Ptk7

UniProt ID: A0A8I6ALM9
Organism: Rattus norvegicus
Review Status: COMPLETE
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Gene Description

PTK7 is a single-pass receptor pseudokinase with seven extracellular immunoglobulin-like domains. It organizes signaling at cell contacts, including Src-dependent control of junctional actomyosin, and contributes to planar cell polarity and tissue morphogenesis. Its kinase-like domain has an occluded nucleotide pocket and lacks the catalytic machinery of an active receptor tyrosine kinase. The rat A0A8I6ALM9 protein retains the characteristic pseudokinase-domain residues and membrane-spanning region.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001736 establishment of planar polarity
ISO
GO_REF:0000121
ACCEPT
Summary: Planar polarity is a defining PTK7 function. Mammalian cell and mouse auditory-epithelium experiments connect junctional PTK7-Src signaling to polarized actomyosin. The selected rat sequence retains the receptor and pseudokinase architecture supporting this ortholog transfer.
Supporting Evidence:
PMID:24703874
PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
file:rat/Ptk7/Ptk7-bioinformatics/RESULTS.md
| 948 | A | 957 | A |
GO:0001822 kidney development
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: The original mouse screen’s Table 1 reports moderate cystic kidneys in all three examined Ptk7 mutants. This directly supports the kidney-development annotation via the mouse ortholog; it is retained as a tissue-specific non-core phenotype.
Supporting Evidence:
file:rat/Ptk7/Ptk7-bioinformatics/kidney-table.md
Ptk7 | 3 | β€” | β€” | 100% | β€” | β€” | β€”
GO:0001843 neural tube closure
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: The original mouse Ptk7 mutation study directly reports failed neural-tube closure. This conserved morphogenetic role is retained as a developmental consequence of PCP signaling.
Supporting Evidence:
PMID:15229603
disrupts neural tube closure and stereociliary bundle orientation
GO:0003281 ventricular septum development
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: The chuzhoi study directly reports ventricular septal defects in Ptk7 mutant hearts. This independently supports the septum-development annotation; the tissue-specific phenotype is non-core.
Supporting Evidence:
PMID:20704721
Chuzhoi mutants exhibit defects in the heart including double outlet right ventricle (DORV) with a ventricular septal defect (VSD), or parallel arterial trunks.
GO:0003401 axis elongation
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: Axis elongation is consistent with the conserved PTK7 role in polarized tissue rearrangement and convergent-extension morphogenesis. Retain the ortholog-derived developmental annotation as non-core.
Supporting Evidence:
PMID:24703874
PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
GO:0004714 transmembrane receptor protein tyrosine kinase activity
ISO NOT
GO_REF:0000121
ACCEPT
Summary: The annotation explicitly asserts NOT receptor tyrosine kinase activity, and that negation is correct. PTK7 is a receptor pseudokinase. Human structural evidence identifies an occluded ATP site and noncanonical catalytic motifs; the corresponding rat residues are conserved. PTK7-dependent phosphorylation is mediated by associated active kinases such as Src, not intrinsic receptor tyrosine kinase activity.
Supporting Evidence:
PMID:32619402
ATP binding to PTK7 and ROR2 is prevented by projection of a tyrosine side-chain from the Ξ²5/Ξ±D hinge region
file:rat/Ptk7/Ptk7-bioinformatics/RESULTS.md
| 948 | A | 957 | A |
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
GO:0004715 non-membrane spanning protein tyrosine kinase activity
IBA
GO_REF:0000033
REMOVE
Summary: The inherited active non-receptor tyrosine kinase function does not apply to the PTK7 branch: its conserved pseudokinase architecture obstructs ATP binding, and the protein also has an extracellular receptor and transmembrane topology. The objection concerns target-specific catalytic divergence, not the number or identity of IBA donors.
Supporting Evidence:
PMID:32619402
ATP binding to PTK7 and ROR2 is prevented by projection of a tyrosine side-chain from the Ξ²5/Ξ±D hinge region
file:rat/Ptk7/Ptk7-bioinformatics/RESULTS.md
| 948 | A | 957 | A |
file:rat/Ptk7/Ptk7-uniprot.txt
TRANSMEM 714..735
GO:0005524 ATP binding
ISO NOT
GO_REF:0000121
ACCEPT
Summary: Retain the explicit NOT ATP binding annotation. PTK7 fails to bind ATP in the characterized receptor pseudokinase mechanism. The rat protein retains the human pocket-occluding residues and ALG motif, providing a sequence-supported reason not to transfer ATP binding from active kinase relatives.
