PKD2
entrez
5311
canonical
uniprot
Q13563
canonical
ensembl
ENSG00000118762
resolver
ensp
ENSP00000237596
resolver
ensp
ENSP00000654600
resolver
genesymbol
PKD2
resolver
genesymbol_syn
TRPP1
resolver
genesymbol_syn
TRPP2
resolver
hgnc
HGNC:9009
resolver
uniprot
O60441
resolver
uniprot
Q15764
resolver
uniprot
Q2M1Q3
resolver
uniprot
Q2M1Q5
resolver
uniprot
Q9UEU6
resolver
uniprot_entry
PKD2_HUMAN
resolver
uniprot_entry
Q9UEU6_HUMAN
resolver
uniprot_sec
O60441
resolver
uniprot_sec
Q15764
resolver
uniprot_sec
Q2M1Q3
resolver
uniprot_sec
Q2M1Q5
resolver
activity_regulation
ACTIVITY REGULATION: Channel activity is regulated by phosphorylation (PubMed:16551655, PubMed:20881056, PubMed:26269590). Channel activity is regulated by intracellular Ca(2+) (PubMed:11854751, PubMed:14742446). At the endoplasmic reticulum membrane (ER), TMEM33 enhances its channel activity (By similarity). TMEM120A inhibits the channel activity of PKD2, and mediates mechanosensitivity of the PKD2-TMEM120A channel complex (PubMed:36420836). PKD1/PKD2 complex on the plasma membrane is activated by PKD1 N-terminus (PubMed:33164752). {ECO:0000250|UniProtKB:O35245, ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:14742446, ECO:0000269|PubMed:16551655, ECO:0000269|PubMed:20881056, ECO:0000269|PubMed:26269590, ECO:0000269|PubMed:33164752, ECO:0000269|PubMed:36420836}.
uniprot
proteins
amino_acid_sequence
MVNSSRVQPQQPGDAKRPPAPRAPDPGRLMAGCAAVGASLAAPGGLCEQRGLEIEMQRIRQAAARDPPAGAAASPSPPLSSCSRQAWSRDNPGFEAEEEEEEVEGEEGGMVVEMDVEWRPGSRRSAASSAVSSVGARSRGLGGYHGAGHPSGRRRRREDQGPPCPSPVGGGDPLHRHLPLEGQPPRVAWAERLVRGLRGLWGTRLMEESSTNREKYLKSVLRELVTYLLFLIVLCILTYGMMSSNVYYYTRMMSQLFLDTPVSKTEKTNFKTLSSMEDFWKFTEGSLLDGLYWKMQPSNQTEADNRSFIFYENLLLGVPRIRQLRVRNGSCSIPQDLRDEIKECYDVYSVSSEDRAPFGPRNGTAWIYTSEKDLNGSSHWGIIATYSGAGYYLDLSRTREETAAQVASLKKNVWLDRGTRATFIDFSVYNANINLFCVVRLLVEFPATGGVIPSWQFQPLKLIRYVTTFDFFLAACEIIFCFFIFYYVVEEILEIRIHKLHYFRSFWNCLDVVIVVLSVVAIGINIYRTSNVEVLLQFLEDQNTFPNFEHLAYWQIQFNNIAAVTVFFVWIKLFKFINFNRTMSQLSTTMSRCAKDLFGFAIMFFIIFLAYAQLAYLVFGTQVDDFSTFQECIFTQFRIILGDINFAEIEEANRVLGPIYFTTFVFFMFFILLNMFLAIINDTYSEVKSDLAQQKAEMELSDLIRKGYHKALVKLKLKKNTVDDISESLRQGGGKLNFDELRQDLKGKGHTDAEIEAIFTKYDQDGDQELTEHEHQQMRDDLEKEREDLDLDHSSLPRPMSSRSFPRSLDDSEEDDDEDSGHSSRRRGSISSGVSYEEFQVLVRRVDRMEHSIGSIVSKIDAVIVKLEIMERAKLKRREVLGRLLDGVAEDERLGRDSEIHREQMERLVREELERWESDDAASQISHGLGTPVGLNGQPRPRSSRPSSSQSTEGMEGAGGNGSSNVHV
uniprot
proteins
disease_involvement
DISEASE: Polycystic kidney disease 2 with or without polycystic liver disease (PKD2) [MIM:613095]: An autosomal dominant disorder characterized by progressive formation and enlargement of cysts in both kidneys, typically leading to end-stage renal disease in adult life. Cysts also occurs in the liver and other organs. It represents approximately 15% of the cases of autosomal dominant polycystic kidney disease. PKD2 is clinically milder than PKD1 but it has a deleterious impact on overall life expectancy. {ECO:0000269|PubMed:10411676, ECO:0000269|PubMed:10541293, ECO:0000269|PubMed:10835625, ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:11968093, ECO:0000269|PubMed:12707387, ECO:0000269|PubMed:14993477, ECO:0000269|PubMed:15772804, ECO:0000269|PubMed:21115670, ECO:0000269|PubMed:27071085, ECO:0000269|PubMed:27214281, ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:39009345, ECO:0000269|PubMed:9326320}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Forms a nonselective cation channel (PubMed:11854751, PubMed:11991947, PubMed:15692563, PubMed:26269590, PubMed:27071085, PubMed:31441214, PubMed:39009345). Can function as a homotetrameric ion channel or can form heteromer with PKD1 (PubMed:31441214, PubMed:33164752). Displays distinct function depending on its subcellular localization and regulation by its binding partners (PubMed:11854751, PubMed:11991947, PubMed:27214281, PubMed:29899465). In primary cilium functions as a cation channel, with a preference for monovalent cations over divalent cations that allows K(+), Na(+) and Ca(2+) influx, with low selectivity for Ca(2+) (PubMed:27071085). Involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (By similarity). In the endoplasmic reticulum, likely functions as a K(+) channel to facilitate Ca(2+) release (By similarity). The heterotetrameric PKD1/PKD2 channel has higher Ca(2+) permeability than homomeric PKD2 channel and acts as a primarily Ca(2+)-permeable channel (PubMed:31441214). Interacts with and acts as a regulator of a number of other channels, such as TRPV4, TRPC1, IP3R, RYR2, ultimately further affecting intracellular signaling, to modulate intracellular Ca(2+) signaling (PubMed:11854751, PubMed:11991947, PubMed:27214281, PubMed:29899465). Together with TRPV4, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). In cardiomyocytes, PKD2 modulates Ca(2+) release from stimulated RYR2 receptors through direct association (By similarity). Also involved in left-right axis specification via its role in sensing nodal flow; forms a complex with PKD1L1 in cilia to facilitate flow detection in left-right patterning (By similarity). Acts as a regulator of cilium length together with PKD1 (By similarity). Mediates systemic blood pressure and contributes to the myogenic response in cerebral arteries though vasoconstriction (By similarity). {ECO:0000250|UniProtKB:O35245, ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:11991947, ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:26269590, ECO:0000269|PubMed:27071085, ECO:0000269|PubMed:27214281, ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:31441214, ECO:0000269|PubMed:33164752, ECO:0000269|PubMed:39009345}.
uniprot
proteins
mass_dalton
109691
uniprot
proteins
mutagenesis
MUTAGEN 76; /note="S->A: Abolishes phosphorylation of the N-terminal domain. Abolishes the ability to complement a pkd2-deficient zebrafish mutant; when associated with A-80."; /evidence="ECO:0000269|PubMed:16551655"; MUTAGEN 80; /note="S->A: Decreases phosphorylation of the N-terminal domain. Abolishes the ability to complement a pkd2-deficient zebrafish mutant; when associated with A-76."; /evidence="ECO:0000269|PubMed:16551655"; MUTAGEN 201; /note="W->A: Abolishes increased channel activity due to a gain of function mutation; when associated with P-604."; /evidence="ECO:0000269|PubMed:29899465"; MUTAGEN 331; /note="C->S: Does not affect localization to the cilium. Loss of ion channel function."; /evidence="ECO:0000269|PubMed:32332171"; MUTAGEN 604; /note="F->A,I: No effect on channel activation."; /evidence="ECO:0000269|PubMed:27071085"; MUTAGEN 604; /note="F->P: Gain-of-function mutation resulting in increased channel activity. Absence of gain of function; when associated with F-605 DEL; when associated with A-201; when associated with V-511; when associated with G-414; when associated with G-420; when associated with Y-684 DEL; when associated with A-684; when associated with R-632; when associated with R-632; when associated S-629. Increased channel activity; when associated with 736-L-N-737 DEL. Coexpression of PKD1 with PKD2- F604P dramatically reduces the current in comparison with that measured when PKD2-P-604 is expressed by itself."; /evidence="ECO:0000269|PubMed:27071085, ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:36420836, ECO:0000269|PubMed:39009345"; MUTAGEN 