O08852 · PKD1_MOUSE

  • Protein
    Polycystin-1
  • Gene
    Pkd1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

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. Both PKD1 and PKD2 are required for channel activity (By similarity).
Involved in renal tubulogenesis (PubMed:24939912).
Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (PubMed:12514735).
Acts as a regulator of cilium length, together with PKD2 (PubMed:20096584).
The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. 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. May be an ion-channel regulator. Involved in adhesive protein-protein and protein-carbohydrate interactions. Likely to be involved with polycystin-1-interacting protein 1 in the detection, sequestration and exocytosis of senescent mitochondria (By similarity).

Features

Showing features for site.

142935001,0001,5002,0002,5003,0003,5004,000
TypeIDPosition(s)Description
Site3040-3041Cleavage; by autolysis

GO annotations

AspectTerm
Cellular Componentbasolateral plasma membrane
Cellular Componentcalcium channel complex
Cellular Componentcation channel complex
Cellular Componentcell surface
Cellular Componentcilium
Cellular Componentcytoplasm
Cellular Componentendoplasmic reticulum
Cellular Componentextracellular exosome
Cellular ComponentGolgi apparatus
Cellular Componentlateral plasma membrane
Cellular Componentmembrane
Cellular Componentmigrasome
Cellular Componentmotile cilium
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentpolycystin complex
Molecular Functioncalcium channel activity
Molecular Functioncarbohydrate binding
Molecular Functionmonoatomic cation channel activity
Molecular Functionprotein domain specific binding
Molecular Functionprotein kinase binding
Molecular Functiontranscription regulator inhibitor activity
Molecular Functiontransmembrane transporter binding
Molecular FunctionWnt receptor activity
Biological Processblood vessel development
Biological Processbranching morphogenesis of an epithelial tube
Biological Processcalcium ion transmembrane transport
Biological Processcalcium ion transport
Biological Processcartilage condensation
Biological Processcell surface receptor signaling pathway via JAK-STAT
Biological Processcell-cell adhesion
Biological Processdetection of mechanical stimulus
Biological Processdigestive tract development
Biological Processembryonic placenta development
Biological Processestablishment of epithelial cell polarity
Biological Processgenitalia development
Biological Processheart development
Biological Processin utero embryonic development
Biological Processkidney development
Biological Processliver development
Biological Processlung epithelium development
Biological Processlymph vessel morphogenesis
Biological Processmesonephric duct development
Biological Processmetanephric ascending thin limb development
Biological Processmetanephric collecting duct development
Biological Processmetanephric distal tubule morphogenesis
Biological Processmetanephric proximal tubule development
Biological Processmitocytosis
Biological Processneural tube development
Biological Processpeptidyl-serine phosphorylation
Biological Processplacenta blood vessel development
Biological Processpositive regulation of cytosolic calcium ion concentration
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processprotein export from nucleus
Biological Processprotein heterotetramerization
Biological Processregulation of cell adhesion
Biological Processregulation of cell cycle
Biological Processregulation of G1/S transition of mitotic cell cycle
Biological Processregulation of mitotic spindle organization
Biological Processregulation of proteasomal protein catabolic process
Biological Processresponse to fluid shear stress
Biological Processskin development
Biological Processspinal cord development
Biological ProcessWnt signaling pathway

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Polycystin-1
  • Alternative names
    • Autosomal dominant polycystic kidney disease 1 protein homolog

Gene names

    • Name
      Pkd1

Organism names

  • Taxonomic identifier
  • Strain
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    O08852
  • Secondary accessions
    • E9QJR6

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Endoplasmic reticulum
Golgi apparatus
Vesicle
Note: PKD1 localization to the plasma and ciliary membranes requires PKD2, is independent of PKD2 channel activity, and involves stimulation of PKD1 autocatalytic cleavage at the GPS region of the GAIN-B domain (PubMed:12514735, PubMed:25405894).
PKD1:PKD2 interaction is required to reach the Golgi apparatus from endoplasmic reticulum and then traffic to the cilia (PubMed:25405894).
Ciliary localization of PKD1 requires BBS1 and ARL6/BBS3 (PubMed:24939912).
Cell surface localization requires GANAB (By similarity).
Detected on migrasomes and on extracellular exosomes in urine (By similarity).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain24-3066Extracellular
Transmembrane3067-3087Helical
Topological domain3088-3269Cytoplasmic
Transmembrane3270-3290Helical
Topological domain3291-3315Extracellular
Transmembrane3316-3336Helical
Topological domain3337-3549Cytoplasmic
Transmembrane3550-3570Helical
Topological domain3571-3572Extracellular
Transmembrane3573-3593Helical
Topological domain3594-3655Cytoplasmic
Transmembrane3656-3676Helical
Topological domain3677-3891Extracellular
Transmembrane3892-3912Helical
Topological domain3913-3925Cytoplasmic
Transmembrane3926-3946Helical
Topological domain3947-3974Extracellular
Transmembrane3975-3995Helical
Topological domain3996-4017Cytoplasmic
Transmembrane4018-4038Helical
Topological domain4039-4080Extracellular
Transmembrane4081-4100Helical
Topological domain4101-4293Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Knockin mice expressing non-cleavable PKD1 show a hypomorphic phenotype. They are viable, show rapid cystic dilation in renal collecting duct and distal convoluted tubule, but not in the proximal portion of the nephron, during the postnatal period, and die with severe uremia, mostly at 3 weeks of age. Additionally, they show dilation of the common bile duct and intrahepatic biliary ducts, but develop a normal pancreas within their life span.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 269 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for signal, chain, glycosylation, disulfide bond, modified residue.