Supporting Evidence:
PMID:32619402
ATP binding to PTK7 and ROR2 is prevented by projection of a tyrosine side-chain from the Ξ²5/Ξ±D hinge region
file:rat/Ptk7/Ptk7-bioinformatics/RESULTS.md
| 948 | A | 957 | A |
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: The complete receptor architecture and conserved membrane helix support plasma-membrane localization, consistent with PTK7 junctional signaling in mammalian cells. The IBA agrees with this experimentally grounded receptor mechanism.
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
file:rat/Ptk7/Ptk7-uniprot.txt
TRANSMEM 714..735
GO:0005886 plasma membrane
IEA
GO_REF:0000120
ACCEPT
Summary: Plasma-membrane localization is supported by the retained receptor topology and mammalian PTK7 cell-contact localization. The less-conserved N-terminal segment is a product-level trafficking caveat, not evidence of a different organelle.
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
file:rat/Ptk7/Ptk7-uniprot.txt
TRANSMEM 714..735
GO:0005886 plasma membrane
ISO
GO_REF:0000121
ACCEPT
Summary: The ortholog-based plasma-membrane annotation fits the conserved single-pass receptor architecture and directly observed mammalian cell-contact signaling.
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
file:rat/Ptk7/Ptk7-uniprot.txt
TRANSMEM 714..735
GO:0005886 plasma membrane
ISO
GO_REF:0000121
ACCEPT
Summary: This independent orthology annotation identifies the same well-supported receptor compartment. It does not imply an additional molecular activity.
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
file:rat/Ptk7/Ptk7-uniprot.txt
TRANSMEM 714..735
GO:0005911 cell-cell junction
IEA
GO_REF:0000120
ACCEPT
Summary: PTK7 organizes Src signaling along cell-cell contacts; junctional localization is directly relevant to its conserved polarity function.
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
PMID:24703874
PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
GO:0005911 cell-cell junction
ISO
GO_REF:0000121
ACCEPT
Summary: Cell-contact localization in the mammalian PCP study supports transfer of the cell-cell-junction compartment to the intact rat receptor.
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
file:rat/Ptk7/Ptk7-uniprot.txt
TRANSMEM 714..735
GO:0005911 cell-cell junction
ISO
GO_REF:0000121
ACCEPT
Summary: The junctional annotation agrees with the conserved PTK7-Src mechanism and is retained as a core receptor location.
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
PMID:24703874
PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
GO:0007507 heart development
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: Direct Ptk7/chuzhoi mutant heart malformations support the ortholog-derived developmental role. Heart development is a tissue-level consequence of the receptor mechanism and is retained as non-core.
Supporting Evidence:
PMID:20704721
Chuzhoi mutants exhibit defects in the heart including double outlet right ventricle (DORV) with a ventricular septal defect (VSD), or parallel arterial trunks.
GO:0010976 positive regulation of neuron projection development
IEA
GO_REF:0000107
UNDECIDED
Summary: The human donor annotation traces to PMID:17910947, an RNAi screen of retinoic-acid-stimulated SH-SY5Y differentiation. The cached abstract reports the screening design and emphasizes twinfilin-2; it does not list the PTK7-specific data. This does not establish wrong-gene attribution, but the exact PTK7 response cannot be independently assessed without the full screen.
Supporting Evidence:
PMID:17910947
Phenotype-based screening of differentiating SH-SY5Y cells following retinoic acid (RA) stimulation
GO:0010976 positive regulation of neuron projection development
ISO
GO_REF:0000121
UNDECIDED
Summary: The human donor annotation traces to PMID:17910947, an RNAi screen of retinoic-acid-stimulated SH-SY5Y differentiation. The cached abstract reports the screening design and emphasizes twinfilin-2; it does not list the PTK7-specific data. This does not establish wrong-gene attribution, but the exact PTK7 response cannot be independently assessed without the full screen.
Supporting Evidence:
PMID:17910947
Phenotype-based screening of differentiating SH-SY5Y cells following retinoic acid (RA) stimulation
GO:0016020 membrane
IEA
GO_REF:0000107
MODIFY
Summary: Membrane localization is correct but unnecessarily broad for a single-pass cell-surface receptor supported at cell contacts.
Proposed replacements: plasma membrane
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
file:rat/Ptk7/Ptk7-uniprot.txt
TRANSMEM 714..735
GO:0016020 membrane
ISO
GO_REF:0000121
MODIFY
