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Symbol PKD2 contributors: mct/shn/pgu - updated : 19-01-2021
HGNC name polycystic kidney disease 2 (autosomal dominant)
HGNC id 9009
  • N terminus containing a 15-AA sequence that mediates trafficking to the cilium, and a related N-terminal ciliary-targeting sequence similarly to PKD1, that binds ARF4
  • six transmembrane spans, a pore forming region, and cytoplasmic N- and C-terminal tails
  • N and C terminal second dimerization domain leading to homotetrameric form (N-terminal dimerization domain is not critical for the function of ER PKD2 channels but is required for the function of surface PKD2 channels)
  • a PKHD1-binding domain in the intracellular N terminus
  • phosphorylation site within its N-terminal domain having significant role for the maintenance of normal glomerular and tubular morphology
  • six transmembrane segments (6TM)
  • a large extracellular loop between TM1 and 2
  • five N-glycosylation sites
  • several phosphorylation sites
  • a transient receptor potential channel subunit motif (TRP), dimerizing with TRPC1 or PKD1
  • a coiled-coil domain including an EF hand calcium binding domain in the C terminus critical for the formation of the complex PKD2/PKD1 , that functions as a homodimerization domain essential for PKD1 binding but not for its self-oligomerization
  • C terminus required for the interaction with the
  • AKAP5 complex
  • Cterm protein contains a Ca(2+)-binding site responsible for channel gating and function
  • mono polymer homomer , heteromer , dimer , tetramer
    interspecies ortholog to Pkd2, Mus musculus
    ortholog to Pkd2, Rattus norvegicus
    intraspecies homolog to TRPC1,PKD1
  • voltage gated Ca+ channels family
  • polycystin protein family
  • transient receptor potential superfamily of cation channels
  • CATEGORY signaling , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
    intracellular,cytoplasm,organelle,endoplasmic reticulum
  • basolateral plasma membrane of kidney tubular epithelial cells
  • localized on the ER membrane as a Ca release channel
  • Type II membrane protein
  • ER localization plays an important role in the development of normal Left-Right asymmetry
  • localized at the endoplasmic reticulum (ER) membrane significantly enhanced Ca2+ release from the ER upon muscarinic acetylcholine receptor (mAChR) stimulation
  • besides its localization in the primary cilium, is present in the endoplasmic reticulum (ER), the PM, the adherens junctions and the basolateral cell surface of kidney epithelial cells
  • with PKD1, colocalize to cilia, where they may enable a mechano/chemosensory response triggering a rise in intracellular Ca2+
  • located in the primary cilium where it is thought to transmit mechanical stimuli into the cell interior
  • basic FUNCTION
  • Ca2+ permeable non selective cation channel with a high permeability to Ca2+
  • modulating Ca2+ entry in response to G-protein coupled receptor activation and/or store depletion
  • mediating mechanosensation in the primary cilium of kidney cells
  • function as a nonselective cation channel in the plasma membrane
  • acting as a negative regulator of cell growth, and may also play an important role in the regulation of tubulogenesis
  • playing a necessary role for the proper growth and differentiation of kidney epithelial cells
  • traffics to cilia independently of polycystin-1 by using an N-terminal RVXP motif
  • showing a pattern of single-channel conductance, amiloride sensitivity and ion permeability distinct from that of PKD2 alone
  • TRP-type Ca(2+)-permeable non-selective cation channel, present and functional in microtubule-containing primary cilia of renal epithelial cells, and having a regulatory role in the sensory function of primary cilia
  • in the ER plays a role in cellular Ca2+ homeostasis
  • represses cell proliferation through promoting the phosphorylation of eukaryotic translation initiation factor eIF2A by pancreatic ER-resident eIF2 alpha kinase (EIF2AK3)
  • important regulator of the translation machinery
  • important for regulation of RyR2 function
  • calcium permeable nonselective cation channel implicated in the regulation of cardiac development, renal tubular differentiation, and left-to-right (L-R) axis determination
  • may be assuming distinct subcellular localizations to exert tissue-specific functions
  • protects cells from apoptosis by lowering the Ca2+ concentration in the endoplasmic reticulum (ER)
  • having an important function in the modulation of intracellular Ca2+ signalling
  • modulating the cleavage of PKD1
  • functions as a Ca2+-permeable nonselective cation channel, ER-localized, interacting with the ER Ca2+ channel, inositol 1,4,5-trisphosphate receptor (ITPR1), to promote ER Ca2+ release
  • inhibits stretch-activated ions channels
  • acting as a Ca2+ release channel of intracellular stores and functionally interact with inositol 1,4,5-trisphosphate receptor-induced Ca2+ release
  • also acts as an intracellular Ca2+-release channel in the endoplasmic reticulum (ER) where it interacts with the inositol-1,4,5 trisphosphate (InsP3) receptor and ryanodine receptor
  • RP2 and PKD2 function in a common developmental process (
  • its expression is required for the movement of PKD1 to the plasma and ciliary membranes
  • functions as a non-selective cation channel in the endoplasmic reticulum and possibly at the plasma membrane
  • mediates sensory perception on cilia and flagella
  • PKD1L1 and PKD2 form a complex that functions as the nodal flow sensor in the motile cilia of the medaka Kupffer's vesicle