605; /note="Missing: Abolishes increased channel activity due to a gain of function mutation; when associated with P-604."; /evidence="ECO:0000269|PubMed:27071085"; MUTAGEN 629; /note="F->S: Abolishes increased channel activity due to a gain of function mutation; when associated with P-604. Reduces but do not abolish ion channel function; when associated with A-677 and A-681."; /evidence="ECO:0000269|PubMed:39009345"; MUTAGEN 638; /note="R->C: Abolishes increased channel activity due to a gain of function mutation; when associated with P-604. Reduces but do not abolish ion channel function; when associated with A-677 and A-681. Abolishes the Ca(2+) permeability and alters its monovalent cation selectivity; when associated with A-677 and A-681."; /evidence="ECO:0000269|PubMed:39009345"; MUTAGEN 677; /note="L->A: Constitutive active channel; when associated with A-681. Reduces but do not abolish ion channel function; when associated with S-629 and A-681. Reduces but do not abolish ion channel function; when associated with C-638 and A-681."; /evidence="ECO:0000269|PubMed:31441214, ECO:0000269|PubMed:39009345"; MUTAGEN 677; /note="L->N: Gain of function mutation."; /evidence="ECO:0000269|PubMed:29899465"; MUTAGEN 681; /note="N->A: Constitutive active channel; when associated with A-677. Reduces but do not abolish ion channel function; when associated with S-629 and A-677. Reduces but do not abolish ion channel function; when associated with C-638 and A-677."; /evidence="ECO:0000269|PubMed:31441214, ECO:0000269|PubMed:39009345"; MUTAGEN 684; /note="Y->A: Abolishes increased channel activity due to a gain of function mutation; when associated with P-604."; /evidence="ECO:0000269|PubMed:29899465"; MUTAGEN 688; /note="K->A: Abolishes increased channel activity due to a gain of function mutation; when associated with P-604."; /evidence="ECO:0000269|PubMed:29899465"; MUTAGEN 721; /note="T->A: Decreases phosphorylation; when associated with A-801; A-812; A-831 and A-943."; /evidence="ECO:0000269|PubMed:16551655"; MUTAGEN 736..737; /note="Missing: Increased channel activity; when associated with P-604."; /evidence="ECO:0000269|PubMed:27071085"; MUTAGEN 768; /note="Q->G: Strongly increases calcium binding affinity."; /evidence="ECO:0000269|PubMed:24990821"; MUTAGEN 771; /note="T->A: Loss of calcium-binding site; when associated with A-774."; /evidence="ECO:0000269|PubMed:18694932"; MUTAGEN 774; /note="E->A: Loss of calcium-binding site; when associated with A-771."; /evidence="ECO:0000269|PubMed:18694932"; MUTAGEN 774; /note="E->Q: Abolishes calcium binding via the EF-hand."; /evidence="ECO:0000269|PubMed:24990821"; MUTAGEN 801; /note="S->A: Decreases phosphorylation; when associated with A-721; A-812; A-831 and A-943."; /evidence="ECO:0000269|PubMed:16551655"; MUTAGEN 801; /note="S->D: Phosphomimetic mutant. No effect on release of Ca(2+) stores from the endoplasmic reticulum."; /evidence="ECO:0000269|PubMed:20881056"; MUTAGEN 801; /note="S->G: Loss of phosphorylation at this site. Impairs release of Ca(2+) stores from the endoplasmic reticulum."; /evidence="ECO:0000269|PubMed:20881056"; MUTAGEN 804; /note="S->N: Loss of phosphorylation at Ser-801."; /evidence="ECO:0000269|PubMed:20881056"; MUTAGEN 812; /note="S->A: Decreases interaction with PACS1 and enhances expression at the cell membrane. Decreases phosphorylation; when associated with A-721; A-801; A-831 and A-943."; /evidence="ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:16551655"; MUTAGEN 812; /note="S->D: No effect on interaction with