Summary: The ortholog-based generic membrane term can be specified to the plasma membrane on the conserved receptor topology and junctional evidence.
Proposed replacements: plasma membrane
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
file:rat/Ptk7/Ptk7-uniprot.txt
TRANSMEM 714..735
GO:0016301 kinase activity
ISO NOT
GO_REF:0000121
ACCEPT
Summary: The NOT kinase activity annotation correctly captures catalytic inactivity. A kinase-like fold does not confer kinase catalysis. The conserved PTK7 pocket blocks ATP binding; Src is the active kinase in the experimentally resolved junctional module.
Supporting Evidence:
PMID:32619402
ATP binding to PTK7 and ROR2 is prevented by projection of a tyrosine side-chain from the Ξ²5/Ξ±D hinge region
file:rat/Ptk7/Ptk7-bioinformatics/RESULTS.md
| 948 | A | 957 | A |
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
GO:0016477 cell migration
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: The human donor experiment links membrane PTK7 levels and proteolytic shedding to actin remodeling and cell invasion. The direction depends on the tested condition, but the broad cell-migration role is supported and retained as non-core.
Supporting Evidence:
PMID:20837484
The enforced expression of membrane PTK7 in cancer cells leads to the actin cytoskeleton reorganization and the inhibition of cell invasion.
GO:0016477 cell migration
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: The human donor experiment links membrane PTK7 levels and proteolytic shedding to actin remodeling and cell invasion. The direction depends on the tested condition, but the broad cell-migration role is supported and retained as non-core.
Supporting Evidence:
PMID:20837484
The enforced expression of membrane PTK7 in cancer cells leads to the actin cytoskeleton reorganization and the inhibition of cell invasion.
GO:0016740 transferase activity
IEA
GO_REF:0000104
REMOVE
Summary: No intrinsic transferase chemistry follows from this inactive kinase fold. Conserved structural defects prevent the ATP-dependent phosphotransfer reaction; activity of an associated Src kinase is not PTK7 transferase activity.
Supporting Evidence:
PMID:32619402
ATP binding to PTK7 and ROR2 is prevented by projection of a tyrosine side-chain from the Ξ²5/Ξ±D hinge region
file:rat/Ptk7/Ptk7-bioinformatics/RESULTS.md
| 948 | A | 957 | A |
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
GO:0030036 actin cytoskeleton organization
IEA
GO_REF:0000107
ACCEPT
Summary: Spatial actomyosin organization is directly connected to PTK7-Src-ROCK signaling in mammalian cells and auditory epithelium, making it a core process of the receptor mechanism.
Supporting Evidence:
PMID:24703874
PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
GO:0030036 actin cytoskeleton organization
ISO
GO_REF:0000121
ACCEPT
Summary: The ortholog-based actin-organization term is supported by the direct PTK7 depletion and junctional-contractility results, with preserved rat receptor architecture.
Supporting Evidence:
PMID:24703874
PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
file:rat/Ptk7/Ptk7-bioinformatics/RESULTS.md
| 948 | A | 957 | A |
GO:0042060 wound healing
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: The mouse wound-repair paper explicitly tests Ptk7 mutant genetic interactions and reports failed healing. Retain this ortholog-derived tissue response as non-core; it is not inferred merely from a cell-migration phenotype.
Supporting Evidence:
PMID:20643356
Mice carrying mutant alleles of PCP genes Vangl2, Celsr1, PTK7, and Scrb1, and the transcription factor Grhl3, interact genetically, exhibiting failed wound healing
GO:0045198 establishment of epithelial cell apical/basal polarity
ISO
GO_REF:0000121
UNDECIDED
Summary: The mouse donor annotation traces to PMID:15229603. Its accessible abstract establishes planar polarity, whereas the annotated apical-basal axis is distinct. The full text was not accessible for verification; the curator may have inspected additional data, so this is neither removed nor called a mislabeled PCP result.
Supporting Evidence:
PMID:15229603
disrupts neural tube closure and stereociliary bundle orientation
GO:0060026 convergent extension
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: Convergent extension is a tissue-level manifestation of the conserved polarized morphogenesis program in which PTK7 participates. It is retained as a developmental process rather than intrinsic kinase activity.
Supporting Evidence:
PMID:24703874
PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
GO:0060484 lung-associated mesenchyme development
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: Ptk7/chuzhoi mutant lung sections directly show thickened interstitial mesenchyme and reduced septation. This supports the specific developmental annotation as a non-core manifestation of the polarity/morphogenesis mechanism.
