PKD1

PKD1 is a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1).

Polycystin 1, transient receptor potential channel interacting

Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281).
Both PKD1 and PKD2 are required for channel activity (PubMed:27214281).
Involved in renal tubulogenesis (PubMed:12482949).
Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity).
Acts as a regulator of cilium length, together with PKD2 (By similarity).
The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling (By similarity).
The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling (By similarity).
May be an ion-channel regulator. Involved in adhesive protein-protein and protein-carbohydrate interactions.

Anatomical structure morphogenesisManual Assertion Based On ExperimentTAS:ProtInc
Branching morphogenesis of an epithelial tubeManual Assertion Based On ExperimentIDA:UniProtKB
Calcium ion transmembrane transportISS:BHF-UCL
Calcium ion transportManual Assertion Based On ExperimentIDA:ComplexPortal
Calcium-independent cell-matrix adhesionManual Assertion Based On ExperimentTAS:ProtInc
Cartilage condensationIEA:Ensembl
Cartilage developmentManual Assertion Based On ExperimentIEP:UniProtKB
Cell-cell signaling by wntManual Assertion Based On ExperimentIDA:UniProtKB
Cell-matrix adhesionManual Assertion Based On ExperimentTAS:ProtInc
Cytoplasmic sequestering of transcription factorISS:BHF-UCL
Detection of mechanical stimulusISS:BHF-UCL
Digestive tract developmentManual Assertion Based On ExperimentIEP:UniProtKB
Embryonic placenta developmentISS:BHF-UCL
Establishment of cell polarityIEA:Ensembl
Genitalia developmentManual Assertion Based On ExperimentIEP:UniProtKB
Heart developmentManual Assertion Based On ExperimentIEP:UniProtKB
Homophilic cell adhesion via plasma membrane adhesion moleculesManual Assertion Based On ExperimentTAS:ProtInc
In utero embryonic developmentISS:BHF-UCL
Kidney developmentISS:BHF-UCL
Liver developmentIEA:Ensembl
Lung epithelium developmentManual Assertion Based On ExperimentIEP:UniProtKB
Lymph vessel morphogenesisIEA:Ensembl
Mesonephric duct developmentManual Assertion Based On ExperimentIEP:UniProtKB
Mesonephric tubule developmentManual Assertion Based On ExperimentIEP:UniProtKB
Metanephric ascending thin limb developmentManual Assertion Based On ExperimentIEP:UniProtKB
Metanephric collecting duct developmentManual Assertion Based On ExperimentIEP:UniProtKB
Metanephric distal tubule morphogenesisManual Assertion Based On ExperimentIEP:UniProtKB
Metanephric proximal tubule developmentManual Assertion Based On ExperimentIEP:UniProtKB
Neural tube developmentManual Assertion Based On ExperimentIEP:UniProtKB
Peptidyl-serine phosphorylationISS:BHF-UCL
Placenta blood vessel developmentISS:BHF-UCL
Positive regulation of cyclin-dependent protein serine/threonine kinase activityManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cytosolic calcium ion concentrationIEA:Ensembl
Positive regulation of protein bindingISS:BHF-UCL
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Protein export from nucleusISS:BHF-UCL
Protein heterotetramerizationManual Assertion Based On ExperimentIDA:UniProtKB
Receptor signaling pathway via JAK-STATISS:BHF-UCL
Regulation of cell adhesionIEA:Ensembl
Regulation of cell cycleISS:BHF-UCL
Regulation of G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of mitotic spindle organizationIEA:Ensembl
Regulation of proteasomal protein catabolic processManual Assertion Based On ExperimentIDA:MGI
Response to fluid shear stressIEA:Ensembl
Skin developmentManual Assertion Based On ExperimentIEP:UniProtKB
Spinal cord developmentManual Assertion Based On ExperimentIEP:UniProtKB

Cell membrane
Cell projection, cilium
Endoplasmic reticulum
Golgi apparatus
PKD1 localization to the plasma and ciliary membranes requires PKD2, is independent of PKD2 channel activity, and involves stimulation of PKD1 autoproteolytic cleavage at the GPS domain. PKD1:PKD2 interaction is required to reach the Golgi apparatus from endoplasmic reticulum and then traffic to the cilia (By similarity).
Ciliary localization of PKD1 requires BBS1 and ARL6/BBS3 (By similarity).
Cell surface localization requires GANAB (PubMed:27259053).

Polycystic kidney disease 1 with or without polycystic liver disease (PKD1):
An autosomal dominant disorder characterized by renal cysts, liver cysts and intracranial aneurysm. Clinical variability is due to differences in the rate of loss of glomerular filtration, the age of reaching end-stage renal disease and the occurrence of hypertension, symptomatic extrarenal cysts, and subarachnoid hemorrhage from intracranial 'berry' aneurysm.

Extracellular: 24-3074
Helical: 3075-3095
Cytoplasmic: 3096-3277
Helical: 3278-3298
Extracellular: 3299-3323
Helical: 3324-3344
Cytoplasmic: 3345-3559
Helical: 3560-3580
Extracellular: 3581-3582
Helical: 3583-3603
Cytoplasmic: 3604-3665
Helical: 3666-3686
Extracellular: 3687-3901
Helical: 3902-3922
Cytoplasmic: 3923-3935
Helical: 3936-3956
Extracellular: 3957-3984
Helical: 3985-4005
Cytoplasmic: 4006-4027
Helical: 4028-4048
Extracellular: 4049-4090
Helical: 4091-4110
Cytoplasmic: 4111-4303

After synthesis, undergoes cleavage between Leu-3048 and Thr-3049 in the GPS domain. Cleavage at the GPS domain occurs through a cis-autoproteolytic mechanism involving an ester-intermediate via N-O acyl rearrangement. This process takes place in the early secretory pathway, depends on initial N-glycosylation, and requires the REJ domain. There is evidence that cleavage at GPS domain is incomplete. Uncleaved and cleaved products may have different functions in vivo.