PACS1."; /evidence="ECO:0000269|PubMed:15692563"; MUTAGEN 815..817; /note="DDD->AAA: Strongly decreases interaction with PACS1 and enhances expression at the cell membrane."; /evidence="ECO:0000269|PubMed:15692563"; MUTAGEN 829; /note="S->A: Abolishes increased channel opening in response to cAMP and phosphorylation by PKA."; /evidence="ECO:0000269|PubMed:26269590"; MUTAGEN 831; /note="S->A: Decreases phosphorylation; when associated with A-721; A-801; A-812 and A-943."; /evidence="ECO:0000269|PubMed:16551655"; MUTAGEN 842; /note="L->A: Abolishes oligomerization and interaction with PKD1; when associated with A-846; A-849; A-860; A-863 and A-867."; /evidence="ECO:0000269|PubMed:19556541"; MUTAGEN 842; /note="L->P: Loss of protein solubility."; /evidence="ECO:0000269|PubMed:18694932"; MUTAGEN 846; /note="V->A: Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-849; A-860; A-863 and A-867."; /evidence="ECO:0000269|PubMed:19556541"; MUTAGEN 846; /note="V->E: Loss of protein solubility."; /evidence="ECO:0000269|PubMed:18694932"; MUTAGEN 849; /note="M->A: Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-846; A-860; A-863 and A-867."; /evidence="ECO:0000269|PubMed:19556541"; MUTAGEN 849; /note="M->K: Loss of protein solubility."; /evidence="ECO:0000269|PubMed:18694932"; MUTAGEN 853; /note="I->P: Loss of protein solubility."; /evidence="ECO:0000269|PubMed:18694932"; MUTAGEN 856; /note="I->K: Loss of protein solubility."; /evidence="ECO:0000269|PubMed:18694932"; MUTAGEN 860; /note="I->A: Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-846; A-849; A-863 and A-867."; /evidence="ECO:0000269|PubMed:19556541"; MUTAGEN 863; /note="V->A: Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-846; A-849; A-860 and A-867."; /evidence="ECO:0000269|PubMed:19556541"; MUTAGEN 863; /note="V->E: Loss of protein solubility; when associated with K-849."; /evidence="ECO:0000269|PubMed:18694932"; MUTAGEN 867; /note="L->A: Abolishes oligomerization and interaction with PKD1; when associated with A-842; A-846; A-849; A-860 and A-863."; /evidence="ECO:0000269|PubMed:19556541"; MUTAGEN 943; /note="S->A: Decreases phosphorylation; when associated with A-721; A-801; A-812 and A-831."; /evidence="ECO:0000269|PubMed:16551655
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Phosphorylation is important for protein function; a mutant that lacks the N-terminal phosphorylation sites cannot complement a zebrafish pkd2-deficient mutant (PubMed:16551655). PKD-mediated phosphorylation at the C-terminus regulates its function in the release of Ca(2+) stores from the endoplasmic reticulum (PubMed:20881056). Phosphorylation at Ser-812 regulates PKD2 trafficking (PubMed:15692563). Phosphorylation at Ser-76 is required for PKD2 trafficking to or retention at the lateral plasma membrane (PubMed:16551655). Phosphorylation at Ser-801, Ser-812 and Ser-829 regulates PKD2 channel activity (PubMed:20881056, PubMed:26269590). {ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:16551655, ECO:0000269|PubMed:20881056, ECO:0000269|PubMed:26269590}.; PTM: N-glycosylated. The four subunits in a tetramer probably differ in the extent of glycosylation; simultaneous glycosylation of all experimentally validated sites would probably create steric hindrance. Thus, glycosylation at Asn-305 is not compatible with glycosylation at Asn-328; only one of these two residues is glycosylated at a given time. {ECO:0000269|PubMed:28092368}.; PTM: Sumoylated by SUMO1; sumoylation regulates PKD2 membrane recycling and is necessary for intravascular pressure-induced arterial contractility. {ECO:0000250|UniProtKB:O35245}.