Supporting Evidence:
PMID:20704721
thickened interstitial mesenchyme and reduced sepatation in chuzhoi mutants.
GO:0060976 coronary vasculature development
ISO
GO_REF:0000121
UNDECIDED
Summary: Coronary-vasculature development requires the specific donor developmental evidence; a general morphogenetic receptor role cannot resolve this narrower annotation.
Supporting Evidence:
PMID:24703874
PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
GO:0070161 anchoring junction
IEA
GO_REF:0000044
MODIFY
Summary: Junctional PTK7 signaling is established, but the evidence is most directly stated as cell-cell-junction localization rather than assuming a particular anchoring-junction subtype.
Proposed replacements: cell-cell junction
Supporting Evidence:
PMID:24703874
PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
GO:0071300 cellular response to retinoic acid
IEA
GO_REF:0000107
UNDECIDED
Summary: The human donor annotation traces to PMID:17910947, an RNAi screen of retinoic-acid-stimulated SH-SY5Y differentiation. The cached abstract reports the screening design and emphasizes twinfilin-2; it does not list the PTK7-specific data. This does not establish wrong-gene attribution, but the exact PTK7 response cannot be independently assessed without the full screen.
Supporting Evidence:
PMID:17910947
Phenotype-based screening of differentiating SH-SY5Y cells following retinoic acid (RA) stimulation
GO:0071300 cellular response to retinoic acid
ISO
GO_REF:0000121
UNDECIDED
Summary: The human donor annotation traces to PMID:17910947, an RNAi screen of retinoic-acid-stimulated SH-SY5Y differentiation. The cached abstract reports the screening design and emphasizes twinfilin-2; it does not list the PTK7-specific data. This does not establish wrong-gene attribution, but the exact PTK7 response cannot be independently assessed without the full screen.
Supporting Evidence:
PMID:17910947
Phenotype-based screening of differentiating SH-SY5Y cells following retinoic acid (RA) stimulation
GO:0090103 cochlea morphogenesis
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: The primary study directly assays mouse auditory sensory epithelium and PTK7-dependent planar polarity. Cochlear morphogenesis is a supported tissue-specific manifestation of that core signaling function.
Supporting Evidence:
PMID:24703874
PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
GO:0090263 positive regulation of canonical Wnt signaling pathway
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: The donor experiment directly reports reduced Wnt3a-induced beta-catenin/TCF activity after PTK7 depletion. This supports a positive canonical Wnt role in that setting. Retain the orthology annotation as context-dependent and non-core; conflicting effects in other models do not invalidate the measured positive effect.
Supporting Evidence:
PMID:21132015
PTK7-deficient cells exhibit weakened Ξ²-catenin/T-cell factor transcriptional activity on Wnt3a stimulation.
GO:0090263 positive regulation of canonical Wnt signaling pathway
ISO
GO_REF:0000121
KEEP AS NON CORE
Summary: The donor experiment directly reports reduced Wnt3a-induced beta-catenin/TCF activity after PTK7 depletion. This supports a positive canonical Wnt role in that setting. Retain the orthology annotation as context-dependent and non-core; conflicting effects in other models do not invalidate the measured positive effect.
Supporting Evidence:
PMID:21132015
PTK7-deficient cells exhibit weakened Ξ²-catenin/T-cell factor transcriptional activity on Wnt3a stimulation.

Core Functions

Organizes Src-dependent junctional signaling and spatial actomyosin contractility during planar cell polarity.

Supporting Evidence:
  • PMID:24703874
    PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts.
  • PMID:24703874
    PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
  • file:rat/Ptk7/Ptk7-bioinformatics/RESULTS.md
    | 948 | A | 957 | A |

References

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Suggested Questions for Experts

Q: Does the selected rat N-terminal product reach the cell surface with the same efficiency and topology as canonical PTK7?

Deep Research

Falcon

(Ptk7-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(Ptk7-notes.md)

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Bioinformatics Results

(RESULTS.md)

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Protnlm Function Review

(Ptk7-protnlm-function-review.md)

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πŸ“„ View Raw YAML

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