PLN (phospholamban) review notes
UniProt P26678, 52 aa, single-pass SR/ER membrane protein, PE1. Regulin family (PANTHER
node PTN002722410 in the IBA rows). No deep-research file was generated for this gene
(Tier 2/4 microproteins batch; instructions say not to run deep research).
Core biology
- Reversible SERCA2a inhibitor. "In cardiac muscle, SERCA is regulated by phospholamban (PLB),
a small inhibitory phosphoprotein that decreases the Ca(2+) affinity of SERCA and attenuates
contractile strength." PMID:23996003
- Crystal structure of the PLB-SERCA complex: "PLB4 as an α-helix bound within a groove formed
between transmembrane helices M2, M4, M6, and M9 of SERCA" and the two Ca sites "are both
severely disrupted by PLB4 binding" PMID:23996003. The PLB4 construct is a
monomerising/superinhibitory variant; SERCA1a was used ("regulated identically by PLB").
- Reconstitution kinetics (human-type PLB with SERCA in proteoliposomes): "Only three steps in
the reaction scheme were affected by the presence of PLB, namely, binding of the first calcium
ion, a subsequent conformational change in SERCA, and binding of the second calcium ion."
PMID:19708671. This is the IDA source for GO:0042030 and GO:0141110.
- Phosphorylation relief: "Cyclic AMP-dependent phosphorylation of PLN reverses its inhibitory
effect on the Ca2+ pump." PMID:22679139; PKA motif disrupted by R14del:
"Deletion of Arg(14) disrupts the protein kinase A recognition motif, which abrogates
phospholamban phosphorylation and results in constitutive SERCA inhibition." PMID:22707725
- Pentamer: "Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a
30-kDa homopentamer" held together by "leucine/isoleucine zipper motifs" PMID:16043693.
Monomer is the inhibitory species; "Phosphorylation of PLN monomers promotes association into
inactive pentamers." PMID:22679139
- Channel claim for the pentamer PMID:26673394: GUV patch clamp "highlight a preference for
Cs(+) over K(+) and do not conduct Ca(2+)". Physiological relevance debated; not in GOA as an
MF; not proposed.
- Mouse knockout: "phospholamban acts as a critical repressor of basal myocardial contractility"
and KO mice show "enhanced myocardial performance without changes in heart rate" PMID:8062415.
This bears on the "negative regulation of heart rate" rows (both MARK_AS_OVER_ANNOTATED).
- Human disease: R9C PMID:12610310, R14del PMID:16432188 dilated cardiomyopathy.
- Hetero-oligomers with other regulins: "PLB was a universal partner for all other micropeptides
tested" PMID:36523160.
Protein-binding rows (63)
- 61 rows come from HT Y2H screens (HuRI PMID:32296183, PMID:25416956, PMID:25910212,
PMID:31515488, PMID:24722188). Partners are mostly unrelated membrane proteins (EDA, BCL2L13,
LDLRAD1, TMEMs, SLCs), typical of sticky TM-helix baits in Y2H. REMOVE as uninformative.
- PMID:28890335 ATP2A2 (P16615) row: the paper describes the "SERCA/PLN/SLN inhibitory complex",
so MODIFY to ATPase inhibitor activity. VMP1 row: REMOVE (VMP1 competes with PLN; binding term
uninformative).
- PMID:15598648 DMPK: PLN is a kinase substrate; no MF for PLN; REMOVE.
Other decisions
- Spermatid / sleep / visual learning / locomotor rhythm rows are mouse ISS/IEA transfers of
indirect or tissue-specific phenotypes; flagged as over-annotation.
- Rat IEA "response to zinc / insulin / testosterone" are expression-response transfers; REMOVE.
- 26673394 (GUV channel paper, abstract only) supports IDA rows for regulation of Ca transport
and cardiac muscle cell contraction; abstract describes only an isolated vesicle channel
assay that does not conduct Ca2+. Full text unavailable, so per "do not overrule curators"
these rows are ACCEPTed or MODIFYed (to the SR Ca2+ import term) because the functions are
clearly correct for PLN; the mismatch is recorded in the reference_review.
Regulin MF comparison (Tier 4)
| gene |
MF in GOA (non-binding) |
MF chosen in repo review |
| PLN |
GO:0042030 ATPase inhibitor (IBA/IDA/ISS/IEA), GO:0141110 transporter inhibitor (IDA), GO:0004857 (ISS) |
GO:0042030 core; GO:0141110 accepted |
| SLN |
GO:0004857 enzyme inhibitor (ISS), GO:0030234 (IEA), GO:0051117 |
not yet reviewed in repo |
| MRLN |
GO:0004857 (ISS/IEA) |
MODIFY -> GO:0042030 |
| ERLN |
none |
NEW GO:0042030 |
| STRIT1 (DWORF) |
GO:0008047 enzyme activator (ISS) |
GO:0141109 transporter activator activity |
QuickGO (2026-10-08): GO:0141110 is used on PLN (IDA), CALM, PCSK9, Agrn; GO:0042030 on PLN,
ATP5IF1, FNIP1/2, TSC1. The PLN IBA for GO:0042030 sits on PTN002722410, so the regulin node
already carries the ATPase-inhibitor framing. Recommendation: GO:0042030 for the inhibitory
regulins (PLN, SLN, MRLN, ERLN), GO:0141110 acceptable as a parallel; inconsistency with DWORF
(GO:0141109 rather than GO:0001671 ATPase activator activity) should be resolved one way.