id: A0A8C4MKL2
gene_symbol: ENTR1
taxon:
  id: NCBITaxon:9793
  label: Equus asinus
status: COMPLETE
description: Assessment of 2 ProtNLM2 GO predictions for donkey ENTR1 (A0A8C4MKL2), using human
  ENTR1 experimental findings, the donkey and human ENTR1 gene reviews, and a donkey-human sequence
  comparison. The donkey entry (356 aa) conserves the C-terminal coiled-coil region (81% identity to
  human ENTR1) but lacks the region corresponding to human residues 9-85. Endocytic recycling is a
  correct process prediction, transferred by orthology from human IMP evidence, that is absent
  from donkey GOA (COR). Retromer complex is uncertain (UNC), because human ENTR1 associates with
  retromer indirectly through the WASH complex and colocalizes with it rather than being an
  established subunit. ProtNLM2 also emitted a non-GO subcellular location ("Membrane") for this
  accession, which is not scored here.
source_documents:
- projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv
- genes/EQUAS/ENTR1/ENTR1-uniprot.txt
- genes/EQUAS/ENTR1/ENTR1-goa.tsv
- genes/EQUAS/ENTR1/ENTR1-bioinformatics/human_Q96C92-uniprot.txt
- genes/EQUAS/ENTR1/ENTR1-bioinformatics/RESULTS.md
- genes/EQUAS/ENTR1/ENTR1-bioinformatics/RESULTS-rereview.md
- genes/EQUAS/ENTR1/ENTR1-ai-review.yaml
- genes/human/ENTR1/ENTR1-ai-review.yaml
predictions:
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0032456
    label: endocytic recycling
  predicted_term_type: GO_BP
  review:
    assessment: COR
    confidence_score: 2
    summary: Human ENTR1 (SDCCAG3) was identified in the VPS35 interactome, and its siRNA depletion
      reduces surface and total GLUT1, an SNX27-retromer recycling cargo, with minor effects on
      other cargo such as CD97 (PMID:25278552); the human gene review accepts endocytic recycling
      as an experimentally supported core process, while noting that the effect is cargo-selective
      and that ENTR1 also promotes lysosomal sorting of Fas (PMID:31308371). Transfer to donkey is
      an orthology inference, as donkey A0A8C4MKL2 (PTHR31259:SF3) and human ENTR1 (hominid-only
      SF6) are the single ENTR1 ortholog in each species, and the conserved C-terminal coiled-coil
      region shares 81% identity. The donkey gene review describes the recycling role in its
      description and core-function text but does not carry it as a GO annotation, because PAINT
      did not propagate this human term, and the term is absent from donkey GOA. The prediction is
      therefore a correct, novel annotation for this accession, with the caveat that it rests on
      human knockdown data rather than on the donkey protein.
    supported_by:
    - reference_id: PMID:25278552
      supporting_text: Depletion of these proteins resulted in trafficking defects of retromer-dependent
        cargo
    - reference_id: file:EQUAS/ENTR1/ENTR1-bioinformatics/human_Q96C92-uniprot.txt
      supporting_text: |-
        Involved in the endosome-to-plasma
        CC       membrane trafficking and recycling of SNX27-retromer-dependent cargo
        CC       proteins, such as GLUT1
    - reference_id: PMID:25278552
      supporting_text: Suppression of SDCCAG3 led to a decrease in GLUT1 surface expression and a
        reduction in whole-cell levels
    - reference_id: file:EQUAS/ENTR1/ENTR1-bioinformatics/RESULTS.md
      supporting_text: The donkey sequence A0A8C4MKL2 (356 residues) aligns to human Q96C92 (435
        residues) with 81.41% identity across 355 paired residues.
- source_method: ProtNLM2
  source_version: UniProt API snapshot 2026-10-14
  predicted_term:
    id: GO:0030904
    label: retromer complex
  predicted_term_type: GO_CC
  review:
    assessment: UNC
    confidence_score: 1
    summary: Human ENTR1 co-purifies with VPS35 and colocalizes with the retromer cargo-selective
      complex on endosomes (PMID:25278552), but its association with retromer is mediated by the
      WASH complex (PMID:24980502), and the human gene review accepts the retromer term only with
      the colocalizes_with qualifier, as an accessory association rather than subunit membership.
      An unqualified retromer complex term implies membership, which no evidence establishes; the
      indirect, WASH-dependent association argues against a stable subunit role but does not
      exclude a peripheral one. The prediction is thus plausible as an association but neither
      supported nor refuted as complex membership. The term is absent from donkey GOA.
    supported_by:
    - reference_id: file:EQUAS/ENTR1/ENTR1-bioinformatics/human_Q96C92-uniprot.txt
      supporting_text: |-
        Colocalizes in a WASHC2-dependent manner with the retromer CSC
        CC       complex at endosomes
    - reference_id: PMID:25278552
      supporting_text: This has identified a number of new interacting proteins, including ankyrin-repeat
        domain 50 (ANKRD50), seriologically defined colon cancer antigen 3 (SDCCAG3)
    - reference_id: PMID:24980502
      supporting_text: Together, these data establish that the association of ANKRD50, SDCCAG3, and
        RME-8 to retromer is mediated through binding to the WASH complex
references:
- id: PMID:24980502
  title: Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked
    VPS35(D620N) mutation.
  findings: []
- id: PMID:31308371
  title: Apoptotic signalling targets the post-endocytic sorting machinery of the death receptor
    Fas/CD95.
  findings: []
- id: PMID:25278552
  title: Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma-membrane
    recycling.
  findings: []
- id: file:EQUAS/ENTR1/ENTR1-bioinformatics/human_Q96C92-uniprot.txt
  title: UniProtKB Swiss-Prot record Q96C92 (human ENTR1), fetched 2026-10-14
  findings: []
- id: file:EQUAS/ENTR1/ENTR1-bioinformatics/RESULTS.md
  title: 'ENTR1: donkey-human sequence comparison'
  findings: []