCUS67308-notes.md)

NCGR_LOCUS67308 (A0A811SRM7) - Review Notes

Gene Identity

NCGR_LOCUS67308 from Miscanthus lutarioriparius (taxon 422564) encodes a protein annotated as
"Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial" (SDH2/SDHB). The protein
is 406 amino acids, derived from whole genome shotgun (WGS) preliminary data.

Key Finding: SDH2-RPS14 Fusion Locus

This gene model represents the grass-specific nuclear SDH2-RPS14 fusion locus, a well-characterized
phenomenon in Poaceae. The mitochondrial rps14 gene was transferred to the nucleus via endosymbiotic
gene transfer, integrating into an intron of the sdh2 gene.

Literature Evidence

Kubo et al. 1999 PMID:10430921: Discovered in rice that the nuclear sdh2 locus contains
an inserted rps14 gene. Alternative splicing produces two transcripts: one encoding SDH2 (~280 aa)
and one encoding a chimeric SDH2(transit peptide)-RPS14 precursor.
Figueroa et al. 1999 PMID:10417711: Demonstrated the same arrangement in maize (Zea mays),
where rps14 was transferred from mitochondria to the nucleus into the sdh2 locus.
Figueroa et al. 2000 PMID:10799306: Showed that the SDH2-RPS14 chimeric precursor is imported
into mitochondria and proteolytically cleaved to yield mature RPS14 protein.
Covello & Gray 2006 PMID:16549027: Documented pervasive survival of rps14 pseudogenes
across grasses, confirming this is a lineage-specific event in Poaceae.

Protein Architecture

The 406 aa protein represents an unspliced/combined reading frame of both SDH2 and RPS14:
- SDH2 portion (~280 aa): Contains 2Fe-2S ferredoxin domain (49-141), 4Fe-4S ferredoxin domain (184-214)
- RPS14 portion (~100-120 aa): C-terminal region matching ribosomal protein S14

In vivo, alternative splicing produces two separate proteins:
1. SDH2 (iron-sulfur subunit of Complex II) - functions in electron transfer from succinate to ubiquinone
2. RPS14 (mitochondrial ribosomal protein S14) - structural component of mitochondrial ribosome

Domain Matches

InterPro matches reflect both protein products:
- IPR004489: Succinate dehydrogenase/fumarate reductase Fe-S protein
- IPR025192: Succinate dehydrogenase/fumarate reductase N-terminal
- IPR001041: 2Fe-2S ferredoxin-type
- IPR009051: Helical ferredoxin
- IPR001209: Ribosomal uS14
- IPR018271: Ribosomal uS14 conserved site

Annotation Issues

The current GO annotations are a mix of SDH2-appropriate and RPS14-appropriate terms, applied to
the single combined protein entry. Many are incorrect when considered as annotations of a single
protein product:

Likely correct for SDH2 product:
- GO:0009055 (electron transfer activity)
- GO:0008177 (succinate dehydrogenase (quinone) activity) - but this is a complex-level activity
- GO:0051536 (iron-sulfur cluster binding)
- GO:0016491 (oxidoreductase activity)
- GO:0006099 (tricarboxylic acid cycle)
- GO:0022904 (respiratory electron transport chain)
- GO:0005743 (mitochondrial inner membrane)
- GO:0045273 (respiratory chain complex II)

Likely correct for RPS14 product:
- GO:0003735 (structural constituent of ribosome)
- GO:0006412 (translation)
- GO:0005840 (ribosome)

Problematic annotations:
- GO:0051537 (flavin binding) - SDH1/flavoprotein subunit binds FAD, NOT the iron-sulfur subunit SDH2
- GO:0045273 labeled as "respiratory chain complex I" in GOA - this is Complex II, not Complex I
- GO:0009536 (plastid) - SDH2 is mitochondrial; plastid SDH exists but the primary function is mitochondrial

Organism Context

Miscanthus lutarioriparius is a perennial grass in the Poaceae family (subfamily Panicoideae),
closely related to Saccharum (sugarcane) and Sorghum. It is used as a bioenergy crop.
The genome was sequenced from WGS data (submitted Oct 2020), and gene models are preliminary.

