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A2A259 (PK2L1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 56. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Polycystic kidney disease 2-like 1 protein
Alternative name(s):
Polycystin-2 homolog
Gene names
Name:Pkd2l1
Synonyms:Trpp3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length760 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Pore-forming subunit of a ciliary calcium channel that controls calcium concentration within primary cilia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD1L1 in primary cilia and forms a calcium-permeant ciliary channel that regulates sonic hedgehog/SHH signaling and GLI2 transcription. May act as a sour taste receptor by forming a calcium channel with PKD1L3 in gustatory cells; however, its contribution to sour taste perception is unclear in vivo and may be indirect. May play a role in the perception of carbonation taste. Ref.1 Ref.5 Ref.6 Ref.8 Ref.10 Ref.12 Ref.13 Ref.14

Enzyme regulation

The calcium channel is gated following an off-response property by acid: gated open after the removal of acid stimulus, but not during acid application. Ref.9

Subunit structure

Homotrimer; trimerization is independent of calcium-binding. Calcium channels are probably composed of 3 subunit of PKD2L1 and 1 subunit of some PKD1 protein (PKD1, PKD1L1, PKD1L2 or PKDL3). Interacts with PKD1L1; to form ciliary calcium channel. Interacts with PKD1L3, to form putative sour taste receptor. Interacts with PKD1. Interacts with GNB2L1; inhibits the channel activity possibly by impairing localization to the cell membrane. Ref.1 Ref.5

Subcellular location

Cell projectioncilium membrane; Multi-pass membrane protein By similarity. Cell membrane; Multi-pass membrane protein. Endoplasmic reticulum. Note: Interaction with PKD1 or PKD1L3 is required for localization to the cell membrane. Ref.1 Ref.5 Ref.11

Tissue specificity

Expressed in all 4 taste areas in taste buds: circumvallate papillae, foliate papillae, fungiform papillae and palate. Expressed in cells distinct from those mediating sweet, umami and bitter taste (at protein level). Expressed in type III taste cells (at protein level). Ref.1 Ref.6 Ref.7 Ref.12

Domain

The EF-hand domain probably mediates calcium-binding. It is not required for channel activation By similarity.

Disruption phenotype

Intestinal malrotation in 50% of animals, while other organs do not show major organ laterality defects Intestinal malformations are associated with SHH pathway defects during early development (Ref.13). Partial reduction of chorda tympani nerve response to sour stimuli, without affecting sweet, salty, bitter, and umami perception (Ref.12). Ref.12 Ref.13

Sequence similarities

Belongs to the polycystin family.

Contains 1 EF-hand domain.

Caution

Pkd1l3 and Pkd2l1 have been defined as sour taste receptor in gustatory cells based on a number of indirect evidences: Pkd2l1 is expressed in a subset of taste receptor cells distinct from those responsible for sweet, bitter and unami taste and genetic elimination of cells expressing Pkd2l1 reduces gustatory nerve responses to sour taste stimuli (Ref.1, Ref.6). However, a number of experiments have recently shown that the sour taste receptor activity is probably indirect: mice lacking Pkd2l1 only show partial defects in sour taste perception (Ref.12). Moreover, the PKD1L3-PKD2L1 heteromer, when expressed in cells does not respond to acid stimuli used to evoke proton currents in taste cells (Ref.10).

Ontologies

Keywords
   Biological processCalcium transport
Ion transport
Transport
   Cellular componentCell membrane
Cell projection
Cilium
Endoplasmic reticulum
Membrane
   DomainCoiled coil
Transmembrane
Transmembrane helix
   LigandCalcium
   Molecular functionCalcium channel
Ion channel
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcation transport

Inferred from direct assay Ref.1. Source: BHF-UCL

cellular response to acidity

Inferred from direct assay Ref.1. Source: BHF-UCL

detection of chemical stimulus involved in sensory perception of sour taste

Inferred from direct assay Ref.1. Source: BHF-UCL

detection of mechanical stimulus

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentciliary membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum

Inferred from direct assay Ref.5. Source: MGI

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from physical interaction Ref.5. Source: MGI

   Molecular_functioncalcium channel activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

calcium ion binding

Inferred from direct assay PubMed 20408813. Source: BHF-UCL

calcium-activated potassium channel activity

Inferred from electronic annotation. Source: Ensembl

cation channel activity

Inferred from physical interaction Ref.5. Source: MGI

identical protein binding

Inferred from physical interaction PubMed 20408813. Source: BHF-UCL

sodium channel activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 760760Polycystic kidney disease 2-like 1 protein
PRO_0000425551

