Details for: KREMEN2

Gene ID: 79412

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: KREMEN2

Ensembl ID: ENSG00000131650

Description: kringle containing transmembrane protein 2

Cell Significance Landscape

Associated with

Significant Cells

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

  • precursor B cell CL0000817
    CSI 5.35
    rCSI 4.69%
    PRS 99.55
  • immature B cell CL0000816
    CSI 4.54
    rCSI 3.37%
    PRS 99.73
  • small pre-B-II cell CL0000954
    CSI 4.02
    rCSI 3.86%
    PRS 99.57
  • intestinal tuft cell CL0019032
    CSI 3.68
    rCSI 5.62%
    PRS 98.98
  • intestine goblet cell CL0019031
    CSI 3.36
    rCSI 2.99%
    PRS 98.95
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.14
    rCSI 3.02%
    PRS 99.14
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.41
    rCSI 1.71%
    PRS 92.27

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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Legend:
  • Query Gene
  • 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 [KREMEN2](/details-gene/79412) (Kringle containing transmembrane protein 2) is a protein-coding gene located on chromosome 16p13.3. It encodes a transmembrane receptor known primarily for its role as a negative regulator of the [Wnt signaling pathway](/details-go/GO:0016055) [Link](https://doi.org/10.1038/ng1285). The gene's expression profile suggests a highly specialized function, with significant expression observed in hematopoietic cells, particularly during B-lymphocyte development. **Overall**, it is a key marker for [precursor B cell](/details-cell/CL0000817) and [immature B cell](/details-cell/CL0000816). Additionally, [KREMEN2](/details-gene/79412) shows notable expression in specialized secretory epithelial cells, including [intestinal tuft cell](/details-cell/CL0019032) and [intestine goblet cell](/details-cell/CL0019031), indicating a role in regulating signaling within mucosal tissues. ## Cellular Roles and Expression Landscape The expression pattern of [KREMEN2](/details-gene/79412) points to specific roles in both the immune system and epithelial tissues. The most significant expression is found within the B cell lineage, with the highest Cell Significance Index (CSI) scores in [precursor B cell](/details-cell/CL0000817) (CSI: 5.35), [immature B cell](/details-cell/CL0000816) (CSI: 4.54), and [small pre-B-II cell](/details-cell/CL0000954) (CSI: 4.02). This strong association suggests that [KREMEN2](/details-gene/79412) is integral to the regulation of B lymphocyte development and differentiation. Beyond the hematopoietic system, [KREMEN2](/details-gene/79412) is also significantly expressed in several specialized epithelial cell types. These include [intestinal tuft cell](/details-cell/CL0019032) (CSI: 3.68), [intestine goblet cell](/details-cell/CL0019031) (CSI: 3.36), and [fallopian tube secretory epithelial cell](/details-cell/CL4030006) (CSI: 3.14). This pattern indicates a potential role in maintaining tissue homeostasis, regulating cellular differentiation, or modulating signaling pathways within these secretory and sensory epithelial environments. A more moderate but still notable expression in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 1.41) suggests it may also contribute to the function or maintenance of long-lived T cell populations. The highly specific expression profile suggests that its function is tightly restricted to these particular cell contexts. ## Pathways and Molecular Function Functionally, [KREMEN2](/details-gene/79412) is annotated as a [transmembrane signaling receptor](/details-go/GO:0004888) that resides in the [plasma membrane](/details-go/GO:0005886) and [early endosome membrane](/details-go/GO:0031901) [Link](https://doi.org/10.1101/gr.2596504). Its primary role is in the [Wnt signaling pathway](/details-go/GO:0016055), where it acts as a high-affinity receptor for DKK1, an antagonist of Wnt signaling. By binding DKK1, KREMEN2 facilitates the internalization of the Wnt co-receptor LRP5/6, thereby inhibiting Wnt-dependent signaling. This is reflected in its association with Reactome pathways such as [Negative regulation of tcf-dependent signaling by wnt ligand antagonists](/details-pathway/R-HSA-3772470) and [Signaling by wnt](/details-pathway/R-HSA-195721). This molecular function is consistent with its cellular expression profile. The Wnt pathway is critical for lymphocyte development, and the high expression of [KREMEN2](/details-gene/79412) in developing B cells suggests it acts as a key modulator to ensure proper differentiation. Similarly, Wnt signaling is a master regulator of intestinal crypt homeostasis and cell fate determination, aligning with the gene's expression in [intestinal tuft](/details-cell/CL0019032) and [goblet cells](/details-cell/CL0019031). The gene's involvement in pathways such as [Signaling by wnt in cancer](/details-pathway/R-HSA-4791275) highlights its potential relevance to pathology when its regulatory function is compromised. ## Research Directions The role of [KREMEN2](/details-gene/79412) as a Wnt antagonist in specific cell types opens several avenues for future investigation, particularly concerning development and cancer. **Proposed Hypotheses:** 1. Given its high expression in early B cell stages, **[KREMEN2](/details-gene/79412) likely functions as a critical checkpoint during B cell lymphopoiesis by fine-tuning Wnt signaling.** Dysregulation or loss of [KREMEN2](/details-gene/79412) could lead to developmental arrest or contribute to the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL), where Wnt signaling is often altered. 2. Based on its expression in intestinal epithelial cells and its function as a Wnt inhibitor, **[KREMEN2](/details-gene/79412) may act as a tumor suppressor in the colon.** Its downregulation could be a key event in the initiation or progression of colorectal cancers that are driven by aberrant Wnt pathway activation. **Experimental Approach:** To test the hypothesis that [KREMEN2](/details-gene/79412) is a tumor suppressor in the intestine, a compelling experiment would be to use a mouse model of intestinal cancer (e.g., APCmin/+ mice) and cross it with a conditional *Kremen2* knockout model specific to the intestinal epithelium (e.g., using a Villin-Cre driver). The resulting offspring would be monitored for an accelerated rate of adenoma formation, increased tumor burden, and enhanced Wnt signaling activity (via immunohistochemistry for beta-catenin and qPCR for Wnt target genes like *Axin2* and *c-Myc*) compared to APCmin/+ controls. This would provide in vivo evidence for its tumor-suppressive role. **Therapeutic Potential:** As a transmembrane protein that negatively regulates a major oncogenic pathway, [KREMEN2](/details-gene/79412) presents an interesting therapeutic opportunity. Rather than inhibition, a therapeutic strategy would likely focus on **activation** or mimicking its function. For Wnt-driven cancers where [KREMEN2](/details-gene/79412) is downregulated, re-introducing its function could be beneficial. This could potentially be achieved with an agonist antibody that promotes LRP5/6 internalization or with a soluble, engineered form of the KREMEN2 ectodomain that can sequester Wnt ligands or potentiate DKK1 activity. However, the systemic effects of modulating Wnt signaling would require careful consideration to avoid toxicity in tissues that rely on this pathway for normal homeostasis.

Genular Protein ID: 3485990322

Symbol: KREM2_HUMAN

Name: Kremen protein 2

UniProtKB Accession Codes:

Q8NCW0 B4DXF6 I3L2S2 Q8N2J4 Q8NCW1 Q96GL8 Q9BTP9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 4 CDD 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 11 Ensembl 6 GO 5 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIRSF 1 PRINTS 1 PRO 1 PROSITE 4 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 6 RNAct 1 Reactome 3 RefSeq 4 SIGNOR 1 SMART 3 SMR 1 STRING 1 SUPFAM 2 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: 15616553

Title: The sequence and analysis of duplication-rich human chromosome 16.

PubMed ID: 15616553

DOI: 10.1038/nature03187

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

Sequence Information:

  • Length: 462
  • Mass: 48849
  • Checksum: CE33015917A9AA68
  • Sequence:
    • MGTQALQGFL FLLFLPLLQP RGASAGSLHS PGLSECFQVN GADYRGHQNR TGPRGAGRPC 
LFWDQTQQHS YSSASDPHGR WGLGAHNFCR NPDGDVQPWC YVAETEEGIY WRYCDIPSCH 
MPGYLGCFVD SGAPPALSGP SGTSTKLTVQ VCLRFCRMKG YQLAGVEAGY ACFCGSESDL 
ARGRLAPATD CDQICFGHPG QLCGGDGRLG VYEVSVGSCQ GNWTAPQGVI YSPDFPDEYG 
PDRNCSWALG PPGAALELTF RLFELADPRD RLELRDAASG SLLRAFDGAR PPPSGPLRLG 
TAALLLTFRS DARGHAQGFA LTYRGLQDAA EDPEAPEGSA QTPAAPLDGA NVSCSPRPGA 
PPAAIGARVF STVTAVSVLL LLLLGLLRPL RRRSCLLAPG KGPPALGASR GPRRSWAVWY 
QQPRGVALPC SPGDPQAEGS AAGYRPLSAS SQSSLRSLIS AL

Genular Protein ID: 1534296333

Symbol: Q53F67_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q53F67

Database IDs:

ARBA 5 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 2 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 Gene3D 2 InterPro 8 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 7 PROSITE-ProRule 1 PeptideAtlas 1 Pfam 3 RefSeq 4 SAM 2 SMART 3 SUPFAM 2

Citations:

PubMed ID: 8125298

Title: Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.

PubMed ID: 8125298

DOI: 10.1016/0378-1119(94)90802-8

PubMed ID: 9373149

Title: Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.

PubMed ID: 9373149

DOI: 10.1016/S0378-1119(97)00411-3

Sequence Information:

  • Length: 420
  • Mass: 44447
  • Checksum: 4270169C67BE5C6D
  • Sequence:
    • MGTQALQGFL FLLFLPLLQP RGASAGSLHS PGLSECFQVN GADYRGHQNR TGPRGAGRPC 
LFWDQTQQHS YSSASDPHGR WGLGAHNFCR NPDGDVQPWC YVAETEEGIY WRYCDIPSCH 
MPGYLGCFVD SGAPPALSGP SGTSTKLTVQ VCLRFCRMKG YQLAGVEAGY ACFCGSESDL 
ARGRLAPATD CDQICFGHPG QLCGGDGRLG VYEVSVGSCQ GNWTAPQGVI YSPDFPDEYG 
PDRNCSWALG PPGAALELTF RLFELADPRD RLELRDAASG SLLRDFDGAR PPPSGPLRLG 
TAALLLTFRS DARGHAQGFA LTYRGLQDAA EDPEAPEGSA QTPAAPLDGA NVSCSPRPGA 
PPAAIGGAVC WLREKGPRRW GLPGAPGEAG LCGTNSPEGW PCPAPPGTPR LRVLPRATGL