Conclusion

This protein entry represents a gene model artifact where two functionally distinct proteins
(SDH2 and RPS14) encoded by alternatively spliced transcripts from the same locus are combined
into a single predicted protein. The annotations reflect this duality. The SDH2 annotations are
generally appropriate for the SDH2 product, and the ribosomal annotations are appropriate for
the RPS14 product, but they should not all be applied to a single protein entry.

📄 View Raw YAML

id: A0A811SRM7
gene_symbol: NCGR_LOCUS67308
product_type: PROTEIN
status: DRAFT
tags:
  - chimeric-gene-model
  - sdh2-rps14-fusion
  - grass-specific
  - wgs-preliminary
taxon:
  id: NCBITaxon:422564
  label: Miscanthus lutarioriparius
description: >-
  This entry represents a chimeric gene model from WGS preliminary data that combines
  two functionally distinct proteins encoded by alternatively spliced transcripts from
  the grass-specific SDH2-RPS14 fusion locus. In grasses (Poaceae), the mitochondrial
  rps14 gene was transferred to the nucleus via endosymbiotic gene transfer and inserted
  into an intron of the sdh2 gene. Alternative splicing produces two distinct proteins:
  (1) SDH2 (succinate dehydrogenase iron-sulfur subunit), the iron-sulfur protein (IP)
  component of mitochondrial Complex II that transfers electrons from succinate to
  ubiquinone via three iron-sulfur clusters ([2Fe-2S], [3Fe-4S], [4Fe-4S]); and
  (2) RPS14 (mitochondrial ribosomal protein S14), a structural component of the
  mitochondrial small ribosomal subunit. The 406 aa protein entry represents the
  unspliced combined reading frame and is not a single biological protein product.
functional_isoforms:
  - id: NCGR_LOCUS67308_SDH2
    name: SDH2 (succinate dehydrogenase iron-sulfur subunit)
    type: SPLICE_CLASS
    description: >-
      The SDH2 splice product (~280 aa mature) is the iron-sulfur protein (IP) subunit
      of mitochondrial Complex II. Contains three iron-sulfur clusters ([2Fe-2S], [3Fe-4S],
      [4Fe-4S]) that relay electrons from succinate to ubiquinone. Peripheral membrane
      protein on the matrix side of the mitochondrial inner membrane. This is the primary
      protein product that the UniProt entry is named after.
    isoform_specific_terms:
      - id: GO:0009055
        label: electron transfer activity
      - id: GO:0051536
        label: iron-sulfur cluster binding
      - id: GO:0045273
        label: respiratory chain complex II (succinate dehydrogenase)
  - id: NCGR_LOCUS67308_RPS14
    name: RPS14 (mitochondrial ribosomal protein S14)
    type: SPLICE_CLASS
    description: >-
      The RPS14 splice product is produced from a chimeric SDH2(transit peptide)-RPS14
      precursor that is imported into mitochondria and proteolytically cleaved. The mature
      RPS14 (~16.5 kDa) assembles into the mitochondrial small ribosomal subunit. The SDH2
      N-terminal domain serves only as a mitochondrial targeting signal and is degraded
      after processing.
    isoform_specific_terms:
      - id: GO:0003735
        label: structural constituent of ribosome
      - id: GO:0006412
        label: translation
      - id: GO:0005840
        label: ribosome
references:
  - 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 EC number mapping.
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping.
    findings: []
  - id: GO_REF:0000117
    title: Gene Ontology annotation by ARBA (Association-Rule-Based Annotator).
    findings: []
  - id: GO_REF:0000118
    title: Gene Ontology annotation by TreeGrafter.
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods.
    findings: []
  - id: PMID:10430921
    title: "A single nuclear transcript encoding mitochondrial RPS14 and SDHB of rice is processed by alternative splicing: common use of the same mitochondrial targeting signal for different proteins."
    findings:
      - statement: In rice, rps14 was transferred from the mitochondrial genome to the nuclear sdh2 locus, producing alternatively spliced transcripts for SDH2 and a chimeric SDH2-RPS14 precursor
        supporting_text: "the two gene transcripts result from a single mRNA precursor by alternative splicing"
  - id: PMID:10417711
    title: Transfer of rps14 from the mitochondrion to the nucleus in maize implied integration within a gene encoding the iron-sulphur subunit of succinate dehydrogenase and expression by alternative splicing.
    findings:
      - statement: The same SDH2-RPS14 fusion arrangement exists in maize, confirming it is a grass-wide phenomenon
        supporting_text: "Transferred rps14 was found integrated between both exons of a gene encoding the iron-sulphur subunit of the respiratory complex II (sdh2)"
  - id: PMID:10799306
    title: The nuclear-encoded SDH2-RPS14 precursor is proteolytically processed between SDH2 and RPS14 to generate maize mitochondrial RPS14.
    findings:
      - statement: The SDH2-RPS14 chimeric precursor is imported into mitochondria and proteolytically processed to yield mature RPS14
        supporting_text: "the chimeric precursor undergoes proteolytical processing between SDH2 and RPS14. This processing generates RPS14, which is found assembled into mitochondrial ribosomes"
  - id: PMID:16842621
    title: 'Pervasive survival of expressed mitochondrial rps14 pseudogenes in grasses and their relatives for 80 million years following three functional transfers to the nucleus.'
    findings:
      - statement: rps14 pseudogenes are pervasive across grasses, documenting the lineage-specific endosymbiotic gene transfer
  - id: file:9POAL/NCGR_LOCUS67308/NCGR_LOCUS67308-notes.md
    title: "NCGR_LOCUS67308 review notes"
existing_annotations:
  # === Molecular Function annotations ===
  - term:
      id: GO:0003735
      label: structural constituent of ribosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    supporting_entities:
      - InterPro:IPR001209
      - InterPro:IPR018271
    review:
      summary: >-
        This annotation derives from the RPS14 portion of the chimeric gene model. Ribosomal protein
        S14 is indeed a structural constituent of the mitochondrial ribosome. However, this annotation
        should apply to the RPS14 protein product from alternative splicing, not to the SDH2 iron-sulfur
        subunit. Since this UniProt entry is named as SDH2, this annotation is misleading when applied
        to the combined entry.
      action: KEEP_AS_NON_CORE
      reason: >-
        Correct for the RPS14 alternative splice product but not for the SDH2 product that this entry
        primarily represents. The InterPro match to ribosomal uS14 (IPR001209) is real and reflects
        the RPS14 coding region within the chimeric gene model.
      supported_by:
        - reference_id: PMID:10430921
          supporting_text: "the two gene transcripts result from a single mRNA precursor by alternative splicing"