Regions

Topological domain1 – 103103Cytoplasmic Potential
Transmembrane104 – 12421Helical; Potential
Topological domain125 – 313189Extracellular Potential
Transmembrane314 – 33421Helical; Potential
Topological domain335 – 34713Cytoplasmic Potential
Transmembrane348 – 36821Helical; Potential
Topological domain369 – 38517Extracellular Potential
Transmembrane386 – 40621Helical; Potential
Topological domain407 – 47670Cytoplasmic Potential
Transmembrane477 – 49721Helical; Potential
Topological domain498 – 53942Extracellular Potential
Transmembrane540 – 56021Helical; Potential
Topological domain561 – 760200Cytoplasmic Potential
Domain630 – 66536EF-hand
Calcium binding643 – 65412 Potential
Region701 – 76060Required for protein homotrimerization By similarity
Coiled coil559 – 58022 Potential
Coiled coil650 – 68233 Potential
Motif195 – 20713Polycystin motif

Amino acid modifications

Glycosylation1771N-linked (GlcNAc...) Potential
Glycosylation2071N-linked (GlcNAc...) Potential
Glycosylation2411N-linked (GlcNAc...) Potential
Glycosylation5051N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis5231D → E: Little or no effect on calcium channel activity. Ref.11
Mutagenesis5231D → N: Impaired calcium channel activity. Ref.11
Mutagenesis5251D → N: Little or no effect on calcium channel activity. Ref.11
Mutagenesis5301D → N: Little or no effect on calcium channel activity. Ref.11
Mutagenesis5681K → A: Induces localization to the cell surface when expressed in absence of PKD1. Ref.5
Mutagenesis5761D → A: Induces localization to the endoplasmic reticulum when expressed in absence of PKD1. Ref.5
Sequence conflict1141I → V in AAK58371. Ref.2
Sequence conflict1141I → V in AAI16324. Ref.4
Sequence conflict1141I → V in AAI16298. Ref.4
Sequence conflict202 – 2032QL → HV in AAK58371. Ref.2
Sequence conflict4381Y → D in AAK58371. Ref.2
Sequence conflict4821I → V in AAK58371. Ref.2
Sequence conflict7561L → P in AAI16324. Ref.4
Sequence conflict7561L → P in AAI16298. Ref.4

Sequences

Sequence LengthMass (Da)Tools
A2A259 [UniParc].

Last modified February 20, 2007. Version 1.
Checksum: 4C76777051CFC2EF

FASTA76087,234
        10         20         30         40         50         60 
MNSMESPKNQ ELQTLGNRAW DNPAYSDPPS PNRTLRICTV SSVALPETQP KKPEVRCQEK 

        70         80         90        100        110        120 
TQRTLVSSCC LHICRSIRGL WGTTLTENTA ENRELYVKTT LRELVVYIVF LVDICLLTYG 

       130        140        150        160        170        180 
MTSSSAYYYT KVMSELFLHT PSDSGVSFQT ISSMSDFWDF AQGPLLDSLY WTKWYNNQSL 

       190        200        210        220        230        240 
GRGSHSFIYY ENLLLGAPRL RQLRVRNDSC VVHEDFREDI LNCYDVYSPD KEDQLPFGPQ 

       250        260        270        280        290        300 
NGTAWTYHSQ NELGGSSHWG RLTSYSGGGY YLDLPGSRQA SAEALQGLQE GLWLDRGTRV 

       310        320        330        340        350        360 
VFIDFSVYNA NINLFCILRL VVEFPATGGT IPSWQIRTVK LIRYVNNWDF FIVGCEVVFC 

       370        380        390        400        410        420 
VFIFYYVVEE ILEIHLHRLR YLSSVWNILD LVVILLSIVA VGFHIFRTLE VNRLMGKLLQ 

       430        440        450        460        470        480 
QPDTYADFEF LAFWQTQYNN MNAVNLFFAW IKIFKYISFN KTMTQLSSTL ARCAKDILGF 

       490        500        510        520        530        540 
AIMFFIVFFA YAQLGYLLFG TQVENFSTFV KCIFTQFRII LGDFDYNAID NANRILGPVY 

       550        560        570        580        590        600 
FVTYVFFVFF VLLNMFLAII NDTYSEVKEE LAGQKDQLQL SDFLKQSYNK TLLRLRLRKE 

       610        620        630        640        650        660 
RVSDVQKVLK GGEPEIQFED FTSTLRELGH EEHEITAAFT RFDQDGDHIL DEEEQEQMRQ 

       670        680        690        700        710        720 
GLEEERVTLN AEIENLGRSV GHSPPGELGA EAARGQSWVS GEEFDMLTRR VLQLQCVLEG 

