id: A0A9L0S9P8
gene_symbol: DYNLT2B
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9796
  label: Equus caballus
description: Dynein light chain Tctex-type 2B (DYNLT2B, also known as TCTEX1D2) is a small non-catalytic
  Tctex-1-fold light chain of cytoplasmic dynein-2, the minus-end-directed motor that powers retrograde
  intraflagellar transport in cilia and flagella. In the experimentally characterized human and mouse
  orthologues it forms a heterodimer with DYNLT1 or DYNLT3 that binds the dynein-2-specific intermediate
  chain WDR60/DYNC2I1; loss of the human protein impairs retrograde ciliary protein trafficking and causes
  a short-rib thoracic dysplasia ciliopathy, and loss of the mouse protein disrupts sperm flagellum
  assembly. The equine gene (Ensembl ENSECAG00000015913, chromosome 19) is a one-to-one orthologue in the
  DYNLT2B-specific PANTHER subfamily PTHR21255:SF7, and these functions are inferred for it by orthology;
  no equine experiment has been reported. A0A9L0S9P8 is the 145-residue UniProt reference-proteome
  gene-centric entry for the gene. Its sequence from the second helix to the C-terminus (human residues
  38-142) is 100% identical to the other full-length equine models and highly conserved with human, but
  its first 40 residues are an unrelated sequence with no initiator methionine that replaces the human
  N-terminus, including the first beta-strand of the Tctex fold; the human-like full-length product is
  represented instead by A0A9L0TLH8 and the Ensembl canonical model A0A9L0S150.
existing_annotations:
- term:
    id: GO:0045505
    label: dynein intermediate chain binding
  evidence_type: ISO
  original_reference_id: PMID:29742051
  review:
    summary: Proposed by orthology to human DYNLT2B, grounded phylogenetically. PAINT placed dynein
      intermediate chain binding at the Tctex family node PTN000478852, which is ancestral to the
      DYNLT2B-specific subfamily PTHR21255:SF7 containing this equine gene; the human SF7 member carries
      the term both by IBA and by direct experiment (the WDR60-TCTEX1D2-DYNLT1/DYNLT3 subcomplex). Horse
      has no GOA rows for this gene, so the family-node assertion has not been propagated to it.
    action: NEW
    reason: The equine gene is a one-to-one SF7 orthologue of human DYNLT2B, so the curated family-node
      assertion applies to the gene product. Experimental evidence is human (and mouse) only. For this
      particular protein model the caveat is the divergent, Met-less N-terminus that lacks the
      human-like first beta-strand; the region carrying the helices and the last four strands of the
      fold is intact, but whether this exact form can dimerize and bind WDR60 is untested.
    supported_by:
    - reference_id: PMID:29742051
      supporting_text: The dynein-2 complex can be divided into three subcomplexes, namely DYNC2H1-DYNC2LI1,
        WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2, and WDR60-TCTEX1D2-DYNLT1/DYNLT3.
    - reference_id: file:HORSE/DYNLT2B__A0A9L0S9P8/DYNLT2B__A0A9L0S9P8-uniprot.txt
      record_section: ["DR:PANTHER"]
      supporting_text: PANTHER; PTHR21255:SF7; DYNEIN LIGHT CHAIN TCTEX-TYPE PROTEIN 2B; 1.
- term:
    id: GO:0005868
    label: cytoplasmic dynein complex
  evidence_type: ISO
  original_reference_id: PMID:38454149
  review:
    summary: Proposed by orthology to human DYNLT2B, grounded phylogenetically. PAINT asserts cytoplasmic
      dynein complex membership at node PTN000478852, ancestral to SF7; human DYNLT2B is an experimentally
      established dynein-2 light chain and is resolved in the reconstituted dynein-2 complex.
    action: NEW
    reason: Complex membership is inherited from the family node and demonstrated directly for the human
      SF7 orthologue; it is the cellular-component counterpart of the core light-chain function. Not
      demonstrated in horse.
    supported_by:
    - reference_id: PMID:38454149
      supporting_text: The subunits in the final construct are the dynein-2 heavy chain (DYNC2H1),
        two intermediate chains (WDR60/DYNC2I1 and WDR34/DYNC2I2), light intermediate chain (DYNC2LI1),
        and single isoforms of the four dynein-2 light chains (DYNLRB1, DYNLL1, DYNLT1, and DYNLT2B/TCTEX1D2).
