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A2A259

- PK2L1_MOUSE

UniProt

A2A259 - PK2L1_MOUSE

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Protein
Polycystic kidney disease 2-like 1 protein
Gene
Pkd2l1, Trpp3
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.8 Publications

Enzyme regulationi

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.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi643 – 65412 Reviewed prediction
Add
BLAST

GO - Molecular functioni

  1. calcium channel activity Source: UniProtKB
  2. calcium ion binding Source: BHF-UCL
  3. calcium-activated potassium channel activity Source: Ensembl
  4. cation channel activity Source: MGI
  5. identical protein binding Source: BHF-UCL
  6. protein binding Source: BHF-UCL
  7. sodium channel activity Source: Ensembl
Complete GO annotation...

GO - Biological processi

  1. cation transport Source: BHF-UCL
  2. cellular response to acidity Source: BHF-UCL
  3. detection of chemical stimulus involved in sensory perception of sour taste Source: BHF-UCL
  4. detection of mechanical stimulus Source: RefGenome
  5. protein homotrimerization Source: UniProtKB
  6. smoothened signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Protein family/group databases

TCDBi1.A.5.2.2. the polycystin cation channel (pcc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Polycystic kidney disease 2-like 1 protein
Alternative name(s):
Polycystin-2 homolog
Gene namesi
Name:Pkd2l1
Synonyms:Trpp3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 19

Organism-specific databases

MGIiMGI:1352448. Pkd2l1.

Subcellular locationi

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.3 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 103103Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei104 – 12421Helical; Reviewed prediction
Add
BLAST
Topological domaini125 – 313189Extracellular Reviewed prediction
Add
BLAST
Transmembranei314 – 33421Helical; Reviewed prediction
Add
BLAST
Topological domaini335 – 34713Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei348 – 36821Helical; Reviewed prediction
Add
BLAST
Topological domaini369 – 38517Extracellular Reviewed prediction
Add
BLAST
Transmembranei386 – 40621Helical; Reviewed prediction
Add
BLAST
Topological domaini407 – 47670Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei477 – 49721Helical; Reviewed prediction
Add
BLAST
Topological domaini498 – 53942Extracellular Reviewed prediction
Add
BLAST
Transmembranei540 – 56021Helical; Reviewed prediction
Add
BLAST
Topological domaini561 – 760200Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. calcium channel complex Source: UniProtKB
  2. ciliary membrane Source: UniProtKB-SubCell
  3. endoplasmic reticulum Source: MGI
  4. nonmotile primary cilium Source: UniProtKB
  5. plasma membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Disruption phenotypei

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 (1 Publication). Partial reduction of chorda tympani nerve response to sour stimuli, without affecting sweet, salty, bitter, and umami perception (1 Publication).2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi523 – 5231D → E: Little or no effect on calcium channel activity. 1 Publication
Mutagenesisi523 – 5231D → N: Impaired calcium channel activity. 1 Publication
Mutagenesisi525 – 5251D → N: Little or no effect on calcium channel activity. 1 Publication
Mutagenesisi530 – 5301D → N: Little or no effect on calcium channel activity. 1 Publication
Mutagenesisi568 – 5681K → A: Induces localization to the cell surface when expressed in absence of PKD1. 1 Publication
Mutagenesisi576 – 5761D → A: Induces localization to the endoplasmic reticulum when expressed in absence of PKD1. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 760760Polycystic kidney disease 2-like 1 protein
PRO_0000425551Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi177 – 1771N-linked (GlcNAc...) Reviewed prediction
Glycosylationi207 – 2071N-linked (GlcNAc...) Reviewed prediction
Glycosylationi241 – 2411N-linked (GlcNAc...) Reviewed prediction
Glycosylationi505 – 5051N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Glycoprotein

Proteomic databases

PRIDEiA2A259.

Expressioni

Tissue specificityi

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).4 Publications

Gene expression databases

GenevestigatoriA2A259.

Interactioni

Subunit structurei

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.2 Publications

Structurei

3D structure databases

ProteinModelPortaliA2A259.
SMRiA2A259. Positions 597-672, 698-739.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini630 – 66536EF-hand
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni701 – 76060Required for protein homotrimerization By similarity
Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili559 – 58022 Reviewed prediction
Add
BLAST
Coiled coili650 – 68233 Reviewed prediction
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi195 – 20713Polycystin motif
Add
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the polycystin family.
Contains 1 EF-hand domain.