       730        740        750        760 
VVSQIDAVGS KLKMLERKGE LAPSPGMGEP AVWENLYNPS 

« Hide

References

« Hide 'large scale' references
[1]"Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor."
Ishimaru Y., Inada H., Kubota M., Zhuang H., Tominaga M., Matsunami H.
Proc. Natl. Acad. Sci. U.S.A. 103:12569-12574(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PKD1L3, TISSUE SPECIFICITY.
Strain: C57BL/6.
[2]"Cloning and gene targeting of murine Pkdl gene."
Guo L., Zhou J.
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
Tissue: Brain.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Genomic organization and functional analysis of murine PKD2L1."
Murakami M., Ohba T., Xu F., Shida S., Satoh E., Ono K., Miyoshi I., Watanabe H., Ito H., Iijima T.
J. Biol. Chem. 280:5626-5635(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PKD1, MUTAGENESIS OF LYS-568 AND ASP-576.
[6]"The cells and logic for mammalian sour taste detection."
Huang A.L., Chen X., Hoon M.A., Chandrashekar J., Guo W., Trankner D., Ryba N.J., Zuker C.S.
Nature 442:934-938(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[7]"The candidate sour taste receptor, PKD2L1, is expressed by type III taste cells in the mouse."
Kataoka S., Yang R., Ishimaru Y., Matsunami H., Sevigny J., Kinnamon J.C., Finger T.E.
Chem. Senses 33:243-254(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[8]"The taste of carbonation."
Chandrashekar J., Yarmolinsky D., von Buchholtz L., Oka Y., Sly W., Ryba N.J., Zuker C.S.
Science 326:443-445(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Activation of polycystic kidney disease-2-like 1 (PKD2L1)-PKD1L3 complex by acid in mouse taste cells."
Kawaguchi H., Yamanaka A., Uchida K., Shibasaki K., Sokabe T., Maruyama Y., Yanagawa Y., Murakami S., Tominaga M.
J. Biol. Chem. 285:17277-17281(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[10]"A proton current drives action potentials in genetically identified sour taste cells."
Chang R.B., Waters H., Liman E.R.
Proc. Natl. Acad. Sci. U.S.A. 107:22320-22325(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"The single pore residue Asp523 in PKD2L1 determines Ca2+ permeation of the PKD1L3/PKD2L1 complex."
Fujimoto C., Ishimaru Y., Katano Y., Misaka T., Yamasoba T., Asakura T., Abe K.
Biochem. Biophys. Res. Commun. 404:946-951(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-523; ASP-525 AND ASP-530.
[12]"Sour taste responses in mice lacking PKD channels."
Horio N., Yoshida R., Yasumatsu K., Yanagawa Y., Ishimaru Y., Matsunami H., Ninomiya Y.
PLoS ONE 6:E20007-E20007(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[13]"Primary cilia are specialized calcium signalling organelles."
Delling M., DeCaen P.G., Doerner J.F., Febvay S., Clapham D.E.
Nature 504:311-314(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[14]"Direct recording and molecular identification of the calcium channel of primary cilia."
DeCaen P.G., Delling M., Vien T.N., Clapham D.E.
Nature 504:315-318(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB290927 mRNA. Translation: BAF45380.1.
AF271381 mRNA. Translation: AAK58371.1.
AC125101 Genomic DNA. No translation available.
BC116297 mRNA. Translation: AAI16298.1.
BC116323 mRNA. Translation: AAI16324.2.
RefSeqNP_852087.2. NM_181422.3.
UniGeneMm.308481.

3D structure databases

ProteinModelPortalA2A259.
SMRA2A259. Positions 477-563, 597-672, 698-739.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

TCDB1.A.5.2.2. the polycystin cation channel (pcc) family.

Proteomic databases

PRIDEA2A259.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000042026; ENSMUSP00000045675; ENSMUSG00000037578.
GeneID329064.
KEGGmmu:329064.
UCSCuc008hpm.2. mouse.

Organism-specific databases

CTD9033.
MGIMGI:1352448. Pkd2l1.

Phylogenomic databases

eggNOGNOG325704.
GeneTreeENSGT00700000104221.
HOGENOMHOG000230858.
HOVERGENHBG014945.
InParanoidA2A259.
KOK04990.
OMAFSTFVKC.
OrthoDBEOG7N8ZTW.
PhylomeDBA2A259.
TreeFamTF316484.

Gene expression databases

GenevestigatorA2A259.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR013122. PKD1_2_channel.
IPR003915. PKD_2.
[Graphical view]
PfamPF08016. PKD_channel. 1 hit.
[Graphical view]
PRINTSPR01433. POLYCYSTIN2.
PROSITEPS50222. EF_HAND_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio398558.
PROA2A259.
SOURCESearch...

Entry information

Entry namePK2L1_MOUSE
AccessionPrimary (citable) accession number: A2A259
Secondary accession number(s): Q14B55, Q14B73, Q80ZH4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 19, 2014
Last sequence update: February 20, 2007
Last modified: April 16, 2014
This is version 56 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot