Details for: LIAT1

Gene ID: 400566

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: LIAT1

Ensembl ID: ENSG00000187624

Description: ligand of ATE1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • ciliated epithelial cell CL0000067
    CSI 8.21
    rCSI 7.22%
    PRS 98.27
  • lung ciliated cell CL1000271
    CSI 5.19
    rCSI 6%
    PRS 98.75
  • multi-ciliated epithelial cell CL0005012
    CSI 3.44
    rCSI 3.44%
    PRS 98.71
  • choroid plexus epithelial cell CL0000706
    CSI 3.26
    rCSI 5.33%
    PRS 98.54
  • ciliated cell CL0000064
    CSI 2.96
    rCSI 4.8%
    PRS 98.15
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.59
    rCSI 2.49%
    PRS 99.33
  • retinal cone cell CL0000573
    CSI 1.99
    rCSI 3.2%
    PRS 98
  • deuterosomal cell CL4033044
    CSI 1.48
    rCSI 4.99%
    PRS 98.03
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.26
    rCSI 2.88%
    PRS 98.16

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 [LIAT1](/details-gene/400566) (Ligand of ATE1) is a protein-coding gene located on chromosome 17p13.3. It is primarily known for its role in protein arginylation, a post-translational modification, by binding to the arginyltransferase ATE1 ([Link](https://pubmed.ncbi.nlm.nih.gov/25369936/)). More recent studies indicate that [LIAT1](/details-gene/400566) is an intrinsically disordered protein that functions as a scaffold for molecular condensates, participating in nucleolar phase separation ([Link](https://pubmed.ncbi.nlm.nih.gov/33443146/)). **Overall**, expression data reveals a highly specific and significant enrichment in ciliated epithelial cells, suggesting a crucial role in the biology of these specialized cell types across various tissues. ## Cellular Roles and Expression Landscape The expression profile of [LIAT1](/details-gene/400566) demonstrates a strong and specific association with ciliated cells. It is most significantly expressed in [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 8.21), [lung ciliated cell](/details-cell/CL1000271) (CSI: 5.19), and [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 3.44). This pattern extends to other related cell types, including [choroid plexus epithelial cell](/details-cell/CL0000706), [ciliated cell](/details-cell/CL0000064), and [ciliated columnar cell of tracheobronchial tree](/details-cell/CL0002145). Furthermore, its high significance in [deuterosomal cell](/details-cell/CL4033044) (CSI: 1.48), a cell type responsible for centriole amplification during the formation of multiple cilia, strongly suggests a function related to ciliogenesis. The gene's relevance is also noted in cells containing primary or modified cilia, such as [fallopian tube secretory epithelial cell](/details-cell/CL4030006) and [retinal cone cell](/details-cell/CL0000573). This consistent and highly specific expression pattern across multiple tissues firmly establishes [LIAT1](/details-gene/400566) as a key molecular player in cells defined by the presence or development of cilia. ## Pathways and Molecular Function The functional annotations for [LIAT1](/details-gene/400566) are highly consistent with its observed cellular roles. Its primary molecular function is to facilitate [protein arginylation](/details-gene/GO:0016598) through its interaction with ATE1. This post-translational modification can alter protein stability and function, which may be critical for the complex proteome of cilia. Recent research has expanded this view, showing that [LIAT1](/details-gene/400566) also possesses [molecular condensate scaffold activity](/details-gene/GO:0140693) and is involved in [non-membrane-bounded organelle assembly](/details-gene/GO:0140694) ([Link](https://pubmed.ncbi.nlm.nih.gov/33443146/)). This activity is particularly relevant to its localization in the [cytoplasm](/details-gene/GO:0005737) and the [nucleolus](/details-gene/GO:0005730), a major site of ribosome biogenesis. The high metabolic and protein synthesis demands required for the assembly and maintenance of cilia may depend on the efficient organization of the nucleolus, a process in which [LIAT1](/details-gene/400566) appears to play a direct role. ## Research Directions The specific enrichment of [LIAT1](/details-gene/400566) in ciliated cells, coupled with its known molecular functions, points toward a critical role in ciliary biology, a field with direct relevance to a class of genetic disorders known as ciliopathies. **Proposed Hypotheses:** 1. [LIAT1](/details-gene/400566)-mediated protein arginylation is essential for the proper assembly or structural integrity of the ciliary axoneme. The arginylation of key structural proteins, such as tubulins or dyneins, may be a required step for their incorporation or function within the cilium. 2. The role of [LIAT1](/details-gene/400566) in nucleolar phase separation is a rate-limiting step in ribosome biogenesis specifically required to meet the high demand for protein synthesis during multiciliogenesis in epithelial tissues. **Experimental Approach:** To test the first hypothesis, a targeted knockout or knockdown of [LIAT1](/details-gene/400566) could be performed in human bronchial epithelial cells grown at an air-liquid interface (ALI) to induce differentiation into a ciliated epithelium. The resulting culture could be analyzed using transmission electron microscopy (TEM) to identify ultrastructural defects in the ciliary axoneme. Concurrently, mass spectrometry-based proteomics could be used to compare the arginylated proteome of control versus [LIAT1](/details-gene/400566)-deficient ciliated cells, aiming to identify specific ciliary protein substrates whose arginylation status is dependent on [LIAT1](/details-gene/400566). **Therapeutic Potential:** Given its highly specific expression pattern, [LIAT1](/details-gene/400566) could represent a potential therapeutic target for ciliopathies characterized by defects in ciliary structure or function. Since these are often loss-of-function disorders, a therapeutic strategy would likely involve enhancing the [LIAT1](/details-gene/400566)-ATE1 pathway or its downstream effects rather than inhibition. For example, small molecules that stabilize the LIAT1-ATE1 interaction or promote its activity could be explored as a means to restore ciliary function in diseases where this pathway is compromised. However, the systemic effects of modulating such a fundamental post-translational modification would require careful investigation.