  - term:
      id: GO:0008177
      label: succinate dehydrogenase (quinone) activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000003
    supporting_entities:
      - EC:1.3.5.1
    review:
      summary: >-
        GO:0008177 represents the overall catalytic activity of the entire SDH complex (Complex II),
        not the activity of an individual subunit. SDH2 is the iron-sulfur subunit that transfers
        electrons within the complex but does not independently catalyze the succinate-to-ubiquinone
        reaction. The SDH2 subunit contributes to this activity as part of the complex.
      action: MODIFY
      reason: >-
        SDH2 does not independently enable succinate dehydrogenase (quinone) activity — this is a
        complex-level activity requiring all four SDH subunits (SDH1-4). Per GO annotation guidelines,
        the qualifier should be contributes_to (not enables) for the complex activity, since SDH2
        cannot catalyze the overall reaction alone. The subunit-specific function that SDH2 independently
        enables is electron transfer activity (GO:0009055).
      proposed_replacement_terms:
        - id: GO:0009055
          label: electron transfer activity
      supported_by:
        - reference_id: file:9POAL/NCGR_LOCUS67308/NCGR_LOCUS67308-notes.md
          supporting_text: "SDH2 is the iron-sulfur protein (IP) component of mitochondrial Complex II that transfers electrons from succinate to ubiquinone via three iron-sulfur clusters"

