Details for: ZNF185

Gene ID: 7739

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: ZNF185

Ensembl ID: ENSG00000147394

Description: zinc finger protein 185 with LIM domain

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • squamous epithelial cell CL0000076
    CSI 6.26
    rCSI 14.87%
    PRS 96.38
  • nasal mucosa goblet cell CL0002480
    CSI 5.42
    rCSI 6.29%
    PRS 98.19
  • secretory cell CL0000151
    CSI 4.12
    rCSI 4.3%
    PRS 98.54
  • epithelial cell CL0000066
    CSI 3.8
    rCSI 5.84%
    PRS 94.28
  • conjunctival epithelial cell CL1000432
    CSI 3.22
    rCSI 4.92%
    PRS 98.13
  • respiratory suprabasal cell CL4033048
    CSI 3.08
    rCSI 3.95%
    PRS 99.14
  • ciliated cell CL0000064
    CSI 2.76
    rCSI 4.48%
    PRS 96.3
  • club cell CL0000158
    CSI 2.5
    rCSI 3.66%
    PRS 98.49
  • platelet CL0000233
    CSI 1.92
    rCSI 7.96%
    PRS 96.08
  • megakaryocyte CL0000556
    CSI 1.46
    rCSI 6.32%
    PRS 97.6
  • parietal epithelial cell CL1000452
    CSI 1.38
    rCSI 3.69%
    PRS 97.78
  • epithelial cell of esophagus CL0002252
    CSI 0.92
    rCSI 9.06%
    PRS 96.79

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):
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    • High
    • Medium
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    • 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 [ZNF185](/details-gene/7739) is a protein-coding gene located on the X chromosome that encodes a zinc finger protein containing a LIM domain. Functionally, it is associated with protein binding, zinc ion binding, and localizes to the cytoplasm, specifically to the [cytoskeleton](/details-go/GO:0005856) and [focal adhesion](/details-go/GO:0005925) sites. Its expression profile indicates a significant role in epithelial tissues, with high significance scores in [squamous epithelial cell](/details-cell/CL0000076)s, [nasal mucosa goblet cell](/details-cell/CL0002480)s, and other secretory and epithelial cell types. Notably, it is also highly expressed in the megakaryocyte-platelet lineage. Research suggests [ZNF185](/details-gene/7739) functions as an actin-cytoskeleton-associated growth inhibitory protein, pointing towards a potential role in maintaining tissue homeostasis and suppressing oncogenesis ([Link](https://doi.org/10.1038/sj.onc.1209769)). ## Cellular Roles and Expression Landscape The **Overall** expression pattern of [ZNF185](/details-gene/7739) highlights its importance in two primary cellular contexts: epithelial barrier function and hematopoiesis. Its most significant role appears to be within epithelial tissues. The gene shows high significance in a variety of epithelial cell types that form mucosal and barrier surfaces, including [squamous epithelial cell](/details-cell/CL0000076) (CSI: 6.26), [conjunctival epithelial cell](/details-cell/CL1000432) (CSI: 3.22), and [epithelial cell of esophagus](/details-cell/CL0002252) (CSI: 0.92). This is complemented by high significance in specialized secretory cells within these barriers, such as [nasal mucosa goblet cell](/details-cell/CL0002480) (CSI: 5.42) and [club cell](/details-cell/CL0000158) (CSI: 2.50). This expression pattern is consistent with its localization to focal adhesions, which are critical for maintaining the structural integrity of epithelial layers. A second key area of function is in the megakaryocyte-platelet lineage. [ZNF185](/details-gene/7739) is significantly expressed in [platelet](/details-cell/CL0000233)s (CSI: 1.92) and their precursors, [megakaryocyte](/details-cell/CL0000556)s (CSI: 1.46). This finding is corroborated by phosphoproteomic studies of human platelets ([Link](https://doi.org/10.1021/pr0704130), [Link](https://doi.org/10.1021/ac9004309)). Given the protein's association with the actin cytoskeleton, it may play a crucial role in the dynamic cytoskeletal rearrangements required for platelet formation, activation, and aggregation. ## Pathways and Molecular Function The molecular function and cellular localization of [ZNF185](/details-gene/7739) are consistent with its observed cellular expression patterns. * **Molecular Function:** Gene Ontology annotations describe its molecular function as [protein binding](/details-go/GO:0005515) and [zinc ion binding](/details-go/GO:0008270). The zinc-binding capability is intrinsic to its zinc finger and LIM domains, which are well-known protein-protein interaction modules. * **Cellular Component:** It is localized to the [cytoplasm](/details-go/GO:0005737), with specific enrichment at the [cytoskeleton](/details-go/GO:0005856) and at [focal adhesion](/details-go/GO:0005925) sites. The connection of [ZNF185](/details-gene/7739) to the actin cytoskeleton and focal adhesions provides a mechanistic link to its cellular roles. In epithelial cells, this association likely contributes to cell-matrix adhesion and the maintenance of tissue architecture. In platelets, this link is fundamental to the rapid and extensive cytoskeletal remodeling that governs their hemostatic functions. One study identified [ZNF185](/details-gene/7739) as a growth inhibitory protein directly associated with the actin cytoskeleton, reinforcing its role as a structural and regulatory component ([Link](https://doi.org/10.1038/sj.onc.1209769)). ## Research Directions Based on its established association with the cytoskeleton and its specific expression profile, several research avenues for [ZNF185](/details-gene/7739) can be proposed. **Proposed Hypotheses:** 1. **Role in Epithelial Barrier Integrity:** The loss or downregulation of [ZNF185](/details-gene/7739) in mucosal epithelial cells compromises barrier function by destabilizing focal adhesions and disorganizing the actin cytoskeleton, rendering the tissue more susceptible to pathogens and physical stress. 2. **Regulation of Platelet Activation:** [ZNF185](/details-gene/7739) acts as a negative regulator of platelet activation. Upon agonist stimulation, its phosphorylation or displacement from the actin cytoskeleton is a necessary step to permit the cytoskeletal rearrangements required for platelet shape change and aggregation. 3. **Tumor Suppressor Function:** Consistent with previous findings in prostate cancer ([Link](https://doi.org/10.1038/sj.onc.1209769)), epigenetic silencing or loss-of-function mutations in [ZNF185](/details-gene/7739) contribute to the progression of other epithelial-derived carcinomas by dismantling its growth-inhibitory function and promoting increased cell motility. **Experimental Approach:** To test the first hypothesis regarding its role in epithelial barrier integrity, a robust experimental plan could be implemented. One could utilize CRISPR-Cas9 to generate a [ZNF185](/details-gene/7739) knockout in a human respiratory epithelial cell line (e.g., Calu-3) cultured at an air-liquid interface to form a polarized monolayer. Barrier function could be quantitatively assessed by measuring transepithelial electrical resistance (TEER) and paracellular flux of fluorescently-labeled dextran. The structural consequences of the knockout on cell adhesion and cytoskeletal architecture would be examined via immunofluorescence microscopy, staining for key focal adhesion proteins (e.g., paxillin, vinculin) and F-actin (phalloidin). **Therapeutic Potential:** The characterization of [ZNF185](/details-gene/7739) as a growth inhibitory protein suggests it functions as a tumor suppressor. Therefore, it is not a candidate for therapeutic inhibition. Instead, its therapeutic potential lies in strategies that could restore its expression or function in cancer cells where it is lost. As an intracellular cytoskeletal protein, it is not an ideal target for conventional antibody-based therapies. However, future approaches could explore gene therapies to re-introduce the gene or the development of small molecules that reactivate its silenced promoter or stabilize the protein, potentially restoring its anti-proliferative effects in specific epithelial cancers.

