Skip Header

Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot Q13563 (PKD2_HUMAN)

Last modified February 9, 2010. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Hide | Top

Names and origin

Protein namesRecommended name:
    Polycystin-2
Alternative name(s):
    Polycystic kidney disease 2 protein
    Autosomal dominant polycystic kidney disease type II protein
    Polycystwin
    R48321
Gene names
Name: PKD2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

Sequence length968 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

Hide | Top

General annotation (Comments)

Function

Functions as a calcium permeable cation channel. PKD1 and PKD2 may function through a common signaling pathway that is necessary for normal tubulogenesis.

Subunit structure

Forms homooligomers. Interacts with PKD1. PKD1 requires the presence of PKD2 for stable expression. Interacts with CD2AP. Interacts with HAX1. Ref.5 Ref.6 Ref.10

Subcellular location

Membrane; Multi-pass membrane protein Potential. Endoplasmic reticulum Ref.6.

Tissue specificity

Strongly expressed in ovary, fetal and adult kidney, testis, and small intestine. Not detected in peripheral leukocytes. Ref.1

Domain

The C-terminal coiled-coil domain binds calcium and undergoes a calcium-induced conformation change. It is implicated in oligomerization and the interaction with PKD1. Ref.10

Involvement in disease

Defects in PKD2 are the cause of polycystic kidney disease autosomal dominant type 2 (ADPKD2) [MIM:173900]. ADPKD2 represents approximately 15% of the cases of ADPKD, a common genetic disease affecting about 1:400 to 1:1000 individuals. ADPKD is 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. ADPKD2 is clinically milder than ADPKD1 but it has a deleterious impact on overall life expectancy. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18

Sequence similarities

Belongs to the polycystin family.

Contains 1 EF-hand domain.

Hide | Top

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 968968Polycystin-2
PRO_0000164356

Regions

Topological domain1 – 223223Cytoplasmic Potential
Transmembrane224 – 24421 Potential
Topological domain245 – 468224Extracellular Potential
Transmembrane469 – 48921 Potential
Topological domain490 – 50516Cytoplasmic Potential
Transmembrane506 – 52621 Potential
Topological domain527 – 55024Extracellular Potential
Transmembrane551 – 57121 Potential
Topological domain572 – 59827Cytoplasmic Potential
Transmembrane599 – 61921 Potential
Topological domain620 – 65839Extracellular Potential
Transmembrane659 – 67921 Potential
Topological domain680 – 968289Cytoplasmic Potential
Domain750 – 78536EF-hand
Calcium binding763 – 77412 Ref.10
Region704 – 79491EF-hand domain
Region803 – 82220Linker
Region828 – 968141C-terminal coiled coil domain
Coiled coil838 – 92689 Potential
Motif316 – 32813Polycystin motif
Compositional bias95 – 10713Poly-Glu
Compositional bias153 – 1575Poly-Arg

Amino acid modifications

Modified residue1661Phosphoserine Ref.8
Modified residue2541Phosphoserine Ref.9
Modified residue2601Phosphothreonine Ref.9
Modified residue2631Phosphoserine Ref.9
Modified residue8121Phosphoserine By similarity
Modified residue8521Phosphoserine Ref.9
Modified residue8581Phosphoserine Ref.9
Glycosylation2991N-linked (GlcNAc...) Potential
Glycosylation3051N-linked (GlcNAc...) Potential
Glycosylation3281N-linked (GlcNAc...) Potential
Glycosylation3621N-linked (GlcNAc...) Potential
Glycosylation3751N-linked (GlcNAc...) Potential