    - reference_id: file:HORSE/DYNLT2B__A0A9L0S9P8/DYNLT2B__A0A9L0S9P8-uniprot.txt
      record_section: ["DR:PANTHER"]
      supporting_text: PANTHER; PTHR21255:SF7; DYNEIN LIGHT CHAIN TCTEX-TYPE PROTEIN 2B; 1.
core_functions:
- description: Non-catalytic Tctex-type light chain of cytoplasmic dynein-2 that, as a heterodimer with
    DYNLT1/DYNLT3, binds the WDR60/DYNC2I1 intermediate chain and supports retrograde intraflagellar transport.
    Assigned to the equine gene by one-to-one orthology (PANTHER PTHR21255:SF7, the DYNLT2B-specific
    subfamily; PAINT node PTN000478852) to the experimentally characterized human protein; no equine
    experiment exists. A0A9L0S9P8 lacks the human-like N-terminus and first beta-strand, so whether this
    particular protein model is competent for the function is unresolved.
  molecular_function:
    id: GO:0045505
    label: dynein intermediate chain binding
  in_complex:
    id: GO:0005868
    label: cytoplasmic dynein complex
  supported_by:
  - reference_id: PMID:29742051
    supporting_text: The dynein-2 complex can be divided into three subcomplexes, namely DYNC2H1-DYNC2LI1,
      WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2, and WDR60-TCTEX1D2-DYNLT1/DYNLT3.
  - reference_id: file:HORSE/DYNLT2B__A0A9L0S9P8/DYNLT2B__A0A9L0S9P8-uniprot.txt
    record_section: ["DR:PANTHER"]
    supporting_text: PANTHER; PTHR21255:SF7; DYNEIN LIGHT CHAIN TCTEX-TYPE PROTEIN 2B; 1.
  - reference_id: file:HORSE/DYNLT2B__A0A9L0S9P8/DYNLT2B__A0A9L0S9P8-bioinformatics/RESULTS.md
    supporting_text: '| STRAND | 128-140 | DSLFCVVAAFGCF | 13 | 13 | 13 |'
references:
- id: file:HORSE/DYNLT2B__A0A9L0S9P8/DYNLT2B__A0A9L0S9P8-uniprot.txt
  title: 'UniProtKB A0A9L0S9P8: horse DYNLT2B, reference-proteome gene-centric entry'
  findings:
  - statement: Unreviewed TrEMBL record derived from the Ensembl gene ENSECAG00000015913; protein name
      and gene symbol are imported from Ensembl, and there is no equine experimental characterization.
    record_section: ["DR:Ensembl"]
    supporting_text: Ensembl; ENSECAT00000082879.1; ENSECAP00000071582.1; ENSECAG00000015913.4.
    reference_section_type: DATABASE_ENTRY
  - statement: Domain and family signatures place the protein in the Tctex-1-like fold and in the
      DYNLT2B-specific PANTHER subfamily.
    record_section: ["DR:InterPro"]
    supporting_text: InterPro; IPR005334; Tctex-1-like.
    reference_section_type: DATABASE_ENTRY
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Source record for the reviewed protein. The family SIMILARITY note is ARBA-derived
      and is not used as support; PANTHER, InterPro and Pfam cross-references establish family identity
      but no equine function.
- id: file:HORSE/DYNLT2B__A0A9L0S9P8/DYNLT2B__A0A9L0S9P8-bioinformatics/RESULTS.md
  title: A0A9L0S9P8 (horse DYNLT2B, UniProt gene-centric entry) vs human Q8WW35
  findings:
  - statement: The model has no initiator methionine and is 78.83% identical to human over the aligned
      region; identity is continuous only from human residue 38 onward.
    supporting_text: 'Horse length 145; starts with Met: False. Global alignment to human (142 aa): 137
      aligned pairs, 108 identical (78.83% of aligned).'
    reference_section_type: RESULTS
  - statement: The first beta-strand of the human Tctex fold is aligned but essentially not conserved
      (1 of 8 identical), whereas the helices and the four C-terminal strands are conserved.
    supporting_text: '| STRAND | 4-11 | SIGVSFSV | 8 | 1 | 8 |'
    reference_section_type: RESULTS
  - statement: The final Tctex beta-strand, absent from the benchmark model A0A9L0SWY1, is fully conserved
      in A0A9L0S9P8.
