PKD2_BOVIN
ID PKD2_BOVIN Reviewed; 970 AA.
AC Q4GZT3;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Polycystin-2;
DE AltName: Full=Polycystic kidney disease 2 protein homolog;
DE AltName: Full=Transient receptor potential cation channel subfamily P member 2 {ECO:0000250|UniProtKB:Q13563};
GN Name=PKD2 {ECO:0000250|UniProtKB:Q13563};
GN Synonyms=TRPP2 {ECO:0000250|UniProtKB:Q13563};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=Holstein;
RX PubMed=15998908; DOI=10.1101/gr.3806705;
RA Cohen-Zinder M., Seroussi E., Larkin D.M., Loor J.J.,
RA Everts-van der Wind A., Lee J.-H., Drackley J.K., Band M.R.,
RA Hernandez A.G., Shani M., Lewin H.A., Weller J.I., Ron M.;
RT "Identification of a missense mutation in the bovine ABCG2 gene with a
RT major effect on the QTL on chromosome 6 affecting milk yield and
RT composition in Holstein cattle.";
RL Genome Res. 15:936-944(2005).
CC -!- FUNCTION: Component of a heteromeric calcium-permeable ion channel
CC formed by PKD1 and PKD2 that is activated by interaction between PKD1
CC and a Wnt family member, such as WNT3A and WNT9B. Can also form a
CC functional, homotetrameric ion channel (By similarity). Functions as a
CC cation channel involved in fluid-flow mechanosensation by the primary
CC cilium in renal epithelium. Functions as outward-rectifying K(+)
CC channel, but is also permeable to Ca(2+), and to a much lesser degree
CC also to Na(+) (By similarity). May contribute to the release of Ca(2+)
CC stores from the endoplasmic reticulum (By similarity). Together with
CC TRPV4, forms mechano- and thermosensitive channels in cilium. PKD1 and
CC PKD2 may function through a common signaling pathway that is necessary
CC to maintain the normal, differentiated state of renal tubule cells.
CC Acts as a regulator of cilium length, together with PKD1. The dynamic
CC control of cilium length is essential in the regulation of
CC mechanotransductive signaling. The cilium length response creates a
CC negative feedback loop whereby fluid shear-mediated deflection of the
CC primary cilium, which decreases intracellular cAMP, leads to cilium
CC shortening and thus decreases flow-induced signaling. Also involved in
CC left-right axis specification via its role in sensing nodal flow; forms
CC a complex with PKD1L1 in cilia to facilitate flow detection in left-
CC right patterning. Detection of asymmetric nodal flow gives rise to a
CC Ca(2+) signal that is required for normal, asymmetric expression of
CC genes involved in the specification of body left-right laterality (By
CC similarity). {ECO:0000250|UniProtKB:O35245,
CC ECO:0000250|UniProtKB:Q13563}.
CC -!- ACTIVITY REGULATION: Channel activity is regulated by phosphorylation.
CC Channel activity is regulated by intracellular Ca(2+).
CC {ECO:0000250|UniProtKB:Q13563}.
CC -!- SUBUNIT: Homotetramer. Heterotetramer with PKD1, giving rise to a
CC complex formed by one PKD1 chain and three PKD2 chains (By similarity).
CC Interaction with PKD1 is required for ciliary localization (By
CC similarity). Isoform 1 interacts with PKD1 while isoform 3 does not.
CC Interacts with PKD1L1. PKD1 requires the presence of PKD2 for stable
CC expression. Interacts with CD2AP. Interacts with HAX1. Interacts with
CC NEK8. Part of a complex containing AKAP5, ADCY5, ADCY6 and PDE4C.
CC Interacts (via C-terminus) with TRPV4 (via C-terminus). Interacts (via
CC C-terminal acidic region) with PACS1 and PACS2; these interactions
CC retain the protein in the endoplasmic reticulum and prevent trafficking
CC to the cell membrane (By similarity). Interacts with TMEM33 (By
CC similarity). {ECO:0000250|UniProtKB:O35245,
CC ECO:0000250|UniProtKB:Q13563}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane
CC {ECO:0000250|UniProtKB:Q13563}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q13563}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q13563}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q13563}. Cell membrane
CC {ECO:0000250|UniProtKB:Q13563}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q13563}. Basolateral cell membrane
CC {ECO:0000250|UniProtKB:Q13563}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:Q13563}. Golgi apparatus
CC {ECO:0000250|UniProtKB:O35245}. Note=PKD2 localization to the plasma
CC and ciliary membranes requires PKD1. PKD1:PKD2 interaction is required
CC to reach the Golgi apparatus form endoplasmic reticulum and then
CC traffic to the cilia (By similarity). Retained in the endoplasmic
CC reticulum by interaction with PACS1 and PACS2. Detected on kidney
CC tubule basolateral membranes and basal cytoplasmic vesicles. Cell
CC surface and cilium localization requires GANAB.