  • PKD2 modulates intracellular calcium cycling, contributing to the development of heart failure
  • PKD2 contributes to Ca2+ transport and cell signaling in renal epithelia and other tissues
  • PKD1, PKD2 form an ion channel complex that may mediate ciliary sensory processes and regulate endoplasmic reticulum (ER) Ca2+ release
  • role for PKD1, PKD2 in sensing and responding to cellular O2 levels
    text cation channel
    for normal tubulogenesis
    a component
  • homodimerizing or heterodimerizing with PKD1 or TRPC1 through their cytoplasmic C terminal tail, 3 PKD2 and 1 PKD1 (disruption of the complex PKD1/PKD2 is involved in the pathogenesis of cyst formation through a mechanosensor action in renal primary cilia for fluid flow)
  • heterodimerizing with CBY1, CD2AP, DIAPH1
  • forming with TRPC1 a channel with a unique constellation of new and TRPP2/TRPC1-specific properties, activated in response to G-protein-coupled receptor activation
  • RP2 forms a calcium-sensitive complex with polycystin 2 (
  • member of the TRP family of cation channels and an important PKD1 binding partner
  • homodimerization is regulated by three distinct domains and these events regulate formation of the tetrameric PC2 channel
  • PKD2 and PDE4C are unique components of an AKAP complex in primary cilia
  • its Ca2+ channel activity is important for regulating cAMP signaling
  • filamins are important regulators of PKD2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein
    small molecule other,
  • forms a Ca(2+)-permeable channel in the cell membrane and its function is regulated by cytosolic Ca(2+) levels
  • protein
  • polycystic kidney disease 1, PKD1
  • transient receptor potential cation channel, subfamily C, member 1, TRPC1
  • coassembling with PKD1, by their C terminus coiled coil domains to produce a new channel regulate renal tubular morphology and function and to activate JAK2
  • HCLS1 associated protein X-1, HAX1
  • GSK3 (N-terminal domain (Ser(76)) is phosphorylated by glycogen synthase kinase 3)
  • functionally interacts with ciliary chemosensors
  • HAVCR1 (interaction dependent on the ciliary sorting signal of PKD2 and the functionally relevant tyrosine 350 in HAVCR1 supporting recent evidence that PKD2 functionally interacts with chemosensors)
  • HERPUD1 (promotes degradation of PKD2 through the ERAD pathway)
  • STX5 (STX5 functions to inactivate PKD2 and prevent leaking of Ca2+ from ER stores)
  • may form functional homo- or heterotetramers with other subunits, similar to other TRP channels
  • CD2-associated protein, CD2AP
  • tropomyosin-1, TPM1
  • mammalian Diaphanous or Diaphanous-related formin 1 protein, mDia1/Drf1
  • Pericentrin, PCNT
  • PACS-1 and PACS-2
  • Alpha-actinin
  • ACTN2 associates with polycystin-2 and regulates its channel activity
  • TRPC1 (form homotetramers, with distinct functional and regulatory properties, among which there are the presence of four subconductance states in PKD2)
  • PKD2 interacts with LCK and regulates NFAT activity in T cells
  • PKD1 and ITPR1 in a complementary way to maintain Ca2+ homeostasis
  • C terminus of PKD2 strongly interacts with PDZ domains 8-10 and to a weaker extent with PDZ domains 1-3 of INADL
  • PKD1Ll1 and PKD2 localise to the cilium and biochemical experiments demonstrate that they can physically interact
  • NEK1 phosphorylates WWTR1 at a site essential for the ubiquitination and proteasomal degradation of PKD2
  • interacts with ADCY5 through its C terminus
  • AURKA binds, phosphorylates, and reduces the activity of PKD2, and, thus, limits the amplitude of Ca(2+) release from the endoplasmic reticulum
  • CAMK2A is a PKD2 target that promotes pronephric kidney development and stabilizes cilia
  • stimulates the inositol trisphosphate (IP(3)) receptor (IP(3)R), a Ca(2+)-release channel in the endoplasmic reticulum (ER)
  • PKD1, PKD2 are both required to amplify inositol-trisphosphate-induced Ca2+ release
  • reciprocal functional link between PKD1 and PKD2 which is critically dependent on their interaction
  • BBS4 and BBS5 interact directly and coordinate the ciliary removal of polycystin 2
  • PKD1L1 acts as an upstream genetic repressor of PKD2
  • PKD2-dependent channel of renal primary cilia also requires TRPM3
  • in addition to its channel function, PKD2 interacts with and acts as a regulator of a number of other channels, ultimately further affecting intracellular signaling and leading to dysfunction in its absence
  • cell & other
    Other ciliary trafficking of PKD2 is regulated by the BBSome
    Ca2+ sensing mechanism for PKD2 expression and functional regulation in renal epithelial cells
    corresponding disease(s) PKD2
    related resource Polycystickidneyresearchfoundation
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in PKD2 cysts
    Variant & Polymorphism
    Candidate gene
    Therapy target
    modulation of the PKD2/STX5 interaction may be a useful target for impacting dysregulated intracellular Ca2+ signaling associated with polycystic kidney disease
  • Pkd2-/- mice die in utero between embryonic day (E) 13.5 and parturition with structural defects in cardiac septation and cyst formation in maturing nephrons and pancreatic ducts. Pkd2WS25/- mice have pancreatic ductal and kidney cysts associated with renal failure and early death
  • Pkd2 (+/-) and Pkd1(+/-) : Pkd2 (+/-) mice have mild renal cystic lesions with no adverse effect on survival at 1 year
  • Pkd2 (+/-) mice develop hypertension, intracranial vascular abnormalities and vascular smooth muscle cells and have significantly altered intracellular Ca(2+) homeostasis