Details for: SERPINI2

Gene ID: 5276

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: SERPINI2

Ensembl ID: ENSG00000114204

Description: serpin family I member 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • ependymal cell CL0000065
    CSI 10.14
    rCSI 20.58%
    PRS 73.88
  • lung ciliated cell CL1000271
    CSI 9.44
    rCSI 10.91%
    PRS 85.71
  • pancreatic acinar cell CL0002064
    CSI 7.49
    rCSI 9.96%
    PRS 93.58
  • glioblast CL0000030
    CSI 7.47
    rCSI 11.91%
    PRS 83.71
  • cardiac muscle cell CL0000746
    CSI 5.02
    rCSI 7.2%
    PRS 83.29
  • choroid plexus epithelial cell CL0000706
    CSI 4.25
    rCSI 6.95%
    PRS 84.18
  • podocyte CL0000653
    CSI 3.53
    rCSI 15.69%
    PRS 91.21
  • ionocyte CL0005006
    CSI 3.49
    rCSI 3.74%
    PRS 92.24
  • Bergmann glial cell CL0000644
    CSI 2.89
    rCSI 3.95%
    PRS 83.61
  • ciliated epithelial cell CL0000067
    CSI 2.85
    rCSI 2.51%
    PRS 82.64
  • alveolar macrophage CL0000583
    CSI 2.63
    rCSI 4.33%
    PRS 92.48
  • macroglial cell CL0000126
    CSI 2.37
    rCSI 6.09%
    PRS 87.38
  • multi-ciliated epithelial cell CL0005012
    CSI 2.23
    rCSI 2.22%
    PRS 85.73
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.15
    rCSI 4.82%
    PRS 78.84
  • ciliated cell CL0000064
    CSI 2.06
    rCSI 3.35%
    PRS 85.46
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.83
    rCSI 6.91%
    PRS 78.6
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.59
    rCSI 3.63%
    PRS 84.32
  • indirect pathway medium spiny neuron CL4023029
    CSI 1.32
    rCSI 31.82%
    PRS 76.39
  • deuterosomal cell CL4033044
    CSI 1
    rCSI 3.39%
    PRS 86.02
  • regular atrial cardiac myocyte CL0002129
    CSI 0.95
    rCSI 3.07%
    PRS 87.43
  • direct pathway medium spiny neuron CL4023026
    CSI 0.37
    rCSI 8.86%
    PRS 76.24