Natural variations

Natural variant241P → L
VAR_058820
Natural variant281R → P Common polymorphism; possibly damaging. dbSNP rs1805044. Ref.13 Ref.15 Ref.17 Ref.3 Ref.19
VAR_011072
Natural variant1901A → T
VAR_058821
Natural variant3061R → Q in ADPKD2. Ref.17
VAR_058822
Natural variant3221R → Q in ADPKD2. Ref.18
VAR_058823
Natural variant3221R → W in ADPKD2. Ref.15
VAR_058824
Natural variant3561A → P in ADPKD2. Ref.13 Ref.16
VAR_011073
Natural variant4141W → G in ADPKD2. Ref.11 Ref.16
VAR_009195
Natural variant4201R → G in ADPKD2. Ref.17
VAR_058825
Natural variant4521I → V: dbSNP rs1801612.
VAR_014919
Natural variant4791Missing in ADPKD2; somatic mutation.
VAR_011074
Natural variant4821F → C
VAR_058826
Natural variant504 – 5129Missing in ADPKD2; somatic mutation.
VAR_011075
Natural variant5111D → V in ADPKD2. Ref.12
VAR_058827
Natural variant6321C → R in ADPKD2. Ref.16
VAR_058828
Natural variant6841Missing in ADPKD2; somatic mutation.
VAR_011076
Natural variant8001M → L: dbSNP rs2234917. Ref.15
VAR_058829
Natural variant8071R → Q in ADPKD2. Ref.16
VAR_058830

Experimental info

Mutagenesis7711T → A: Loss of calcium-binding site; when associated with A-774. Ref.10
Mutagenesis7741E → A: Loss of calcium-binding site; when associated with A-771. Ref.10
Mutagenesis8421L → P: Loss of protein solubility. Ref.10
Mutagenesis8461V → E: Loss of protein solubility. Ref.10
Mutagenesis8491M → K: Loss of protein solubility. Ref.10
Mutagenesis8531I → P: Loss of protein solubility. Ref.10
Mutagenesis8561I → K: Loss of protein solubility. Ref.10
Mutagenesis8631V → E: Loss of protein solubility; when associated with K-849. Ref.10
Sequence conflict451G → R in AAC16004. Ref.2
Sequence conflict4491G → V in AAC50933. Ref.4

Secondary structure

1 ....... 968
Helix Strand Turn

Details...

Hide | Top

Sequences

Sequence LengthMass (Da)Tools
Q13563-1 [UniParc].

Last modified October 17, 2006. Version 3.
Checksum: F8D2E760EBEA8B47

FASTA968109,691
        10         20         30         40         50         60 
MVNSSRVQPQ QPGDAKRPPA PRAPDPGRLM AGCAAVGASL AAPGGLCEQR GLEIEMQRIR 

        70         80         90        100        110        120 
QAAARDPPAG AAASPSPPLS SCSRQAWSRD NPGFEAEEEE EEVEGEEGGM VVEMDVEWRP 

       130        140        150        160        170        180 
GSRRSAASSA VSSVGARSRG LGGYHGAGHP SGRRRRREDQ GPPCPSPVGG GDPLHRHLPL 

       190        200        210        220        230        240 
EGQPPRVAWA ERLVRGLRGL WGTRLMEESS TNREKYLKSV LRELVTYLLF LIVLCILTYG 

       250        260        270        280        290        300 
MMSSNVYYYT RMMSQLFLDT PVSKTEKTNF KTLSSMEDFW KFTEGSLLDG LYWKMQPSNQ 

       310        320        330        340        350        360 
TEADNRSFIF YENLLLGVPR IRQLRVRNGS CSIPQDLRDE IKECYDVYSV SSEDRAPFGP 

       370        380        390        400        410        420 
RNGTAWIYTS EKDLNGSSHW GIIATYSGAG YYLDLSRTRE ETAAQVASLK KNVWLDRGTR 

       430        440        450        460        470        480 
ATFIDFSVYN ANINLFCVVR LLVEFPATGG VIPSWQFQPL KLIRYVTTFD FFLAACEIIF 

       490        500        510        520        530        540 
CFFIFYYVVE EILEIRIHKL HYFRSFWNCL DVVIVVLSVV AIGINIYRTS NVEVLLQFLE 

