PKD2L1 polycystin 2 like 1, transient receptor potential cation channel [Homo sapiens (human)] - Gene

Summary

Official Symbol: PKD2L1provided by HGNC
Official Full Name: polycystin 2 like 1, transient receptor potential cation channelprovided by HGNC
Primary source: HGNC:HGNC:9011
See related: Ensembl:ENSG00000107593 MIM:604532; AllianceGenome:HGNC:9011
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PCL; PKDL; PKD2L; TRPP3
Summary: This gene encodes a member of the polycystin protein family. The encoded protein contains multiple transmembrane domains, and cytoplasmic N- and C-termini. The protein may be an integral membrane protein involved in cell-cell/matrix interactions. This protein functions as a calcium-regulated nonselective cation channel. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
Expression: Biased expression in spleen (RPKM 1.0), testis (RPKM 0.9) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q24.31

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (100288149..100330228, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (101172443..101214450, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (102047906..102089985, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Genetic Variants in WNT16 and PKD2L1 Locus Affect Heel Ultrasound Bone Stiffness: Analyses from the General Population and Patients Evaluated for Osteoporosis.
Title: Genetic Variants in WNT16 and PKD2L1 Locus Affect Heel Ultrasound Bone Stiffness: Analyses from the General Population and Patients Evaluated for Osteoporosis.
Polycystic kidney disease 2-like 1 channel contributes to the bitter aftertaste perception of quinine.
Title: Polycystic kidney disease 2-like 1 channel contributes to the bitter aftertaste perception of quinine.
Molecular Mechanism of L-Pyroglutamic Acid Interaction with the Human Sour Receptor.
Title: Molecular Mechanism of L-Pyroglutamic Acid Interaction with the Human Sour Receptor.
Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population.
Title: Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population.
Opening TRPP2 (PKD2L1) requires the transfer of gating charges.
Title: Opening TRPP2 (PKD2L1) requires the transfer of gating charges.
Charge-neutralizing mutations (K452Q, K455Q and K461Q) in transmembrane segment 4 reduced gating charges, positively shifted the Boltzmann-type activation curve [i.e., open probability (P open)-V curve] and altered the time-courses of activation/deactivation of PKD2L1, indicating that this region constitutes part of a voltage sensor.
Title: Integrative Approach with Electrophysiological and Theoretical Methods Reveals a New Role of S4 Positively Charged Residues in PKD2L1 Channel Voltage-Sensing.
The related primary cilium-specific polycystin-2 protein, encoded by PKD2, shares a high degree of sequence similarity, yet has distinct permeability characteristics. Here the authors show that these differences are reflected in the architecture of polycystin 2-l1.
Title: Cryo-EM structure of the polycystin 2-l1 ion channel.
Clustered phosphorylation sites, Ser-682, Ser-685, and Ser-686 are significant for the channel regulation by phosphorylation.
Title: Identification of clustered phosphorylation sites in PKD2L1: how PKD2L1 channel activation is regulated by cyclic adenosine monophosphate signaling pathway.
The pore helix and transmembrane segment 6 of PKD2L1 are involved in upper and lower-gate opening, adopt an open conformation.
Title: Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1.
PKD2 and PKD1 genes are mutated in autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to respond to ligand(s) and/or mechanical stimuli. Here, we identify a two-residue hydrophobic gate in PKD2L1, and a single-residue hydrophobic gate in PKD2.
Title: Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic determinants influencing human serum metabolome among African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortiu EBI GWAS Catalog EBI GWAS CatalogPubMed
Human metabolic individuality in biomedical and pharmaceutical research. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S603 (e-PCR), detects polymorphism
- UniSTS:37404

D10S603 (e-PCR), detects polymorphism
- UniSTS:50380

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables alpha-actinin binding	IPI Inferred from Physical Interaction more info	PubMed
enables calcium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables calcium-activated cation channel activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium-activated potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium-activated potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables cytoskeletal protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	ISS Inferred from Sequence or Structural Similarity more info
enables monoatomic cation channel activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to monoatomic cation transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables muscle alpha-actinin binding	IBA Inferred from Biological aspect of Ancestor more info
enables muscle alpha-actinin binding	IPI Inferred from Physical Interaction more info	PubMed
enables pH-gated monoatomic ion channel activity	IDA Inferred from Direct Assay more info	PubMed
enables pH-gated monoatomic ion channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables sodium channel activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to sour taste receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables transmembrane transporter binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in calcium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in cellular response to acidic pH	ISS Inferred from Sequence or Structural Similarity more info
involved_in detection of chemical stimulus involved in sensory perception of sour taste	ISS Inferred from Sequence or Structural Similarity more info
involved_in detection of chemical stimulus involved in sensory perception of taste	ISS Inferred from Sequence or Structural Similarity more info
involved_in detection of mechanical stimulus	IBA Inferred from Biological aspect of Ancestor more info
involved_in inorganic cation transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in monoatomic cation transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in monoatomic cation transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in protein homotetramerization	IDA Inferred from Direct Assay more info	PubMed
involved_in response to water	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sour taste	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in smoothened signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in sodium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in actin cytoskeleton	IDA Inferred from Direct Assay more info
part_of calcium channel complex	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with cell surface	ISS Inferred from Sequence or Structural Similarity more info
located_in ciliary membrane	IEA Inferred from Electronic Annotation more info
located_in cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in non-motile cilium	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
part_of receptor complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: polycystin-2-like protein 1

Names: polycystic kidney disease 2-like 1 protein; polycystin-2 homolog; polycystin-2L1; polycystin-L; polycystin-L1; transient receptor potential cation channel, subfamily P, member 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_047099.1 RefSeqGene

Range

21297..63376

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001253837.2 → NP_001240766.1 polycystin-2-like protein 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice junction at the 5' end of coding exon compared to variant 1, that causes a frameshift. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AF073481, BC025665, DQ084244

UniProtKB/TrEMBL

Q1L4F0

Conserved Domains (1) summary

pfam08016
Location:99 → 520

PKD_channel; Polycystin cation channel
NM_016112.3 → NP_057196.2 polycystin-2-like protein 1 isoform 1

See identical proteins and their annotated locations for NP_057196.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AL139819

Consensus CDS

CCDS7492.1

UniProtKB/Swiss-Prot

O75972, Q5W039, Q9P0L9, Q9UP35, Q9UPA2

UniProtKB/TrEMBL

Q1L4F0

Related

ENSP00000325296.3, ENST00000318222.4

Conserved Domains (2) summary

pfam08016
Location:147 → 567

PKD_channel; Polycystin cation channel

pfam18109
Location:702 → 735

Fer4_24; Ferredoxin I 4Fe-4S cluster domain