    supporting_text: '| STRAND | 128-140 | DSLFCVVAAFGCF | 13 | 13 | 13 |'
    reference_section_type: RESULTS
  - statement: A0A9L0S9P8 shares its last 105 residues exactly with the human-like equine model A0A9L0TLH8;
      only the 40-residue N-terminal prefix differs, replacing the TLH8 N-terminus that carries the
      first strand.
    supporting_text: '| A0A9L0TLH8 | 148 | 105 | GESSHSWLLTLIDLKVKKIKNGSLEVKLTAPSPSLKCSST | MAAPRDASFSAGVSFSVADSLPETEKNAGESENTYILRPIFQQ
      |'
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Reproducible script (compare_s9p8.py) aligning the cached horse and human records and
      live UniProt sibling models; identity is counted per identical residue, not merely aligned pairs.
      Sequence comparison only; it does not assess transcript support, folding or binding.
- id: file:HORSE/DYNLT2B/DYNLT2B-bioinformatics/RESULTS-rereview.md
  title: DYNLT2B horse gene models vs human Q8WW35 (re-review)
  findings:
  - statement: A0A9L0S9P8 is the UniProt reference-proteome gene-centric entry for the equine DYNLT2B
      gene, while the Ensembl canonical transcript corresponds to a different model.
    supporting_text: 'Ensembl canonical transcript of ENSECAG00000015913: ENSECAT00000082191. UniProt reference-proteome
      gene-centric entry: A0A9L0S9P8.'
    reference_section_type: RESULTS
  - statement: The human-like full-length equine model A0A9L0TLH8 covers the whole human sequence with
      all strands and the human C-terminus.
    supporting_text: '| A0A9L0TLH8 | 148 | False | False | True | 92.25 | 100.0 | True | DNYTHDVFMNDSLFCVVAAFGCFYY
      |'
    reference_section_type: RESULTS
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Gene-model survey from the sibling A0A9L0SWY1 review folder; used here for the
      gene-centric/canonical status of the equine models. Its "all human strands" column counts aligned,
      not identical, positions, which is why A0A9L0S9P8 scores True there despite the divergent first strand.
- id: file:human/DYNLT2B/DYNLT2B-uniprot.txt
  title: 'UniProtKB Q8WW35: human DYNLT2B/TCTEX1D2 (curated reference ortholog)'
  findings:
  - statement: Human DYNLT2B is a non-catalytic accessory subunit of the cytoplasmic dynein-2 complex
      and is required for retrograde ciliary transport.
    record_section: ["CC:FUNCTION"]
    supporting_text: 'FUNCTION: Acts as one of several non-catalytic accessory components of'
    reference_section_type: DATABASE_ENTRY
  - statement: DYNLT2B is one of the dynein-2-specific subunits rather than a light chain shared with
      dynein-1.
    record_section: ["CC:SUBUNIT"]
    supporting_text: intermediate chain (DYNC2LI1), and a light chain (DYNLT2B) are unique
    reference_section_type: DATABASE_ENTRY
  - statement: The DYNLT2B-DYNLT1/DYNLT3 dimer binds the WDR60/DYNC2I1 intermediate chain.
    record_section: ["CC:SUBUNIT"]
    supporting_text: DYNLT2B-DYNLT1/DYNLT3 interacts with DYNC2I1; this interaction is
    reference_section_type: DATABASE_ENTRY
  - statement: Biallelic human loss of function causes short-rib thoracic dysplasia with polydactyly
      (SRTD17).
    record_section: ["CC:DISEASE"]
    supporting_text: '(SRTD17) [MIM:617405]: A form of short-rib thoracic dysplasia, a group'
    reference_section_type: DATABASE_ENTRY
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Curated Swiss-Prot record for the experimentally characterized SF7 orthologue, with
      ECO:0000269 evidence tied to PMID:26044572 and PMID:29742051.
