PIN1 (PIN-FORMED 1, AtPIN1) — Arabidopsis thaliana — curation notes

UniProt: Q9C6B8 (PINI_ARATH); locus AT1G73590; TCDB 2.A.69.1.1 (auxin efflux carrier / AEC family).

Core identity and molecular function

PIN1 is a plasma-membrane, polytopic (10-TM) secondary transporter that mediates
cellular auxin efflux. Its polar (asymmetric) localization at the plasma membrane
sets the direction of intercellular (polar) auxin transport, generating the local auxin
gradients/maxima that drive organogenesis, vascular patterning, embryo axis formation
and phyllotaxis.

• Founding identification as auxin efflux carrier component, basal localization in vascular
  cells, polar auxin transport: PMID:9856939. Disruption phenotype: naked, pin-shaped inflorescences.
• Direct demonstration of active auxin efflux and structural mechanism: PIN1 expressed in
  HEK293F cells mediates active IAA efflux (enhanced by D6PK), inhibited by NPA
  PMID:35917925.
• Substrate recognition: binds IAA (and IBA, IPA, 4-Cl-IAA) at an intracellular pocket;
  residues V51, N112, N478, I582 coordinate IAA PMID:35917925.
• Fold: 10-TM NhaA fold, TM1–TM5 / TM6–TM10 inverted repeats; inward-facing conformation
  PMID:35917925.
• Homodimer: cryo-EM shows a dimeric PIN1 (TM1, TM2, TM7 dimer interface)
  PMID:35917925. This supports the GOA
  IDA annotations GO:0042802 identical protein binding and GO:0042803 protein
  homodimerization activity.

So the appropriate, informative MF terms are:
- GO:0010329 auxin efflux transmembrane transporter activity (IDA + IMP) — ACCEPT, core.
- GO:0042803 protein homodimerization activity / GO:0042802 identical protein binding — ACCEPT (homodimer is structurally established), non-core.

Localization

• Plasma membrane is the functional site (multiple IDA/EXP): PMID:9856939, PMID:20439545,
  PMID:33705718.
• Polar PM domains: apical vs basal localization is phosphorylation-dependent
  PMID:20407025.
  Basal PM localization in vascular cells PMID:9856939. Apical/basal domains:
  GO:0016324 apical plasma membrane, GO:0009925 basal plasma membrane, GO:0045177 apical
  part of cell — all reflect the polar PM domain (cell periphery GO:0071944).
• GO:0005737 cytoplasm (HDA, PMID:15610358): PIN1 cycles between PM and endosomal
  compartments via GNOM-dependent recycling (UniProt FUNCTION). Cytoplasmic/endosomal
  signal is real (trafficking intermediates) but not the functional compartment; keep as
  non-core.
• GO:0009506 plasmodesma (HDA, PMID:21533090, proteomics): high-throughput proteome; PIN1
  is a PM protein and plasmodesmal PM is continuous with PM; weak/peripheral, keep non-core.
• GO:0009505 plant-type cell wall (IDA, PMID:18539115): PIN1 is an integral membrane
  protein; cell-wall assignment is not biologically meaningful for an auxin efflux carrier
  and likely reflects PM/apoplast-adjacent signal; mark as over-annotated.
• GO:0010168 ER body (IDA, PMID:36398993): PMID:36398993 is a tomato BIG/rosette paper
  about calcium and wound-induced rooting; it concerns ER localization of BIG, not PIN1
  ER-body localization. ER bodies are ER-derived structures found in Brassicaceae; there is
  no strong support that PIN1 is an ER-body resident. The long PINs (incl. PIN1) are PM
  proteins; only short PINs (PIN5/PIN8) are ER PMID:35917925. Treat ER body as a dubious annotation -> REMOVE/over-annotated. Marked UNDECIDED-leaning-REMOVE; chose MARK_AS_OVER_ANNOTATED conservatively is not appropriate since it appears to be a mis-assignment; chose REMOVE with rationale.

Regulation / interactors (the "protein binding" GO:0005515 IPI rows)

All GO:0005515 rows are uninformative bare "protein binding"; replace with specific
interactor context in reason, action MARK_AS_OVER_ANNOTATED (interaction is real but term
uninformative; per project guidance avoid bare protein binding as core).