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG325704.
GeneTreeiENSGT00700000104221.
HOGENOMiHOG000230858.
HOVERGENiHBG014945.
InParanoidiA2A259.
KOiK04990.
OMAiFSTFVKC.
OrthoDBiEOG7N8ZTW.
PhylomeDBiA2A259.
TreeFamiTF316484.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR013122. PKD1_2_channel.
IPR003915. PKD_2.
[Graphical view]
PfamiPF08016. PKD_channel. 1 hit.
[Graphical view]
PRINTSiPR01433. POLYCYSTIN2.
PROSITEiPS50222. EF_HAND_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

A2A259-1 [UniParc]FASTAAdd to Basket

« Hide

MNSMESPKNQ ELQTLGNRAW DNPAYSDPPS PNRTLRICTV SSVALPETQP    50
KKPEVRCQEK TQRTLVSSCC LHICRSIRGL WGTTLTENTA ENRELYVKTT 100
LRELVVYIVF LVDICLLTYG MTSSSAYYYT KVMSELFLHT PSDSGVSFQT 150
ISSMSDFWDF AQGPLLDSLY WTKWYNNQSL GRGSHSFIYY ENLLLGAPRL 200
RQLRVRNDSC VVHEDFREDI LNCYDVYSPD KEDQLPFGPQ NGTAWTYHSQ 250
NELGGSSHWG RLTSYSGGGY YLDLPGSRQA SAEALQGLQE GLWLDRGTRV 300
VFIDFSVYNA NINLFCILRL VVEFPATGGT IPSWQIRTVK LIRYVNNWDF 350
FIVGCEVVFC VFIFYYVVEE ILEIHLHRLR YLSSVWNILD LVVILLSIVA 400
VGFHIFRTLE VNRLMGKLLQ QPDTYADFEF LAFWQTQYNN MNAVNLFFAW 450
IKIFKYISFN KTMTQLSSTL ARCAKDILGF AIMFFIVFFA YAQLGYLLFG 500
TQVENFSTFV KCIFTQFRII LGDFDYNAID NANRILGPVY FVTYVFFVFF 550
VLLNMFLAII NDTYSEVKEE LAGQKDQLQL SDFLKQSYNK TLLRLRLRKE 600
RVSDVQKVLK GGEPEIQFED FTSTLRELGH EEHEITAAFT RFDQDGDHIL 650
DEEEQEQMRQ GLEEERVTLN AEIENLGRSV GHSPPGELGA EAARGQSWVS 700
GEEFDMLTRR VLQLQCVLEG VVSQIDAVGS KLKMLERKGE LAPSPGMGEP 750
AVWENLYNPS 760
Length:760
Mass (Da):87,234
Last modified:February 20, 2007 - v1
Checksum:i4C76777051CFC2EF
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti114 – 1141I → V in AAK58371. 1 Publication
Sequence conflicti114 – 1141I → V in AAI16324. 1 Publication
Sequence conflicti114 – 1141I → V in AAI16298. 1 Publication
Sequence conflicti202 – 2032QL → HV in AAK58371. 1 Publication
Sequence conflicti438 – 4381Y → D in AAK58371. 1 Publication
Sequence conflicti482 – 4821I → V in AAK58371. 1 Publication
Sequence conflicti756 – 7561L → P in AAI16324. 1 Publication
Sequence conflicti756 – 7561L → P in AAI16298. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS29846.1.
RefSeqiNP_852087.2. NM_181422.3.
UniGeneiMm.308481.

Genome annotation databases

EnsembliENSMUST00000042026; ENSMUSP00000045675; ENSMUSG00000037578.
GeneIDi329064.
KEGGimmu:329064.
UCSCiuc008hpm.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS29846.1.
RefSeqi NP_852087.2. NM_181422.3.
UniGenei Mm.308481.

3D structure databases

ProteinModelPortali A2A259.
SMRi A2A259. Positions 597-672, 698-739.
ModBasei Search...

Protein family/group databases

TCDBi 1.A.5.2.2. the polycystin cation channel (pcc) family.

Proteomic databases

PRIDEi A2A259.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000042026 ; ENSMUSP00000045675 ; ENSMUSG00000037578 .
GeneIDi 329064.
KEGGi mmu:329064.
UCSCi uc008hpm.2. mouse.

Organism-specific databases

CTDi 9033.
MGIi MGI:1352448. Pkd2l1.

Phylogenomic databases

eggNOGi NOG325704.
GeneTreei ENSGT00700000104221.
HOGENOMi HOG000230858.
HOVERGENi HBG014945.
InParanoidi A2A259.
KOi K04990.
OMAi FSTFVKC.
OrthoDBi EOG7N8ZTW.
PhylomeDBi A2A259.
TreeFami TF316484.

Miscellaneous databases

NextBioi 398558.
PROi A2A259.
SOURCEi Search...

Gene expression databases

Genevestigatori A2A259.

Family and domain databases

Gene3Di 1.10.238.10. 1 hit.
InterProi IPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR013122. PKD1_2_channel.
IPR003915. PKD_2.
[Graphical view ]
Pfami PF08016. PKD_channel. 1 hit.
[Graphical view ]
PRINTSi PR01433. POLYCYSTIN2.
PROSITEi PS50222. EF_HAND_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PKD1, MUTAGENESIS OF LYS-568 AND ASP-576.
  6. 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. 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. 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.

Entry informationi

Entry nameiPK2L1_MOUSE
AccessioniPrimary (citable) accession number: A2A259
Secondary accession number(s): Q14B55, Q14B73, Q80ZH4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 19, 2014
Last sequence update: February 20, 2007
Last modified: September 3, 2014
This is version 58 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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 (1 Publication, 1 Publication). 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 (1 Publication). Moreover, the PKD1L3-PKD2L1 heteromer, when expressed in cells does not respond to acid stimuli used to evoke proton currents in taste cells (1 Publication).

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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