       550        560        570        580        590        600 
DQNTFPNFEH LAYWQIQFNN IAAVTVFFVW IKLFKFINFN RTMSQLSTTM SRCAKDLFGF 

       610        620        630        640        650        660 
AIMFFIIFLA YAQLAYLVFG TQVDDFSTFQ ECIFTQFRII LGDINFAEIE EANRVLGPIY 

       670        680        690        700        710        720 
FTTFVFFMFF ILLNMFLAII NDTYSEVKSD LAQQKAEMEL SDLIRKGYHK ALVKLKLKKN 

       730        740        750        760        770        780 
TVDDISESLR QGGGKLNFDE LRQDLKGKGH TDAEIEAIFT KYDQDGDQEL TEHEHQQMRD 

       790        800        810        820        830        840 
DLEKEREDLD LDHSSLPRPM SSRSFPRSLD DSEEDDDEDS GHSSRRRGSI SSGVSYEEFQ 

       850        860        870        880        890        900 
VLVRRVDRME HSIGSIVSKI DAVIVKLEIM ERAKLKRREV LGRLLDGVAE DERLGRDSEI 

       910        920        930        940        950        960 
HREQMERLVR EELERWESDD AASQISHGLG TPVGLNGQPR PRSSRPSSSQ STEGMEGAGG 


