Lcp3

UniProt ID: A0A0B4KEF3
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

Lcp3 (Larval cuticle protein 3, LCP-III, CG2043) is a small secreted structural protein of the Drosophila melanogaster larval chitin-based cuticle. It is one of the major third-instar larval cuticle proteins and is encoded in the 44D larval cuticle protein gene cluster together with the related Lcp1, Lcp2 and Lcp4 genes, which are expressed in the epidermis of third-instar larvae. The 112-residue precursor carries an N-terminal signal peptide (residues 1-16) and a Rebers-Riddiford (R&R, chitin-binding type-4) cuticle-protein domain, placing it in the CPR cuticular protein family (PANTHER PTHR10380, subfamily SF237). The mature protein was sequenced from larval cuticle, and it resides in the extracellular chitin-protein matrix secreted by the larval epidermis, where it contributes to the structure of the larval cuticle. Direct chitin binding, its precise layer within the procuticle and an organismal loss-of-function phenotype have not been established for Lcp3 itself.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005214 structural constituent of chitin-based cuticle
IEA
GO_REF:0000002 		MODIFY
Summary: Correct but general; Lcp3 is a structural constituent of the larval chitin-based cuticle specifically.
Reason: The InterPro-based structural annotation is biologically correct (R&R/CPR domain, signal peptide, sequenced from larval cuticle), but the evidence supports the more specific descendant GO:0008010 (is_a GO:0005214, verified via OLS hierarchicalAncestors). A0A0B4KEF3 encodes exactly the same 112-residue polypeptide as the reviewed Lcp3 record P07188 (same FlyBase gene FBgn0002534), whose function is curated as a component of the larval cuticle and whose mature protein was sequenced from third-instar larval cuticle. The larval qualifier is gene-specific evidence; it is not transferable to the whole SF237 subfamily, which also contains the Drosophila pupal cuticle protein Pcp and lobster cuticle proteins.
Supporting Evidence:
file:DROME/Lcp3/Lcp3-reference-P07188-uniprot.txt
Component of the larval cuticle.
file:DROME/Lcp3/Lcp3-bioinformatics/RESULTS.md
The selected A0A0B4KEF3 sequence is identical to reviewed Lcp3 P07188: 112 of 112 residues match without gaps.
PMID:6817923
Amino acid sequences of four of the five major third instar cuticle proteins have been determined.
GO:0042302 structural constituent of cuticle
IEA
GO_REF:0000104 		MODIFY
Summary: Correct but general; Lcp3 is a structural constituent of the larval chitin-based cuticle specifically.
Reason: Same claim as the InterPro row at a still broader level (GO:0042302 is an ancestor of both GO:0005214 and GO:0008010). The structural cuticle role is well supported for Lcp3, so the action is consistent with the sister row - MODIFY to the specific larval term carried by the identical reviewed polypeptide P07188.
Supporting Evidence:
file:DROME/Lcp3/Lcp3-reference-P07188-uniprot.txt
Component of the larval cuticle.
file:DROME/Lcp3/Lcp3-bioinformatics/RESULTS.md
The selected A0A0B4KEF3 sequence is identical to reviewed Lcp3 P07188: 112 of 112 residues match without gaps.
PMID:6817923
Amino acid sequences of four of the five major third instar cuticle proteins have been determined.
GO:0062129 chitin-based extracellular matrix
IEA
GO_REF:0000002 		ACCEPT
Summary: Lcp3 is a component of the extracellular chitin-based larval cuticle.
Reason: The location follows from the characterized protein, not only from the InterPro signature. The mature protein was isolated and sequenced from larval cuticle, it carries a signal peptide consistent with secretion by the epidermis, and the identical reviewed polypeptide (P07188) is curated by FlyBase to the chitin-based extracellular matrix. GO:0062129 is the appropriate precision; no evidence resolves a particular procuticle layer.
Supporting Evidence:
file:DROME/Lcp3/Lcp3-reference-P07188-uniprot.txt
Component of the larval cuticle.
file:DROME/Lcp3/Lcp3-bioinformatics/RESULTS.md
The selected A0A0B4KEF3 sequence is identical to reviewed Lcp3 P07188: 112 of 112 residues match without gaps.
PMID:6817923
Amino acid sequences of four of the five major third instar cuticle proteins have been determined.
PMID:6441593
Proteins, soluble in 7 M urea, were extracted from third-instar larval and pupal cuticles of Drosophila melanogaster.

