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Symbol PKD2 contributors: mct/shn/pgu - updated : 07-02-2011
HGNC name polycystic kidney disease 2 (autosomal dominant)
HGNC id 9009
Corresponding disease
PKD2 polycystic kidney disease 2
Location 4q22.1      Physical location : 88.928.819 - 88.998.928
Synonym name
  • R48321
  • autosomal dominant polycystic kidney disease type II protein
  • polycystic kidney disease 2 protein
  • polycystin-2
  • polycystwin
  • transient receptor potential cation channel, subfamily P, member 2
  • Synonym symbol(s) PKD4, CD119, TRPP2, PC2, MGC138466, MGC138468, APKD2, PC-2
    TYPE functioning gene
    STRUCTURE 70.11 kb     15 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure transcription factor binding sites E2F, EGRF, Ets, MZF1, Sp1, and ZBP-89
    MAPPING cloned Y linked N status confirmed
    Map cen - D4S2462 - D4S1542 - PKD2 PKD2 - D4S2929 - D4S1563 - qter
    Physical map
    PTPN13 4q21.3 protein tyrosine phosphatase, non-receptor type 13 (APO-1/CD95 (Fas)-associated phosphatase) SOAT 4q22.1 sodium-dependent organic anion transporter MGC26744 4q22.1 hypothetical protein MGC26744 LOC260422 4q21.3 actin related protein 2/3 complex subunit 1A pseudogene LOC389210 4 similar to hypothetical protein LOC391676 4 similar to Synaptic glycoprotein SC2 MLLT2 4q21 myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 2 KLHL8 4q22.1 kelch-like 8 (Drosophila) GAPDL4 4pter-p16.2 glyceraldehyde-3-phosphate dehydrogenase-like 4 SCDR9 4q22.1 short-chain dehydrogenase/reductase 9 DHRS8 4q22.1 dehydrogenase/reductase (SDR family) member 8 NUDT9 4q21.3 nudix (nucleoside diphosphate linked moiety X)-type motif 9 SPARCL1 4q27 SPARC-like 1 (mast9, hevin) DSPP 4q21.3 dentin sialophosphoprotein DMP1 4q21.2-q21.3 dentin matrix acidic phosphoprotein LOC391677 4 similar to chromosome 7 open reading frame 17 protein; 16.7kD protein IBSP 4q21-q25 integrin-binding sialoprotein (bone sialoprotein, bone sialoprotein II) MEPE 4q21.1 matrix, extracellular phosphoglycoprotein with ASARM motif (bone) HSPCP1 4q21-q25 heat shock 90kDa protein 1, beta pseudogene 1 SPP1 4q21-q25 secreted phosphoprotein 1 (osteopontin, bone sialoprotein I, early T-lymphocyte activation 1) PKD2 4q22 polycystic kidney disease 2 (autosomal dominant) ABCG2 4q22 ATP-binding cassette, sub-family G (WHITE), member 2 DKFZp761G058 4q22.1 hypothetical protein DKFZp761G058 CEB1 4q22.1-q23 hypothetical protein DKFZp761G058 MGC14156 4q22.1 hypothetical protein MGC14156 HERC3 4q21 hect domain and RLD 3 DRLM FAM13A1 4q21 family with sequence similarity 13, member A1 LOC389211 4 similar to expressed sequence AW060714 TIGD2 4q21.3 tigger transposable element derived 2 LOC285513 4q22.1 hypothetical protein LOC285513 SNCA 4q21-q22 synuclein, alpha (non A4 component of amyloid precursor)
    TRANSCRIPTS type messenger
    text alternatively spliced
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    15 - 5073 110 968 adult and fetal kidney (basolateral plasma membrane of kidney tubular epithelial cells), fetal brain and fetal liver 2009 10770959
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately Homo sapiens
    Digestiveliver   moderately Homo sapiens
    Nervousbrain   moderately Homo sapiens
    Reproductivemale systemseminal vesicles  lowly Homo sapiens
    Respiratorylung   moderately Homo sapiens
    Urinarykidney   highly Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscular   moderately Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period fetal
    Text kidney, term syncytiotrophoblast
  • 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
    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
    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
    small molecule
  • 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
  • PKD1L1 acts as an upstream genetic repressor of PKD2 (pMID: 27272319)
  • cell & other
    Other ciliary trafficking of PKD2 is regulated by the BBSome
    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