CC {ECO:0000250|UniProtKB:O35245, ECO:0000250|UniProtKB:Q13563}.
CC -!- TISSUE SPECIFICITY: Expressed in mesenchymally derived structures in
CC the developing embryo at day 12.5. In adult, mostly expressed in
CC kidney.
CC -!- DOMAIN: The C-terminal coiled-coil domain is involved in
CC oligomerization and the interaction with PKD1. The isolated coiled-coil
CC domain forms a homotrimer in vitro; the homotrimer interacts with a
CC single PKD1 chain. The coiled-coil domain binds calcium and undergoes a
CC calcium-induced conformation change (in vitro).
CC {ECO:0000250|UniProtKB:Q13563}.
CC -!- PTM: Phosphorylated. Phosphorylation is important for protein function;
CC a mutant that lacks the N-terminal phosphorylation sites cannot
CC complement a zebrafish pkd2-deficient mutant. PKD-mediated
CC phosphorylation at the C-terminus regulates its function in the release
CC of Ca(2+) stores from the endoplasmic reticulum. PKA-mediated
CC phosphorylation at a C-terminal site strongly increases the open
CC probability of the channel, but does not increase single channel
CC conductance. {ECO:0000250|UniProtKB:Q13563}.
CC -!- PTM: N-glycosylated. The four subunits in a tetramer probably differ in
CC the extent of glycosylation; simultaneous glycosylation of all
CC experimentally validated sites would probably create steric hindrance.
CC {ECO:0000250|UniProtKB:Q13563}.
CC -!- SIMILARITY: Belongs to the polycystin family. {ECO:0000305}.
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DR EMBL; AJ871176; CAI38797.1; -; Genomic_DNA.
DR RefSeq; NP_001039777.1; NM_001046312.1.
DR AlphaFoldDB; Q4GZT3; -.
DR BMRB; Q4GZT3; -.
DR SMR; Q4GZT3; -.
DR STRING; 9913.ENSBTAP00000026682; -.
DR PaxDb; Q4GZT3; -.
DR Ensembl; ENSBTAT00000026682; ENSBTAP00000026682; ENSBTAG00000020031.
DR GeneID; 530393; -.
DR KEGG; bta:530393; -.
DR CTD; 5311; -.
DR VEuPathDB; HostDB:ENSBTAG00000020031; -.
DR VGNC; VGNC:32935; PKD2.
DR eggNOG; KOG3599; Eukaryota.
DR GeneTree; ENSGT00940000159025; -.
DR HOGENOM; CLU_012097_0_0_1; -.
DR InParanoid; Q4GZT3; -.
DR OrthoDB; 426073at2759; -.
DR TreeFam; TF316484; -.
DR Proteomes; UP000009136; Chromosome 6.
DR Bgee; ENSBTAG00000020031; Expressed in intramuscular adipose tissue and 105 other tissues.
DR ExpressionAtlas; Q4GZT3; differential.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0034703; C:cation channel complex; ISS:UniProtKB.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0002133; C:polycystin complex; ISS:UniProtKB.
DR GO; GO:0005262; F:calcium channel activity; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0005261; F:cation channel activity; ISS:UniProtKB.
DR GO; GO:0051371; F:muscle alpha-actinin binding; IBA:GO_Central.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0005267; F:potassium channel activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IBA:GO_Central.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0198738; P:cell-cell signaling by wnt; ISS:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0050982; P:detection of mechanical stimulus; IBA:GO_Central.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISS:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; ISS:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IBA:GO_Central.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR013122; PKD1_2_channel.
DR InterPro; IPR003915; PKD_2.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR Pfam; PF08016; PKD_channel; 1.