• PMID:17237354 WITH UniProtKB:Q9LJX0 = ABCB19/PGP19 — PIN–P-glycoprotein co-action in auxin transport.
• PMID:17889649 / PMID:20080776 WITH O64682 = PID (PINOID kinase) — phosphorylates PIN1 HL, controls polarity.
• PMID:33705718 WITH Q0WL52 = NPY5/MEL1 (MAB4/MEL family) — recruited to PM by PIN1, maintains polarity.
• PMID:22715043 WITH Q9LHE7 (FYPP1) and Q9SX52 (FYPP3) — PP6 phosphatase, dephosphorylates PIN.
• PMID:36226797 WITH AT3G55880 = SUE4 — PIN1-interacting membrane protein, acropetal transport under S deficiency.
• PMID:17586653 WITH Q9LY87 — K63 ubiquitin ligase context (apical dominance).

UniProt SUBUNIT: "Homodimer. Interacts with TOPP4 ... Interacts with FYPP1 and FYPP3 ...
Component of a complex made of PINs, MAB4/MELs and AGC kinases at the plasma membrane.
Binds directly to NPY5/MEL1."

Biological processes (mostly IMP / acts_upstream_of_or_within)

Core BP:
- GO:0009926 auxin polar transport (IMP, PMID:16601150) — CORE.
- GO:0060918 auxin transport (IEA/IMP) — CORE (parent of polar transport).
- GO:0010315 auxin export across the plasma membrane (IDA, PMID:35917925) — CORE, most precise BP for the efflux event.
- GO:0055085 transmembrane transport (IEA) — accept as broad-but-correct parent.

Downstream developmental processes (pleiotropic; PIN1 acts upstream-of-or-within via auxin
gradients) — keep as non-core:
- GO:0009908 flower development; GO:0010229 inflorescence development (PMID:20407025; pin1 = pin-shaped naked inflorescence).
- GO:0048825 cotyledon development (IGI PMID:15371311); GO:0048826 cotyledon morphogenesis; GO:0009793 embryo development (PMID:20407025).
- GO:0010358 leaf shaping (PMID:16971475); GO:0010051 xylem and phloem pattern formation (PMID:16943276).
- GO:0009630 gravitropism (PMID:16601150); GO:0009640 photomorphogenesis (TAS PMID:16141452).
- GO:0048364 root development; GO:0048367 shoot system development (PMID:9856939/PMID:11060241).
- GO:0010262 somatic embryogenesis (IMP PMID:36345646); GO:0048830 adventitious root development (IMP PMID:36398993 — tomato ro/big paper; PIN1 accumulation Ca-sensitive). The adventitious-root annotation rests on an indirect tomato study; keep as non-core but flagged.

Deep research synthesis (Falcon / Edison Scientific, 2026-06-06)

The Falcon deep-research report (file:ARATH/PIN1/PIN1-deep-research-falcon.md) corroborates
the existing review and adds no contradicting evidence. Key points used to strengthen the
review:

• Disambiguation: the target is the Arabidopsis PIN-FORMED1 auxin transporter (Q9C6B8,
  At1g73590), not the animal PIN1 prolyl isomerase; the 2022 cryo-EM study explicitly
  references Q9C6B8 ["demonstrates PIN1-mediated auxin (IAA) efflux and inhibitor (NPA)
  binding, matching the UniProt record provided"].
• Core MF: PIN1 "exports auxin from the cytosol toward the apoplast" via "a defined
  intracellular binding pocket that coordinates IAA" (apo/IAA-bound/NPA-bound inward-facing
  states); IAA Kd = 83 ± 10 µM vs NPA Kd = 0.15 ± 0.08 µM (ITC, pH 7.0), NPA a competitive
  inhibitor of the same site. Supports GO:0010329 (auxin efflux transmembrane transporter
  activity) and GO:0010315 (auxin export across the PM).
• Polar transport: polar PM distribution "determines the direction of auxin flow between
  neighboring cells"; PIN1 "frequently described as basally localized" in vascular tissue
  and root stele. Supports GO:0009926 (auxin polar transport) and GO:0009925 (basal PM).
• Transport mechanism: elevator-like alternating-access; energetics consistent with a
  uniport-like mechanism, though the in vivo energy source remains unresolved (no GO change
  warranted).
• Developmental output: "pin1 mutants exhibit severe organ initiation failures, producing
  'pin-like' stems with reduced or absent flowers/organs" — supports the non-core
  inflorescence/flower-development annotations.
• Regulation context (2023–2024): D6PK activates PIN1 transport; PID/WAG bias apical sorting;
  GNOM-dependent recycling and K63-ubiquitin/vacuolar turnover; phosphoinositide/CLE-peptide
  hubs and ENHANCER OF PINOID modulate PIN1 patterning. These reinforce (but do not change)
  the MARK_AS_OVER_ANNOTATED decisions on the bare protein-binding (GO:0005515) interactor rows.

