This review distinguishes direct human experiments, ortholog experiments, curated propagation and candidate-gene observations. Source annotation identities and evidence codes are retained; the review actions describe their biological interpretation.
PMID:34845226(https://pmc.ncbi.nlm.nih.gov/articles/PMC8630017/), Results/Figures 1–4 and Methods on expression, purification and SHH release, directly assays human DISP1 and human SHH in human cells with mouse SCUBE2. Wild-type and engineered cleavage-site constructs support ligand release; transport-inactive NNN material supplies the principal structures. Direct protein recognition is supported, but SHH lipid termini were unresolved. The exact lipid route and transient SCUBE interface remain models, and a release defect for SHH-N81A is partly confounded by reduced cell-surface delivery. No stable DISP1–SCUBE–SHH complex is established.
PMID:34707294(https://pmc.ncbi.nlm.nih.gov/articles/PMC8785653/), Results/Figures 2–4 and construct/release Methods, concerns mouse DISP1, including the engineered Disp1-A deletion. Sodium coordination and extracellular-gradient manipulation support coupling to SHH release. The structural SHH fragment is unlipidated mouse protein; functional release assays use lipid-modified ligand. These data support a mechanistic comparison, not a direct human sodium-flux measurement or a demonstrated exact transport stoichiometry.
PMID:22902404(https://pmc.ncbi.nlm.nih.gov/articles/PMC3682496/), Results/Figures 1–5 and the main photocrosslinking/secretion Methods, distinguishes mouse DispA from its human SHH cargo and human host cells. Controlled secretion assays and sterol-dependent interactions support cooperation with SCUBE2. Some SCUBE-only release and nonspecific serum-mediated release occur, so efficient DISP1-dependent secretion is not an assertion of absolute dependence under every condition.
The human official sequence is 1524 residues. Experimental point mutants, artificial protease sites and terminal deletions are not natural isoforms. Protease-mediated maturation facilitates DISP1 function but does not make DISP1 a protease. Protein transporter activity describes ligand relocation from the cell surface; neither passage of the SHH protein through the bilayer nor a carrier that travels with its cargo is asserted.
Ligand release is the performed DISP1 step in Hedgehog signaling, so the existing GO:0007224 assertion is retained as core alongside protein secretion. Its definition names the signals generated after Smoothened activation; curated pathway use also includes ligand-side participants. The valid PAINT assignment and the human release experiments above support this classification without assigning downstream Smoothened transduction to DISP1. Human SHH, UniProtKB:Q15465, is recorded as the cargo; the relevant transported species is the lipid-modified N-terminal signaling product. No separate positive-regulation or NEW process annotation is introduced.
PMID:19184110(https://pmc.ncbi.nlm.nih.gov/articles/PMC2774849/), functional-analysis Methods, truncation Results and family descriptions, links human DISP1 truncations to microform craniofacial features. The clinically unaffected carrier mothers and normal CT/MRI in the affected daughters limit a simple severe-HPE interpretation. The functional assay is specifically murine Disp1 carrying human-equivalent alterations in Drosophila S2R+ cells; human wild-type DISP1 did not enhance export in that system.
PMID:38529886(https://doi.org/10.1016/j.gim.2024.101126) was assessed from its complete accessible abstract; the cohort findings are recorded once in the review reference entry. The full original, detailed pedigrees and functional assays were not independently read, so no uniform inheritance model or variant-specific pathogenicity judgment is assigned.
Rolland et al., PMID:25416956, Results “A proteome-wide binary interactome map” and Experimental Procedures “Generation of the binary protein-protein interaction map,” describes repeated pair testing, sequence confirmation and sampled orthogonal validation. The IntAct DISP1–LAPTM5 query resolves Table S2G records EBI-10386352, EBI-10230189 and EBI-10548906. These are three assay-stage records for one pair, not three independent physiological studies. Both proteins' recorded sequence checksums match their current reviewed human sequences. The protected main HTML cache contains only part of the original; the separately fetched XML extraction supplied the claim-bearing Results and Methods without overwriting that cache.
Haenig et al., PMID:32814053, original Methods “Automated Y2H interaction screening,” was read from the institutional full-original PDF. It describes bait-autoactivation testing and reporter selection. The IntAct DISP1–WFS1 query resolves Table S2 records EBI-25899640, EBI-26054738 and EBI-26208885 for array, pooling and validated two-hybrid assays. Checksums match the 1524-residue human DISP1 and 890-residue WFS1 sequences. Mammalian validation of other dataset pairs is not transferred to this pair. The publication cache remains abstract-only.
Official LAPTM5 and WFS1 records identify multipass membrane proteins. WFS1's calcium-homeostasis and ER-stress roles do not establish enzyme, receptor or cytoskeletal partner classes. The interaction findings therefore retain protein binding as non-core; they do not assign the partners' functions to DISP1 or establish an endogenous complex.