DR PRINTS; PR01433; POLYCYSTIN2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
PE 2: Evidence at transcript level;
KW Calcium; Calcium channel; Calcium transport; Cell membrane;
KW Cell projection; Coiled coil; Cytoplasmic vesicle; Disulfide bond;
KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Ion channel;
KW Ion transport; Membrane; Metal-binding; Methylation; Phosphoprotein;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel;
KW Wnt signaling pathway.
FT CHAIN 1..970
FT /note="Polycystin-2"
FT /id="PRO_0000243983"
FT TOPO_DOM 1..221
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TRANSMEM 222..243
FT /note="Helical; Name=S1"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TOPO_DOM 244..470
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TRANSMEM 471..491
FT /note="Helical; Name=S2"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TOPO_DOM 492..507
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TRANSMEM 508..528
FT /note="Helical; Name=S3"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TOPO_DOM 529..554
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TRANSMEM 555..575
FT /note="Helical; Name=S4"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TOPO_DOM 576..599
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TRANSMEM 600..621
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TOPO_DOM 622..633
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT INTRAMEM 634..648
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TOPO_DOM 649..656
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TRANSMEM 657..677
FT /note="Helical; Name=S6"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT TOPO_DOM 678..970
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT DOMAIN 750..785
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 1..182
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 766..833
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 805..824
FT /note="Linker"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT REGION 812..823
FT /note="Important for interaction with PACS1 and PACS2"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT REGION 921..970
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 835..874
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT MOTIF 643..645
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT COMPBIAS 94..113
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 766..796
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 939..960
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 765
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT BINDING 767
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT BINDING 769
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT BINDING 771
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT BINDING 776
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT MOD_RES 139
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O35245"
FT MOD_RES 803
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT MOD_RES 810
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35245"
FT MOD_RES 814
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT MOD_RES 831
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13563"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 330
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 333..346
FT /evidence="ECO:0000250|UniProtKB:Q13563"
SQ SEQUENCE 970 AA; 109789 MW; D02B28B5A21A7FD0 CRC64;
MVNSSRVQPQ QPGDARRSPA PRAPGPGRLM AGGAIAGAGL AAPGGLREQR GLEIEMERIR
QAAARDPPAG ASASPSPPLS SCSRQAWSRD NPGFEAEEEE EEEEVEGEEG GMVVEMDVEW
RPGSRRSASS SAVSSAGARG RGLGGYHGAG HPSGRRRQRE DQGPPSPSPA GGGDPLHRHL
PLDGQHPRVA WAERLVRGLR GLWGTRLMEE SSTDREKYLK SVLRELATYL LFLIVLCILT
YGMMSSSVYY YTRIMSQLFL DTPVSKMEKT NFKTLSSMED FWKFTEGALL DGLYWKTQPS
NRTEADNRSF IYYENLLLGV PRIRQLRVRN GSCSIPLDLR DEIKECYDVY SVSSEDRAPF
GPRNGTAWIY TSEKDLNGSS HWGMIATYSG AGYYLDLSRT REETAAQVAN LKKNVWLDRG
TRAIFIDFTV YNANINLFCV IRLLIEFPAT GGVIPSWQFQ PVKLIRYVTT FDFFLAACEI
IFCLFILYYV VEEILEIRIH KLHYFRSFWN CLDVVIIVLS VVAIGINIYR TSNVEALLQF
LEDQNTFPNF ENLAYWQTQF NNIAAVIVFF VWIKLFKFIN FNRTMSQLST TMSRCAKDLF
GFAIMFFIIF LAYAQLAYLV FGTQVDDFST FQECIFTQFR IILGDINFAE IEEANRVLGP
IYFTTFVFFM FFILLNMFLA IINDTYSEVK SDLAQQKAEM ELSDLIRKGY HKALIKLKLK
KNTVDDISES LRQGGGKLNF DELRQDLKGK GHTDAEIEAI FTKYDQDGDQ ELTEHEHQQM
RDDLEKERED LDLDHSSLPR PMSSRSFPRS LDDSEEEDDD DSGHSSRRRG SISSGVSYEE
FQVLVRRVDR MEHSIGSIVS KIDAVIVKLE IMERAKLKRR EVLGRLLDGV AEDERLGRDN
EIHREQMERL VREELERWES DDAASQISHG LGTPLGLNGQ PRPRSSRPSS SQSTEGMEGG
GGNGSANIHV