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 [SERPINI2](/details-gene/5276), or serpin family I member 2, is a protein-coding gene that functions as a serine-type endopeptidase inhibitor. As a member of the serpin superfamily, its primary role involves the negative regulation of peptidase activity, predominantly in the extracellular environment. Expression data indicates that [SERPINI2](/details-gene/5276) is a significant marker for a diverse array of specialized cell types, with particularly high significance in [ependymal cell](/details-cell/CL0000065)s of the central nervous system, [lung ciliated cell](/details-cell/CL1000271)s, and [pancreatic acinar cell](/details-cell/CL0002064)s. Emerging research suggests a potential role as a tumor suppressor, as its expression is reportedly downregulated in pancreatic cancer and it may inhibit breast cancer progression ([Link](https://doi.org/10.1002/(sici)1098-2264(199807)22:3<179::aid-gcc3>3.3.co;2-u), [Link](https://doi.org/10.1073/pnas.96.7.3700)). ## Cellular Roles and Expression Landscape The expression profile of [SERPINI2](/details-gene/5276) highlights its importance across multiple distinct physiological systems, suggesting a role in maintaining tissue-specific homeostasis through the regulation of extracellular proteolysis. - **Central Nervous System:** **Overall**, [SERPINI2](/details-gene/5276) shows its highest significance in [ependymal cell](/details-cell/CL0000065)s (CSI: 10.14), which line the cerebral ventricles. It is also highly significant in [glioblast](/details-cell/CL0000030)s (CSI: 7.47), [choroid plexus epithelial cell](/details-cell/CL0000706)s (CSI: 4.25), and other macroglial cells such as [Bergmann glial cell](/details-cell/CL0000644)s and [astrocyte](/details-cell/CL0002605)s. This pattern suggests a critical function in modulating the composition of the cerebrospinal fluid and protecting neural tissue from unregulated protease activity. - **Epithelial and Secretory Tissues:** The gene is a prominent marker in multiple epithelial contexts. It is highly significant in [lung ciliated cell](/details-cell/CL1000271)s (CSI: 9.44) and related ciliated cell types, pointing towards a protective role at mucosal surfaces. Furthermore, its high significance in [pancreatic acinar cell](/details-cell/CL0002064)s (CSI: 7.49) is consistent with its initial characterization as a pancreas-specific gene ("pancpin") and suggests it may regulate digestive enzymes or prevent auto-digestion within the pancreas ([Link](https://doi.org/10.1002/(sici)1098-2264(199807)22:3<179::aid-gcc3>3.3.co;2-u)). - **Other Specialized Tissues:** Notable significance is also observed in [cardiac muscle cell](/details-cell/CL0000746)s (CSI: 5.02) and renal [podocyte](/details-cell/CL0000653)s (CSI: 3.53). This widespread but specific expression pattern indicates that [SERPINI2](/details-gene/5276) likely serves as a key regulator of the extracellular matrix and tissue integrity in organs requiring tight control over proteolytic activity. ## Pathways and Molecular Function The functional annotations for [SERPINI2](/details-gene/5276) align closely with its identity as a secreted protease inhibitor. - **Molecular Function:** The gene product's primary molecular function is annotated as [serine-type endopeptidase inhibitor activity](/details-go/GO:0004867), which directly supports its role in controlling the action of serine proteases. - **Biological Process:** This activity contributes to the broader biological processes of [negative regulation of peptidase activity](/details-go/GO:0010466) and [negative regulation of endopeptidase activity](/details-go/GO:0010951). By inhibiting proteases, SERPINI2 can influence a wide range of physiological events, including tissue remodeling, inflammation, and cell signaling. - **Cellular Component:** Consistent with its function, the SERPINI2 protein is primarily found in the [extracellular space](/details-go/GO:0005615) and has been identified within [extracellular exosome](/details-go/GO:0070062)s. This localization allows it to act on secreted proteases in the immediate cellular microenvironment, which is essential for its proposed protective roles in the lungs, pancreas, and central nervous system. ## Research Directions The specific expression pattern of [SERPINI2](/details-gene/5276) and its reported dysregulation in cancer provide a foundation for several compelling research avenues. ### Proposed Hypotheses 1. **Tumor Suppression in Pancreatic Cancer:** Given its high expression in healthy [pancreatic acinar cell](/details-cell/CL0002064)s and its reported downregulation in pancreatic cancer ([Link](https://doi.org/10.1002/(sici)1098-2264(199807)22:3<179::aid-gcc3>3.3.co;2-u)), it is hypothesized that the loss of [SERPINI2](/details-gene/5276) expression is a key step in pancreatic tumorigenesis, leading to unchecked extracellular protease activity that facilitates cancer cell invasion and metastasis. 2. **Cerebrospinal Fluid Homeostasis:** The prominent expression in [ependymal cell](/details-cell/CL0000065)s and [choroid plexus epithelial cell](/details-cell/CL0000706)s suggests that [SERPINI2](/details-gene/5276) is secreted into the cerebrospinal fluid (CSF) to regulate protein turnover and protect the brain from proteolytic damage. Its dysregulation could therefore be a contributing factor in neuroinflammatory or neurodegenerative diseases associated with blood-brain barrier disruption. ### Key Experiments To test the hypothesis that [SERPINI2](/details-gene/5276) functions as a tumor suppressor in pancreatic cancer, a key experiment would involve the re-introduction of [SERPINI2](/details-gene/5276) into a SERPINI2-deficient pancreatic ductal adenocarcinoma (PDAC) cell line. The effects on invasive potential could be quantified using a 3D organoid co-culture system with cancer-associated fibroblasts to model the tumor microenvironment. Changes in the proteolytic activity of secreted matrix metalloproteinases (MMPs) and other serine proteases in the culture supernatant would be measured to establish a direct mechanistic link between SERPINI2 expression and the inhibition of pro-invasive pathways. ### Therapeutic Potential The existing evidence points to [SERPINI2](/details-gene/5276) as a tumor suppressor, making it a candidate for therapies aimed at **activation** or functional restoration rather than inhibition. In cancers where its expression is epigenetically silenced or lost, strategies to restore its function could be beneficial. Because it is a secreted protein, therapeutic approaches could include the systemic or local delivery of recombinant SERPINI2 protein, which could potentially inhibit tumor-promoting proteases within the tumor microenvironment. This approach may be particularly relevant for cancers like pancreatic and breast cancer where its loss has been documented.