TypeIDPosition(s)Description
Signal1-23
ChainPRO_000035405424-4293Polycystin-1
Glycosylation50N-linked (GlcNAc...) asparagine
Glycosylation89N-linked (GlcNAc...) asparagine
Glycosylation116N-linked (GlcNAc...) asparagine
Glycosylation121N-linked (GlcNAc...) asparagine
Glycosylation187N-linked (GlcNAc...) asparagine
Glycosylation239N-linked (GlcNAc...) asparagine
Glycosylation370N-linked (GlcNAc...) asparagine
Disulfide bond436↔529
Disulfide bond507↔521
Glycosylation627N-linked (GlcNAc...) asparagine
Disulfide bond635↔648
Disulfide bond642↔660
Glycosylation662N-linked (GlcNAc...) asparagine
Glycosylation740N-linked (GlcNAc...) asparagine
Glycosylation804N-linked (GlcNAc...) asparagine
Glycosylation835N-linked (GlcNAc...) asparagine
Glycosylation848N-linked (GlcNAc...) asparagine
Glycosylation859N-linked (GlcNAc...) asparagine
Glycosylation884N-linked (GlcNAc...) asparagine
Glycosylation915N-linked (GlcNAc...) asparagine
Glycosylation998N-linked (GlcNAc...) asparagine
Glycosylation1004N-linked (GlcNAc...) asparagine
Glycosylation1028N-linked (GlcNAc...) asparagine
Glycosylation1084N-linked (GlcNAc...) asparagine
Glycosylation1096N-linked (GlcNAc...) asparagine
Glycosylation1107N-linked (GlcNAc...) asparagine
Glycosylation1172N-linked (GlcNAc...) asparagine
Glycosylation1188N-linked (GlcNAc...) asparagine
Glycosylation1234N-linked (GlcNAc...) asparagine
Glycosylation1263N-linked (GlcNAc...) asparagine
Glycosylation1330N-linked (GlcNAc...) asparagine
Glycosylation1342N-linked (GlcNAc...) asparagine
Glycosylation1376N-linked (GlcNAc...) asparagine
Glycosylation1444N-linked (GlcNAc...) asparagine
Glycosylation1449N-linked (GlcNAc...) asparagine
Glycosylation1468N-linked (GlcNAc...) asparagine
Glycosylation1535N-linked (GlcNAc...) asparagine
Glycosylation1548N-linked (GlcNAc...) asparagine
Glycosylation1557N-linked (GlcNAc...) asparagine
Glycosylation1643N-linked (GlcNAc...) asparagine
Glycosylation1657N-linked (GlcNAc...) asparagine
Glycosylation1706N-linked (GlcNAc...) asparagine
Glycosylation1730N-linked (GlcNAc...) asparagine
Glycosylation1788N-linked (GlcNAc...) asparagine
Glycosylation1831N-linked (GlcNAc...) asparagine
Glycosylation1863N-linked (GlcNAc...) asparagine
Glycosylation1876N-linked (GlcNAc...) asparagine
Glycosylation1987N-linked (GlcNAc...) asparagine
Glycosylation2046N-linked (GlcNAc...) asparagine
Glycosylation2070N-linked (GlcNAc...) asparagine
Glycosylation2121N-linked (GlcNAc...) asparagine
Glycosylation2244N-linked (GlcNAc...) asparagine
Glycosylation2349N-linked (GlcNAc...) asparagine
Glycosylation2391N-linked (GlcNAc...) asparagine
Glycosylation2408N-linked (GlcNAc...) asparagine
Glycosylation2414N-linked (GlcNAc...) asparagine
Glycosylation2563N-linked (GlcNAc...) asparagine
Glycosylation2640N-linked (GlcNAc...) asparagine
Glycosylation2713N-linked (GlcNAc...) asparagine
Glycosylation2749N-linked (GlcNAc...) asparagine
Glycosylation2813N-linked (GlcNAc...) asparagine
Glycosylation2836N-linked (GlcNAc...) asparagine
Glycosylation2873N-linked (GlcNAc...) asparagine
Glycosylation2948N-linked (GlcNAc...) asparagine
Glycosylation2986N-linked (GlcNAc...) asparagine
Disulfide bond3007↔3035
Glycosylation3728N-linked (GlcNAc...) asparagine
Glycosylation3780N-linked (GlcNAc...) asparagine
Modified residue4156Phosphoserine; by PRKX; in vitro

Post-translational modification

N-glycosylated.
After synthesis, undergoes autoproteolytic cleavage between Leu-3040 and Thr-3041 in the GPS region of the GAIN-B domain (PubMed:25405894).
Cleavage at the GPS region occurs through a cis-autoproteolytic mechanism involving an ester-intermediate via N-O acyl rearrangement (By similarity).
This process takes place in the early secretory pathway, depends on initial N-glycosylation, and requires the REJ domain (By similarity).
PKD1 is ubiquitously and incompletely cleaved in wild-type mice, so that uncleaved and cleaved PKD1 molecules coexist. The differential patterns of cleavage during embryonic development, as well as in adult mice, suggest different functions of uncleaved and cleaved molecules (PubMed:18003909).

