Details for: PKD1L3

Gene ID: 342372

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PKD1L3

Ensembl ID: ENSG00000277481

Description: polycystin 1 like 3, transient receptor potential channel interacting

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • mesothelial cell CL0000077
    CSI 1.61
    rCSI 6.29%
    PRS 99.32

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PKD1L3](/details-gene/342372) (Polycystin 1 Like 3) is a protein-coding gene located on chromosome 16q22.2. It encodes a member of the polycystin family of proteins, which function as transient receptor potential (TRP) channels. Functionally, [PKD1L3](/details-gene/342372) is best characterized as a component of a cation channel complex that acts as a sour taste receptor in sensory perception ([Link](https://doi.org/10.1016/j.bbrc.2009.05.069)). This channel, typically formed with PKD2L1, is activated by acidic pH, leading to calcium ion influx. Expression data indicates that **Overall**, [PKD1L3](/details-gene/342372) is a significant marker for [mesothelial cell](/details-cell/CL0000077), suggesting potential functions beyond gustatory sensation. ## Cellular Roles and Expression Landscape The primary role of [PKD1L3](/details-gene/342372) has been extensively studied in the context of taste perception, where it is a critical component of the sour taste receptor in specialized taste bud cells ([Link](https://doi.org/10.1371/journal.pone.0007347)). Its interaction with PKD2L1 is essential for the proper localization and function of this acid-sensing channel complex at the taste pore ([Link](https://doi.org/10.1096/fj.10-162925)). However, a broader analysis of gene expression reveals a distinct pattern. **Overall**, the gene shows its most significant expression enrichment in [mesothelial cell](/details-cell/CL0000077) (CSI: 1.61). Mesothelial cells form the epithelial lining of the body's serous cavities, such as the pleura and peritoneum. This specific expression in a non-gustatory cell type suggests that the chemosensory or mechanosensory capabilities of [PKD1L3](/details-gene/342372)-containing channels may be co-opted for physiological monitoring within these body cavities, such as detecting pH changes or other stimuli associated with inflammation or tissue stress. ## Pathways and Molecular Function The functional annotations for [PKD1L3](/details-gene/342372) are highly consistent with its role as an ion channel component. Its molecular functions are dominated by activities such as *Sour taste receptor activity* ([GO:0033040](https://www.ebi.ac.uk/QuickGO/term/GO:0033040)), *Calcium channel activity* ([GO:0005262](https://www.ebi.ac.uk/QuickGO/term/GO:0005262)), and *Monoatomic cation channel activity* ([GO:0005261](https://www.ebi.ac.uk/QuickGO/term/GO:0005261)). These activities support biological processes including *Sensory perception of sour taste* ([GO:0050915](https://www.ebi.ac.uk/QuickGO/term/GO:0050915)), *Cellular response to acidic ph* ([GO:0071468](https://www.ebi.ac.uk/QuickGO/term/GO:0071468)), and *Calcium ion transmembrane transport* ([GO:0070588](https://www.ebi.ac.uk/QuickGO/term/GO:0070588)). Cellularly, [PKD1L3](/details-gene/342372) is localized to the *Plasma membrane* ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)) and the *Cell surface* ([GO:0009986](https://www.ebi.ac.uk/QuickGO/term/GO:0009986)), where it assembles into a *Cation channel complex* ([GO:0034703](https://www.ebi.ac.uk/QuickGO/term/GO:0034703)). Research confirms that it forms a heteromeric channel with PKD2L1, and the assembly is critical for its function ([Link](https://doi.org/10.1038/ncomms2257)). This complex detects acidic stimuli, triggering a cation influx that serves as the basis for sour taste signaling ([Link](https://doi.org/10.1038/embor.2008.89)). ## Research Directions The well-defined role of [PKD1L3](/details-gene/342372) in gustation contrasts sharply with its high expression specificity in [mesothelial cell](/details-cell/CL0000077), opening new avenues for investigation into its function in monitoring the microenvironment of serous cavities. **Proposed Hypotheses:** 1. [PKD1L3](/details-gene/342372) functions as a pH sensor in mesothelial cells, detecting acidosis associated with local inflammation, ischemia, or malignancy within the peritoneal or pleural cavities. Activation of this channel could trigger downstream calcium-dependent signaling pathways involved in inflammatory responses or tissue repair. 2. In [mesothelial cell](/details-cell/CL0000077), [PKD1L3](/details-gene/342372) may partner with a different ion channel subunit, not PKD2L1, to form a complex that responds to mechanical stretch or other non-acidic stimuli, contributing to the regulation of fluid transport or lubrication within serous cavities. **Experimental Approach:** To test the hypothesis that [PKD1L3](/details-gene/342372) is a functional acid sensor in mesothelial cells, one could perform a knockdown of [PKD1L3](/details-gene/342372) in primary human peritoneal mesothelial cells using siRNA. Control and knockdown cells would then be loaded with a ratiometric calcium indicator dye (e.g., Fura-2). Using live-cell imaging, the intracellular calcium response upon perfusion with an acidic extracellular solution (e.g., pH 6.0) would be measured. A significantly blunted calcium influx in the [PKD1L3](/details-gene/342372)-knockdown cells compared to controls would provide strong evidence for its role as a functional acid-sensing channel in this cell type. **Therapeutic Potential:** As a cell-surface ion channel, [PKD1L3](/details-gene/342372) is a potentially druggable target. If its role in mesothelial cells is linked to sensing pathological acidosis during inflammation (e.g., peritonitis) or in the tumor microenvironment, targeted inhibition could be a therapeutic strategy. A small molecule inhibitor could potentially mitigate excessive inflammatory signaling or alter the cellular response to acidic conditions, thereby representing a novel approach for modulating diseases affecting mesothelial-lined cavities. Inhibition, rather than activation, would likely be the goal to prevent pathological calcium signaling.

