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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

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 – 65412PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

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

GO - Biological processi

  1. cation transport Source: BHF-UCL
  2. cellular response to acidic pH 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 By similarity; 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.

GO - Cellular componenti

  1. calcium channel complex Source: UniProtKB
  2. endoplasmic reticulum Source: MGI
  3. nonmotile primary cilium Source: UniProtKB
  4. 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 (PubMed:24336288). Partial reduction of chorda tympani nerve response to sour stimuli, without affecting sweet, salty, bitter, and umami perception (PubMed:21625513).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 proteinPRO_0000425551Add
BLAST

Amino acid modifications

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

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 477-563, 597-672, 698-739.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 103103CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini125 – 313189ExtracellularSequence AnalysisAdd
BLAST
Topological domaini335 – 34713CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini369 – 38517ExtracellularSequence AnalysisAdd
BLAST
Topological domaini407 – 47670CytoplasmicSequence AnalysisAdd
BLAST
Topological domaini498 – 53942ExtracellularSequence AnalysisAdd
BLAST
Topological domaini561 – 760200CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei104 – 12421HelicalSequence AnalysisAdd
BLAST
Transmembranei314 – 33421HelicalSequence AnalysisAdd
BLAST
Transmembranei348 – 36821HelicalSequence AnalysisAdd
BLAST
Transmembranei386 – 40621HelicalSequence AnalysisAdd
BLAST
Transmembranei477 – 49721HelicalSequence AnalysisAdd
BLAST
Transmembranei540 – 56021HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini630 – 66536EF-handPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni701 – 76060Required for protein homotrimerizationBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili559 – 58022Sequence AnalysisAdd
BLAST
Coiled coili650 – 68233Sequence AnalysisAdd
BLAST

Motif

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

Domaini

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

Sequence similaritiesi

Belongs to the polycystin family.Curated
Contains 1 EF-hand domain.PROSITE-ProRule annotation

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

        10         20         30         40         50
MNSMESPKNQ ELQTLGNRAW DNPAYSDPPS PNRTLRICTV SSVALPETQP
60 70 80 90 100
KKPEVRCQEK TQRTLVSSCC LHICRSIRGL WGTTLTENTA ENRELYVKTT
110 120 130 140 150
LRELVVYIVF LVDICLLTYG MTSSSAYYYT KVMSELFLHT PSDSGVSFQT
160 170 180 190 200
ISSMSDFWDF AQGPLLDSLY WTKWYNNQSL GRGSHSFIYY ENLLLGAPRL
210 220 230 240 250
RQLRVRNDSC VVHEDFREDI LNCYDVYSPD KEDQLPFGPQ NGTAWTYHSQ
260 270 280 290 300
NELGGSSHWG RLTSYSGGGY YLDLPGSRQA SAEALQGLQE GLWLDRGTRV
310 320 330 340 350
VFIDFSVYNA NINLFCILRL VVEFPATGGT IPSWQIRTVK LIRYVNNWDF
360 370 380 390 400
FIVGCEVVFC VFIFYYVVEE ILEIHLHRLR YLSSVWNILD LVVILLSIVA
410 420 430 440 450
VGFHIFRTLE VNRLMGKLLQ QPDTYADFEF LAFWQTQYNN MNAVNLFFAW
460 470 480 490 500
IKIFKYISFN KTMTQLSSTL ARCAKDILGF AIMFFIVFFA YAQLGYLLFG
510 520 530 540 550
TQVENFSTFV KCIFTQFRII LGDFDYNAID NANRILGPVY FVTYVFFVFF
560 570 580 590 600
VLLNMFLAII NDTYSEVKEE LAGQKDQLQL SDFLKQSYNK TLLRLRLRKE
610 620 630 640 650
RVSDVQKVLK GGEPEIQFED FTSTLRELGH EEHEITAAFT RFDQDGDHIL
660 670 680 690 700
DEEEQEQMRQ GLEEERVTLN AEIENLGRSV GHSPPGELGA EAARGQSWVS
710 720 730 740 750
GEEFDMLTRR VLQLQCVLEG VVSQIDAVGS KLKMLERKGE LAPSPGMGEP
760
AVWENLYNPS
Length:760
Mass (Da):87,234
Last modified:February 20, 2007 - v1
Checksum:i4C76777051CFC2EF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti114 – 1141I → V in AAK58371. 1 PublicationCurated
Sequence conflicti114 – 1141I → V in AAI16324. (PubMed:15489334)Curated
Sequence conflicti114 – 1141I → V in AAI16298. (PubMed:15489334)Curated
Sequence conflicti202 – 2032QL → HV in AAK58371. 1 PublicationCurated
Sequence conflicti438 – 4381Y → D in AAK58371. 1 PublicationCurated
Sequence conflicti482 – 4821I → V in AAK58371. 1 PublicationCurated
Sequence conflicti756 – 7561L → P in AAI16324. (PubMed:15489334)Curated
Sequence conflicti756 – 7561L → P in AAI16298. (PubMed:15489334)Curated

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 477-563, 597-672, 698-739.
ModBasei Search...
MobiDBi 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: October 29, 2014
This is version 60 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 (PubMed:16891422, PubMed:16929298). 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 (PubMed:21625513). Moreover, the PKD1L3-PKD2L1 heteromer, when expressed in cells does not respond to acid stimuli used to evoke proton currents in taste cells (PubMed:21098668).4 Publications

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