id: A0A8M2BI60
gene_symbol: prom1b
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:7955
  label: Danio rerio
description: prom1b (prominin 1 b) is one of two zebrafish co-orthologs of vertebrate PROM1 (prominin-1, CD133),
  retained from the teleost-specific genome duplication; its paralog is prom1a. It encodes a pentaspan membrane
  glycoprotein of the prominin family, which sits in cholesterol-rich protrusions of the apical plasma membrane;
  a GFP fusion of Prom1b is enriched at the apical surface of retinal neuroepithelial cells. prom1b is zygotic only,
  rises strongly at 3-5 dpf, and is the more abundant prominin transcript in rod and cone photoreceptors; it is also
  expressed on the scleral side of the retinal inner nuclear layer, in the pineal organ, and in adult brain germinative
  zones of the hindbrain. Loss of prom1b disrupts photoreceptor outer-segment morphogenesis and causes early cone
  degeneration, while rods survive with abnormal outer segments; the outer-segment protein Prph2 is mislocalized and
  its oligomerization disrupted. This matches the role of mammalian PROM1 in outer-segment disc formation and retinal
  degeneration.
existing_annotations:
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  supporting_entities:
  - InterPro:IPR008795
  review:
    summary: Membrane, from the prominin InterPro signature.
    action: ACCEPT
    reason: Correct; Prom1b is a multi-pass membrane protein with the five transmembrane segments of the family.
    supported_by:
    - reference_id: file:DANRE/prom1a/prom1a-bioinformatics/RESULTS.md
      supporting_text: All five transmembrane segments of human PROM1 align without gaps in both copies
- term:
    id: GO:0016324
    label: apical plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:22492354
  qualifier: located_in
  review:
    summary: Apical plasma membrane, from a Prom1b-GFP transgene used as an apical marker in retinal neuroepithelia.
    action: ACCEPT
    reason: Direct localization of the tagged zebrafish protein, consistent with the conserved apical location of prominins.
    supported_by:
    - reference_id: PMID:22492354
      supporting_text: We also generated a transgenic line in which GFP is fused with Prominin1b (Prom1b-GFP), a cholesterol-interacting
        pentaspan membrane protein that is enriched at the apical region of polarized cells, including retinal neuroepithelia
- term:
    id: GO:0031528
    label: microvillus membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  supporting_entities:
  - UniProtKB-SubCell:SL-0294
  review:
    summary: Microvillus membrane, from an ARBA-derived UniProt subcellular location.
    action: ACCEPT
    reason: Family-level location of prominins; no zebrafish data, but nothing argues against it.
    supported_by:
    - reference_id: PMID:32201384
      supporting_text: They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular
        vesicles derived thereof.
- term:
    id: GO:0035845
    label: photoreceptor cell outer segment organization
  evidence_type: IMP
  original_reference_id: PMID:31362982
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - ZFIN:ZDB-GENO-200511-1
  review:
    summary: Photoreceptor outer segment organization, from prom1b knockout zebrafish with disrupted outer-segment
      morphogenesis.
    action: ACCEPT
    reason: Core process. The prom1b mutant phenotype (malformed outer segments in rods and cones, cone degeneration,
      mislocalized Prph2) reproduces the structural role of mammalian PROM1 in disc morphogenesis, and the protein
      is expressed in photoreceptors. Only the abstract is cached; the full text on PMC describes a frameshift allele.
    supported_by:
    - reference_id: PMID:31362982
      supporting_text: 'Loss of prom1b disrupted OS morphogenesis, with rods and cones exhibiting differences in impairment:
        cones degenerated at an early age, whereas rods remained viable but with an abnormal OS, even at 9 months postfertilization.'
    - reference_id: PMID:31362982
      supporting_text: Moreover, we found that Prom1b deletion causes mislocalization of Prph2 and disrupts its oligomerization.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied
    by conservative changes to GO terms applied by UniProt
  findings: []
- id: PMID:22492354
  title: Loss of Llgl1 in retinal neuroepithelia reveals links between apical domain size, Notch activity and neurogenesis.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text. Prom1b-GFP transgene used as an apical membrane marker in retinal neuroepithelia.
- id: PMID:31362982
  title: Deletion of the transmembrane protein Prom1b in zebrafish disrupts outer-segment morphogenesis and causes photoreceptor
    degeneration.
  findings: []
  full_text_unavailable: true
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract cached; full text read on PMC (not cached). TALEN frameshift alleles of prom1b and prom1a;
      only prom1b mutants have outer-segment defects. The claim that prom1a plays no photoreceptor role was questioned
      by Corbeil et al. (PMID:31704774).
- id: PMID:31704774
  title: Deciphering the roles of prominins in the visual system.
  findings: []
  full_text_unavailable: true
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Letter; no text cached.
- id: PMID:31704775
  title: 'Reply to Corbeil et al.: Deletion of the transmembrane protein Prom1b in zebrafish disrupts outer-segment morphogenesis
    and causes photoreceptor degeneration.'
  findings: []
  full_text_unavailable: true
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Authors' reply; no text cached.
- id: PMID:21407811
  title: Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text. Both copies in the adult ONL, prom1b more robust; prom1b on the scleral side of the INL.
- id: PMID:23723983
  title: Spatial distribution of prominin-1 (CD133)-positive cells within germinative zones of the vertebrate brain.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text. prom1b mainly in rhombencephalic germinative zones, complementary to prom1a.
- id: PMID:20503380
  title: Expression of the zebrafish CD133/prominin1 genes in cellular proliferation zones in the embryonic central
    nervous system and sensory organs.
  findings: []
  full_text_unavailable: true
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Abstract only. Embryonic expression of both copies, complementary and overlapping.
- id: PMID:32201384
  title: 'Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish
    prominin-3.'
  findings: []
  full_text_unavailable: true
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Abstract only; family-level location of prominins.
- id: file:DANRE/prom1a/prom1a-bioinformatics/RESULTS.md
  title: prom1a / prom1b sequence, synteny and expression analysis
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Manual audit verified the sidecar supports both PROM1 duplicates retaining full prominin topology,
      duplicated-block synteny and photoreceptor expression, with prom1a broader and prom1b retinally enriched.
  findings: []
core_functions:
- description: Pentaspan prominin glycoprotein of photoreceptors and apical membranes, required for outer-segment
    morphogenesis and for proper localization and oligomerization of Prph2; the photoreceptor-dominant zebrafish
    PROM1 co-ortholog.
  directly_involved_in:
  - id: GO:0035845
    label: photoreceptor cell outer segment organization
  locations:
  - id: GO:0016324
    label: apical plasma membrane
  supported_by:
  - reference_id: PMID:31362982
    supporting_text: The Prom1 orthologs in zebrafish include prom1a and prom1b, and our results showed that prom1b,
      rather than prom1a, plays an important role in zebrafish photoreceptors.
  - reference_id: PMID:21407811
    supporting_text: Of the two prominin-1 paralogues, expression of prominin-1b appeared to be more robust in line
      with gene expression profiling reported earlier on embryonic retina [33].
suggested_questions:
- question: Where is Prom1b in the zebrafish photoreceptor (outer-segment base, rim, calyceal processes)? The published
    antibody did not work for immunofluorescence.
- question: Is prom1a upregulated in prom1b mutants, and would a prom1a; prom1b double mutant worsen the rod phenotype?
suggested_experiments:
- hypothesis: Prom1b acts at the base of nascent discs with Cdhr1a and Prph2, as mammalian PROM1 does.
  description: Knock in an epitope tag at prom1b and image it by expansion or immuno-electron microscopy in rods and
    cones, together with Prph2 and Cdhr1a.
  experiment_type: localization