  - term:
      id: GO:0009055
      label: electron transfer activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    supporting_entities:
      - InterPro:IPR025192
    review:
      summary: >-
        Electron transfer activity is the core molecular function of the SDH2 iron-sulfur subunit.
        SDH2 transfers electrons from succinate (received via FAD on SDH1) through its three
        iron-sulfur clusters ([2Fe-2S], [3Fe-4S], [4Fe-4S]) to ubiquinone at the membrane-embedded
        SDH3/SDH4 subunits.
      action: ACCEPT
      reason: >-
        This correctly captures the subunit-specific molecular function of SDH2. The iron-sulfur
        clusters serve as an electron relay chain within Complex II.
      supported_by:
        - reference_id: file:9POAL/NCGR_LOCUS67308/NCGR_LOCUS67308-notes.md
          supporting_text: "SDH2 transfers electrons from succinate to ubiquinone via three iron-sulfur clusters"

  - term:
      id: GO:0016491
      label: oxidoreductase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    supporting_entities:
      - InterPro:IPR004489
    review:
      summary: >-
        Oxidoreductase activity is a broad parent term. The more specific electron transfer activity
        (GO:0009055) already captures the SDH2 function more precisely.
      action: KEEP_AS_NON_CORE
      reason: >-
        While technically correct as a parent of electron transfer activity, this is too general
        to be informative. The more specific GO:0009055 is already annotated and is preferable.

  - term:
      id: GO:0051536
      label: iron-sulfur cluster binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    supporting_entities:
      - InterPro:IPR001041
      - InterPro:IPR009051
      - InterPro:IPR025192
      - InterPro:IPR036010
    review:
      summary: >-
        SDH2 binds three distinct iron-sulfur clusters: [2Fe-2S], [3Fe-4S], and [4Fe-4S]. These
        are essential cofactors for the electron relay function of the subunit within Complex II.
        The 2Fe-2S ferredoxin domain (residues 49-141) and 4Fe-4S ferredoxin domain (residues 184-214)
        are confirmed by PROSITE domain predictions.
      action: ACCEPT
      reason: >-
        Core cofactor binding function of SDH2. The iron-sulfur clusters are essential for
        electron transfer within the respiratory chain complex.

  - term:
      id: GO:0051537
      label: 2 iron, 2 sulfur cluster binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    supporting_entities:
      - InterPro:IPR006058
    review:
      summary: >-
        SDH2 binds one [2Fe-2S] cluster via the 2Fe-2S ferredoxin domain at residues 49-141.
        This is a more specific child term of iron-sulfur cluster binding (GO:0051536) and
        correctly captures one of the three iron-sulfur cluster types bound by SDH2.
      action: ACCEPT
      reason: >-
        SDH2 binds one [2Fe-2S] cluster as confirmed by UniProt cofactor annotation and the
        2Fe-2S ferredoxin domain. This is a core cofactor binding function.

  # === Biological Process annotations ===
  - term:
      id: GO:0006099
      label: tricarboxylic acid cycle
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    supporting_entities:
      - InterPro:IPR004489
      - UniPathway:UPA00223
    review:
      summary: >-
        Complex II (succinate dehydrogenase) is the only enzyme shared between the TCA cycle and
        the electron transport chain. SDH2 is an essential subunit of this complex. The complex
        catalyzes the oxidation of succinate to fumarate (TCA cycle step) while simultaneously
        reducing ubiquinone (respiratory chain function).
      action: ACCEPT
      reason: >-
        SDH2 is directly involved in the TCA cycle as a subunit of succinate dehydrogenase, which
        catalyzes the succinate-to-fumarate step.

  - term:
      id: GO:0006412
      label: translation
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    supporting_entities:
      - InterPro:IPR001209
      - InterPro:IPR018271
    review:
      summary: >-
        This annotation derives from the RPS14 portion of the chimeric gene model. RPS14 is a
        mitochondrial ribosomal protein involved in mitochondrial translation. This annotation
        is correct for the RPS14 alternative splice product but not for the SDH2 protein.
      action: KEEP_AS_NON_CORE
      reason: >-
        Correct for the RPS14 product from alternative splicing of this locus, but not for SDH2.
        The InterPro match to ribosomal uS14 reflects the genuine RPS14 coding region in the
        chimeric gene model.
      supported_by:
        - reference_id: PMID:10430921
          supporting_text: "the two gene transcripts result from a single mRNA precursor by alternative splicing"

  - term:
      id: GO:0009060
      label: aerobic respiration
    evidence_type: IEA
    original_reference_id: GO_REF:0000118
    supporting_entities:
      - PANTHER:PTN002629819
    review:
      summary: >-
        Complex II functions in aerobic respiration as part of the mitochondrial electron transport
        chain. SDH2 is essential for this process, transferring electrons from the TCA cycle
        intermediate succinate to the respiratory chain via ubiquinone.
      action: ACCEPT
      reason: >-
        SDH2 is directly involved in aerobic respiration through its role in Complex II, which
        links the TCA cycle to the electron transport chain.