Genular Protein ID: 2339530697

Symbol: LIAT1_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6ZQX7 A5D8T6 Q6NSI2 Q6PFW9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 ExpressionAtlas 1 GO 5 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 RNAct 1 RefSeq 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 25369936

Title: Liat1, an arginyltransferase-binding protein whose evolution among primates involved changes in the numbers of its 10-residue repeats.

PubMed ID: 25369936

DOI: 10.1073/pnas.1419587111

PubMed ID: 33443146

Title: The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6.

PubMed ID: 33443146

DOI: 10.1073/pnas.2015887118

Sequence Information:

  • Length: 453
  • Mass: 49656
  • Checksum: B6EB88592B0ED514
  • Sequence:
    • METRGPGLAV RAESRRLVGI GPRAPPGRVG LQPSGRLDRR GGAGTMGYKD NDGEEEEREG 
GAAGPRGSRL PPITGGASEL AKRKVKKKKR KKKTKGSGKG DDKHQSQSLK SQPLSSSFHD 
ILSPCKERGP KPEHRQSKVE KKHLPSDSST VSLPDFAEIE NLANRINESL RWDGILADPE 
AEKERIRIYK LNRRKRYRCL ALKGFHPDPE ALKGFHPDPD ALKGFHPDPE ALKGFHPDPE 
ALKGFHPDPE ALKGFHPDPE ALKGIHPDPE ALKGIHPDPE ALKGFHPDPE ALKGFHPDPE 
ALKGFHTDPE ALKGFHIDPE ALKGFHPDPK ALKGFHPDPK ALKGFHTDPE ALKGFHPDPK 
ALKGFHPDPE ALKGFHPDPE ALKGFHPDPE ALKGFHTDPN AEEAPENLPY LSDKDGSSSH 
RQPTSKAECP NLCFEGNLTP KLLHSDLAPT LLE

Genular Protein ID: 370975991

Symbol: A0A0H4IV28_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A0H4IV28

Database IDs:

AlphaFoldDB 1 Antibodypedia 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 ExpressionAtlas 1 InterPro 1 KEGG 1 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PhylomeDB 1 RefSeq 1 SAM 1 VEuPathDB 1

Sequence Information:

  • Length: 423
  • Mass: 46413
  • Checksum: 2011EBEE9EDE9001
  • Sequence:
    • METRGPGLAV RAESRRLVGI GPRAPPGRVG LQPSGRLDRR GGAGTMGYKD NDGEEEEREG 
GAAGPRGSRL PPITGGASEL AKRKVKKKKR KKKTKGSGKG DDKHQSQSLK SQPLSSSFHD 
ILSPCKERGP KPEHRQSKVE KKHLPSDSST VSLPDFAEIE NLANRINESL RWDGILADPE 
AEKERIRIYK LNRRKRYRCL ALKGFHPDPE ALKGFHPDPD ALKGFHPDPE ALKGFHPDPE 
ALKGIHPDPE ALKGFHPDPE ALKGFHPDPE ALKGFHTDPE ALKGFHIDPE ALKGFHPDPK 
ALKGFHPDPK ALKGFHTDPE ALKGFHPDPK ALKGFHPDPE ALKGFHPDPE ALKGFHPDPE 
ALKGFHTDPN AEEAPENLPY LSDKDGSSSH RQPTSKAECP NLCFEGNLTP KLLHSDLAPT 
LLE