TULP3

TUB like protein 3

Ensembl:
ENSG00000078246
UniProt:
O75386
OMIM:
604730
Synonyms:
TUBL3

Cilia effects upon perturbation of TULP3

Cilia number / % ciliated:
Decreased cilia number
Loss-of-function effect:
Shorter cilia
Overexpression effect:
Unknown

Ciliogenesis screen results (4 screens)

  • Kim2016: No effect
  • Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-6.00) PMID:26167766
  • Breslow et al. 2018 (CRISPR) [CRISPR]: Positive Regulator (Hh signaling, casTLE effect=-2.26) PMID:29459680
  • Roosing et al. 2015 (siRNA) [siRNA]: Joubert Candidate / Ciliogenesis Defect (robust z=-2.13, ciliated=21.3%) PMID:26595381

Phenotypes

Mouse phenotype:
preweaning lethality, complete penetrance, decreased prepulse inhibition, impaired glucose tolerance, increased total body fat amount, decreased fasting circulating glucose level, decreased lean body mass, abnormal response to new environment
Mouse ciliopathy phenotype:
increased circulating alanine transamise level, increased circulating bilirubin level, increased circulating aspartate transamise level
Human ciliopathy phenotype:
hepatorenocardiac degenerative fibrosis

Ciliopathy associations

  • Hepatorenocardiac Degenerative Fibrosis
  • Neonatal Sclerosing Cholangitis

Subcellular localization

basal body, nucleus, transition zone

Functional category

  • Ciliary assembly/disassembly
  • Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
  • Cell migration & adhesion
  • Signaling (Hedgehog, GPCRs, ion channels)
  • Transition zone

Function

Role in intracellular transport, cell differentiation, sig ling, and motility (33187986). Associates with IFT-A in a complex to regulate trafficking and localisation of G protein-coupled receptors into cilia. Negative regulator of Hedgehog sig ling (20889716). Adapter for ciliary trafficking of membrane cargo, regulates PC1/2 complex trafficking (28154160). Required for proper Shh-dependent limb patterning, as it inhibits Gli2 activity (19286674). Essential for trafficking of Arl13b and INPP5E into cilia. Loss of function causes ciliopathy-associated polycystic kidney disease, downregulates the formation of cilia and their length (30799240, 30583862).

Model organism evidence

Mus musculus (3 references)

Critically, disrupting ciliary GPCR trafficking via Tulp3 knockdown - while preserving cilia structure - recapitulated the signaling and secretory deficits, demonstra

Critically, disrupting ciliary GPCR trafficking via Tulp3 knockdown - while preserving cilia structure - recapitulated the signaling and secretory deficits, demonstrating a specific requirement for the ciliary receptor pool.

PMIDs: 41895439, 41757129, 41091799

Danio rerio (2 references)

Correction: Tulp3 deficiency results in ciliopathy phenotypes during zebrafish embryogenesis.

Tulp3 deficiency results in ciliopathy phenotypes during zebrafish embryogenesis.

PMIDs: 41526457, 40940409