  - term:
      id: GO:0022904
      label: respiratory electron transport chain
    evidence_type: IEA
    original_reference_id: GO_REF:0000118
    supporting_entities:
      - PANTHER:PTN002629819
    review:
      summary: >-
        SDH2 is a core component of the respiratory electron transport chain as part of Complex II.
        It facilitates electron transfer from succinate to ubiquinone, feeding electrons into the
        downstream respiratory chain (Complex III and Complex IV).
      action: ACCEPT
      reason: >-
        Core biological process for SDH2. The electron transfer function of SDH2 is integral
        to the respiratory electron transport chain.

  # === Cellular Component annotations ===
  - term:
      id: GO:0005739
      label: mitochondrion
    evidence_type: IEA
    original_reference_id: GO_REF:0000118
    supporting_entities:
      - PANTHER:PTN002629819
    review:
      summary: >-
        Both SDH2 and RPS14 products from this locus are targeted to mitochondria. SDH2 is
        located at the mitochondrial inner membrane as part of Complex II. RPS14 is a component
        of the mitochondrial ribosome in the matrix.
      action: ACCEPT
      reason: >-
        Correct localization for both alternative splice products of this locus.

  - term:
      id: GO:0005743
      label: mitochondrial inner membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    supporting_entities:
      - UniProtKB-SubCell:SL-0168
    review:
      summary: >-
        SDH2 is a peripheral membrane protein on the matrix side of the mitochondrial inner membrane,
        anchored to the membrane-embedded SDH3/SDH4 subunits. This is the correct subcellular
        localization for SDH2 function in Complex II.
      action: ACCEPT
      reason: >-
        Correct and well-supported localization for SDH2 as part of the inner membrane-associated
        Complex II.

  - term:
      id: GO:0005840
      label: ribosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    supporting_entities:
      - InterPro:IPR001209
      - InterPro:IPR018271
    review:
      summary: >-
        This annotation derives from the RPS14 portion of the chimeric gene model. RPS14 is a
        component of the mitochondrial small ribosomal subunit. More specifically, this should
        be annotated to the mitochondrial small ribosomal subunit (GO:0005763).
      action: MODIFY
      reason: >-
        The generic "ribosome" term is too broad. The RPS14 product is specifically a component
        of the mitochondrial small ribosomal subunit. Additionally, this annotation applies to
        the RPS14 splice product, not to SDH2.
      proposed_replacement_terms:
        - id: GO:0005763
          label: mitochondrial small ribosomal subunit

  - term:
      id: GO:0009536
      label: plastid
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    supporting_entities:
      - UniProtKB-SubCell:SL-0209
    review:
      summary: >-
        While plants do have a plastidial succinate dehydrogenase, the primary and well-characterized
        function of SDH2 is mitochondrial. The plastid annotation is based on automated subcellular
        location prediction and lacks specific experimental evidence for this gene product.
      action: KEEP_AS_NON_CORE
      reason: >-
        Plastid SDH exists in plants but the evidence for plastid localization of this specific
        SDH2 is from automated prediction only. The primary function is mitochondrial.

  - term:
      id: GO:0045273
      label: respiratory chain complex II (succinate dehydrogenase)
    qualifier: part_of
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    supporting_entities:
      - ARBA:ARBA00027643
    review:
      summary: >-
        SDH2 is the iron-sulfur protein (IP) subunit of respiratory chain complex II. In plants,
        Complex II is composed of eight subunits: the four classical SDH1-4 subunits plus four
        plant-specific subunits. SDH2 is essential for the electron relay function within the complex.
      action: ACCEPT
      reason: >-
        Core component annotation. SDH2 is a defining subunit of Complex II. The part_of qualifier
        is appropriate.