Core Functions

Secreted structural constituent of the larval chitin-based cuticle, deposited by the larval epidermis into the extracellular chitin-protein matrix.

Molecular Function:
structural constituent of chitin-based larval cuticle
Cellular Locations:
chitin-based extracellular matrix
Supporting Evidence:
  • file:DROME/Lcp3/Lcp3-reference-P07188-uniprot.txt
    Component of the larval cuticle.
  • file:DROME/Lcp3/Lcp3-bioinformatics/RESULTS.md
    The selected A0A0B4KEF3 sequence is identical to reviewed Lcp3 P07188: 112 of 112 residues match without gaps.
  • PMID:6817923
    Amino acid sequences of four of the five major third instar cuticle proteins have been determined.
  • file:DROME/Lcp3/Lcp3-deep-research-falcon.md
    This molecular assignment is strong at the protein-family level but remains **unverified directly for purified Drosophila LCP3**.

References

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Suggested Questions for Experts

Q: Does Lcp3 bind chitin directly through its R&R domain, as shown for some other CPR proteins, and should GO chitin binding (GO:0008061) be propagated across the PTHR10380 SF237 subfamily or only to members with direct binding data?

Q: Is the larval stage restriction of Lcp3 (as opposed to the pupal Pcp in the same PANTHER subfamily) a property of the protein or only of its transcriptional program, i.e. could Lcp3 substitute for other CPR proteins in pupal or adult cuticle?

Suggested Experiments

Experiment: Express recombinant Lcp3 R&R domain (or GST fusion) and measure binding to purified chitin, with conserved R&R aromatic residues mutated as controls.

Hypothesis: Lcp3 binds polymeric chitin through its Rebers-Riddiford domain like other CPR-family proteins.

Experiment: Generate a clean CRISPR Lcp3 null (leaving Lcp1, Lcp2 and Lcp4 intact) and assess larval cuticle ultrastructure, permeability and mechanical properties.

Hypothesis: Loss of Lcp3 alone has little organismal effect because of redundancy within the 44D cluster, but alters larval procuticle composition.

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM External predictions

View prediction review YAML · Lcp3-protnlm-predictions-review.yaml · Review status: COMPLETE

ProtNLM2 emitted no GO or EC predictions for A0A0B4KEF3 in the frozen 2026-09-08 API snapshot. It emitted a protein name, a Secreted location, and the function text "Component of the rigid cuticle of the spider". The absence of GO output is an informative coverage omission: the current target is identical over all 112 residues to reviewed Lcp3 P07188 at the same FlyBase locus, which has experimental FlyBase annotations for GO:0008010 structural constituent of chitin-based larval cuticle and GO:0062129 chitin-based extracellular matrix. The target itself carries electronic GOA rows for GO:0005214, GO:0042302 and GO:0062129, and its gene review takes GO:0008010 with GO:0062129 as the core function. These are well-supported expected functions, not predictions emitted by ProtNLM, so any cuticle-structure GO term it could have emitted would not be novel. The separate function-description review supports the broad cuticle claim, leaves the rigid qualifier uncertain, and rejects the spider attribution. This record assesses missing GO output without assigning a VDCL score to an absent prediction or asserting a benchmark-wide recall value; the prediction-time input sequence and training-set membership remain unknown.

Source documents: genes/DROME/Lcp3/Lcp3-protnlm-source.json · genes/DROME/Lcp3/Lcp3-protnlm-function-review.md · genes/DROME/Lcp3/Lcp3-bioinformatics/RESULTS.md · genes/DROME/Lcp3/Lcp3-reference-P07188-uniprot.txt

No GO/EC predictions in the reviewed source.

Deep Research

Falcon

(Lcp3-deep-research-falcon.md)

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📚 Additional Documentation

Notes

(Lcp3-notes.md)

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Bioinformatics Results

(RESULTS.md)

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Protnlm Function Review

(Lcp3-protnlm-function-review.md)

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📄 View Raw YAML

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