Genular Protein ID: 794429027

Symbol: SPI2_HUMAN

Name: Serpin I2

UniProtKB Accession Codes:

O75830

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 3 ExpressionAtlas 1 GO 3 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9624529

Title: Isolation and characterization of a novel human pancreas-specific gene, pancpin, that is down-regulated in pancreatic cancer cells.

PubMed ID: 9624529

DOI: 10.1002/(sici)1098-2264(199807)22:3&lt;179::aid-gcc3&gt;3.3.co;2-u

PubMed ID: 10097100

Title: Suppression of breast cancer growth and metastasis by a serpin myoepithelium-derived serine proteinase inhibitor expressed in the mammary myoepithelial cells.

PubMed ID: 10097100

DOI: 10.1073/pnas.96.7.3700

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: 405
  • Mass: 46145
  • Checksum: 5BA18C60E4FDE9A4
  • Sequence:
    • MDTIFLWSLL LLFFGSQASR CSAQKNTEFA VDLYQEVSLS HKDNIIFSPL GITLVLEMVQ 
LGAKGKAQQQ IRQTLKQQET SAGEEFFVLK SFFSAISEKK QEFTFNLANA LYLQEGFTVK 
EQYLHGNKEF FQSAIKLVDF QDAKACAEMI STWVERKTDG KIKDMFSGEE FGPLTRLVLV 
NAIYFKGDWK QKFRKEDTQL INFTKKNGST VKIPMMKALL RTKYGYFSES SLNYQVLELS 
YKGDEFSLII ILPAEGMDIE EVEKLITAQQ ILKWLSEMQE EEVEISLPRF KVEQKVDFKD 
VLYSLNITEI FSGGCDLSGI TDSSEVYVSQ VTQKVFFEIN EDGSEAATST GIHIPVIMSL 
AQSQFIANHP FLFIMKHNPT ESILFMGRVT NPDTQEIKGR DLDSL

Genular Protein ID: 1814981569

Symbol: B4DDY9_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DDY9

Database IDs:

AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 Gene3D 2 InterPro 6 KEGG 1 MEROPS 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 1 PeptideAtlas 1 Pfam 1 RefSeq 2 RuleBase 1 SAM 1 SMART 2 SUPFAM 1

Sequence Information:

  • Length: 413
  • Mass: 46994
  • Checksum: BCBA74F931E174BB
  • Sequence:
    • MDTIFLWSLL LLFFGSQASR CSAQKNTEFA VDLYQEVSLS HKDNIIFSPL GITLVLEMVQ 
LGAKGKAQQQ IRQTLKQQET SAGEEFFVLK SFFSAISEKK QEFTFNLANA LYLQEGFTVK 
EQYLHGNKEF FQSAIKLVDF QDAKACAGMI STWVERKTDG KIKDMFSGEE FGPLTRLVLV 
NAIYFKGDWK QKFRKEDTQL INFTKKNGST VKIPMMKALL RTKYGYFSES SLNYQVLELS 
YKGDEFSLII ILPAEGMDIE EVEKLITAQQ ILKWLSEMQE EEVEISLPRF KVEQKVDFKD 
VLYSLNITEI FSGGCDLSGI TDSSEVYVSQ VTQKVFFEIN EDGSEAATST GIHIPVIMSL 
AQSQFIANHP FLFIMKHNPT ESILFMGRVT NPDTQEIKGR DLDSLWMKST ASE