core_functions:
  - description: >-
      Iron-sulfur subunit of mitochondrial Complex II (succinate dehydrogenase) that transfers
      electrons from succinate to ubiquinone via three iron-sulfur clusters ([2Fe-2S], [3Fe-4S],
      [4Fe-4S]). This dual-function complex links the TCA cycle (succinate to fumarate oxidation)
      with the respiratory electron transport chain. SDH2 does not independently catalyze the
      overall succinate dehydrogenase reaction but contributes to it as the electron relay component
      within the multi-subunit complex.
    molecular_function:
      id: GO:0009055
      label: electron transfer activity
    contributes_to_molecular_function:
      id: GO:0008177
      label: succinate dehydrogenase (quinone) activity
    directly_involved_in:
      - id: GO:0006099
        label: tricarboxylic acid cycle
      - id: GO:0022904
        label: respiratory electron transport chain
    in_complex:
      id: GO:0045273
      label: respiratory chain complex II (succinate dehydrogenase)
    locations:
      - id: GO:0005743
        label: mitochondrial inner membrane
    supported_by:
      - reference_id: PMID:10417711
        supporting_text: "Transferred rps14 was found integrated between both exons of a gene encoding the iron-sulphur subunit of the respiratory complex II (sdh2)"

suggested_questions:
  - question: >-
      Should this UniProt entry (A0A811SRM7) be split into two separate entries representing the
      SDH2 and RPS14 alternative splice products, or should it be annotated as a single locus
      with isoform-specific annotations?
  - question: >-
      Has the SDH2-RPS14 alternative splicing been experimentally confirmed in Miscanthus
      lutarioriparius specifically, or is it inferred from the well-characterized rice and maize
      orthologs?
  - question: >-
      Is there evidence for plastid-localized SDH2 function in Miscanthus, or is the plastid
      annotation purely an artifact of automated prediction?

suggested_experiments:
  - description: >-
      RT-PCR or RNA-seq analysis of the NCGR_LOCUS67308 locus in Miscanthus lutarioriparius
      to confirm alternative splicing produces separate SDH2 and RPS14 transcripts, as demonstrated
      in rice and maize.
  - description: >-
      Subcellular fractionation and immunoblotting to confirm SDH2 localization to mitochondrial
      inner membrane and determine whether any SDH2 is present in plastids.

NCGR_LOCUS67308

Gene Description

Functional Isoforms

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Tags

Deep Research

Falcon

Research report: Functional annotation of NCGR_LOCUS67308 (UniProt A0A811SRM7) in Miscanthus lutarioriparius

Executive summary

1) Target verification (critical identity checks)

2) Key concepts and definitions (current understanding)

2.1 Succinate dehydrogenase (SDH; mitochondrial Complex II)

2.2 SDHB (iron–sulfur subunit; “Ip” subunit)

3) Functional annotation for NCGR_LOCUS67308 / A0A811SRM7 (inferred)

3.1 Primary molecular function

3.2 Cellular and subcellular localization

4) Pathway context and biological processes

4.1 Respiration and energy metabolism

4.2 Succinate as a signaling/metabolic hub (broader context)

5) Recent developments (prioritizing 2023–2024 sources)

5.1 Noncanonical Complex II assemblies and megacomplex biology (2023)

5.2 Complex II within broader mitochondrial redox-cofactor frameworks (2024)

6) Current applications and real-world implementations

6.1 Functional assays used in research and annotation

6.2 Chemical inhibition as a probe of function

7) Relevant quantitative data and statistics (recent studies)

7.1 Kinetic/assay parameters from a 2023 review

7.2 Plant stress-linked regulation dataset (maize; publication date 2022-12-23, volume year 2023)

8) Expert opinion and synthesis (authoritative sources)

9) Practical functional annotation statement (recommended)

Synthesis table

Key figure (visual evidence)

Source URLs and publication dates (where available in retrieved texts)

Limitations

Citations

📚 Additional Documentation

Notes

NCGR_LOCUS67308 (A0A811SRM7) - Review Notes

Gene Identity

Key Finding: SDH2-RPS14 Fusion Locus

Literature Evidence

Protein Architecture

Domain Matches

Annotation Issues

Organism Context

Conclusion

📄 View Raw YAML