- id: PMID:29742051
  title: Interaction of WDR60 intermediate chain with TCTEX1D2 light chain of the dynein-2 complex is
    crucial for ciliary protein trafficking.
  findings:
  - statement: Human TCTEX1D2 is in a WDR60-TCTEX1D2-DYNLT1/DYNLT3 subcomplex of dynein-2, mapped by
      visible immunoprecipitation.
    supporting_text: The dynein-2 complex can be divided into three subcomplexes, namely DYNC2H1-DYNC2LI1,
      WDR34-DYNLL1/DYNLL2-DYNLRB1/DYNLRB2, and WDR60-TCTEX1D2-DYNLT1/DYNLT3.
    reference_section_type: ABSTRACT
  - statement: TCTEX1D2 knockout cells have a milder retrograde trafficking defect than WDR60 knockouts,
      indicating an auxiliary role within the complex.
    supporting_text: our results demonstrated that WDR60 plays a major role and TCTEX1D2 plays an auxiliary
      role in the dynein-2 complex to mediate retrograde ciliary protein trafficking.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text cached. Human cell experiments; primary experimental basis for the
      intermediate-chain binding function transferred here by orthology.
- id: PMID:38454149
  title: Structure and tethering mechanism of dynein-2 intermediate chains in intraflagellar transport.
  findings:
  - statement: DYNLT2B/TCTEX1D2 is one of the four light chains in the reconstituted human dynein-2
      complex.
    supporting_text: The subunits in the final construct are the dynein-2 heavy chain (DYNC2H1), two intermediate
      chains (WDR60/DYNC2I1 and WDR34/DYNC2I2), light intermediate chain (DYNC2LI1), and single isoforms
      of the four dynein-2 light chains (DYNLRB1, DYNLL1, DYNLT1, and DYNLT2B/TCTEX1D2).
    reference_section_type: RESULTS
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text cached. Source of the human DYNLT1-DYNLT2B structure (PDB 8RGI) whose
      secondary-structure assignments are mapped onto the equine model in RESULTS.md.
- id: PMID:25830415
  title: Tctex1d2 associates with short-rib polydactyly syndrome proteins and is required for ciliogenesis.
  findings:
  - statement: Tctex1d2 localizes with Wdr60 to the ciliary base, and their depletion causes ciliogenesis
      defects.
    supporting_text: Tctex1d2 and Wdr60 localize to the base of the cilium and their depletion causes defects
      in ciliogenesis.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text cached. Ciliary-base localization and ciliogenesis phenotypes are not
      transferred as equine annotations; PAINT did not propagate them from the human node.
- id: PMID:39827215
  title: TCTEX1D2 is essential for sperm flagellum formation in mice.
  findings:
  - statement: Mouse Tctex1d2 knockouts are male-infertile with flagellar dysplasia and disrupted axonemes.
    supporting_text: Tctex1d2-/- mice generated in this study exhibited male infertility due to flagellar
      dysplasia, and the axonemal structures were disrupted inside the flagella.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text cached. Organismal mouse phenotype; recorded as context and not annotated
      as process participation for the equine gene.
suggested_questions:
- question: Is A0A9L0S9P8 a real equine transcript product? Its 40-residue N-terminal prefix lacks an
    initiator methionine and replaces the conserved N-terminus and first Tctex beta-strand found in
    A0A9L0TLH8, which suggests an incomplete or mis-joined 5' gene model rather than a distinct isoform.
  experts: []
- question: Should the UniProt gene-centric representative for equine DYNLT2B be a model that encodes
    the complete human-like Tctex fold (A0A9L0TLH8 or the Ensembl canonical A0A9L0S150) instead of
    A0A9L0S9P8?
  experts: []
suggested_experiments:
- hypothesis: The equine DYNLT2B locus produces a transcript whose 5' exon encodes the human-like
    N-terminus (as in A0A9L0TLH8), and the A0A9L0S9P8 prefix is a gene-model artefact.
  description: 5' RACE and long-read cDNA sequencing of DYNLT2B transcripts from horse testis and a
    ciliated epithelium, mapping start sites and the first coding exon against the three model variants.
  experiment_type: full-length transcript sequencing / gene-model validation
- hypothesis: The equine protein, like the human orthologue, heterodimerizes with DYNLT1 and binds
    WDR60/DYNC2I1, and loss of the first beta-strand (as in A0A9L0S9P8) abolishes dimerization.
  description: Co-immunoprecipitation of horse A0A9L0TLH8 and A0A9L0S9P8 sequences with DYNLT1 and WDR60
    in the visible-immunoprecipitation format used for the human subcomplexes (PMID:29742051), with
    human TCTEX1D2 as positive control.
  experiment_type: pairwise interaction mapping / co-immunoprecipitation