The current PANTHER PTHR45951 tree places human DISP1 leaf PTN002473772 below both PTN002244706 and PTN002244707. The PAINT IBD file records GO:0007224 at PTN002244706 (2024-11-21, taxon 2759; zebrafish disp1 seed) and GO:0016020 at PTN002244707 (2025-12-20; canine DISP1 and worm CHE-14 seeds). The seed identities and target descent are actual source records, not guessed from family labels. The family metadata contains an explicitly unreviewed LLM description, which is not used as independent biological evidence.
Schwend and Ahlgren, PMID:19948063, Methods “Animals” and Results on the two con/disp1 alleles and Shh rescue, identifies zebrafish mutants and distinguishes rescue by soluble non-lipid-modified ShhN from full-length Shh. This is experimental grounding for the pathway IBD. It does not make the zebrafish craniofacial outcomes separate human core functions.
The mouse Q3TDN0 donor has experimental peptide-transport records from PMID:12372301(https://pubmed.ncbi.nlm.nih.gov/12372301/) and PMID:12421714(https://pubmed.ncbi.nlm.nih.gov/12421714/), and a carrier record from 12372301. Their genuine caches are abstract-only. Those positive release findings are retained; current term distinctions are resolved using the directly read later human and mouse originals. The Ensembl protein identifier in the imported transfer matches the current mouse record, not a natural human isoform.
Etheridge et al., PMID:20023168, Methods on canine constructs, MDCK localization, miRNA knockdown and the Shh transport assay, and Results/Figures 1–4, provides the actual source behind the canine A0A8I3S3W7 basolateral and secretion-regulation records. These are canine constructs and canine endogenous depletion; human HEK293T host cells in parallel experiments do not change the protein species. Separate mouse embryoid-body experiments examine signaling range. The historical proton-driven and multivesicular-body models are distinguished from later sodium-coupling evidence and are not asserted as settled human mechanisms. A stable trimer is not installed as a core complex merely from the older native-gel interpretation.
CHE-14, PMID:10996790 supplies current experimental apical-membrane grounding for the worm membrane seed. Its cache is abstract-only; full detailed Methods were not independently recovered. Apical worm polarity is not transferred to human DISP1. Current dog A0A8I3P4D2 annotations do not reproduce every historical experimental seed, so that current sequence record is not represented as a newly read experiment.
The IPR004869 entry explicitly maps the RND-like transmembrane domain to membrane. A current Q96F81 match at residues 973–1123 and the official twelve-transmembrane topology support the broad electronic location. Human release assays justify refining it to plasma membrane without asserting exclusion from intracellular compartments.
Kantarci et al., PMID:20799323, Methods on sequencing, mosaicism, in situ hybridization and Shh lineage tracing, Results and Discussion, was read in the genuine full-text cache. A human mosaic A1471G candidate variant and wild-type mouse pleuroperitoneal-fold expression are observed. No controlled DISP1 diaphragm perturbation or variant functional assay resolves the causal developmental claim. Shh fate mapping concerns another gene. The authors themselves identify the mechanism and mutant diaphragm phenotype as open questions. This supports UNDECIDED, without declaring the candidate association false or assigning pathogenicity.
GO:0140104 explicitly distinguishes a carrier that travels with cargo from a transporter. GO:0140318 covers direct protein binding and delivery to a location, matching membrane-resident ligand export. GO:0009306 is the performed secretion process. Replacing regulation of protein secretion is a mechanistic recasting: regulation is not an is_a ancestor of secretion. No NEW process or redundant duplicate annotation is introduced.
The official human sequence has 1524 residues and no alternative-products comment. Current sequence checks establish identity for the interaction records; engineered human or mouse constructs remain separately described. No current RefSeq transcript cross-reference is treated as proof of a distinct natural functional protein.
The three core originals, 20023168, 19948063 and 20799323 have genuine full-text caches; only selected claim-bearing Methods/Results were read, not every figure pixel or supplement. Main 25416956 is a partial HTML extraction despite its positive full-text flag; its normal XML counterpart supplied additional original text. Main 32814053 remains abstract-only, with separate institutional original Methods. The 12372301, 12421714 and 10996790 donor caches are abstract-only. No cached publication flags or bytes were edited.
Three short exact anchors appear once each in the review YAML: the human structural interaction (34845226), canine basolateral localization (20023168), and the candidate variant's unresolved domain function (20799323). Other support entries are reference-only. The excerpts remain below 25 words per source across the authored review, notes and guide; quotation count is not evidence count.
The follow-up adds two normal publication caches without altering their availability flags: PMID:19184110 has a genuine full original used in the selected scope above; PMID:38529886 remains abstract-only. No new quotation is added.