No UNDECIDED actions were present and none were created; no new GO term with a verifiable ID
emerged from the report (the regulatory/interactor findings remain best captured by specific
interactor context rather than bare protein binding, consistent with existing decisions).
Status remains DRAFT.

Summary of decisions

• ACCEPT (core MF/BP/CC): auxin efflux transmembrane transporter activity (x2), auxin export across PM, auxin polar transport, auxin transport (x2), plasma membrane (multiple), transmembrane transport.
• ACCEPT non-core / homodimer: identical protein binding, protein homodimerization activity.
• KEEP_AS_NON_CORE: polar PM subdomains (apical/basal PM, apical part of cell, cell periphery), cytoplasm, plasmodesma, and all developmental BPs.
• MARK_AS_OVER_ANNOTATED: bare protein binding rows; plant-type cell wall.
• REMOVE: ER body (mis-assignment / wrong paper context).

PR #1417 review fix: bare-title supporting_text (2026-06-06)

Reviewer (ai4c-agent) flagged ~12 supporting_text entries that were merely the
publication TITLE rather than evidentiary excerpts. Each cited PMID was opened and
checked against the specific GO term claim.

Replaced title with a real verbatim quote (publication substantiates the claim):
- PMID:17237354 (GO:0005515, ABCB19/PGP19 interaction) — Y2H + coIP statement.
- PMID:20439545 (GO:0005886 plasma membrane) — "those PINs were localized in the plasma membrane...".
- PMID:36226797 (GO:0005515, SUE4 interaction) — "SUE4...interacts with the polar auxin transporter PIN1".
- PMID:22715043 (GO:0005515, FYPP1/3 interaction) — "FyPP1 and FyPP3 interact with a subset of PIN proteins...".
- PMID:17586653 (GO:0005515, RGLG2 interaction) — "RGLG2 and PIN1 can interact in the yeast two-hybrid system".
- PMID:15371311 (GO:0048825 cotyledon development) — pin1/pid disrupt cotyledon symmetry.
- PMID:16107478 (GO:0045177 apical part of cell) — PIN1 polarity in the apex.
- PMID:11060241 (GO:0048367 shoot system development) — pin1 organ-initiation/naked inflorescence.
- PMID:16601150 (GO:0009926 auxin polar transport, + same in core_functions[1]) — PINs mediate efflux in heterologous cells.
- PMID:36345646 (GO:0010262 somatic embryogenesis) — PIN-FORMED1 efflux drives PAT required for proembryo transition (full text).

Set to UNDECIDED (cited paper does NOT substantiate the claim / no usable PIN1-specific text):
- PMID:17889649 (GO:0005515, PID) — abstract reports PP2A/PINOID colocalization, not a PIN1-PID binding assay.
- PMID:20080776 (GO:0005515, PID) — states in vitro results do NOT support the site as a PID target; no PIN1-PID binding assay.
- PMID:15610358 (GO:0005737 cytoplasm) — generic GFP-fusion methods paper; no PIN1-specific localization.
- PMID:21533090 (GO:0009506 plasmodesma) — plasmodesmal proteome text does not mention PIN1 at all.
- PMID:18337510 (GO:0005886 plasma membrane) — ATI/actin/vesicle study; no PIN1 PM localization data in available text.
- PMID:19825598 (GO:0005886 plasma membrane) — about SCAR complex (BRK1/SCAR1) PM localization; PIN1 not mentioned.
- PMID:18539115 (GO:0005886 plasma membrane) — WOX2/WOX8 paper; PIN1 only as a reporter for auxin response, no PM localization.
- PMID:16971475 (GO:0010358 leaf shaping) — AS1/KNOX paper; PIN1 not mentioned.
- PMID:16943276 (GO:0010051 xylem/phloem patterning) — HVE/CAND1 paper explicitly states pathway involves "...but not...PIN1...".
- PMID:16141452 (GO:0009640 photomorphogenesis) — BR/PAT/tropism via PIN2 protein; no PIN1-specific photomorphogenesis evidence.
- PMID:16601150 (GO:0009630 gravitropism) — rate-limiting efflux paper; does not mention gravitropism.

Note: PIN1 plasma-membrane localization itself remains well supported by other rows
(PMID:33705718, PMID:35917925, PMID:20439545); the UNDECIDED PM rows reflect that those
particular citations don't substantiate localization, hence the validator's
"inconsistent review actions for GO:0005886" warning (expected/acceptable).
Status kept DRAFT; validation: ✓ Valid.