Genular Protein ID: 1990823607

Symbol: PK1L3_HUMAN

Name: Polycystin-1-like protein 3

UniProtKB Accession Codes:

Q7Z443

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 EMBL 1 Ensembl 1 GO 12 Gene3D 4 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 4 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TCDB 1 UCSC 1 VEuPathDB 1 eggNOG 2 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 12782129

Title: Identification of two novel polycystic kidney disease-1-like genes in human and mouse genomes.

PubMed ID: 12782129

DOI: 10.1016/s0888-7543(03)00048-x

PubMed ID: 18535624

Title: Off-response property of an acid-activated cation channel complex PKD1L3-PKD2L1.

PubMed ID: 18535624

DOI: 10.1038/embor.2008.89

PubMed ID: 19464260

Title: Acetic acid activates PKD1L3-PKD2L1 channel--a candidate sour taste receptor.

PubMed ID: 19464260

DOI: 10.1016/j.bbrc.2009.05.069

PubMed ID: 19812697

Title: Sour ageusia in two individuals implicates ion channels of the ASIC and PKD families in human sour taste perception at the anterior tongue.

PubMed ID: 19812697

DOI: 10.1371/journal.pone.0007347

PubMed ID: 20538909

Title: Interaction between PKD1L3 and PKD2L1 through their transmembrane domains is required for localization of PKD2L1 at taste pores in taste cells of circumvallate and foliate papillae.

PubMed ID: 20538909

DOI: 10.1096/fj.10-162925

PubMed ID: 22420714

Title: The response of PKD1L3/PKD2L1 to acid stimuli is inhibited by capsaicin and its pungent analogs.

PubMed ID: 22420714

DOI: 10.1111/j.1742-4658.2012.08566.x

PubMed ID: 23212381

Title: Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex.

