LCIA (NAR1.2; Q75NZ3; Cre06.g309000) notes

Deep research status

• 2026-10-03: scripts/deep_research_wrapper.py CHLRE LCIA falcon --fallback perplexity-lite
  was run once. Falcon timed out (600 s; falcon currently returns HTTP 402) and the
  perplexity-lite fallback failed ("Provider 'perplexity' not available"). Not retried.
  No -deep-research-*.md file exists; the review is built from the cached primary
  literature below.

Identity

• UniProt Q75NZ3 (TrEMBL, unreviewed, PE 1), 336 aa, gene LciA, also NAR1.2;
  KEGG cre:CHLRE_06g309000v5. FNT transporter family (TC 1.A.16), Pfam PF01226,
  PANTHER PTHR30520:SF6. Six predicted TM helices (106-322). Cryo-EM structure
  PDB 9V2A (residues 39-336, five chains A-E, i.e. an FNT-type pentamer).
• Same protein as NAR1.2: PMID:25336519.
• Has an N-terminal chloroplast transit peptide: PMID:16905358. Removing the predicted 73-aa
  transit peptide sends LCIA:GFP to the cytosol in tobacco
  PMID:26538195.

Expression

• Identified as a CCM1(CIA5)-dependent low-CO2-inducible gene
  PMID:15235119
• Unlike other NAR1 paralogs it is carbon-regulated, not nitrogen/Nit2-regulated
  PMID:16905358.
• Expression depends on the Ca2+-binding protein CAS (retrograde signal from the
  pyrenoid) PMID:27791081.

Location: chloroplast envelope

• Immunofluorescence (cup-shaped chloroplast signal) and envelope membrane fractionation
  [PMID:26015566 "LCIA was highly enriched in the CE fraction, where CE protein CCP1 (30)
  was also enriched."; "we concluded that HLA3 and LCIA were localized to the PM and CE,
  respectively."]
• Venus fusion in Chlamydomonas and GFP in tobacco/Arabidopsis
  PMID:26538195.
• Which envelope membrane: Nolke et al. place transgenic LCIA in the inner envelope of
  tobacco PMID:29888874. Not resolved for the native protein in Chlamydomonas, so chloroplast
  envelope (GO:0009941) is the safe level; inner membrane (GO:0009706) is plausible
  because the outer envelope is generally porous to small anions.
• Plasma membrane location of bacterial FNT members (IBA donors) does not transfer: LCIA
  carries a transit peptide and is not at the plasma membrane in Chlamydomonas.

Activity: bicarbonate (and nitrite) transport

• Xenopus oocytes, electrophysiology (Mariscal 2006, abstract only):
  PMID:16905358
• Xenopus oocytes, H14CO3- uptake with mature LCIA (no transit peptide)
  PMID:26538195.
• Complementation of E. coli lacking carbonic anhydrases and Arabidopsis beta-ca5
  (Forster 2023, abstract only) PMID:36987927
• Cryo-EM structure (Guo 2026, abstract only): FNT-type channel with a bicarbonate
  selectivity filter (Lys220; Ala117/Val267); K136A/A114F increase activity; bacterial
  nitrite channel NirC could be engineered to conduct bicarbonate, and Chlamydomonas
  NAR1.1/NAR1.5 have some bicarbonate transport capacity PMID:41507353.
• Mechanism: FNT family proteins are pentameric anion channels; the 2026 abstract calls
  LciA "a chloroplast envelope bicarbonate channel". GO has GO:0160133 bicarbonate
  channel activity (is_a GO:0015106). I used the parent GO:0015106 in core_functions
  because the channel mechanism for LCIA rests on an abstract-only structural paper and
  family inference; flagged as a question.
• Formate: no report that LCIA transports formate. Its bicarbonate selectivity is set by
  a specific filter, and the IBA formate terms come from bacterial FocA-type members
  (P0AC23 FocA, P77733 FocB). Formate IBA rows modified to bicarbonate.
• Nitrite: oocyte currents with NO2- (PMID:16905358); physiological relevance unclear
  because LCIA is not nitrogen-regulated. Not proposed as a NEW annotation.

In vivo role in the CCM

• Off-target LCIA knockdown together with HLA3 RNAi strongly reduced Ci uptake at pH 9
  PMID:19321421.
• lcia/lcib double mutant cannot survive very low CO2; LCIA associated with HCO3-
  uptake, LCIB with CO2 uptake PMID:25336519
• Insertion mutants and overexpression: cooperative HLA3/LCIA HCO3- uptake; LCIA loss
  also lowers HLA3 mRNA (retrograde) PMID:26015566.
• Heterologous expression in Arabidopsis gave no growth advantage (PMID:26538195);
  Nolke 2019 reported increased CO2 uptake and biomass in tobacco (PMID:29888874).

Module check (modules/pyrenoid_ccm.yaml, annoton lcia_envelope_uptake)

• Module asserts GO:0015106 bicarbonate transmembrane transporter activity at GO:0009941
  chloroplast envelope. Both supported (oocyte uptake, E. coli/Arabidopsis
  complementation, structure; IF/fractionation/fluorescent fusions).