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Component of the heterotetrameric polycystin channel complex with PKD2; the tetramer contains one PKD1 chain and three PKD2 chains (By similarity).
Interacts with PKD2; the interaction is required for ciliary localization (PubMed:25405894).
Interacts with PKD2L1 (PubMed:15548533).
Interacts with PRKX; involved in differentiation and controlled morphogenesis of the kidney. Interacts (via extracellular domain) with WNT3A, WNT4 and WNT9B (By similarity).
Interacts with WNT5A, DVL1 and DVL2 (PubMed:27214281).
Interacts with NPHP1 (via SH3 domain) (PubMed:20856870).
Interacts with BBS1, BBS4, BBS5 and TTC8. Interacts with RGS7 (By similarity).
Interacts (via C-terminal domain) with RABEP1; the interaction connects PKD1:PKD2 to GGA1 and ARL3 that mediate the ciliary targeting (PubMed:25405894).
Interacts (via the PKD repeats in the N-terminal extracellular region) with EPCIP; the interaction is not dependent on N-glycosylation of either protein (By similarity).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
XENO O08852PKD2 Q13563-12EBI-6666305, EBI-9837017

Protein-protein interaction databases

Miscellaneous

Structure

3D structure databases

Family & Domains

Features

Showing features for domain, repeat, region, compositional bias, coiled coil.

TypeIDPosition(s)Description
Domain24-67LRRNT
Repeat68-91LRR 1
Repeat92-113LRR 2
Domain125-178LRRCT
Domain177-271WSC
Domain272-359PKD 1
Domain415-530C-type lectin
Region613-632Disordered
Domain633-666LDL-receptor class A; atypical
Domain849-922PKD 2
Domain929-1014PKD 3
Domain1017-1123PKD 4
Domain1121-1209PKD 5
Domain1207-1292PKD 6
Domain1288-1377PKD 7
Domain1376-1463PKD 8
Domain1462-1545PKD 9
Domain1544-1629PKD 10
Domain1630-1718PKD 11
Domain1716-1802PKD 12
Domain1804-1886PKD 13
Domain1885-1970PKD 14
Domain1972-2053PKD 15
Domain2056-2144PKD 16
Domain2142-2828REJ
Domain2857-3055GAIN-B
Region3007-3055GPS
Domain3110-3225PLAT
Region4150-4197Disordered
Compositional bias4154-4197Polar residues
Coiled coil4210-4241
Region4235-4293Disordered
Compositional bias4261-4293Polar residues

Domain

The LDL-receptor class A domain is atypical; the potential calcium-binding site is missing.

Sequence similarities

Belongs to the polycystin family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    4,293
  • Mass (Da)
    466,577
  • Last updated
    2011-07-27 v2
  • Checksum
    FA12403171DBBCE0

Computationally mapped potential isoform sequences

There are 7 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A2I3BPP4A0A2I3BPP4_MOUSEPkd1237
A0A2I3BQ02A0A2I3BQ02_MOUSEPkd180
A0A2I3BQE7A0A2I3BQE7_MOUSEPkd127
A0A2I3BQG6A0A2I3BQG6_MOUSEPkd172
A0A2I3BRL4A0A2I3BRL4_MOUSEPkd1234
A0A2I3BRP8A0A2I3BRP8_MOUSEPkd127
A0A2I3BRZ6A0A2I3BRZ6_MOUSEPkd11231

Features

Showing features for sequence conflict, compositional bias.

TypeIDPosition(s)Description
Sequence conflict3in Ref. 1; AAC53207
Sequence conflict771in Ref. 1; AAC53207
Sequence conflict871in Ref. 1; AAC53207
Sequence conflict1180in Ref. 1; AAC53207
Sequence conflict1292in Ref. 1; AAC53207
Sequence conflict1632in Ref. 1; AAC53207
Sequence conflict1684in Ref. 1; AAC53207
Sequence conflict1770in Ref. 1; AAC53207
Sequence conflict2085in Ref. 1; AAC53207
Sequence conflict2507in Ref. 1; AAC53207
Sequence conflict3956in Ref. 1; AAC53207
Sequence conflict3962in Ref. 1; AAC53207
Compositional bias4154-4197Polar residues
Sequence conflict4237in Ref. 1; AAC53207
Compositional bias4261-4293Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U70209
EMBL· GenBank· DDBJ
AAC53207.1
EMBL· GenBank· DDBJ
mRNA
AC132367
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.

Genome annotation databases

Similar Proteins

Disclaimer

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