Genular Protein ID: 1726315283

Symbol: ZN185_HUMAN

Name: Zinc finger protein 185

UniProtKB Accession Codes:

O15231 A4FTV3 A6NME5 B4DLE9 B7Z771 B8K2L9 B8K2M0 B8K2M1 B8K2M2 E9PFR6 F5GXF7 F5GZL4 F8W8V7 H0Y4M8 O00345 Q8N1R8 Q9NSD2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 7 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 12 Ensembl 14 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 8 Pumba 1 RNAct 1 RefSeq 14 SMART 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9268636

Title: Genomic structure of a novel LIM domain gene (ZNF185) in Xq28 and comparisons with the orthologous murine transcript.

PubMed ID: 9268636

DOI: 10.1006/geno.1997.4810

PubMed ID: 16799630

Title: ZNF185, an actin-cytoskeleton-associated growth inhibitory LIM protein in prostate cancer.

PubMed ID: 16799630

DOI: 10.1038/sj.onc.1209769

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 10854409

Title: Comparative genome sequence analysis of the Bpa/Str region in mouse and man.

PubMed ID: 10854409

DOI: 10.1101/gr.10.6.758

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 18088087

Title: Phosphoproteome of resting human platelets.

PubMed ID: 18088087

DOI: 10.1021/pr0704130

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 689
  • Mass: 73525
  • Checksum: 0CCA739701FE1423
  • Sequence:
    • MSISALGGRT KGKPLPPGEE ERNNVLKQMK VRTTLKGDKS WITKQDESEG RTIELPSGRS 
RATSFSSAGE VPKPRPPSTR APTGYIIRGV FTKPIDSSSQ PQQQFPKANG TPKSAASLVR 
TANAGPPRPS SSGYKMTTED YKKLAPYNIR RSSTSGDTEE EEEEEVVPFS SDEQKRRSEA 
ASGVLRRTAP REHSYVLSAA KKSTGPTQET QAPFIAKRVE VVEEDGPSEK SQDPPALARS 
TPGSNSADGG RTKASRAIWI ECLPSMPSPA GSQELSSRGE EIVRLQILTP RAGLRLVAPD 
VEGMRSSPGN KDKEAPCSRE LQRDLAGEEA FRAPNTDAAR SSAQLSDGNV GSGATGSRPE 
GLAAVDIGSE RGSSSATSVS AVPADRKSNS TAAQEDAKAD PKGALADYEG KDVATRVGEA 
WQERPGAPRG GQGDPAVPAQ QPADPSTPER QSSPSGSEQL VRRESCGSSV LTDFEGKDVA 
TKVGEAWQDR PGAPRGGQGD PAVPTQQPAD PSTPEQQNSP SGSEQFVRRE SCTSRVRSPS 
SCMVTVTVTA TSEQPHIYIP APASELDSSS TTKGILFVKE YVNASEVSSG KPVSARYSNV 
SSIEDSFAME KKPPCGSTPY SERTTGGICT YCNREIRDCP KITLEHLGIC CHEYCFKCGI 
CSKPMGDLLD QIFIHRDTIH CGKCYEKLF

Genular Protein ID: 3987663354

Symbol: B3KPM4_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KPM4

Database IDs:

ARBA 1 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 GO 1 Gene3D 1 InterPro 2 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 3 PROSITE-ProRule 1 PeptideAtlas 1 RefSeq 8 SMART 1

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 147
  • Mass: 16246
  • Checksum: D929458BCBD78E66
  • Sequence:
    • MVTVTVTATS EQPHIYIPAP ASELDSSSTT KGILFVKEYV NASEVSSGKP VSARYSNVSS 
IEDSFAMEKK PPCGSTPYSE RTTGGICTYC NREIRDCPKI TLEHLGICCH EYCFKCGICS 
KPMGDLLDQI FIHRDTIHCG KCYEKLF