PubMed ID: 23212381

DOI: 10.1038/ncomms2257

Sequence Information:

  • Length: 1732
  • Mass: 195894
  • Checksum: 64847A1C8BE5A6A1
  • Sequence:
    • MFFKGGSWLW LYIRTSIILG SELNSPAPHG QNNCYQLNRF QCSFEEAQHY CHVQRGFLAH 
IWNKEVQDLI RDYLEEGKKW WIGQNVMPLK KHQDNKYPAD VAANGPPKPL SCTYLSRNFI 
RISSKGDKCL LKYYFICQTG DFLDGDAHYE RNGNNSHLYQ RHKKTKRGVA IARDKMPPGP 
GHLPTTCHYP LPAHLSKTLC HPISQFPSVL SSITSQVTSA ASEPSSQPLP VITQLTMPVS 
VTHAGQSLAE TTSSPKEEGH PNTFTSYLQV SLQKASGQVI DEIAGNFSRA VHGLQALNKL 
QEACEFLQKL TALTPRFSKP AQVNLINSLI YLSEELLRIP FQNNNSLGFK VPPTVCPFHS 
LNNVTKAGEG SWLESKRHTE PVEDILEMSL VEFGNIGEAF LEQNQSPESS VTLTSANATL 
LLSRQNISTL PLSSYTLGHP APVRLGFPSA LALKELLNKH PGVNVQITGL AFNPFKDLDN 
RNIVGSIGSV LLSANRKLLQ VHDLMEDIEI MLWRNVSLET HPTSLNMSTH QLTITVNVTS 
LEKSLIVSID PDSPLLMTLY LGFQYQPNCT HFHLNITLPK DKVWQKDEEY TWVLNPEHLQ 
HGIGTYYITA VLSERQEGAQ QTPSLVSVIT AVTQCYYWEI HNQTWSSAGC QVGPQSTILR 
TQCLCNHLTF FASDFFVVPR TVNVEDTIKL FLRVTNNPVG VSLLASLLGF YVITVVWARK 
KDQADMQKVK VTVLADNDPS AQFHYLIQVY TGYRRSAATT AKVVITLYGS EGRSEPHHLC 
DPQKTVFERG GLDVFLLTTW TSLGNLHSLR LWHDNSGVSP SWYVSQVIVC DMAVKRKWHF 
LCNCWLAVDL GDCELDRVFI PVSKRELFSF RHLFSSMIVE KFTQDYLWLS IATRHPWNQF 
TRVQRLSCCM TLLLCNMVIN VMFWKINSTT AKRDEQMRPF AVAWSELLVS IHTAVILFPI 
NLVIGRLFPL IEPQETLPLF PPIQASCLSD ASVEPLSATM VVEELKETVR FLLRRNTYLL 
SKCEQPPWSS WDITKLVKLL SSLVSSHLEG QGCHQQGERH WARVVPENHH HFCCYLHRVL 
QRLKSHLGTL GLTQGHQSCD FLDAASQLQK LQELLETHIL PTEQEPSREV TSFAILSSEE 
GKKPISNGLS KWLTSVCWLL LGFTSLASAF FTALYSLELS KDQATSWMIS IILSVLQNIF 
ISQPVKVVFF TFLYSLMMSR MPRLNKENEQ QTKRILALLA KCSSSVPGSR DKNNPVYVAP 
AINSPTKHPE RTLKKKKLFK LTGDILVQIL FLTLLMTAIY SAKNSNRFYL HQAIWKTFSH 
QFSEIKLLQD FYPWANHILL PSLYGDYRGK NAVLEPSHCK CGVQLIFQIP RTKTYEKVDE 
GQLAFCDNGH TCGRPKSLFP GLHLRRFSYI CSPRPMVLIP TDELHERLTS KNENGFSYIM 
RGAFFTSLRL ESFTSLQMSK KGCVWSIISQ VIYYLLVCYY AFIQGCQLKQ QKWRFFTGKR 
NILDTSIILI SFILLGLDMK SISLHKKNMA RYRDDQDRFI SFYEAVKVNS AATHLVGFPV 
LLATVQLWNL LRHSPRLRVI SRTLSRAWDE VVGFLLIILI LLTGYAIAFN LLFGCSISDY 
RTFFSSAVTV VGLLMGISHQ EEVFALDPVL GTFLILTSVI LMVLVVINLF VSAILMAFGK 
ERKSLKKEAA LIDTLLQKLS NLLGISWPQK TSSEQAATTA VGSDTEVLDE LP