NGSSNVHV

« Hide

Hide | Top

References

« Hide 'large scale' references
[1]"PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein."
Mochizuki T., Wu G., Hayashi T., Xenophontos S.L., Veldhuisen B., Saris J.J., Reynolds D.M., Cai Y., Gabow P.A., Pierides A., Kimberling W.J., Breuning M.H., Deltas C.C., Peters D.J.M., Somlo S.
Science 272:1339-1342(1996) [PubMed: 8650545] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"Characterization of the exon structure of the polycystic kidney disease 2 gene (PKD2)."
Hayashi T., Mochizuki T., Reynolds D.M., Wu G., Cai Y., Somlo S.
Genomics 44:131-136(1997) [PubMed: 9286709] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-28.
[4]"A gene similar to PKD1 maps to chromosome 4q22: a candidate gene for PKD2."
Schneider M.C., Rodriguez A., Nomura H., Zhou J., Morton C.C., Reeders S.T., Weremowicz S.
Genomics 38:1-4(1996) [PubMed: 8954772] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 361-968.
Tissue: Mammary gland.
[5]"In vivo interaction of the adapter protein CD2-associated protein with the type 2 polycystic kidney disease protein, polycystin-2."
Lehtonen S., Ora A., Olkkonen V.M., Geng L., Zerial M., Somlo S., Lehtonen E.
J. Biol. Chem. 275:32888-32893(2000) [PubMed: 10913159] [Abstract]
Cited for: INTERACTION WITH CD2AP.
[6]"The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton."
Gallagher A.R., Cedzich A., Gretz N., Somlo S., Witzgall R.
Proc. Natl. Acad. Sci. U.S.A. 97:4017-4022(2000) [PubMed: 10760273] [Abstract]
Cited for: INTERACTION WITH HAX1, SUBCELLULAR LOCATION.
[7]"Polycystin channels and kidney disease."
Stayner C., Zhou J.
Trends Pharmacol. Sci. 22:543-546(2001) [PubMed: 11698076] [Abstract]
Cited for: REVIEW.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, MASS SPECTROMETRY.
Tissue: Epithelium.
[9]"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry."
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-254; THR-260; SER-263; SER-852 AND SER-858, MASS SPECTROMETRY.
[10]"Domain mapping of the polycystin-2 C-terminal tail using de novo molecular modeling and biophysical analysis."
Celic A., Petri E.T., Demeler B., Ehrlich B.E., Boggon T.J.
J. Biol. Chem. 283:28305-28312(2008) [PubMed: 18694932] [Abstract]
Cited for: 3D-STRUCTURE MODELING, PROTEIN SEQUENCE OF 711-715; 720-724; 804-808 AND 823-827, MASS SPECTROMETRY, DOMAIN, CALCIUM-BINDING, CIRCULAR DICHROISM ANALYSIS, SUBUNIT, MUTAGENESIS OF THR-771; GLU-774; LEU-842; VAL-846; MET-849; ILE-853; ILE-856 AND VAL-863.
[11]"A spectrum of mutations in the second gene for autosomal dominant polycystic kidney disease (PKD2)."
Veldhuisen B., Saris J.J., de Haij S., Hayashi T., Reynolds D.M., Mochizuki T., Elles R., Fossdal R., Bogdanova N., van Dijk M.A., Coto E., Ravine D., Noerby S., Verellen-Dumoulin C., Breuning M.H., Somlo S., Peters D.J.M.
Am. J. Hum. Genet. 61:547-555(1997) [PubMed: 9326320] [Abstract]
Cited for: VARIANT ADPKD2 GLY-414.
[12]"Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease."
Reynolds D.M., Hayashi T., Cai Y., Veldhuisen B., Watnick T.J., Lens X.M., Mochizuki T., Qian F., Maeda Y., Li L., Fossdal R., Coto E., Wu G., Breuning M.H., Germino G.G., Peters D.J.M., Somlo S.
J. Am. Soc. Nephrol. 10:2342-2351(1999) [PubMed: 10541293] [Abstract]
Cited for: VARIANT ADPKD2 VAL-511.
[13]"Seven novel mutations of the PKD2 gene in families with autosomal dominant polycystic kidney disease."
Torra R., Viribay M., Telleria D., Badenas C., Watson M., Harris P.C., Darnell A., San Millan J.L.
Kidney Int. 56:28-33(1999) [PubMed: 10411676] [Abstract]
Cited for: VARIANT ADPKD2 PRO-356, VARIANT PRO-28.
[14]"Mutations of PKD1 in ADPKD2 cysts suggest a pathogenic effect of trans-heterozygous mutations."
Watnick T.J., He N., Wang K., Liang Y., Parfrey P., Hefferton D., St George-Hyslop P.H., Germino G.G., Pei Y.
Nat. Genet. 25:143-144(2000) [PubMed: 10835625] [Abstract]
Cited for: VARIANTS ADPKD2 ILE-479 DEL; 504-ARG--VAL-512 DEL AND TYR-684 DEL.
[15]"Four novel mutations of the PKD2 gene in Czech families with autosomal dominant polycystic kidney disease."
Reiterova J., Stekrova J., Peters D.J.M., Kapras J., Kohoutova M., Merta M., Zidovska J.
Hum. Mutat. 19:573-573(2002) [PubMed: 11968093] [Abstract]
Cited for: VARIANT ADPKD2 TRP-322, VARIANTS LEU-24; PRO-28 AND LEU-800.
[16]"Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease."
Magistroni R., He N., Wang K., Andrew R., Johnson A., Gabow P., Dicks E., Parfrey P., Torra R., San-Millan J.L., Coto E., Van Dijk M., Breuning M., Peters D., Bogdanova N., Ligabue G., Albertazzi A., Hateboer N. expand/collapse author list , Demetriou K., Pierides A., Deltas C., St George-Hyslop P., Ravine D., Pei Y.
J. Am. Soc. Nephrol. 14:1164-1174(2003) [PubMed: 12707387] [Abstract]
Cited for: VARIANTS ADPKD2 PRO-356; GLY-414; ARG-632 AND GLN-807.
[17]"PKD2 mutations in a Czech population with autosomal dominant polycystic kidney disease."
Stekrova J., Reiterova J., Merta M., Damborsky J., Zidovska J., Kebrdlova V., Kohoutova M.
Nephrol. Dial. Transplant. 19:1116-1122(2004) [PubMed: 14993477] [Abstract]
Cited for: VARIANTS ADPKD2 GLN-306 AND GLY-420, VARIANT PRO-28.
[18]"Genetics and phenotypic characteristics of autosomal dominant polycystic kidney disease in Finns."
Peltola P., Lumiaho A., Miettinen R., Pihlajamaeki J., Sandford R., Laakso M.
J. Mol. Med. 83:638-646(2005) [PubMed: 15772804] [Abstract]
Cited for: VARIANT ADPKD2 GLN-322.
[19]"Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal dominant polycystic kidney disease."
Tan Y.-C., Blumenfeld J.D., Anghel R., Donahue S., Belenkaya R., Balina M., Parker T., Levine D., Leonard D.G.B., Rennert H.
Hum. Mutat. 30:264-273(2009) [PubMed: 18837007] [Abstract]
Cited for: VARIANTS PRO-28; THR-190 AND CYS-482.
+Additional computationally mapped references.