uniprot
proteins
protein_family
Polycystin family
uniprot
proteins
pubmed
10411676
uniprot
proteins
pubmed
10541293
uniprot
proteins
pubmed
10760273
uniprot
proteins
pubmed
10770959
uniprot
proteins
pubmed
10835625
uniprot
proteins
pubmed
10913159
uniprot
proteins
pubmed
11854751
uniprot
proteins
pubmed
11968093
uniprot
proteins
pubmed
11991947
uniprot
proteins
pubmed
12707387
uniprot
proteins
pubmed
14742446
uniprot
proteins
pubmed
14993477
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15692563
uniprot
proteins
pubmed
15772804
uniprot
proteins
pubmed
16192288
uniprot
proteins
pubmed
16551655
uniprot
proteins
pubmed
18694932
uniprot
proteins
pubmed
18695040
uniprot
proteins
pubmed
18837007
uniprot
proteins
pubmed
19139490
uniprot
proteins
pubmed
19193631
uniprot
proteins
pubmed
19556541
uniprot
proteins
pubmed
19850920
uniprot
proteins
pubmed
20439752
uniprot
proteins
pubmed
20881056
uniprot
proteins
pubmed
21115670
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24990821
uniprot
proteins
pubmed
26269590
uniprot
proteins
pubmed
27071085
uniprot
proteins
pubmed
27214281
uniprot
proteins
pubmed
27259053
uniprot
proteins
pubmed
27768895
uniprot
proteins
pubmed
27991905
uniprot
proteins
pubmed
28092368
uniprot
proteins
pubmed
29899465
uniprot
proteins
pubmed
30093605
uniprot
proteins
pubmed
31441214
uniprot
proteins
pubmed
31806353
uniprot
proteins
pubmed
32332171
uniprot
proteins
pubmed
33164752
uniprot
proteins
pubmed
36420836
uniprot
proteins
pubmed
37681898
uniprot
proteins
pubmed
38483987
uniprot
proteins
pubmed
39009345
uniprot
proteins
pubmed
8650545
uniprot
proteins
pubmed
8954772
uniprot
proteins
pubmed
9286709
uniprot
proteins
pubmed
9326320
uniprot
proteins
sequence_length
968
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell projection, cilium membrane {ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:20881056, ECO:0000269|PubMed:27259053}; Multi-pass membrane protein {ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368, ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:30093605}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:10760273, ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:20881056, ECO:0000269|PubMed:28092368, ECO:0000305|PubMed:10913159}; Multi-pass membrane protein {ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368, ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:30093605}. Cell membrane {ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:19556541, ECO:0000269|PubMed:26269590, ECO:0000269|PubMed:27071085, ECO:0000269|PubMed:27214281, ECO:0000269|PubMed:27259053, ECO:0000269|PubMed:28092368, ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:30093605}; Multi-pass membrane protein {ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368, ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:30093605}. Basolateral cell membrane {ECO:0000269|PubMed:10770959}. Cytoplasmic vesicle membrane {ECO:0000269|PubMed:10770959}. Golgi apparatus {ECO:0000250|UniProtKB:O35245}. Vesicle {ECO:0000269|PubMed:37681898}. Secreted, extracellular exosome {ECO:0000269|PubMed:37681898}. Note=PKD2 localization to the plasma and ciliary membranes requires PKD1. PKD1:PKD2 interaction is required to reach the Golgi apparatus form endoplasmic reticulum and then traffic to the cilia (By similarity). Retained in the endoplasmic reticulum by interaction with PACS1 and PACS2 (PubMed:15692563). Detected on kidney tubule basolateral membranes and basal cytoplasmic vesicles (PubMed:10770959). Cell surface and cilium localization requires GANAB (PubMed:27259053). Detected on migrasomes and on extracellular exosomes in urine (PubMed:21406692). Preferentially localized to the dorsal side of immotile cilia (By similarity). {ECO:0000250|UniProtKB:O35245, ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:27259053}.
uniprot
proteins
transmembrane_region
TRANSMEM 220..241; /note="Helical; Name=S1"; /evidence="ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"; TRANSMEM 469..489; /note="Helical; Name=S2"; /evidence="ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"; TRANSMEM 506..526; /note="Helical; Name=S3"; /evidence="ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"; TRANSMEM 553..573; /note="Helical; Name=S4"; /evidence="ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"; TRANSMEM 598..619; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"; TRANSMEM 655..675; /note="Helical; Name=S6"; /evidence="ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368
uniprot
proteins