Details for: TMEM139

Gene ID: 135932

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: TMEM139

Ensembl ID: ENSG00000178826

Description: transmembrane protein 139

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • fallopian tube secretory epithelial cell CL4030006
    CSI 4.52
    rCSI 4.35%
    PRS 98.53
  • intestinal epithelial cell CL0002563
    CSI 4.27
    rCSI 4.46%
    PRS 98.43
  • stem cell CL0000034
    CSI 4.15
    rCSI 4%
    PRS 98.67
  • enterocyte CL0000584
    CSI 4.1
    rCSI 6.61%
    PRS 97.84
  • colon epithelial cell CL0011108
    CSI 3.84
    rCSI 4.02%
    PRS 98.73
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 3.73
    rCSI 5.29%
    PRS 98.45
  • neural progenitor cell CL0011020
    CSI 3.22
    rCSI 14.15%
    PRS 94.42
  • pancreatic ductal cell CL0002079
    CSI 2.56
    rCSI 4.98%
    PRS 98.76
  • kidney epithelial cell CL0002518
    CSI 2.37
    rCSI 4.52%
    PRS 99.67
  • dopaminergic neuron CL0000700
    CSI 1.19
    rCSI 6.74%
    PRS 95.37

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
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    • 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 [TMEM139](/details-gene/135932) is a protein-coding gene located on chromosome 7q34 that encodes Transmembrane protein 139. As its name suggests, it is localized to the [membrane](/details-cell/GO:0016020) and is known to participate in [protein binding](/details-cell/GO:0005515). **Overall**, expression data indicates that [TMEM139](/details-gene/135932) is a significant marker for various epithelial cell types, particularly those involved in secretory and transport functions, such as [fallopian tube secretory epithelial cell](/details-cell/CL4030006) and [intestinal epithelial cell](/details-cell/CL0002563). Its demonstrated interaction with an anion exchanger in the kidney suggests a potential role in regulating ion transport and cellular homeostasis. ## Cellular Roles and Expression Landscape The expression profile of [TMEM139](/details-gene/135932) highlights its importance in diverse epithelial tissues. The gene shows the highest significance in [fallopian tube secretory epithelial cell](/details-cell/CL4030006) (CSI: 4.52), as well as in multiple cell types of the gastrointestinal tract, including [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 4.27), [enterocyte](/details-cell/CL0000584) (CSI: 4.10), and [colon epithelial cell](/details-cell/CL0011108) (CSI: 3.84). This pattern suggests a conserved role in the secretory or absorptive functions of these mucosal linings. Furthermore, [TMEM139](/details-gene/135932) is prominently expressed in specialized epithelial cells of the kidney, such as [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111) (CSI: 3.73) and [kidney epithelial cell](/details-cell/CL0002518) (CSI: 2.37), and in [pancreatic ductal cell](/details-cell/CL0002079) (CSI: 2.56). This expression is consistent with its known interaction with the kidney anion exchanger kAE1, pointing toward a functional role in ion and fluid transport. Interestingly, the gene also shows significant expression in progenitor populations, including [stem cell](/details-cell/CL0000034) (CSI: 4.15) and [neural progenitor cell](/details-cell/CL0011020) (CSI: 3.22), which may indicate a role in differentiation or maintenance of pluripotency. ## Pathways and Molecular Function Functional annotation of [TMEM139](/details-gene/135932) is currently limited, confirming its identity as a [membrane](/details-cell/GO:0016020) protein involved in [protein binding](/details-cell/GO:0005515). A key piece of functional evidence comes from a study demonstrating a direct interaction between [TMEM139](/details-gene/135932) and the human kidney isoform of anion exchanger 1 (kAE1) [Link](https://doi.org/10.1016/j.bbrc.2015.05.128). This interaction strongly supports the gene's high expression in kidney epithelial cells and suggests a specific function in regulating ion transport, potentially by modulating the activity, trafficking, or stability of kAE1. The widespread expression across other secretory epithelia suggests it may interact with similar transport proteins in other tissues. ## Research Directions While [TMEM139](/details-gene/135932) is broadly expressed in epithelial tissues, its precise molecular roles remain largely uncharacterized. The available data support several testable hypotheses. 1. **Hypothesis 1:** [TMEM139](/details-gene/135932) is a direct modulator of kAE1 function in the kidney. Based on its demonstrated interaction [Link](https://doi.org/10.1016/j.bbrc.2015.05.128), it may act as an accessory or chaperone protein required for the proper cell surface localization and anion exchange activity of kAE1 in [kidney epithelial cell](/details-cell/CL0002518). 2. **Hypothesis 2:** Given its high expression in progenitor populations like [stem cell](/details-cell/CL0000034) and [neural progenitor cell](/details-cell/CL0011020), [TMEM139](/details-gene/135932) may play a role in regulating cell fate decisions or maintaining an undifferentiated state. It could be part of a membrane-associated signaling complex that senses environmental cues to control proliferation or differentiation. 3. **Hypothesis 3:** In secretory cells like those in the fallopian tube and intestine, [TMEM139](/details-gene/135932) may be involved in the general machinery of vesicular transport and exocytosis, potentially interacting with components of the secretory pathway to facilitate the release of cellular products. **Proposed Experiment:** To test the first hypothesis regarding the modulation of kAE1 function, a CRISPR-Cas9 knockout of [TMEM139](/details-gene/135932) could be generated in a polarized renal epithelial cell line (e.g., MDCK) that endogenously or exogenously expresses kAE1. The functional consequences could be assessed by measuring intracellular pH recovery rates following an acid load (a measure of anion exchange activity) and by quantifying the surface expression level of kAE1 via biotinylation and western blotting. **Therapeutic Potential:** As a multi-pass transmembrane protein, [TMEM139](/details-gene/135932) is structurally amenable to targeting by small molecules or biologics. Its specific, high expression in certain epithelial tissues could make it a candidate target for diseases affecting these cells, such as inherited renal transport disorders or certain types of epithelial cancers. However, a clear association with a specific pathology must first be established. If it proves to be a critical partner for a disease-driving ion transporter, its inhibition could be a viable therapeutic strategy.

Genular Protein ID: 3574479159

Symbol: TM139_HUMAN

Name: Transmembrane protein 139

UniProtKB Accession Codes:

Q8IV31 B2RCL5 D3DXD4 Q6ZME2 Q8NC22 Q96AU8

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 10 Ensembl 5 GO 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 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 1 RNAct 1 RefSeq 6 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16303743

Title: Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.

PubMed ID: 16303743

DOI: 10.1093/dnares/12.2.117

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

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: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 23186163

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

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 26049106

Title: Transmembrane protein 139 (TMEM139) interacts with human kidney isoform of anion exchanger 1 (kAE1).

PubMed ID: 26049106

DOI: 10.1016/j.bbrc.2015.05.128

Sequence Information:

  • Length: 216
  • Mass: 23729
  • Checksum: DF5A7DB1E4126063
  • Sequence:
    • MVPMHLLGRL EKPLLLLCCA SFLLGLALLG IKTDITPVAY FFLTLGGFFL FAYLLVRFLE 
WGLRSQLQSM QTESPGPSGN ARDNEAFEVP VYEEAVVGLE SQCRPQELDQ PPPYSTVVIP 
PAPEEEQPSH PEGSRRAKLE QRRMASEGSM AQEGSPGRAP INLRLRGPRA VSTAPDLQSL 
AAVPTLEPLT PPPAYDVCFG HPDDDSVFYE DNWAPP