Hide | Top

Web resources

GeneReviews
Functional Glycomics Gateway - Glycan Binding

Polycystin 2 - Not a C-type lectin

Hide | Top

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U50928 mRNA. Translation: AAC50520.1.
AF004873 expand/collapse EMBL AC list , AF004859, AF004860, AF004861, AF004862, AF004863, AF004864, AF004865, AF004866, AF004867, AF004868, AF004869, AF004870, AF004871, AF004872 Genomic DNA. Translation: AAC16004.1.
BC112261 mRNA. Translation: AAI12262.1.
BC112263 mRNA. Translation: AAI12264.1.
U56813 mRNA. Translation: AAC50933.1.
IPIIPI00299040.
PIRG02640.
RefSeqNP_000288.1.
UniGeneHs.181272

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KLDNMR-A680-796[»]
2KLENMR-A680-796[»]
3HRNX-ray1.90A833-895[»]
3HROX-ray1.90A833-872[»]
ModBaseSearch...

Protein-protein interaction databases

STRINGQ13563.

Protein family/group databases

TCDB1.A.5.2.1. polycystin cation channel (PCC) family.

PTM databases

PhosphoSiteQ13563.

Proteomic databases

PeptideAtlasQ13563.
PRIDEQ13563.

Genome annotation databases

EnsemblENST00000237596; ENSP00000237596; ENSG00000118762; Homo sapiens. [Genome view]
GeneID5311.
KEGGhsa:5311.
UCSCuc003hre.1. human.

Organism-specific databases

CTD5311.
GeneCardsGC04P089147.
HGNCHGNC:9009. PKD2.
HPACAB004544.
HPA015794.
MIM173900. phenotype.
173910. gene+phenotype.
Orphanet730. Polycystic kidney disease, autosomal dominant.
PharmGKBPA33343.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG19057.
HOGENOMHBG358335.
HOVERGENQ13563.
InParanoidQ13563.
OMASTEGMEG.
OrthoDBEOG9KH5DW.
PhylomeDBQ13563.

Gene expression databases

ArrayExpressQ13563.
BgeeQ13563.
CleanExHS_PKD2.
GenevestigatorQ13563.
GermOnlineENSG00000118762. Homo sapiens.

Family and domain databases

InterProIPR011992. EF-hand-like_dom.
IPR018249. EF_HAND_2.
IPR003915. PKD_2.
[Graphical view]
Gene3DG3DSA:1.10.238.10. EF-Hand_type. 1 hit.
PRINTSPR01433. POLYCYSTIN2.
PROSITEPS00018. EF_HAND_1. False negative.
PS50222. EF_HAND_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio20536.
SOURCESearch...

Hide | Top

Entry information

Entry namePKD2_HUMAN
AccessionPrimary (citable) accession number: Q13563
Secondary accession number(s): O60441 expand/collapse secondary AC list , Q15764, Q2M1Q3, Q2M1Q5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: October 17, 2006
Last modified: February 9, 2010
This is version 103 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Hide | Top

Relevant documents

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents